Mortality could be predicted in a stepwise logistic regression model by the following: education (<10 yr vs. ≥10 yr; OR, 3.2; 95% CI, 1.3–7.6), SLICC score (≥1 vs. 0; OR, 2.8; 95% CI, 1.2–6.4), time of follow-up (≥20 mo vs. <20 mo; OR, 0.26; 95% CI, 0.10–0.65), marital status (single vs. others; OR, 2.4; 95% CI, 1.0–5.7), medical coverage (partial or no coverage vs. full medical coverage; OR, 2.7; 95% CI, 1.1–6.5), and country (Argentina vs. the rest; OR, 3.0; 95% CI, 1.3–7.1).
We describe the GLADEL cohort, a multicenter, multinational, prospective inception cohort of Latin American SLE patients seen in their countries of origin and treated by their local physicians. Both the size and origin of this cohort make it unique. An effort was made to keep equilibrium so no single group with a large number of patients would predominate and introduce a bias. Data were entered into a user-friendly database that requires no writing and crosses language barriers, thus allowing participation of Portuguese-speaking groups. Throughout the study, a supervising group conducted quality control of the data entered, facilitated by built-in characteristics of the database that detect contradictions. In addition, individuals coordinating the cohort were in regular communication and had periodic meetings to set policies and define variables and terms. The ultimate size of the cohort will now be predetermined in order to have patient representation from each country according to its population.
Latin America is a large subcontinent rich in the variety of racial admixtures between and within countries. In addition, socioeconomic, educational, and demographic variations are prominent, and these sometimes are related to ethnic groups through their economic predominance. Thus, the apparent homogeneity of Latin Americans is a myth, and within the subcontinent lies great diversity. The reason for the apparent homogeneity is the predominance of 2 related languages, Spanish and Portuguese, which has resulted in the unfortunate terminology of “Hispanic” based mainly on the former language being spoken by many Latin Americans and their descendants now living in English- speaking North America.
The influences of ethnic, social, and demographic variables on the clinical characteristics of SLE patients have already been demonstrated by other studies. Thus, in series from both the United States and Europe, more severe disease was noticed in nonwhite patients 5,10,28,29,45,56,63,72,74,75,80. In our study, both ALA and mestizos had more severe disease than did whites, as evidenced by a higher frequency of renal disease, pericarditis, polyadenopathy, and discoid lesions in ALA. In addition, both ALA and mestizos had higher maximum disease activity indices than whites, but this was lost when controlled by country. However, damage scores tended to be lower in ALA than in both mestizos and whites, a surprising finding that might be explained by shorter disease duration or by the more recent incorporation of Brazilian and Cuban groups into the study. Longer follow-up in the GLADEL cohort may help determine if ethnicity does actually play a role in the resulting damage from SLE.
A peculiar observation was that of a significantly lower frequency of both xerophthalmia and sicca syndrome (both xerophthalmia and xerostomia) in ALA than in mestizos and, particularly, in whites. This was not apparently related to a lower frequency of anti-Ro and anti-La in ALA.
Mestizos and ALA had lower socioeconomic status, fewer years of formal education, and less accessibility to medical care than did whites, and these socioeconomic factors may have a bearing on the more severe disease found in nonwhites. The possible association of more severe disease and social inequalities has also been recorded in “Hispanics” in the United States 10 and North American Indians 50,53.
Possible genetic factors associated with ethnicity such as FcγRIIA gene alleles could be influencing this, since these may be a risk factor for lupus nephritis in African Americans 67. The finding made here that ALA have significantly shorter delay to diagnosis than both mestizos and whites may indicate that they have an inherently more severe disease from early onset, thus prompting earlier diagnoses despite their aforementioned deficiencies in accessibility to medical care and socioeconomic status.
Health disparities in SLE have led to the analysis of the interplay of socioeconomic status, ethnicity, education, and psychosocial and behavioral variables in contributing to poor outcome 10,25,29,43,44,56,72,82. A proposal has been made to identify mediators to target interventions designed to reduce such health disparities in SLE, and the observations recorded here and more yet to arise from the continued follow-up of the GLADEL cohort may contribute to this goal.
Physicians and health authorities in Latin America, as well as those of the United States, Canada, and European countries where Latin American individuals live, should be aware that social inequities may result in increased severity of a disease that, due to its pathogenic complexity, might seem remote from these seemingly mundane factors. It is already a well-known fact that an epidemiologic transition has occurred in Latin America, where infectious and parasitic diseases, once commonly thought to be more prevalent, have been surpassed by chronic diseases such as SLE. Interest in SLE by Latin American physicians and investigators thus is not gratuitous and is supported by the findings presented herein.
An interesting observation was obtained from the comparison between Argentine mestizos and whites and their comparison with Mexican mestizos. The geographic distance between the 2 countries and the lack of a significant migration between the 2 indicate that their resulting similarities may be truly ethnic and probably of an ancient origin, albeit influenced by socioeconomic similarities. Except for lower frequencies of polyadenopathy, serositis, and hemolytic anemia in Mexican mestizos, these tended to be more akin to Argentine mestizos than to Argentine whites.
Another interesting observation from our study resulted from multiple logistic analysis that provided a model for maximal disease activity in SLE. It included lesser formal education, partial or lack of medical coverage, older age at onset, and longer follow-up. Conversely, longer delay to diagnosis and longer disease duration seemed to have a protective effect, possibly by reflecting milder disease and a decrease in disease activity with time, respectively.
Although our cohort is still young, it is thought provoking that patients who died within the GLADEL cohort had both poorer education and poorer medical coverage than those who are still alive. As in other series 2,3,24,57,66,76,77,82, infection was an important cause of death of lupus patients in the GLADEL cohort. A bimodal mortality pattern has been shown in systemic lupus erythematosus 76. Our inception cohort has a median follow-up of 32 months. This was a limiting factor for reporting events that occur later in the disease course (second peak of mortality) such as cardiovascular mortality. The study of this would be among the objectives of continued follow-up of this cohort. In addition, SLE is a paradigm of complex disease where predisposing disease-modifying and pharmacodynamic-influencing genes interplay with environmental and hormonal factors to cause an extraordinary heterogeneity 12. Continued analysis of a cohort with the characteristics described herein, ideally with the concurrent study of participating genes, may help us to dissect and, in time, understand the role of each in its diversity. A recent observation of the association with SLE of allele A of the SNP PD-1.3 of the PD-1 gene in the 2q37.3 chromosome region in Europeans, less frequent in Mexicans and practically absent in African-Americans, suggests it to be a recent mutation affecting mostly Europeans and, to a lesser extent, populations admixed with them 59. Analyses of European populations and their admixtures within the Latin American subcontinent as included in the GLADEL cohort for associations with this and other genetic markers may help determine the role of the various lupus-predisposing genes in the clinical spectrum of SLE.
Our analysis of 3 major ethnic groups in this Latin American lupus cohort gives us further insight into the role of ethnicity and the associated social inequalities on the clinical manifestations and outcomes of lupus. We also see clearly that, at least as pertaining to SLE, “Hispanics” is not a homogenous group.
The differences between Hispanic whites, mestizos, and ALA are well recognized in patients living in Latin America. However the differences should be of particular relevance for Latin American patients living in North America or Europe, where most of these patients would be grouped together as Hispanics. The differences found in the GLADEL cohort should be helpful for diagnosis and treatment of these patients, since their clinical behavior may be different. When a physician encounters a “Hispanics” patient with SLE, further efforts to characterize his or her country of origin and ethnic background should provide useful information.
The authors express their gratitude to Daniel Wojdyla for assistance in handling the database and statistical analysis of the GLADEL cohort and to Daniel Villalba and Leonardo Grasso for assistance with the software ARTHROS 6.0.
APPENDIX: GLADEL CO-AUTHORS
Coordinators: Bernardo A. Pons-Estel and Donato Alarcón-Segovia. The following participants are members of Grupo Latinoamericano de Estudio del Lupus (GLADEL) and have incorporated at least 20 patients into the database.
ARGENTINA: Patricia M. Imamura, Sección Reumatología, Servicio de Clínica Médica Hospital Italiano, Buenos Aires; Jorge A. Manni, Sebastián Grimaudo, and Judith Sarano, Departamento de Inmunología, Instituto de Investigaciones Médicas “Alfredo Lanari”, Buenos Aires; José A. Maldonado-Cocco, Maria S. Arriola, and Graciela Gómez, Servicio de Reumatología, Instituto de Rehabilitación Psicofísica, Buenos Aires; Mercedes A. García, Ana Inés Marcos, and Juan Carlos Marcos, Servicio de Reumatología, Hospital Interzonal General de Agudos General San Martín, La Plata; Hugo R. Scherbarth, Pilar C. Marino, and Estela L. Motta, Servicio de Reumatología, Hospital Interzonal General de Agudos “Dr. Oscar Alende” Mar del Plata; Cristina Drenkard, Susana Gamron, and Carlos M. Onetti, Servicio de Reumatología, UHMI1, Hospital Nacional de Clínicas, Córdoba; Verónica Saurit, Servicio de Reumatología, Hospital Privado, Centro Medico de Córdoba, Córdoba; Norberto Quagliatto, Alberto A. Gentiletti, and Daniel Machado, Servicio de Reumatología, Hospital Provincial de Rosario, Rosario; Marcelo Abdala and Simón Palatnik, Servicio de Reumatología, Hospital Provincial del Centenario, Rosario; Guillermo Berbotto and Carlos A. Battagliotti, Servicio de Reumatología Hospital Escuela Eva Perón, Granadero Baigorria, Rosario, Argentina.
BRAZIL: Emilia Sato, Elaine M. C. Sella, and Alexandre W. S. Souza, Disciplina de Reumatología, Universidade Federal da São Paulo (UNIFESP), São Paulo; Lilian T. Lavras Costallat, Manoel Barros Bertolo, and Ibsen Bellini Coimbra, Divisao de Reumatología, Faculdade de Ciencias Medicas, Universidade Estadual da Campinas, Campinas; Eduardo Ferreira Borba Neto and Eloisa Bonfá, Divisao de Reumatología, Faculdade da Medicina, Universidade da São Paulo, São Paulo; João Carlos Tavares Brenol, Ricardo Xavier, and João Marasca, Serviço de Reumatología, Hospital da Clinicas da Porto Alegre, Universidade Federal do Rio Grande do Sul; Fernando de Souza Cavalcanti, Ângela Luzia Branco Duarte, and Cláudia Diniz Lopes Marques, Disciplina de Reumatología, Centro de Ciencias da Saúde, Universidade Federal da Pernambuco, Pernambuco; Nilzio Antonio Da Silva, Ana Carolina de O. e Silva, and Tatiana Ferracine Pacheco, Serviço da Reumatología, Faculdade de Medicina, Universidade Federal de Goias, Goiania.
COLOMBIA: José Fernando Molina-Restrepo, Servicio de Reumatología, Hospital Pablo Tobon Uribe, and Javier Molina-López, Sección de Reumatología, Universidad de Antioquia, Hospital Universitario San Vicente de Paul, Medellín; Antonio Iglesias-Gamarra, Facultad de Medicina, Universidad Nacional de Colombia, and Antonio Iglesias-Rodríguez, Servicio de Reumatología, Hospital San Juan de Dios, Facultad de Medicina, Universidad Nacional, Bogotá; Eduardo Egea-Bermejo, Departamento de Inmunología, Universidad del Norte, Barranquilla; Oscar Uribe-Uribe, Luis A. Ramírez, and Oscar Felipe, Sección de Reumatología, Universidad de Antioquia, Hospital Universitario San Vicente de Paul, Medellín; Renato A. Guzmán-Moreno and José F. Restrepo-Suárez, Departamento de Medicina Interna e Inmuno-Reumatología, Clínica Saludcoop 104 y Hospital San Juan de Dios, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá.
CUBA: Marlene Guibert-Toledano, Gil Alberto Reyes-Llerena, and Alfredo Hernández-Martínez, Servicio de Reumatología, Centro de Investigaciones Médico Quirúrgicas (CIMEQ), La Habana.
CHILE: Loreto Massardo, Néstor Gareca, and Sergio Jacobelli, Departamento de Inmunología Clínica y Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago; Oscar J. Neira, Leonardo R. Guzmán, and María A. Alvarado, Sección Reumatología, Hospital del Salvador, Facultad de Medicina, Universidad de Chile, Santiago.
GUATEMALA: Abraham García-Kutzbach, Ivette Castro-Ampie, and Cesar Garcia, Servicio de Reumatología, Hospital Universitario Esperanza, Ciudad de Guatemala.
MÉXICO: Virginia Pascual-Ramos, Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF; Leonor A. Barile-Fabris and Juan Manuel Miranda-Limón, Departamento de Reumatología, Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano de Seguro Social, México DF; Mary-Carmen Amigo and Luis H. Silveira, Departamento de Reumatología y Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, México DF; Ignacio García De La Torre, Gerardo Orozco-Barocio, and Magali L. Estrada-Contreras, Departamento de Inmunología y Reumatología, Hospital General de Occidente de la Secretaría de Salud, Guadalajara, Jalisco; Maria Josefina Sauza del Pozo, Laura E. Aranda Baca, and Adelfia Urenda Quezada, Servicio de Reumatología, Instituto Mexicano de Seguro Social, Hospital de Especialidades No 25, Monterrey, NL; Guillermo F. Huerta-Yáñez, Servicio de Reumatología, Hospital de Especialidades Miguel Hidalgo, Aguascalientes.
PERU: Eduardo M. Acevedo-Vásquez, José Luis Alfaro-Lozano, and Jorge M. Cucho-Venegas, Servicio de Reumatología, Hospital Nacional Guillermo Almenara Irigoyen, ESSALUD, Lima; Maria Inés Segami, Cesar A. Ugarte, and Felipe E. Becerra, Servicio de Reumatología, Hospital Nacional Edgardo Rebagliatti Martins, ESSALUD, Lima.
VENEZUELA: Rosa Chacón-Díaz and Soham Al Snih Al Snih, Servicio de Reumatología, Centro Nacional de Enfermedades Reumáticas, Hospital Universitario de Caracas, Caracas; Maria H. Esteva-Spinetti and Jorge Vivas, Unidad de Reumatología, Hospital Central de San Cristóbal, San Cristóbal.
1. Abadi I#, Gonzalez N. Epidemiologia del lupus eritematoso sistemico en Venezuela. In: Sanchez A, Diaz M, Rondon F, eds. Lupus Eritematoso Sistemico. Sindrome Clinico e Inmunologico
. Bogota: Ediciones Acta Medica Colombiana. 1990:17–22.
2. Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death. J Rheumatol. 1995; 22:1259–1264.
3. Abu-Shakra M, Urowitz MB, Gladman DD, Gough J. Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality. J Rheumatol. 1995; 22:1265–1270.
4. Alarcon GS, Cianfrini L, Bradley LA, Sanchez ML, Brooks K, Friedman AW, Baethge BA, Fessler BJ, Bastian HM, Roseman JM, McGwin G Jr, Reveille JD. Systemic lupus erythematosus in three ethnic groups. X. Measuring cognitive impairment with the cognitive symptoms inventory. Arthritis Rheum. 2002; 47:310–319.
5. Alarcon GS, Friedman AW, Straaton KV, Moulds JM, Lisse J, Bastian HM, McGwin G Jr, Bartolucci AA, Roseman JM, Reveille JD. Systemic lupus erythematosus in three ethnic groups. III. A comparison of characteristics early in the natural history of the LUMINA cohort. Lupus. 1999; 8:197–209.
6. Alarcon GS, McGwin G Jr, Bartolucci AA, Roseman J, Lisse J, Fessler BJ, Bastian HM, Friedman AW, Reveille JD. Systemic lupus erythematosus in three ethnic groups. IX. Differences in damage accrual. Arthritis Rheum. 2001; 44:2797–2806.
7. Alarcon GS, McGwin G Jr, Bastian HM, Roseman J, Lisse J, Fessler BJ, Friedman AW, Reveille JD, for the LUMINA study group. Systemic lupus erythematosus in three ethnic groups. VIII. Predictors of early mortality in the LUMINA cohort. Arthritis Care Res. 2001; 45:191–202.
8. Alarcon GS, McGwin G Jr, Brooks K, Roseman JM, Fessler BJ, Sanchez ML, Bastian HM, Friedman AW, Baethge BA, Reveille JD. Systemic lupus erythematosus in three ethnic groups. XI. Sources of discrepancy in perception of disease activity: a comparison of physician and patient visual analog scale scores. Arthritis Rheum. 2002; 47:408–413.
9. Alarcon GS, McGwin G Jr, Petri M, Reveille JD, Ramsey-Goldman R, Kimberly RP. Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus. 2002; 11:95–101.
10. Alarcon GS, Rodriguez JL, Benavides G Jr, Brooks K, Kurusz H, Reveille JD. Systemic lupus erythematosus in three ethnic groups. V. Acculturation, health-related attitudes and behaviors, and disease activity in Hispanic patients from the LUMINA cohort. Arthritis Care Res. 1999; 12:267–276.
11. Alarcon GS, Roseman J, Bartolucci AA, Friedman AW, Moulds JM, Goel N, Straaton KV, Reveille JD. Systemic lupus erythematosus in three ethnic groups. II. Features predictive of disease activity early in its course. Arthritis Rheum. 1998; 41:1173–1180.
12. Alarcon-Segovia D, Alarcon-Riquelme ME. Etiopathogenesis of systemic lupus erythematosus: A tale of three troikas. Systemic lupus erythematosus. In: Lahita RG, ed. Systemic Lupus Erythematosus
. New York: Academic Press. 1999:55–65.
13. Barr SG, Zonana-Nacach A, Magder LS, Petri M. Patterns of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1999; 42:2682–2688.
14. Bastian HM, Mikhail I, Straaton KV, Friedman AW, Lisse JR, Burst N, Reveille JD, Alarcon GS, for the LUMINA study group. Factors associated with early death in African-American and Hispanic patients with SLE [abstract]. Arthritis Rheum. 1997; 40(Suppl 9):S160.
15. Bastian HM, Roseman JM, McGwin G Jr, Alarcon GS, Friedman AW, Fessler BJ, Baethge BA, Reveille JD. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus. 2002; 11:152–160.
16. Bellomio V, Spindler A, Lucero E, Berman A, Santana M, Moreno C, Hidalgo RP, Paira S, Graf C, Maldonado Cocco JA, Citera G, Arriola MS, Gomez G, Barreira JC, Messina O, Asnal C, Carrillo D, Gervilla A, Garcia L, Mascolo M, De la Sota MD, Rosso G, Somma LF, Sosa RF, Rillo O, Caracciolo JA, Lancioni G, Gomez A. Systemic lupus erythematosus: mortality and survival in Argentina. A multicenter study. Lupus. 2000; 9:377–381.
17. Blanco FJ, Gomez-Reino JJ, de la Mata J, Corrales A, Rodriguez-Valverde V, Rosas JC, Gomez de la Camara A, Pascual E. Survival analysis of 306 European Spanish patients with systemic lupus erythematosus. Lupus. 1998; 7:159–163.
18. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, and the Committee on prognosis studies in SLE. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum. 1992; 35:630–640.
19. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Aydintug AO, Jedryka-Goral A, de Ramon E, Fernandez-Nebro A, Galeazzi M, Haga HJ, Mathieu A, Houssiau F, Ruiz-Irastorza G, Ingelmo M, Hughes GR. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. Medicine (Baltimore). 1999; 78:167–175.
20. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Domenech I, Aydintug AO, Jedryka-Goral A, de Ramon E, and the European Working Party on systemic lupus erythematosus. Systemic lupus erythematosus:Clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. Medicine (Baltimore). 1993; 72:113–124.
21. Devins GM, Edworthy SM and the ARAMIS Lupus State Models Research Group. Illness intrusiveness explains race-related quality-of-life differences among women with systemic lupus erythematosus. Lupus. 2000; 9:534–541.
22. Drenkard C, Alarcon-Segovia D. The new prognosis of systemic lupus erythematosus: treatment-free remission and decreased mortality and morbidity. Isr Med Assoc J. 2000; 2:382–387.
23. Drenkard C, Villa AR, Garcia-Padilla C, Perez-Vasquez ME, Alarcon-Segovia D. Remission of systemic lupus erythematosus. Medicine (Baltimore). 1996; 75:88–98.
24. Duffy KN, Duffy CM, Gladman DD. Infection and disease activity in SLE: a review of hospitalized patients. J Rheumatol. 1991; 18:1180–1184.
25. Esdaile JM, Sampalis JS, Lacaille D, Danoff D. The relationship of socioeconomic status to subsequent health status in systemic lupus erythematosus. Arthritis Rheum. 1998; 31:423–427.
26. Fernandez RN, Rego J, Neves AL. LES: Experiencia de 5 anos. Rev Brasil Rheumatol Suppl. 1992; 32:41.
27. Friedman AW, Alarcon GS, McGwin G Jr, Straaton KV, Roseman J, Goel N, Reveille JD, for the LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups. IV. Factors associated with self-reported functional outcome in a large cohort study. Arthritis Care Res. 1999; 12:256–266.
28. Ginzler E, Berg A. Mortality in systemic lupus erythematosus. J Rheumatol. 1987; 14(Suppl 13):218–222.
29. Ginzler EM, Diamond HS, Weiner M, Schlesinger M, Fries JF, Wasner C, Medsger TA Jr, Ziegler G, Klippel JH, Hadler NM, Albert DA, Hess EV, Spencer-Green G, Grayzel A, Worth D, Hahn BH, Barnett EV. A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis. Arthritis Rheum. 1982; 25:601–611.
30. Gladman DD. Prognosis and treatment of systemic lupus erythematosus. Curr Opin Rheumatol. 1996; 8:430–437.
31. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, Bacon P, Bombardieri S, Hanly J, Hay E, Isenberg D, Jones J, Kalunian K, Maddison P, Nived O, Petri M, Richter M, Sanchez-Guerrero J, Snaith M, Sturfelt G, Symmons D, Zoma A. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. Arthritis Rheum. 1996; 39:363–369.
32. Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Kalunian K, Nived O, Petri M, Sanchez-Guerrero J, Snaith M, Sturfelt G. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum. 1997; 40:809–813.
33. Graffar M. Une methode de classification sociale d’echantillons de population. Courrier VI. 1956: 445–459.
34. Guzman J, Cardiel MH, Arce-Salinas A, Sanchez-Guerrero J, Alarcon-Segovia D. Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol. 1992; 19:1551–1558.
35. Halberg P, Alsbjom B, Balslev JT, Lorenzen I, Gerstoft J, Wiik A. Systemic lupus erythematosus: follow-up study of 148 patients. II. Predictive factors of importance for course and outcome. Clin Rheumatol. 1987; 6:22–26.
36. Harris EN, Williams E, Shah DJ, De Ceulaer K. Mortality of Jamaican patients with systemic lupus erythematosus. Br J Rheumatol. 1989; 28:113–117.
37. Hernandez-Cruz B, Tapia N, Villa-Romero AR, Reyes E, Cardiel MH. Risk factors associated with mortality in systemic lupus erythematosus. A case-control study in a tertiary care center in Mexico City. Clin Exp Rheumatol. 2001; 19:395–401.
38. Hochberg MC. Mortality from systemic lupus erythematosus in England and Wales, 1974–1983. Br J Rheumatol. 1987; 26:437–441.
39. Jacobsen S, Petersen J, Ullman S, Junker P, Voss A, Rasmussen JM, Tarp U, Poulsen LH, van Overeem Hansen G, Skaarup B, Hansen TM, Podenphant J, Halberg P. Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus. Scand J Rheumatol. 1999; 28:75–80.
40. Jacobsen S, Petersen J, Ullman S, Junker P, Voss A, Rasmussen JM, Tarp U, Poulsen LH, van Overeem Hansen G, Skaarup B, Hansen TM, Podenphant J, Halberg P. A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value. Clin Rheumatol. 1998; 17:478–484.
41. Johnson AE, Cavalcanti FS, Gordon C, Nived O, Palmer RG, Sturfelt G, Viner NJ, Bacon PA. Cross-sectional analysis of the differences between patients with systemic lupus erythematosus in England, Brazil and Sweden. Lupus. 1994; 3:501–506.
42. Johnson AE, Gordon C, Palmer RG, Bacon PA. The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum. 1995; 38:551–558.
43. Karlson EW, Daltroy LH, Lew RA, Wright EA, Partridge AJ, Fossel AH, Roberts WN, Stern SH, Straaton KV, Wacholtz MC, Kavanaugh AF, Grosflam JM, Liang MH. The relationship of socioeconomic status, race, and modifiable risk factors to outcomes in patients with systemic lupus erythematosus. Arthritis Rheum. 1997; 40:47–56.
44. Karlson EW, Daltroy LH, Lew RA, Wright EA, Partridge AJ, Roberts WN, Stern SH, Straaton KV, Wacholtz MC, Grosflam JM, Liang MH. The independence and stability of socioeconomic predictors of morbidity in systemic lupus erythematosus. Arthritis Rheum. 1995; 38:267–273.
45. Kaslow RA. High rate of death caused by systemic lupus erythematosus among U.S. residents of Asian descent. Arthritis Rheum. 1982; 25:414–418.
46. Kiss E, Regeczy N, Szegedi G. Systemic lupus erythematosus survival in Hungary. Results from a single center. Clin Exp Rheumatol. 1999; 17:171–177.
47. Massardo L, Martinez ME, Jacobelli S, Villarroel L, Rosenberg H, Rivero SJ. Survival of Chilean patients with systemic lupus erythematosus. Semin Arthritis Rheum. 1994; 24:1–11.
48. McCarty DJ, Manzi S, Medsger TA Jr, Ramsey-Goldman R, Laporte RE, Kwoh CK. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum. 1995; 38:1260–1270.
49. Molina JF, Drenkard C, Molina J, Cardiel MH, Uribe O, Anaya JM, Gomez LJ, Felipe O, Ramirez LA, Alarcon-Segovia D. Systemic lupus erythematosus in males. A study of 107 Latin American patients. Medicine (Baltimore). 1996; 75:124–130.
50. Morton RO, Gershwin ME, Brady C, Steinberg AD. The incidence of systemic lupus erythematosus in North American Indians. J Rheumatol. 1976; 3:186–190.
51. Nossent JC. Course and prognostic value of Systemic Lupus Erythematosus Disease Activity Index in black Caribbean patients. Semin Arthritis Rheum. 1993; 23:16–21.
52. Nossent JC. SLICC/ACR damage index in Afro-Caribbean patients with systemic lupus erythematosus: changes in and relationship to disease activity, corticosteroid therapy and prognosis. J Rheumatol. 1998; 25:654–659.
53. Peschken CA, Esdaile JM. Systemic lupus erythematosus in North American Indians: a population based study. J Rheumatol. 2000; 27:1884–1891.
54. Petri M. Hopkins Lupus Cohort 1999 update. Rheum Dis Clin North Am. 2000; 26:199–213.
55. Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991; 34:937–944.
56. Petri M, Perez-Gutthann S, Longenecker JC, Hochberg M. Morbidity of systemic lupus erythematosus: role of race and socioeconomic status. Am J Med. 1991; 91:345–353.
57. Pistiner M, Wallace DJ, Nessim S, Metzger AL, Klinenberg JR. Lupus erythematosus in the 1980s: a survey of 570 patients. Semin Arthritis Rheum. 1991; 21:55–64.
58. Pons-Estel B, Villalba D, Alvarellos A, Caeiro F, Catoggio LJ, Soriano ER. ARTHROS 2.0: A rheumatology database [abstract]. Ann Rheum Dis. 1999: 58153.
59. Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002; 32:666–669.
60. Quintero-Del-Rio AI, Bacino D, Kelly J, Aberle T, Harley JB. Familial systemic lupus erythematosus: a comparison of clinical manifestations and antibody presentation in three ethnic groups. Cell Mol Biol (Noisy-le-grand). 2001; 47:1223–1227.
61. Rahman P, Gladman DD, Urowitz MB, Hallett D, Tam LS. Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus. Lupus. 2001; 10:93–96.
62. Ramos Niembro F. Lupus eritematoso generalizado. In: Ramos Niembro F, ed. Enfermedades Reumaticas. Criterios y Diagnostico
. Mexico: McGraw-Hill Interamericana; 1999:79–137.
63. Reveille JD, Bartolucci A, Alarcon GS. Prognosis in systemic lupus erythematosus. Negative impact of increasing age at onset, black race, and thrombocytopenia, as well as causes of death. Arthritis Rheum. 1990; 33:37–48.
64. Reveille JD, Moulds JM, Ahn C, Friedman AW, Baethge B, Roseman J, Straaton KV, Alarcon GS. Systemic lupus erythematosus in three groups. I. The effects of HLA Class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. Arthritis Rheum. 1998; 41:1161–1172.
65. Rojas-Serrano J, Cardiel MH. Lupus patients in an emergency unit. Causes of consultation, hospitalization and outcome. A cohort study. Lupus. 2000; 9:601–606.
66. Rosner S, Ginzler EM, Diamond HS, Weiner M, Schlesinger M, Fries JF, Wasner C, Medsger TA Jr, Ziegler G, Klippel JH, Hadler NM, Albert DA, Hess EV, Spencer-Green G, Grayzel A, Worth D, Hahn BH, Barnett EV. A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death. Arthritis Rheum. 1982; 25:612–617.
67. Salmon JE, Millard S, Schachter LA, Arnett FC, Ginzler EM, Gourley MF, Ramsey-Goldman R, Peterson MG, Kimberly RP. Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. J Clin Invest. 1996; 97:1348–1354.
68. Seleznick MJ, Fries JF. Varibles associated with decreased survival in systemic lupus erythematosus. Semin Arthritis Rheum. 1991; 21:73–80.
69. SPSS/PC v 10.0. Chicago: SPSS Inc, 2000.
70. Stokes M, Davis C, Koch G. Categorical data analysis using the SAS System
. 2nd ed. Cary, NC: SAS Institute Inc, 2000.
71. Stoll T, Sutcliffe N, Klaghofer R, Isenberg DA. Do present damage and health perception in patients with systemic lupus erythematosus predict extent of future damage? A prospective study. Ann Rheum Dis. 2000; 59:832–835.
72. Studensky S, Allen NB, Caldwell DS, Rice JR, Polisson RP. Survival in systemic lupus erythematosus. A multivariate analysis of demographic factors. Arthritis Rheum. 1987; 30:1326–1332.
73. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982; 25:1271–1277.
74. Thumboo J, Uramoto K, O’Fallon WM, Fong KY, Boey ML, Feng PH, Thio ST, Gabriel SE, Chng HH, Howe HS, Koh ET, Koh WH, Leong KH, Leong KP. A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992. Arthritis Rheum. 2001; 45:494–500.
75. Trager J, Ward M. Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol. 2001; 13:345–351.
76. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med. 1976; 60:221–225.
77. Urowitz MB, Gladman DD, Abu-Shakra M, Farewell VT. Mortality studies in systemic lupus erythematosus: results from a single center. III. Improved survival over 24 years. J Rheumatol. 1997; 24:1061–1065.
78. Valenzuela Yuraidini J, Diaz Andrade E, Klagges Valenzuela B. Clasificacion social y estado nutritivo. Empleo de un nuevo metodo de clasificacion social. Cuadernos Medico Sociales. XVIII ( 1), 1976.
79. Vila LM, Mayor AM, Valentin AH, Garcia-Soberal M, Vila S. Clinical and immunological manifestations in 134 Puerto Rican patients with systemic lupus erythematosus. Lupus. 1999; 8:279–286.
80. Walsh SJ, Algert C, Gregorio DI, Reisine ST, Rothfield NF. Divergent racial trends in mortality from systemic lupus erythematosus. J Rheumatol. 1995; 22:1663–1668.
81. Walsh SJ, DeChello LM. Geographical variation in mortality from systemic lupus erytematosus in the United States. Lupus. 2001; 10:637–646.
82. Ward MM, Pyun E, Studenski S. Long-term survival in systemic lupus erythematosus: patient characteristics associated with poorer outcomes. Arthritis Rheum. 1995; 38:274–283.
83. Ward MM, Pyun E, Studenski S. Causes of death in systemic lupus erythematosus. Long-term follow-up of an inception cohort. Arthritis Rheum. 1995; 38:1492–1499.
84. Zonana-Nacach A, Roseman JM, McGwin G Jr, Friedman AW, Baethge BA, Reveille JD, Alarcon GS, for the LUMINA Study Group. Systemic lupus erythematosus in three ethnic groups. VI. Factors associated with fatigue within 5 years of criteria diagnosis. Lupus. 2000; 9:101–109.