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Abstracts, 20th PANLAR Meeting: Buenos Aires, April 2018

JCR: Journal of Clinical Rheumatology: April 2018 - Volume 24 - Issue - p S1-S174
doi: 10.1097/RHU.0000000000000802
Erratum

In the April 2018 online-only Supplemental issue of , in the article titled “Abstracts, 20th PANLAR Meeting: Buenos Aires, April 2018,” abstract #217 was omitted from the original publication. The document has since been amended to include this abstract.

JCR: Journal of Clinical Rheumatology. 24(5):271, August 2018.

The Pan-American League of Associations of Rheumatology (PANLAR) Congress is the most important gathering of Pan-American Rheumatology, and this year marks the Congress’s 20th year, being held in Buenos Aires Argentina in April 2018. This gathering is very special for several reasons. PANLAR will return to Argentina after 21 years since the last Congress was held in this region at a very special moment for PANLAR, which is celebrating its 75th anniversary.

This supplement includes all the abstracts that were selected for presentation. This year the selection process was very difficult, as there were a record number of abstract submissions (more than 500 abstracts) from all around the world. The supplement includes all scientific investigation abstracts, but does not include case reports. Case reports are an important part of the Congress, and will be presented at the meeting, but have not been included in this supplement. The abstracts have been organized by the type of presentation and topic.

The PANLAR Congress organizers thank all the authors for their hard work, and for choosing to submit their abstracts to present their investigation at the 2018 PANLAR meeting. We believe that the PANLAR Congress encourages rheumatologists and allied health professionals to continue their rheumatologic research. Through scientific investigation, rheumatology care in the Americas continues to improve.We especially thank Dr. Graciela S. Alarcón and her team for their incredible work in the editing of all the abstracts.

PLENARY SESSION

434

ANTIPHOSPHOLIPID SYNDROME IN PEDIATRICS: MORBIDITY BEYOND THROMBOSIS, MULTICENTER IBERO-AMERICAN STUDY

C. Vargas-Rincon1,5, C. Malagon2,5, J. Anton3, C. Mosquera2,5, M.P. Gomez4,5, and R. Yepez4,5. 1Universidad del Valle, Cali, Colombia; 2Universidad El Bosque, Bogotá, Colombia; 3Sant Joan de Déu Hospital, Barcelona, Spain; 4Universidad Libre, Cali, Colombia; 5Pediatric Rheumatology and Immunology Group, Colombia.

Objectives: To describe the clinical and paraclinical characteristics of a group of pediatric patients with positive antiphospholipid antibodies.

Methods: Descriptive multi-center study of case series. Review of medical records with data collection format in Bogotá, Cali and Barcelona. Data analysis with SPSS 20.

Results: N = 117. Average age of diagnosis 12.5 years. 82% women with a F: M ratio for the general group of 4.7: 1 and with thrombosis 2: 1. 58% were associated with SLE, 41% were primary and one case with SS. 42% had at least one thrombotic event, 53% venous, 40% arterial and 14% cerebrovascular disease. 2.5% developed CAPS and 10% presented recurrence of thrombosis mainly in the lower limbs and CNS. Male sex was a factor associated with risk of thrombosis (p = 0.001). 70% presented non-thrombotic manifestations and were more frequent in patients <10 years. Hematological compromise was dominated by thrombocytopenia in 44%, hemolytic anemia 25% and Evans syndrome 11%. Neurological manifestations: migraine 16%, seizures 6.8% and chorea 6%. 18% had ANA titers ≥1,280 and 70% had at least one aCL or positive LA. The presence of aCL-IgM antibodies was associated with non-thrombotic manifestations. There were no significant differences in the recurrence of thrombosis between primary APS or associated with another autoimmune disease, nor association with positivity of autoantibodies.

Conclusions: APS generates an important morbidity in pediatrics and should be considered as a cause of thrombosis in children, even in the absence of other autoimmune diseases. The criteria for diagnosis of APS were developed for adults and may fail to recognize a group of patients with non-thrombotic manifestations, present in 70% of our cases, especially when the compromise is hematological or neurological isolated. Therefore, validated criteria for pediatric patients that consider APS not necessarily as a thrombotic disease should be developed.

193

MECHANIMS INVOLVED IN THE INDUCTION OF IL-6 IN FIBROBLAST-LIKE SYNOVIOCYTES BY STIMULATION WITH SPONDYLOARTHRITIS SYNOVIAL FLUID

M.S. Di Genaro1,2, E. Callegari3, R. Blas4, A. Munarriz5, R. Pardo-Hidalgo6, and H. Tamashiro7. 1Instituto Multidisciplinario de Investigaciones Biológicas-San Luis (IMIBIO-SL), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Luis, Argentina; 2Universidad Nacional de San Luis, San Luis, Argentina; 3SD Biochemical Research Infrastructure Network (SD BRIN), Vermillion, USA; 4Centro Médico MEDICI, San Luis, Argentina; 5Centro Médico CENYR, San Luis, Argentina; 6Centro de Rehabilitación Médica CER, San Juan, Argentina; 7Clínica Bolívar, San Luis, Argentina.

Objectives: In previous studies we have reported that synovial fluid (SF) of spondyloarthritis (SpA) patients induces interleukin (IL)-6 production in fibroblast-like synoviocytes (FLS), and this cytokine modulates metalloproteinase-9 activity of these cells. However, the molecules of the SpA synovial microenvironment that trigger this pro-inflammatory circuit are unknown. The purpose of the present work was to examine the candidate endogenous molecules of SpA SF, and the mechanisms involved in the induction of IL-6 in FLS.

Methods: The SF of SpA patients were pooled (n=9). Human synovial fibroblasts of the SW982 cell line were stimulated with SpA SF pool at dilution 1:10 in DMEM culture medium in absence or presence of anti-tumor necrosis factor (TNF) (Infliximab, 200 g/ml), TNF inhibitor (Etanercept, 100 g/ml), anti-IL-17 (Sekukinumab, 100 g/ml), anti-IL-6 receptor (IL-6R) (Tocilizumab, 200 g/ml), Toll-like receptor 4 (TLR4) activation inhibitor (Polymyxin B, 50 g/ml), ERK, JNK or p38 mitogen-activated protein kinase (MAPK) inhibitor (10 M), or Janus kinase (JAK) 1/3 inhibitor (Tofacitinib, 1000nM). SF treated with Hyaluronidase (50 g/ml) (H-SF) or Proteinase K (500 g/ml) (P-SF) was also used for stimulation of FLS. The IL-6 levels in the supernatants were measured by a commercial enzyme-linked immunosorbent assay (ELISA) kit. In addition, IL-6-inducter alarmins in SpA SF were identified by a Gel-free and Gel-LC botton-up mass spectrometry-based proteomics through the 2D-nano-liquid chromatography-tandem mass spectrometry (2D-nano-LC-MS/MS) analysis. The data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey multiple comparison test. A p value ≤ 0.05 was considered statistically significant.

Results: We found that anti-TNF, anti-IL-17 and anti-IL-6R significantly reduced IL-6 secretion by FLS (p<0.05, p<0.01 and p<0.01, respectively). No difference in IL-6 induction was detected when H-SF was used for stimulation, or when JNK or JAK1/3 was inhibited. In contrast, P-SF stimulation (p<0.001), and TLR4, ERK or p38 inhibition significantly affected IL-6 production by FLS (p<0.01). The proteomic analysis showed that the most abundant proteins of the SpA SF come from extracellular location and cytoplasm. The IL-6-inducter alarmin S1008A8 (calcium binding protein A8) was detected in position 116 in the rank of the most abundant proteins of SpA SF.

Conclusions: The results indicate that TNF, IL-17 and IL-6 themselves enhance SpA SF- induced IL-6 production by FLS, supporting a fine-tuning cytokine in the inflammation process in the synovial microenvironment. In addition, S1008A8, as an endogenous molecule released to the extracellular synovial milieu, may be involved in IL-6 induction in FLS by SpA SF. TLR4 pathway, and ERK and p38 MAPKs participate in the IL-6 production by FLS. Understanding the pathogenic mechanisms associated with the synovial microenvironment may contribute to suggest new therapeutic approaches for SpA.

364

ARTHRITIS: PRIMARY RESULTS THROUGH 52 WEEKS FROM A PHASE-3 RANDOMIZED PLACEBO-CONTROLLED STUDY (FUTURE 4)

A. Kivitz1, P. Nash2, H. Tahir3, A. Everding4, P. Pellet5, A. Widmer5, L. Pricop6, K. Abrams6, and on behalf of the FUTURE 4 Study Group. 1Altoona Centre for Clinical Research, Duncansville, PA, United States; 2University of Queensland, Brisbane, Australia; 3Barts Health NHS Trust, London, United Kingdom; 4Hamburger Rheuma Forschungszentrum II, Mönckebergstraße, Hamburg, Germany; 5Novartis Pharma AG, Basel, Switzerland; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.

Objectives: To assess efficacy and safety of secukinumab (SEC) 150mg sc administered with or without loading dose (LD) in patients (pts) with active psoriatic arthritis (PsA) in the FUTURE 4 study (NCT02294227).

Methods: Patients aged ≥18 years with active PsA were randomized 1:1:1 to receive SEC 150mg sc with LD, SEC 150mg sc with no LD and placebo (PBO). All received SEC or PBO at Weeks (Wks) 0, 1, 2, 3, 4 and every 4 Wks thereafter. PBO pts were switched to SEC 150mg sc at Wk 16 (non-responders) or at Wk 24 (responders). Pts were stratified for randomization by prior anti-TNF therapy (anti–TNF-naïve and intolerant/inadequate response [IR]). The primary endpoint was ACR20 response at Wk 16. ACR20 was analyzed by logistic regression with treatment and TNF-α status as a factor, and weight as a covariate. Missing values were imputed as non-responders. Secondary endpoints included DAS28-CRP, PASI 75 response, SF-36 PCS, and ACR50 at Wk 16.

Results: Of 341 randomized pts, 326 (95.6%) completed 16 wks and 288 (84.5%) completed 52 wks of treatment. Primary endpoint was met; ACR20 response rate was significantly greater at Wk 16 in the SEC 150mg sc LD (41.2%; P<0.001) and 150mg sc no LD (39.8%; P<0.001) groups vs. PBO (18.4%). Significant improvements in the secondary endpoints were also observed at Wk 16 for SEC vs. PBO. Clinical responses observed at Wk 16 were sustained or continued to improve up to Wk 52 in both SEC groups (Table). Improvements across the endpoints were also observed in both anti–TNF-naïve and -IR pts, with better responses in anti-TNF-naïve pts (Table, ACR20). SEC LD provided earlier and better responses than the no LD regimen from Wk 4 onwards across most endpoints; this trend was most pronounced for higher hurdle endpoints and in the TNF-IR group. The most common AEs up to Wk 16 were nasopharyngitis (11.4% and 9.7% vs. 13.2%) and upper respiratory tract infections (6.1% and 6.2% vs. 5.3%) for LD, no LD vs. PBO, respectively. Exposure adjusted incidence rates through 52 Wks for SEC for AEs of interest were: Crohn’s disease (0.4), malignancies (1.1) and major adverse cardiac events (0.4). No deaths were reported.

Conclusions: SEC 150mg administered with and without LD demonstrated significant and sustained improvements in the signs and symptoms of PsA. Numerically greater and earlier responses were observed with LD mainly in the TNF-IR pts and the higher hurdle endpoints. The safety profile was similar with and without LD, and consistent with previous reports.

CONCURRENT ORAL SESSIONS

66

EDUCATIONAL NEEDS OF LATIN-AMERICAN LUPUS PATIENTS: INSIGHTS FROM AN ONGOING FACEBOOK PROGRAM

Y. Fuentes-Silva1,2, C. Acosta2, C. Elera-Fitzcarrald3, S. Ibañez4, E. García-Carrión5, C. Reátegui-Sokolova3, B. Pons-Estel6, and C. Drenkard7. 1Universidad de Oriente, Ciudad Bolívar, Bolívar, Venezuela; 2Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Bolívar, Venezuela; 3Hospital Guillermo Almenara Irigoyen, Lima, Perú; 4Sanatorio Güemes, Buenos Aires, Argentina; 5Hospital Dr. Raúl Leoni, Ciudad Guayana, Bolívar, Venezuela; 6Centro Regional de Enfermedades Autoinmunes y Reumatología (CREAR), Sanatorio Parque, Rosario, Santa Fe, Argentina; 7Emory School of Medicine, Atlanta, GA, USA.

Objectives: Education is critical to support effective management in people with lupus. We described the educational needs of Latin-American patients with lupus and explored associations with sociodemographic characteristics.

Methods: We conducted a 6-month survey to evaluate Let’s Talk about Lupus (Hablemos de Lupus), a Facebook (FB) program in Spanish that aims at educating the Latin-American population living with lupus. Since May 2017, FB/Hablemos de Lupus delivers information about lupus and self-management through animated videos (AV) and live videochats (LVC) with providers. Using open-ended questions, we asked users to propose topics for AV and LVC, and overall suggestions (OS). Using 38 predefined topics, we codified up to five needs (N1 to N5) per responder, which were classified in eight themes within three domains: lupus knowledge, self-management/quality of life, and lupus awareness/healthcare resources. We used Chi-square test to examine associations between needs and sociodemographic characteristics.

Results: Within 20 days of its initial posting, 936 followers responded the survey, and 806 (86%) of them reported to have lupus (mean age 37 ± 11 years, 97% females, 48% ≤ 5 years since diagnosis). Most respondents were from North America (32%), followed by the South Cone (31%), Bolivarian Region (24%) and Central American/Caribbean (10%). While 51% of the sample achieved a university degree, only 36% reported working fulltime. There were 579, 582, and 187 respondents that proposed at least one topic for AV, LVC, and OS, respectively. Table 1 shows the frequency of N1 to N5. There were not significant associations between educational needs and sociodemographic factors (age, gender, region, education, occupation, disease duration).

TABLE 1
TABLE 1:
Educational Needs of Latin-American Patients with Lupus

Conclusions: There is consistency in the educational needs of Latin-American lupus patients across regions and sociodemographic groups suggesting that there is a substantial gap in the education of this population. The role of social media-based education on patients’ empowerment and behavioral change warrants further assessment.

170

RADIOGRAPHIC KNEE OSTEOARTHRITIS IN PATIENTS COMPLAINING OF KNEE PAIN: ULTRASOUND FEATURES

I.J. Gandino, M. Brom, S. Ruta, M. Scolnik, J. Zacariaz, J. Marin, J. Rosa, R. Garcia-Monaco, and E.R. Soriano. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Objectives: To date, the diagnosis of knee osteoarthritis (OA) is based on clinical examination and radiological features. Our objective was to evaluate the diagnostic test properties of ultrasound (US) for the detection of radiographic knee OA.

Exclusion criteria were: Younger than 18 years of age, history of knee surgery or trauma, severe knee deformities and a corticosteroid injection within the preceding 2 months. US examinations were performed by an experienced rheumatologist, blinded to clinical and radiological data, using a MyLab 70 machine (Esaote) provided with a multi-frequency linear transducer (4–13 MHz). Standardized scanning method was adopted in order to evaluate the following US abnormal findings: osteophytes (protrusions at the joint margin seen in two planes and visualized as either proximal or distal to the joint) and degenerative femoral hyaline cartilage involvement (presence of at least two of the following: loss of sharpness of the cartilage margins, loss of homogeneity of the cartilage layer and cartilage thinning focal or extend to the entire cartilaginous layer)

Weight-bearing anteroposterior (AP) and lateral knee radiographs were read by an experienced rheumatologist, blinded to the clinical and US data, who determine the presence or absence of radiological degenerative changes and classified the severity of knee OA using Kellgren-Lawrence (KL) grading scale.

Results: 281 patients (mean age 64 ± 17 years, 173 (61,6%) female) were included for a total of 322 knees evaluated (41 patients complained of bilateral knee pain). Both the presence of osteophytes and/or femoral hyaline cartilage involvement detected by US were more frequent in those knees with radiographic changes indicative of OA regardless of its severity according with the KL grading scale (Table 1).

TABLE 1
TABLE 1:
Frequency of abnormal US findings according to radiographic knee OA features

Table 2 shows the diagnostic test properties of the US abnormal findings for the detection of knee OA using radiological data as reference method.

TABLE 2
TABLE 2:
Diagnostic properties of the US abnormal findings for the detection of knee OA using radiological data as the reference method.

Conclusions: US demonstrate an excellent sensitivity with an adequate specificity for the detection of radiographic knee OA. US femoral hyaline cartilage involvement and/or US osteophytes showed the best sensitivity while isolated US osteophytes showed the best specificity. US could be used in patients with knee pain when OA is suspected.

211

EFFICACY AND SAFETY OF CONTINUING VERSUS WITHDRAWING ADALIMUMAB IN MAINTAINING REMISSION IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

R. Landewé1, J. Sieper2, P. Mease3, R.D. Inman4, X. Wang5, M. Li5, A. L. Pangan5, and J. K. Anderson4. 1University of Amsterdam, Amsterdam, Netherlands; 2Charité Universitätsmedizin Berlin, Berlin, Germany; 3Swedish Medical Center and University of Washington, Seattle, WA, USA; 4University of Toronto, Toronto, Canada; 5AbbVie, North Chicago, IL, United States.

Objectives: It is not known whether TNF blockers can be stopped in non-radiographic (nr-axSpA) patients who are in remission. ABILITY-3 (NCT01808118), reported here, assessed if ADA can be discontinued or should be continued in nr-axSpA pts in sustained remission after a 28-wk open-label period.

Methods: ABILITY-3 enrolled adult pts diagnosed with nr-axSpA, fulfilling ASAS criteria but NOT modified New York criteria who had objective evidence of active MRI inflammation in the SI joints or spine or elevated high-sensitivity CRP at screening, active disease at baseline (ASDAS ≥2.1, BASDAI ≥4, total back pain ≥4), and inadequate response to ≥2 NSAIDs. Pts who achieved ASDAS inactive disease (ASDAS <1.3) with open-label ADA 40 mg every other wk at wk 16, 20, 24, and 28 were randomized to 40-wk, double-blind PBO (withdrawal) or ADA (continuation) in period 2. The primary efficacy endpoint was the proportion of patients who did not experience a flare (ASDAS ≥2.1 at 2 consecutive study visits) during period 2. Secondary endpoints were also assessed up to wk 68 (nonresponder imputation).

Results: Of 673 enrolled pts, 305 (45%) were randomized to double-blind treatment. A significantly greater proportion of patients treated with ADA vs. PBO had no flares (70% vs. 47%; P < 0.001) at wk 68; the relative risk of flare with treatment withdrawal was 1.77. Time to flare analysis showed significantly lower risk of flare for ADA vs. PBO. At wk 68, significantly greater proportions of ADA vs. PBO patients achieved secondary endpoints, except for HAQ-S (Table). Among pts who received ADA at any time, 77% reported adverse events (AEs) and 4% reported a serious AE; nasopharyngitis (17%), upper respiratory tract infection (12%), worsening of axSpA (9%), headache (8%), and diarrhea (6%) were the most common. During period 2, incidence of AEs was similar for ADA and PBO (65% vs. 69%), incidence of serious AEs was higher for PBO vs. ADA (7% vs. 1%), and the most common AEs in both the ADA and PBO groups were nasopharyngitis (16% vs. 13%), upper respiratory tract infection (13% vs. 8%), and worsening of axSpA (6% vs. 14%; none serious).

TABLE 1
TABLE 1:
Outcomes at Week 68

Conclusion: In pts with nr-axSpA who achieved sustained remission with ADA, continued therapy was associated with significantly more patients maintaining remission and lower disease activity than treatment withdrawal. These results support the continuation of ADA therapy after achievement of sustained remission. Safety findings were consistent with the established safety profile of ADA.

358

ULTRASOUND DEFINITIONS AND SCORES FOR PEDIATRIC ENTHESIS

J. Roth1, L. Barzola2, L. Campos3, C. Hernandez4, D. Petry5, L. Ventura4, and T. Cazenave6. 1Childrens Hospital of Eastern Ontario and University of Ottawa, Ontario, Canada; 2Reumatologia, Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina; 3Pediatric Rheumatology Unit, Instituto da Criança - Hospital das Clínicas, University of São Paulo Medical School, Sao Paulo, Brazil; 4Laboratorio de ultrasonido músculo esquelético y articular. Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, México City, México; 5Department of Pediatrics and Division of Rheumatology, Department of Medicine, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil; 6Instituto de Rehabilitacion Psicofisica, Buenos Aires, Argentina.

Background and Aims: Musculoskeletal ultrasound (MSUS) is increasingly being utilized in children but validation has been limited to synovitis so far. The enthesis is an equally important structure and pediatric specific definitions as well as reliable scoring systems are needed given the unique pediatric anatomy. The aim of this study was to develop and assess reliability of B-Mode and Doppler definitions and scoring systems for the pediatric enthesis.

Methods: As part of the PANLAR ultrasound group, seven rheumatologists developed B-Mode and Doppler definitions for the assessment of lower extremity entheses in children. This was done through a comprehensive literature review followed by a practical exercise and consensus process. Similarly, a Doppler scoring system was developed through both literature review and consensus process and subsequently validated by a practical exercise. A total of six children (3 healthy, 3 enthesitis related juvenile arthritis) were scanned during this exercise by six rheumatologists each and all images were analyzed by all participants. B-Mode assessments included thickness, hypoechogenicity, erosions, enthesophytes and bony irregularities and increased blood flow was assessed with Power Doppler. The following entheses were assessed: Quadriceps tendon into the patella, proximal and distal patella tendon and Achilles tendon. Agreement with the definitions was determined using definition as 4 or 5. Presence of structural changes on B-Mode were scored dichotomously as present and absent and agreement between raters on the Doppler scores was determined using two-way single score intraclass correlation coefficients (ICC).

Results: An overall definition for findings of the healthy and pathologic enthesis on B-mode, separate definitions for hypoechogenicity and thickening and a definition for Doppler findings reached 89 % agreement among the participants. Agreement on the presence and absence of structural changes was 92 % but the presence of structural changes was overall low. ICC for all Doppler images was 0.78 (CI 0.70-0.85) but Doppler signals were present in both healthy children and children with enthesitis related arthritis and even among the children with enthesitis related arthritis in entheses without B-mode changes as well as those with abnormal B-mode findings.

Conclusion: B-Mode and Doppler definitions for the healthy and pathologic entheses in children as well as a Doppler Scoring system were developed and validated through a consensus process. The presence of structural changes was overall low and Doppler signals may be present in a relatively large proportion of healthy entheses as well. Future studies will address criteria to differentiate findings suggestive of pathology from physiologic findings.

163

PATTERNS OF CHANGE OF A SECOND BIOLOGICAL DMARD IN A COHORT OF RHEUMATOID ARTHRITIS PATIENTS

R. Rolón Campuzano1, AL Coronel Ale1, O.L. Cerda1, F. Dal Pra1, E.E. Schneeberger1, M.A. Correa1, M.G. Rosemffet1, E. Buschiazzo2, R. García Salinas3, S.B. Papasidero4, B.I. Barrios4, Ficco H. Maldonado5, and G. Citera1. 1Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina; 2Hospital Señor del Milagro, Salta, Argentina; 3Hospital Italiano La Plata, Buenos Aires, Argentina; 4Hospital General de Agudos “Dr E Tornú”, Buenos Aires, Argentina; 5Hospital San Antonio de Padua, Río Cuarto, Córdoba, Argentina.

Objectives: To evaluate the survival of the second biological disease modifying anti-rheumatic drug (bDMARD), the causes of its discontinuation and the time that had elapsed between the discontinuation of the first bDMARD and the beginning of the second one.

Methods: Patients ≥ 18 years of age who met ACR/EULAR 2010 criteria for RA and who had started their second bDMARD between 01/2006 and 12/2017 were included. Socio-demographic variables (age, sex, employment status, marital status, health coverage, education, number of cohabitants), and clinical variables (comorbidities, smoking status, date of symptoms onset, the time elapsed between the interruption of the first bDMARD and the beginning of the second bDMARD and the response to this second bDMARD) were obtained. Statistical analysis: Chi2 test, Student’s t test and ANOVA. Cumulative survival was evaluated using Kaplan Meier curves and log rank test for comparisons.

Results: 347 patients were included, with a median age of 57.8 years (IQR: 48–65), 89.6% were women, 96.5% were RF positive and 60.8% were anti-CCP antibodies positive. 70.6% had health coverage, 16,3% were smokers and 51.2% had some comorbidities. 187 (53.9%) patients discontinued the 1st b-DMARD of which 96 (27.6%) started a 2nd bDMARD (Abatacept, 41,2% Etanercept 25%, Adalimumab 16.7%, Tocilizumab 14.6%, Certolizumab 6.3% and Rituximab 1%). The time between the 1st and the 2nd bDMARD was 9.5 months (SD 17.8). Thirty-eight patients (41.3%) discontinued the 2nd bDMARD, being the causes of discontinuation: lack of efficacy 35.9%, inability to get the compound 30.8% and adverse events (AE) 20.5%. The median survival time of the 2nd bDMARD was 11 months (95% CI: 4–17.9), with no significant difference between the different drugs. In almost 90% of patients who had received an anti-TNF agent as 1st bDMARD, the cause of its discontinuation was inability to get the compound; a TNF inhibitor was started a again. On the other hand, we opted for a change in the compound’s mechanism of action for those patients who discontinued a bDMARD due to AE (69.2%) or lack of efficacy (77.7%). There was no difference in the survival of the 2nd bDMARD with respect to its use as monotherapy or combined with c-DMARD. In those patients, in whom the cause of discontinuation of the 1st bDMARD was AE, the survival of the second bDMARD was significantly lower (3.6 months) compared to those who stopped the 1st bDMARD due to lack of efficacy (21.5 months) or inability to get the compound (20.5 months), Log Rank: p = 0.03.

Conclusions: The survival of the 2nd bDMARD was 11 months; no difference between the different bDMARDs was observed. The most frequent cause of treatment discontinuation was lack of efficacy. For most patients who failed an anti-TNF or presented an AE to it, a change in the compound’s mechanism of action was preferred. The only variable associated with a decreased survival of the 2nd bDMARD was the discontinuation of the 1st one due to an AE.

251

CORTICAL AND TRABECULAR BONE RESPONSES IN THE PROXIMAL FEMUR OF WOMEN WITH OSTEOPOROSIS TREATED WITH DENOSUMAB OR ZOLENDRONIC ACID USING 3D MODELLING TECHNIQUES OBTAINED FROM DXA

F. Cons-Molina*1, M. Feuchter1, L. Bejarano1, D. Wiluzanski2, C. Altieri2, E. Romero2, J.L. Mansur3, Y. Martelli4, and L. Humbert4. 1Centro de Investigación en Artritis y Osteoporosis, Mexicali, México; 2CENTROSEO, Montevideo, Uruguay; 3Centro de Endocrinología y Osteoporosis, La Plata, Argentina; 4Galgo Medical, Barcelona, Spain.

Objectives: The purpose of this study was to assess the changes that occur after 2 years of treatment with Denosumab(DMAb) or Zolendronic acid (ZOL) in the areal bone mineral density (aBMD) obtained by DXA and in volumetric BMD (vBMD) evaluating 3 bone compartments (trabecular, cortical and integral). All of them were assessed with 3D modelling techniques from a standard proximal femur DXA (hip-DXA).

Methods: We examined the data from 260 patients with postmenopausal osteoporosis. The cohort was stratified by treatments for comparison purposes: DMAb naïve n=50; DMAb Pretreated n=50; Naïve treatment n=30, Zolendronic Acid (ZOL) n=30. Patients came from 3 osteoporosis care centers in Mexico, Uruguay and Argentina. From a hip-DXA acquisition in addition to aBMD, volumetric trabecular total (vBMDTrab), cortical surface density(CSD) and volumetric BMD Integral (vBMDInt) were assessed using a 3D-Shaper software (Galgo Medical, Spain). The changes observed at 2 years were evaluated in terms of percent change in vBMD. Paired Students’ t tests were used to compare parameters from baseline. All hip-DXA were acquired using GE-Prodigy devices.

Results: After 2 years, in the naïve treatment group, a significant decrease was observed in all 3D parameters when compared to baseline, additionally a decrease in aDMO was also observed. In the ZOL group only a significant increase was observed in CSD (2.3%) and in vBMDInt (2.4%). A greater trabecular response was observed in DMAb naïve group vBMDTrab (6.9%) compared to DMAb Pretreated (2.4%). The cortical response(CSD) was higher in both DMAb groups compared to ZOL (2.6%, 2.8% vs.2.3%) whereas trabecular response (vBMDTrab) was only superior in DMAb naïve (6.9% vs.2.8%). Changes in aBMD were greater in both DMAb groups (2.5%, 2.0% vs.1.3%) in ZOL group. The response was analyzed in both DMAb groups divided in tertiles vBMD at baseline (low, medium, high) for all 3D parameters showing only in DMAb naïve group a greater response in those from THE lowest tertile vs. the medium and high (vBMDTrab 13.3%, 4.0%, 0.2%), CSD 6.2%, 2.2%,1.3%), vBMDInt (5.7%, 2.5%, 0.1%). On the other hand, DMAb Pretreated group showed no differences between tertiles in response to treatment (vBMDTrab (2.8%, 1.4%, 2.5%), CSD (4.0%, 3.3%, 3.2%), vBMDInt (3.8%, 2.6%, 2.3%).

Conclusions: As expected, treatment naïve group after 2 years showed a significant loss in aBMD & vBMD; aBMD response after 2 years of ZOL (1.3%) and DMAb (2.5%) was lower than expected. Significant vBMD increases were observed in cortical & trabecular compartments in the ZOL group and the DMAb groups. Applying 3D modelling techniques, may allow us to obtain better results using DMAb in the subgroup of patients at high risk of fractures. 3D modelling techniques are a promising new technology for identification/monitoring of vBMD changes in patients with osteoporosis. More studies are required to confirm these results.

212

EPIDEMIOLOGY AND MANAGEMENT PRACTICES IN CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: A LATIN AMERICA SURVEY

J. C. Ferreira1, V. C. Trindade1, G. Espada2, Z. Morel3, E. Bonfá4, C. S. Magalhães5, and C. A. Silva1. 1Children’s Institute, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; 2Hospital de Niños Dr Ricardo Gutierrez, Buenos Aires, Argentina; 3Pediatric Service, Hospital de Clinicas, Universidad Nacional De Asuncion, Paraguay; 4Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; 5São Paulo State University (UNESP) – Faculdade de Medicina de Botucatu.

Objectives: The objective of the present cross-sectional survey study was to assess childhood-onset systemic lupus erythematosus (cSLE) patients’ reports regarding the epidemiology, classification criteria, disease activity and other instruments used in clinical practice, laboratory and other exams availability, general supportive care, drugs availability, infections, non-live vaccines use, issues observed in adolescents, reproductive health issues and transition-focused program to adult care among Latin America Pediatric Rheumatologist (LAPR).

Methods: A cross-sectional study consisting of a web-base survey about cSLE practices was carried out among 288 LAPR from 21 countries. All physicians are members of the Pan-American League of Association for Rheumatology (PANLAR).

Results: The response rate of web-based survey by LAPR was 170/288(59%); the majority of the responders worked at University Hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas the damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging and biopsies were generally available (>75%); however, there was low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (>75%), except for belimumab (11%). Endemic illnesses were reported by LAPR in at least one cSLE patient during the previous year: tuberculosis (16%) and Hansen’s disease (2%). Emerging mosquito-borne diseases were also reported: Dengue (20%), Chikungunya (11%) and Zika (8%). Groups were further divided in two, according to the number of cSLE patients followed by LAPR in the last year: group A (25 patients) and group B (<25 patients). Frequencies of condom use in combination with other contraceptive methods were significantly higher in group A than B (69% vs. 48%, p = 0.01). The frequencies of reported pregnancies (50% vs. 16%, p < 0.001) and non-adherence to therapy were significantly higher in group A (100% vs. 93%, p = 0.023). Alcohol intake (42% vs. 21%, p = 0.004) and illicit drug use (19% vs. 5%, p = 0.007) were also reported more frequently reported by group A in at least one cSLE patient.

Conclusion: This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy of cSLE by LAPR, probably related to their high rate of practicing at tertiary care places (University Hospitals). Adherence to therapy, pregnancy and substance abuse were identified as major challenges in this population, particularly in larger centers.

76

IS THERE ACHILLES TENDON DAMAGE IN RHEUMATOID ARTHRITIS PATIENTS?

M. Fornaro1, T. Cazenave1, M.C. Orozco1, M.V. Martire1, E. Reyes1, H. Schmulevich1, G. Citera1, and M.G. Rosemffet1. 1Instituto de Rehabilitación Psicofísica, CABA, Buenos Aires. Argentina.

Background: Ankle involvement is common in Rheumatoid Arthritis (RA). It has been reported that more than 90 % of patients develop ankle symptoms over the course of the disease. In spite of this, it remains a neglected anatomical area since clinical implications of ankle involvement appear to be continuously underestimated.

Objectives: To examine the ultrasonographic (US) features of the Achilles Tendon (AT), paratenon (AP) and enthesis in patients with RA and compare them to those of healthy athletes. To define the relationship between these findings and clinical and physical therapy parameters.

Methods: Consecutive patients aged ≥18 with RA according to ACR/EULAR 2010 criteria were included. We recorded socio-demographic data, disease duration, physical activity and Body Mass Index (BMI). Clinical evaluation relied on the Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ), Routine Assessment of Patient Index Data 3 (RAPID 3), as well as on a visual analog scale (VAS), and entheseal pain. Separately, AT thickness, AP thickness, and echogenicity were examined bilaterally with US in 60 ankles from 30 RA patients and 36 from 18 controls. US examinations were performed by two experienced rheumatologists. To evaluate AT involvement, the Madrid Sonographic Enthesitis Index (MASEI) was used to assess elementary lesions: bursitis, calcification, erosion, Power Doppler (PD), thickening of tendon, and structural change. Statistical analysis: Standard descriptive results were expressed as means ± standard deviation (SD). Chi-square test and Fisher’s exact tests were used for categorical variables whereas T tests were used for continuous variables.

Results: For the 30 RA patients, their mean (±SD) age and disease duration were 58.3 ± 9.5 and 4.5 ± 5.9 years, respectively. 30% of the RA patients had foot and ankle pain at the intake visit. The mean (±SD) DAS28, HAQ and RAPID3 were 3.46 ± 0.9, 0.9 ± 0.6, and 11 ± 6.5, respectively. 26.7% of the patients were obese and 30% performed some physical activity. By US, at least 1 AT lesion was found in all RA patients. The most frequent US abnormality in these patients was tibialis posterior tenosynovitis followed by peroneus longus tenosynovitis. A statistically significant difference was found between RA patients and healthy controls in mean (±SD) MASEI (3.56 ± 2.4 vs. 2.33 ± 1.7, p = 0.01), and sub-item scores such as: structural changes (0.66 ± 0.4 vs. 0.2 ± 0.4, p = <0.01), erosion (0.8 ± 1.3 vs. 0.02 ± 0.16, p = <0,01) and PD (0.3 ± 0.9 vs. 0.02 ± 0.16, p = 0.03).

Conclusions: Achilles tendon involvement is rather frequent in RA patients. The MASEI score was significantly higher in patients with RA compared with those of the athletes.

133

TOBACCO EXPOSURE AND ITS RELATIONSHIP WITH SEVERE DAMAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

M.A. Cosatti1, S.A. Muñoz2, M. Natalia Tamborenea3, M. García4, A. Curti5, A. Cappuccio6, O. Rillo7, P.M. Imamura8, E. Schneeberger9, F. Dal Pra9, M. Ballent10, M.L. Cousseau11, J. Velasco Zamora12, V. Saurit13, S. Toloza14, M.C. Danielsen15, V.I. Bellomio16, C. Graf17, S. Paira18, J. Cavallasca19, B. Pons Estel20, J.L.C. Moreno21, M. Díaz22, P. Alba23, M. Verando24, G. Tate3, E. Mysler3, J. Sarano25, E.E. Civit26, F. Risueño27, P. Álvarez Sepúlveda28, M.S. Larroude6, M.F. Méndez29, A. Conforti30, D. Sohn31, C.A. Helling3, S. Roverano18, S. Malm-Green24, D. Medina Bornachera32, A. Alvarez32, A. Eimon1, G. Pendón33, M. Mayer34, J. Marin8, C. Catoggio1, and C.N. Pisoni1. 1CEMIC, Ciudad Autónoma de Buenos Aires; 2Hospital General de Agudos Juan A. Fernández, Ciudad Autónoma de Buenos Aires; 3Organización Médica de Investigaciones (OMI), Ciudad Autónoma de Buenos Aires; 4Hospital Interzonal General de Agudos “General José de San Martín”, Ciudad de La Plata, Provincia de Buenos Aires; 5Hospital de Clínicas “José de San Martín”, Ciudad Autónoma de Buenos Aires; 6Hospital Cesar Milstein, Ciudad Autónoma de Buenos Aires; 7Hospital General de Agudos “Dr. Ignacio Pirovano”, Ciudad Autónoma de Buenos Aires; 8Hospital Italiano, Ciudad Autónoma de Buenos Aires; 9Instituto de Rehabilitación Psicofísica (IREP), Ciudad Autónoma de Buenos Aires; 10Hospital Ramón Santamarina, Tandil, Provincia de Buenos Aires; 11Policlínica Privada Paz, Tandil, Provincia de Buenos Aires; 12Instituto Médico CER, Quilmes, Provincia de Buenos Aires; 13Hospital Privado Centro Médico de Córdoba, Córdoba, Provincia de Córdoba; 14Hospital Interzonal San Juan Bautista, Fernando del Valle de Catamarca, Provincia de Catamarca; 15Hospital Regional Ramón Carrillo, Santiago del Estero, Provincia de Santiago del Estero; 16Hospital A.C. Padilla, Tucumán, San Miguel de Tucumán, Provincia de Tucumán; 17Centro Médico Mitre, Paraná, Provincia de Entre Ríos; 18Hospital José MaríaCullen, Santa Fe, Provincia de Santa Fe; 19Hospital José Bernardo Iturraspe, Santa Fe, Provincia de Santa Fe; 20Sanatorio Parque, Rosario, Provincia de Santa Fe; 21Instituto Médico CER, San Juan, Provincia de San Juan; 22Centro Traumatológico Bariloche, San Carlos de Bariloche, Provincia de Río Negro; 23Hospital de Córdoba, Universidad Nacional de Córdoba, Provincia de Córdoba; 24Hospital General de Agudos Bernardino Rivadavia, Ciudad Autónoma de Buenos Aires; 25Instituto de Investigaciones Médicas “Dr. Alfredo Lanari”, Ciudad Autónoma de Buenos Aires; 26Hospital del Carmen, Godoy Cruz, Provincia de Mendoza; 27Itemédica, Bahía Blanca, Provincia de Buenos Aires; 28Hospital de San Isidro, San Isidro, Provincia de Buenos Aires; 29Consultorios Pilar, Puerto Madryn, Provincia de Chubut; 30OSEP Mendoza, Mendoza, Provincia de Mendoza; 31Consultorio privado de reumatología, Escobar, Provincia de Buenos Aires; 32Hospital Penna, Ciudad Autónoma de Buenos Aires; 33Hospital Ricardo Gutiérrez, La Plata, Provincia de Buenos Aires; 34Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires. All centers are from Argentina.

Objective: To assess the relationship between smoking exposure and organ damage accrual measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) in consecutive Argentinean patients with systemic lupus erythematosus (SLE).

Methods: 623 SLE patients (fulfilling ≥4, 1997 ACR criteria) were included in this cross-sectional study. Sociodemographic and disease related variables, SDI score and smoking status were collected. Patients currently smoking were considered “smokers” and those who had never smoked or those who had previously smoked: “non-smokers”. The SDI was divided into 2 categories < 3 and ≥ 3 severe damage.

Results: Eighty-nine percent of the 623 patients were women, median age was 38 (IQR 30–46) years. Eighty-four percent were non-smokers and 16 % were smokers. Fifty- seven percent were white, and 43% were non-white (mestizo and Amerindian). Seventy-four percent had >12 years of formal education. The median disease duration was 9 years (IQR 4–13). The median number ACR criteria met were 6 (IQR 5–7); the mean SDI score was 1.16 (SD 1.75) for non-smokers and 1.43 (SD 1.89) for smokers (p = 0.915).

When the ACR criteria were compared between smokers and non-smokers only discoid lupus was significantly associated with smoking exposure.

Eighty-three percent of patients had SDI <3 and 17 % had ≥ 3. Twenty one percent of patients with SDI ≥ 3vs.15% of patients with <3 SLICC-SDI were smokers (p= 0.081).

Univariable analyses comparing demographical and clinical characteristics of both groups are depicted in Table 1.

In the multivariable regression analysis considering an SDI score ≥3 as the dependent variable (adjusting by smoking exposure, age, sex, race, disease duration, > 12 years of education, corticosteroids, CP, AZA and HCQ exposure), we found that smoking (OR 1. 90, CI 95% 1.04- 3.46, p 0.035), age (OR 1.33, CI 95% 1.00-1.75, p 0.044), and CP exposure (OR 2.64, CI 95% 1.41-4.97, p 0.002) were associated with an SDI ≥3.

Conclusion: Tobacco exposure, older age and cyclophosphamide use were associated with an SDI ≥3.

226

WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT IN PRIMARY SJOGREN SYNDROME (pSS)

M. Bejarano1, A. Secco1, A. Catalán Pellet1, M. Mamani1, S. Papasidero2, J. Demarchi2, CA Asnal3, CE Crow3, A. Nitsche3, L. Encinas4, F. Caeiro4, C. Gobbi5, E. Albiero5, A. Gomez6, JC Barreira6, R. Aguila Maldonado7, M. Garcia7, M.A Gallardo8, E. Soriano8, L. Raiti9, G. Salvatierra10, and A. Eimon11. 1Hospital Rivadavia, Ciudad Autónoma de Buenos Aires, Argentina; 2Hospital Tornú, Ciudad Autónoma de Buenos Aires, Argentina; 3Hospital Alemán, Ciudad Autónoma de Buenos Aires, Argentina; 4Hospital Privado de Córdoba, Córdoba, Argentina; 5Hospital Córdoba, Córdoba, Argentina; 6Hospital Británico, Ciudad Autónoma de Buenos Aires, Argentina; 7Hospital San Martín de La Plata, La Plata, Argentina; 8Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; 9Clínica Bessone, Ciudad Autónoma de Buenos Aires, Argentina; 10IPRI, Santiago del Estero, Argentina; 11CEMIC, Ciudad Autónoma de Buenos Aires, Argentina.

Objectives: To describe the work productivity and activity impairment in adult patients diagnosed with pSS. To evaluate the potential association between activity impairment and clinical manifestations, depression and anxiety. To compare activity impairment according to educational level and site of care (public or private centers) as surrogates of socio-economic status.

Methods: We included patients with diagnosis of pSS according to the American-European criteria (2002) treated at 11 private and public Argentine rheumatologic centers between November 2013 and December 2016. All patients with another autoimmune rheumatic or chronic disease were excluded. The WPAI questionnaire was used.

Design: Observational, analytic, cross-sectional study. For the descriptive analysis, continuous variables were informed as means and SD. Categorical variables were reported in percentages. A multivariable linear regression model was performed, taking impaired activity due to health as the dependent variable, adjusted by potential confounders. The performance of the model was evaluated (assumptions, atypical observations, multicollinearity). If linearity and/or homoscedasticity was not fulfilled transformation of variables or robust regression was performed, as appropriate.

Results: 252 patients were included, 98.38% were female, mean age of 52.64 years (+/−14.84). The mean percentage of working time lost due to health was 15.74% (+/−30.12. 95% CI: 9.58- 21.90); disability work due to health was 27.18% (+/−30.19. 95% CI:21.25-33.11), the total disability percentage due to health was 33.70% (+/−35.76. 95% CI: 26.39-41.01) and impaired activity due to health was 34.17% (+/−30.94. 95% CI:30.35-37.99). The following variables showed significantly and independent association in the multivariable analysis of robust regression: xerostomia (β coefficient: 0.25. 95%CI: 0.13-0.37), arthritis (β coefficient: 11.15. 95%CI:0.55-21.74), mild depression (β coefficient: 8.77. 95%CI: 1.43-16.12), moderate depression (β coefficient: 25.47. 95%CI: 13.84-37.10), moderately severe depression (β coefficient: 36.92. 95%CI: 26.91-46.93), severe depression (β coefficient: 32.12. 95%CI: 16.31- 48.10). The mean impaired activity due to health was 38.24% (+/− 30.67) in patients treated in public centers vs 28.04% (+/−30.61) on private centers, being this difference statistically significant. No statistically significant differences were found between patients with full or higher secondary education ((32.96% (+/− 31.03)) vs patients with lower educational level [(35.73% (+/−31.08)]

Conclusion: We found all WPAI scales to be compromised. Arthritis, xerostomia and depression were significantly and independently associated with impaired activity due to health. Patients treated in public centers presented a greater impaired activity. This could be an expression of the impact of the socio-economic status.

320

CLINICAL PREDICTORS OF REMISSION AND LOW DISEASE ACTIVITY IN LATIN AMERICAN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: DATA FROM THE GLADAR COHORT

Rocio Gamboa-Cárdenas1, Manuel Ugarte-Gil1, Loreto Massardo2, Mónica Sacnun3, Verónica Saurit3, Mario Cardiel4, Enrique Soriano3, Cecilia N Pisoni3, Claudio Galarza5, Carlos Rios5, Sebastiao C Radominski6, Geraldo Castelar6, Rozana Coconelli Mezquita6, Inês Guimaraes da Silveira6, Cristiano A Zerbini de Freitas6, Carlo V Caballero7, Adriana Rojas-Villarraga7, Elías Forero Illera7, Marlene Guibert Toledano8, Francisco Ballesteros2, Rubén Montufar9, Vianna J Khoury10, Janitzia Vazquez-Mellado4, Jorge Esquivel4, Ignacio Garcia De La Torre4, Leonor A Barile-Fabris4, Lilia Andrade Ortega4, José F Díaz-Coto11, Raquel Teijeiro12, Angel Achurra-Castillo13, Maria H Esteva14, Graciela S Alarcón15, and Bernardo A Pons-Estel3. 1GLADAR Peru; 2GLADAR Chile; 3GLADAR Argentina; 4GLADAR Mexico; 5GLADAR Ecuador; 6GLADAR Brazil; 7GLADAR Colombia; 8GLADAR Cuba; 9GLADAR El Salvador; 10GLADAR Dominican Republic; 11GLADAR Costa Rica; 12GLADAR Uruguay; 13GLADAR Panama; 14GLADAR Venezuela; 15University of Alabama at Birmingham, USA.

Objectives: Achieving remission or low disease activity (LDA) are treatment goals in rheumatoid arthritis (RA) and identifying their predictors in early disease is relevant in our region. The objective of this study was to identify the baseline predictive factors of remission and LDA in patients from GLADAR, at one and two years from cohort entry.

Methods: The GLADAR cohort, initially constituted to describe the use of disease modifying antirheumatic drugs (DMARDS) in the region, includes consecutive RA patients with disease <1 year in duration from 46 centers in 14 Latin American countries. For these analyses, patients with complete clinical and laboratory assessments at the baseline, one- and two-year follow up visits were included. Remission and LDA were defined by the 28-joint disease activity score (DAS28-ESR) obtained at one and two years (<2.6 and ≤ 3.2, respectively). Gender, age at diagnosis, socioeconomic status (by the Graffar scale), ethnicity, rheumatoid factor (RF) positivity, disability (measured with the HAQ-DI), DMARDs and corticosteroid use were examined as potential predictive factors of these outcomes. Continuous variables were expressed as means and SDs, and categorical variables as percentages and 95% confidence intervals (95% CIs). Univariable and multivariable binary logistic regression models were examined in order to determine the predictors of remission and LDA/remission at 1- and 2-years after cohort entry.

Results: Five hundred and twenty-six patients were included, 451 (85.7%) patients were female; the mean (SD) age at diagnosis was 45.9 (13.7) years; 384/498 patients (77.1%) were RF positive, the mean baseline DAS28-ESR was 6.1 (1.6). Before the baseline visit, 346 (65.8%) patients have received glucocorticoids, 413 (78.5%) at least one DMARD [258 (49.0%) one DMARD and 155 (29.5%) two DMARDS] and 5 (1.0%) patients had received at least one biologic compound. Remission was met by 103 (19.6%) and LDA/remission by 175 patients (33.3%) at the 1-year follow up. Two hundred and ninety-four patients were followed for at least two years; remission and LDA/remission were met by 72 (24.5%) and 117 (39.8%) of these patients respectively. Predictors of remission and LDA/remission at 1 and 2-years of follow up are depicted in Table 1. A lower DAS28-ESR baseline score predicted remission and LDA/remission after one and two years of follow up.

TABLE 1
TABLE 1:
Clinical Predictors of Remission and LDA/remission in the GLADAR Cohort

Conclusions: We have now identified clinical predictors of remission and LDA/remission in Latin American patients with early RA from the GLADAR cohort. A lower disease activity at the baseline evaluation consistently predicted remission and remission/LDA. Our data suggest that an early diagnosis and a more aggressive treatment approach at disease onset is needed to prevent the deleterious effects of persistently active RA.

365

COST-EFFECTIVENESS OF SECUKINUMAB VERSUS OTHER BIOLOGICS IN THE TREATMENT OF PSORIATIC ARTHRITIS: AN ARGENTINEAN PERSPECTIVE

Eleonora Aiello1, Pablo Manuel Bianculli2, Devarshi Bhattacharyya3, Praveen Gunda3, and Gustavo Citera4. 1Independent Consultant, Buenos Aires, Argentina; 2Novartis Argentina S.A., Buenos Aires, Argentina; 3Novartis Healthcare Pvt. Ltd., Hyderabad, India; 4Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina.

Objective: Psoriatic Arthritis (PsA) is a chronic, systemic inflammatory disease which primarily affects the peripheral joints, connective tissues, and the axial skeleton. This study assessed the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, versus currently prescribed biologics in patients with PsA from the Argentinean social security perspective.

Methods: A semi-Markov decision analytic model was used to evaluate the cost-effectiveness of subcutaneous (SC) treatment secukinumab 150 mg and 300 mg against other SC treatments adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous (IV) treatment infliximab in biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a life-time horizon (60 years). Response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic were allowed to switch to subsequent-line biologics. Model input parameters (PsARC response, Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], drug withdrawal rates, costs, resource use, utilities, and mortality inputs) were derived from PsA clinical trials, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained. An annual discount rate of 5% was applied to costs and benefits. Sensitivity analyses and an alternative scenario with higher cost option from the private payer perspective were conducted to test the robustness of the results.

Results: Among biologic-naïve PsA patients without psoriasis, secukinumab 150 mg provided highest QALYs (7.18) versus all SC biologics at lowest cost ($3,755,678 Argentine Peso), thus dominated all SC biologics. Infliximab provided slightly higher QALYs (7.31), but at greater costs ($6,543,069 Argentine Pesos), resulting into a very high ICER against Secukinumab 150 mg. Among biologic-naïve PsA patients with psoriasis and among biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab and was cost-effective versus other SC biologics. Deterministic sensitivity analyses indicated that the results were sensitive to variation in PsARC response rates, drug acquisition costs, change in HAQ, and utility values. Probabilistic sensitivity analysis showed that both secukinumab 150 mg and 300 mg had maximum net monetary benefits values. Results based on cost inputs from the private payer perspective were similar.

Conclusions: Secukinumab for the treatment of PsA in biologic-naïve and biologic-experienced patients is either a dominant or cost-effective treatment option compared to currently prescribed biologics in Argentina.

178

CLINICAL ASSOCIATIONS OF NOVEL ANTIPHOSPHOLIPID ANTIBODIES

Tomas Urrego1, Alejandro Hernández2, Sebastian Ruiz2, Sandra M. Osorno3, Carolina Rua4, Julieta Duque Botero2, Adriana L. Vanegas-García2, Carlos H. Muñoz5–6, Luis A. González5, Gloria Vásquez1–5, and Jose A. Gómez-Puerta3–7. 1Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia; 2Departamento de Medicina Interna, Universidad de Antioquia, Medellín, Colombia; 3Dinámica IPS, Medellín, Colombia; 4Grupo de Investigación en Trombosis, Medellín, Colombia; 5Grupo de Reumatología, Universidad de Antioquia, Medellín, Colombia; 6Servicio de Reumatología, Hospital San Vicente Fundación, Medellín, Colombia; 7Servicio de Reumatología, Hospital Clínic, Barcelona, España.

Background: Novel antiphospholipid antibodies (aPL) have been described recently, including anti-phosphatidylserine/prothrombin (PS/PT) antibodies and anti-domain 1 against ß2 glycoprotein I (anti-D1-B2GP1). Clinical associations with “classic” aPL are well known (including anticardiolipin[aCL], lupus anticoagulant, [LA] and anti-B2GP1 antibodies); however, information about the relationship between clinical features of antiphospholipid syndrome (APS) and novel antibodies is more limited.

Objective: Our aim was to examine the clinical associations of 2 novel aPL (Anti PS/PT and anti-D1 B2GPI antibodies) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and primary APS.

Methods: In this cross-sectional study, anti-D1- B2GPI antibodies were tested using a chemiluminescent immunoassay (QUANTA Flash, Inova Diagnostics). In addition, anti-PS/PT (IgG and IgM), aCL (IgG and IgM) and anti-B2GP1 (IgG and IgM) were measured at the same time by ELISA techniques (QUANTA Lite, Inova Diagnostics). The LA was detected according to the guidelines of the International Society on Thrombosis and Hemostasis. Spearman's rank correlation was used to assess the association between antibodies.

Results: One-hundred and seventy-three patients were included, 87% of them were female with a mean age of 33 ± 12 years. 150 patients had SLE and 23 patients primary APS. Anti-PS/PT and anti-D1-B2GP1 had some strong association with several APS features (See Table). Noteworthy, is the association between anti-PS/PT IgG and obstetric morbidity. No other association were found with other non-criteria APS features. LA was associated with all the panel of aPL antibodies (p<0.05 for all). At the same time IgG anti PS/PT and IgM anti PS/PT had a moderate positive correlation (r ranging from 0.42 to 0.49) with IgG anti B2GP1 and aCL and IgM anti B2GP1 and aCL, respectively.

TABLE
TABLE:
Clinical Associations of anti-PS/PT and anti-D1 B2GP1 antibodies

Conclusions: We found a strong association between 2 novel aPL (Anti PS/PT and anti-D1-B2GP1) antibodies with several clinical APS features including deep vein thrombosis, arterial thrombosis, thrombocytopenia and obstetric morbidity. A wider use of these 2 novel aPL in the future will bring us more information about their- clinical utility and potentially, differential management in APS patients.

Acknowledgements: Anti-D1-B2GPI antibodies were provided by Inova, Werfen, Colombia. ELISA determination of aCL and anti-B2GP1 were provided by Dinámica IPS.

188

INTEGRATED SAFETY SUMMARY OF TOFACITINIB IN PSORIATIC ARTHRITIS CLINICAL STUDIES

G.R. Burmester1, O. FitzGerald2, K. Winthrop3, V.F. Azevedo4, W.F.C. Rigby5, K.S. Kanik6, C. Wang6, P. Biswas7, T. Jones8, S. Menon6, N. Palmetto7, and R. Rojo6. 1Charité – University Medicine Berlin, Berlin, Germany; 2St Vincent’s University Hospital, Dublin, Ireland; 3Oregon Health and Science University, Portland, OR, USA; 4Universidade Federal do Paraná, Curitiba, Brazil; 5Geisel School of Medicine at Dartmouth, Lebanon, NH, USA; 6Pfizer Inc, Groton, CT, USA; 7Pfizer Inc, New York, NY, USA; 8Pfizer Inc, Collegeville, PA, USA.

Objective: To describe the safety profile of tofacitinib, an oral Janus kinase inhibitor under investigation for the treatment of psoriatic arthritis (PsA), from integrated Phase (P)3 and long-term extension (LTE) studies.

Methods: Data were analyzed for patients (pts) with active PsA who received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and an LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analyzed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analyzed over 12 months in pts randomized to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomized to PBO were excluded from this analysis. Cohort 3 (C3) consisted of all tofacitinib-treated pts in the P3 and LTE studies, and evaluated deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer [NMSC], and NMSC). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported.

Results: C1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively. In pts randomized to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomized to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]), and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]) in C3.

Conclusions: In patients with active PsA, tofacitinib demonstrated a safety profile consistent with that seen with tofacitinib in rheumatoid arthritis; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA.

202

RISK FACTORS FOR BONE LOSS IN JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A LONGITUDINAL STUDY

L. Sousa1, J. Paupitz1, N. Aikawa1, L. Takayama1, V. Caparbo1, and R. Pereira1. 1Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.

Objectives: Juvenile-onset systemic lupus erythematosus (JoSLE) is associated with low bone mass relative to the patients’ age and with fractures; nevertheless, risk factors and predictors of bone involvement are poorly understood in this condition. The aim of this study was to evaluate the risk factors for bone mass loss in patients with JoSLE examining clinical and laboratory data, besides bone microarchitecture parameters.

Methods: This study enrolled a sample of 49 female JoSLE patients, all of them diagnosed according to the ACR classification and 2012 SLICC criteria. All patients were evaluated at baseline and after 3.5 years of follow-up for clinical data associated with the disease, lifestyle habits, treatment, laboratory tests including bone turnover markers (N-terminal propeptide of type 1 collagen - P1NP; C-terminal telopeptide of type 1 collagen - CTX), areal bone mineral density (aBMD) by dual X-ray absorptiometry (DXA) at lumbar spine and hip and parameters of bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) at distal tibia and radius. Vertebral fractures were examined using DXA (VFA, Genant’s method). aBMD changes above the least significant change were considered significant. Based on the difference between final and baseline aBMD value, the patients were divided into 3 groups: aBMD gain (BG), aBMD loss (BL) and aBMD no change (NC).

Results: The mean age of the patients was 18.7 ± 3.3 years and the mean disease duration was 6.0 ± 3.9 years. Sixty-one percent of patients presented aBMD gain, 18.4% aBMD loss and 22.4% remained stable over this period of follow-up. Comparing the BL and the BG groups, there was a higher frequency of alcohol consumption (33.3 vs. 0%, p=0.009), a higher frequency of inadequate calcium intake (66.7 vs. 26.7%, p=0.047) and lower serum levels of baseline P1NP (52.42 ± 33.56 vs. 119.72 ± 85.78 ng/mL, p=0.036) in the BL group. Moreover, a worse evolution of HR-pQCT bone parameters: trabecular volumetric density at tibia (−16.36 ± 15.71 vs. −1.55 ± 10.83 mg/cm3, p=0.003) and cortical thickness at tibia (−0.025 ± 0.09 vs. 0.054 ± 0.07 mm, p= 0.009) was observed in the BL group. In addition, a higher frequency of renal activity was observed when the BL and NC groups were examined together and compared to the BG group (52.6 vs. 23.3%, p=0.036). No significant differences were observed regarding other clinical, laboratorial and microarchitecture bone parameters and treatment.

Conclusions: This is the first longitudinal study in the literature that examines the risk factors for bone mass loss in JoSLE patients. The authors emphasize the importance of evaluating not only renal disease activity, but also lifestyle habits, mainly alcoholism and calcium intake in these young women. Furthermore, this study suggests that trabecular and cortical bone compartments were deteriorated in this disease and that low serum levels of P1NP may be a predictor of bone involvement in JoSLE.

302

DISCREPANT PERCEPTION OF LUPUS DISEASE ACTIVITY. A COMPARISON BETWEEN PATIENTS’ AND PHYSICIANS’ DISEASE ACTIVITY SCORES IN PERUVIAN PATIENTS

Claudia Elera-Fitzcarrald1,2, Karen Vega3,4, Rocío V. Gamboa-Cárdenas1, Katiuska Zúñiga3,4, Mariela Medina1, Victor Pimentel-Quiroz1, César Pastor-Asurza1, Risto Perich-Campos1, Zoila Rodríguez Bellido1, Graciela S. Alarcón4,5, Armando Calvo3,4, and Manuel F. Ugarte-Gil1,2. 1Servicio de Reumatología. Hospital Guillermo Almenara Irigoyen. EsSalud; 2Facultad de Medicina Universidad Científica del Sur; 3Servicio de Inmunología y Reumatología. Hospital Cayetano Heredia; 4Facultad de Medicina. Universidad Peruana Cayetano Heredia; 5School of Medicine, The University of Alabama at Birmingham, USA, United States.

Objectives: To compare patient’s and physician’s (MD’s) assessment of disease activity in Peruvian systemic lupus erythematosus (SLE) patients.

Methods: This is a cross sectional study of SLE patients conducted between August 2016 and December 2017 at two hospitals in Lima, Perú, one from the Social Security and the other from the Public Health Systems. Disease activity was assessed by the patient with either a Visual Analog Scale (VAS), 0–100 mm) or a Numerical Rating Scale (NRS, 0–4), before and after MD’s assessment. Disease activity was assessed by the MD with the Mex-SLEDAI (0–32) and damage with the SLICC/ACR Damage Index (SDI). Health-related quality of life (HRQoL) was ascertained with the LupusQoL. VAS and NRS scores obtained before and after the MD evaluation were compared using the Wilcoxon signed-rank test. The correlation between disease activity as assessed by the patient and the Mex-SLEDAI, SDI and LupusQoL was examined using Spearman Rank Correlation.

Results: Two hundred and forty patients were included. Their mean (SD) age at diagnosis was 34.9 (12.9) years; nearly all patients were Mestizo. Disease duration was 10.1 (7.0) years. The Mex-SLEDAI was 1.9 (2.7) and the SDI 1.2 (1.5). Disease activity as assessed by the patient, either by VAS [29.3 (26.5) and 26.5 (24.9) or NRS [1.5 (1.2) and 1.4 (1.1), before and after MD evaluation, respectively] did not correlate with the Mex-SLEDAI (MD assessment). Likewise, there was no correlation between either measure and the SDI. In contrast, disease activity as assessed by the patient, regardless of the scale or time obtained, correlated with several components of the LupusQoL (physical health, pain, planning, emotional health and fatigue). These data are shown in Table 1.

TABLE 1
TABLE 1:
Correlation between disease activity measured by the patient and Mex-SLEDAI, SDI and LupusQoL

Conclusions: Physician and patient’s assessment of disease activity are discrepant with patients scoring, overall, higher than their MDs. Disease activity as perceived by patients correlates with how they perceive the disease is affecting them rather than with disease activity per se. Further studies are needed to assess how this discrepant perception between patients and their physicians may affect patients’ treatment adherence and outcomes.

363

SECUKINUMAB PROVIDES SUSTAINED REDUCTION IN FATIGUE IN PATIENTS WITH ANKYLOSING SPONDYLITIS THROUGH 3 YEARS: LONG-TERM RESULTS OF TWO RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 3 STUDIES

T.K. Kvien1, A. Deodhar2, L. Gossec3, P.G. Conaghan4, V. Strand5, M. Østergaard6, N. Williams7, B. Porter8, K. Gandhi8, and S. Jugl9. 1Diakonhjemmet Hospital, Oslo, Norway; 2Oregon Health & Science University, Portland, Oregon, United States; 3UPMC University Paris 06, Paris, France; 4University of Leeds, Leeds, United Kingdom; 5Stanford University School of Medicine, Palo Alto, CA, United States; 6Copenhagen Center for Arthritis Research (COPECARE), Glostrup, Denmark; 7RTI Health Solutions, Durham, NC; 8Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 9Novartis Pharma AG, Basel, Switzerland.

Objectives: In patients (pts) with ankylosing spondylitis (AS), fatigue is a common symptom negatively affecting health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC), a fully human anti–IL-17A mAb, rapidly improved signs and symptoms, physical functioning, and HRQoL in pts with AS.1,2 Here, we present the long-term effects of SEC on fatigue in TNF inhibitor (TNF)-naïve and TNF inhibitor inadequate responder/intolerant (TNF-IR) AS pts in MEASURE 1 and MEASURE 2.

Methods: 371 and 219 pts were randomized to SEC or placebo (PBO) in MEASURE 1 (10 mg/kg IV followed by 150 or 75 mg SC) and MEASURE 2 (150 or 75 mg SC), respectively. At Week (Wk) 16, non-responder PBO pts were re-randomized to SEC 150 or 75 mg SC (in MEASURE 1, PBO pts achieving ASAS20 response at Wk 16 were switched to SEC at Wk 24). Fatigue was measured at baseline (BL) and Wks 4, 8, 12, 16, 24, 52, 104 and 156 using FACIT-F, which assesses fatigue in the previous 7 days using 13 questions graded on a 0–4 scale (higher scores = less fatigue). An increase from BL in FACIT-F score of ≥4 points (based on MCID) was used to define “response.” Approximately 69% of pts were TNF-naïve and 31% were TNF-IR across both trials. Analyses were based on the full analysis set and subgroups stratified by prior TNF therapy. Correlations between BL characteristics and improvements in fatigue were investigated using a logistical regression model. Only data from the approved dose (SEC 150 mg) are presented.

Results: FACIT-F was 24.5–25.6 and 22.6–24.3 at BL across groups in MEASURE 1 and 2, respectively. Improvements in FACIT-F with SEC at Wk 16 were sustained through Wk 156 in MEASURE 1 and Wk 104 in MEASURE 2 (Table). Rapid and sustained fatigue responses were also seen in subgroups stratified by prior TNF use. In the overall population, LS mean changes (±SEM) from BL in FACIT-F scores were significantly greater with SEC vs PBO at Wk 16 in both MEASURE 1 (7.60 ± 0.99 vs 3.34 ± 1.00, P = 0.002) and MEASURE 2 (8.10 ± 1.09 vs 3.27 ± 1.09, P = 0.018). Reductions in fatigue were sustained throughout the entire follow up period in both trials (MEASURE 1 Wk 156: 9.81 ± 0.95; MEASURE 2 Wk 104: 9.27 ± 1.13). Similar results were reported in both TNF-naïve and TNF-IR pts. Correlational analyses based on pooled data from both trials did not identify any BL factors that consistently predicted improvement in fatigue response at Wks 16, 52, and 104. A one-unit increase in BL BASDAI score (i.e., worsening based on MCID) was a significant factor impacting FACIT-F response at Wk 104 (P = 0.02).

Conclusions: SEC provided sustained improvements in fatigue for up to 156 wks in both TNF-naïve and TNF-IR pts with AS. Fatigue response was generally higher in TNF-naïve pts.

References:

[1] Baeten. NEJM 2015;373:2534–48.

[2] Kvien. ARD 2016;75(Suppl2):823.

TABLE 1
TABLE 1:
FACIT-F responders in MEASURE 1 and MEASURE 2 with secukinumab 150 mga

POSTERS

1. BASIC SCIENCE

35

SM04690, A WNT PATHWAY INHIBITOR: ANTI-INFLAMMATORY AND CARTILAGE PROTECTIVE EFFECTS IN PRECLINICAL OSTEOARTHRITIS MODELS

V. Deshmukh, T. Seo, M. Grifman, C. Swearingen, Y. Yazici. Samumed, LLC, San Diego, USA.

Objectives: Osteoarthritis (OA) is characterized by pain, swelling, and reduced function in the knee joint. Upregulated Wnt signaling drives OA through synovial inflammation, increased subchondral bone, and thinning cartilage. SM04690, a small molecule Wnt pathway inhibitor that demonstrated chondrogenic and anti-inflammatory properties preclinically1, was further evaluated to determine its potential to reduce inflammation, protect cartilage, improve joint health and modify pain in OA.

Methods: Cytokine secretion (IL-6 and TNF-α) from IL-1β-stimulated and SM04690-treated synovial fibroblasts was measured by ELISA. A single intra-articular injection of SM04690 or vehicle was evaluated in an in vivo rat knee monosodium iodoacetate (MIA) OA model. Joint inflammation was evaluated by H&E staining, inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α and IFN-γ) by qPCR, and cartilage protection by qPCR for matrix metalloproteinases (MMPs). Histological evaluation of cartilage health was performed using OARSI score and thickness by Safranin-O staining. Pain was measured as paw withdrawal threshold using Von Frey apparatus and weight distribution using incapacitance meter and analyzed using generalized estimating equation regression.

Results: SM04690 dose-dependently inhibited IL-1β-induced cytokine secretion in synovial fibroblasts (EC50 ~30nM; Fig.1). In the rat MIA OA model, compared to vehicle, SM04690 injection reduced visible knee swelling, inflammatory cells, proinflammatory cytokine and MMP production (p < 0.05). SM04690 increased (p < 0.01) paw withdrawal threshold from day 6 and improved weight distribution to the affected limb in treated rats, at multiple timepoints, compared to vehicle (Fig.2). SM04690 increased Safranin-O stained cartilage thickness and decreased OARSI score (p < 0.05) compared to vehicle.

FIGURE 1
FIGURE 1:
SM04690 inhibited inflammatory cytokine production in synovial fibroblasts in vitro.
FIGURE
FIGURE:
SM04690 inhibited inflammatory cytokine production and decreased inflammation and pain in the MIA model of OA.

Conclusion: In a rat MIA OA model, SM04690 injection reduced inflammation, protease production, and pain, with improved cartilage and joint health, compared to vehicle. Previously demonstrated regenerative effects in nonclinical studies1, along with anti-inflammatory properties, show SM04690 may improve symptoms and potentially provide disease modification in OA. Clinical studies are ongoing.

1Deshmukh et al. OAC 2017

73

HISTOMORPHOMETRIC ASSESSMENT OF THE TIBIAL METAPHYSIS AREA IN NOD MICE WITH SJÖGREN SYNDROME

B. Busamia B1, SJ Renou2, C. Gobbi1, S. Fontana1, E. Albiero1, P. Alba1, and M. Yorio1. 1Unidad de Reumatologìa, Hospital Córdoba, UNC; 2Cátedra de Anatomía Patológica FOUBA.

Background: Primary Sjögren syndrome (SSp) is a chronic, autoimmune, systemic disease characterized by lymphocytic infiltration of the exocrine glands with consequent drying of the mucosa, mainly oral (xerostomia) and ocular (xerophthalmia). Our group has previously described bone disorders in NOD mice with Sjögren Syndrome, both radiologically and histologically, compared with controls. Bone disorders related to SS have not been described accurately in the current literature.

Objective: To assess by histomorphometry of the tibial metaphysis area of NOD mice with SS, compared to controls NOD mice without SS.

Methods: We used 10 NOD female mice with SS (group SS) and 10 controls NOD without SS (group C, control). They were cared in the animal facilities of the Faculty of Chemistry of the UNC. At 4 months of age (weight 80 g ± 10) mice were anesthetized with ketamine-xylazine, both tibias were extracted, and then they were taken to euthanasia, respecting the ethical principles of animal experimentation. The bones were fixed in formalin buffer, decalcified with EDTA and processed for their inclusion in paraffin; cuts were oriented to eosin in order to perform the histological assessment. The histomorphometrically assessment of tibial metaphysis area and the length of trabecular bone were performed.

Results: The area of bone tissue and the length of trabecular bone were smaller in SS Group than in the C Group, with statistically significant difference: bone tissue área C group: 142079,3 ± 32250 μm2; SS Group: 103356,9 ± 19445 μm2. Trabecular lenght 557±31 μm; SS Group: 331±70 μm), p<0,05. The percentage of trabecular bone tissue in C group was: 16,5% - SS group: 9,6 %.

Conclusion: These results, in addition to our previous research, confirms that there is a bone disorder in this experimental model of SS. It is necessary to carry out immunostaining techniques of quality and activity of bone tissue, with the purpose of objectify the response in NOD mice with SS.

77

ASSESSMENT OF BONE MINERAL DENSITY OF THE LOWER JAW, SPINE AND TIBIAL BONE IN NOD MICE WITH SJÖGREN' SYNDROME

B. Busamia1, C. Gobbi1, K. Rhys1, M. Mariani2, S. Fontana2, S. Marchegiani S3, M Belletti3, E. Albiero1, P. Alba1, and M. Yorio1. 1Cátedra de Fisiología, Facultad de Odontología. UNC; 2Unidad de Reumatología, Hospital Córdoba. UNC; 3Servicio de Radiología, Sanatorio Allende, Córdoba.

Introduction: The model of NOD mice for experimental diabetes, concomitantly produces an alteration in the submandibular and lacrimal glands; histopathologically these changes are equivalent to Sjögren's syndrome (SS) that develops in humans. Only few data are found in the literature about bone diseases in SS.

Objective: To assess the bone mineral density in the lower jaw, spine and tibial bone in non-obese diabetic mice with Sjögren's syndrome (SS-NOD) compared to control mice C57, (C).

Methods: We used 10 female NOD mice and 10 C57 controls from animal facilities of the Faculty of Chemical Sciences at UNC. These animals were cared for under special conditions, free of specific pathogens. At 4 months of age (weight 80 g ± 10) animals were anesthetized with ketamine Xylazine. Bone Mineral Density (BMD) was measured with Densitometer Hologic QDR Discovery W 4500w; Scan Type: Lumbar Spine anteroposterior, jaw bones and tibia. We used Rx- dual-energy (DXA) with ionization chamber. Mice position: prone position, upper and lower limbs, and tail extended. A "bone map" of the bone area to study was performed and divided into into five sectors with "spinal lines": lower jaw (LJ), lumbar spine (LC), both tibial bones (TB), right and left epiphysis (RE and LE). Mineral density was expressed in grams of calcium/cm2. Statistical analysis was performed by ANOVA using, InfoStat 2015. BMD controls were: LJ 0.21, LC 0.11, LE 0.04, ED 0.03 and T 0.04 and in NODSS mice 0.19, 0.11, 0.01, 0.01, 0.01 g/cm2, respectively.

Results: The different bone regions within each group of mice and between both groups were compared. Variations between the bony regions in each experimental group were observed, a significant decrease in BMD values of the tibiae from NOD SS vs C57, was found; it was statistically significant for the left tibial epiphysis BMD (p <0.0001) in comparison to the other bones studied.

Conclusion: Tibial bone abnormalities were found in the NOD SS mice when compared with the controls, but not in the other skeletal sites studied. Pathologic correlation is necessary to determine and the significance of these findings.

80

IMMUNOSTIMULATORY CAPACITY OF MICROPARTICLES FROM PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS ON T LYMPHOCYTES

MA. Cardona-Carvajal1,2, K. Julio-Hoyos1,2, K. Álvarez2, L. Carmona2, M. Rojas2, and G. Vásquez2. 1Escuela de Microbiología y Bioanálisis. Universidad de Antioquia.2Grupo de Inmunología Celular e Inmunogenética. Facultad de Medicina. Universidad de Antioquia.

Objective: To evaluate the immunogenicity of microparticles (MPs) from healthy controls (HC) and patients with systemic lupus erythematosus (SLE), by the capacity to induce activation and proliferation of HC T-lymphocytes, suggesting a specific recognition, event that should explain the role of these cellular fragments in the pathogenesis of SLE.

Materials and Methods: To establish the proliferation, mononuclear cells from human peripheral blood isolated by density gradient were staining with CFSE (carboxyfluorescein succinimidyl ester) and stimulated during 96 hours with phytohaemagglutinin (PHA), anti-CD3/CD28 and two different concentrations of isolated MPs from five SLE patients and HC. The expression of CD25 and CD28 in T cells was established by flow cytometry.

Results: Although, PHA and anti-CD3/CD28 induced CD25 and CD28 expression and T cell proliferation, it was not changed by the treatment with 50 ug/ml and 150 ug/ml MPs derivatives from controls and patients. Proliferation and division indexes do not differ between the MPs concentrations, source or PHA and anti-CD3/CD28 combination either.

Conclusions: SLE patients and controls’ MPs, neither induce healthy controls T lymphocytes activation, nor proliferation. In addition, this work showed that MPs do not promote T lymphocytes activation or proliferation induced by PHA and anti CD3/CD28. The observed effects are not dependent on the dose or MPs isolation source.

97

POLYMORPHISMS OF DICKKOPF 1 IN EARLY RHEUMATOID ARTHRITIS COULD MODULATE THE PRESENTATION OF RADIOLOGICAL DAMAGE

Alex Darío Cardona-Rincón1,2, Mónica Acevedo-Godoy3, Ángela Arias-Arias4, Lorena Chila-Moreno3, Sandra J Perdomo-Lara3, Philippe Chalem Ch5, Wilson Bautista-Molano2,3, Rafael Valle-Oñate1, Juan Manuel Bello G1,2, and Consuelo Romero-Sánchez1,2,3. 1Hospital Militar Central, Bogotá, Colombia; 2Universidad Militar Nueva Granada, Bogotá-Colombia; 3Universidad El Bosque, Bogotá-Colombia; 4Universidad Colegio Mayor de Cundinamarca, Bogotá-Colombia; 5Fundación Instituto de Reumatología Fernando Chalem.

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovitis, joint destruction and excessive bone loss. Recent evidence suggests that Dickkopf-1 (DKK-1) may have an active role in the regulation of bone biology. In addition, those patients with RA that carry genetic variants of DKK-1 have higher serum levels and greater bone damage. The objective of this study was to investigate the bone resorption marker DKK-1 and its polymorphisms in patients with early RA (eRA) and its association with rheumatic indexes and radiological score.

Methods: A cross-sectional study was conducted to explore the association of bone marker DKK-1 and its polymorphisms with radiological and rheumatic outcomes in patients with eRA according to the criteria of the American College of Rheumatology/EULAR 2010. Patients selected were over 18 and less than 65 years of age, had early disease, and treatment with conventional DMARDS (Disease Modifying AntiRheumatic Drugs). Disease activity was assessed by scales DAS 28 and SDAI. Radiographs of hands and feet were obtained and scored using the Sharp-van der Heijde score (SHS) and the Simple Erosion Narrowing Score (SENS). DKK-1 polymorphisms rs1896368, rs1896367 and rs1528873 were determined using the High Resolution Melting technique (Bio-Rad®) and serum levels by ELISA- MyBiosource®). A bivariate analysis was performed to determine the variables associated to the presence of radiological, and a penalized regression model was performed to confirm these associations. This study was approved by the Ethics Committee of the Institution.

Results: 63 patients with eRA were included, with a mean age of 48.5 years (SD = 11.5 years).79.4% of the patients were female, 6.3% were current smokers and 61.7% and 43.3% had positive RF (Rheumatoid Factor, Spinreact®) and ACPAs IgG/IgA (Innova, Diagnosis®) (Anti Citrullinated Peptides Antibodies) respectively. No association was found between DKK-1 levels and disease activity indexes or radiological damage scores. Patients heterozygous for the rs1896367 polymorphism more frequently had erosions (p = 0.026), JSN (Joint Space Narrowing) in the feet (p = 0.005), higher SHS score (p = 0.016) and higher frequency score > 6 (p = 0.001) by SENS. As for the polymorphism rs1896368, those with homozygous expression had a lower frequency of JSN (p = 0.026) and homozygosity was negatively associated with JSN in the feet (p = 0.002); these patients did not present scores of SENS > 6 (p = 0.001). In a penalized regression model, patients homozygous for the rs1896368 polymorphism of DKK-1 have a lower risk of presenting radiological damage, (OR: 0.04 CI: 0.01-0.93, p = 0.05).

Conclusions: Serum levels of DKK-1 may have a preponderant role as a marker in bone or joint damage in more advanced stages than in eRA, however, the presence of polymorphisms of DKK-1, specifically of rs1896368 in eRA could modulate the presentation of radiological damage.

129- ASSOCIATION BETWEEN ANTIBODIES TO CARBAMYLATED PROTEINS AND SPECIFIC PEPTIDES OF THE HUMAN FIBRINOGEN B-CHAIN IN EARLY RHEUMATOID ARTHRITIS

L. Chila-Moreno3,4, L.S. Rodríguez4, J. De Avila3, W. Bautista-Molano2,3, J.M. Bello-Gualtero1,2, and C. Romero-Sánchez1,2,3. 1Hospital Militar Central, Bogotá- Colombia; 2Universidad Militar Nueva Granada, Bogotá-Colombia; 3Universidad El Bosque, Bogotá-Colombia; 4Pontificia Universidad Javeriana, Bogotá-Colombia.

Background: The presence of autoantibodies is one of the hallmarks of rheumatoid arthritis (RA). Anti-carbamylated protein(anti-CarP) antibodies are new autoantibodies present in RA and which are detected before the onset of RA and have been associated with disease severity; however, the precise target antigen of anti-CarP antibodies has not been elucidated. The objective of this study was to associate the anti-carbamylated protein and peptides antibodies with genetic and activity clinical indexes in patients with early RA(eRA).

Methods: A cross-sectional study of 51 RA patients with the diagnosis of eRA according to the ACR/EULAR 2010 criteria Bogota-Colombia was carried out. Anti-CarP antibodies were measured for the presence of anti-carbamylated-fetal calf serum (anti-CarP-FCS) by chemiluminescence by Inova-Diagnostics and antibodies directed to specific epitopes of the human Fibrinogen β-Chain peptide(anti-CarP-Fib), two peptides with specific homocitrulline were synthesized and one with lysine as negative control by in-house ELISA method. Disease activity was assessed by DAS28 and SDAI. Radiographs of hands and feet were obtained and scored using the Sharp-van der Heijde score (SVdH) and the Simple Erosion Narrowing Score-SENS. HLA-DRB1 typing was carried out by Luminex 200 TM technique. The association was examined by Chi-square and Fisher tests and the comparison using kappa concordance coefficient.

Results: Fifty-one patients were evaluated. 19.6% were male and 80.4% were female. 29.4% were positive for RF and 45.1% positive for ACPA. The positivity of Anti-Carp -FCS antibodies was 47.1% and the positivity of the antibodies against carbamylated peptides was: Anti-CarP-Fib2 47.1% and anti-CarP-Fib3 31.4%. Twenty-eight patients (54.9%) showed the shared epitope. A negative association was found between the presence of anti-CarP-FCS antibodies passive exposure to tobacco (p = 0.037). Interestingly, anti-Carp-Fib2 antibodies resulted associated with the presence of positive RF (79.2%) (p = 0.022) and higher level of ACPA(p = 0.032). Additionally, the anti-CarP-Fib2 antibodies were associated with joint space narrowing in the feet by the SVdH whereas 83.3% were positive for both (p = 0.043), and space narrowing in feet by SENS score (p = 0.043). No associations were found with the HLADR B1, serological and clinical markers related with RA. In addition, a concordance analysis was performed between the results of anti-CarP-FSC protein and specific anti-peptides anti-CarP-Fib with the following results: 21/24 patients were positive for anti-CarP-FCS and anti-CarP-Fib2 (p =0.00001 and Kappa = 0.685) and anti-CarP-FCS and anti-CarP-Fib3 (p =0.007 and kappa = 0.36)

Conclusions: Anti-CarP-Fib2 appear to target regions of the human fibrinogen β-chain that contain homocitrulline in a specific place and could be in the future be considered good biomarkers for the presence of joint damage in era. The evaluation of antibodies against carbamylated peptides showed a substantial concordance with the anti-carbamylated protein

183

URINE BIOMARKERS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH OR WITHOUT LUPUS NEPHRITIS: AN EXPLORATORY STUDY IN COLOMBIAN PATIENTS

Y.P. Trujillo1, A. Kerguelen2, S. Amado1,2, D.G. Fernández-Ávila1,2, A. Barreto-Prieto1, and L.S. Rodríguez1*. 1Pontificia Universidad Javeriana, Bogotá, Colombia; 2Hospital Universitario San Ignacio, Bogotá, Colombia.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the production of autoantibodies directed against intracellular antigens; clinical variability makes it difficult to predict damage to specific organs caused by the disease; consequently, new treatments in order to mitigate the pathology of this disease are neccessary This is an important reason to improve the panel of biomarkers. Although the cause of the disease is still unknown, however, the lack of removal of apoptotic cells has been postulated as a possible induction mechanism. It has also been shown that urine is a reliable source of biomarkers allowing an observation window of what may be happening to the patient.

Objective: The objective of this work was to determine if there are differences between the urine levels of molecules related to the removal of apoptotic cells and triggering of the inflammatory process, as well as of cytokines involved in the disease, in patients with SLE with or without lupus nephritis (LN) in comparison to healthy controls.

Material and Methods: To explore this, the study population was divided into three groups: healthy controls (n = 6), SLE patients without LN (n = 5), and SLE patients with LN (n = 4). This population was recruited at the Hospital Universitario San Ignacio, in Bogota Colombia. The urine samples were collected and concentrated by ultrafiltration. We evaluated by Western Blot the following molecules: HMGB1, HISTONE H3, CALRETICULIN (CRT), ANEXIN A1 and CD46, CX3CL1 by ELISA and cytokines IL-8, IL-6, IL-12p70, TNF-α and IL-1β by Cytometric Bead Array.

Results: We detected histone H3 levels in only one SLE patient with LN. The band detected for this patient suggests a posttranslational modification of this molecule. No histone H3 was detected in the age-sex matched healthy controls. There was no difference for HMGB1 and CX3CL1 levels in all groups examined. CD46, ANEXIN A1 and CRT were not detected in our samples. Finally, when we evaluated the cytokines, an increase of IL-8 levels was observed in SLE patients with or without LN in comparison to the healthy controls. For IL-6, an increase was found between patients with SLE without LN in comparison to patients with LN, but no differences were found in the levels of the other cytokines.

Conclusion: Urine levels of IL-8 and histone H3 could be interesting in studying renal damage in SLE. HMGB1 as “danger signal”, CX3CL1 as “find-me signal” do not seem to be useful to predict renal involvement in SLE patients. More patients must be recruited to confirm these findings.

248

CHARACTERIZATION OF EXPRESSION PROFILES OF IKAROS TRANSCRIPTION FACTOR IN AUTOIMMUNE DISEASES

L.K Duque Suárez1, G. Quintana López2, P. Coral Alvarado2, P. Méndez Patarroyo2, H. Groot de Restrepo1, and V. López Segura1. 1Human Genetics Laboratory, Universidad de Los Andes, Bogotá, Colombia; 2EAI-Reumavance Research Group, Hospital Fundación Santa Fe de Bogotá, Bogotá, Colombia.

Background: Autoimmune diseases are syndromes characterized by an immune response against self-antigens. They are complex pathologies associated with a variety of genes, but these do not fully explain all disorders. Ikaros is a transcription factor involves in lymphopoiesis and its involvement in development of hematologic tumors is well known. Ikaros has a high level of alternative splicing, therefore at least 10 isoforms are known. Among these, isoforms arising from non-canonical splicing due to insertions and deletions and dominant negative isoforms, that lack 2 to 4 zinc fingers of their DNA binding domain, theoretically lose their function.

Objective: In this study, we characterized the isoforms expression profile of Ikaros through of the interexonic regions quantification in patients diagnosed with Sjögren Syndrome, systemic lupus erythematosus, systemic sclerosis and rheumatoid arthritis.

Methods: Peripheral blood samples were obtained and RNA was extracted. A novel qRT-PCR design was carried out, where each interexonic region of Ikaros was amplified and non-canonical splicing was detected by melting dissociation curve analysis. REST 2009 2.0.13 software was used for relative quantification and statistical analysis was based on the Kruskal-Wallis, Dunn and Wilcoxon tests. The hierarchical clustering analysis was performed using Cluster 3.0 and Java Treeview 1.1.6r2 programs.

Results: The expression pattern of all Ikaros interexons in the control group has similar proportions, reflecting mainly the presence of complete functional isoforms. Patients with rheumatoid arthritis and Sjögren syndrome have a higher overall expression with an elevated quantity of dominant negative isoforms. Systemic lupus erythematosus patients have the least expression of functional isoforms present, proving the lack of Ikaros expression as a possible cause of the disease and not the imbalance of isoforms. Additionally, non-canonical splicing variants detected affect exons with DNA binding and dimerization domains. Patients and controls were clustered by the expression level of each interexonic region and the presence or absence of non-canonical splicing. Three groups could be distinguished: Rheumatoid arthritis like samples with the greater expression of Ikaros, control characterized by a homogeneous expression and systemic lupus erythematosus like samples with the least expression.

Conclusions: This is the first study conducted in Latin America that sought to determine the relationship between Ikaros and autoimmune diseases and the first description of Ikaros in patients with rheumatoid arthritis, Sjögren syndrome and systemic sclerosis. We also confirmed the alteration of Ikaros expression in systemic lupus erythematosus. The different patterns of expression in arthritis and lupus indicated that Ikaros could be considered a diagnosis biomarker.

253

COLLAGEN V/C57BL6 MOUSE MODEL: A NOVEL PRECLINICAL MODEL TO STUDY PATHOPHYSIOLOGY AND THERAPEUTIC APPROACHES IN SYSTEMIC SCLEROSIS

W. R. Teodoro1, A. P. P. Velosa2, Z. A. de J. Queiroz1, L. A. dos Santos1, S. Catanozi2, A. dos Santos Filho1, C. Bueno1, M. Vendramini1, S. M Fernezlian3, E. M. Eher3, F. D. T. Q. S. Lopes4, P. D. Sampaio-Barros1, and V. L. Capelozzi3. 1Division of Rheumatology; 2Division of Endocrinology; 3Department of Pathology; 4Laboratory of Experimental Therapeutics, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil.

Introduction: Experimental models are important instruments for a better understanding of the pathogenesis of systemic sclerosis (SSc) and can also propose new therapies for the disease.

Objective: In the present work, we aimed to characterize functional, serological and histopathological features of skin and pulmonary parenchyma in SSc patients and in type V collagen (COL V) immunized C57BL6 mice.

Methods: The histopathological patterns in skin and lung biopsies of 23 patients with SSc and five controls were assessed and compared to those of female C57BL/6 mice immunized with human COL V in Freund´s adjuvant. Mice were euthanized after 120 days and skin and lungs were examined by histology, immunofluorescence, immunohistochemistry, histomorphometry, qRT-PCR, ELISA and pulmonary mechanics.

Results: The serum of immunized mice presented antinuclear antibodies (ANA) and anti-collagen type III and IV autoantibodies, while the skin of immunized mice showed increase number of inflammatory cells and deposition of collagen type III and V (p<0.01) coincident with the increase of COL3A1, COL5A1 and COL5A2 gene expression. Skin biopsies of SSc patients showed fibrosis with abnormal dermal histoarchitecture and increased markers of α1(V) and α2(V) chains in the dermis and vessels (p<0.01). Interestingly, the lungs presented a high pulmonary resistance (p<0.01) and elasticy (p<0.01) by mechanic lung evaluation. Characteristic histologic features of lungs 120 days following COLV immunization were a non-specific interstitial pneumonia (NSIP) pattern combined with thickening of small and medium intrapulmonary arteries. Lungs from immunized mice also presented an increase of total collagen and type I collagen fibers (p<0.01), 4-hydroxyproline (p<0.01), CD4+ T lymphocytes (p<0.01), transforming growth factor beta (TGF-β) (p<0.01) and connective tissue growth factor (CTGF) (p<0.01). A significant increase sign of endothelial cell activity by vascular endothelial growth factor (p<0.01) and endothelin-1 (p=0.03) protein and genic expression was detected in thickened arteries, which also revealed elevated signs of endothelial apoptosis by caspase-3 expression (p<0.01). Lung biopsies of SSc patients without clinically evident pulmonary hypertension mimicked all features of IMU-COLV-NSIP, cutaneous and vascular histologic pattern and so demonstrated comparable vascular, inflammatory and fibrotic manifestations.

Conclusion: This experimental model demonstrated that all typical manifestations of SSc-related pulmonary and skin remodeling are mimicked by COLV immunized C57BL6 mice, which constitutes an appropriate preclinical model to study the mechanisms and therapeutic approaches of pulmonary and skin involvement in SSc.

357

METHOTREXATE-LOADED LIPID-CORE NANOCAPSULES PREVENTS JOINT SPACE NARROWING AND SYNOVITIS IN EXPERIMENTAL ARTHRITIS

A.L. Boechat1, C.P. Oliveira2, A.R.C. Barbosa1, R.M. Santos1, S.S. Guterres2, A.R. Pohlmann2, and O.T.F. Costa1. 1Universidade Federal do Amazonas, Manaus, Brasil; 2Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.

Background and Objective: Methotrexate-loaded lipid-core nanocapsules (MTX-LNC) is a new drug delivery formulation that is capable to concentrate the drug at inflamed sites, increasing its therapeutic effect and reducing collateral damage. The objective of this research was to evaluate this new MTX drug delivery formulation for reducing joint space narrowing and synovitis in experimental arthritis compared with conventional methotrexate (MTX).

Methods: The nanocapsules formulation was prepared by self-assembling methodology. The two lipid nanocapules formulations (LNC) were named (1) MTX-LNC, containing 0.250 mg/mL−1 of MTX, and (2) LNC, without MTX. The volume distribution for the nanocapsules formulations was MTX-LNC D [4,3] 264 and LNC D [4,3] 243. Adjuvant Arthritis was induced in Lewis rats. At experimental day 28th, the animals were sacrificed and the hind paws histologically processed to obtain serial sections. The tissue samples were analysed using quantitative morphometry methodology (stereology). For this purpose, the counting points method was applied for Cavalliere’s volume determination and the relative volume of joint components (Delesse). The evaluated structures were synovial space (volume) and synovial membrane (superficial area).

Results: The experimental results showed that MTX-LNC had a greater effect on arthritis than conventional MTX (p < 0.0001). The effect on reducing arthritis was observed earlier for MTX-LNC compared to MTX (p < 0.0001). When the hind paw structures were evaluated by quantitative morphometry, the arthritis group treated with MTX-LNC had a greater synovial space volume compared to the MTX- treated and arthritis groups (0.09 mm3, 0.04 mm3, 0.24 mm3, respectively; p < 0.0001). We also observed that MTX-LNC was able to reduce the synovial membrane superficial area compared with the arthritis and MTX-treated groups (22.61 mm2, 35.8 mm2, 29.35 mm2, respectively; p < 0.0001).

Conclusion: Taken together these data demonstrate that MTX-LNC not only reduces paw edema formation but also reduces synovitis and joint space narrowing more efficiently than conventional MTX.

359

KYNURENINE AS A NEW MOLECULAR MARKER FOR HIGH CARDIOVASCULAR RISK IN RHEUMATOID ARTHRITIS

A.L. Boechat1, N.O. Boechat1, M. Tavares1, V.C. Harraquian1, A.G. da Costa2, A.M. Tarragô1, R.O. dos Santos1, E.S. Lima1, A. Sadahiro1, and Pritesh Lalwani3. 1Universidade Federal do Amazonas, Manaus, Brasil; 2Universidade do Estado do Amazonas, Manaus, Brasil; 3Fundação Oswaldo Cruz, Manaus, Manaus, Brasil.

Objective: To evaluate the role of kynurenine (KYN) and inflammation markers in atherogenesis in RA patients.

Methods: Twenty-five RA patients were consecutively evaluated regarding their clinical variables and common carotid intima-media thickness (cIMT) and common carotid intima-media thickness (cIMT). In addition, KYN, tryptophan (TRP), Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Total Thiols, pro- and anti-inflammatory cytokines were quantified in patients’ serum. RA patients were then divided into cIMT < 0.9 mm or low- cardiovascular risk (CVR) and cIMT > 0.9 mm or high-CVR and compared with the above clinical and serological parameters.

Results: We observed an increased DAS28-CRP and HAQ score in high-CVR group compared to the low risk group. KYN (p = 0.0194) and KYN/TRP ratio (p = 0.0147) serum levels were significantly elevated in the high-risk patients. Furthermore, KYN and KYN/TRP ratios were significantly positively correlated with cIMT increase and KYN efficiently classified RA patients with high-risk profile (AUC = 0.81, p = 0.022), using ROC analysis. Additionally, distinct cytokine profile was observed for those patients with low cardiovascular risk (cIMT < 0.9 mm), showing a low proinflammatory cytokine levels and a high mean levels of T regulatory cell cytokines IL-10 and TGF-β1 (p = 0.004 and p = 0.019) indicating that they have a fully Treg response with a low inflammatory profile. On the other hand, high cardiovascular risk patients show a proinflammatory cytokine profile with high mean level of TNF-α (p = 0.015) and IL-6 (p = 0.015 and p = 0.031) with Th1/Th17 signature cytokines INF-γ (p = 0.024), IL-2 (p = 0.001), IL-17A (p = 0.034) and IL-23 (p = 0.031). No significant differences were founded for TOS and TAS or total serum thiols.

Conclusions: Increased inflammation is associated with increase in KYN and changes in the arterial walls, which subsequently increases cardiovascular disease risk in RA patients. Further studies are needed to understand the importance of these findings; however, we have demonstrated an immunological rationale for stratifying RA patients based on their cIMT measures as high or low cardiovascular risk.

400

RELATIVE EXPRESSION OF IFN-alpha BIOSYNTHETIC PATHWAY GENES IN PERIPHERAL BLOOD CELLS OF PATIENS WITH IgG4-RELATED DISEASE

C. Attallah1, H. Casafú2, L. Costa2, M. Oggero1, E. Fernández2, and S. Paira3. 1School of Biochemistry and Biological Sciences, UNL, CONICET. Santa Fe, Argentina; 2School of Medical Science, UNL. Santa Fe, Argentina; 3Rheumatology Section, JM Cullen Hospital. Santa Fe. Argentina.

Objectives: IgG4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition with characteristic histopathological findings in the organs involved. Although previous data have provided strong evidence that plasmacytoid dendritic cells (pDCs) activation and IFN-alpha production are prominent features of IgG4-related Type 1 Autoimmune Pancreatitis, IgG4-RD immunopathogenesis is scarcely known. The aim of this study was to evaluate the relative expression of IFN-alpha biosynthetic pathway genes in patients with different manifestations of IgG4-RD.

Methods: The study was conducted on 9 diagnosed IgG4-RD patients aged between 23-75 years (median 59.0 [IQR, interquartile range: 42.0, 61.50]), and 8 healthy subjects aged 27-70 years (median 46.5 [IQR 34.25, 60.25]). Patients were diagnosed according to the comprehensive diagnostic criteria for IgG4-RD (2011), resulting as definite (n = 7) and probable (n = 2). Written informed consent was obtained from all subjects. Patients were further sub-divided into two groups: group I included patients with mono-organic involvement (n = 1) and group II included patients with multi-organic involvement (n = 8). The treatment profiles of patients at the moment of blood sampling were as follows: non-treated (n = 2) and under treatment with: steroids (n = 1), steroids and methotrexate (n = 5), and steroids and azathioprine (n = 1).

TLR7, TLR9, IRF5, IRF7, Foxp3 and Fas gene expression were examined using the real-time reverse transcriptase polymerase chain reaction (RT-PCR). From total RNA of peripheral blood mononuclear cells the expression level was quantitated by real-time quantitative PCR (qPCR) and normalized with the values of the housekeeping control of the ?-actin gene. Relative gene expression was calculated using the comparative 2-??Ct method. A melting curve was done to increase the sensibility and specificity of the test.

Statistical analyses were performed using the nonparametric Mann-Whitney U test. Results were considered significant when the p value was less than 0.05. Statistical analyses were carried out using the Graph-Pad software (Prism).

Results: Neither the genes involved in IFN-alpha biosynthetic pathway (IRF5, IRF7, TLR7 and TLR9) nor the Fas or transcription factor Foxp3 showed differences in the relative expression of their transcripts between patients and healthy donors.

Conclusions: Although these results are preliminary due to the small number of patients studied, no differences were found in the gene expression of IFN-alpha biosynthetic pathway members. It is interesting to continue this study since innate immunity has been considered by other investigators as having a central role in the development of the disease.

446

ASSOCIATION BETWEEN URIC ACID TRANSPORTASOME POLYMORPHISMS AND GOUT RISK IN MEXICAN POPULATION

A. Francisco-Balderas1,2, J. F. Peralta-Aguilar1, E. O. Méndez-Salazar1, G. A. Martínez-Nava1, J. Fernández-Torres1,3, A. López-Reyes1, D. Garrido-Rodríguez4, C. F. Pérez-Beltrán5, L. Silveira-Torre5, and D. Clavijo-Cornejo1. 1Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, México City, México; 2Instituto Politécnico Nacional, México City, México; 3Universidad Autónoma Metropolitana, México City, México; 4Instituto Nacional de Enfermedades Respiratorias, México City, México; 5Instituto Nacional de Cardiología Ignacio Chávez, México City, México.

Background and Objective: Gout is a disorder characterized by arthritis caused by the deposition of monosodium urate crystals; its prevalence in Mexico is estimated to be of 0.3%. It is preceded by chronic hyperuricemia (UA) in serum (over 6.8 mg/dl). The renal urate excretion is carried out by a transport system named the UA transportasome; it is known that single nucleotide polymorphisms (SNP) in this system are related to the development of gout. Therefore, this study aimed at evaluating the association between transportasome gene polymorphisms and gout susceptibility in the Mexican population.

Methods: A total of 41 SNP of transportasome and 11 ancestry-informative markers were genotyped using TaqMan probes in a Quant Studio 12 k Flex instrument (Applied Biosystems). We examined 62 gout cases diagnosed according to the ACR/EULAR criteria, 23 individuals with asymptomatic hyperuricemia (AH) and 165 healthy individuals. The allelic discrimination and ancestry analysis were carried out using the TaqMan genotyper and STRUCTURE1.2.1 software, respectively. To assess the associations between the genetic variants and gout as well as AH state, we calculated odds ratios (ORs) with 95% confidence intervals by multinomial logistic regression models. To assess the association between SNP and UA serum levels and gout, we performed lineal regression models, both analyses adjusted by clinical parameters (age, body mass index, gender and ancestry) in STATA v.14 software.

Results: Seven SNPs of six different genes were associated with gout. ABCG2 rs2231142 (T) and BCAS3 rs2079742 (C) minor alleles were associated positively (OR = 3.48, p < 0.01 and OR = 3.02, p < 0.01; respectively). A significantly declined risk for gout was found in the carriers of the minor allele of ATXN2 rs653178 (C allele OR = 0.44 p = 0.047) and SFMBT1 rs6770152 (G allele OR = 0.42 p < 0.01) SNP. Despite that, we did not observe a significant association between the diagnosis of gout and the minor allele of GCKR rs780094 and rs1260326, OVOL rs642803 and PRKG2 rs10033237 SNP; these showed a significant association when examined by genotype in a co-dominant inheritance model. SNPs related to glomerular filtration process, UBE2Q2 rs1394125 and INHBC rs3741414, presented a positive association with AH state (A allele OR = 4.25, p = 0.005; T allele OR = 2.45, p = 0.04; respectively); however, they were not significantly associated with gout. The intergenic variant rs17786744 (OR = 0.312 p = 0.005) minor allele (G) was negatively associated with AH. The lineal regression shows that ABCG2 rs2231142 SNP had a significantly estimated average difference in UA serum levels.

Conclusions: These data suggest that SNPs in the transportasoma are genetic risk factors for gout and AH state. In this Mexican population, ABCG2 rs2231142 SNP showed the most consistent results and could prove to be a useful genetic susceptibility marker for gout and to identify individuals at high risk of developing it. Larger sample size studies are required before drawing definitive conclusions.

464

PARTICIPATION OF ANTIMICROBIAL PEPTIDES (AMPS) IN THE PHYSIOPATHOGENESIS OF JOINT DAMAGE MEDIATED BY METALLOPROTEINASES (MMPS) IN ARTHRITIS INDUCED BY TYPE II COLLAGEN

G. Méndez1, S. Godina2, R. González3, D.P. Portales4, J.A. Enciso1, and M.H. García1. 1Unit of Biomedical Research of Zacatecas, IMSS, Zacatecas, México; 2Autonomus University of Zacatecas, UAZ, Zacatecas, México; 3Center of Applied Research in Health and Biomedicine, San Luis Potosí, México; 4Autonomus University of San Luís Potosí, UASLP, San Luis Potosí, México.

Introduction: Antimicrobial peptides (AMPs) are molecules with antimicrobial activity; however, they are also able to modulate different cellular activities such as secretion of metalloproteinases (MMPs), cytokines and different processes like T cell chemotaxis and monocytes. It has been reported that AMPs may have inflammatory or anti-inflammatory activity depending on the type of receptor with which they interact, the type of cell, and the inflammatory environment in which they are found. In chronic inflammatory diseases such as rheumatoid arthritis (RA), increased levels of AMPs have been observed and have been positively associated with the presence of bone erosions. Moreover, in type II collagen-induced arthritis (CIA) different phases have been described, in which different cytokines and receptors are present. In this study we determined the expression of AMPs, rCRAMP, mBD-3, mBD-4 and MMP-3 during the progression of CIA, with the purpose of associating their expression levels with the histopathological changes of the different phases of CIA.

Objective: The aim of this study was to evaluate the expression of AMPs, rCRAMP, mBD-3, mBD-4 as well as MMP-3 during the development and progression of CIA and examine the association of these with parameters of cellular infiltration and cartilage loss.

Methodology: CIA was induced by type II collagen and complete Freund's adjuvant in DBA1/J mice. Clinical severity was assessed using a scoring system, according to this score the joints were classified as onset, peak and remission CIA phases. After the animals were sacrificed, the joints were dissected, and histological sections were prepared, stained with hematoxylin-eosin (H & E) and safranin O, respectively. Detection of the peptides rCRAMP, mBD-3, mBD-4 as well as MMP-3, was carried out by immunohistochemistry.

Results: Cell infiltration was found to be increased in the peak and remission phases, as was the degradation of cartilage. MMP-3 expression increased in the peak phase and was localized in infiltrated cells. CRAMP expression is constitutively present and increased in the peak and remission phases; in addition, it was associated with cellular infiltration, cartilage degradation and MMP-3 expression. The expression of mBD4 showed a tendency to increase in infiltrated cells and synovial membrane in the peak phase, this showed a positive association with cellular infiltration. AMP mBD3 showed low expression in all phases.

Conclusions: These results suggest that the antimicrobial peptide CRAMP is associated with the development and progression of CIA.

510

LEVELS OF TRANSFORMING GROWTH FACTOR BETA ISOFORMS (TGF-B1, TGF-B2, TGF-B3) IN SYSTEMIC SCLEROSIS

R.A. Carranza- Muleiro1,2, L. Manuel-Apolinar3, I.M. Arciniega Martínez1, A.A. Reséndiz-Albor1, E.J. Rodríguez-Rodríguez1, M.A. Martínez-Bencomo4, M.P. Jimenez-Arellano6, J. Martínez-Varillas6, T. Pérez-Capistran1, D. Martínez-Rodríguez1, G. García-Collinot1, G. Medina2, J. Jara-Quezada2, and M.P. Cruz-Domínguez2. 1Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional IPN). México City; 2Hospital de Especialidades Centro Medico la Raza, Instituto Mexicano del Seguro Social. México City; 3UMAE Unidad de Enfermedades endocrinológicas y metabólicas, HECM Siglo XXI Instituto Mexicano del Seguro Social, México City; 4Universidad Nacional Autónoma de México (UNAM), México, México; 6. Universida Veracruzana (UV), Xalapa, Veracruz.

Background and Objectives: Systemic sclerosis (SSc) or scleroderma is a chronic, progressive, autoimmune and rheumatologic disease which has three hallmarks: fibrosis, small vessel vasculopathy and aberrant immune responses. Transforming growth factor beta (TGF-β) is a pleiotropic and essential cytokine of human survival with both autocrine and paracrine effects. TGF-β1 is a cytokine that orchestrates the fibrotic changes in systemic sclerosis (SSc), but the role of TGF-β2 and TGF-β3 has not been well studied.

The aim of our study was to compare levels of TGF-β1, TGF-β2 and TGF-β3 between SSc and healthy controls (HC), and the possible correlation between clinical and biochemical parameters in these patients.

Methods: We performed a cross-sectional study in fifty-eight patients out of a cohort of 126 individuals with SSc, at the Hospital de Especialidades Centro Médico Nacional La Raza, México City, according to the criteria of ACR/EULAR 2013 of SSc, and 24 apparently healthy volunteers. The study was approved by the ethics local committee. Written informed consent was obtained from each subject. TGF-β isoforms (TGF-β1, TGF-β2 and TGF-β3) concentrations in serum were determined by specific ELISA kits. Statistical analysis was performed using the software Statistical Package for the Social Sciences (SPSS) version 21.0 (SPSS Inc., Chicago, IL, USA), and Graph Pad Prism 6.0 (GraphPad Software Inc., San Diego, CA) statistical program. To compare HC vs SSc, HC vs lSSc, HC vs dSSc, and lSSc vs dSSc TGF-β isoforms serum levels, the Mann-Withney U tests was used. To analyze the relationship between TGF-β isoforms and serum biomarkers or clinical findings we use Spearman’s correlation coefficients. A p value ≤ 0.05 was considered statistically significant.

Results: We studied 56 females of 52 ± 11 years of age, and 2 males of 39 and 55 years of age. Twenty-two female volunteers of 51 ± 7 years of age, and 2 males 39 and 46 years of age were also studied. Level of TGF-β1 was 36.95 ± 15.28 ng/mL (0.015-67.67), TGF-β2 was 98.65 (0.015-40.01 ng/mL), TGF-β3 was 0.015 (0.015-14.069 ng/mL). We found the mean levels of TGF-β1 to be higher in the SSc patients than in the HC (37.45 vs 17.91 ng/mL, p = 0.0001**); by subtype the levels were also higher in the lSSc vs the HC (37.62 vs 17.91 ng/mL, p = 0.0001**) and in the dSSc vs the HC (17.91 vs 36.28 ng/mL, p = 0.0001**). For TGF-β2, the levels were also higher in the SSc patients than in the HC (9.86 vs 1.87 ng/mL, p = 0.0058*), independently of subtype lSSc vs. HC (9.89 vs 1.87 ng/mL, p = 0.0025*) and dSSc vs HC (9.83 vs 1.87 ng/mL, p = 0.0052*). However, TGF-β3 was similar between groups HC vs SSc (0.0015 vs 0.0025 ng/mL). TGF-β2 showed correlation with nitric oxide (r-0.360; p = 0.046*) and TGF-β3 with osteonectin (r 0.421; p = 0.044*) but not with other biochemical parameters.

Discussion: Fibrosis is a major player in SSc pathogenesis. We found TGF-β1 to be increased in SSc similar to other studies, recognizing their regulatory role in this disease but not as a biomarker of clinical disease. We found also TGF-β2 elevation in SSc in inverse correlation with nitric oxide that suggest the possibility to be regulatory of vascular reactivity and fibrosis opening the field for future studies. TGF-β3 levels seems to be of a minor relevance in SSc.

Conclusion: TGF-β1 and TGF-β2 superfamily proteins isoforms are significantly increased in SSc confirming the findings of other authors; we also found isoform TGF-β2 increased in inverse relationship with nitric oxide suggesting its possibly role on vascular dysfunction that need to be investigated.

LUPUS

27

NON-PROTOCOLIZED RE-BIOPSY IN PATIENTS WITH ANCA-ASSOCIATED GLOMERULONEPHRITIS: IS IT NECESSARY?

V. Scaglioni1, M. Scolnik1, FS. Pierini1, L.J. Catoggio1, S.B. Christiansen1, C.F. Varela1, G. Greloni1, G. Rosa-Diez1, and E.R. Soriano1. 1Hospital Italiano de Buenos Aires. Buenos Aires. Argentina.

Background/Objective: Non-protocolized repeat renal biopsies are rarely performed in ANCA glomerulonephritis (GN). Their role in predicting long term renal outcomes and aiding in clinical decisions have not been examined in detail. The aim of this study was to evaluate the usefulness of renal re-biopsy in patients with ANCA GN in treatment decisions.

Methods: We included all patients with biopsy-proven ANCA GN: granulomatosis with polyangiitis (GPA), granulomatosis with polyangiitis and eosinophilia (GPAE), microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV) between January 2002 and May 2017. We examined patient’s baseline characteristics, induction and maintenance treatments, renal response after induction and time to renal relapse/rebiopsy. The histology of re-biopsies was reviewed and correlation with clinical findings (hematuria) and first biopsy histology was examined. Histological classification was made according to 2010 classification criteria for ANCA glomerulonephritis. Data of physicians' decisions after re-biopsy were collected.

Results: 60 patients (77% females) were included. Of those, 15 (25%) underwent renal re-biopsy during the follow up based on clinical manifestations. Mean time until re-biopsy was 38.4 months (SD 20.4). In the re-biopsy group, 73% of patients had new onset hematuria vs. 7.5% in the no-rebiopsy group. New onset or worsening proteinuria was present in 73% of patients in the re-biopsy group (40% and 33%, respectively) vs. only 2.5% in the no-rebiopsy group. Decline in the GFR was present in 60% of patients in the re-biopsy group vs. 2.5% in the other. When examining the histological changes in the repeat biopsy we did not find a correlation between active lesions (crescents, necrosis etc.) and hematuria. All patients that underwent repeat biopsy were considered to be active but renal histology showed progression in terms of chronicity and rare active histological lesions (Table 1). Despite this lower percentage of active lesions, in 67% of patients, physicians made a treatment change, initiating a new induction therapy regimen and achieving renal response in 85% of patients.

TABLE 1
TABLE 1:
Comparison of histological classification in the first and second renal biopsy

Conclusions: Renal histology in repeat biopsies did not show active lesions justifying clinical renal manifestations that lead to re-biopsy. Despite this, physicians made a change in treatment in the majority of cases after re-biopsy. Patients who presented with new onset hematuria, proteinuria and worsening in the GFR had a good response to this new induction treatment achieving renal laboratory remission in 85% of patients. Role of histological findings in rebiopsies needs to be further examined.

33

AUTOIMMUNE INTERSTITIAL LUNG DISEASE IN LATIN AMERICA. RESULTS OF THE EPIMAR COHORT STUDY

F. Vivero1, F. Campins1, S. Babini1, P Malfante1, D. Lancellotti1, E. Gandara1, J. Sebastiani1, V. Basso1, and J. Enghelmayer2. 1Hospital Privado de Comunidad, Mar del Plata, Argentina; 2Hospital de Clinicas, Buenos Aires, Argentina.

Objectives: Autoimmune (Ai) interstitial lung diseases (ILD) represents a specific subgroup of ILD, for which information about prognosis and natural history is lacking. The objective of this study was to evaluate the characteristics and course of patients treated for AI-ILD.

Methods: We conducted a multicenter cohort study in 39 centers from Argentina, Colombia and Uruguay between January 2015 and July 2017. Patients were included if they were diagnosed with AI-ILD by a multidisciplinary team as suggested by current reviews. Patients were classified in the following sub-groups: ILD associated tissue connective disease (ILD-CTD), interstitial pneumonia with autoimmune features (IPAF) and ANCA-associated ILD (ILD-ANCA). All images were reviewed by a blinded board-certified radiologist.

Results: Among the 223 patients included during the study period, 166 (74%) were women. Mean age was 60 years (SD 14). One-hundred and eighty-nine (85%) patients were classified as ILD-CTD (rheumatoid arthritis 32%, systemic sclerosis 27%, dermatomyositis 14%). Sixteen patients were classified as IPAF and 8 as ILD-ANCA. The mean time between the diagnosis of CTD and ILD was 3.3 years. Antinuclear antibodies (52%) were the most frequent autoantibodies followed as rheumatoid factor (36%), anti-Ro (21%) and anti-cyclic citrullinated peptide (21%). Fifty-three percent of patients showed slight restriction at moment of diagnosis. The most common treatment strategy was the combination of steroids and cyclophosphamide (23%) or azathioprine (16%).

Conclusions: To the best of our knowledge, this is the first study to evaluate the characteristics and treatment strategies used in patients affected by AI-ILD in Latin-America. Future studies should evaluate the impact of current treatment strategies in the outcome of AI-ILD.

36

PREVALENCE OF HYPOVITAMINOSIS D IN ADULTS WITH SYSTEMIC LUPUS ERYTHEMATOUS AND ITS RELATIONSHIP WITH SLEDAI-2K COMPONENTS IN PATIENTS TREATED IN TWO RHEUMATOLOGY SERVICES, BOGOTA 2017

R.A. Guzman1, L.G. Piñeros2, J. García3, L.M. Pombo4, A.A. Teherán5, M.C. Mejía6, V. Cadavid7, J. Bustillo8, and K. Guzman9. 1Internal Medicine and Reumatology specialist, COMPLEXUS research group, Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 2Family Medicine and Alternatives Therapeutics and Vegetal Pharmacology specialist, GIFVTA research group, Fundación Universitaria Juan N. Corpa, Bogotá, Colombia; 3Family medicine specialist, Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 4Chemical Engineer, GIFVTA research Group. Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 5Emergency Medicine´s student, Epidemiologist, Complexus research group; 5Physician, Epidemiology´s student, Complexus Research Group. Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 7Physician, COMPLEXUS research group, Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 8Internal Medicine specialist. Fundación Universitaria Juan N. Corpas, Bogotá, Colombia; 9Medicine´s student. Fundación Universitaria Juan N. Corpas Bogotá Colombia.

Objective: To establish the prevalence of hypovitaminosis D in patients with SLE and its relationship with SLEDAI – 2K.

Methods: A cross sectional study was carried out. The medical records of 60 patients, >18 years of age and who met at least 4 of the 11 criteria for the diagnoses of SLE or CIE-10 M30-M36 were identified and were included in this study. The analysis included means, SD and Kruskall Wallis test; a p-value < 0.05 was considered significant.

Results: The majority of the patients were women (94%), with an average age of 39.9 years, married (41%), with secondary education (56.7%) and different occupations. Patients with higher disease activity, had lower vitamin D levels. Additionally, in those patients with lupus nephritis, vitamin D levels were even lower (See figure).

FIGURE 1
FIGURE 1

Conclusion: So far, the results show that in SLE patients with severe activity by SLEDAI-2K, serum vitamin D levels were significantly lower than in those with no/mild disease activity. There is a direct relationship between hypovitaminosis D and lupus activity; very low Vit D levels are associated with kidney involvement.

38

INCIDENCE OF CANCER IN A COHORT OF PATIENTS WITH PRIMARY SJÖGREN SYNDROME

M. Brom1, S. Moyano1, M. Scolnik1, J.I. Gandino1, and ER. Soriano1. 1Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Objectives: To evaluate the incidence of all types of cancer in a cohort of patients with primary Sjögren Syndrome (SS).

Methods: We performed a descriptive study in a university hospital with its own health insurance and captive population. We included patients fulfilling ACR 2012 or American-European Consensus Group (AECG) 2002 SS criteria, or patients diagnosed as Primary SS by the treating rheumatologist. We reviewed the electronic medical records of SS patients between 01/01/2000 and 12/31/2015 and examined demographic, clinical and histopathologic information available on their medical records. The incidence rate of cancer with its 95% CI was calculated. Patients were followed up until the end of study, death, loss to follow up, or diagnosis of cancer. Incidence was compared with statistics from the United Kingdom (UK)’ general population as there are no data available in our country.

Results: One hundred fifty-seven patients with Primary SS were included and followed for 1158 patient/years. Table 1 shows patients’ characteristics. 15 patients developed a neoplasia during follow up: 3 lymphomas (two MALT lymphomas of the parotid and one disseminated non-Hodgkin lymphoma), 1 Multiple Myeloma, 4 Skin (non – melanoma) neoplasia and 7 solid organ cancers (4 Breast, 1 Lung, 1 Uterus, 1 Tongue). Table 2 shows the cohort cancer incidence rates and comparison with the data from the general population. Non- Hodgkin Lymphomas showed an increased incidence in SS patients. All 3 patients with lymphoma were females, with anemia, leukopenia and high erythrocyte sedimentation rate. In multivariate logistic regression analysis, only thrombocytopenia was associated with an increased risk of cancer in general (OR 7, CI 95% 1.9-25.7).

TABLE 1
TABLE 1:
SS patients’ characteristics
TABLE 2
TABLE 2:
Neoplasia incidence rate in current SS cohort compared to the UK general population

Conclusions: We only found an increased rate of non- Hodgkin lymphomas in this cohort of SS patients. The incidence rates for all other types of cancer were in the ranges expected for the general population.

46

WHAT IS THE EFFECT OF LUPUS NEPHRITIS (LN) ON PREGNANCY OUTCOME AND FETAL AND MATERNAL COMPLICATIONS?

C. Otaduy, P. Alba, C. Gobbi, A. Alvarez, A. Albiero, E. Albiero, and M. Yorio. Rheumatology Unit, Córdoba State University, Materno Neonatal Hospital. Córdoba, Argentina.

Background: Previous studies have suggested that LN before pregnancy or active renal disease may be associated with poor fetal and maternal outcomes in patients with systemic lupus erythematosus (SLE).

Objective: To evaluate the effect of previous LN on pregnancy with respect to fetal and maternal outcomes, maternal complications and lupus activity.

Patients and Methods: We studied SLE pregnant patients according to the 1997 ACR criteria with and without previous LN, who attended to Lupus Pregnancy Clinic at Materno Neonatal Hospital in Cordoba city from January 2015 to April 2017. We examined demographic, clinical and laboratory data, as well as the presence of Antiphospholipid Antibodies (APL), Antiphospholipid Syndrome (APS) according to the Sydney criteria, and Lupus activity as measured by the modified pregnancy Selena SLEDAI score at conception, during pregnancy and puerperium. Renal biopsies were classified according to the ISN/RNP 2004 classification. All patients were followed by an established medical protocol. Maternal and fetal outcomes were evaluated. A p value <0.05 was considered significant.

Results: There were 121 pregnancies in 77 women. Of these 69 occurred in patients with previous LN and 52 in those without it. The presence of APL, APS and higher baseline SLEDAI were observed in the LN group compared to non-LN. There was not difference in maternal age at first pregnancy, previous abortions and SLE disease duration in both groups. 47.5% of the patients had Class IV LN. A higher rate of lupus flare was found in the LN than in the non LN group (25.8% vs 10.9 % p=0.041), as well as renal flares but none of the patients developed chronic renal failure. 18.8% of LN patients developed Preeclampsia vs in 6.3% of those without LN (p=0.047). Cesarean section rate was similar in both groups. Fetal outcome was similar in both groups in terms of live birth (90,4% in the LN group vs 91,3% in the non LN (p=0.552), weight at birth (2,600 grs.±741.8 in the LN group vs 2.748 grs ±699.9 in the non LN group, p=0.289) and gestational age (36.54 weeks in the LN group vs 36.87 in the non LN group, p=0.523).

Conclusions: LN occurring during pregnancy does not lead to less favorable pregnancy or fetal outcomes. Pregnancy-induced hypertension as well as a disease flares were associated with previous LN.

52

BELIMUMAB IN SYSTEMIC LUPUS ERYTHEMATOSUS. A ONE YEAR FOLLOW UP STUDY

V. Aldasoro1, M. Varela1, R. Ibáñez1, L. Garrido1, C. Fito1, N. del Val1, L. Horcada1, I. Paniagua1, R. Gutiérrez1, and E. Loza1. 1Complejo hospitalario de Navarra, Pamplona, Spain.

Objectives: To describe patients with Systemic Lupus Erythematosus (SLE) treated with Belimumab (BLM).

Material and Methods: A review of patients with SLE treated with BLM from 2012 to 2017.

Results: Table 1 shows the baseline characteristics of the patients studied. The median BLM bolus received was 8.5 (IQR 2-32.7) and it was stopped in 4 patients due to lack of efficacy; these 4 patients had persistence of arthritis and none of them had received bDMARD before.13 patients had at least one antiphospholipid autoantibody positive and 4 developed antiphospholipid syndrome. At the initiation of BLM, 5 patients had renal involvement; 3 of them improved after 3 months of treatment. Among 14 patients with joint involvement, 3 improved at month 3, 2 at month 6 and 1 at month 7 after treatment BLM began. 3 patients had heart and lung disease; none of them improved with BLM. In the 9 patients with skin disease only one showed improvement after 12 months of treatment. 9 patients had haematological disorders: 1 improved at month one, 1 at month 3, one at month 5 and 2 at month 6 of treatment.

TABLE 1
TABLE 1:
Baseline Characteristics

Table 2 shows SLEDAI, C3 and C4, antiDNA levels.

TABLE 2
TABLE 2:
One year follow up after BLM treatment.

Conclusions: BLM improved SLEDAI and complement levels allowing sparing of maintenance corticosteroid therapy.

54

FINGER CAPILLARY CHARACTERISTICS IN DOMINICAN REPUBLIC PATIENTS WITH PRIMARY SJÖGREN SYNDROME, WITH OR WITHOUT RAYNAUD'S PHENOMENON

I. Mercedes-Núñez1, E. Tejada-Reyes1, Y. Cruz-Rojas1, E. Rodríguez-Bautista1, V. Rosario1, R. Muñoz-Louis1, R. Peña-Blanco1, T. Valdez-Lorie1, and R. Alba-Fériz1. 1Hospital Docente Padre Billini, Santo Domingo, Dominican Republic.

Objective: To examine the nailfold capillaroscopy characteristics of patients with primary Sjogren syndrome (SS) with or without Raynaud's phenomenon.

Methods: Cross-sectional study with data collected from digital records of two hospitals in Santo Domingo that included patients who met ACR 2012 classification criteria for SS and who had agreed to undergo nailfold video capillaroscopy (NVC) with a x200 magnification lens (Optilia). The following capillaroscopic characteristics were evaluated per square millimeter (mm2): density, number of abnormal shapes defined by the EULAR study group on microcirculation in Rheumatic Diseases2, 4. Data was analyzed using SPSS V22 for Windows 10.

Results: We studied 23 SS patients, all of them were women, their mean age was 49.1 years, 17.4% presented RP, 21% had interstitial lung disease, 34.8% were treated with chloroquine and low dose prednisone, 26% with rituximab, one patient (3.4%) was on rituximab and mycophenolate mofetil; 21.7% had parotid gland hypertrophy, 78.3% were ANA positive at low titers (speckled pattern in all), 95% were anti-SSA positive, 65% wererheumatoid factor positive; 52% had a positive Schirmer test, 56% of the salivary gland biopsies were informed as positive (≥1 focus score); 34.8% of the cases were described as capillary findings of normal morphology whereas 60.9% had tortuous capillaries and one patient (3.4%) had scleroderma 'early' pattern (few giant capillaries, few capillary micro-haemorrhages, no evidence of capillaries loss and relatively well-preserved capillary distribution); 17.4% of patients with tortuous capillaries had RP.

Conclusions: The most frequent capillaroscopic finding in our study were tortuous capillaries with good density. In patients with SS, it has not yet been the meaning of these findings as there are no defined patterns for this disease. One patient presented scleroderma 'early' pattern so we should continue to evaluate larger cohorts to fully assess their prognostic value in the development of microangiopathy as seen in patients with systemic sclerosis.

55

ANTIPHOSPHOLIPID SYNDROME: MATERNAL AND FETAL OUTCOMES

C. Otaduy1, P. Alba1, C. Gobbi1, F. Guiñazú1, A. Alvarez2, A. Albiero1, E. Albiero1, and M. Yorio1. Rheumatology Unit, Córdoba State University, Materno Neonatal Hospital, Córdoba, Argentina.

Background: Antiphospholipid antibodies (APLAs) have been associated with pregnancy loss and other obstetric complications, such as preeclampsia, fetal growth restriction and preterm delivery.

Objective: To evaluate maternal and fetal outcomes in pregnant Primary Antiphospholipid Syndrome patients (PAPS).

Patients and Methods: We studied PAPS patients according to the Sydney criteria who attended the Pregnancy Clinic at Materno Neonatal Hospital in Cordoba city during the last 8 years. We examined demographic, clinical, obstetric and laboratory data. All patients were followed by an established medical protocol at each visit. Maternal complications were evaluated: Preeclampsia, HELLP, Gestational Diabetes, Premature rupture of fetal membranes, arterial and venous thrombosis, mortality, how pregnancy ended, and others. Fetal outcome was evaluated as live birth, gestational age, and weight at birth.

Results: 96 pregnancies in 68 patients were included. Maternal mean age was 30.75 years old, 84% were from Cordoba city, 70.5% did not have health insurance and they had a mean of 4 previous pregnancies with 1 live birth. Maternal complications were: Preeclampsia in 12 patients (12.5%), preterm delivery in 6 patients (6.25%), premature rupture of fetal membranes in 8 (8.33%), gestational diabetes in 7 (7,29%), arterial thrombosis in 2 (2,08%), venous thrombosis in 3 (3,12%). 33,69% had a normal labour, and 66,33% cesarean section. 86% of patients had a live birth with a mean gestational age of 36 weeks, with a mean weight at birth of 2.558 g; in 73% of the patients the weight at birth corresponded to their gestational age.

Conclusion: PAPS patients experienced good maternal and fetal outcomes in this study.

57

SYSTEMIC VASCULITIS: INCIDENCE OF GLUCOCORTICOID-RELATED ADVERSE EVENTS

L. Lo Giudice1, M. Scolnik1, J. Martinez Perez1, A. Luissi1, F. Mollerach1, V. Scaglioni1, and E.R. Soriano1. 1Hospital Italiano, Buenos Aires, Argentina.

Introduction: Treatment of systemic vasculitis with glucocorticoids (GC) tends to be sustained over time. The glucocorticoids toxicity index (GTI) is useful to assess the impact of the morbidity associated with these drugs. It is made up of two components, a compound and a specific index. This specific index includes clinical serious adverse effects derived from the toxicity of GCs.

Objective: To assess the incidence of the items included in the specific component of the GTI in patients with Giant Cell Arteritis (GCA), Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA).

Methods: Clinical records of incident cases between 2000 and 2015 of GCA, GPA, MPA were scanned for serious adverse effects associated withGC treatment defined in the specific component of GTI over the first two years of treatment. Incidence density of serious adverse events was compared in patients with GCA and ANCA associated vasculitis (GPA and MPA). Multivariate logistic regression analysis was performed to evaluate the association between total cumulative GC dose and severe adverse effects, adjusted by confounders.

Results: 130 patients were included (92 GCA, 18 GPA, 20 MPA). 15 patients with ANCA vasculitis (39.5%, IC 95%: 25.1-55.9) and 36 with GCA (39.1%, IC 95%29.6- 49.6) presented one of the serious adverse events included in the GTI (p = 0.97). DMARDs usage in patients with GCA did not conduct to a lower cumulative GC dose at 2 years of treatment.

The adverse event incidence was 22.2/100 patients-year for ANCA vasculitis and 19.9/100 patients-year for GCA (p = 0.73). The serious infection rate was greater in the ANCA vasculitis without any relation with the GC dose received. The greater cumulative GC dose was only associated with having ANCA vasculitis as a diagnosis (p = 0.019) and having received GC pulses (p < 0.001) as per the linear regression analysis.

Conclusion: The incidence of GC-related adverse events at 2 years of treatment was similar in ANCA vasculitis and GCA. Presenting a serious adverse effects was not associated with the total cumulative or initial GC dose, or having received GC pulses.

71

WHAT ARE THE EDUCATIONAL NEEDS OF LATIN-AMERICAN LUPUS PATIENTS’ CAREGIVERS?

S. Ibañez1, C. Acosta2, C. Reátegui-Sokolova3, Y. Fuentes-Silva 22,4, E. García-Carrión5, C. Elera-Fitzcarrald3, B. Pons-Estel6, and C. Drenkard7. 1Sanatorio Güemes, Buenos Aires, Argentina; 2Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Bolívar, Venezuela; 3Hospital Guillermo Almenara Irigoyen, Lima, Perú; 4Universidad de Oriente, Ciudad Bolívar, Bolívar, Venezuela; 5Hospital Dr. Raúl Leoni, Ciudad Guayana, Bolívar, Venezuela; 5Centro Regional de Enfermedades Autoinmunes y Reumatología (CREAR), Sanatorio Parque, Rosario, Santa Fe, Argentina; 7Emory School of Medicine, Atlanta, GA, USA.

Objectives: Previous studies have demonstrated that lupus patients have considerable educational needs, but data about their caregivers are limited. We assessed the educational needs of a sample of Latin-American lupus caregivers and examined the association between their needs and demographic characteristics.

Methods: We conducted a 6-month survey to evaluate Let’s Talk about Lupus (Hablemos de Lupus), a Facebook (FB) program in Spanish that aims to educate the Latin-American population living with lupus. Launched in May 2017, FB/Hablemos de Lupus has built a social community of 55.000 followers through the delivery of animated videos (AV) and live videochats (LVC) with providers, along with an open education channel between followers and lupus educators. We asked followers to propose topics for AV and LVC, and overall suggestions (OS). Using 38 predefined topics, we codified up to five needs (N1 to N5) per responder, which were classified in eight themes within three domains: lupus knowledge, self-management/quality of life, and lupus awareness/healthcare resources. We used Chi-square test to examine associations between needs and sociodemographics characteristics.

Results: Among 936 survey respondents, 130 (14%) self-reported to be a caregiver, a close one, or a healthcare provider of somebody with lupus. Mean age of the sample was 39±10 years, with 90% females, 56% followers of the page for ≥ 3 months, 43% with a university degree, and 45% working fulltime). Over 50% were from Mexico and Argentina (31% and 20%, respectively), followed by countries from the Bolivarian Region (21%) and Central-America/Caribbean (11%). Educational needs (N1 to N5) are showed in table 1. There were not significant associations between educational needs and sociodemographic factors (age, gender, region, education, occupation, disease duration).

TABLE 1
TABLE 1:
Educational Needs of Latin-American in Relatives of Lupus Patients

Conclusions: The most frequent topics brought up by relatives, friends and caregivers of lupus patients were related to disease knowledge, followed by self-management and quality of life. These findings can be used to produce tailored resources and inform interventions to address the educational needs of caregivers and people who are close to Latin American patients with lupus.

75

FACTORS ASSOCIATED WITH DAMAGE ACCRUAL IN PUERTO RICAN HISPANIC PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

P. Jordán-González1, R. Gago-Piñero1, I. Vázquez-Sanabria1, E. Santiago-Rodríguez2, and L. Vilá1. 1University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico; 2Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico.

Objectives: Factors linked with damage accrual in primary Sjögren’s syndrome (pSS) have not been well established. Furthermore, geographical location and ethnicity may impact the disease presentation, course, and outcome of pSS patients. Therefore, we sought to compare the demographic factors, clinical manifestations, serologic tests, comorbidities and pharmacotherapy between Puerto Rican patients with and without disease damage.

Methods: A cross-sectional study was performed in 100 patients with pSS. All patients were ≥ 21 years of age, were of Puerto Rican ethnicity (self and four grandparents), and fulfilled the 2012 American College of Rheumatology Classification Criteria for pSS. Demographic features, health-related behaviors, clinical manifestations, autoantibodies, serum complements, comorbidities, pharmacologic treatment, disease activity (per EULAR Sjögren's syndrome disease activity index [ESSDAI]), and disease damage (per Sjögren’s Syndrome Disease Damage Index [SSDDI]) were determined. Patients with disease damage (SSDDI score ≥1) were compared to those without damage (SSDDI score = 0), using Chi-square test, Fisher’s Exact test, Student’s t test and Mann-Whitney test, as appropriate.

Results: The mean (SD) age of the study population was 52.8 (12.3) years; 94% were woman (female: male ratio = 15.7: 1). The disease duration was 5.9 (4.7) years. Thirty-nine patients had disease damage, whereas 69 patients did not present damage. Disease damage was mainly attributed to peripheral neuropathy and pulmonary fibrosis. No significant differences were found for age, sex and disease duration between patients with and without damage. Patients with disease damage were more likely to have C3 (18.4% vs. 3.6%, p=0.028) and C4 (23.7% vs. 7.1%, p=0.023) hypocomplementemia, coronary artery disease (10.3% vs. 0.0%, p=0.021), infectious disorders (38.5% vs. 20.0 %, p=0.044), and higher activity index score (1.00 vs. 0.43, p=0.001) than those without damage. Also, patients with disease damage were more frequently exposed to corticosteroids (59.0% vs. 16.4%, p<0.001) and azathioprine (12.8% vs. 0.0%, p=0.008).

Conclusion: In this population of Puerto Rican Hispanics with pSS, C3 and C4 hypocomplementemia, coronary artery disease, infections, and exposure to corticosteroids and azathioprine were associated with damage accrual. Clinicians should be aware of these associations to provide prompt and effective management to these patients.

87

ASSOCIATION OF HISTOPATHOLOGIC FINDINGS OF ANTIPHOSPHOLIPID SYNDROME NEPHROPATHY WITH THE OUTCOME OF LUPUS NEPHRITIS

S. Rodriguez1, and C. Pastor2. 1Virgen de la Puerta Hospital - EsSalud, Trujillo, La Libertad, Peru; 2National University of San Marcos, Lima, Perú.

Objectives: To determinate the clinic correlations of histopathologic findings of antiphospholipid syndrome nephropathy (APSN) with the outcome in lupus nephritis patients.

Methods: Sixty lupus nephritis patients, older than 18 years of age and who underwent renal biopsy were studied. The renal biopsies were examined for the presence of APSN. Some clinic and histopathological features were compared between patients with and without APSN at the time of kidney biopsy. At the end of follow-up (2010) the following parameters were recorded: serum creatinine level, development of renal failure and end-stage renal disease, mortality and the lupus damage index.

Results: Histopathologic findings of APSN were found in 17 (28%) patients with lupus nephritis. There was a higher prevalence of hypertension in APSN patients at the time of kidney biopsy (p = 0.03); there were no statistically significant differences between both groups in the other clinic and laboratory parameters. The activity and chronicity indices were also significantly higher in APSN patients (p = 0.03 and p = 0.0007 respectively); there was also higher prevalence of interstitial fibrosis (p = 0.0017) and of tubular atrophy (p = 0.0031) in this group of patients. There was no statistically significant difference between patients with and without APSN in the proportion of each lupus nephritis class. At the end of follow-up, higher frequencies of renal failure (47% vs. 21%) and end-stage renal disease (35% vs. 14%) were found in the APSN patients, but the differences were not statistically significant.

Also, the histopathologic findings of APSN were associated with hypertension (p = 0.03) and renal failure (OR 3.36, 95% CI 1.01-11.18, p = 0.04); and highly associated with interstitial fibrosis (p = 0.0006) and tubular atrophy (OR 16.76, 95% CI 2.04-137.83, p = 0.0012).

Conclusions: The histopathologic findings of APSN are risk factors for renal failure and tubular atrophy; they are associated with hypertension and interstitial fibrosis; all of these features are poor renal prognostic indicators. Given that, APSN must be searched for in all renal biopsies of lupus patients.

89

CORRELATION BETWEEN PROTEIN/CREATININE URINARY INDEX AND TWENTY-FOUR HOUR URINARY PROTEIN IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

E. Picco, R.V. Juárez, E.A. Buschiazzo, N.L. Cucchiaro, P. Talocchino, G. Rua, R.I. Rojas Tessel, M.M. Aciar, M.V. Lencina, and M.E. Crespo Espíndola. Hospital Señor del Milagro, Salta, Argentina.

Background: Twenty-four hours proteinuria (24hp) has been the gold standard for the screening and follow up of glomerular disease. The use of protein/creatinine urinary index (PCI) in a spot urine sample, has been proposed as an alternative to 24hp due to its low cost and simple sample collection. This method has been validated in patients with diabetic and non-diabetic nephropathy but less data in patients with Systemic Lupus Erythematosus (SLE) are available. The aim of this study was to measure the correlation between these two methods in patients with SLE.

Methods: Paired samples of 24hp and PCI (first urine sample) in patients with SLE (according to rheumatologist opinion), with or without lupus nephropathy were collected between June 2015 and January 2016, in Señor del Milagro Hospital. The Walser’s index (WI), which evaluates the quality of the on 24hp samples collected, and which is calculated with estimated and measured urine creatinine, age and weight was carried out. A WI between 0.75 to 1.25 reflects a well collected 24hp sample.

Statistics - Qualitative data were expressed as frequencies and percentages, quantitative data as medians and interquartile ranges (IQR) or means and standard deviations (SD), as appropriate. Spearman test was performed to assess the correlation between the 24hp and the PCI samples. A p value < 0.05 was considered significant.

Results: 44 SLE patients and 82 paired urine samples were included; the patients’ mean age was 36.7 (SD 11) years and 36 (81.8%) female. The median values of the 24hp, PCI and WI were 0.39 g/24h (IQR: 0.19-0.81), 302 mg/g (IQR: 146-1079) and 0.72 (IQR: 0.6-0.9), respectively. Twenty samples (24.4) had normal 24ph and 15 (18.3) a normal WI. Correlation between 24ph and PCI was good (rho = 0.82, p < 0.0001). Examining only those samples with a normal WI, the correlation was better (rho = 0.92, p < 0.0001) but even the samples with abnormal WI had a good correlation (rho = 0.81, p < 0.0001). Considering only those with abnormal proteinuria (24ph > 0.2 g/24h) the correlation was still good (rho = 0.77, p < 0.0001).

Conclusion: In the SLE patients studied, there was a good correlation between the 24ph and the PCI samples; that was the case even for the group with abnormal WI. The use of PCI could replace a 24ph collection in the assessment of glomerular disease in SLE patients.

101

ESOPHAGEAL INVOLVEMENT IN SYSTEMIC SCLEROSIS

E. Nufio Chó1, E. R. Arreola2, and M. Herrera Méndez2. 1Guatemalan Social Security Institute IGSS. Guatemala City, Guatemala; 2University of San Carlos of Guatemala Roosevelt Hospital. Guatemala City, Guatemala.

Background: Systemic sclerosis is an autoimmune disorder in which the gastrointestinal tract may be involved (1); 50% of these patients do not present symptoms for about 10 years from disease onset, although this may vary.

Objectives: To determine the clinical manifestations associated with esophageal involvement in patients with systemic sclerosis.

Methods: A cross-sectional observational study was carried out. Patients treated at the Roosevelt Hospital in the period between May 2013 to June 2015 were studied; they were divided into three groups: systemic sclerosis, rheumatic disease and no rheumatic disease. Sociodemographic data were obtained, and tests to evaluate symptoms associated with esophageal involvement were performed; all patients underwent endoscopy, manometry and esophageal biopsy to directly establish secondary damage to systemic sclerosis. Statistical analysis. Descriptive statistics were used. Pearson’s Chi-square, ANOVA and Student's t-test wre used as appropriate; the prevalence rate of esophageal involvement was calculated.

Results: We included 52 patients with systemic sclerosis, 29 patients with rheumatic disease who presented esophageal symptoms and 49 patients without rheumatic disease. No differences in their demographic variables were found between these patients’ groups; 100% of the patients with systemic sclerosis presented Raynaud's phenomenon and proximal sclerosis; FANA was also documented in 14 patients (26.9%). Within the esophageal clinical manifestations, 30.6% of the control patients presented nausea and 24.5 % vomiting, with p values of 0.049 and 0.002, respectively; patients with systemic sclerosis presented with solid and liquid dysphagia and gastroesophageal reflux, with differences being found. In these patients, Esophagitis B findings were present in 16 patients (30.7%). Ineffective esophageal motility was present in 29 patients with systemic sclerosis for 56%. The incompetent inferior esophageal sphincter (IES) was documented in 18 patients (34.6%) with systemic sclerosis and the histological diagnosis associated with the presentation of esophageal involvement of fibrosis, atrophy and esophagitis was documented in 25 patients (49%) being the difference with other groups significant (p < 0.001). The prevalence ratio of presenting esophageal involvement in systemic sclerosis was 4.76 (3.92-5.97).

Conclusions: Patients with systemic sclerosis present esophageal involvement without presenting relevant clinical manifestations; and we can invasive studies such as esophageal manometry may be needed to detect this involvement.

105

OBESITY IN PATIENTS WITH SLE

F.J. Hüttmann1, V.I. Bellomio1, L. González Lucero1, A.L. Barbaglia1, M.P. León1, M. Santana1, L. Galindo1, M.C. Bertolaccini1, H.R. Sueldo1, and E.V. Lucero1. 1Hospital Ángel C. Padilla, Tucumán, Argentina.

Objectives: To determine the prevalence of obesity and overweight in patients with SLE in a public hospital. To study the effect of obesity on the quality of life, disease activity and cumulative damage in these patients.

Material and Methods: We performed a cross-sectional study. Consecutive patients with SLE attending a public hospital in the period between April-June 2016 were recruited. Demographic and clinical variables were included: weight, height allowed to calculate the body mass index (BMI) classify patients as normal, overweight or obese. Abdominal perimeter, metabolic syndrome (MetS), diabetes mellitus (DM), smoking, arterial hypertension, presence of cardiovascular events (stroke, myocardial infarction); depression (Patient Health Questionnaire -PHQ9-); and hypothyroidism were also recorded. Variables related to SLE: SLEDAI, cumulative damage (SLICC/SDI), quality of life (LupusQol) and treatment variables were also obtained. Statistical analysis: descriptive statistics, Chi square test, Fisher's exact test, T test, ANOVA and regression analysis were carried out as appropriate.

Results: 100 patients with SLE were evaluated, 89 were women; their mean age was 37.8 years ± 12.3, disease duration 10.3 years ± 7.1, SLEDAI 1.48 ± 2.5, SDI 1.31 ± 1.6. At the time of the evaluation, 41 patients were receiving between 0 - 10 mg of meprednisone; 7 subjects between 10-20 mg and 10 were being treated with > 20 mg. Fifteen patients had received methylprednisolone pulses at some time. The cumulative dose of meprednisone was 20.4 g in those with normal weight, 22 g in those overweight and 24 g in the obese (p = NS). 38% of the patients were overweight (95% Confidence Interval, CI: 29.7-47.5) and 27% were obese (95% CI: 17.8-35.6). These frequencies were not significantly different from those of the general population (p = NS). There were 49% of de subjects with high abdominal perimeter (46% female and 3% male); 5% with DM and 24% had MetS. According to the PHQ 9 score, 27% of the patients had depression. There was no association between obesity and age, sex, comorbidities (hypothyroidism, DM, MetS, arterial hypertension, smoking), educational level, socioeconomic level, cardiovascular events and depression. Overweight and obese patients had lower SLEDAI score (p = 0.053) and greater cumulative damage (p = 0.045) than those with normal BMI. The highest and the cumulative dose of corticosteroids received were not significantly different between the three groups. However, within the group of patients who used hydroxychloroquine, the frequency of obesity was significantly lower (p = 0.025). LupusQoL scores were similar within the three groups of patients (p = 0.41).

Conclusion: The prevalence of obesity and overweight were 27% and 38%, respectively. Overweight and obese lupus patients had greater cumulative damage and lower SLEDAI than those with normal BMI. Obesity and overweight did not seem to affect the patients’ quality of life.

112

BRIEF GROUP PSYCHOANALYTIC PSYCHOTHERAPY IMPROVES QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A LONG-TERM FOLLOW-UP STUDY

C. Conceição1, I. Meinão1, S. Blay1, and E. Sato1. 1Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil.

Objectives: To evaluate the effects of brief group psychoanalytic psychotherapy (BGPP) in improving the quality of life in systemic lupus erythematosus (SLE) patients.

Methods: Randomized clinical trial, with 80 SLE patients, in an outpatient University hospital. Two groups: therapy (TG n=37); control (CG n=43). Inclusion criteria: female, SLE (ACR-1997 classification criteria), age ≥ 18 years, minimum outpatient follow-up of six months, and signed informed consent. Exclusion criteria: illiterate; severe physical and mental comorbidities, inclusion in other studies. Approved by the Institutional Ethic Committee. Both groups continued to receive clinical care. TG received BGPP in weekly sessions for 20 consecutive weeks, performed by a specialized psychologist. CG remained in the waiting list. Assessments: at baseline (T1), after 20 weeks (T2) and at 24 months after the end of the study (T3). Clinical evaluation: Damage (SLICC/ACR-DI) and disease activity (SLEDAI); psychological evaluation: symptoms (SLE-SSC), quality of life (SLEQOL), anxiety and depression (HAD) and coping strategies (CSI). Statistical analysis was intent to treat. Comparisons of variance between groups over time (ANOVA repeated measures). SPSS version 17. Value of p <0.05 considered significant.

Results: At baseline, TG and CG were homogeneous in all variables, including medication. In T2, TG showed significant improvement in majority domains of SLEQOL (Table 1), all domains of HADS and several domains of CSI. Some of these improvements were maintained at the 24 months follow-up after the end of the therapy (T3), mainly in quality of life.

TABLE 1
TABLE 1:
SLEQOL scores in SLE patients’ assessments

Conclusion: BGPP had long-lasting improvement in the quality of life of SLE patients and seems to be good complement in the treatment of these patients.

114

QUALITY OF LIFE IN MALE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

T. Lerner1, R. Dias1, E. Neto1, and E. Sato1. 1Federal University of São Paulo, São Paulo, Brazil.

Objectives: To evaluate quality of life (QoL) in men and women with systemic lupus erythematosus (SLE); to compare disease activity, damage, depression, anxiety and fatigue between men and women with SLE.

Methods: Cross-sectional study with 37 men and 69 women with SLE followed in the Autoimmune Rheumatic Diseases Outpatient Clinic at a tertiary hospital in São Paulo, Brazil. Quality of life was evaluated through the SF-36 and SLEQoL questionnaires; depression and anxiety were assessed by HADS and fatigue by FSS. Disease activity was evaluated by the Mex-SLEDAI and damage by the SLICC/ACR-DI or SDI. Descriptive analysis with mean and median, T-student, Mann-Whitney, and Chi-square tests, Pearson and Spearman correlations and multivariate linear regression analysis were performed.

Results: The median age, disease duration and years of education were comparable between men and women. However, there was a higher frequency of men who self-declared as non-white (76% vs. 57%, p=0.051). The median per capita income of men was greater than women [R$ 1,500.00 (600-15,000 .00) vs 1,000.00 (250-3,000.00), p=0.011]. There was no difference in disease activity scores at the time of assessment (p=0.552), however, men presented more frequent renal involvement (p=0.022), while women had more acute cutaneous lupus (p=0.001), non-scarring alopecia (p=0.009) and thrombocytopenia (p=0.010). Although more men were on pulse therapy with methylprednisolone (8.1% vs. 0%, p=0.04) at the time of the study, there was no difference regarding the need of pulse therapy throughout the evolution of the disease between the genders. Damage (SDI ≥ 1) due the disease or its treatment was observed in over half of the patients (51.4% of men and 56.5% of women, p=0.610). Related to quality of life, men had higher functional capacity (p=0.002), vitality (p=0.012) and mental health (p=0.040), as evaluated by the SF-36. There was also a tendency to lower values of SLEQoL in men (p=0.060). Fibromyalgia was more frequent among women, which has anegative impact on QoL. There were no differences in the frequency of anxiety, depression and fatigue. When excluding patients with prior diagnosis of fibromyalgia, only functional capacity maintained the difference between groups (p=0.026).

Conclusions: Men with SLE had better functional capacity, vitality and mental health as per the SF-36 than women with SLE. Fibromyalgia, more frequent among women, was the variable that most interfered with the quality of life of the SLE patients studied.

116

CLINICAL AND THERAPEUTIC CHARACTERISATION OF A COLOMBIAN COHORT WITH JUVENILE MYOSITIS

R. Fuentes1, M. Cañola1, J.C. Diaz-Coronado1, A. Rojas-Villarraga1, D. Hernandez-Parra1, P. Perez-Estrada1, J.C. Salazar-Uribe2, and R. Pineda-Tamayo1. 1Artmedica, Medellín, Colombia; 2National University of Colombia, Medellin, Colombia.

Objectives: To describe a Colombian cohort of patients with Juvenile Myositis recruited at a specialized multi-centered clinic.

Methods: Cross-sectional study with univariate and multivariate analysis. A a survival curve in which age and clinical outcomes during the assessment period of time are considered is also included.

Results: Out of 37 patients, 1 was excluded for having a positive dystrophy myopathy gene, 73% fulfilled definitive and 16% probable Bohan and Peter criteria; the majority were female 75,8% (28), age at onset 7,2 years (mean age), and clinical remission was obtained at 4 years (median) of the disease. There was a high prevalence of Gottron's sign and papules (89%), heliotrope rash (62%) and xalcinosis (37%). Other organs involved were: articular (24%), cardiac (5%), gastrointestinal (16%) and pulmonary (10%). There were 24% patients with amyopathic presentation (9). Antinuclear antibodies were present in 51.8%. Electromyography (EMG) was indicative of myopathy in 39,1% of the cases and only 10% had Myopathic changes by biopsy. Up to 32% of the patients had a negative biopsy. The most common treatments were metrothexate in 91% of the patients and corticosteroids in 56,7% of them. Antimalarials were used by 72% of the patients. In severe forms of the disease, the medications most frequently used were Cyclophosphamide (5%), Rituximab (16%) and IV Immunoglobulin (5%). Survival curves showed a faster rate relapse in patients younger than 15 years compared to the older ones (RR: 2,529 95% CI: 1,084-5,901; p=0.0319) as well for patients having Gottron's sign (RR:8,25 95% CI: 1,076-63,3; p=0,042).

TABLE 1
TABLE 1:
Sociodemographic and clinical characteristics of Colombian patients with Juvenile Myositis

Conclusions: Our patients have similar characteristics to those of other multi-centered studies, including those from Latin American. Gottron´s sign and papules were the most common finding followed by calcinosis and articular involvement. Patients younger than 15 years of age relapsed within a shorter time than the older patients.

118

EVALUATION OF PULMONARY INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS IN DAILY PRACTICE

M.A. Cusa1, J.I. Enghelmayer2, M.E. Fonrouge1, M.A. Lázaro1, and S.O. Scarafia1. 1Instituto de Asistencia Reumatológica Integral (I.A.R.I), Buenos Aires, Argentina; 2Pulmonology Section -Interstitial Lung Disease, Hospital de Clínicas "José de San Martín", Buenos Aires, Argentina.

Background: Systemic Sclerosis (SS) is a multi-systemic autoimmune disease. Pulmonary involvement has high morbility and mortality (up to 85%). High resolution computed tomography scan (HRCT) (gold standard), pulmonary function tests and the 6-minute walk test (6MWT) are used for diagnosis, prognostic evaluation and treatment.

Objective: To estimate the proportion of patients with SS who can complete pulmonary tests and describe their clinical features.

Methods: We evaluated patients with SS according to ACR/EULAR 2013 criteria with HRCT in the last 12 months. They were referred to a joint interview: rheumatologist/pulmonologist. Demographic and clinical data were collected. 6MWT and spirometry were performed. Patients with COPD history and uncontrolled pulmonary arterial hypertension (PAH) were excluded.

Results: Twenty-four patients were included, the median age and follow up time were 56.9 years (IQR 72.5-44.5) and 86.7 month (IQR 37.9-129), respectively. 41,6% of the patients had Diffuse cutaneous SS, 95.8% were ANA positive, 58% antibody anti-centromere positive, 4% anti- SCl70 positive; 20% had digital ulcers, 100% had Raynaud´s phenomenon (RP), median modified Rodnan Skin Score was7.5 (IQR 5.5-13), 33% presented capillaroscopy with an SD pattern. 74% had normal HRCT, 13% NSIP with less 20% commitment and 9% with greater than 20%, 4% had UIP. 75% were able to perform DLCO, half were normal, 28% had mild and 22 % moderate decrease. 96% performed spirometry which was normal in 86%; microstomia was the limiting factor in these tests. Sixty-six percent of the patients underwent the 6MWT, median 420 meters (IQR 475-393), baseline oxygen saturation 97.5% (DS 4.4) and final 88% (DS10.3) p 0.027. In 33% of the patients the pulse oximetry could not be performed due the RP. Initial median Borg median dyspnea score was 0 (IQR 0-3). The main limitation was musculoskeletal involvement, then R and microstomia.

Conclusions: 46% of the patients completed all lung assessment tests. Musculoskeletal involvement, RP and microstomia were the limiting factor on the evaluation of SS patients with these tools.

126

SEVERE DYSPHAGIA: "A POOR PROGNOSTIC MARKER" IN IDIOPATHIC INFLAMMATORY MYOPATHIES

Ana Carolina Costi, Lucila García, Claudia Elizabeth Pena, Rodrigo Aguila, Florencia savy, Sofia Velloso, Viviana Nagua, Adriana Testi, Pierina Sansinanea, and Mercedes Argentina García. Hospital Interzonal De Agudos General José De San Martín, La Plata.

Introduction: In Idiopathic Inflammatory Myopathies (MII), 18-20% of patients have dysphagia.

Objectives: To evaluate the frequency of dysphagia in patients with MII, association with other manifestations of the disease, treatment and evolution.

To evaluate clinical characteristics and evolution of severe dysphagia.

To compare clinical characteristics and evolution of mild-moderate versus severe dysphagia.

Patients and Methods: Historical, observational study. Patients with a diagnosis of MII were included according to modified classification criteria of Bohan and Peter. Demographic, clinical and complementary studies were recorded. Serious dysphagia was considered: contraindication of oral feeding. Descriptive statistics were performed. Chi2 test, Student's test or Mann Whitney as appropriate.

Results: We included 91 of 106 patients evaluated from 1992 to 2017: 76% female, mean age at diagnosis 48 ± 14 years. Fifty-three percent presented dysphagia: mild/moderate 62.5% (30/48 pts), severe 37.5% (18/48). Idiopathic dermatomyositis was the most frequent MII in these patients (71%).In patients with dysphagia, proximal muscle weakness was 90%, weakness of neck muscles 45%, weakness of respiratory muscles 27%.

A significant association was found between dysphagia and weakness of respiratory muscles, weak neck muscles, glucocorticoid pulses, gammaglobulin, grave infections and death. (Data not shown in the summary).

In patients with severe dysphagia, we observed a significant association with the requirement for mechanical ventilation, hospitalization in an intensive care unit, serious infections and death. (Table 1).

TABLE 1
TABLE 1

When comparing mild-moderate dysphagia vs severe dysphagia, a statistically significant association was found with neck muscles weakness, respiratory muscle weakness, glucocorticoid pulses, gamma globulin use, requirement for mechanical ventilation, hospitalization in an intensive care unit, severe infections and mortality. (Table 2)

TABLE 2
TABLE 2

Conclusion: Fifty-three percent of patients with MII had dysphagia at some time of the disease. Severe dysphagia was associated with parameters of disease severity, poor prognosis and increased mortality.

127

WAITING ROOM PROJECT: AN EDUCATIONAL PROGRAM FOR SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS AND THEIR FAMILIES

V.O. Bicalho2, F.A.P. Oliveira2, A.G. Cerqueira2, J.C.L. Pereira2, M.G.C. Assis2, G.A. Ferreira1,2, D.C. Calderaro1,2, F.M. M. Santos1,2, R.W. Telles1,2, and C.C.D. Lanna1,2. 1Rheumatology Unit, Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil; 2School of Medicine, Universidade Federal de Minas Gerais, Brazil.

Objective: To present an Educational Program for lupus patients and their families in order to improve adherence to treatment and the patient’s prognosis.

Methods: This Project is part of an Extension Program of the Medical School of our Institution entitled “Systemic Lupus Erythematosus patients care and their families”. It was initiated in 2011, under the approval of the Board of Education, Research and Extension of the institution. A total of 600 patients, currently under treatment, are involved. Medical School students and rheumatology residents, altogether, developed high quality informative texts, with clear content and layman language appropriate for patients, under the supervision of the rheumatology faculty. The texts included information regarding some common clinical conditions in lupus patients and the importance of a healthy life style, with a focus on health promotion and disease prevention. The texts approached the traditional risk factors for coronary artery disease (Smoking, Arterial Hypertension, Diabetes Mellitus, Obesity, Physical Activity), medical conditions related to general health and lupus treatment damage (Sun Protection, Healthy Food, Oral Health, Vaccination, Osteoporosis). They were illustrated by the team of the Communication Department of the Medical School, and printed in a leaflet format.

Results: The leaflets are handed and discussed with the patients, by the medical students, while they wait for their appointment with the rheumatologist. While it is an opportunity for the patients to make changes in their life styles, it is also an opportunity for the students to improve their knowledge about the comorbidities, health habits and their communication abilities. A study conducted in 2014 showed a high recognition rate of those lupus patients who attended the Unit about the risk factors for coronary artery disease, suggesting that the leaflets were an effective tool for patient education. The online version is available on the website of the Medical School of UFMG (https://site.medicina.ufmg.br/alo/material-didatico/).

Conclusions: Improving patients’ access to information must be a goal for health professionals who deal with SLE patients. When exposed to good quality information patients can take an active part in the decision-making process about their health care. We consider that the leaflets have been an important source of information and education for lupus patients and their families.

137

INCREASED RENAL DAMAGE IN HYPOCOMPLEMENTEMIC PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

L. García, C.E. Pena, M. Mamberti, R. Aguila Maldonado, A.C. Costi, A.C. Testi, V. Nagua, and M.A. García. Hospital San Martín, La Plata, Argentina.

Objective: To compare clinical manifestations, laboratory values, renal prognosis and mortality in normal and hypocomplementemic patients with AAV.

Methods: Observational, analytical study. Data from the medical records of patients older than 18 years of age were evaluated between the years 2000-2017. Patients with diagnosis of AAV who met the 1990 ACR Classification criteria or the 2012 Chapel Hill Consensus Conference were included. Hypocomplementemia was defined as C3 values below 80 mg/dl or C4 below 15 mg/dl. Chi-square or Fisher's exact tests were used for dichotomous variables, as appropriate. A p-value <0.05 was considered statistically significant. Logistic regression analysis was used to identify predictors of survival.

Results: We examined 87 patients with AAV (female 56.2%, mean follow-up 24 months, mean age at disease onset 49 years ± 14.9 SD). Most frequent type of vasculitis was Granulomatosis with polyangiitis (49.4%). Hypocomplementemia was present in 7/57 patients (12.28%) and it was significantly associated with renal damage (p=0.034 OR 12.8 95% CI 0.69-236), particularly with decreased glomerular filtrate (p=0.045 OR: 8.2 95% CI 0.92-74.0). A higher prevalence of proteinuria greater than 1 g/24 hours was observed in hypocomplementemic patients 57 % vs 25% (p=0.068). All renal biopsies were classified as pauci-immune glomerulonephritis. Average number of glomeruli affected was 13 [IQR 25-75% (7-17)], predominating the sclerosing type (44%). The degree of interstitial fibrosis, tubular atrophy (52%) and vascular damage (57%) was mild. In 3 samples we observed deposits of immunocomplexes (IgG+), complement (C3+) or fibrinogen by immunofluorescence. These patients showed creatinine values above 4 mg/dl. There were no statistically significant differences in renal histology between groups (p: 0.091). No associations between hypocomplementemia and other organic involvement were found; the same was the case for the analytical and immunological parameters. The mortality rate was 18% (16/87), and there no differences between groups (p: 0.300).

Conclusions: Hypocomplementemia was associated with increased renal damage: decreased glomerular filtrate and greater values of proteinuria; as reported in the literature. There were no other statistically significant differences between groups in terms of outcomes.

139

HOSPITALIZATIONS IN ARGENTINEAN PATIENTS WITH SYSTEMIC SCLEROSIS, 2010-2014

S.S. Porta1, G.G. Sequeira1, E.M. Kerzberg1, C.G. Guevel2, and M.M. Fernández2. 1Servicio de Reumatología, Hospital J. M. Ramos Mejía; 2Dirección de Estadísticas e Información de Salud. Ministerio de Salud, de la República Argentina.

Introduction: Systemic Sclerosis (SSc) is an autoimmune disease that results in substantial morbidity and mortality. However, no data have been published regarding the features of SSc-related hospitalizations in Latin America.

Objective: To examine the discharge records of patients with SSc in Argentina.

Methods: All cases diagnosed with SSc (ICD-10 codes: M340, 341,348 and 349) between 2010 and 2014 were selected. SSc was either the leading or the secondary cause of hospitalization. The records were obtained from inpatient care facilities of Argentina’s public sector, under national, provincial and municipal purview. The data were anonymous and identified discharges, not patients. SSc diagnosis was performed at the discretion of the treating physicians who filled out the reports according to the recommendations of the Health Statistics System. A p<0.05 was considered significant.

Results: One thousand and sixty-four discharges were analyzed. The patients ‘median age was 49 years, and 75% of them were female. SSc was the leading cause of hospitalization in 944 (88.7%) of the cases, and the secondary cause in 120 (11.3%). In terms of age and gender, non-statistically significant differences were observed for discharges when SSc was either the leading or the secondary cause of hospitalization. The median inpatient length of stay was 3 days when SSc was the leading cause of hospitalization (range 25-75%: 1-8) vs 5 days (range 25- 75%: 2-8) in the secondary cases (p=0.006). Mortality was 3.8% in the former and 9.2% in the latter (p=0.01). Patients who died had a higher average age than those who did not: 54 (SD 18) vs 47 years (SD 18) (p=0.004), and their median inpatient length of stay was longer: 5 (range 25-75%:1-16) vs 3 days (range 25% 75%:1-8) (p=0.03). Although there was a higher proportion of female patients among those who died (83% vs 75%), these differences were not statistically significant (p=0.3).

Conclusions: When SSc is the secondary cause of hospitalization, patients have longer inpatient length of stay and higher intrahospital mortality than those in whom SSc is the leading cause of hospitalization. Age and longer length of stay appear to be associated with higher intrahospital mortality in SSc.

148

PREGNANCY AND RHEUMATIC DISEASES

N.L. Cucchiaro1, M.M. Aciar1, E. Picco1, R.V. Juarez1, and M.E. Crespo1. 1Hospital Señor del Milagro, Salta, Argentina.

Background: Rheumatic diseases (RD) are more prevalent in women during childbearing age, and pregnancy can influence their disease activity.

Aim: To describe the course of RD in a population of pregnant women and their maternal-fetal outcomes.

Methods: Pregnant women with RD registered in the database of Hospital Público Materno Infantil from Salta, who carried their offsprings at that institution during the period between January 2006 and December 2016 were included. Clinical records were reviewed to collect data regarding socio-demographic, RD and its characteristics, obstetric background, pregnancy complications and fetal outcomes. Statistics: qualitative data was expressed as frequencies and percentages, quantitative data in medians and interquartile ranges (IQR). Data was analyzed by Chi square or Fisher´s exact test, Student’s test or Mann Whitney test. A p value < 0.05 was considered.

Results: 51 patients with a median age 27 (IQR 23 – 32) were included; 70 pregnancies were registered during this period. Obstetric backgrounds showed 148 previous pregnancies, 49 (33) miscarriages. Twenty-six (50.1) patients had systemic lupus erythematosus (SLE), 13 (25.5) rheumatoid arthritis (RA), 4 (7.8) antiphospholipid syndrome (APS), 4 (7.8) overlap syndrome (OS), 2 (2) undifferentiated connective tissue disease (uCTD), 2 (3.9) SLE+APS. They had a median of 3 years (IQR 0.75 – 6) of disease duration since diagnosis. There were 56 hospitalizations and the more frequent causes were: threatened premature delivery 12 (21.4), scheduled control 10 (17.85), urinary tract infection 9 (16) and threatened abortion 4 (7.1). Eight pregnancies (11.4) ended with an abortion, 11 (15.7) with a vaginal delivery, 25 (35.7) with an emergency cesarean section and 26 (37.1) with an scheduled cesarean section. Fifty pregnancies ended with 52 live fetuses (1 twin), of which 1 (2) was post-term and 19 (38) premature. The more frequent causes of emergency termination of pregnancy were: fetal death (FD) 10 (14.3), preeclampsia 4 (5.7), nephrotic syndrome 4 (5.7), pregnancy-induced hypertension 3 (4.2) and abruptio placenta (PA) 3 (4.2). SLE patients had more complications compared with other RD, but this did not reach statistical significance. The mean fetal birth weight was 2830 g (IQR 2300 – 3250 g) in all RD, and significantly less in SLE patients versus the rest (2423 g versus 2888 g p=0.03). There were 2 maternal deaths, both in SLE patients, due to complications of pulmonary thromboembolism and PA.

Conclusions: SLE and RA were the more prevalent RD in this sample of patients. Thirty – three percent had a history of fetal losses, and 63.7% of the pregnancies ended prematurely because of complications: 25.7%, fetal losses and 38%, prematurity. SLE diagnosis was associated with low birth weight and more severe pregnancy-associated complications.

167

FIBROBLAST SUBPOPULATIONS IN LESIONAL SKIN OF SYSTEMIC SCLEROSIS PATIENTS

G.F. Mora1, E. Santini Araujo2, M. Mamani3, M. Uemura3, M. Maguna Laville4, and R. Cabrini5. 1Sección Inmunología Clínica – Hospital Militar Central – Buenos Aires, Argentina; 2International Academy of Pathology; 3Servicio de Reumatología – Hospital Rivadavia – Buenos Aires, Argentina; 4Servicio de Cirugía – Hospital Militar Central – Buenos Aires, Argentina; 5Laboratorio de Patología Quirúrgica. Facultad de Odontología – Universidad de Buenos Aires, Argentina.

Background: Systemic Sclerosis (SSc) is a rare disease, with an estimated prevalence rate of 3:100.000 cases/year and a female predominance. Systemic fibrosis in scleroderma resembles a wound healing process “gone awry”, in which cells of the immune system, fibroblasts and their subpopulations have a central role. Stromal mesenchymal stem cells role in fibrosis and their engagement to fibroblast lineage determine the subpopulation (residents, mesenchymal precursors) that would prevail in the scleroderma scenario.

Objectives: To study the pathologic and immunohistochemical features and fibroblast cell subpopulations in the affected skin of patients with the diagnosis of SSc, compared with the skin of healthy individuals.

Methods: The design of the study was cross-sectional, on ambulatory and hospitalized patients between 2008 and 2013. Skin biopsies were obtained by incision in the forearm of patients with the diagnosis of SSc (ACR). These were compared with the skin from the forearm of healthy volunteers who underwent orthopaedic surgery. Clinical and serological characteristics of patients were revisited. All patients and controls signed an informed consent for participation in the study, and it was approved by the ethics committee of all participating institutions. Skin slides were incubated with murine monoclonal antibodies: anti-smooth-muscle actin (AML), anti-CD45+RO, anti-CD34+ and anti CD105+ −Leica®-. As positive controls were used: for AML colon carcinoma; for CD45+RO, normal tonsil and for CD34+, angiosarcoma. As negative controls, slides were incubated with PBS.

Results: 19 patients with SSc were enrolled (10 diffuse, 7 limited, 1 overlap syndrome –all female- and 1 graft-versus host disease -male-) and 7 controls (all women). Mean age was 49 years for patients (18-74), and 52 for the controls (45-77). Time from the diagnosis of SSc to this study was 79 months (4-360). Mean fibroblast count per 40X field was 65.8 for cases and 23 for controls. There was an average of 54.9 AML positive fibroblasts per 40X field in patients and 12.4 in controls (p < 0,05). Fibroblasts positive for CD45+RO were a mean of 48 per field in patients, while there was no CD45+RO expression in controls. For CD34+, patients had a mean of 13,2 positive fibroblasts per field, and controls showed no expression. Neither slides from patients nor from controls showed CD105+ expression in fibroblasts. No significative correlation on any fibroblast expression and clinical findings was found. The presence of antinuclear antibodies in sera of SSc patients showed a tendency to correlate to AML expression in fibroblasts (p=0,06). A mild correlation was found between the expression of AML and CD45RO+ in SSc fibroblasts (r=0,6). This finding may suggest the presence of anidated circulating fibrocytes in affected skin of SSc patients.

Conclusions: Skin fibroblast from SSc patients showed more prominently the expression of AML compared to controls (p<0,05). There was a tendency to correlate the expression of AML and CD45RO+ in SSc fibroblasts (r=0.6). This could suggest the presence of mesenchymal precursors, as fibrocytes. No correlation was found between immunohistochemical and clinical findings in SSc patients. There was a mild association between the presence of antinuclear antibodies and fibroblast AML expression in SSc.

169

CANCER AND RHEUMATIC DISEASE

J. Quevedo1, and M. Herrera1. 1University of San Carlos of Guatemala, Roosevelt Hospital, Guatemala, Guatemala.

Objectives: To determine the most frequent types of malignancies in patients with rheumatic disease (RD).

Methods: An observational descriptive study was performed in patients with RD and malignancy. The inclusion criteria were: patients of both sexes, who met criteria for RD classification and with diagnosis of malignancy before or after the diagnosis of RD. The diagnosis of cancer was made by histopathology and demographic and clinical data were collected from the medical records. Data analysis were performed using descriptive statistics.

Results: Thirty patients (100% female) with RD were identified and 32 cases of cancer were documented. The mean age was 49.3 (26-70) years at the time of RD diagnosis. It was documented that 5 (16.6%) had previous diagnosis of cancer and 25 (83.4%) developed a malignancy. The most frequent diagnoses were Rheumatoid Arthritis (RA) in 17 (56.6%), Systemic Lupus Erythematosus (SLE) in 6 (20%) and Dermatomyositis (DM) in 2 (6.6%). Table 1.

TABLE 1
TABLE 1:
Rheumatic Disease
TABLE 2
TABLE 2:
Type of Cancer and Rheumatic Disease

Conclusions: A larger number of cancer cases were documented in patients with RA and SLE, as in previous studies. The most frequent cancers in this study were cervix, breast and gastric, unlike the types of cancer presented in patients with RD in other populations.

It cannot be established if certain types of cancer are more frequent RD, since the incidence of cancer varies according to the different populations. In Guatemala, cervical, breast and gastric cancer are the most frequent.

177

CLINICAL COMPARISON OF THE NEW VS. THE OLD CRITERIA FOR INFLAMMATORY MYOPATHY IN A COLOMBIAN COHORT

R. Fuentes1, D. Gil-Calderon1, M. Cañola1, J.C. Diaz-Coronado1, A. Rojas-Villarraga1, D. Hernandez-Parra1, P. Perez-Estrada1, J.C. Salazar-Uribe2, and R. Pineda-Tamayo1. 1Artmedica, Medellín, Colombia; 2National University of Colombia, Medellín, Colombia.

Objectives: To compare ACR/EULAR 2017 versus Peter and Bohan criteria for Idiopathic Inflammatory Myopathy in a Colombian cohort.

Methods: A cross-sectional research was done with data collected between 2014 and 2017 from a population diagnosed with Idiopathic Myopathy according to Peter and Bohan criteria and followed up for at least six months. The new ACR/EULAR criteria were applied to each individual using the online tool (http://www.imm.ki.se/biosatistics/calculators/iim). Both sets of criteria were compared using Cohen´s kappa coefficient and concordance was evaluated.

Results: Data of 149 patients were obtained. Anti-Jo1 results were not available for 75% of the patients. Biopsy was available in 44,3% of patients. Biopsy results were compatible with inflammatory myopathy in 66,7% and non-compatible in 33,3%. According to Peter and Bohan criteria the diagnosis of idiopathic inflammatory myopathy was definite in 63,1% of the patients, and probable in 27,5%. Using ACR/EULAR 2017 criteria instead the diagnosis was definite in 63,1%, probable 10,1% and non-possible in 20,8%. According to the new criteria, 31 patients had polymyositis, 47 dematomyositis, 4 amyopathic dermatomyositis, 35 juvenile myositis and 1 inclusion body myositis. The concordance analysis between the two sets of criteria showed agreement of 54% (kappa 0,22 p <0,001) for the entire group, 59% (kappa 0,21 p<0,001) for adults, 32% (kappa 0,18 p=0,05) for children, 44% (kappa 0,05 p=0,3) for polymyositis and 42% (kappa 0,16 p=0,1) for dermatomyositis.

Conclusions: We found a very low rate of positive anti-Jo1, probably because the test was not done most patients (poor test availability). Similarly, biopsies were frequently unavailable and showed a high rate of negativity for inflammatory myopathy. In contrast with the main ACR/EULAR criteria study where an 89% agreement (kappa 0,7 p<0,00001) was reported, we found a very low rate of agreement. This could be explained as already mentioned by the poor availability of anti-Jo1. Another reason could be the more frequent use of electromyogram among our patients which was considered in Peter and Bohan’s criteria but not in the ACR/EULAR criteria.

179

EFFECT OF STEROID DOSE IN SLEEP DISTURBANCE IN A SLE COHORT

A. Betancourt1, S. Sapag Durán1, R. Quiroz1, R. Gómez1, A. Seewald1, M. García Carrasco1, A.M. Berón1, and D. Dubinky1. 1Hospital de Clínicas “José de San Martín”, Universidad de Buenos Aires, Buenos Aires, Argentina.

Objectives: Primary: To describe sleep disturbances in SLE patients and compare them to healthy controls. Secondary: To evaluate the effect of corticosteroids in sleep disturbances in SLE patients.

Methods: Descriptive, cross-sectional, observational study. Cases were defined as patients >18 years of age with SLE (ACR 1997), evaluated between 01-07/2017 who responded the questionnaires. Pregnant and obese patients, those with COPD, diabetes, narcolepsy, obstructive sleep apnea, kidney failure and heart failure were excluded. Educational and socioeconomic level (Graffar) were evaluated. We assessed time of diagnosis, current treatment, demographic data, disease activity (SLEDAI) and damage accrual (SLICC Damage Index or SDI). Controls were healthy individuals who responded to the questionnaires. Sleep disturbance was assessed by self administered questionnaires. Insomnia was evaluated by ISI, sleep quality by PSQI, depression by BECK, fatigue by FACIT, and function by HAQ. The statistic analyses wer performed using Epi-info 7. Descriptive data are shown as means ± SD. Percentages and prevalence as 95% CI. Chi square or Fisher´s tests were used as appropriate (α=0.05).

Results: 51 cases were included (Mean age 39.6 ± 12.9 years, 92% female) and 49 controls (mean age 41.8 ± 13.0 years, 88% female).

Conclusions: SLE patients presented more insomnia, sleep disturbances depression, fatigue and functional incapacity compared to controls. In this study, despite previously published data, no differences in sleep disturbances were found related to the dose of steroids used.

189

USE OF CONTRACEPTIVE METHODS IN AN ARGENTINEAN SINGLE CENTER SYSTEMIC LUPUS ERYTHEMATOSUS COHORT: 1 YEAR FOLLOW-UP

J. Portilla1, R. Gomez1, M. García Carrasco1, A.M. Beron1, and D. Dubinsky1. 1Hospital de Clínicas “José de San Martín”, Universidad de Buenos Aires. Argentina.

Objectives: The primary objective of this study was to describe the use of contraceptive methods (CM) in ambulatory patients with SLE. The secondary objective was to compare its use with previous data from this cohort.

Methods: Descriptive, observational study. In June 2016, an initial group was defined from the electronic database of our hospital’s SLE unit; it included female patients ≥16 years of age with SLE (SLICC 2012), with sexual status reported and ≥1 evaluation during the previous 12 months. Menopausal patients were excluded. 121 patients were included in the study and we analyzed demographic data; disease duration; socioeconomic status (Graffar scale); disease activity (SELENA-SLEDAI) and damage accrual (SLICC Damage Index or SDI); use of teratogens: Methotrexate (MTX), Mycophenolate mofetil (MMF), Cyclophosphamide (CYC), Rituximab (RTX) and Belimumab (BEL), self-reported sexual status (active/non active) and CM: intrauterine device (IUD), condom (Cdm), hormonal contraceptive pill (CP) and surgical method (Qx). In November 2017, the same variables were reevaluated in the same group. Results were compared between the original and the new data.

Results: From the original cohort defined in June 2016, 19/121 (15.7%) patients were not included in the reevaluation: 4 (3.3%) became menopausal and 15 (12.4%) were lost to follow up. 102/121 (84.3%) patients were reevaluated. Median age 30 years (IQR 25-39.5 years), Median SLEDAI 2 (IQR 0-6). Sexually active 80/102 (78.4%), use of CM 71/80 (88%): CP 5/80 (7%), Cdm 52/80 (73.2%), IUD 12/80 (16.9%) and Qx 2/80 (2.8%).

Conclusions: The most used CM in our SLE cohort was Cdm, as it is in the general Argentine population (80%). In the 2017 reevaluation, the use of CM was even higher. This might be due to the constant evaluation of its use by the attending physicians.

We deem necessary the education, counseling and evaluation of CM use in every SLE patient’s visit, to prevent unplanned pregnancies in active patients and to avoid sexually transmitted infections in those immunosuppressed.

TABLE 1
TABLE 1:
Use of CM by SLEDAI in Sexually Active SLE Patients
TABLE 2
TABLE 2:
Use of CM by Teratogen in Sexually Active SLE Patients
TABLE 3
TABLE 3:
Use of CM by SLEDAI in Sexually Active Patients, 2016/2017 Comparison
TABLE 4
TABLE 4:
Use of CMin Sexually Active Patients Using Teratogens, 2016/2017 Comparison

196

MEASUREMENT OF ANTIMÜLLERIAN HORMONE AS A PARAMETER OF OVARIAN RESERVE IN LUPUS PATIENTS. RELATIONSHIP WITH ETHNICITY AND EXPOSURE TO IMMUNOSUPPRESSANTS

María Victoria Collado1, Diana Ortiz de Zárate1, Maite Mayer2, Noelia Antoniol3, Karin Kirmayr4, Juan Manuel Bande5, Susana Roverano6, Graciela Gómez1, Silvana Roveto1, Judith Sarano1, Gargiulo María de los Ángeles1, Perez Nicolás1, Khoury Marina1, Suarez Lorena1, Papasidero Silvia5, Perandones Carlos3, Barreira Juan Carlos2, and Rimoldi Daniel1. 1Instituto de Investigaciones Médicas A. Lanari; 2Hospital Británico; 3FLENI, CABA, Argentina; 4Clínica San Carlos de Bariloche, Rio Negro, Argentina; 5Hospital de Agudos Dr. E. Tornú, CABA, Argentina; 6Hospital Cullen, Santa Fe, Argentina.

Objective: To describe Antimüllerian Hormone (AMH) values in a lupus patients sample from Argentina and to evaluate their relationship with ethnicity and exposure to immunosuppressants.

Methods: Women (≥18-40 years of age) who fulfilled the American College of Rheumatology Systemic Lupus Erythematosus (SLE) classification criteria were included. A control group was integrated by same age range healthy women who presented regular menses (25-35 days). Women with polycystic ovarian syndrome, endometriosis, oophorectomy, radiotherapy or amenorrhea of known cause (not due to lupus) were excluded from both groups. AMH levels were analyzed in serum samples with ultrasensitive enzyme immunoassay (AMH Gen II by Beckman Coulter). An Elisa reader (THERMO Electro Corporation) was used for absorbance measurements. Ethnicity data were collected according to GLADEL criteria. Exposed to Immunosuppressant (EIS) treatment was considered if patient received cyclophosphamide (Cy), mycophenolate (MMF), azathioprine (AZA), belimumab, rituximab, tacrolimus or methotrexate before AMH determination. Numerical variables are shown as mean ± standard deviation or median (range). The Mann-Whitney, Kruskal-Wallis and Fisher's exact tests were used for the comparisons.

Results: Data from 30 controls and 52 SLE patients were analyzed. Age (years) at the time of AMH measurement: 29.83±6.85 in controls and 31.59±6.53 in SLE (p=0.3017). AMH level (ng/ml) was 2.66 (0.6-6.67) in controls and 0.93 (0-7.42) in SLE (p=0.0003).

Time between SLE diagnosis and AMH determination: 59.5 months (1-244). Caucasian (n = 32), mestizo (n = 16), Amerindian (n = 3), missing data (n = 1). EIS: Cy (n=21), MMF (n=18), AZA (n=12), belimumab (n=3), rituximab (n=2), others (n=8). Cumulative dose of Cy: 5.5 g (0.5-24). Age (years) was 31.6±6 in 32 Caucasian (Ca) and 31.9±6 in 19 No-Caucasian (NoCa) (p=0.9376). EIS: 75% of Ca (n=24) and 47.37% of NCa (n=9). AMH level: 1.385 (0-5.31) in Ca and 0.78 (0-7.42) in NoCa (p=0.0858). The comparison between groups, according to ethnicity and EIS treatment, is shown in the table.

Conclusions: SLE patients had AMH levels significantly lower than controls of similar age. Caucasian women not exposed to immunosupressants presented the highest AMH levels. Caucasian women exposed to immunosuppressants had lower levels of AMH than those not exposed to them. SLE women who received the highest cumulative doses of corticosteroids had the lowest levels of AMH, but they were no Caucasians and had been exposed to immunosuppressants too. More studies are needed to analyze the relation between these factors and the ovarian reserve.

204

TEMPORAL ARTERY BIOPSY IN ARGENTINEAN PATIENTS

M. L. de la Torre1, A. Kostianovsky1, and C. N. Pisoni1. 1CEMIC, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”, Buenos Aires, Argentina.

Objectives: Giant cell arteritis (GCA) is the most frequent systemic vasculitis in individuals over the age of 50. Its diagnosis relies on clinical evaluation, laboratory and imaging tests and it is confirmed on the basis of histologic findings. However, the biopsy can be inconclusive in up to 40% of the patients.

Since there is a lack of studies on this subject in Latin America, and in Argentina, our aim was to describe the clinical characteristics and histologic findings of patients with temporal artery biopsy (TAB) performed at our hospital.

Methods: We conducted a descriptive study of 63 consecutive patients with TAB performed at our hospital over a period of 11 years (2005-2016).

We collected of the following variables: epidemiology, clinical symptoms, laboratory results, histopathology, imaging studies, treatment, and follow up.

Results: Sixty-three patients were included, 43 females (68%), mean age 72 years (SD 8.4). Sixty seven percent had polymyalgia rheumatica 11.5 months prior to the TAB.

Seventeen biopsies (27%) were positive. The mean post fixation length was 1.68 cm (SD 1.2). Histologic features in positive biopsies were: 17 (100%) had inflammatory infiltrates, 14 (82.3%) giant cells, 10 (58.8%) elastic fibers fragmentation and 2 (11.8%) endothelial proliferation.

Table 1 shows epidemiological clinical, laboratory and treatment of patients grouped by biopsy result.

TABLE 1
TABLE 1

Patients with positive biopsy results had higher erythrocyte sedimentation rate (ESR) and platelets and more frequent jaw claudication.

Multivariate analysis of positive biopsies did not show a significant association, probable due to small number of patients with positive biopsy.

Conclusions: Twenty seven percent of biopsies were positive. Jaw claudication, higher levels of ESR and greater number of platelets were associated with a positive biopsy. Course, treatment and relapses/recurrences did not differ between patients with positive or negative biopsies.

208

EVALUATION OF THE PERFORMANCE OF THE 2016 ACR-EULAR CLASSIFICATION CRITERIA FOR PRIMARY SJOGREN`S SYNDROME IN DIFFERENT ARGENTINEAN CENTERS

F. Melo1, E. Guerra1, C. Troitiño1, A. Secco1, F. Romanini1, M. Mamani1, S. Papasidero2, M. J. Santa Cruz2, J. C. Barreira3, J. Demarchi3, P. Quevedo Mayorga3, I. Remolina Rincón3, M. Garcia4, R. Aguila Maldonado4, M. Rivero5, V. Perdomo5, and A. Catalan Pellet1. 1Hospital “Bernardino Rivadavia”, Ciudad Autónoma de Buenos Aires, Argentina; 2Hospital “Dr. E. Tornú”, Ciudad Autónoma de Buenos Aires, Argentina; 3Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina; 4Hospital San Martín de La Plata, La Plata, Provincia de Buenos Aires, Argentina; 5Hospital Municipal Nuestra Señora de la Merced, Alberti, Provincia de Buenos Aires, Argentina.

Introduction: Primary Sjögren`s Syndrome (pSS) is a multisystemic, autoimmune disease characterized mainly by the hypofunction of the salivary and lacrimal glands; however, the clinical spectrum of this disease extends from SICCA symptoms to the presence of extra-glandular manifestations being able to compromise multiple systems. The recent 2016 ACR-EULAR classification criteria were designed to be applied not only to patients with Sicca symptoms, but also to those with clinical manifestations included in the ESSDAI domains (EULAR primary Sjögren's syndrome disease activity) which would allow to classify those patients who first presented with extra-glandular manifestations.

Objectives: To evaluate the performance of the 2016 ACR-EULAR classification criteria for pSS in adult patients from different Argentinean centers.

Methods: A multi-center study of 5 national centers was carried out. We included patients older than 18, who presented clinical and/or analytical manifestations suggestive of pSS. To discriminate between cases and controls, the opinion of experts from different centers, blind to the previous diagnosis of these patients (with a degree of agreement ≥ 70%) was used as the gold standard. The exclusion criteria were similar to those present in the 2002 American-European and the 2012 ACR classification criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive likelihood ratio (LR +) were evaluated.

Results: A total of 226 patients were included, 97.3% were women, with an average age of 55 years (SD ± 12), and a mean duration of symptoms of 7.9 years (SD ± 6.8). 178 patients (78.7%) had a diagnosis of pSS according to the expert’s opinion, of which 171/178 (96.1%) had xerophthalmia, 172/178 (96.6%) xerostomia, 162/178 (91%) positivity at least for one domain of the ESSDAI and 3/178 (1.7%) did not present xerostomia or xerophthalmia at the time of diagnosis. A sensitivity of 94.9% (95% CI: 92.1 - 97.8%), a specificity of 95.8% (95% CI: 93.2 - 98.4%), a PPV of 98.8% (95% CI: 97.4 – 100%), a NPV of 83.6% (95% CI: 78.8 - 88.4%) and an LR + of 22.7 (95% CI: 13.6 - 62.7) was obtained.

Conclusions: The recent classification criteria showed a performance comparable to the precedent 2002 American-European and 2012 ACR classification criteria, with the advantage that the new criteria allows to classify those patients who first present with extra-glandular manifestations.

209

WHITE BLOOD CELL ABNORMALITIES IN SLE PATIENTS: RELATIONSHIP TO DISEASE MANIFESTATIONS, MEDICATIONS, ANTIBODIES AND RISK OF INFECTIONS

B. M. Virasoro1, and C. N. Pisoni1. 1Inmunology and Rheumatology Section, CEMIC, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” CABA, Argentina.

Background and Objective: Most Systemic Lupus Erythematosus (SLE) patients will develop hematological abnormalities during their disease course. The relationship of leukopenia, lymphopenia and neutropenia with infections in SLE patients is not well defined. Neither is the association between white blood cell counts and autoantibodies.

The aim of this study was to examine the behavior of leucocytes and lymphocytes in SLE patients and their relationship with clinical manifestations, autoantibodies and infections.

Methods: This is a historical study. White blood cell, lymphocyte and neutrophil counts were collected during the total follow up period. Patients were grouped into the following categories: normal white blood cell counts, persistent and intermittent leucopenia and lymphopenia. Persistence was defined if the abnormalities were seen in more than 75% of the determinations and intermittent if they were seen less than 75%. Leukopenia and lymphopenia were defined as having leukocyte counts below 4000 and 1500, respectively. Demographic features, disease manifestations, organ involvement defined according to the American College of Rheumatology (ACR) classification criteria, accumulated autoantibodies (ANA and ENAs), damage measured by the Systemic Lupus International Collaborating Clinics Damage Index(SLICC-SDI) score, mortality, infections and immunosuppressants ever received were retrieved from medical records.

Results: Ninety-seven patients were included. The most common hematologic abnormality identified was lymphopenia in 57 patients (65%) followed by leukopenia in 26 (27%). Forty three percent had intermittent and 11.2% persistent leukopenia; 43% had intermittent and 44.9 had persistent lymphopenia.

In the univariate analysis 49% of patients exposed to mycophenolate mofetil had normal leukocyte counts compared to 31.6% and 10% in the intermittent and persistent leukopenia groups (p=0.052). Patients with neurological disorder were more likely to have normal lymphocyte counts (22%) than intermittent (0 %) or persistent lymphopenia (7.5%) (p=0.027). Forty seven percent of patients in the persistent lymphopenia group had positive anti-nRNP compared to 15.4% in the intermittent lymphopenia group and 20% in the normal lymphocyte count group (p=0.007). No association was found between infections and any of the previously described groups. When patients with leukopenia and lymphopenia were dichotomized (YES/NO) we found that mycophenolate mofetil was associated with normal leukocyte counts. In the multivariate analysis mycophenolate mofetil was negatively associated to leukopenia (OR 0,33 p=0.042). We did not find any significant association of lymphopenia as a dichotomous variable.

Conclusions: Mycophenolate mofetil was associated with normal leukocyte count when adjusted for other significant variables. Anti nRNP and neurological manifestations were associated with lymphopenia and normal lymphocyte counts, respectively but only in the univariate analysis. Infections were not associated with any of the categories studied.

210

USEFULLNESS OF METHOTREXATE IN POLYMYALGIA RHEUMATICA

M. L. de la Torre1, A. M. Rodríguez2, M. A. Cosatti1, and C. N. Pisoni1. 1CEMIC, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”, Buenos Aires, Argentina; 2Hospital General de Agudos “Juan A. Fernández”, Buenos Aires, Argentina.

Background and Objectives: Polymyalgia rheumatica (PMR) is a frequent inflammatory condition in patients over 50 years of age. Nearly 60% of patients experience relapses of their symptoms during steroid tapering and steroid dependency is frequent. There is a need to find other therapeutic options to avoid the risks of long term steroid treatment. Methotrexate use in PMR has been studied with contradictory results regarding reduction of relapses. Our objective was to evaluate the efficacy of methotrexate in patients with PMR.

Methods: This is an observational longitudinal cohort study. We included 84 consecutive patients with PMR fulfilling EULAR/ACR 2012 criteria. Clinical symptoms, laboratory results, treatments received, and disease course information were extracted from the medical records. Patients were assigned to 3 groups according to the treatment prescribed by the treating physician. Group 1: treated with steroids alone, group 2: steroids initially and methotrexate following a relapse and group 3: steroids and methotrexate from the time of diagnosis.

Definitions: • Relapse: recurrence of symptoms and an increase of erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) in patients still receiving steroids. We evaluated the frequency of relapses and the time free of relapses.

• Remission: time of prednisone discontinuation.

• Recurrence: recurrence of the original symptoms and an increase of ESR or CRP after discontinuing prednisone.

Results: Eighty-four patients were included, 81.9% women, mean age 76 years (SD 8.3). The median time of follow up was 39 months (IQR 11-55). Patients were assigned to one of 3 treatment groups: 48 (57.1%) in Group 1, 26 (31.3%) in Group 2 and 9 (10.8 %) in Group 3. Table 1 shows a comparison between groups.

TABLE 1
TABLE 1

Conclusions: The use of methotrexate in PMR patients who had already had a relapse reduces the number of future relapses and increases the relapse free time. The time to the first relapse was longer in patients receiving combination therapy from diagnosis.

227

ARE URIC ACID LEVELS PREDICTORS OF LONG-TERM RENAL OUTCOMES IN LUPUS NEPHRITIS?

M. Lopes1, S. Gavinier2, E. Leon2, V. Viana2, E.F. Borba1, and E. Bonfa3. 1Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 2Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; 3Rheumatology Divison, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background and Objective: Hyperuricemia has been reported to be associated with chronic kidney disease (CKD) in several clinical conditions, and an association between increased uric acid (UA) serum levels and renal damage in lupus has also been described in some recent studies. However, the predictive value of UA for the development of long-term renal dysfunction in lupus nephritis is unknown. The purpose of this study was to evaluate if the UA level may be considered a predictor of long-term renal outcome in patients with lupus nephritis.

Methods: 75 biopsy-proven lupus nephritis patients with more than 7 years of follow-up were consecutively selected for this study. Clinical and laboratorial data were obtained using a standardized electronic chart database protocol carried out at 1-6 months interval. UA levels were measured in sera stored at −70°C for all SLE patients at biopsy during nephritis flare and in 31 patients, for whom sera were available, at 6 and 12 months post-biopsy. The renal outcome was examined after 7 years of follow-up to determine if UA levels were a predictor of good long-term renal outcome (Cr<1.5 mg/dL in 7 years). SLE patients were divided in two groups according to the renal outcome [good outcome (Cr<1.5 mg/dL in 7 years) and poor outcome (Cr≥1.5 mg/dL in 7 years)] to assess whether UA levels at different time-points of follow-up were able to differentiate such groups. ROC curves were plotted to assess UA accuracy.

Results: At baseline, patients had a mean SCr of 1.7±1.3 mg/dl, proteinuria of 5.7±4.7 g/24h, albumin of 2.4±0.8 g/dl, and SLEDAI scores of 9.5±5.0. Almost two-third of the patients (66%) patients had positive anti-dsDNA and 28 patients (35%) had SCr≥1.5 mg/dl. The distribution of histological classes among studied patients was: class II (6%), class III/IV (53%) and pure class V (36%). Serum UA levels were not able to differentiate good from poor long-term renal outcomes in patients with lupus nephritis at any of the time points examined: baseline, 6, 12 months (respectively p=0.96, p=0.76, p=0.77). As expected, the ROC curve with higher AUC (12 months) showed a low accuracy (AUC=0.59). The cut-off for UA was 5.46 mg/dL (Sensitivity=0.63, Specificity=0.65, Positive Predictive Value=0.38, Negative Predictive Value=0.16, 95% CI=0.2-0.7, p<0.05). The AUC was only associated with the current creatinine levels: at baseline (p=0.01), 6 months (p=0.03) and 12 months (p=0.01).

Conclusion: This study demonstrates that serum UA levels in lupus patients reflect solely the current renal function and they are not good predictors of long-term renal outcome in lupus nephritis.

229

DEVELOPMENT OF LYMPHOMA IN PATIENTS WITH SJOGREN'S SYNDROME

N. Lloves Schenone1, A. Secco1, M. Mamani1, F. Melo1, M. Adrover1, J. Barreira2, J. Dermarchi2, C. Segura Escobar2, L. Santiago3, G. Salvatierra4, A. Nitsche5, C. Asnal5, C. Amitrano5, P. Pucci5, C. Crow5, L. Ratti6, V. Cruzat6, S. Papasidero7, F. Caeiro8, S. Retamozo8, V. Saurit8, D. Baenas8, N. Riscanevo8, C. Gobbi9, E. Albiero9, and A. Catalán Pellet1. Hospital Bernardino Rivadavia (1), Hospital Británico (2), Organización Médica de Investigación (3), IPRI (4), Hospital Alemán (5), Clínica Bessone (6), Hospital Tornú (7), Hospital Privado Universitario de Córdoba (8), Hospital Córdoba (9).

Introduction: Non-Hodgkin lymphoma (NHL) is one of the most feared complications of primary Sjogren's syndrome (pSS). The most frequent is MALT type lymphoma, with localization in the parotid glands being common. There are no multicentric data in the Argentinean population regarding the frequency of appearance of this type of cancer in patients with pSS and the possible predictors of this outcome.

Objectives: To describe the prevalence and incidence rate of lymphoma in patients with pSS in nine centers in Argentina. To determine the frequency of involvement of the domains of the baseline clinical ESSDAI in those patients who developed lymphoma during their follow-up and compare them with the rest of the sample.

Materials and Methods: To respond to the primary objective, the design was observational, descriptive and historical. We included patients older than 18 years of age with a diagnosis of pSS according to ACR/EULAR 2002 criteria, included in a multi-center Argentinean database. Patients diagnosed with another associated autoimmune rheumatic disease were excluded.

Results: We included 708 patients, 95% female, with a mean age of 54.4 years (SD +/− 13.67), mean age at diagnosis of 49.7 years (SD +/− 13.32) and mean age at symptom onset of 47.19 (SD +/− 13.03). Fifteen patients presented lymphoma (prevalence: 2.12%). Six hundred thirty-six patients provided information for the survival analysis. The average follow-up time was 5 years (SD +/− 6.5). The incidence rate of lymphoma was 0.47 per 100 patient-years. The median time from the diagnosis of pSS to the development of lymphoma was 4 years (IQR: 1-6). The most frequently lymphoma type was MALT. The main predictor of lymphoma development was recurrent parotid gland enlargement (H.R: 4.17, 95% CI: 1.42-12.22). Table 1 reports the results regarding the clinical ESSDAI/.

TABLE 1
TABLE 1

Conclusion: The prevalence of lymphoma was 2.12% and the incidence rate of 0.47 lymphomas per 100 patients/year. Patients who developed lymphoma had a higher frequency of involvement of most of the domains of the baseline clinical ESSDAI compared to patients who did not present this complication. We found recurrent parotid glands enlargement as the main predictor of the development of this cancer.

230

SYSTEMIC SJÖGREN PRESENTING WITHOUT SICCA SYNDROME: CHARACTERIZATION OF 240 PATIENTS ACCORDING TO THE NEW 2017 ACR/EULAR CLASSIFICATION CRITERIA

Soledad Retamozo1,2,3, Gabriela Hernandez-Molina4, Valeria Valim5, Virginia Fernandes Moça Trevisani6, Sandra G. Pasoto7, Nihan Acar-Denizli8, Margit Zeher9, Kathy Sivils10, Thomas Mandl11, Raphaele Seror12, Xiaomei Li13, Chiara Baldini14, Xavier Mariette12, Jacques-Ericn Gottenberg15, Debashish Danda16, Roberta Priori17, Luca Quartuccio18, Berkan Armagan19, Aike A. Kruize20, Seung-Ki Kwok21, Marie Wahren-Herlenius22, Sonja Praprotnik23, Damien Sene24, Elena Bartoloni25, Maureen Rischmueller26, Roser Solans27, Yasunori Suzuki28, David Isenberg29, Piotr Wiland30, Gunnel Nordmark31, Guadalupe Fraile32, Hendrika Bootsma33, Takashi Nakamura34, Roberto Giacomelli35, Valerie Devauchelle-Pensec36, Benedikt Hofauer37, Michele Bombardieri38, Daniel Hammenfors39, Steven E. Carsons40, Tamer A Gheita41, Fabiola Atzeni42, Jacques Morel43, Cristina Vollenveider44, Manuel Ramos-Casals1, and Pilar Brito-Zerón1,45 on behalf of the Sjogren Big Data Consortium. 1Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain; 2Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba- Argentina; 3Instituto De Investigaciones En Ciencias De La Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Córdoba - Argentina; 4Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México City, Mexico; 5Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil; 6Federal University of São Paulo, Sao Paulo, Brazil; 7Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil; 8Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Istanbul, Turkey; 9Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 10Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; 11Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden; 12Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France; 13Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei, China; 14Rheumatology Unit, University of Pisa, Pisa, Italy; 15Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France; 16Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India; 17Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy; 18Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy; 19Department of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 20Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; 21Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; 22Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; 23Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia; 24Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France; 25Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy; 26Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia; 27Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain; 28Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; 29Centre for Rheumatology, Division of Medicine, University College London, London, UK; 30Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland; 31Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 32 Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain; 33 Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 34Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 35Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy; 36Rheumatology Department, Brest University Hospital, Brest, France; 37Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany; 38Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK; 39Department of Clinical Science, University of Bergen; and Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; 40 Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, Mineola, NY, USA; 41Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt; 42IRCCS Galeazzi Orthopedic Institute, Milan, Italy; 43Department of Rheumatology, Teaching hospital and University of Montpellier, Montpellier, France; 44German Hospital, Buenos Aires, Argentina; 45Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain.

Background: To examine the epidemiological, clinical and immunological characteristics of patients presenting with systemic disease in the absence of sicca manifestations in a large international cohort of patients diagnosed with primary Sjögren syndrome (SS).

Methods: The new 2017 ACR/EULAR Classification Criteria for SS allows the application of these criteria to any patient with a suspicion of SS due to systemic features with at least 1 positive ESSDAI domain. We have identified how many patients from the Big Data Sjögren Registry showed this early systemic presentation at the time of disease diagnosis. As a control group, we selected those patients who presented with the typical sicca syndrome (subjective dry mouth and dry eyes).

Results: We have identified 240 (2.5%) patients presenting with a non-sicca systemic disease among the 9545 patients included in the Registry: 211 (88%) were women and 29 (12%) were men (female: male ratio, 7:1), with a mean age at diagnosis of 46.6 years. The frequency of fulfilment of the 2017 criteria was: 63% for positive ocular staining, 76% for abnormal Schirmer test, 79% for abnormal unstimulated whole salivary flow, 84% for positive salivary gland biopsy and 88% for Ro autoantibodies. Other immunological tests included positive ANA (88%), RF (54%), low C3 levels (25%), low C4 levels (13%), and cryoglobulins (9%). In comparison with patients presenting with the typical sicca syndrome, those presenting as systemic Sjögren with no sicca syndrome were younger (46.6 vs 52.9, p<0.001), more frequently males (12% vs 6%, p<0.001) and less frequently classified ethnically as White (36% vs 79%, p<0.001). Immunologically, patients with systemic Sjögren had a higher frequency of anti-Ro antibodies (88% vs 71%, p<0.001), positive antinuclear antibodies (88% vs 81%, p=0.014) and low C3 levels (25% vs 13%, p<0.001). Systemic activity at diagnosis was significantly higher in patients with systemic non-sicca Sjögren in comparison with those with sicca syndrome, including higher mean ESSDAI (6.5 vs 6.0, p<0.001) and clinESSDAI (6.6 vs 6.2, p=0.003) scores. In addition, moderate systemic activity (moderate-DAS) was found in a higher frequency in patients with systemic presentation (41% vs 30%, p=0.001). With respect to the ESSDAI domains, patients with non-sicca systemic disease had a higher frequency of activity in the constitutional (13% vs 8%, p=0.01), renal (12% vs 4%, p<0.001), hematological (31% vs 22%, p=0.005) and biological (64% vs 49%, p<0.001) domains, but a lower frequency of activity in the glandular (12% vs 22%, p<0.001) and peripheral nervous system (3% vs 6%, p=0.05) domains.

Conclusions: Primary Sjögren syndrome at diagnosis is presenting as a systemic disease in the absence of the typical sicca symptoms in less than 3% of cases. These patients are characterized for being younger, less frequently women and White, with a higher frequency of immunological markers (Ro, ANA and low C3), higher activity in the hematological (cytopenias) and biological (hypergammaglobulinemia) domains, and higher activity in the constitutional (fever) and renal clinical domains in comparison with patients presenting with the classical sicca syndrome.

232

CLINICAL AND IMMUNOLOGICAL PRIMARY SJÖGREN SYNDROME’ DISEASE PATTERNS ARE DRIVEN BY GENDER AND AGE AT DIAGNOSIS

Soledad Retamozo1,2,3, Gabriela Hernandez-Molina4, Valeria Valim5, Virginia Fernandes Moça Trevisani6, Sandra G. Pasoto7, Belchin Kostov8, Margit Zeher9, Kathy Sivils10, Thomas Mandl11, Raphaele Seror12, Xiaomei Li13, Chiara Baldini14, Xavier Mariette12, Jacques-Ericn Gottenberg15, Debashish Danda16, Roberta Priori17, Luca Quartuccio18, Berkan Armagan19, Aike A. Kruize20, Seung-Ki Kwok21, Marie Wahren-Herlenius22, Sonja Praprotnik23, Damien Sene24, Elena Bartoloni25, Maureen Rischmueller26, Roser Solans27, Yasunori Suzuki28, David Isenberg29, Piotr Wiland30, Gunnel Nordmark31, Guadalupe Fraile32, Hendrika Bootsma33, Takashi Nakamura34, Roberto Giacomelli35, Valerie Devauchelle-Pensec36, Benedikt Hofauer37, Michele Bombardieri38, Daniel Hammenfors39, Steven E. Carsons40, Tamer A Gheita41, Fabiola Atzeni42, Jacques Morel43, Cristina Vollenveider44, Manuel Ramos-Casals1, and Pilar Brito-Zerón1,45 on behalf of the Sjogren Big Data Consortium. 1Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain; 2Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba- Argentina; 3Instituto De Investigaciones En Ciencias De La Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Córdoba - Argentina; 4Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México City, Mexico; 5Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil; 6Federal University of São Paulo, Sao Paulo, Brazil; 7Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil; 8Primary Care Research Group, IDIBAPS, Centre d’Assistència Primària ABS Les Corts, GESCLINIC, Barcelona, Spain; 9Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 10Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; 11Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden; 12Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France; 13Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei, China; 14Rheumatology Unit, University of Pisa, Pisa, Italy; 15Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France; 16Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India; 17Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy; 18Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy; 19Department of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 20Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; 21Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; 22Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; 23Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia; 24Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France; 25Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy; 26Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia; 27Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain; 28Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; 29Centre for Rheumatology, Division of Medicine, University College London, London, UK; 30Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland; 31Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 32Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain; 33Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 34Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 35Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy; 36Rheumatology Department, Brest University Hospital, Brest, France; 37Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany; 38Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK; 39Department of Clinical Science, University of Bergen; and Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; 40Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, Mineola, NY, USA; 41Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt; 42IRCCS Galeazzi Orthopedic Institute, Milan, Italy; 43Department of Rheumatology, Teaching hospital and University of Montpellier, Montpellier, France; 44German Hospital, Buenos Aires, Argentina; 45Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain.

Objective: To examine how the epidemiological profile modifies systemic involvement measured at the time of diagnosis in a large international cohort of patients diagnosed with primary Sjögren syndrome (SS).

Patients: The Big Data Sjögren Project is an international, multicentre registry formed in 2014 to take a “high-definition” picture of the main features of primary SS at diagnosis by merging international SS databases. By October 2017, the database included 9545 consecutive patients recruited from 22 countries of the five continents.

Results: Baseline ESSDAI score was available in 9118 patients (93% female, mean age at diagnosis 53 years). The median ESSDAI score at diagnosis of the entire cohort was 4 (IQR 1-8). Men showed a higher systemic activity at diagnosis than women, including a higher median ESSDAI score (5 vs 4, p<0.001), clinESSDAI score (5 vs 3, p<0.001), a higher frequency of patients presenting with a high DAS (24.1% vs 13.7%, p<0.001), a higher frequency of patients with high activity in at least one domain (14.5% vs 7.8%, p<0.001) and a lower frequency of patients having no activity (ESSDAI = 0) (16% vs 19%, p<0.001). With respect to the ESSDAI domains, men had a higher risk of having activity at diagnosis in the lymphadenopathy (OR 1.5, CI95% 1.20-1.88), glandular (OR 1.3, CI95% 1.14-1.49), pulmonary (OR 1.44, CI95% 1.18-1.76), peripheral nervous system (OR 2.0, CI95% 1.60-2.57) and central nervous system (OR 2.2, CI95% 1.49-3.41) domains in comparison with women. A younger onset of the disease (<35 years) was also associated with a higher systemic activity at diagnosis in comparison with patients with older onset, including a higher median ESSDAI score (4 vs 3, p<0.001), clinESSDAI score (4 vs 3, p=0.001) and a lower frequency of patients having no activity (ESSDAI = 0) (13% vs 22%, p<0.001). With respect to the ESSDAI domains, a younger onset was associated with an enhanced risk of presenting activity at diagnosis in the constitutional (OR 1.27, CI95% 1.05-1.53), lymphadenopathy (OR 1.59, CI95% 1.34-1.89), glandular (OR 1.16, CI95% 1.04-1.29), cutaneous (OR 1.35, CI95% 1.13-1.49), renal (OR 1.4, CI95% 1.09-1.81), hematological (OR 1.18, CI95% 1.06-1.32) and biological (OR 1.33, CI95% 1.27-1.40) domains, while older onset was associated with an enhanced risk for presenting activity at articular (OR 0.89, CI95% 0.82-0.97) pulmonary (OR 0.54, CI95% 0.42-0.70), muscular (OR 0.55, CI95% 0.33-0.94) and peripheral nervous system (OR 0.59, CI95% 0.42-0.81) domains.

Conclusion: Gender and age at diagnosis play a key role in the severity of systemic involvement measured at the diagnosis of primary Sjögren syndrome, with men and patients diagnosed before 35 years being those presenting with the highest systemic profile. Some organs are more active when the disease is diagnosed at younger ages (constitutional, lymph nodes, glands, skin and kidneys) and others when the disease is diagnosed in the elderly (joints, lungs and neuromuscular). Clinically, the ESSDAI provides a reliable picture of systemic involvement and may help identify epidemiological subsets with high systemic activity at diagnosis and, therefore, at high risk of suffering a complicated clinical course.

233

HOW ETHNICITY MODIFIES SYSTEMIC ACTIVITY OF PRIMARY SJÖGREN SYNDROME: ANALYSIS OF BASELINE ESSDAI SCORES IN A MULTI-ETHNIC INTERNATIONAL COHORT

Soledad Retamozo1,2,3, Gabriela Hernandez-Molina4, Valeria Valim5, Virginia Fernandes Moça Trevisani6, Sandra G. Pasoto7, Belchin Kostov8, Margit Zeher9, Kathy Sivils10, Thomas Mandl11, Raphaele Seror12, Xiaomei Li13, Chiara Baldini14, Xavier Mariette12, Jacques-Ericn Gottenberg15, Debashish Danda16, Antonina Minniti17, Luca Quartuccio18, Berkan Armagan19, Aike A. Kruize20, Seung-Ki Kwok21, Marie Wahren-Herlenius22, Sonja Praprotnik23, Damien Sene24, Elena Bartoloni25, Maureen Rischmueller26, Roser Solans27, Yasunori Suzuki28, David Isenberg29, Piotr Wiland30, Gunnel Nordmark31, Guadalupe Fraile32, Hendrika Bootsma33, Takashi Nakamura34, Roberto Giacomelli35, Valerie Devauchelle-Pensec36, Benedikt Hofauer37, Michele Bombardieri38, Daniel Hammenfors39, Steven E. Carsons40, Tamer A. Gheita41, Fabiola Atzeni42, Jacques Morel43, Cristina Vollenveider44, Manuel Ramos-Casals1, and Pilar Brito-Zerón1,45 on behalf of the Sjogren Big Data Consortium. 1Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain; 2Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba- Argentina; 3Instituto De Investigaciones En Ciencias De La Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Córdoba - Argentina; 4Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México City, Mexico; 5Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil; 6Federal University of São Paulo, Sao Paulo, Brazil; 7Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil; 8 Primary Care Research Group, IDIBAPS, Centre d’Assistència Primària ABS Les Corts, GESCLINIC, Barcelona, Spain; 9Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 10Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; 11Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden; 12Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France; 13Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei, China; 14Rheumatology Unit, University of Pisa, Pisa, Italy; 15Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France; 16Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India; 17Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy; 18Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy; 19Department of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 20Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; 21Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; 22Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; 23Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia; 24Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France; 25Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy; 26Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia; 27Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain; 28Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; 29Centre for Rheumatology, Division of Medicine, University College London, London, UK; 30Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland; 31Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 32Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain; 33Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 34Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 35Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy; 36Rheumatology Department, Brest University Hospital, Brest, France; 37Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany; 38Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK; 39Department of Clinical Science, University of Bergen; and Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; 40Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, Mineola, NY, USA; 41Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt; 42IRCCS Galeazzi Orthopedic Institute, Milan, Italy; 43Department of Rheumatology, Teaching hospital and University of Montpellier, Montpellier, France; 44German Hospital, Buenos Aires, Argentina; 45Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain.

Objectives: To examine the influence of ethnicity on the clinical presentation of primary Sjögren syndrome (SjS) by measuring the systemic activity (ESSDAI score) at the time of diagnosis.

Methods: The Big Data Sjögren Project is an international, multicentre registry formed in 2014 to take a “high-definition” worldwide picture of the main features of primary SjS at diagnosis by merging international SjS databases. By October 2017, the database included 9545 consecutive patients recruited from 22 countries of the five continents. Systemic involvement was defined according to the ESSDAI/clinESSDAI. Disease activity states (DAS) were categorized according to the global ESSDAI score as low-activity (ESSDAI<5), moderate-activity (5≤ESSDAI≤13) and high-activity (ESSDAI≥14).

Results: Ethnicity data were available for 8746 (95%) of 9118 patients with available information on ESSDAI: 6614 (76%) patients were classified as White, 1306 (15%) as Asian, 520 (6%) as Hispanic, 130 (1%) as Black/African American –BAA- and 176 (2%) as other ethnicities. The highest median ESSDAI score at diagnosis was found in BAA patients (6 vs 4 in W, 4 in A and 3 in H, p<0.001), as well as for median clinESSDAI score (5 vs 4 in W, 3 in A and 3 in H, p<0.001). The highest frequency of patients presenting at diagnosis with a high DAS was also found in BAA (16.2% vs 15.8% in W, 11.6% in A and 8.5% in H, p<0.001). With respect to the ESSDAI domains, BAA patients had an enhanced risk of presenting activity at diagnosis in peripheral nervous system (OR 2, 95% CI 1.27-3.15) and biological (OR 1.2, 95% CI 1.03-1.4) domains in comparison with White patients. In contrast, Asian patients had a lower risk of presenting activity at diagnosis in the lymphadenopathy (OR 0.54, 95% CI 0.43-0.69), glandular (OR 0.41, 95% CI 0.35-0.49), articular (OR 0.57, 95% CI 0.51-0.63), cutaneous (OR 0.82, 95% CI 0.67-0.99), muscular (OR 0.41, 95% 0.25-0.7) CI, peripheral nervous system (OR 0.54, 95% CI 0.4-0.73) and central nervous system (OR 0.47, 95% CI 0.27-0.81) domains, but a higher risk of having activity at renal (OR 2.58, 95% CI 2.11-3.16), hematological (OR 1.16, 95% CI 1.05-1.29) and biological (OR 1.19, 95% CI 1.13-1.26) domains in comparison with White patients. Finally, Hispanic patients had a lower risk of presenting activity at diagnosis in glandular (OR 0.63, 95% CI 0.52-0.78), pulmonary (OR 0.49, 95% CI 0.34-0.71), muscular (OR 0.35, 95% CI 0.14-0.84) and hematological (OR 0.73, 95% CI 0.6-0.89) domains in comparison with White patients.

Conclusions: This study provides the first evidence of a strong influence of ethnicity on the systemic phenotype of primary SjS at diagnosis. BAA and White people had the highest median ESSDAI and clinESSDAI scores and the highest frequencies of patients classified as high DAS, in contrast to Asian and Hispanic people. Organ-by-organ activity also varied significantly across ethnicities.

234

HOW DIFFERENT SYSTEMIC ORGAN INVOLVEMENTS OVERLAP IN PATIENTS WITH PRIMARY SJÖGREN SYNDROME: ANALYSIS USING A MATHEMATICAL MODEL

Soledad Retamozo1,2,3, Gabriela Hernandez-Molina4, Valeria Valim5, Virginia Fernandes Moça Trevisani6, Sandra G. Pasoto7, Belchin Kostov8, Margit Zeher9, Kathy Sivils10, Thomas Mandl11, Raphaele Seror12, Xiaomei Li13, Chiara Baldini14, Xavier Mariette12, Jacques-Ericn Gottenberg15, Debashish Danda16, Roberta Priori17, Luca Quartuccio18, Berkan Armagan19, Aike A. Kruize20, Seung-Ki Kwok21, Marie Wahren-Herlenius22, Sonja Praprotnik23, Damien Sene24, Elena Bartoloni25, Maureen Rischmueller26, Roser Solans27, Yasunori Suzuki28, David Isenberg29, Piotr Wiland30, Gunnel Nordmark31, Guadalupe Fraile32, Hendrika Bootsma33, Takashi Nakamura34, Roberto Giacomelli35, Valerie Devauchelle-Pensec36, Benedikt Hofauer37, Michele Bombardieri38, Daniel Hammenfors39, Steven E. Carsons40, Tamer A Gheita41, Fabiola Atzeni42, Jacques Morel43, Cristina Vollenveider44, Manuel Ramos-Casals1, and Pilar Brito-Zerón1,45 on behalf of the Sjogren Big Data Consortium. 1Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain; 2Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba- Argentina; 3Instituto De Investigaciones En Ciencias De La Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Córdoba - Argentina; 4Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México City, Mexico; 5Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil; 6Federal University of São Paulo, Sao Paulo, Brazil; 7Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil; 8Primary Care Research Group, IDIBAPS, Centre d’Assistència Primària ABS Les Corts, GESCLINIC, Barcelona, Spain; 9Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary; 10Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; 11Department of Rheumatology, Malmö University Hospital, Lund University, Lund, Sweden; 12Center for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, Université Paris Sud, INSERM, Paris, France; 13Department of Rheumatology and Immunology, Anhui Provincial Hospital, Hefei, China; 14Rheumatology Unit, University of Pisa, Pisa, Italy; 15Department of Rheumatology, Strasbourg University Hospital, Université de Strasbourg, CNRS, Strasbourg, France; 16Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India; 17Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Rome, Italy; 18Clinic of Rheumatology, Department of Medical and Biological Sciences, University Hospital "Santa Maria della Misericordia", Udine, Italy; 19Department of Internal Medicine, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey; 20Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; 21Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; 22Department of Medicine, Solna, Unit of Experimental Rheumatology, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; 23Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia; 24Service de Médecine Interne 2, Hôpital Lariboisière, Université Paris VII, Assistance Publique-Hôpitaux de Paris, 2, Paris, France; 25Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy; 26Department of Rheumatology, School of Medicine, The University of Western Australia, Crawley, Australia; 27Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain; 28Division of Rheumatology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan; 29Centre for Rheumatology, Division of Medicine, University College London, London, UK; 30Department of Rheumatology and Internal Medicine, Wroclaw Medical Hospital, Wroclaw, Poland; 31Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 32Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain; 33Department of Rheumatology & Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 34Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 35Clinical Unit of Rheumatology, University of l'Aquila, School of Medicine, L'Aquila, Italy; 36Rheumatology Department, Brest University Hospital, Brest, France; 37Hals-Nasen-Ohrenklinik und Poliklinik, Technische Universität München, München, Germany; 38Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, UK; 39Department of Clinical Science, University of Bergen; and Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; 40Division of Rheumatology, Allergy and Immunology Winthrop-University Hospital, Stony Brook University School of Medicine, Mineola, NY, USA; 41Rheumatology Department, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt; 42IRCCS Galeazzi Orthopedic Institute, Milan, Italy; 43Department of Rheumatology, Teaching hospital and University of Montpellier, Montpellier, France; 44German Hospital, Buenos Aires, Argentina; 45Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain.

Background and Objectives: To examine the degree of overlap of the different systemic organ involved in patients with primary Sjögren syndrome (SjS) in a large international cohort using a mathematical model.

Methods: We have quantified at diagnosis systemic involvement (defined according to the 10 domains of the ESSDAI score) in patients included in the Big Data Sjögren Registry. We quantified how many patients had activity in more than one domain, how many patients had involvement of an isolated domain and we measured the degree of overlap between the main pairs and triplets of associated groups of active domains. Using a mathematical model, we represented the overlap between groups by means of Venn diagrams.

Results: 9118 patients were included in the Registry with ESSDAI values available at the time at diagnosis: 5758 (63%) had activity in at least one ESSDAI domain. Among them, 3167 (55%) had only one active domain, 1532 (27%) two, 628 (11%) three and 431 (7%) four or more active domains. Three domains showed activity at diagnosis in at least 10% of patients: articular (37.9%), glandular (21.4%) and pulmonary (10.4%). The frequency of patients having concomitant activity in other organs varied widely in each domain: among patients with articular involvement, 54% of cases had another domain active, a figure that was 68% for patients with glandular involvement; 88% of patients with muscular involvement had concomitant activity in other organs, 78% of those with peripheral neuropathy and 74% of those with renal involvement. Numerically, the most frequent associations among two different domains were between articular and glandular (n=944), pulmonary (n=487), constitutional (n=464) or cutaneous (n=410) domains, while the most frequent associations among 3 organs were between articular/glandular plus pulmonary (n=224), constitutional (n=216) or lymphadenopathy (n=173) domains. Mathematical model identified the highest degree of overlap among the different domains for the following pairs: % of patients with muscular activity who had concomitant glandular activity (Δ30.2% with respect to the expected frequency of glandular activity), those with lymphadenopathy who had concomitant glandular activity (Δ22.9%), and those with constitutional who had concomitant articular (Δ21.6%) or glandular (Δ21.1%) activities.

Conclusions: Primary Sjögren syndrome is presenting at diagnosis as a systemic disease in two thirds of cases; in more than half the cases, there was only one active domain, although 7% of patients presented with a multisystemic disease affecting 4 or more different organs. An enhanced degree of overlap in comparison with the expected values found for the total cohort was identified in the concomitant activity for the clusters glandular-lymphadenopathy-muscular and constitutional-articular-glandular (Figures 1a and 1b).

FIGURE 1
FIGURE 1

236

DEVELOPMENT OF HIGH SYSTEMIC ACTIVITY IN PRIMARY SJÖGREN SYNDROME: ANALYSIS OF 1487 SPANISH PATIENTS (GEAS-SS REGISTRY)

Soledad Retamozo1, Alejandra Flores-Chávez1, Roser Solans2, Guadalupe Fraile3, Brenda Maure4, Carles Feijoo5, Roberto Pérez-Alvarez6, Francisco Javier Rascón7, Mónica Zamora8, Miguel López-Dupla9, Miguel Ángel Duarte-Millán10, Mar Ripoll11, Pablo Guisado-Vasco12, Eva Fonseca13, Gloria de-la-Red14, Antonio Chamorro15, Elena Sanchez Vizcaíno16, Blanca Pinilla17, María José Soto-Cárdenas18, Miriam Akasbi19, Patricia Fanlo20, Alberto Gato21, Iratxe Jiménez-Heredia22, Borja De-Miguel23, Sofía Arteaga1,24, Belchin Kostov25, Manuel Ramos-Casals1, and Pilar Brito-Zerón1,16 on behalf of the SS Study Group GEAS-SEMI*. 1Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona; 2Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona; 3Department of Internal Medicine, Hospital Ramón y Cajal, Madrid; 4Department of Internal Medicine, Complejo Hospitalario Universitario, Vigo; 5Department of Internal Medicine, Hospital Parc Taulí, Sabadell; 6Department of Internal Medicine, Hospital Alvaro Cunqueiro, Vigo; 7Department of Internal Medicine, Hospital Son Espases, Palma de Mallorca; 8Department of Internal Medicine, Hospital Virgen de las Nieves, Granada; 9Department of Internal Medicine, Hospital Joan XXIII, Tarragona; 10Department of Internal Medicine, Hospital de Fuenlabrada, Fuenlabrada; 11Department of Internal Medicine, Hospital Infanta Sofía, Madrid; 12Department of Internal Medicine, Complejo Hospitalario Ruber Juan Bravo, Madrid; 13Department of Internal Medicine, Hospital de Cabueñes, Gijón; 14Department of Internal Medicine, Hospital Esperit Sant, Santa Coloma de Gramenet; 15Department of Internal Medicine, Hospital de Salamanca, Salamanca; 16Unit of Clinical Investigation, Hospital CIMA-Sanitas, Barcelona; 17 Department of Internal Medicine, Hospital Gregorio Marañón, Madrid; 18Department of Medicine, University of Cádiz, Cádiz; 19Department of Internal Medicine, Hospital Infanta Leonor, Madrid; 20Department of Internal Medicine, Hospital Virgen del Camino, Pamplona; 21Department of Internal Medicina, Hospital de Albacete, Albacete; 22Department of Internal Medicine, Hospital de Sagunto, Valencia; 23Department of Internal Medicine, Hospital 12 de Octubre, Madrid; 24Universidad de Antioquía, Medellín, Colombia; 25Transverse group for research in primary care, IDIBAPS, Barcelona.

Background and Objective: To characterize high systemic involvement in primary Sjögren syndrome (SS) in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI).

Methods: The GEAS-SS Study Group was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SjS. Systemic involvement was characterized using ESSDAI definitions for its12 domains, and patients scoring as high in the domains that specifically contain high activity (lymphadenopathy, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular) were identified and analysed.

Results: Of the 1487 patients included in the Registry, 186 (12.5%) presented with 197 systemic features classified as high according to the corresponding organ-by-organ ESSDAI domains. There were 159 women and 27 men, with a mean age of 59,06 years (range 15–89 years) at the time of the diagnosis of high activity. High systemic activity was scored in the lymphadenopathy (n=53), peripheral nervous system (n=31), central nervous system (n=25), pulmonary (n=24), renal (n=21), articular (n=16), skin (n=16), hematological (n=7) and muscular (n=4) domains. Men were overrepresented in the muscular (33%), lymphadenopathy (19%) and cutaneous (19%) domains. The domains diagnosed at younger ages included muscular (mean age of 45 years), CNS (49,7 years), articular (54,3 yrs) and hematological (55,4 yrs), while cutaneous (63,2 yrs) and pulmonary (67,1 years) were diagnosed at older ages. The main clinical syndromes responsible for high systemic activity were lymphoma (n=53), ataxic neuronopathy (n=14), pulmonary fibrosis (n=12), diffuse leukocytoclastic vasculitis (n=10), severe polyneuropathy (n=10), myelitis (n=8), meningitis (n=7), multiple mononeuritis (n=7), membranous/membranoproliferative glomerulonephritis (n=6) and severe thrombocytopenia (n=5). Notably, 13 (81%) out of the 16 patients presenting with high activity in the articular domain (>6 joints involved) were finally diagnosed with rheumatoid arthritis during their follow-up.

Conclusions: Primary Sjögren syndrome at diagnosis is presenting with high systemic activity in 12.5% of cases; half the cases were related to either the development of lymphoma or of severe neurological features. Nearly all the patients presenting with severe polyarthritis were finally diagnosed with associated rheumatoid arthritis.

238

SJÖGREN SYNDROME AS THE MAIN MATERNAL DISEASE IN MOTHERS WITH BABIES AFFECTED WITH RO-ASSOCIATED CONGENITAL HEART BLOCK (SPANISH REGISTRY REBACC-GEAS-SEMI)

Soledad Retamozo1,2,3, Gerard Espinosa4, Ángel Robles5, Pilar Rosich6, Luis Sáez Comet7, Olga Capdevila8, José Antonio Vargas9, Lucio Pallarés10, Luis Trapiella11, José Antonio González Nieto12, Aleida Martínez Zapico13, Mónica Rodriguez14, Carles Tolosa6, Francesca Mitjavila8, Mercedes Pérez-Conesa6, José Mario Sabio9, Luis Caminal11, Joaquim Oristrell6, César Morcillo15, Alejandra Flores-Chavez1, Belchin Kostov16, Manuel Ramos-Casals1,4, and Pilar Brito-Zerón1,4 on behalf of the REBACC-GEAS-SEMI Registry. 1Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona; 2Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba- Argentina; 3Instituto De Investigaciones En Ciencias De La Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Córdoba - Argentina; 4Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain; 5Department of Internal Medicine, Hospital La Paz, Madrid; 6Department of Internal Medicine, Hospital Parc Taulí, Sabadell; 7Systemic Autoimmune Diseases Unit, Hospital Miguel Servet, Zaragoza; 8Department of Internal Medicine, Hospital de Bellvitge; 9Department of Internal Medicine, Hospital Virgen de las Nieves, Granada; 10Department of Internal Medicine, Hospital Son Espases, Palma de Mallorca; 11Department of Internal Medicine, Hospital de Cabueñes, Gijón; 12Department of Internal Medicine, Hospital Can Misses, Ibiza; 13Department of Internal Medicine, Hospital Universitario Central de Asturias; 14Department of Internal Medicine, Hospital Mutua de Terrasa, Sabadell; 15Department of Internal Medicine, Hospital CIMA-Sanitas; 16Transversal Research Group Primary Care, IDIBAPS, Barcelona.

Objective: To examine both, the already-diagnosed and the underlying maternal autoimmune diseases of mothers with pregnancies affected by autoimmune congenital heart block (CHB) associated with maternal anti-Ro antibodies.

Methods: The REBACC Spanish Multicenter Registry was started on March 2014. It is integrated by 12 centers with substantial experience in the management of systemic autoimmune diseases. Autoimmune CHB was defined as: a) CHB of any type (I, II or III), fetal endocardial fibroelastosis (FEF) and/or cardiomyopathy, b) cardiac block diagnosed in utero or in the first postpartum month, and c) mothers carrying anti-Ro52, Ro60 and/or La autoantibodies.

Results: As of October 2017, the REBACC Registry included a total of 45 anti-Ro+ mothers with 50 single pregnancies with CHB. Mean maternal age at the time of first affected pregnancy with CHB was 32.97 years (range: 22-44). All mothers were anti-Ro60 (+), 17/17 anti-Ro52 (+) and 32/44 (73%) anti-La (+). The mean gestational age at diagnosis of CHB was 23 weeks (range 16-37). Information about fetal outcomes was available in 45 pregnancies: AV blocks were of type I in 2 pregnancies (4.5%), type II in 15 (33%) and type III in 27 (60%); 1 had an isolated FEF (2.5%); therapies used included dexamethasone or betamethasone (n=25), intravenous immunoglobulins (n=5), and plasma exchanges (n=3); 11 pregnancies were interrupted due to bad fetal prognosis (24%) and 34 (76%) were successfully carried to term; pacemaker implantation was required in 18/34 babies (53%). At diagnosis of the first affected pregnancy, 31 (69%) mothers did not have any autoimmune disease and the remaining 14 (31%) had Sjögren syndrome (n=7), SLE (n=5) and undifferentiated autoimmune disease (n=2). At the last visit, of the 33 women who initially did not have any autoimmune diagnosis (none/undifferentiated autoimmune disease), 22 (67%) had developed a systemic autoimmune disease (SS in 16, SLE in 5 and SS+ SLE in 1). Also, 1 mother previously diagnosed with SLE, was subsequently diagnosed with Sjögren syndrome.

Conclusions: At the last visit, 23/45 (51%) mothers with affected babies with Ro-associated CHB have a diagnosis of Sjögren syndrome (overwhelmingly primary); in contrast, 70% of mothers have no identified systemic autoimmune disease at the first affected pregnancy, as anti-Ro antibodies can be detected several years before Sjögren syndrome is diagnosed. Autoimmune CHB is one of the first early signs of primary SS in women of childbearing age.

239

EARLY AND LATE ONSET BIOPSY-PROVEN LUPUS NEPHRITIS WITHOUT OTHER ASSOCIATED AUTOIMMUNE DISEASES: SEVERITY AND LONG-TERM OUTCOME

M. Lopes1, L. Santos2, L. Seguro3, and E. Bonfa4. 1Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 2Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil; 3Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; 4Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Objective: Lupus nephritis (LN) usually develops within the first years of Systemic Lupus Erythematosus (SLE) onset and rarely after that. There are scarce studies comparing early versus late onset nephritis (before vs. five years of diagnosis). In the only two reports available, the lack of renal biopsy and inclusion of elderly patients in one and the non-exclusion of concomitant APS and other associated autoimmune diseases in the other, preclude a definitive conclusion about their findings. The aim of this study was to compare the severity and long-term outcome (after 7 years) in these two groups: early and late-onset nephritis.

Methods: 77 patients with biopsy-proven LN with more than 7 years of follow-up were included. Patients were divided in two groups: early-onset nephritis (n=62) and late-onset nephritis (n=15). Clinical and laboratorial data were obtained using a standardized electronic chart database protocol carried out at 1-6 months interval and established in 2000. To minimize bias, patients >50 years or with concomitant autoimmune diseases were excluded. Variables evaluated at the LN presentation were SLEDAI, creatinine, albumin, anti-DNA positivity and nephritis class. Variables evaluated at the long-term outcome (after 7 years) were SDI, creatinine, dialysis and mortality. Student’s test, Fisher and Mann Whitney tests were used for comparison.

Results: The average time of LN presentation was 0.9±1.4 years for the early-onset group and 10.6±3.6 years for the late-onset group. Of note, both groups had similar nephritis duration (13.5±4.2 vs. 13.1±2.9 years, p=0.69) and comparable mean ages (30.1±10.5 vs. 35.4±10.0 years, p=0.08) allowing a more accurate comparison between groups. Regarding severity, groups were alike at nephritis onset: SLEDAI (8.5 [min-max: 4-22] vs. 7[min-max: 6-17] p=0.14), creatinine (1.49 mg/dl±1.21 vs. 1.48±0.99, p=0.95); albumin (2.59 mg/dl±0.84 vs. 2.84±0.65 p=0.23); proteinuria (5.27±4.7 vs. 3.95±2.1 mg/dl, p=0.05); proliferative nephritis (53%[n=33] vs. 40%[n=6] p=0.37). There was also no difference in the long-term outcomes between the groups: SDI (1 [min-max 0 – 5] vs. (1 [min-max.:0 – 4], p=0.73); creatinine (1.93 mg/dl±2.4 vs. 2.1±2.6, p=0.34); dialysis (16.1% [n=10] vs. 20.0% [n=3], p=0.70); mortality (14.5% [n=9] vs. 0% [n=0], p=0.19).

Conclusion: On the present study we demonstrated that at ptresentation, late-onset nephritis is comparable to early-onset nephritis concerning clinical, laboratorial and histological features. In addition, we provided novel evidence that long-term outcomes in biopsy proven severe lupus patients without other associated autoimmune diseases are comparable in both groups. These findings suggest that treatment targets and therapeutic interventions should be the same for these patients.

244

ESOPHAGEAL INVOLVEMENT CHARACTERISTICS AND ASSOCIATED FEATURES IN A LARGE COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

H. C. da Silva1, A. B. Bortoluzzo2, A. P. Luppino-Assad1, D. C. O. Andrade1, and P. D. Sampaio-Barros1. 1Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil; 2Insper Institute of Education and Research, Sao Paulo, Brazil.

Introduction: Esophageal involvement is the most frequent visceral manifestation in patients with systemic sclerosis (SSc).

Objective: To evaluate the frequency and associated features of esophageal manifestations over the course of the disease in a large group Brazilian SSc patients.

Methods: Six-hundred and twenty-six patients with SSc according to the ACR/EULAR criteria, being followed at a single rheumatology service between 2010 and 2016 were included. There was predominance of female gender (87%) and limited SSc (72%). Patients with a confirmed diagnosis of esophageal dismotility, gastroesophageal reflux disease (GERD) and Barrett's esophagus were evaluated in relation to their demographic, clinical and laboratory characteristics. Statistical significance was considered when p <0.05.

Results: Esophageal involvement was found in 551 patients (88%), and 537 patients (85.8%) reported a motility disorder, including 464 patients who were confirmed by barium contrasted esophagogram. Four-hundred and eighty-five patients (72.5%) had GERD and 43 (6.9%) had Barrett's esophagus. Esophageal dismotility was associated with calcinosis (p = 0.035), telangiectasias (p = 0.010), digital ischemic ulcers (p < 0.001), GERD (p < 0.001), Barrett's esophagus (p = 0.006), stomach involvement (p = 0.038), interstitial lung disease (p < 0.001) and cardiac involvement (p = 0.020); several autoantibodies were associated with esophageal involvement, including anticentromere (p = 0.037), anti-Scl70 (p = 0.047), anti-RNA polymerase III (p = 0.047) and anti-Ku antibodies (p = 0.012). GERD was positively associated with calcinosis (p = 0.022), esophageal motility disorder (p < 0.001), Barrett's esophagus (p < 0.001), esophageal surgery (p = 0.041); intestinal malabsorption (p = 0.014) and anti-Th TO RNP antibody (p = 0.025). Barrett's esophagus was associated with esophageal motility disorder (p = 0.006), GERD (p < 0.001), esophageal stenosis (p < 0.001), esophageal surgery (p < 0.001), stomach involvement (p < 0.001), fecal incontinence (p = 0.029), cancer (p = 0.001), and anti-Th TO RNP antibody (p = 0.046).

Conclusions: Esophageal involvement was very frequent in this large SSc Brazilian cohort, with both motility disorder and GERD being associated with several clinical manifestations and different SSc autoantibodies.

246

PERIPHERAL NEUROPATHY IN SYSTEMIC SCLEROSIS

J. M. A. Teixeira1, S. Gavinier1, A. B. Bortoluzzo2, A. P. Luppino-Assad1, H. C. da Silva1, D. C. O. Andrade1, and P. D. Sampaio-Barros1. 1Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil; 2Insper Institute of Education and Research, Sao Paulo, Brazil.

Introduction: The description of peripheral neuropathy is not frequent in systemic sclerosis (SSc), commonly affecting less than 10% of these patients. There are no descriptions of peripheral neuropathy in SSc patients from Latin –America.

Objective: To examine the frequency of peripheral neuropathy in a large Brazilian group of patients with SSc and its correlations into the clinical spectrum of the disease.

Methods: 626 patients classified as SSc according to the ACR/EULAR criteria, being followed at a single referral scleroderma outpatient clinic in Brazil between 2010 and 2016 were included in this study. Patients with a confirmed diagnosis of peripheral neuropathy were evaluated regarding demographic, clinical and laboratory features. Statistical significance was considered when p ≤ 0.05.

Results: 44 SSc patients (7%) with a diagnosis of peripheral neuropathy were found. SSc patients with peripheral neuropathy, had a similar disease duration when compared to SSc patients without peripheral neuropathy (13,66±8.42 years vs. 13,56±9.26 years; p = 0.388); they were, however, significantly older at disease onset (47,50±14.24 years vs. 41,46±13.98 years; p = 0.009) and at diagnosis (49,86±14.24 years vs. 43,95±14.10 years; p = 0.011). When clinical variables were examined, peripheral neuropathy occurred in both clinical variants of SSc, presenting statistical association with esophageal involvement (p = 0.040) and cancer (p = 0.007). No association with specific SSc auto-antibodies was observed.

Conclusions: Peripheral neuropathy is uncommon in SSc patients; when present, it is significantly associated with esophageal involvement and cancer in Brazilian patients.

252

CLINICAL AND LABORATORY PROFILE OF JUVENILE-ONSET SYSTEMIC SCLEROSIS IN A LARGE BRAZILIAN COHORT

P. D. Sampaio-Barros1, A. B. Bortoluzzo2, A. P. T. Del Rio3, A. P. Luppino-Assad1, D. C. O. Andrade1, and J. F. Marques Neto3. 1Division of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil; 2Insper Institute of Education and Research, Sao Paulo, Brazil; 3Unit of Rheumatology, University of Campinas, Campinas, Brazil.

Objective: To characterize the clinical and laboratory profile of juvenile-onset compared to adult-onset systemic sclerosis (SSc) in a large Brazilian cohort.

Methods: Historical analysis of a cohort of 1016 SSc patients followed at the Scleroderma Outpatient Clinic from two referral university centers in Brazil. Patients were classified as SSc according to the 1980 ACR criteria. Juvenile-onset SSc was defined if age of onset was < 16 years.

Results: Thirty-one (3.1%) patients were classified as juvenile onset SSc. These patients were predominantly female (90.3%), Caucasian (71.0%) and presented diffuse SSc (51.6%), with mean age at onset of 12.7 years. Compared to the adult-onset patients, juvenile onset was associated with diffuse SSc (p < 0.001), calcinosis (p < 0.001), myositis (p = 0.050), and lower frequency of interstitial lung disease (p = 0.050), pulmonary hypertension (p = 0.035) and esophageal (p = 0.005) involvement.

Conclusion: Juvenile-onset SSc is characterized by a distinct clinical pattern in this large series of SSc patients, since it was predominantly associated with diffuse SSc but without significant organ involvement.

255

INDUCTION TREATMENT IN LUPUS NEPHRITIS IN A REAL-LIFE SITUATION: CYCLOPHOSPHAMIDE OR MYCOPHENOLATE MOFETIL?

G. A. Munhoz1, M. L. M. Lacerda1, L. P. C. Seguro1, M. R. Ugolini-Lopes1, E. F .B Borba1, and E. Bonfá1. 1Hospital das Clínicas da HCFMUSP. Universidade de São Paulo, São Paulo, Brazil.

Background/Purpose: Low-dose intravenous cyclophosphamide (Euro-lupus) and Mycophenolate mofetil (MMF) are well established induction therapies in lupus nephritis, but there are few studies comparing both treatments.

Objective: Our aim was to compare the efficacy and safety of these two modalities 6-month after induction therapy.

Methods: Historical analysis of data from a cohort from a single tertiary center.

Patients with active lupus nephritis were treated with Euro-lupus (500 mg, 15/15 days for 3 months, followed by MMF/azathioprine) or MMF (3 g/day) as induction therapy. Clinical and laboratory data were evaluated at baseline and after 6 months. Serious infectious were defined as infections requiring hospitalization and/or intravenous antibiotics. Exclusion criteria were a creatinine clearance <10 mL/min and pregnancy.

Results: 40 patients received Euro-lupus and 70 patients received MMF. Patients in the Euro-lupus and MMF group were of comparable in age (35.23 ± 10.32 vs. 37.43 ± 11.43 years, p=0.316), female gender (85.0 vs. 84.2%, p=1.0), white race (75.0 vs. 62.9%, p=0.212) and disease duration (5.65 ± 5.64 vs. 6.20 ± 6.44 years, p=0.653). Baseline laboratory parameters, SLEDAI and glucocorticoid therapy data are shown in Table 1. The frequency of previous nephritis (70.0 ± 60.0%, p=0.312), systolic blood pressure (BP) levels (p=0.597) and diastolic BP (p=0.217) were comparable in the two groups. Six-month laboratory parameters, SLEDAI and glucocorticoid therapy data are shown in Table 2. After 6 months, patients in the Euro-lupus group had a higher increase in C3 (p=0.038) and C4 (p=0.046) levels and a greater reduction in the daily dose of prednisone (−24.69 ± 14.72 vs. -18.43 ± 13.97 mg/day, p=0.029) than MMF. Patients in the Euro-lupus group presented higher frequency of serious infections (22.5 vs. 7.1%, p=0.034) than those in the MMF group.

Conclusion: Euro-lupus and MMF protocols were effective as induction therapies for active lupus nephritis with a comparable frequency of patients achieving the proteinuria target despite of worse baseline parameters in the former group. The higher frequency of serious infection in Euro-lupus group may be associated with more aggressive glucocorticoid regimen in these patients.

257

COST OF TREATMENT FOR SYSTEMIC SCLEROSIS IN BRAZIL

S. C. Kowalski1, A. F. de Queiroz1, B. Grassetti1, B. Vilaça1, B. Domingues1, C. V. Baroncini1, J. P. P. da Cunha1, and R. K. Ostapiuk1. 1Universidade Federal do Paraná, Curitiba, Paraná, Brazil.

Objectives: Considering the absence of cost-of-illness studies in Systemic Sclerosis (SS) in Brazil and the data available in our rheumatology outpatient clinic, the present study aims at identifying and describing the resources used in a one-year period and their costs for the Unified Health System (Sistema Único de Saúde - SUS) and for the institution.

Methods: This was an observational and historical study of SS patients aged 18 to 76 years being followed from April to September 2017. The sample was selected according to the following criteria. Inclusion criteria: patients with SSc, according to the criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR); older than 18 years. Exclusion criteria: patients who had difficulty on communicating; patients who had the diagnosis of SS or were followed at the institution for less than 12 months. The medical records were reviewed to clinically characterize the patients and to identify the resources used in a one-year period. The resources evaluated in this study were: hospitalizations, complementary exams, laboratory tests, rheumatology visits, visits to specialists and physiotherapy (rehabilitation). The medical-hospital costs were extracted from the Management System of Procedures, Medications and Orthosis-Prosthesis-Materials Unified Table (Sistema de Gerenciamento da Tabela de Procedimentos - SIGTAP) and from the Hospital procedures table. Descriptive analysis (measures of central tendency, dispersion and frequencies) using Software R, version 3.4.0 were conducted.

Results: 35 patients participated in the study, 94% female and 6% male. The mean age was 55 years (+/− 14). 85.7% presented LCSS and 5.7% presented DCSS. 8.6% of the patients did not have this information in their medical record (unspecified SS). 71% of the patients had at least one associated disease. The total costs reimbursed by the SUS were R$ 85.184,06 but the actual hospital costs was R$ 496.317,39. Hospitalization accounted for 54.4% of the SUS costs. As for the institution, 62.5% of the costs was related to complementary exams, except for laboratory tests, among which the most requested were: spirometry, 6-minute walk test, computed tomography of the chest, echocardiography and upper digestive endoscopy. The second highest cost (23.6%) of the hospital identified were hospitalizations. The average annual cost per patient reimbursed by SUS was R$ 2.433,83 (SUS) but the actual cost was R$ 14.180,50 (hospital).

Conclusions: Rational resource allocation can be best planned based on these figures. The difference of costs reimbursed by SUS and the actual cost for our Hospital was R$ 411.133,33 (83% of our Hospital total costs) enabling decision makers to explore alternative financial policies.

258

LOSS OF PRODUCTIVITY AND FUNCTIONAL CAPACITY IN PATIENTS WITH SYSTEMIC SCLEROSIS

S. C. Kowalski1, A. F. de Queiroz1, B. Grassetti1, B. Vilaça1, B. Domingues1, C. V. Baroncini1, J. P. P. da Cunha1, and R. K. Ostapiuk1. 1Universidade Federal do Paraná, Curitiba, Paraná, Brazil.

Objectives: The aim of the present study was to evaluate patients with Limited Cutaneous Systemic Sclerosis (LCSS) and Diffuse Cutaneous (DCSS), through standardized questionnaires for rheumatic diseases, loss of productivity (WPAI-GH) and functional capacity (HAQ and SQHAQ).

Methods: This was an observational and historical study of SS patients, as per the American College of Rheumatology (ACR) classification criteria, aged 18 to 76 years of age, selected from April to September 2017. Exclusion criteria: patients who had difficulty communicating; patients who had the diagnosis of SS or were followed in the institution for less than 12 months. The questionnaires were applied by trained researchers. The questionnaires applied assessed productivity losses (work and leisure) and functional capacity - The Health Assessment Questionnaire (HAQ) and The Scleroderma Health Assessment Questionnaire (SHAQ). Identification data and clinical characteristics were included as disease type (LCSS or DCSS), presence of symptoms related to the disease and presence of comorbidities. Descriptive statistical analysis using Software R, version 3.4.0 were carried out.

Results: 35 patients participated in the study, 94% female and 6% male. The mean age was 55 years (+/− 14). 85.7% presented LCSS and 5.7% presented DCSS. 8.6% of the individuals did not have this information in the medical record (unspecified SS). 71% of patients had at least one associated disease. The analysis of productivity loss measured by the WPAI-GH questionnaire showed that 20% of the patients worked, were wage earners and presented the LCSS form. There was no loss of work productivity or deterioration in daily activities. Among those who did not work, the average deterioration of the daily activities' efficiency was 54%, 44% for women and 30% for men. The mean yield deterioration according to disease type was: 30% in DCSS, 41% in LCSS and 70% in unspecified SS. The functional capacity measured by the HAQ questionnaire showed that the mean disability index (MDI) was 0.6 (0-3 scale, with no disability and maximum disability, respectively). The mean MDI by disease type was: 0.2 for the DCSS; 0.6 for the LCSS and 0.7 for the unspecified SS. 65% of the patients quantified the intensity of their pain according to a Visual Analogue Scale (VAS). The mean was 1.4 (+/− 1.2) (0-3 scale, with no pain and disabling pain, respectively).

Conclusions: The HAQ score was relatively low (0.55 of 3) indicating that these patients have good functional capacity; this may reflect either an aggressive therapeutic approach or patients being in the initial phase of their disease. Patients with the lowest WPAI-GH, loss of productivity accounted for 20% of those interviewed who worked and were wage earners. It is possible that patients who exhibited lost of productivity at work, had retired due to disability caused by SS; those who were working could be in the early stages of the disease, having no health problems that affect their productivity.

264

HOSPITALIZATIONS IN PATIENTS WITH INFLAMMATORY MYOPATHIES IN A UNIVERSITY HOSPITAL

N. Perez1, M. Khoury1, M. Collado1, M. Gargiulo1, L. Suarez1, and G. Gomez1. 1Instituto de Investigaciones Médicas Afredo Lanari, Buenos Aires, Argentina.

Objective: To describe the hospitalization requirements and the reasons for them in patients with inflammatory myopathies.

Material and Methods: We included all patients followed at the Immunology Service, with a diagnosis of inflammatory myopathy and who registered between January 1997 and August 2017.

Results: Data from 40 patients with inflammatory myopathies (29 women), mean age 51.57 ± 15 years, 22 with dermatomyositis (DM) and 18 with polymyositis (PM) were examined. Hospitalizations occurred in 18 patients (45%), in 14 patients once and more than once in 4 patients. Of the 14 patients, 7 were hospitalized for their diagnosis. In 5 previously diagnosed patients, the reason for admission was muscle weakness (one was referred from another center suffering from septic arthritis associated with muscle weakness and the other was diagnosed with bladder cancer at hospitalization). The two remaining cases were admitted to complete their studies (an overlap syndrome with scleroderma and the other with calcinosis). One patient had 5 hospital admissions (two for diagnosis, one for the study of a non-neoplastic pulmonary nodule, one for mucinosis and one due to disseminated histoplasmosis). A patient with DM had 4 hospitalizations: the first one in the context of muscle weakness, the second due to lesions on the scalp (with a biopsy compatible with discoid lupus), another due to suicidal ideation and the last one due to a surgery for colorectal cancer. A woman with overlap syndrome with rheumatoid arthritis was admitted 3 times, the first one with muscular weakness and pneumonia who required mechanical ventilation, the remaining two hospital admissions were for diaphragmatic weakness and required non-invasive ventilation at the intensive care unit. One patient had two hospitalizations, the first one for diagnosis and the next for weakness of the swallowing muscles. Steroid pulses were used only in 3 patients and 5 patients received gamma globulin (1 due to associated infection, 1 due to diaphragmatic compromise, 2 due to weakness of the swallowing muscles and 1 due to lack of response to immunosuppressive treatment). Of these 5 patients, 4 corresponded to the group that had more than one hospitalization.

Conclusions: 45% of myositis patients required at least one hospitalization. The most frequent reason was to perform or re-evaluate the diagnosis or for complications related to muscle weakness. A single patient required admission to intensive care unit due to weakness of respiratory muscles. All those who required more than one hospital stay received gamma globulin during their disease course.

266

HEALTH-RELATED QUALITY OF LIFE (HR-QOL) IN PATIENTS WITH PRIMARY SJÖGREN SYNDROME (PSS)

A. Secco1, M. Mamani1, S. Papasidero2, J. Demarchi2, P. L. Encinas3, F. Caeiro3, C. Gobbi4, E. Albiero4, A. Gomez5, J. Barreira5, Pucci6, C. Amitrano6, A. Nitsche6, R. Aguila Maldonado7, M. Garcia7, M. Gallardo8, E. Soriano8, L. Raiti9, G. Salvatierra10, and A. Eimon11. 1Hospital Rivadavia. CABA, Argentina; 2Hospital Tornú. CABA, Argentina; 3Hospital Privado de Córdoba. Córdoba. Argentina; 4Hospital Córdoba. Córdoba, Argentina; 5Hospital Británico. CABA, Argentina; 6Hospital Alemán. CABA, Argentina; 7Hospital San Martín. La Plata, Buenos Aires, Argentina; 8Hospital Italiano. CABA, Argentina; 9Clínica Bessone. Buenos Aires, Argentina; 10IPRI. Santiago del Estero, Argentina; 11CEMIC. CABA, Argentina.

Objectives: To describe the HR-QOL in patients with pSS. To evaluate the relationship between HR-QOL and clinical manifestations. To assess HR-QOL according to the education level and health care site (public vs private centers) as surrogates of socio-economic status.

Methods: We included patients with diagnosis of pSS according to the American-European criteria (2002) being seen at 11 private or public Argentinean rheumatologic centers between November 2013 and December 2016. All patients with another severe chronic disease or autoimmune rheumatic disease were excluded. The SF-36 questionnaire was used. Design: observational, analytic, cross-sectional study. Continuous variables were informed as means and SD. Categorical variables were reported in percentages. Multiple linear regression models were performed for each of the 8 SF-36 scales as the dependent variables; adjustment for potential confounders was done. The performance of each model was evaluated. In cases where linearity and/or homoscedasticity was not fulfilled, transformation of variables or robust regression were performed, as appropriate.

Results: 252 patients were included; 98,38% were female, mean age 52,64 years (+/−14,84). The mean of the SF-36 scales were as follow: General Health, 48,84 (+/−22,24. 95% CI: 46,08-51,60); Physical Role Functioning: 43,06 (+/−42,71. 95% CI: 37,79-48,33); Body Pain: 52,87 (+/−25,92. 95% CI: 49,66-56,08); Physical Functioning: 64,34 (+/−26,81. 95% CI: 61,02-67,66); Vitality: 45,93 (+/−20,83. 95% CI: 43,31-48,55), Social Functioning: 62,10 (+/−27,36. 95% CI: 58,71-65,49); Emotional Role Functioning: 51,72 (+/−43,24. 95% CI: 46,38-57,06) and Mental Health: 57,10 (+/−21,19. 95% CI:54,44-59,76). The most frequent variables independently associated with the different scales of the SF-36 questionnaire were: fatigue, xerostomia, depression and anxiety. Statistically significant differences between public and private centers were observed in the following scales: physical role functioning (34,93 vs 54,41), body pain (48,96 vs 58,73) and emotional role functioning (46,81 vs 59,48). Statistically significant differences were also found among patients with lower and those with full or higher secondary education level, in physical role functioning (36,65 vs 47,29) and body pain (47,71 vs 56,45).

Conclusion: We found a decrease in the score of all the SF-36 questionnaire scales. The most frequent variables independently associated with the different scales of the SF-36 were: fatigue, xerostomia, depression, and anxiety. Subjects with lower educational level and treated in public centers presented significant lower scores in the physical role functioning and body pain scales. Patients treated in public centers also exhibited lower scores in the emotional role functioning scale. These results could be an expression of the impact of the patients’ socio-economic status in their overall quality of life.

271

VASCULITIS AT ROOSEVELT HOSPITAL

E. I. Nufio Chó 1, E. R. Arreola2, and M. Herrera Méndez2. 1Guatemalan Social Security Institute IGSS. Guatemala City, Guatemala; 2University of San Carlos of Guatemala Roosevelt Hospital. Guatemala City, Guatemala.

Introduction: Vasculitis are heterogeneous diseases, they are rare and are about 20 different forms are noted in the 2012 updated Chapel Hill Criteria. Clinical expression of the vasculitis depends on the site, type and size of the vessels involved. Clinically, systemic vasculitis ranges from a benign regional processes to the involvement of life-threatening organs. Epidemiological data of vasculitis associated with ANCAS (anti-Neutrophil cytoplasmic antibodies) come from white populations of European descent and the annual global incidence is estimated to be approximately 10-20/million with an age of appearance between 65 and 74 years.

Objectives: To characterize patients with primary systemic vasculitis

Methods: An observational study was conducted at the Rheumatology Unit of the Roosevelt Hospital from January 2000 to December 2015. A review of the clinical files was done to obtain epidemiological, clinical, radiological, serological and histological data. This information was transcribed to an Excel sheet. We included 56 patients who met the EMA 2012 criteria and divided them into 2 groups, ANCA-associated (23) and non-ANCA associated (33). Descriptive statistics, including Chi square and Student’s tests were performed, as appropriate. Analysis of variance was used to establish differences between these 2 groups. Statistical significance was set at p value <0.05.

Results: The most frequent vasculitis were Granulomatosis with Polyangiitis and hypersensitivity vasculitis with 23.2%; there were no differences in sociodemographic variables, the age in the ANCA associated was 46.5 years ± 17.1 and in the not associated it was 41.1 ± 16.4 (p 0.946). The most frequent manifestation was skin in males: 7 in the ANCA- associated (14.5%) and 12 in the Non-ANCA-associated (25%) (p 0.052); in contrast the most frequent manifestations in females were constitutional symptoms (weight loss, fever, and asthenia) in 30 (46%) for the ANCA-associated and 12 (18 %) for the non-ANCA-associated (p 0.004) and renal manifestations 25 (52%) for the ANCA-associated and 5 (10.5%) for the non-ANCA-associated (p 0.001). In females PCR (m ± σ) was 6.98 ± 6.88 for the ANCA-associated and 4.07 ± 3.9 for the non-ANCA-associated, Hemoglobin (m ± σ) was 10.22 ± 1.82 for the ANCA-associated and 11.1 ± 0.91 for the non-ANCA-associated and creatinine (m ± σ) was 2.94 ± 2.73 for the ANCA-associated and 1.33 ± 0.91for the non-ANCA-associated. Imaging and invasive studies were performed, documenting diagnostic findings in 42.3%. The anatomopathological findings, corresponded to the skin in 18% of the patients; no perivascular inflammatory infiltrate was reported.

Conclusions: This study provides a vision of primary vasculitis in the population serviced at the Roosevelt Hospital; however, because of the difficult in diagnosing these condition, it is necessary to carry out different diagnostic studies; the valuable contribution of anatomopathological findings are still rarely sought.

272

MYCOPHENOLATE MOFETIL VS CYCLOPHOSPHAMIDE AS MAINTENANCE DRUG THERAPY IN PEDIATRIC PATIENTS WITH LUPUS GLOMERULONEPHRITIS

M. Etcheverry, V. Cervetto, A. Pringe, R. Cuttica, I. Brusco, A. Narchi, M. Marcantoni, M. Gomez Sosa, and M. Galan. Hospital de Niños Pedro de Elizalde, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.

Objective: To compare the RATE and time of relapses in pediatric patients suffering from lupus with lupus glomerulonephritis who received either mycophenolate or cyclophosphamide as maintenance treatment and to compare the safety profile of these treatments.

Methods: A comparative, historical, cross-sectional study was conducted. Inclusion criteria: Patients with Juvenile systemic lupus erythematous diagnosis, from January 2000 to December 2014; lupus glomerulonephritis (GN) class III, IV or V; renal remission after induction with cyclophosphamide administered monthly and steroids (defined as ≤500 mg/day of proteinuria (pu), < 10 white blood cells/field, creatinine (Cr) < 130 % of the patient’s lowest value); two or more years of monitoring since nephritis diagnosis. The patients were divided into two groups according to the maintenance therapy received, cyclophosphamide (group C) or mycophenolate (group M). The characteristics of each group were compared, including steroid doses and pu at the end of the induction treatment. The relapse rate between both groups and the presence of adverse effects were compared. The presence of a rate pu/ucr > 1 or worsening of Cr higher than 50 % was considered a relapse.

Results: 36 patients met the selection criteria out of a total of 168 patients suffering from lupus diagnosed during the study period. Average age: 13.42 years (2, 1-17, 8); female 69.4 %. The time of evolution to GN was of 98 days (0-849). 30 patients out of 36 presented GN Class IV (83.3 %), 3 patients presented GN Class III and 3 patients Class V. Monitoring average 3.66 years. 27 of the patients were in group C and 9 patients in group M. A global renal relapse (flare) was detected in 46.8 % of the patients, in 12/27 (44 %) of group C and 1/9 (11 %) of group M (OR 6, 4 95% CI 0, 7-58, 5; p=0, 1). Regarding adverse effects, they were detected in 19/27 (70.37 %) patients of group C and 6/9 (66.6 %) of group M. There were only severe adverse effects in patients of group C (severe sepsis, cryptococcal meningitis, seizures). A difference in pu was observed at the end of the induction between patients who had relapsed and those who had not with an average of 422.31 mg/dl and 191.25 mg/dl, respectively (p=0.047).

Conclusions: No significant differences were observed with respect to the rate of relapse between both groups, which could be a Beta-type statistical error. However, mycophenolate appears, at least, to be not inferior to cyclophosphamide. It was even observed that there is a certain tendency which, if sustained, would indicate a higher risk of flare in patients treated with cyclophosphamide. It should be noted that severe adverse effects were only observed in the cyclophosphamide group. The significant difference in the levels of pu at the end of the induction period is remarkable, with higher levels in patients who presented flare. The sample size makes it difficult to reach accurate conclusions but given the characteristics of the disease and its frequency we consider these results a matter of importance.

273

PREVALENCE OF SYSTEMIC LUPUS ERYTHEMATOSUS NEUROPSYCHIATRIC MANIFESTATIONS: A COHORT FROM A THIRD LEVEL UNIVERSITY HOSPITAL, SAN RAFAEL, BOGOTÁ

A. Beltran1, C. Mora2, K. Arrieta3, E. Aviles4, and A. Bastidas5. 1Internist, Rheumatologist. Clinical Professor Hospital Universitario San Rafael Bogotá Colombia; 2Internist, Rheumatologist. Clinical Professor Universidad de la Sabana Bogotá-Colombia; 3.-4Residents III Year of Internal Medicine Universidad de la Sabana; 4Residents III Year of Internal Medicine Universidad de la Sabana; 5Internist, Pulmonologist, Clinical Epidemiologist. Clinical Professor Universidad de La Sabana. Bogotá Colombia.

Background and Objectives: Epidemiological data regarding the prevalence of neuropsychiatric (NP) syndromes in systemic lupus erythematosus (SLE) patients in Colombia is unknown. Few of the published studies around the world have shown registers with variability in prevalence and reported frequencies. The present study aims to determine the prevalence of neuropsychiatric manifestations in patients with the diagnosis of SLE in a tertiary care hospital in Colombia, Bogota.

Methods: Cross-sectional descriptive study designed to determine the prevalence of NPSLE syndromes in medical registers of patients being care for at a tertiary hospital in Bogotá. Variables studied included the diagnosis of SLE confirmed by a rheumatologist and included also descriptive variables such as age, gender and the most common NP manifestations found during follow up. Random sampling of medical records (n: 274) were reviewed, subjects older than 18 years of age were included; patients whose medical records, follow up visits, images and serological data were not available, were excluded. The prevalence was calculated based on the number of subjects with NP manifestations and the entire study population. 95% confidence intervals were also estimated; the correlation between disease activity by SLEDAI (SLE activity index) and mortality with the type of NP manifestation was also obtained (p < 0.05).

Results: 306 medical records were included; however only 274 were included in the final analysis. Median age was 43 years (IQR: 23), 89,1% were women and the prevalence of the NP manifestations was 26,2% (IC95%:21,2-31) in the total cohort. The most frequent NPSLE manifestations were headache 13.1% (95% CI: 9.1-17.2), cerebrovascular disease 8% (95% CI: 5.1-11.3), acute confusional state 6.6% (95% CI: 4-9.1), seizures 4.7% (95% CI: 2.6-7.3), aseptic meningitis 2.2% (95% CI: 0.7-4), autonomic neuropathy 0.7% (95% CI:0-1.8), polyneuropathy 0.7% (95% CI:0-1.8) and myelopathy 0.7% (95% CI:0-1.8). Cranial neuropathy, mononeuropathy, myasthenia gravis, Guillain Barre and plexopathies were not found in our patients. Neither mood disorder (anxiety or depression) nor cognitive dysfunction were evaluated. SLEDAI scores were as follows: 45,8% of the patients had severe disease activity, 31,9% moderate activity and 22,3% had no activity.

Conclusions: Neuropsychiatric manifestations are frequently found in patients with SLE. Headache is the most frequently reported NP manifestation followed by cerebrovascular disease, acute confusional state, seizure disorders and aseptic meningitis. Additional studies are necessary to stablish the possible association or predisposing factors in patients with NPSLE syndromes.

274

CORRELATION OF NAILFOLD CAPILLAROSCOPY AND MODIFIED RODNAN SKIN SCORE IN PATIENTS WITH SYSTEMIC SCLEROSIS

C. Amitrano1, M. J. Molina2, C. Asnal1, P. Pucci1, C. Crow1, and A. Nitsche1. 1Hospital Alemán (CABA). Argentina; 2Hospital de San Isidro (Buenos Aires). Argentina.

Introduction: Systemic Sclerosis (SSc) is a systemic autoimmune and heterogeneous disease. The endothelial injury is the first and predominant mechanism involved in its pathogenesis. The alterations on nailfold capillaries reflect an expression of systemic endothelial damage, therefore nailfold capillaroscopy (NC) becomes a fundamental tool for evaluation of SSc patients. The extent of cutaneous involvement in these patients is a prognostic marker. An objective and reproducible way to evaluate cutaneous involvement is using the Modified Rodnan Skin Score (mRSS).

Objective: To evaluate the correlation of different alterations on nailfold capillaroscopy with the degree of cutaneous involvement employing mRSS.

Materials and Methods: A cross-sectional and observational study. We include 81 patients with SSc. Each patient underwent NC using a triocular lens of 40x. The findings were classified as either normal or pathological. The following capillaroscopic patterns were considered in accordance with Cutolo’s classification: 1) Early pattern; 2) Active pattern; 3) Late pattern. Skin involvement was assessed with the mRSS with a maximum score of 51. Pearson's correlation coefficient was calculated. Fisher’s exact and X2 tests were performed.

Results: Of the 81 SSc patients, 75 were women (92.59%) and 6 men (7.41%) with a mean age of 52.75 ± 15.29 years and mean disease duration of 6.6 ± 6.4 years. Forty one patients (50.62%) showed diffuse scleroderma (dSSc) and 40 (49.38%) limited scleroderma (lSSc). Pathological capillaroscopy was present in 78 SSc patients: 39 in dSSc group and 39 in lSSc. Both groups had similar mean follow up time: 6.87 years vs. 6.34 years (p=0.85) while the mean mRSS was 17.82 vs. 8.85 respectively (p=0.00059). No difference was found between both groups when comparing capillaroscopic alterations (p=0.26). At the same time, in the group of patients with abnormal capillaroscopy, 18 (23.08%) showed an early pattern, 33% (42.30%) an active pattern and 27 (34.62%) a late pattern with a mean mRSS of 11.77 ± 10.25; 8.75 ± 5.33 and 20.18 ± 14.02, respectively and an average evolution time of 3.5 years, 5.78 years and 10.22 years for each group. The correlation observed between pathological capillaroscopy and mRSS was of r=0.3232 and with disease follow up time was of r=0.4057.

Conclusions: No capillaroscopic differences were found between patients with dSSc and lSSc forms. Higher mRSS and longer follow up time were associated with a higher frequency of an active and late pattern. Positive correlation was observed between abnormal capillaroscopy and mRSS and follow up time in patients with SSc.

284

DIFFUSE ALVEOLAR HEMORRHAGE IN ANCA- ASSOCIATED VASCULITIS: IS IT PREDICTIVE OF POOR PROGNOSIS?

L. García1, CE. Pena1, R. Aguila Maldonado1, C. Costi1, AC. Testi1, V. Arturi1, P. Sansinanea1, MA. Pera1, V Nagua1, A. Vulcano1, F. Savy1, S. Velloso1, and MA. García1. 1Hospital San Martín, La Plata, Argentina.

Objective: To compare clinical manifestations, laboratory and immunological values, morbidity and mortality in patients with ANCA-associated vasculitis (AAV) with and without Diffuse Alveolar hemorrhage (DAH).

Methods: Historical cohort study. Data from the medical records of patients over the age of 18 were evaluated between the years 2000-2017. Ninety patients with diagnosis of AAV who met the ACR 1990 Classification or 2012 Chapel Hill Consensus Conference criteria were included. DAH was diagnosed based on minor or major hemoptysis and/or respiratory insufficiency together with at least 1 positive result on chest radiograph and/or computed tomography scan. The sample was divided in two groups: with DAH (group 1) and without DAH (group 2) along the disease. We compared demographic data, Birmingham Vasculitis Activity Score (BVAS) and Five Factor Score (FFS) at the onset of the disease, CBC, creatinine and ANCA antibodies by immunofluorescence and/or ELISA, clinical manifestations as renal, neurological, mucocutaneous, articular, cardiological, ophthalmological and ear, nose and throat (ENT) damage and mortality between groups. Chi-square or Fisher's exact test were used for dichotomous variables as appropriate. A p-value <0.05 was considered statistically significant. Logistic regression analysis was used to identify predictors of survival.

Results: Group 1 included 24 patients (66% male, mean age at disease onset 54 years). The most frequent type of vasculitis was Granulomatosis with polyangiitis (GPA) 54%. Mean BVAS 21 points and FFS 1 point. Group 2 included 66 patients: 36% male, mean age at disease onset 52 years, GPA 45%, BVAS was 17 points and FFS 0 points. Table 1 shows demographic, clinical data and mortality data for each group. Logistic regression analysis showed statistically significant difference between DAH and male sex (p: 0.017 OR 6.08 95% CI 1.37-26.92).

Conclusions: DAH was associated with increased morbidity, but it did not influence mortality in this group of patients. The results seem to agree with the FSS which does not include DAH within its parameters.

289

DERMATOMYOSITIS: ANTIBODIES AND CLINICAL CHARACTERISTICS IN 105 PATIENTS OF THE ARGENTINE REGISTER OF IDIOPATHIC INFLAMMATORY MYOPATHIES

Amelia Granel1, Ana Ines Marcos1, M. Angeles Gargiulo2, Ramiro Gomez3, Carolina Costi4, M. Celina De la Vega5, Veronica Wernicke6, Silvia Papasidero7, Juan Carlos Barreira8, and Graciela Gomez2. 1Hospital San Roque De Gonnet, La Plata, Buenos Aires; 2Instituto de Investigaciones Medicas, Lanari, CABA; 3Hospital de Clinicas Jose de San Martin, CABA; 4Hospital San Martin, La Plata, Buenos Aires; 5Hospital Argerich, CABA; 6Hospital Rossi, La Plata, Buenos Aires; 7Hospital Tornu, CABA; 8Hospital Britanico, CABA.

Background and objectives: Dermatomyositis (DM) is one of the major subgroups within the inflammatory autoimmune myopathies(MII) and it is characterized by typical cutaneous manifestations, muscle weakness in the myopathic form and extra muscular manifestations. Our purpose was to determine the clinical characteristics and their associated antibodies in patients (p) with DM of the Argentine Registry of the SAR.

Materials and Methods: 105 adult patients with DM were included (Bohan& Peter criteria). Clinical, demographic, laboratory and treatment characteristics were recorded. Myositis Specific Antibodies (MSA) anti-Jo-1, PL-12, PL-7, SRP, Mi-2, EJ, OJ, TIF-1ϒ, MDA5, NXP2 and Myositis-Associated Antibodies (MAA) anti Ku, PM-Scl Ro and SAE were evaluated by Immunoblot technique. ANA was performed by IFI. Descriptive analysis, Fischer exact test for proportions and Mann Whitney for numerical variables were conducted.

Results: 105 p were studied: 73 women (69.5%), mean age 44 years (SD 16); 91% with pure DM, 9% DM with overlap and 15/104 (15%) with cancer-associated myositis. Regarding comorbidities: 22% were smokers, 20% had hypertension, 9% diabetes, 21% dyslipemia and 7/103 previously used statins. 12/104 (11%) had no muscle weakness until the time of entry into the Registry. Respiratory compromise was observed in 25/102 p (25%), arthritis in 34/102 (33%), Raynaud's phenomenon in 39/103 (38%) and interstitial lung disease in 11/104 (10.57%). Cutaneous manifestations were: Gottron’s sign in 81%, V sign in 77%, heliotrope erythema in 74%, shawl sign in 63%, cuticle growth in 31% and mechanics hands in 13%. Hospitalization was required in 47/92(51%). ANA (+) was found in 68/95 p (71%), anti-Ro in 8/84 (9.5%) and Pm-Scl 3/70 (4.3%). Of 69 p, 17 had anti-Mi-2 (24.6%), one anti-Jo-1, two anti-PL-7 and one panti-PL-12. Anti Mi-2(+) p had high CK values (p = 0.0001). Other MSA were done in 28 p negative for the previously described abs; we found 4p positive for TIF1ϒ, 2 for MDA5 and 1 for anti-NXP2. Anti-MDA5(+) p had no muscle weakness (p = 0.008). There were no p with anti-SRP, OJ, EJ, SAE or anti Ku. Treatments were corticoids in 101 p (97%), methotrexate in 69 (66%), azathioprine in 38 p (34 %), hydroxychloroquine in 60 p (57%), IVIG in 13 p (12.38%) and cyclophosphamide, mycophenolate and biologics in less than 6%. Up to 3 treatments in 75/105 p (72.5%).

Conclusions: Patients with DM studied had the typical dermatological manifestations of the disease, in addition to muscular and respiratory compromise. Pure DM was more frequent. A small proportion of patients did not have muscle weakness at the time they entered the registry. About half the patients required hospitalization. Most patients received treatment with corticosteroids (97%). Only a minority of the patients received biological therapy. MSA and MAA are not always done. Patients from other from Argentinean regions are needed to better characterize the disease in our country.

290

PULMONARY FIBROSIS AT THE TIME OF DERMATOMYOSITIS/POLIMYOSITIS DIAGNOSIS: A PREDICTIVE FACTOR FOR PULMONARY AND EXTRA-PULMONARY TUBERCULOSIS

Taysa C.M. Da Silva1, Adriana C.T. Proença1, and Samuel K. Shinjo1. 1Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil (BR).

Objective: To examine the predictive factors for tuberculosis (TB) development in DM/PM.

Methods: This single-center, historical cohort study initially included 290 adult patients with DM/PM (Bohan and Peter, 1975) seen between 2002 and 2016. TB (pulmonary and/or extra-pulmonary) was confirmed after or at time DM/PM diagnosis, in 12 patients (4.1%) (TB+ group). For the control group (TB-), 24 patients without TB were arbitrarily selected in the same period and matched for age, ethnicity, gender, age at DM or PM diagnosis, disease duration and type (DM or PM).

Results: TB occurred at a median of 16 months after DM/PM diagnosis, affecting predominantly female patients of white ethnicity. Clinical, laboratory and treatment features were similar in TB+ and TB- groups (p>0.05). However, pulmonary fibrosis at the time of DM/PM diagnosis was more prevalent in the TB+ group (41.7 vs. 8.3%; p=0.029). Moreover, on a multivariate logistic regression model, pulmonary fibrosis was significantly associated with TB (Odds ratio: 9.59, 95% confidence interval: 1.17-78.82). TB affected 3 DM cases for every 1 PM case, with predominantly pulmonary followed by extra-pulmonary involvement (pleura, cutaneous, muscular, joint, soft tissue and hematologic). Two or more sites were affected in 41.7% of cases.

Conclusion: Pulmonary fibrosis at time of DM/PM diagnosis was a predictive factor of TB development. Further studies are needed to confirm these results

303

DIAGNOSTIC USEFULLNESS OF MYOSITIS ANTIBODIES IN PATIENTS WITH INTERSTITIAL LUNG DISEASE AND SUSPECTED UNDERLYING CONNECTIVE TISSUE DISEASE

V. Wolff1,2, J. Maya1, M.C. Cuellar1, M. Florenzano2, A. Peralta1, and V. Balboa1. 1Hospital Del Salvador, Santiago, Chile; 2Instituto Nacional del Tórax, Santiago, Chile.

Introduction: Interstitial Lung Disease (ILD) is a common manifestation of Connective Tissue Diseases (CTD), mainly Scleroderma (SSc), Rheumatoid Arthritis and Idiopathic Inflammatory Myositis (IIM) spectrum diseases. New myositis specific and associated antibodies have shown to be useful in identifying underlying CTD in patients with ILD of unknown etiology. They have helped in identifying new clinical entities such as Anti-synthetase Syndrome (AS), MDA-5 associated myopathy, overlap syndromes (OS) and Interstitial lung disease with autoimmune features (ILAF).

Objectives: To evaluate the diagnostic utility of the determination of myositis antibodies in a group of patients with ILD of unknown etiology and clinical features suggestive of underlying CTD. To describe the more frequent clinical phenotypes and establish the rheumatological underlying diagnoses.

Methods: Between January and December 2017, a commercially available myositis panel (16 antibodies, Immunoblot technique) was performed in 106 patients with confirmed ILD of unknown etiology and clinical features suggestive of underlying CTD, in whom a defined rheumatologic diagnosis could not be determined after clinical and laboratory evaluation.

Results: Among 106 patients, 76 (72%) were female and 30 (28%) male. We found 46 patients (43.4%) having one or more positive antibodies, 40 (37,7%) had a negative myositis panel and 19 (16%) presented indeterminate titles. Among this last group, a positive clinical correlation was found in 7, and the test was considered positive and diagnostic. One patient presented a false positive result. So, the myositis panel contributed to establish the rheumatological diagnosis in 53 (50%) of patients. Antibodies against Ro-52 were the most frequent (34 patients). AS was the most common final diagnosis (14 patients). The distribution of different antibodies and final diagnoses are detailed in Table 1.

TABLE 1
TABLE 1:
Myositis Antibodies And Diagnoses

Conclusion: Myositis antibodies are useful in the study of patients with ILD of unknown etiology and clinical features suggestive of an underlying CTD. They can help establish a definite rheumatological diagnosis, and therefore offer the patient a proper treatment. We highlight the importance of idiopathic inflammatory myopathies in this group of patients, mainly AS and MDA-5 myopathy. We also highlight the concept of ILAF as a new clinical condition and the role of the Ro-52 antibody in its high frequency in this setting.

304

DERMATOMYOSITIS: ANTIBODIES AND CLINICAL CHARACTERISTICS IN 105 PATIENTS OF THE ARGENTINEAN REGISTER OF IDIOPATHIC INFLAMMATORY MYOPATHIES

Amelia Granel1, Ana Ines Marcos1, Nicolas Pérez2, Ramiro Gomez3, Carolina Costi4, M. Celina De la Vega5, Veronica Wernicke6, Silvia Papasidero7, Juan Carlos Barreira8, and Graciela Gomez2. 1Hospital San Roque De Gonnet, La Plata, Buenos Aires; 2Instituto de Investigaciones Medicas, Lanari, CABA; 3Hospital de Clinicas Jose de San Martin, CABA; 4Hospital San Martin, La Plata, Buenos Aires; 5Hospital Argerich, CABA; 6Hospital Rossi, La Plata, Buenos Aires; 7Hospital Tornu, CABA; 8Hospital Britanico, CABA.

Introducción: Dermatomyositis (DM) is one of the major subgroups within inflammatory autoimmune myopathies(MII) characterized by typical cutaneous manifestations, muscle weakness in the myopathic form and extramuscular manifestations.

Objetivos: To determine the clinical characteristics of patients (p) with DM of the Argentine Registry of the SAR and their associated antibodies.

Methods: A historical study of105 adult patients with DM (Bohan& Peter criteria). Clinical, demographic, laboratory and treatment characteristics were recorded. The Myositis Specific Antibodies (MSA) anti-Jo-1, PL-12, PL-7, SRP, Mi-2, EJ, OJ, TIF-1ϒ, MDA5, NXP2 and the Antibodies Associated with Myositis (AAM) anti Ku, PM-Scl Ro and SAE were evaluated by Immunoblot technique. ANA was performed by IFI. Descriptive analysis, Fischer exact test for proportions and Mann Whitney test for numerical variables were carried out.

Results: 105 p were studied: 73 women (69.5%), mean age 44 years (SD 16); 91% with pure DM, 9% DM with overlap and 15/104 (15%) cancer associated myositis. Regarding comorbidities: 22% smokers, 20% hypertension, 9% diabetes, 21% dyslipemia and 7/103 previous use of statins. 12/104 (11%) had no muscle weakness until the moment of entry into the Registry. Respiratory compromise was observed in 25/102 p (25%), arthritis in 34/102 (33%), Raynaud's phenomenon in 39/103 (38%) and interstitial lung disease in 11/104 (10.57%). Cutaneous manifestations were: Gottron 81%, V sign 77%, heliotrope erythema74%, shawl sign 63%, cuticle growth 31% and mechanics hands in 13%. Hospitalization was required in 47/92 (51%).ANA (+) was found in 68/95 p (71%), anti-Ro in 8/84 (9.5%) and Pm-Scl 3/70 (4.3%). Of 69 p 17 had anti-Mi-2 (24.6%) one p anti-Jo-1, two p anti-PL-7 and one p anti-PL-12. Anti Mi-2(+) p had high CK values (p = 0.0001), Other MSA were done in 28 p negative for the previous abs described, we find 4p positive for TIF1ϒ, 2 p MDA5 and 1 p anti-NXP2. Anti-MDA5(+) p had no muscleweakness (p = 0.008). There was no p with anti-SRP, OJ, EJ, SAE or anti Ku. Treatments were corticoids in 101 p (97%), methotrexate in 69 (66%), azathioprine in 38 p (34 %), hydroxychloroquine in 60 p (57%), IVIG in 13 p (12.38%) and cyclophosphamide, mycophenolate and biologics in less than 6% Up to 3 treatment in75/105 p (72.5%).

Conclusion: Patients with DM from our register had the typical dermatological manifestations of the disease, in addition to muscular and respiratory compromise Pure DM (91%) was more frequent, 15% was found associated with cancer, 11% did not have muscle weakness until the time of admission to the registry and 51% required hospitalization. Anti-Mi-2(+) was present in 24% of DM, one JO1, two PL7 and one PL 12. Other MSA found was 4/4 TIF1gama +, 2/2 MDA 5+ and 1 NXP 2 +. No p had anti SRP, OJ, EJ, SAE or Ku and only 1 of them, cancer-associated myositis with TIF1gama +. All MII p that had anti-Mi2, PL7, anti-TIF1gama and anti-MDA5 had DM and those who had MI2 had higher CPK values. Most patients received treatment with corticosteroids (97%) and the most used DMAR was MTX. Only 6% of the patients received biological therapy. Examining AAM is not possible in all centers, and it was carried out by SAR.

305

MBL2 GENE POLYMORPHISMS AND THEIR ASSOCIATION WITH INFECTION IN BRAZILIAN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: A 10-YEAR STUDY

Carla Saldanha1, Gabriela da Silva2, Nadine Glesse2, João Carlos Brenol1, José Artur Chies2, and Odirlei André Monticielo1. 1Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil; 2Department of Genetics, Universidade Federal do Rio Grande do Sul, Brazil.

Introduction: Systemic lupus erythematosus (SLE) is a multifactorial disease and MBL2 genetics variants potentially affect its etiology and increase infection risk in this population.

Objective: To evaluate the relationship between MBL2 gene polymorphisms of their coding and promoter regions and their respective haplotypes and hospitalizations, number of admissions and days of admission for major infection causes in Brazilian SLE patients.

Methods: Three hundred and twenty-five SLE patients from a Southern Brazilian outpatient SLE clinic were genotyped in 2006 for MBL2 gene polymorphisms from their coding and promoter regions (rs1800450, rs1800451, rs5030737, rs11003125, and rs7096206) and followed until 2016. Clinical and laboratory data from each patient was obtained and information regarding the need for hospitalizations, the number of admissions and number of days admitted for the treatment of an infection were compiled and compared with MBL2 gene polymorphisms and haplotypes. A linear regression analysis was constructed considering the variables which demonstrated an association in the bivariate analysis (p<0.05) and variables which had a theoretical basis.

Results: No differences were found in polymorphism prevalence when comparing the groups that were or not admitted for the treatment of an infection. Allele C, and haplotypes LY and HY correlated with more infection hospitalizations (normal homozygosis for C: 2 (IQR 1-3), heterozygosis for C: 3 (IQR 2-6) p=0.038; LY 2 (IQR 1–3) p=0.049; HY 2 (IQR 1-3) p=0.005), Patients with haplotype HY had shorter hospitalization days: 18 (IQR 10–38) p=0.041. When linear regression was applied HY was associated with a shorter hospitalization for infections (−18.11 days, p=0.021) and HY (−1.52 admission, p 0.001); older age at diagnosis was associated with fewer admissions for infection (HY regression model: −0.42, p=0.006).

Conclusion: The presence of the HY promoter haplotype leads to fewer hospitalization days for infection treatment probably due to higher MBL plasma levels. Also, HY haplotype and older age at SLE diagnosis is related to fewer admissions for infection. It is important to consider that infection is a very import cause of mortality in SLE patients and it is not only related to aggressive immunosuppressive treatment.

307

SUBGLOTIC STENOSIS IN GRANULOMATOSIS WITH POLIANGIITIS

F. Giordano1, C. Pena2, L. Garcia2, G. Pendon1, C. Costi2, A. Vulcano2, D. Pereira1, and M. Garcia2. 1Hospital Gutierrez de La Plata; 2Hospital San Martín de La Plata.

Introduction: The characteristic lesion of laryngotracheal involvement in granulomatosis with polyangiitis (GPA) is subglottic stenosis (SGS), due to active disease or resulting from chronic recurrent inflammation; it occurs in 8 to 23% of patients during the course of GPA and as its initial manifestation in 1 to 6% of cases.

Objective: To describe the clinical features and treatment of patients with SGS.

Methods: We reviewed the medical records of 46 patients with SGS due to GPA diagnosed at a Rheumatology department (2000-2017).

Results: 6/46 patients with GPA presented SGS (13 %). 83% women, mean age of 37.8 years (DS ±14.8). Mean time between the presentation of the GPA and the diagnosis of SGS was 18 months. Most frequent clinical manifestations of SGS: dyspnea (83%), stridor (83%), dysphonia (50%), cough (33%), bronchospasm (16%). One patient presented SGS as initial manifestation of the disease, in the other five patients it occurred concomitantly with other manifestations of active disease. Mean BVAS was 14. Two patients presented such complication with evidence of systemic manifestations. Re stenosis was observed in one patient. Treatments received: IV CYC in 83%, oral CYC in 16%, methylprednisolone (MP) in 83%, oral steroids, plasma exchange (16%) in each one. Endoscopic intervention and balloon dilatation in 33%, and intralesional Mitomycin in 16%.

Conclusion: 13% patients with GPA presented SGS, being in the majority of cases associated with other manifestations of the disease. However, 67% had no signs of systemic involvement (localized disease). Local treatment was necessary in only 33% because there was a good response to IS in 67% of the cases.

309

RESPONSE OF THE MODIFIED RODNAN SCALE WITH RITUXIMAB PLUS CYCLOPHOSPHAMIDE TREATMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS. EXPERIENCE IN PANAMA

R. Pérez Acuña1. 1Complejo Hospitalario Metropolitano Dr. Arnulfo Arias Madrid, Panamá, República de Panamá.

Objective: To determine the efficacy of the combination of rituximab and cyclophosphamide in the treatment of severe systemic sclerosis.

Methods: The therapeutic modalities for this condition and their immunological targets were reviewed. The treatment chosen was based on its effectiveness over the cells affected in this disease and their cellular products, whether they are immunological or due to an excessive collagen production. Cyclophosphamide was chosen for affecting overactive cells’s DNA: myofibroblasts, and collagen production; lymphocytes B and T that produce cytokines and antibodies that perpetuate disease response. Rituximab was chosen because it eliminates pre-B cell population that mature produce related antibodies. Patients with severe systemic sclerosis, and poor prognosis or evidence of disease progression including: a) modified Rodnan cutaneous scale ≥20, b) clinical data of rapid progression (increase of the modified Rodnan scale score at least 4 months after last evaluated, c) that both conditions are given. There were 14 patients in total. Patients were given cyclophosphamide 750 mg/m2 IV (maximum 1 g) every month for 6 months and rituximab 1 g IV every 15 days two doses a year. On day 1 the first dose of cyclophosphamide was given and the first dose of rituximab on day 2. The results were evaluated as percent changes in the modified Rodnan scale score.

Results: Clinical improvement was observed as there was a decrease in the modified Rodnan scale score of 28% to 86%.

Conclusions: The combination of cyclophosphamide and rituximab at the doses administered was effective with an observed reduction in the modified Rodnan scale score of 28% to 86% in patients with severe systemic sclerosis.

314

RELIABILITY OF PATIENTS’ ASSESSMENT OF DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: SCALES AND TIMING OF THEIR APPLICATION

Claudia Elera-Fitzcarrald1,2, Karen Vega3,4, Rocío V. Gamboa-Cárdenas1, Katiuska Zúñiga3,4, Francisco Zevallos1, Cristina Reátegui-Sokolova1, César Pastor-Asurza1, Risto Perich-Campos1, Zoila Rodríguez Bellido1, Graciela S. Alarcón4,5, Armando Calvo3,4, and Manuel F. Ugarte-Gil1,2. 1Servicio de Reumatología. Hospital Guillermo Almenara Irigoyen. EsSalud; 2Facultad de Medicina Universidad Científica del Sur; 3Servicio de Inmunología y Reumatología. Hospital Cayetano Heredia; 4Facultad de Medicina. Universidad Peruana Cayetano Heredia; 5School of Medicine, The University of Alabama at Birmingham, United States.

Objective: To determine the reliability of SLE patients’ measurement of disease activity using a visual analogous scale (VAS) or a numerical rating scale (NRS), before or after their visit to their physicians (MD).

Methods: This is a cross sectional study of systemic lupus erythematosus (SLE) patients conducted between August 2016 and December 2017 at two hospitals in Lima, Perú, one from the Social Security and the other from the Public Health Systems. The first hospital used a comprehensive care program and the second a regular one. Patients assessed their disease activity with a VAS (0-100 mm) or a NRS (0-4); the scales were presented in a random order before and after their MD’s assessment. Demographic and disease related characteristics were measured. Patients’ disease activity before and after MD’s assessment were compared using Spearman Rank Correlation. In order to explain the variability between these measures, demographic and disease related characteristics and the type of care program were examined as possible factors; Spearman Rank Correlation and Mann-Whitney u test were used for these assessments.

Results: Two hundred and forty patients were included. Their mean (SD) age at diagnosis was 34.9 (12.9) years; nearly all patients were Mestizo. Disease duration was 10.1 (7.0) years. The Mex-SLEDAI was 1.9 (2.7) and the SDI 1.2 (1.5). The correlation between NRS before and after the MD’s assessment was Rho=0.839; p<0.001 and for the VAS was Rho=0.872; p<0.001. Although both, VAS and NRS were higher before than after the MD assessment, the differences were statistically significant only for the NRS [29.3 (26.5) and 26.5 (24.9); p=0.052], [1.5 (1.2) and 1.4 (1.1); p=0.003], respectively. None of the patients clinical or sociodemographic characteristics were associated with the variability observed for the NRS before and after the MD’s assessment; however, the type of care program was a significantly different variable [−0.1 (0.6) and −0.8 (2.8); p=0.020 for the comprehensive and regular care programs, respectively]. In the comprehensive care program, the reliability of VAS and NRS was Rho=0.917 and Rho=0.861, p<0.001for both cases and in the regular care program was Rho=0.710 and Rho=0.785, p<0.001 for both cases.

Conclusion: Overall, a higher reliability was observed with the VAS than with the NRS when SLE patients assessed their disease activity. A more comprehensive care program was associated with a lower variability in disease activity between assessments but why this should be the case will need to be further explored.

325

GENETIC BIOMARKERS OF SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS OCCURRENCE IN PARAGUAYAN PATIENTS

Marcos Vazquez1, Ana Ayala Lugo2, Valery Jolie2, María Eugenia Acosta2, Ivalena de Guillén2, Jonathan Losanto1, Elías Rojas1, Nelson Ortiz1, Víctor Martínez1, Karin Baunman1, Marcia Melo1, Sara Marsal3, Antonio Julia3, Margarita González1, Hugo Torio4, Margarita Duarte1, Gabriela Avila1, María Teresa Martínez4, and Isabel Acosta Colman1. 1Department of Rheumatology Hospital de Clínicas, Asunción, Paraguay; 2Institute of Investigation in Sciences of the Health, Asunción, Paraguay; 3Group of Recerca of Rheumatology of Barcelona, Spain; 4Curie laboratory, Asunción, Paraguay.

Introduction: Systemic Lupus Erythematosus (SLE) is a complex disease in which a substantial association with loci of the major histocompatibility complex II does exist.

Objectives: To study the association of the main HLA class II haplotypes with the risk of SLE occurrence in patients being care for at the Department of Rheumatology, Hospital de Clínicas, Asunción, Paraguay.

Methodology: A cohort of 104 patients from Hospital de Clínicas, with SLE was recruited, previous informed consent. For each one of the patients the alleles of the HLA II genes were genotyped at the Curie laboratory with Luminex PCR technology: HLADRB1, HLADQA1, HLADQB1, HLADPA1 and HLADPB1. As controls a cohort from the Paraguayan population is still being constituted; thus, to carry out the study genotyping data from 1,493 controls of a Spanish population were included; these genotypes were generated by imputation generated by the cohort of the biomedical consortium IMID Consortium. The association analysis with the SLE risk was performed using the Chi-square allelic test.

Results: Comparing the haplotypes profiles for the 5 HLA class II genes between the patients and the healthy Spanish controls, a high correlation was observed for HLADRB1 (r2=0.91, p=2.5e-6), HLADQB1 (r2=0.68, p=0.011), HLADPA1 (r2=0.99, p=0.00017) and HLADPB1 (r2=0.81, p=0.00039). In the risk association analysis, the association of the known risk allele was corroborated HLADRB1*03:01 (p=0.0086). A significant association was identified between the allele HLADRB1*08:04 and SLE (p=0.0040). In the gene HLADQA1¸ 6 alleles were found to be associated with SLE, HLADQA1*05:01 (p=1.78e-14), HLADQA1*02:01 (p=9.18e-12) and HLADQA1*04:01 (p=6.9e-6). In the HLADQB1 6 alleles were found to be associated with SLE, HLADQB1*04:02 (p=6.38e-6), HLADQB1*06:02 (p=0.0016) and HLADQA1*03:02 (p=0.0021). In the HLADPA1 gene 4 alleles were found to be associated with SLE: HLADPA1*01:03 (p=1.4e-10), HLADPA1*02:02 (p=3.97e-6), HLADPA1*02:01 (p=5.01e-5), HLADPA1*03:01 (p=0.00011). Finally, in the HLADPB1 gene 5 alleles were found to be associated with SLE: HLADPB1*02:01 (p=4.6e-15), HLADPB1*04:01 (p=2.39e-11), HLADPB1*05:01 (p=6.9e-9), HLADPB1*03:01 (p=1.77e-8) y HLADPB1*04:02 (p=6.97e-5).

Conclusion: The haplotype profile of Paraguayan SLE patients is overall similar to that of the Spanish general population. There are a high number of alleles strongly associated with SLE, some of them not previously described.

327

DIAGNOSTIC VALUE OF LABIAL SALIVARY GLAND BIOPSY FOR SJOGREN’S SYNDROME. A MULTICENTER STUDY OF 1101 CASES

D. Baenas1,2, M.J. Haye Salinas1, S. Retamozo1,2, J.P. Pirola1, N. Benzaquén1, M.F. Ceballos1, J. Flores1, N. Riscanevo1, S. Fiorentino1, V. Saurit1, A. Álvarez1, A. Alvarellos1,2, P. Serravalle3, A. Ortiz3, S. Paira3, and F. Caeiro1. 1Hospital Privado Universitario de Córdoba, Córdoba, Argentina; 2Hospital Raúl Ferreyra, Córdoba, Argentine; 3Hospital Hospital Dr. José María Cullen, Santa Fe, Argentina.

Objectives: Labial salivary gland biopsy (LSGB) is a safe and minimally invasive procedure used in the diagnostic evaluation of Sjogren’s Syndrome (SS). The objectives of this study are: to describe the demographic, clinical and histological characteristics of patients submitted for LSGB; to examine the usefulness of this procedure as a diagnostic tool for SS; to assess the association between histological findings and antibodies.

Methods: An observational, analytical, cross-sectional study was performed between June 1996 and July 2017. Patients with SS were classified according the AECG-2002 and ACR-2012 criteria. Grades III and IV biopsy of the Chisholm and Mason´s classification/focus score ≥1 were considered positive. Data was analyzed using the statistical package SPSS 21.

Results: 1101 patients were included, 91 % females. The mean age was 52 ± years (range 18–86). SS was diagnosed in 413 (37.5%) patients. 34% of the biopsies were positive. Table 1 shows the clinical characteristics and complementary studies in patients with nonspecific dryness syndrome (No-SS) and SS.

TABLE 1
TABLE 1
TABLE 2
TABLE 2:
Compares the Serological Characteristics of Patients using LSGB as a "Gold Standard".

In bivariate analysis there was an association between antiRo, ANA and RF antibodies and LSGB. In multivariate analysis the significance for anti-Ro (OR: 6.33; 95% CI 3.22 to 12.15), ANA (OR: 3.26; 95% CI 2.15 to 4.94) and RF (OR: 3.05; 95% CI 2.04 to 4.56) was maintained.

Conclusions: LSGB is a simple, safe, and useful tool for the diagnosis of Sjögren's syndrome. It exhibits an adequate balance between sensitivity, specificity, positive and negative predictive value. Antibodies showed a significant association with a positive LSGB with low sensitivity for SS screening but high specificity. LSGB has a great value in "seronegatives patients".

330

REPRODUCTIVE HISTORY SURVEY ON PATIENTS WITH SYSTEMIC SCLEROSIS

G.F. Mora1-4, M. Lagrutta2-4, V. Durigan3-4, and M. Mamani3-4. 1Sección Inmunología Clínica – Hospital Militar Central – Buenos Aires, Argentina; 2Sección Clínica Médica/Enfermedades Autoinmunes sistémicas – Hospital Provincial del Centenario, Rosario; 3Servicio de Reumatología – Hospital Rivadavia – Buenos Aires, Argentina; 4GESAREA – Grupo de Estudio de Salud Reproductiva en Enfermedades Autoinmunes.

Introduction: Adverse reproductive outcomes may precede by several years the diagnosis of systemic sclerosis –SSc. Women with SSs have as much as twice the rate of spontaneous abortions and three times more fertility disorders after the age of 35 than healthy women. These patients have also more gestational morbidity. The study of the influence of SSc in the reproductive outcomes of Argentinean patients is the objective of this initiative.

Objectives: 1. To estimate the prevalence of aspects related to reproductive life and risk factors for reproductive health in patients with SSc. 2. To investigate the reproductive outcomes in SSc patients.

Methods, Study Design: Survey-based multicentric, descriptive, observational and historical study. Survey: data regarding all aspects of reproductive life were gathered. Forms were sent by e-mail to patients and re-assessed by the treating physician or taken personally during a visit. The study was approved by the respective institutional ethics committees. Inclusion criteria:1. Patients older than 18 years. 2. Diagnosis of SSc according to ACR/EULAR 2013. 3. Signed the informed consent. Exclusion criteria: 1. Patients who did not sign the informed consent. 2. Psychiatric or cognitive impairment or personal reserve that impeded survey completon. Inclusion of surveyed patients was consecutive. Data was expressed as percentages or media ± SS. The Students t test was used for comparing consecutive variables, and Fisher´s test for qualitative ones. Significance was stablished as p <0,05 (CI 95%).

Results: 30 SSc patients were surveyed (29 women, 1 male). Medium age at the time of the study was 48.1 (±13,7) years (27–74). Age at diagnosis of SSc was 40,6 (±13,7) years-old (12–74). Twenty-six out of 29 women included had been pregnant, 87 pregnancies in total. The age at first pregnancy was 22,4 (±6,3) years (14–36). There were 58 live births (48 to term, 10 premature), 2 stillbirths, 12 fetal losses (2° and-3° trimester), 7 abortions with curettage, 5 abortions without curettage, 3 ectopic pregnancies. Pregnancy outcomes were compared with the time at SSC diagnosis. Pregnancies without complications and resulting in live births were considered as good outcomes. Preeclampsia, eclampsia, renal crisis, diabetes, HELLP syndrome, thrombosis, haemorrhage, DIC, placental abruptio, fetal distress, stillbirth and perinatal death were considered as bad clinical outcomes. The latter included those pregnancies with any complication and those culminating with abortion, fetal loss or ectopic pregnancy. The rate of pregnancies with good clinical outcomes was significantly higher in those occurring before SSc diagnosis compared to pregnancies occurring afterward (96,6% vs 3,4% respectively, p <0,001); this difference persisted after adjustment for age at pregnancy. Medium age at pregnancy were similar regardless of the outcome: 24,28 ± 56,2 vs 37,83 ± 6,4 years (p >0.05). Weight at birth was significantly higher in babies born from mothers pregnant before SSc diagnosis compared to those born after or simultaneously to SSc diagnosis: 3341 ± 664 grams (n= 51) vs 2156 ± 863 grams (n= 7), respectively (p <0,001).

Conclusions: 1. Patients with SSc get pregnant normally, but have high gestational morbidity, particularly during the 2° and 3° trimesters. 2. Higher rate of bad outcomes occurred in those patients with established SSc compared to those in which pregnancies occurred previously to SSc diagnosis. 3. Weight at birth was significantly lower for pregnancies occurring after or simultaneously to SSc diagnosis.

335

BETTER PREGNANCY OUTCOMES IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS TAKING HYDROXYCHLOROQUINE

N.L. Cucchiaro1, M.M. Aciar1, E. Picco1, E.A. Buschiazzo1, R.V. Juarez1, M.V. Lencina1, R.I, Rojas Tessel1, M.E. Crespo Espindola1, and O. Montiel Nardini2. 1Hospital Señor del Milagro, Salta, Argentina; 2Hospital Público Materno Infantil, Salta, Argentina.

Objective: To evaluate the influence of using or not HCQ and Aspirin on the pregnancy outcome of a sample of SLE patients.

Methods: Pregnant women with SLE, registered in the database of the Salta Hospital Público Materno Infantil, who had their offsprings at that institution during the period between January 2006 and December 2016 were studied. Clinical records were reviewed to collect data regarding socio-demographics, SLE characteristics including anti- phospholipid antibodies (APSb) and anti-Ro/La, obstetric background, pregnancy complications and fetal outcomes. Statistics: qualitative data was expressed in frequency and percentages, quantitative data in medians and interquartile ranges (IQR). Data was compared by Chi2 or Fisher´s exact tests, Student’s t or Mann Whitney tests, as appropriate. Logistic regression models were carried out taking “birth outcome” (defined as abortions or decease fetuses) as a dependent variable and adjusting for confounders. A p value < 0.05 was considered significant.

Results: Twenty-nine patients with SLE (2 with concomitant APS) and 39 pregnancies were included. When examining these pregnancies, the median age at the time of delivery was 25 years (IQR 24-29), and disease duration from diagnosis was 4 years (IQR 1.5-6.5). Twenty-three (59) patients were using HCQ at the time of their pregnancy, and 11 (28.2) aspirin. The median birth weight was 2430 mg (IQR 2170-2910), there were 9 (23.1) pregnancies that ended in abortion or fetal death, with 16 (53.3) ending at term and 14 (46.7) at preterm among those pregnancies with available data (n=30). When comparing those pregnancies in which the mothers received HCQ or not, the first group had significantly less miscarriages or deceased fetuses (1/23 [4.3] vs 8/14 [57.1], p=0.001). No differences were found in age at the time of pregnancy (25 vs 27, p=0.5), disease duration (4.1 vs 4.5, p=0.2), preterm births (10/22 [45.5] vs 3/6 [50], p=1) or birth weight (2461 mg vs 2269 mg, p=0.4). Both maternal deaths occurred in patients not taking HCQ. There were neither miscarriages nor fetal deaths in those pregnancies in which the mother was taken aspirin compared with those in which it was not (0/11 [0] vs 9/28 [32], p=0.04). In the logistic regression model, the use of HCQ was independently associated with less miscarriages or fetal deaths (p=0.007). No difference was found between those with positive or negative APSb or Ro/La regarding pregnancy outcomes.

Conclusion: In this sample of pregnant SLE patients, the use of HCQ and the use of aspirin were associated with significantly less miscarriages and fetal deaths. All newborns weighted less than 2.5 kgs.

338

SYSTEMIC LUPUS ERYTHEMATOSUS IN COLOMBIA: A BIBLIOMETRIC ANALYSIS

J. Barahona-Correa1. 1Universidad del Rosario, Bogotá, Colombia.

Objective: To perform a bibliometric study on the scientific production on systemic lupus erythematosus (SLE) in Colombia that describes its distribution, development trends, national and international collaboration trends, and its impact on the scientific community.

Methods: A descriptive bibliometric study was performed using three databases (Web of Science, SCOPUS and Scielo). Annual national research output, number of articles, city and institution of origin, national and international collaboration, scientific journals, publication language, and citations number were assessed.

Results: SCOPUS disclosed 307 articles, Web of Science 270, and Scielo 90. The highest number of citations per item (19.8) and the maximum national H index (41) were found in SCOPUS. More than 80 % of articles, regardless of the database, were published during the last 10 years. ‘Universidad del Rosario’ and ‘Universidad de Antioquia’ showed the highest research output. Bogotá and Antioquia, followed by Valle del Cauca, presented the highest number of articles. An important number of national and international collaborations were observed, which differed in each database.

Conclusion: A significant growth of the research on SLE in Colombia was observed, however, its impact is far from being meaningful. Strategies aimed at strengthening the interest in Rheumatology and research in undergraduate students must be encouraged, particularly supporting research seedbeds and young researchers.

348

RELATION BETWEEN THE DEFICIT/DEFICIENCY OF VITAMIN D AND DEPRESSION/ANXIETY IN PATIENTS WITH LUPUS FROM THE DEPARTMENT OF RHEUMATOLOGY OF THE HOSPITAL OF CLINICS

Nelson Ortiz1, Marcos Vázquez1, Víctor Martínez1, Lourdes Román1, Karin Baunman1, Marcia Melo1, Isabel Acosta1, and Margarita Duarte1. 1Departament of Rheumatology Hospital de Clínicas San Lorenzo, Paraguay.

Introduction: It has been postulated that low concentrations of 25-hidroxivitamin D serum [25 (OH) D] are associated with a greater prevalence of depression. People with deficient levels of vitamin D are more likely to experience mood disorders such as depression and anxiety. Vitamin D plays a role in the release of neurotransmitters such as serotonin and dopamine which is why it is interesting tos study this in systemic lupus erythematosus (SLE) patients who are discouraged from sun exposure.

Objective: To determine the association between the vitamin D deficiency anxiety/depression in patients with SLE from the Department of Rheumatology, Hospital de Clínicas

Methods: Observational study of a longitudinal cohort, based in a questionnaire according to the HADS (Hospital Anxiety and Depression Scale) scale and vitamin D levels performed on SLE patients who entered the LUPUS PY cohort with prior informed consent. Vitamin D levels were measured by chemiluminescence. Data and samples were taken in weeks 0 and 24 and the prevalence of depression and anxiety and its association with vitamin D deficiency and insufficiency were identified. Patients with vitamin D deficiency or insufficiency were supplemented with vitamin D. For the descriptive analysis of the quantitative variables, average and SD were used, for the qualitative frequencies and percentages. For the analysis of association, the Chi square test was used. A p value < 0,05 was considered statistically significant.

Results: 90.5% of the patients were female, with an average age of 33 ± 10.2 years. At week 0 the average value of vitamin D concentration was 31.8 ± 10.2 ng/ml; 4,48 % of the patients had depression and 33,69 % had anxiety. At week 24, the average vitamin D level was 31,1 ± 13,6 ng/ml; 6% of patients presented depression and 12 % anxiety. There was no association between vitamin D deficits and the presence of depression or anxiety in these patients both at the weeks 0 and 24 post vitamin D supplementation as noted in Table 1.

TABLE 1
TABLE 1:
Deficit and Insufficiency of Vitamin D Associated with Depression and Anxiety in Patients with SLE.

Conclusion: A significant percentage of patients with Vitamin D deficiency or insufficiency were found, as well as a considerable percentage of depression and/or anxiety; however, no association was found between Vitamin D levels and mood abnormalities. Studies including more patients are needed to obtain conclusive results.

350

DECREASED SIX-MINUTE WALK DISTANCE CORRELATES WITH SKIN INVOLVEMENT AND RESPIRATORY DISABILITY IN SYSTEMIC SCLEROSIS PATIENTS FROM PUERTO RICO

G. Ríos1, E Jiménez1, R. Gago1, Y. De Jesús1, E. J. Santiago, and A. M. Mayor2. 1University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico; 2Universidad Central del Caribe, Bayamón, Puerto Rico.

Background and Objectives: The 6-minute walk test (6MWT) is a simple, safe, non-invasive and reproducible test used to evaluate submaximal exercise capacity. The role of the six-minute walk distance (6MWD), measured by the 6MWT, in the assessment of patients with systemic sclerosis (SSc) remains to be elucidated. Conflicting results and limitations of observational studies have precluded a conclusive association between the 6MWD and organ damage in SSc. Therefore, we evaluated the association between 6MWD and conventional clinical parameters obtained by a standardized assessment of SSc patients followed in a rheumatology clinic in Puerto Rico.

Methods: A cross-sectional study was conducted in 35 patients who fulfilled the American College of Rheumatology criteria for SSc. Patients underwent 6MWT according to published guidelines. Socio-demographic characteristics, SSc clinical manifestations, and pharmacotherapy were determined. The extension of skin involvement was measured by the modified Rodnan Skin Score (mRSS). Dyspnea questionnaires (Borg dyspnea scale, Medical Research Council Dyspnea Scale [MRC] and Oxygen Cost Diagram [OCD]) were administered at study visit. Spearman’s rho was used to evaluate correlations between 6MWD and clinical parameters.

Results: Among the 35 SSc subjects, their mean (SD) age was 50.2 (12.1) years and 91% were female. Their mean (SD) SSc disease duration was 10.1 (7.9) years. Twenty-two subjects (62.9%) had limited SSc and 13(37.8%) had diffuse SSc. Mean (SD) mRSS was 11.2 (6.8). Mean (SD) 6MWD was 377.1 m (75.6), with a range of 258.6-608.5 m. Higher mRSS was associated with lower 6MWD (rho=−0.37, p=0.029). MRC and OCD dyspnea scores correlated significantly with 6MWD (rho=−0.37, p=0.030, rho=0.52, p=0.001). No correlations were found between 6MWD, musculoskeletal involvement, Borg dyspnea scale scores, socio-demographic characteristics, pharmacotherapy and other SSc clinical manifestations.

Conclusions: Decreased 6MWD significantly correlated with higher skin scores and respiratory disability in this group of se SSc patients. Further studies are needed to confirm the clinical value of the 6MWT in a larger SSc population.

351

STUDY OF THE PRESENCE OF HPV WITH ITS DIFERENT SEROTYPES IN PATIENTS WITH SLE AND THEIR ASSOCIATED RISK FACTORS

S. Riquelme-Granada1, L. Roman1, I. Acosta-Colman1, M.E. Acosta2, G. Colman1, M. Duarte1, and M. Melo1. 1Department of Rheumatology. Hospital de Clínicas, Universidad Nacional de Asunción, San Lorenzo, Paraguay; 2Instituto de Investigaciones en Ciencias de la Salud (IICS), San Lorenzo, Paraguay.

Objectives: To determine the prevalence of HPV infections and its distinct serotypes in patients diagnosed with SLE. To determine biomarkers involved in HPV infection.

Materials and Methods: Observational descriptive and cross-sectional study. We included 51patients with an established diagnosis of SLE, in reproductive ages who are being followed at the Department of Rheumatology of the Hospital de Clínicas, Faculty of Medical Sciences, Universidad Nacional de Asunción (UNA). Clinical, epidemiological and gynecological variables were evaluated. The qualitative variables were expressed as frequencies and percentages, the quantitative ones as means and standard deviation while the association analysis of the variables was performed with the IBM-SPSS Statistics program version 23 using Chi-squared distribution for the association of qualitative variables and the Student’s t-distribution for the associations between qualitative dichotomous and quantitative variables.

Results: A total of 51 female patients with a diagnosis of SLE were included; their mean age was 30.49 ± 9.95 years, with a history of menarche at 13.19 ± 1.75 years and beginning of sexual life at 18.01 ± 2.7 years.7,8% (4/51) of the patients were promiscuous according to the criteria established by WHO. Only 27,5% (14/51) used a barrier method during intercourse. The average age at the time of diagnosis of SLE and the time of evolution of the pathology was 25.64 ± 10.29 years and 56.88 ± 57.02 months respectively. 49% of the patients came from Gran Asunción, 37.3% from the interior of the country and 13.7% from the capital. Only 13.7% of patients had complete university education, while 13.7% had complete primary education and 29.4% completed secondary school. 3.9% were tobacco users. 64.7% of the patients presented at least one pregnancy. 94.1% presented normal PAP. 80.4% of the patients presented a positive PCR for HPV, of which 70.6% were high risk, serotype 18 was presented in 23.5% and serotype 73 in 11.8%. Among the low risk serotypes, 42 presented it in 13.7% of the patients, serotype 62/81 in 11.8%. Only 39.2% required a biopsy; of them, in 31.4% (16/31) was from the cervix in which low-grade SIL was observed in 21.6% (11/36) and only in 5.9% (3/36) corresponded to a high grade SIL. 100% of the patients received at least 1 DMARD, 98% Hydroxychloroquine; meanwhile 66.7% (35/51) was receiving prednisone.

In the association analysis between the different clinical, epidemiological and gynecological variables, it was observed that there was a significant association between smoking and the presence of atypia in PAP (p = 0.03); in addition, there was a tendency toward statistical significance between the presence of atypia in PAP and promiscuity (p=0.075). Regarding medications, no significant relationship was found between the use of the different DMARDs or the amounts used and the presence of HPV or atypia in the PAP smear; although there was a statistically significant relationship between the use of high doses of corticosteroids (Methyl prednisolone) and the presence of HPV, both low grade (p = 0.025) and high grade (p = 0.038)

Conclusion: In this population of patients with established SLE of childbearing age. we found a high HPV presence, mostly of the high-grade serotype. It was interesting that atypia by PAP was found in smokers as well as in those using high doses of corticosteroids and the presence of HPV, both low and high grade; the latter corresponding to patients with a greater degree immunosuppression.

353

MORTALITY IN PATIENTS WITH SYSTEMIC SCLEROSIS (SSC) AT CENTRO MEDICO NACIONAL 20 DE NOVIEMBRE ISSSTE

Brenda Isuki Lopez Benjume1, Fedra Consuelo Irazoque Palazuelos1, and Sandra Muñoz Lopez1. 1CMN 20 De Noviembre ISSSTE.

Introduction: SSc is associated with an increased risk of mortality, it is 2.72 times higher than general population. Of the causes of mortality 47% is related to the disease, cardiopulmonary affectation constitutes the main cause of death in these patients, especially in the two last decades.

Objective: To determine the occurrence of mortality in patients with SSc, at CMN 20 de Noviembre ISSSTE hospital.

Materials and Methods: Cross-sectional study in patients with SSc who attend to the rheumatology service. Descriptive statistics were performed. Calculations were performed using the SPSS software version 20.

Results: 42 women with a mean age of 56 years. 5 (11.9%) had a diagnosis of DcSSc and 37 (88.1%) of limited cutaneous variety (LcSSc). The mortality was 16.6% (7 cases) in 7 years. 33.3% had DcSSc, 4.2% of this group was related with primary biliary cirrhosis, 4.2% with PAH and 1.4% with breast cancer treatment. The mortality causes were: 5.7% (4 patients) digestive tract hemorrage (DTH), 2.8% (2 pacientes) heart failure and 1.4% (1 patient) sepsis. All patients were female with mean age of 65 years old, the average time of evolution of the disease was 13 years.

Conclusion: Mortality in our patients was found to be like that reported in the literature; unlike previously reported, the cardiopulmonary cause was the second cause of death, being most frequent DTH in our population.

355

A COMPREHENSIVE CARE PROGRAM REDUCES THE NUMBER AND LENGTH OF HOSPITALIZATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Cristina Reátegui-Sokolova1, Manuel F. Ugarte-Gil1,2, Rocío V. Gamboa-Cárdenas1,3, Mariela Medina-Chinchon1, Francisco Zevallos-Miranda1, Claudia Elera-Fitzcarrald1, Victor R. Pimentel-Quiroz1, Jorge M. Cucho-Venegas1, José L. Alfaro-Lozano1, César A. Pastor-Asurza1,3, Risto A. Perich-Campos1,3, Graciela S. Alarcón4, and Zoila J. Rodríguez-Bellido1,3. 1Rheumatology Deparment, Hospital Guillermo Almenara Irigoyen, EsSalud, Lima, Perú; 2School of Medicine, Universidad Científica del Sur, Lima Perú; 3School of Medicine, Universidad Nacional Mayor de San Marcos, Lima Perú; 4School of Medicine, The University of Alabama at Birmingham, United States.

Objective: To determine the impact of the management of systemic lupus erythematosus (SLE) patients using a comprehensive care program on the number and length of hospitalizations.

Methods: In 2012 we constituted the Almenara Lupus cohort; patients from this cohort are evaluated every six months (interview, medical records review, physical examination and laboratory tests); in addition, these patients are provided with information about their disease, comorbidities and how to prevent complications related to the disease, treatment and/or comorbidities. We have identified all patients’ hospitalizations during the two years before and after the baseline visit. Hospitalizations occurring during the two years before the baseline visit were considered as historical controls, and hospitalizations occurring during the two years after it were considered as exposed ones. Frequency and length of hospitalizations were recorded. Additionally, sociodemographic [age, gender, socioeconomic status and educational level) and disease-related factors (disease activity, as per the SLEDAI, disease damage, as per the SLICC/ACR damage index (SDI)] and comorbidities (Charlson comorbidity index) were evaluated at baseline, in order to determine if there are some subsets of patients in which our program has a better impact. Hospitalizations during these two periods were compared using Wilcoxon signed-rank test, and the association between sociodemographic, disease-related and comorbidities with the differences between hospitalizations during these two periods was evaluated using Kruskal Wallis for independent samples or Spearman correlation, as appropriate.

Results: Of the 314 Almenara Lupus Cohort patients with at least two years of follow-up, 291 (92.7%) were women, with a median age of 40.7 [interquartile rank (IQR) 33.0 – 51.2], disease duration of 5.5 (IQR 2.6-10.3) years, and age at diagnosis of 33.0 years (IQR 25.0-41.8). At the baseline visit the median SDI was 0 (IQR 0-1), SLEDAI was 4 (IQR 2-8), prednisone dose was 5mg/d (IQR 5.0 -10.0). The data are shown in Table 1.

TABLE 1
TABLE 1:
Hospitalization in General and in ICU Before and After Cohort Entry

The only factor associated with a reduction of the number and length of hospitalizations was socioeconomic status; moreover, the reduction in the length of hospitalizations was only significant in the low and middle socioeconomic status (p=0.001 and p=0.005, respectively).

Conclusions: Implementing measures to improve the quality of care for SLE patients resulted in a diminished frequency and duration of hospitalizations, particularly in those patients of low socioeconomic status.

356

PREVALENCE OF METABOLIC SYNDROME (MS) IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN A MEXICAN POPULATION AND ITS RELATIONSHIP WITH INFLAMMATION MARKERS. A MULTICENTER STUDY

S. Muñoz Lopez1, L. Andrade Ortega1, F. Irazoque Palazuelos1, R. Galaviz Pérez2, and S. Hernandez Sandoval3. 1CMN 20 De Noviembre ISSSTE; 2Hospital General Naval de Alta Especialidad; 3Instituto Nacional de Cardiología Ignacio Chavez.

Introduction: The prevalence of MS is higher in SLE than in the general population (16-32%). Inflammatory activity and steroids have been associated with the SM. 25% of deaths in SLE have cardiovascular (CV) origin and are associated with dyslipidemia, elevated BMI, insulin resistance and hypertension.

Objective: To determine the prevalence of MS in Mexicans patients with SLE and its association with disease characteristics and inflammatory markers.

Methods: Cross-sectional study of patients with SLE. Demographics, coronary risk, disease activity and inflammatory markers were studied. The diagnosis of MS was established with the NHLBI/AHA criteria. Statistical analysis was performed using SPSS 20.0 software and a P value <0.05 was considered significant.

Result: 126 patients with SLE, 107 women (84%) and 19 men (15%), age 41 ± 13 years and disease duration 9 ± 7 years. The prevalence of MS was 33.3%. No association was found with age, education level, smoking or steroid use in patients whit MS. In multivariate analysis only the erythrocyte sedimentation rate (ESR) had statistical significance (p = 0.012). Positive association was found between higher values of ESR and hypertriglyceridemia (p= 0.0002), body mass index (p= 0.0043) and lower levels of HDL and C3 (p= 0.0152)

Conclusion: The prevalence of MS in our population (33%) was higher than reported in the SLICC registry (15%). The association of metabolic and inflammatory characteristics increases cardiovascular risk by a proinflamatory state. The results suggest the need for early diagnosis and treatment of MS to reduce cardiovascular comorbidity in patients with SLE.

361

SCLERODERMA IN PERUVIAN PATIENTS: CORRELATION BETWEEN DERMAL, VISCERAL AND INMUNOLOGIC INVOLVEMENT

Claudia Mora T1,2, Jorge N. Cieza1,2, J. Reque1,2, and Germán Valenzuela3. 1Servicio de Reumatología del Hospital Nacional Edgardo Rebagliati Martins. EsSalud.UNMSM. Lima- Perú; 2Unidad de Investigación, Clínica Delgado. Lima-Perú.

Objectives: To evaluate the clinical and epidemiological characteristics of Peruvian scleroderma patients, and to correlate cutaneous manifestations with visceral and immunologic involvement.

Methods: Longitudinal, observational study. We examined the clinical and epidemiological characteristics of Peruvian scleroderma patients from a single center. We included ambulatory patients, older than 18-year of age with scleroderma that met American College of Rheumatology criteria. These patients were taken care of at the Hospital Nacional Edgardo Rebagliati Martins Lima-Perú between June 2001 and June 2015.

Results: Forty-five scleroderma patients were evaluated for this study, 22 with diffuse and 23 with limited cutaneous involvement. The average age was 54.78 years, women, 86.6%. The mean disease duration was 8.31 years (1-50), 64.4% had gastrointestinal complaints (most commonly gastroesophageal reflux disease, 93.1%), 22,2% interstitial lung disease (ILD) and 8.8% pulmonary arterial hypertension (PAH). No patient developed a renal crisis.

We did not find a correlation between age, local or systemic clinical manifestations, such as digital ulcers, the interincisal distance, calcinosis, acroosteolysis, myopathy or visceral involvement (heart, lung or gastrointestinal) and the type of auto-antibodies and the type of dermal involvement (p>0.05). Thyroid disease was significantly more frequent in limited cutaneous scleroderma disease.

Conclusions: In this group of Peruvian scleroderma patients no significant differences were found between the type of cutaneous involvement and disease features and immunologic markers. Thyroid disease was significantly associated with limited cutaneous scleroderma disease.

374

QUALITY OF LIFE AND PERSONALITY FEATURES IN VENEZUELAN PATIENTS WITH LUPUS

M. Solís-García1, R García Hernández1, H. Cipriani1,2, and Y. Fuentes Silva1,2. 1Universidad de Oriente, Ciudad Bolívar, Bolívar, Venezuela; 2Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Bolívar, Venezuela.

Objectives: According to the World Report 2017 of Human Rights Watch, since 2014 Venezuela is in a humanitarian crisis given by severe shortages of medicines and medical supplies. Many patients with lupus are without medication and under poor healthcare conditions. Knowing patient personality helps to create and promote strategies for offering solutions individually. We evaluated the quality of life and personality traits of patients with lupus.

Methods: During 2017, 80 patients with systemic lupus erythematosus (SLE) were interviewed and socio-demographics data, quality of life and personality traits data were collected. All patients fulfilled the 1997 ACR or the 2012 SLICC criteria. Quality of life and personality traits were evaluated using Gencat scale and self-administered questionnaire International Personality Disorder Examination – International Classification of Diseases 10 (IPDE-CIE 10), respectively. Gencat scale contains eight domains and lower percentiles show poor quality of life and vice versa. All patients signed an informed consent. Statistical analysis was done using Chi square and ANOVA.

Results: Of the total population (80 patients) with SLE, 89% were female, mean age was 36.31±10 years, disease duration was ≥ 5 years in 71%. Patients had technical or university degree in 62%, low socio-economical status in 85% and 47.5% had worked.

Table 1 shows scores and quality of life percentiles of and Table 2 shows the frequency of personality traits and their percentiles of quality of life. There were not significant associations between socio-demographic data (gender, age, education, occupation, disease duration and socio-economical status) and quality of life or personality traits. There was no association between different personality traits and quality of life.

TABLE 1
TABLE 1:
Quality of Life (Gencat Scale) in Patients with SLE
TABLE 2
TABLE 2:
Frequency of Personality Traits and Percentiles of Quality of Life.

Conclusions: In general, patients had a poor quality of life, showing the lowest percentiles in material and physical wellbeing and rights; these factors are related with access to and functioning of the health services. On the other hand, self-determination, interpersonal relations and social inclusion had good percentiles; these characteristics indicate that the individual could promote strategies for improving the quality of life of this population. Furthermore, studies with the country’s socio-economic indicators are necessary for a better understanding these issues.

388

SHORT AND LONG-TERM FOLLOW-UP OF PERIPHERAL NEUROPATHY DUE TO SYSTEMIC LUPUS ERYTHEMATOSUS: EVIDENCE OF A FAVORABLE OUTCOME

S. Fargetti1, E. Bonfa1, S.K. Shinjo1, S.G. Pasoto1, L.P.C. Seguro1, M.R.U. Lopes1, C.R. Gonçalves1, and E.F. Borba1. 1Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objective: Our aim was to describe the short and long-term outcome of peripheral neuropathy (PN) attributed exclusively to systemic lupus erythematosus (SLE).

Methods: SLE patients (ACR criteria, 1997) were identified using an electronic medical record database established in our Service in the year 2000. Clinical and laboratory data were evaluated at the PN onset (baseline), and after 1 and 5 years. PN diagnosis was defined by neurological abnormalities (ACR nomenclature and case definitions for neuropsychiatric lupus syndromes, 1999) and electroneuromyography. Exclusion criteria were other conditions associated with PN: comorbidities, vitamin B12 deficiency, drugs (alcohol, thalidomide, leflunomide, statins), infections, and other autoimmune diseases. Age-, sex-, and disease duration-matched SLE patients without PN were selected as controls.

Results: Lupus PN was identified in 38 of 2,074 patients (1.8%) and almost two-thirds had PN onset in the first 5 years of SLE (63.2%). The most common type was polyneuropathy (71.1%) with sensory-motor pattern (68.4%). PN SLE had higher frequencies of cutaneous vasculitis (50% vs. 21.1%, p=0.002), lymphopenia (60.5% vs. 36.8%, p=0.027), anti-Sm (52.6% vs. 27.6%, p=0.013) and higher SLEDAI score (11.5±10.5 vs. 4.9±6.7, p<0.0001) compared to controls. We observed higher SLEDAI scores in patients with early PN onset (<1 year of disease duration) (21.3±9.07 vs. 5.71±6.1, p<0.001). At PN diagnosis, all patients received glucocorticoid and 97.4% (n=37) started immunosuppressive therapy (50% IV cyclophosphamide, 42.1% azathioprine). In multivariate analysis, PN was associated with cutaneous vasculitis (OR 3.91; 95% CI 1.59–9.54, p=0.003), anti-Sm (OR 2.77; 95% CI 1.16–6.61, p=0.022), and lymphopenia (OR 2.48; 95% CI 1.05–5.89, p=0.039). After 1-year follow-up, 92.1% had a favorable outcome with complete (36.8%) or partial remission (55.2%), in parallel with a decrease in prednisone dose (48.3±17.9 vs. 15.3±13.4mg/d, p<0.0001), symptomatic therapy (57.9% vs. 29.7%; p=0.02), and SLEDAI score (p<0.001). Early PN onset group had a better response to treatment (complete remission at 1-year follow-up 61.5% vs. 25%, p=0.039). At 5-year follow-up, 89.3% remained with complete/partial remission.

Conclusions: SLE-attributed PN is a rare and early manifestation associated to high disease activity, but with a high rate of complete remission. Our study strongly suggests a favorable outcome with immunosuppressive therapy in most of these itself after 1 and 5 years of follow-up.

392

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF BRAZILIAN PATIENTS WITH SYSTEMIC SCLEROSIS

V. Hax1,2, L. Schneider1,2, I.F.S. Moreira1, R.R. Piovesan1, T.F. Macedo1, R.K.M. Barreto1, M.A. Streit1, C.Y. Ueda1, H.M.F.S. da Silva1, R.M.S. Chakr1,2, R.M. Xavier1,2, and C.V. Brenol1,2. 1Department of Internal Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; 2Rheumatology Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.

Introduction: Systemic sclerosis (SSc) is a multisystem autoimmune disease of complex etiopathogenesis, which is classified into diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) subsets according to skin involvement. Interstitial lung disease (ILD) is currently the primary cause of death in systemic sclerosis (SSc).

Objective: The objective of this study is to characterize the demographic, clinical and laboratory features of Brazilian patients with SSc and examine their baseline data.

Methods: A total of 105 consecutive patients with SSc were included between October 2016 and December 2017. All patients fulfilled ACR/EULAR 2013 classification criteria for SSc. Demographic, clinical and laboratory data were obtained at baseline; these patients will be followed up. Also, data on thoracic high-resolution computed tomography and pulmonary function tests were recorded. A reduced forced vital capacity (FVC) and a reduced diffusion capacity of carbon monoxide (DLCO) were defined as FVC and DLCO lower than 80%, respectively.

Results: The mean age of SSc patients was 58.4 (±13.3) years, 90.5% were female and 24.8% presented dcSSc. Disease duration was defined as the time interval since the first non-Raynaud’s symptom and was 13.6 (±9.6) years. Men had a lower mean age (48.1±16.8 vs. 59.5±12.5, p=0.009) and a higher frequency of diffuse cutaneous disease (50% vs. 22.1%, p=0.048) than women. However, there was no significant difference for the other variables analyzed between the genders. Most patients considered themselves white (77.9%), while 22.1% considered themselves non-white. Non-white patients presented a lower mean age (52.7±12.4 vs. 59.9±13.2, p=0.003), a higher proportion of reduced DLCO (90.5% vs. 65.3%, p=0.048), a greater prevalence of pitting scars (56.5% vs. 32.1%, p=0.019) and a trend to greater prevalence of amputations (21.7% vs. 7.5%, p=0.051). Patients with diffuse cutaneous disease presented a lower mean age (49.7±13.7 vs. 61.3±11.9, p<0.001), a greater prevalence of digital ulcers (23.1% vs. 6.4%, p=0.016) and a higher level of CRP (13.7±20.9 vs. 6.2±11.6, p=0.023) than patients with limited disease or sine scleroderma. As expected, dcSSc patients presented a greater modified Rodnan skin score (11.6±9.1 vs. 1.5±1.1, p<0.001), higher positivity for anti-Scl70 (23.1% vs. 5.1%, p=0.037) and a higher proportion of reduced FVC (64% vs. 38.5%, p=0.025).

Conclusion: Our results are consistent with data reported in the literature on the differences among gender and disease subtype. Also, this study confirms that gender-related characteristics, skin color and disease subtype are also present in these Brazilian SSc patients.

References

1. Mayes MD, Lacey J V., Beebe-Dimmer J, et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. 2003;48(8):2246-2255.

2. Freire M, Rivera A, Sopeña B, et al. Clinical and epidemiological differences between men and women with systemic sclerosis: a study in a Spanish systemic sclerosis cohort and literature review. Clin Exp Rheumatol. 2017;35(4):89-97.

USEFULLNESS OF THE SPANISH VERSION OF THE SYSTEMIC LUPUS ACTIVITY QUESTIONNAIRE (S-SLAQ) IN CLINICAL PRACTICE: ITS CORRELATION WITH DISEASE ACTIVITY INDICES IN AN ARGENTINEAN POPULATION

C. Catoggio1, A. Martinez Muñoz2, R.E. Chaparro del Moral2, D.S. Klajn2, S.B. Papasidero2, M.A. Machado Escobar, MA3, L Gonzalez Lucero3, E. Lucero3, L. Martinez4, S. Muñoz4, M.V. Collado5, G. Gomez5, J. Sarano5, J. Marin6, M. Scolnik6, J. Romero7, J.C. Barreira7, M.M. Zalaazar8, O.L. Rillo8, and C.N. Pisoni1. 1Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina; 2Hospital General de Agudos “Dr. E. Tornú”, Buenos Aires, Argentina; 3Hospital Angel C. Padilla, Tucumán, Argentina; 4Hospital General de Agudos “Dr. Juan A, Fernández”, Buenos Aires, Argentina; 5Instituto de Investigaciones Médicas Alfredo Lanari, Buenos Aires, Argentina; 6Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 7Hospital Británico, Buenos Aires, Argentina; 8Hospital General de Agudos “Dr. Ignacio Pirovano”, Buenos Aires, Argentina.

Objective: The Systemic Lupus Activity Questionnaire (SLAQ) is a patient self-reported instrument to screen for disease activity in Systemic Lupus Erythematosus (SLE) studies outside the clinical setting. Our objective was to determine the most efficient cut-off value of the validated Spanish Version of SLAQ (S-SLAQ) to identify patients with active SLE and to ascertain the association of S-SLAQ with other clinically relevant, validated patient assessments of health. The most efficient cut-off point was defined as that corresponding to the best combination of specificity and sensitivity for the identification of patients with a SLEDAI score ≥ 6.

Patients and Methods: 97 consecutive SLE patients (fulfilling the 1997 ACR classification criteria) from 8 Rheumatology centers in Argentina were included in the study. We used the translated, adapted and validated Spanish version of SLAQ (S-SLAQ), consisting of 24 questions adapted from the Systemic Lupus Activity Measure (SLAM), with exclusion of laboratory items (SLAM-no lab), but including two questions of Patient Global Assessment, one for presence and severity of flares (0-3) and a Numerical Rating Scale for disease activity (0-10) (NRS). Patients completed the S-SLAQ just before a scheduled visit. One rheumatologist blinded to S-SLAQ results examined each patient and completed the SLAM. Disease activity was also assessed with SLEDAI-2K and Physician Global Assessment (PGA) (VAS 0-100 mm) at the same visit. Correlations between S-SLAQ and SLAM-no lab as well as SLAM, SLEDAI-2K and PGA were assessed with Pearson correlation coefficient. Sensitivity, specificity, and positive and negative predictive values for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points (ranging 0-35) were assessed.

Results: The study included 97 patients [93% female, mean age: 40 years (SD14.7)]. Mean score of S-SLAQ was 8.24 (SD 7.31); mean SLAM-no lab was 2.06 (SD 2.38); mean SLAM was 3.68 (SD 3.17), mean SLEDAI-2K was 2.75 (SD 3.96) and mean PGA was 0.52 (SD 0.79). Correlation of S-SLAQ with patient global assessment was moderate (r= 0.63 p< 0.001); and weak with SLAM-no lab (r=0.41, p=0.0008) and SLAM (r=0.38, p=0.0022). It was very weak with SLEDAI-2K (r= 0.15, p=1.000). Using the S-SLAQ cut-off of five points the sensitivity was 72.2 % and specificity 37.9 %, for clinically significant disease activity (SLEDAI 2K ≥ 6).

Conclusions: The S-SLAQ cut-off point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument. A good correlation, similar to the original instrument was observed with patient´s assessment of global disease. No correlation was found between S-SLAQ and gold standard disease activity measures like the SLEDAI 2K and the SLAM.

397

DECREASED HO-1 EXPRESSION IN INNATE IMMUNE CELLS MIGHT CONTRIBUTE TO KIDNEY DAMAGE IN LUPUS NEPHRITIS (LN)

L. Cuitino, P. Gajardo-Meneses, J. Obreque, A. Villarroel, A.M. Kalergis, G.P. Mendez, and C. Llanos. Pontificia Universidad Católica de Chile (PUC), Santiago, Chile.

Objective: To study HO-1 in LN by exploring its role as an anti-inflammatory enzyme in innate immunity and as a cytoprotective agent in renal tissue. Accordingly, we examined the expression of HO-1 in circulating and in infiltrating renal biopsies monocytes and neutrophils.

Methods: SLE patients with proliferative LN confirmed by renal biopsy (Class III, IV or V ISN/RPS) were recruited at PUC’s Hospital Clínico. All individuals signed an informed consent form. HO-1 expression in circulating monocytes (classical CD14hiCD16dim, intermediate CD14hiCD16hi, non-classical CD14loCD16hi) and neutrophils (total CD11b+/CD15b+, activated CD11b+/CD15+/CD66b+) from peripheral blood were analyzed in LN patients and Healthy Controls (HC) using FACS. In renal biopsies, infiltrating cells were identified by immunofluorescence and the number of cells/mm2 was determined. HO-1 levels were evaluated by immunohistochemistry and immunofluorescence in biopsies.

Results: We found that circulating LN monocytes had significantly lower protein levels of HO-1 than monocytes of HC (LN: 1706±402.2, HC: 4572±639.8; p<0.005). A significant increase of ‘non-classical’ circulating monocytes was observed in LN patients when compared with HC (LN: 10.73±1.525, HC: 5.560±0.8388; p<0.005). No significant differences in the percentages of classical and intermediate monocytes were observed between LN patients and HC. There were no significant differences in HO-1 protein expression in circulating neutrophils; however LN-activated neutrophils presented lower levels of this enzyme than HC (LN: 1.057±0.0584, HC: 1.642±0.1606; p<0.05). In renal biopsies, HO-1 was mostly expressed in the cytoplasm of epithelial tubular cells. Interestingly, monocytes, macrophages and neutrophils from LN biopsies showed significantly lower expression of HO-1 than epithelial cells of LN patients (~90% less; p<0.05).

Conclusion: Decreased HO-1 expression in circulating and infiltrating monocytes and/or neutrophils of LN patients promote a proinflammatory environment that contributes to renal injury. We propose that increased HO-1 levels in epithelial renal cells might be an attempt of the kidney to protect itself from damage. Since HO-1 levels are reduced in innate immune cells promoting a pro-inflammatory role, we speculate that HO-1 induction in renal tissue might exert a cytoprotective role in LN.

FONDECYT N° 1150173.

415

SAFETY AND EFFICACY OF MYCOPHENOLATE MOFETIL IN IDIOPATHIC INFLAMMATORY MYOPATHIES: A CROSS-SECTIONAL STUDY

Pablo Arturo Olivo Pallo, Renata Miossi, Fernando Henrique Carlos de Souza, and Samuel Katsuyuki Shinjo. Department of Rheumatology, Hospital das Clinicas HCMFUSP, School of Medicine, Sao Paulo University - Sao Paulo, Brazil (BR).

Introduction: Several immunosuppressant drugs have been used as glucocorticoid sparing agents in idiopathic inflammatory myopathies (IIM) for maintenance treatment. However, there is a lack of studies on the use of mycophenolate mofetil (MMF) in these patients, especially those with refractory disease to other immunosuppressants.

Objectives: To assess the safety and efficacy of MMF in patients with refractory idiopathic inflammatory myopathies.

Methods: Historical single center study, from 2011 to 2016, in which 21 consecutive adult patients with IIM (dermatomyositis, clinically amiopathic dermatomyositis, anti-syntethase syndrome or polymyositis) were evaluated for 6 consecutive months after MMF initiation. Refractoriness was defined as: persistence of cutaneous, muscular, articular and/or pulmonary activity, difficulty in decreasing the dose of corticosteroid or inadequate response to at least two immunosuppressive agents used at maximum dose and for a minimum period of three months (administered sequentially or simultaneously).

Results: In 18 (85.7%) of the 21 refractory patients (11 dermatomyositis, 4 polymyositis, 2 anti-syntethase syndrome, 1 clinically amiopathic dermatomyositis), MMF was introduced with good tolerance. The mean age of these 18 patients was 47.6 ± 13.9 years, with disease duration of 4.8 ± 3.6 years. Of these, 9 (50%) presented muscular activity, 3 (16.6%) muscular and cutaneous activities, 2 (11.1%) cutaneous activity, 2 (11.1%) pulmonary activity, 1 (5.5%) cutaneous and pulmonary activities, and 1 (5.5%) muscular, cutaneous and pulmonary activities. There were no patients with articular activity. During the 6 months of follow-up, the median dose of prednisone was decreased from 15.0 to 5.0 mg/day (p=0.30), and the reduction of the glucocorticoid dose by more than 50% occurred in 11 patients (61,1%). All presented good clinical and laboratory response to MMF. MMF was effective as monotherapy in 6 (33.3%) patients. In three of the 21 cases (1 dermatomyositis, 1 polymyositis and 1 anti-syntethase syndrome), MMF was discontinued due to gastrointestinal intolerance. There were no cases of serious infections or deaths.

Conclusions: MMF was relatively well tolerated, safe and effective in patients with refractory idiopathic inflammatory myopathies. Further studies are needed to confirm these data.

437

FACTORS PREDICTIVE OF SERIOUS INFECTIONS OVER TIME IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: DATA FROM A MULTI-ETHNIC, MULTI-NATIONAL, LATIN-AMERICAN LUPUS COHORT

Victor R. Pimentel-Quiroz1,2, Manuel F. Ugarte-Gil1,2, Guillermina Harvey3, Daniel Wojdyla3, Guillermo Pons-Estel3, Amadeo Esposto3, Mercedes A. García3, Mario H. Cardiel4, Leonor A. Barile4, Eduardo Borba5, Lilian T. Lavras Costallat5, Oscar Uribe6, Oscar J. Neira7, Marlene Guibert Toledano8, Rosa Chacón-Díaz9, Graciela S. Alarcón10, and Bernardo A. Pons-Estel3. 1Hospital Nacional Guillermo Almenara Irigoyen, Lima – Perú; 2GLADEL – Perú; 3GLADEL – Argentina; 4GLADEL – México; 5GLADEL – Brasil; 6GLADEL – Colombia; 7GLADEL – Chile; 8GLADEL – Cuba; 9GLADEL – Venezuela; 10School of Medicine - University of Alabama at Birmingham, United States and Universidad Peruana Cayetano Heredia, Peru.

Objective: Serious infections are one of mains causes of morbidity and mortality in systemic lupus erythematosus (SLE); however, the factors predisposing to them have been little evaluated and discussed. The aim of the present study was to identify factors predictive of serious infections over time in SLE patients.

Methods: A multi-ethnic, multi-national cohort from nine Latin American countries is the basis for these analyses. Serious infection was defined as an infection that required hospitalization or infections occurring during a hospitalization for an unrelated cause. Potential predictors included were demographic factors (gender, age at diagnosis, ethnicity, marital status, socioeconomic status, educational level, medical coverage, place of residence), clinical manifestations (per organ involved and lymphopenia and leukopenia, independently) and previous infections (serious and global) at baseline. Disease activity (SLEDAI), damage (SLICC Damage Index), glucocorticoid, antimalarial and immunosuppressive drugs use were included as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analysis were performed.

Results: One thousand-two hundred forty-three patients were included; 1116 (89.8%) of them were female. Their mean age at diagnosis was 29.4 (SD: 12.3) years. The mean of follow-up was 43.2 (SD: 26.6) months. Five-hundred thirty-one (42.9%) were Mestizo, 512 (41.4%) were Caucasian, and 150 (12.1%) were African-Latin-American. One-hundred sixty-six (13.4%) patients had at least one serious infection during the follow-up. Predictive factors of serious infections in the multivariable analyses are depicted in Table 01.

TABLE 01
TABLE 01:
Predictive Factors of Serious Infections. Multivariable Analyses

Conclusions: Corticosteroids use, increase in disease activity and damage accrual were predictive of serious infections over time in SLE patients.

Clinical implications: Findings from our study emphasize the importance of adequate control of disease activity and proper use of corticosteroids.

440

PERIPHERAL NERVOUS SYSTEM DISEASE IN SYSTEMIC LUPUS ERYTHEMATOSUS: THE ROLE OF PREDISPOSING CONDITIONS

S. Fargetti1, E. Bonfa1, S.K. Shinjo1, S.G. Pasoto1, L.P.C. Seguro1, M.R.U. Lopes1, C.R. Gonçalves1, and E.F. Borba1. 1Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.

Objective: To describe the main risk factors of peripheral nervous system disease in systemic lupus erythematosus (SLE) and its characteristics.

Methods: We selected SLE patients (ACR criteria, 1997) with peripheral neuropathy (PN) events in an electronic medical record database established in our Lupus Clinic since the year 2000. Demographic data and the presence of PN predisposing conditions in our SLE population were recorded. PN patients were classified according to etiology – SLE itself, comorbidities (diabetes, thyroid disease, renal or hepatic failure, cancer, vitamin B12 deficiency, and associated autoimmune diseases), drugs (alcohol, thalidomide, leflunomide, statins), infections (chronic hepatitis, HIV, herpes zoster) and compressive neuropathies. Presence and characteristics of electroneuromyography were recorded.

Results: A total of 2,074 SLE patients were identified in our cohort, with 257 PN events occurring in 245 patients (11.8%). Of the total number of patients, we found that 985 (47.5%) of them were exposed to a PN risk factor during the course of SLE, primarily thyroid disease (258, 12.4%) and statins use (206, 9.9%). Among PN patients, 207 of them had a predisposing condition at PN onset (84.5%). SLE activity was considered to be the cause of 135 events (52.5%), 37 (14.4%) were attributed to drugs, 34 (13.2%) were compressive neuropathies, 27 (10.5%) were due to comorbidities and 24 (9.3%) were attributed to infections, mostly post-herpetic neuralgia and viral facial nerve paralysis. Patients in PN SLE group were significantly younger at PN onset than patients with PN attributed to other causes (34.1±13.7 vs. 44.9±13.2 years, p<0.001) and had a shorter disease duration (9.4±8.8 vs. 12.4±10.8, p=0.016). Electroneuromyography was performed in 161 cases (65.7%) and it wad abnormal in 138 (85.7%). The most common pattern of PN was polyneuropathy (69%), followed by mononeuropathy (19.5%) and cranial neuropathy (8.5%) which is similar to the distribution observed in SLE-related PN. Of patients exposed to drugs that may cause PN, 77 were using thalidomide and 24 of them had a PN diagnosis (31.2%), corresponding to 64.9% of drug-related PN, while only one patient of 206 exposed to statins had the same diagnosis (0.5%). The median time of thalidomide exposure at PN onset was 1.3 years (0.9–3.75 years).

Conclusions: Our study suggests that SLE patients are constantly exposed to conditions that may cause PN, mainly related to its treatment or complications. PN-related conditions, medications and risk factors need to be considered for an appropriate treatment and a better outcome on these SLE patients.

441

ROLE OF HIGH RESOLUTION MANOMETRY FOR THE DIAGNOSIS OF ESOPHAGEAL DISORDERS IN A GROUP OF PATIENTS WITH SYSTEMIC SCLEROSIS

V. Parra Izquierdo1, S. Bernal Macías1, F. Ávila1, A.M. Leguizamo1, V. Costa1, and A. Hani1. 1Gastrointestinal Autoimmunity Group, Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia.

Introduction and Objectives: Systemic sclerosis (SSc) is an autoimmune disease with multiple manifestations, of which esophageal involvement is frequent. SSc patients exhibit a high mortality and morbidity. The aim of this study was to describe a group of SSc patients with upper digestive symptoms suggestive of esophageal compromise who underwent high resolution esophageal manometry.

Methods: Data from the medical records were reviewed in SSc patients who underwent high resolution esophageal manometry in the gastrointestinal motility laboratory at Hospital Universitario San Ignacio during the years 1/2015 -/2017.

Results: Data were obtained from 53 patients (Table 1) of which 51 were women (96.2%), with a mean age of 58,94 (±12,97) years, and an average disease duration of 8,38 years (±6.04). The main indication for manometry was dysphagia (86,8%), with aperistalsis findings in 73,6% of patients. In addition, it was important to note that Raynaud’s phenomenon (54,7%), interstitial lung disease (18,9%), pulmonary hypertension (24,5%) and diffuse cutaneous involvement (37,74%) were associated with esophageal compromise, which are being studied recently as possible predictors of early esophageal involvement.

Conclusions: The results of our study are comparable with those described in the literature regarding SSc esophageal involvement and manometric findings. Additionally, the role of high resolution esophageal manometry as the best tool for the evaluation of esophageal involvement and the active search for symptomatology that guides its early detection is highlighted. New pathophysiological hypotheses in which extraesophageal manifestations such as Raynaud's phenomenon, diffuse pulmonary and cutaneous involvement may become predictors of its involvement suggest a diagnostic strategy that may lead to improvement this disease outcome.

450

CLINICAL AND EPIDEMIOLOGIC CHARACTERIZATION OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS ADMITTED TO AN INTENSIVE CARE UNIT IN A REFERENCE CENTER IN MEDELLÍN, COLOMBIA

M.F. Alvarez1, W.D. Mcewen2, D. Montoya3, L.M. Rodriguez2, C.J. Velasquez-Franco2,5, and M.A. Mesa-Navas2,5. 1Clínica Cardiovid, Medellín, Antioquia, Colombia; 2Universidad Pontificia Bolivariana, Medellín, Antioquia, Colombia; 3Hospital la Maria, Medellín, Antioquia, Colombia; 4Cínica Universitaria Bolivariana, Medellín, Antioquia, Colombia.

Introduction: The behavior of rheumatologic diseases in the intensive care unit has changed over time. Such change is probably derived from the improved treatment of certain conditions such as rheumatoid arthritis; lupus has does become one of the leading causes rheumatological admissions to the ICU.

Objective: To characterize the clinical and epidemiologic characteristic of lupus patients admitted to the ICU of a reference hospital in Medellín, Colombia.

Methods: This was a historical cohort study in which all patients with systemic lupus erythematosus (SLE) admitted to the ICU between 2004 – 20015 were included. The clinical records were reviewed to obtain the relevant information for the selected variables. Qualitative variables were described using absolute and relative frequencies. For quantitative variables means and standard deviations (SD) or medians with their interquartile range (IQR) depending on data distribution were used.

Results: 33 patients were included with a total of 45 UCI admissions. 29 (87.9%) of the patients were females with a mean age of 32 years. The median time of diagnosis of SLE previous to ICU admission was two years IQR (1.5–5). The most common SLE manifestation and comorbidity were renal disease and hypertension with 27 (81.8%) and 14 (42.4%), respectively. Steroids were the most common treatment used before admission being present in 28 (84.8%) patients. The main reason for admission was lupus flare with 25 events (55.5%) of which 24 (95%) corresponded to nephritis reactivation. Infection was the second cause of admissions with 19 events (42.2%). The median stay time in the ICU was four days IQR (2-7), and in 14 (31.1%) events, mechanical ventilation was required with a median duration of 5.5 (IQR 3–17.75). LODS score was 6.58 (SD±2.8), and APACHE II score was 14 (SD±6). In 22 (48.9%) events pulse steroids were required being the most common rheumatological intervention. There were 29 infections (64.5%) of which 20 (69%) were hospital-acquired being nosocomial pneumonia the leading cause (n 11 (55%)). Four (12.1%) patients died, all of them from infectious complications.

Conclusion: Unlike most of the previously reported series1–3, in our patients, lupus activity was the most common cause of admission to the ICU. A more aggressive disease in our patients and difficulties in the ambulatory setting could explain this behavior in our patients. Despite the high percentage of lupus flares in our patients, we had a low requirement for mechanical ventilation and a low mortality probably reflecting a lower threshold for ICU admission; this is reflected in the low APACHE and LODS scores compared with those of studies. As such, one must consider if having a low thresholds for ICU admission in lupus could be a valid strategy to improve the outcomes in this particular patient population.

References

1. Carrizosa JA, Aponte J, Cartagena D, Cervera R, Ospina MT, Sanchez A. Factors Associated with Mortality in Patients with Autoimmune Diseases Admitted to the Intensive Care Unit in Bogota, Colombia. Front Immunol. 2017;8:337.

2. Bernal-Macías S, Reyes-Beltrán B, Molano-González N, Augusto Vega D, Bichernall C, Díaz LA, et al. Outcome of patients with autoimmune diseases in the intensive care unit: a mixed cluster analysis. Lupus Sci Med. 2015;2(1): e000122.

3. Siripaitoon B, Lertwises S, Uea-Areewongsa P, Khwannimit B. A study of Thai patients with systemic lupus erythematosus in the medical intensive care unit: epidemiology and predictors of mortality. Lupus. 2015 Jan;24(1):98-106.

452

CHARACTERIZATION OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN A UNIVERSITY HOSPITAL

Rachel Daher Vieira Machado1, Nilzio Antônio da Silva1, and Jozelia Rêgo1. 1Rheumatology Service – Hospital das Clínicas – School of Medicine - Federal University of Goiás – Goiânia – Brazil.

Introduction: Systemic lupus erythematosus (SLE) is the most common cause of hospitalizations in our service. Disease activity, notably renal and CNS compromise, and infections, are the main causes of mortality in SLE.

Objectives: To describe the clinical characteristics and disease course of patients with SLE, in a university hospital.

Methodology: Descriptive, longitudinal and historical study. The authors examined the records of patients with SLE, who had been hospitalized from January 2006 to December 2015, including those that included the following variables: sex, age, disease duration, medication used, reason for hospitalization, length of hospitalization and outcome of hospital treatment.

Results: One hundred forty-eight patients were included in the study, of which 134 were female. The average age was 33.04 years; mean disease duration was 5.27 years. The patients had been prescribed the following drugs: corticoid (69.59%); antimalarial drugs (64.19%); azathioprine (24.32%); methotrexate (4.05%); mycophenolate mofetil (2.03%); and infliximab (0.67%). The following were the clinical justifications for hospitalization: disease activity (74.32%); infection (33.78%); pregnancy (20.94%); and thromboembolism (4.73%). Renal compromise was the predominant reason for hospitalization caused by disease activity (n = 110). In hospitalizations caused by infections (n = 50), bacterial infections were predominant, and 7 patients presented with sepsis. Among pregnancy-related hospitalizations (n = 31), in 16 patients it was for delivery; in 7 for hypertensive disease; in 5 pregnancy evolved into fetal death; and in 3 patients it was due to bleeding. One hundred thirty-three patients (89.87%) were discharged from the hospital, and 15 patients (10.13%) died.

Conclusion: In patients with SLE, disease activity is the main cause for hospitalization. Strict and continuous follow up, particularly during the first years after SLE diagnosis, is essential to decrease the morbidity and mortality of this disease.

453

THE PRESENCE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Diana Azeredo de Freitas1, Ana Luiza Menezes Streets de Abreu Zaiden1, Paula Alencar Veloso1, Nilzio Antônio da Silva1, and Jozelia Rêgo1. 1Rheumatology Service – Hospital das Clínicas – School of Medicine - Federal University of Goiás – Goiânia – Brazil.

Introduction: Antineutrophil cytoplasmic antibodies (ANCA) are important serological markers of primary systemic vasculitides, such as granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. However, these autoantibodies can also be found in other autoimmune diseases, including systemic lupus erythematosus (SLE), although their pathogenic role is controversial.

Objective: To evaluate the occurrence of antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus. To evaluate the relationship between these antibodies and disease activity.

Methods: Cross-sectional study performed between April 2015 and February 2016. All patients > 18 years of age with a diagnosis of SLE and with an active disease according to the SLEDAI, were included in the study.

Results: Sixty-four patients were included in the study. In 10 patients (15.38%), ANCA investigation with immunofluorescence yielded a positive result, with perinuclear fluorescence (P-ANCA). All these patients presented with an active disease. Five patients presented with renal manifestations; three patients presented with cutaneous manifestations; one patient presented with hematologic manifestations; and one patient presented with joint manifestations. In four patients ELISA showed reactivity for Lactoferrin, and in 1 patient reactivity for BPI was present. There was no significant correlation between positivity for P-ANCA and disease activity, defined as a SLEDAI ≥4.

Conclusion: In comparison with the literature, we found a lower P-ANCA positivity in our SLE patients with SLE (25 to 56%). In five cases, there was no specificity for a positive ANCA. No association between ANCA and disease activity was found. More studies should be performed to assess the possible association between these antibodies and disease activity in SLE.

454

CHARACTERIZATION OF GRANULOMATOSIS WITH POLYANGIITIS IN PATIENTS FROM A QUITO-ECUADOR HOSPITAL

A. Cevallos1, H. Fernández1, F. Naranjo-Saltos1, P. Abarca1, and K. Chacon1. 1Eugenio Espejo Hospital, Quito, Ecuador.

Objective: The aim of this study was to describe the clinical and laboratory features of 7 patients with granulomatosis with polyangiitis at the time of diagnosis and a year after treatment with rituximab.

Methods: We reviewed the medical records of 7 patients with granulomatosis with polyangiitis and described their clinical and laboratory findings at the time of diagnosis and one year after receiving treatment with rituximab in a hospital in Quito-Ecuador.

Results: 7 patients with granulomatosis with polyangiitis, 5 men and 2 women, between the ages of 19 and 34 were identified. The clinical presentation was heterogeneous with a predominance of upper respiratory tract involvement in 6 patients followed by pulmonary manifestations (5 patients) and glomerulonephritis (5 patients). After one year of treatment with rituximab, prednisone dose was considerably reduced in all patients. The evolution of renal function was discordant among patients, however other parameters such as recovery of hemoglobin was common.

TABLE 1
TABLE 1:
Clinical and Laboratory Findings of 7 Patients With Granulomatosis With Polyangiitis in A Hospital in Quito, Ecuador

Conclusions: Several immunomodulatory therapies have been tested for the management of granulomatosis with polyangiitis. In the case of rituximab, the results of studies with larger sample sizes are encouraging. There was a tendency towards improvement of clinical and laboratory parameters in our patients, opening the door for new therapeutic options for our patients. New studies with and more rigorous studies are needed.

456

IMPACT OF REMISSION AND LOW DISEASE ACTIVITY STATE ON NEW DAMAGE ACCRUAL IN SYSTEMIC LUPUS ERYTHEMATOSUS. DATA FROM A PERUVIAN COHORT

Manuel Ugarte-Gil1,2, Rocio V. Gamboa-Cardenas1, Francisco Zevallos1, Mariela Medina1, Victor Pimentel-Quiroz1, Omar Sarmiento-Velasquez1, Claudia Elera-Fitzcarrald1, Jorge M. Cucho-Venegas1, Jose Alfaro-Lozano1, Zoila Rodriguez-Bellido1,3, Cesar A. Pastor-Asurza1,3, Graciela S. Alarcón4, and Risto Perich-Campos1,3. 1Hospital Guillermo Almenara Irigoyen. EsSalud; 2Universidad Cientifica del Sur; 3Universidad Nacional Mayor de San Marcos; 4University of Alabama at Birmingham, United States.

Objective: To determine the impact of remission and low disease activity state (LDAS) on new damage accrual in patients with systemic lupus erythematosus (SLE).

Methods: Starting in 2012, all SLE patients being evaluated at our Rheumatology Department have been invited to be part of a cohort. Visits are performed every six months, and they include demographic characteristics, disease activity (ascertained with the SLEDAI), disease damage (ascertained with the SLICC/ACR damage index), comorbidities and treatment. Remission off treatment was defined as a SLEDAI=0, without prednisone or immunosuppressive drugs; remission on treatment as a SLEDAI=0, prednisone≤5 mg/d and immunosuppressive drugs on maintenance dose; LDAS was defined as a SLEDAI<4, prednisone ≤7.5 mg/d and immunosuppressive drugs on maintenance dose; all other patients were considered as non-optimally controlled. Antimalarials were allowed in all groups. We included patients with at least two visits; potential predictors of damage were evaluated at the baseline and at the follow up visits (increase in the SDI for the later). Univariable and multivariable Cox regression models (adjusted for age at baseline, gender, socioeconomic status, years of education, disease duration, antimalarial use and SDI at baseline) were performed, using an increase in the SDI as the outcome.

Results: Two hundred and thirty-nine patients with at least two visits were included, 222 (92.9%) were female, mean (SD) age at diagnosis was 36.0 (13.2) years, almost all were Mestizo and disease duration at baseline was 7.4 (6.6) years. Twenty-seven (11.3%) were on remission with or without drugs, 70 (29.3%) were on LDAS and 142 (59.4%) were non-optimally controlled. The mean follow-up time was 2.5 (1.2) years; 107 (44.8%) patients increased their SDI during the follow-up. A better disease control was associated with a lower risk of new damage, as it is shown in Table 01.

TABLE 01
TABLE 01:
Impact of Remission and LDAS on New Damage Accrual

Conclusions: A better control of disease activity is associated with a lower damage accrual in SLE patients from a Peruvian cohort.

471

SOCIODEMOGRAPHIC CHARACTERISTICS OF A LARGE COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Pedro Santos-Moreno1, Laura Villarreal1, Danny Gomez1, Edwin Castillo1, Rodrigo Giraldo1, Sandra Farietta1, Eva Cardozo1, Carlos Castro2, and Diana Buitrago2. 1Biomab, Centro de Artritis Reumatoide, Bogotá, Colombia; 2SIIES, Investigacion y Educacion, Bogotá, Colombia.

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease of unknown etiology than can cause multisystem damage. The disease occurs mainly in women, particularly during the reproductive years SLE disease is characterized by periods of remissions and relapses (1, 2). Thus, it is important to know the particular characteristics of this population in latin America in order to compare with other populations around the world. The aim was to describe the baseline characteristics and pharmacological prescribed treatment of a population with SLE.

Methods: We conducted an observational study at a rheumatic diseases specialized medical center from 2015 to 2017. We extracted information related to sex, age, SLE treatment and comorbidities. Descriptive epidemiology was performed for each variable.

Results: We included 1051 patients 88% were female and 12% were male. The mean age was 47 years ±14. Most patients were between 40 and 60 years (47%) followed by patients between 20 and 40 years (33%) and patients older than 61 years (20%). Regarding pharmacological therapy, 46% of patients received prednisone, followed by azathioprine 20%, chloroquine 10% and combined therapies 24%; additionally, most patients were prescribed with pain medications. Regarding comorbidities 30% of patients had other conditions in addition to SLE, the most common being osteoarthritis followed by Sjogren's syndrome and coagulation disorders, myalgia and osteoporosis, among others.

Conclusions: Patients with SLE being cared for at our center are mainly women as described in the literature; the age groups are similar as those of other world populations and the most common comorbidities are chronic conditions. Additionally, as other studies have shown, the most prescribed therapies for this condition are corticosteroids and combination therapies. Our results match those reported in the literature (2). This description is the basis for further studies related to SLE characteristics.

References

1. Hwang J, Lee J, Ahn JK, Park EJ, Cha HS, Koh EM. Clinical characteristics of male and female Korean patients with systemic lupus erythematosus: a comparative study. The Korean journal of internal medicine. 2015;30(2):242-9.

2. Ahmed N, Shigidi M, Al Agib AN, Abdelrahman H, Taha E. Clinical features and antinuclear antibodies profile among adults with systemic lupus erythematosus and lupus nephritis: a cross-sectional study. The Pan African medical journal. 2017; 27:114.

483

DESCRIPTION OF THE ARGENTINEAN RHEUMATOLOGY SOCIETY SYSTEMIC LUPUS ERYTHEMATOSUS REGISTER. RELESSAR

On behalf of the RELESSAR and SAR Lupus Study groups

Introduction: RELESSAR is a SLE multicentric registry produced as the result of a collaborative work with the Spanish Society of Rheumatology who designed the RELESSER registry; this registry was later adapted for Argentina.

Objective: To describe the characteristics of the disease in SLE Argentinean patients.

Methods: We performed a historical collection of demographic data, clinical and laboratory manifestations, activity index (SLEDAI), damage index (SLICC/ACR), comorbidities, treatments and mortality. Manifestations and treatments were considered at the time of inclusion and at any time during the past. Descriptive data were reported as medians and interquartile range (IQR) and as means ± standard deviations.

Results: 90 centers took part in the RELESSAR registry. 1611 patients were included. 91.5% were female. The predominant ethnic groups were white (43%) and mestizo (44.4%). The median of age at diagnosis was 28.1 years (IQR 20.3-38) and at registry inclusion 37 (IQR 27.55-47.25). The median disease duration was 72 months (IQR 29-142). 55% of the patients had an active disease; at last visit their median SLEDAI score was 4 (IQR 2-8). 21% had low disease activity (SLEDAI ≤4) and 10% had a severe disease with SLEDAI ≥10. 59.5 % had nephropathy and 72.5% of them had proteinuria ≥ 500 mg/24 hours collection at inclusion. 33% of the patients were anti Sm antibodies positive. 51.6% had accrued some damage, median SDI: 1 (IQR 1-2). 216 patients (13.4%) had severe infections that required hospitalization, 26% of them in more than one opportunity. Co-morbidities: 30% were smokers, 23% had arterial hypertension, 12% fibromyalgia, 5% dyslipemia, 4% diabetes, 5% osteoporosis with fractures and 3% cancer. Treatment in these patients were corticosteroids in 96%, antimalarials in 88%, Azathioprine in 30.4%, cyclophosphamide in 29.8%, mycophenolate mofetil or mycophenolic acid in 23.4%, methotrexate in 18.4%, rituximab in 5% and belimumab in 5%. 38 patients (2.3%) had died. 20/38 (52.6%) because of SLE activity and 16/38 (42%) due to infections.

Conclusion: RELESSAR is the largest Argentinean SLE register to date; it provides reliable information about this disease in Argentina.

496

ASSOCIATION BETWEEN AUTOANTIBODIES AND SKIN INVOLVEMENT IN PATIENTS WITH SLE

D.A. Marino1, R.A. Gómez1, A.M. Berón1, M. García Carrasco1, M.S. Pino1, and D. Dubinsky1. 1Rheumatology Division, Hospital de Clínicas José de San Martín, University of Buenos Aires, Argentina.

Objective: To describe the frequency of skin involvement in SLE patients and its relationship with selected autoantibodies. To describe the impact of anti-Ro/SSA on skin manifestations in SLE patients.

Methods: Descriptive and observational study. Patients were selected from the database of the SLE Medical Unit (2013 to 2017). We included patients ≥16 years with SLE (SLICC 2012) with at least one visit in the last 12 months and one o more positive determination of: anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm and anti-U1RNP.Anti-dsDNA, as determined by an indirect immunofluorescence assay. The cutaneous manifestations evaluated were those included in SLICC 2012 criteria grouped into: acute cutaneous lupus (ACLE), subacute cutaneous lupus (SCLE) and chronic cutaneous lupus (CCLE). They were considered positive if present at any time and together were considered as “skin involvement”. The frequency of cutaneous manifestations and their relationship with autoantibodies was evaluated. Statistical analysis was performed using Epi Info v.7.2. Frequencies, odds ratio with 95% CI and Fisher's exact test (p ≤ 0.05) were calculated.

Results: 127 patients were included. The frequency of autoantibodies was: anti-dsDNA 73/127(57,5%), anti-Ro/SSA 52/126 (41%), anti-Sm 42/127 (33%), anti-U1RNP 36/127 (28%), anti-La/SSB 20/124 (16%). Median of SLEDAI was 3 (IQ 0-6): Anti-dsDNA (+) 2 (IQR 0-4), anti-dsDNA (−) 4 (IQR 0-8), anti-Ro/SSA (+) 3 (IQR 1.5-4) and anti-Ro/SSA (−) 2 (IQR 0-6). Cutaneous involvement was observed in 97/127 (76.4%) patients: ACLE plus SCLE 95/127 (74.8%) and CCLE 11/127 (8.7%). Malar rash was the most frequent manifestation and it was present in 78/126 patients (62%). We found a statistically significant association between cutaneous involvement and anti-dsDNA: OR 3,06 (95% CI 1,30-7,16), p=0,01 (Table). No statistically significant association was observed for anti-Ro/SSA: OR 0.52 (95% CI 0.23-1.20), p=0.14. 104/127 (81.9%) patients were on active treatment with hydroxychloroquine (HCQ). We found no difference in HCQ use in with anti-dsDNA (+) vs anti-dsDNA (−) patients; OR 0,70 (95% CI 0,27-3,06), p=0,49.

TABLE
TABLE:
Cutaneous Involvement and Autoantibodies

Conclusions: Cutaneous manifestations were frequent. A statistically significant association was found between anti-dsDNA and cutaneous involvement. No statistically significant association x between the presence of anti-Ro/SSA and cutaneous involvement was found.

498

DEPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IN A DOMINICAN PATIENT COHORT

J. Then1, E. Loyo2, P. Gotschalk3, R. Vásquez4, K. Franco4, and C. Tineo2. 1Hospital Metropolitano de Santiago (HOMS), Santiago, RD; 2Hospital Regional Universitario José María Cabral y Báez, (HRUJMCB) Santiago, RD; 3Clínica Unión Médica del Norte, Santiago, RD; 4Hospital General Plaza de la Salud, Santo Domingo, RD.

Background: Depression is one the most common psychiatric disorders in SLE patients, which significantly impact on these patients’ quality of life. It can purely be due to psychological factors or secondary to organic factors (disease activity).

Objective: the purpose of this study is to describe the frequency of depression and its relationship with the disease activity I patients with SLE.

Methods: This was a cross-sectional, descriptive study conducted at the Rheumatology´s Department of the HRUJMCB; primary and secondary sources were used for data collection; Clinical records were reviewed, and instruments applied. Eighty-six (86) patients with SLE who met ACR criteria were included. Beck Depression Inventory (BDI), the SLICC/ACR - damage index (SDI), and the SELENA-SLEDAI - activity index, were applied at the time of evaluation. For the statistical analysis, frequency tables, and Pearson´s Chi-squared test were used.

Results: All patients were Caribbean (mixed Hispanic, African and Amerindian ancestry); 62% were female. We found depression based on the BDI scale, in 58.1% of the patients, and of those, 7% presented severe depression. We also found that the frequency of depression was less common in the younger group of patients (18 to 26 years) (33%), compared to those aged 37 to 46 in which 79% develop this condition; for the older group in this study (57–66 years) we found that depression was present in 50% of the cases. In relation to gender, 62% of the female group had depression compared to 22% in the male group. We also found that, in general, depressed patients regardless of their age groups (81%) had moderate disease activity according to the SELENA-SLEDAI Scale, and 68% had organ damage according to the SLICC/ACR damage index.

Conclusion: Depression is an important comorbidity in SLE; longitudinal studies are needed to determine the association between disease activity and the presence of depression.

500

PROLACTIN AND DEHYDROEPIANDROSTERONE SULFATE IN WOMEN WITH ACTIVE AND CHRONIC INACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

O. Vera1, and E. Vásquez1. 1National Autonomous University of México, México City, México; 2Mexican Social Security Institute.

Objectives: To determine the concentrations of prolactin (PRL) and (DHEAS) in patients with newly diagnosed systemic lupus erythematosus (SLE), chronic inactive SLE and healthy controls. To compare PRL and DHEAS levels in patients with newly diagnosed active SLE, inactive chronic SLE and healthy controls and determine the possible relationship between them and disease activity and chronicity.

Methods: Two groups of patients with SLE and a group without SLE were studied in a reference center. Group 1: Newly diagnosed and active SLE; group 2: Chronic inactive SLE; Group 3: Healthy controls. SLEDAI was calculated for the SLE groups to determine activity and the SLICC damage index (SDI) was calculated for patients in group 2. PRL and DHEAS were measured by radioimmunoassay in all three groups. Normality of the quantitative variables was checked by Shapiro Wilk test, so parametric statistics were used. Descriptive and inferential statistics were performed by Student t test for mean differences between two samples with equal or different variances depending on the case and Pearson correlation.

Results: A total of 55 subjects were included, 15 SLE patients with acute disease, 20 with inactive disease and 20 controls. The averages SLEDAI and SDI were 13.4 ± 6.64, and 4.1 ± 1.45, respectively. The mean prolactin levels were 27.82 ± 9.96 (min 11.3, Max 50.7) in patients with acute disease, 20 ± 5.02 (min 6.9, max 27.4) in those with chronic disease and 19.58 ± 4.57 (min 9.61, max 25.3) in the controls. The mean DHEAS level for the acute, chronic disease and control groups were 14.58 ± 9.26 (min 6.4, max 44), 19.36 ± 7.21 (min 5.01, max 32.3) and 154.43 ± 50.88 (min28.5, max 200), respectively. The mean PRL levels in patients with acute disease were than in the controls (p = 0.004) and in those with chronic disease (p = 0.01). No difference in PRL levels were observed in patients with chronic disease and controls. The mean DHEAS levels in patients with acute disease were lower than in the controls (p = 0.001) and in patients with chronic disease (p = 0.04); In turn, DHEAS levels were lower in patients with chronic disease than in the controls (p = 0.001). A positive linear correlation was found between prolactin levels and the SLEDAI score (Rho 0.92, p = 0.001). No correlation was found between prolactin levels and the SDI. A negative linear correlation was shown between the DHEAS levels and the SDI score (Rho −0.46, p = 0.03).

Conclusions: We evaluated PRL and DHEAS levels in patients with active SLE, chronic inactive SLE and controls. PRL levels were higher in patients with active SLE than in those with chronic inactive SLE and controls. In active SLE there lower DHEAS levels than in those with chronic inactive SLE and controls. The higher the SLEDAI score, the higher the PRL levels and the higher the SD score the lower the DHEAS levels.

503

ANTIPHOSPHOLIPID SYNDROME: DESCRIPTION OF A PATIENT POPULATION FROM A PUBLIC HOSPITAL

G. Pazos1, S. Consani1, A. Fernández1, and E. De Lisa1. 1Hospital Maciel, Montevideo, Uruguay.

Background and Objectives: The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (APA) associated with venous or arterial thrombosis, and/or defined elements of obstetric morbidity. It is a true systemic autoimmune disease, beyond the aforementioned classificatory manifestations. The objective of this study was to analyze the epidemiological profile, clinical and immunological manifestations, and evolution of patients with APS in a population of patients from a public general hospital in Montevideo, Uruguay.