Systemic lupus erythematosus (SLE) predominantly affects women, with a high incidence during the childbearing age, a decline after menopause, and a frequent exacerbation during pregnancy, suggesting that estrogens act as a precipitating factor. However, SLE can be observed in children and in the elderly. In contrast with childhood SLE, studies on elderly SLE patients are scarce, probably because SLE is uncommon at this age. We conducted the current study to analyze characteristics and outcome of patients with late-onset SLE in a French tertiary referral center, and to compare them with those of randomly selected patients with SLE of younger onset (age below 50 years at SLE diagnosis).
PATIENTS AND METHODS
From 1980 to 2000, we followed 756 patients with SLE fulfilling at least 4 of the 1997 American College of Rheumatology (ACR) revised criteria for SLE27. Patients with drug-induced SLE or pure cutaneous lupus were excluded.
"Late-onset" SLE was defined as SLE with diagnosis made at or over the age of 50 years. Forty-seven patients were identified as having late-onset SLE. The following items were recorded: age, sex, date of diagnosis, presence of the antiphospholipid syndrome (APS) defined according to Wilson's criteria65, clinical and laboratory manifestations, treatment, date of the last visit, status at the last visit, and, in case of death, cause of death. Organ involvement not related to SLE was excluded. Kidney involvement was defined as 1) proteinuria of 1 g/day or more, 2) abnormal renal biopsy by light microscopy examination, or 3) a 30% decrease in creatinine clearance over 1 year37. Renal insufficiency was defined as serum creatinine above 135 micromol/L.
These patients with late-onset SLE were compared with a group of 114 younger patients. This group, randomly designed among all patients aged younger than 50 years at SLE diagnosis, constituted the "early-onset" SLE group.
We performed a pooled data study from studies in the literature identified using a computerized MEDLINE search (PUBMED, National Library of Medicine, Bethesda, MD) with subject headings "systemic lupus erythematosus," "age factor," "late-onset," "elderly," and "geriatrics," for entries from 1964 to January 2004.
Data analysis was performed using Statview (1992-1998 SAS Institute). A Fisher exact test was performed for all qualitative variables, and a Student t-test for comparison of quantitative variables. A log-rank test was performed to compare cumulative probability of survival.
The late-onset SLE group comprised 34 women and 13 men (Table 1). The female to male ratio was significantly lower in the late-onset group compared with early-onset group (2.6 vs. 13 respectively; p = 0.001). Mean age at SLE diagnosis was 59 ± 7 years (mean ± standard deviation; range, 50-77 yr). The delay between SLE onset and diagnosis was 15.8 months (range, 1-72 mo). The ethnic distribution was as follows: 43 patients were white, coming from southern Europe (metropolitan France, n = 38; Italy, n = 2; Portugal, n = 2; Greece, n = 1), 1 came from the French Indies, 1 from Iran, 1 from India, and 1 from Algeria. The mean age at menopause, known in 15/34 women, was 49 years (range, 42-55 yr). In 2 cases, menopause was related to hysterectomy with bilateral oophorectomy, performed at 42 years and 53 years, respectively, for uterine leiomyoma. Menopause occurred before SLE onset in 10 of these 15 patients (mean delay, 9 yr; range, 2-14 yr), after SLE onset in 2 patients (mean delay, 2.5 yr; range, 1-4 yr), and at the same time in 3. Three patients had hormonal replacement therapy.
The mean number of 1997 ACR revised criteria was 4.7 ± 0.36 (range, 4-8). The main presenting features are listed in Table 2. The most frequent manifestations (Table 3) were arthritis (72.3%), fever (48.9%), and pleuritis (31.9%). Pericarditis was present in 12 patients, hypertension in 9 patients, Raynaud phenomenon in 9, discoid lupus in 8, purpura in 6, lymphadenopathy in 6, and seizures in 3. Two patients had renal insufficiency.
Besides pulmonary embolism, which occurred in 5 patients, interstitial pneumonitis was present in 5 patients (10.6%). None of them had anti-SSA antibodies. These 5 patients had pulmonary fibrosis considered to be SLE-related and were treated with corticosteroids, associated in 1 case with cyclophosphamide pulses, and in another case with methotrexate.
Eleven patients had deep venous thrombosis and/or pulmonary embolism; the latter was an isolated event in 5. In these 5 patients with pulmonary embolism, 1 had pulmonary embolism unrelated to APS, 2 had definite APS, and 2 had very probable APS, because of history of recurrent adverse pregnancy outcome, recurrent pulmonary embolism, and thrombocytopenia, but a search for anticardiolipin antibodies (aCL) was not performed at that time. For statistical analysis, these last 2 patients were considered as having APS. In the group of 6 patients with thrombophlebitis without pulmonary embolism, 3 had definite APS. The 3 other patients had no other clinical or laboratory manifestations suggestive of APS, and aCL determination was not performed at that time. Finally, 9 patients in the late-onset group had APS, characterized by thromboses in 9, associated with prior obstetrical events in 2. Vascular events were thrombophlebitis or pulmonary embolism in all besides 1 patient with recurrent arterial strokes.
Renal involvement was found in 8 patients with proteinuria of more than 1 g/day (mean value, 2.5 g/day; range, 1.7-3.5 g/day), associated in 2 cases with renal insufficiency (Table 4). These patients underwent renal biopsy showing mesangial glomerulonephritis (n = 3), focal proliferative glomerulonephritis (n = 2), pure membranous glomerulonephritis (n = 2), and diffuse proliferative glomerulonephritis (n = 1). In the latter, and in 1 case of focal proliferative glomerulonephritis, treatment included high-dose corticosteroids and monthly cyclophosphamide pulses. None of these 8 patients evolved to end-stage renal failure.
Antinuclear antibodies with a titer above 1:100 were present in 45 of 47 patients; anti-dsDNA in 35 of 43 tested patients; and anti-ENA in 17 of 37 tested patients. These consisted of anti-SSA (n = 8), anti-RNP (n = 6), anti-Sm (n = 5), and anti-SSB (n = 5) antibodies. Low serum complement levels were observed in 14 patients. These consisted of low CH50 (n = 8), low C4 fraction (n = 12), and low C3 fraction (n = 4). Rheumatoid factor was found in 14 of 33 tested patients, cryoglobulinemia in 4 of 23, and erythrocyte Coombs test was positive in 9 of 26 patients. Lupus anticoagulant was found in 8 of 30 tested patients, aCL in 8 of 21, and a false positive test for syphilis in 5 of 29. Any of these 3 was present in 14 of 30 tested patients. Main laboratory characteristics are represented in Table 5.
Therapy and Course
Thirty-nine patients were treated with corticosteroids, together with hydroxychloroquine in 21. Eight patients received hydroxychloroquine alone. Daily corticosteroids dose was 1 mg per kg or more in 26 patients, and 0.5 mg per kg or less in 13 patients. Immunosuppressive drugs were associated with high-dose corticosteroids in 9 patients. Seven patients received cyclophosphamide given for proliferative glomerulonephritis (n = 2), severe interstitial pneumonitis (n = 2), recurrent myelitis (n = 1), myocarditis (n = 1), and severe APS (n = 1, treated in 1990). Methotrexate was used in 2 patients with myositis. Two others received azathioprine. Therapy is summarized in Table 6.
Iatrogenic pathology consisted of 5 infectious diseases in patients treated with corticosteroids (pulmonary tuberculosis, Enterobacter pyelonephritis, pneumococcus pneumonia, angiocholitis, and septic shock of unknown origin). Four patients underwent steroid-related complications: osteoporotic vertebral fracture (n = 2) and osteonecrosis of the femoral head (n = 2). One patient developed a subdural hematoma under oral anticoagulation given for associated APS (international normalized ratio at time of hematoma is unknown).
Mean follow-up from SLE diagnosis was 6 years (maximum, 20 yr). At the time of analysis, 9 patients had died. Four patients died of neoplasia: 2 cases of leukemia (1 subacute myelomonocytic leukemia in a patient previously treated with cyclophosphamide, and 1 acute myeloid leukemia following myelodysplastic syndrome); 1 case of breast cancer; and 1 case of neoplastic lymphangitis of unknown origin. Infection was the cause of death in 3 patients: Gram-positive cocci endocarditis; septic shock after surgical excision of an abdominal abscess; and end-stage hepatitis C viral cirrhosis. Finally, 2 patients with APS died of a cardiovascular complication: a postoperative stroke and acute heart failure, respectively.
Comparison With Characteristics of the Early-Onset Group
The early-onset SLE group consisted of 114 patients, 106 women and 8 men. Mean age at SLE diagnosis was 25 ± 9 years. Mean number of 1997 revised ACR criteria was 5.5 ± 0.89 (range, 4-10).
We compared the clinical, laboratory, and therapeutic features of both groups (see Tables 3-6). Fewer women were in the late-onset group compared with the early-onset group (72% vs. 93%; p = 0.001). Considering clinical aspects (see Table 3), arthritis (72.3% vs. 89.5%; p = 0.009) and malar rash (25.5% vs. 47.4%; p = 0.013) were significantly less frequent in the late-onset group compared with the early-onset group. In the late-onset group, fever (48.9% vs. 33.3%), pleuritis (31.9% vs. 18.4%), hypertension (19.1% vs. 12.3%), and venous occlusion (23.4% vs. 13.1%) were slightly more frequent compared to the early-onset group, but differences were not significant. APS was equally distributed in both groups. Renal involvement as defined above (see Table 4) was less frequent in the late-onset group (21.3% vs. 51.2%; p = 0.0004), as were single items such as proteinuria >1 g/day (17% vs. 38.5%; p = 0.009), nephrotic syndrome (0% vs. 10.5%; p = 0.019), and requirement for renal biopsy (21.3% vs. 50.0%; p = 0.0008). Results for renal insufficiency were borderline significant (4.3% vs. 14.9%; p = 0.063). Proliferative glomerulonephritis (WHO class III or IV) rarely occurred in the late- versus early-onset group (3/47 vs. 25/114 cases; p = 0.021), with a striking difference for class IV (1/47 vs. 21/114 cases; p = 0.005). With regard to laboratory findings (see Table 5), the late-onset group was characterized by a lower frequency of hypocomplementemia (29.8% vs. 71%; p < 0.0001) as well as low C3 (8.5% vs. 35.1%; p = 0.0004) and low C4 fraction (25.5% vs. 62.3%; p < 0.0001). In contrast, rheumatoid factor positivity occurred more frequently in the elderly (42.4% vs. 20.0%; p = 0.03). High-dose corticosteroids (55.3% vs. 80.7%; p = 0.0016) and immunosuppressive drugs (19.1% vs. 42.1%; p = 0.006) were less frequently used in the late-onset group (see Table 6).
Survival rates for both groups are compared in Figure 1. The mean follow-up from diagnosis of SLE was shorter in the late-onset group than in the early-onset group (5.8 ± 4 yr vs. 8.6 ± 5.5 yr). At the time of analysis, 7 of 114 patients in the early-onset group had died. The causes of death were infection in 4 patients and cerebral hematoma, uncontrolled SLE flare, and non-Hodgkin lymphoma in 1 case each. The 5-year and 10-year survival rates after diagnosis of SLE were 84% and 71%, respectively, in the late-onset group versus 95% for both in the early-onset group (p < 0.05 and p < 0.01, respectively).
There is no strict definition of late-onset SLE, but the cutoff age used most frequently is 50 years at disease onset or diagnosis3,5,10,13-15,19,20,25,26,28-30,36,41,50,57,58,64. Late-onset SLE frequently presents as drug-induced SLE, therefore requiring a careful search for a possible sustained use of potentially SLE-inducing drugs, including eyedrops containing beta-blockers66.
To our knowledge, 22 studies dedicated to late-onset SLE have been reported: 6 from the United States5,6,14,18,32,64, 4 from Great Britain9,15,38,39, 2 from Brazil13,57, 2 from Spain19,20, 2 from China26,41, and 1 each from Australia23, France22, Japan25, Malaysia54, Singapore36, and Taiwan50. A meta-analysis comparing 170 patients with late-onset SLE and 1612 patients with early-onset SLE was reported in 198960. Most of the previous studies were performed in the 1980s, before the recognition of APS and the current use of immunosuppressive drugs in severe SLE. Our current series reports 1 of the largest groups of patients with late-onset SLE. We performed a pooled analysis of published studies on late-onset SLE, totaling 714 old and 4700 young SLE patients, using the Fisher exact test and the Bonferroni correction for multiple comparisons (Table 7).
Forty-seven late-onset SLE patients, that is, diagnosed at or over the age of 50 years, represented 6.2% of all patients with SLE followed in our department. Different incidences have been previously reported (listed here by first author): 3.6% in Takayasu's study in Brazil57, 3.7% in Costallat's study in Brazil13 and Hashimoto's study in Japan25, 6.1% in Domenech's study in Great Britain15, 9% in a multicenter European study10, 10.3% in Dubois's study in the United States17, 11.4% in Harvey's study in the United States24, 14.9% in Antolin's study in Spain3, 16% in Font's study in Spain19, 20.1% in Jacobsen's study in Denmark29 which used an age at disease onset of 50 years or more, and 18% in Studenski's study in the United States performed on patients diagnosed at or over the age of 55 years56. All of the studies highlight a low prevalence of SLE in the elderly and a decreased incidence with age40.
In our series, female patients represented 72.3% of cases in the late-onset SLE group. The female to male ratio of 2.6 was significantly lower than the 13.2 ratio observed in the early-onset group. Some studies did not confirm this result3,15,20 but most of the literature data indicate that the sex ratio declines with age in SLE. In large cohorts of unselected patients with SLE, it ranges from 3.5 for Harvey24 to 4.9 for Ward62, 8.2 for Dubois17, 9 for Font19, 9.1 for Jacobsen29, 10 for Cervera10, 12 for Hashimoto25, 14.1 for Takayasu57 and 14.4 for Costallat13. In contrast, the sex ratio of late-onset SLE was 1.9 for Studenski56, 2.5 for Takayasu57, 3.2 for Ballou6, 4 for Font19 and Hashimoto25, 4.7 for Jacobsen29, 5.5 for Cervera10, and 9 for Costallat13. The pooled analysis of data from the literature definitely confirms the decline of the female to male ratio observed with age in SLE (4.4:1 vs. 10.6:1; p = 3.10−14 after Bonferroni correction, see Table 7). This probably reflects the relationship between SLE and estrogen status. There is strong evidence that estrogens have immunomodulatory effects. In patients with SLE, mononuclear cells secrete IgG anti-dsDNA when they are activated by estrogens35. Estrogen treatment of lupus-prone mice worsens the disease, whereas oophorectomy ameliorates it55. Bynoe et al7 have suggested that estrogenic stimulation of the immune system leads to increased levels of Bcl-2, and might contribute to disturbances in negative selection of auto-reactive B cells. In humans, estrogen hormone replacement therapy (HRT) is associated with a higher risk of SLE53. SLE flares occur less frequently in patients who have developed cyclophosphamide-induced ovarian failure48. The influence of estrogen-containing contraceptive therapy or HRT on SLE activity remains debatable, however46. In a retrospective study, Jungers et al33 reported a significant increase of SLE flares after estrogen-containing contraceptive therapy was instituted in 26 women. In 2001, Mok et al47 noted the absence of prospective studies showing a deleterious effect of estrogen on SLE activity. Some intervention trials using anti-estrogen or androgen therapy have been performed. Cyproterone acetate was associated with a decrease in SLE flares in 7 women34. SLE seemed to improve under gonadotrophin-releasing hormone analogues8. Dehydroepiandrosterone, a steroid hormone with androgenic properties, seems promising12,59, but available data are too preliminary to recommend its widespread use in women with SLE.
Hence, menopause and reduced estrogen production may explain the decrease of both SLE incidence and its sex ratio with aging. It should be more accurate, therefore, in further prospective studies to compare groups according to hormonal status rather than age. In our series, menopause occurred in 86% of patients before or at the time of SLE diagnosis. We could not collect exhaustive information about menopause in 19 patients. However, among the 10 in whom menopause occurred before disease onset, none had renal involvement, whereas only 1 required high-dose steroids for pulmonary fibrosis, and another required a combination of steroids and intravenous cyclophosphamide for myelitis. Mok et al45 reported a significant decrease of postmenopausal SLE flares in both pre- and postmenopausal-onset SLE patients. These results agree with a lower severity of the disease in elderly SLE, and particularly in postmenopausal women. Three of our patients had received HRT. In 1 case, menopause occurred 11 years before the onset of nonrenal SLE, requiring neither high-dose steroids nor immunosuppressive drugs. In another case, menopause occurred 3 years after the onset of a disease requiring high-dose steroids and methotrexate for pulmonary involvement and severe polyarthritis. The latter featured mesangial glomerulonephritis. Because we could not collect exhaustive data about HRT in our patients, the effect of HRT on SLE course was not analyzed.
Features of Late-Onset SLE
Arthritis and malar rash occurred significantly less frequently, whereas there was just a nonsignificant trend for reduced occurrence of fever, pleural effusion, and hypertension. Previous studies have suggested a high prevalence of pulmonary involvement in late-onset SLE5,29,38,58, but it was no more than 10.6% in our series after exclusion of pleural effusion, pulmonary embolism, and infectious complications. Cervera et al10 noted that pulmonary involvement occurred in only 9% of 90 patients with late-onset SLE. The possible role of associated Sjögren syndrome was not confirmed in our 5 patients with pulmonary fibrosis, who all tested negative for anti-SSA antibodies.
Pooled Literature Data
The clinical presentation of SLE undoubtedly changes with aging. Literature data suggest that pulmonary involvement5,14,29,38,60 and serositis31,41,60 are more frequently observed in patients with late-onset SLE, whereas malar rash, photosensitivity, arthritis, and nephropathy occur less commonly3,10,15,19,26,30. In our pooled data analysis using Bonferroni correction (see Table 7), malar rash (31.1% vs. 62.4%; p = 10−44), photosensitivity (26.2% vs. 38.2%; p = 6.10−6), alopecia/hair loss (24% vs. 44.9%; p = 3.10−11), purpura/cutaneous vasculitis (13.4% vs. 25.9%; p = 9.10−4), Raynaud phenomenon (24.8% vs. 37.2%; p = 3.10−7), neuropsychiatric manifestations (15.3% vs. 20.2%; p = 0.025), lymphadenopathy (9.1% vs. 19.6%; p = 2.10−4), nephritis (28.6% vs. 42.7%; p = 2.10−10), nephrotic syndrome (8.1% vs. 24.3%; p = 0.015), anti-RNP positivity (10.4% vs. 20.9%; p = 9.10−5), anti-Sm positivity (9.1% vs. 17.1%; p = 0.001), and low CH50 complement fraction (45% vs. 64.9%; p = 0.002) occurred less frequently in late-onset SLE, whereas serositis (36.7% vs. 28.6%; p = 7.10−4), pulmonary involvement (21.2% vs. 11.3%; p = 6.10−8), and rheumatoid factor positivity (32.7% vs. 20.1%; p = 3.10−5) occurred more frequently in late-onset SLE. Concerning treatment, the less frequent use of immunosuppressive drugs did not remain significant after Bonferroni correction (see Table 7) in the pooled analysis, but was clearly confirmed in our series, as was the less frequent requirement for high-dose steroids (see Table 6).
Primary Sjögren syndrome usually affects patients older than those with SLE, with a mean age at onset of 52.7 ± 0.85 years21. Sjögren syndrome may also coexist with SLE. In our pooled data analysis, an associated Sjögren syndrome was more frequently present in the late-onset than in the early-onset SLE group (71/343 [20.7%] vs. 242/1907 [12.7%] respectively; p = 2.8.10−7), although no difference was found for anti-SSA and anti-SSB antibodies. Thus, some distinct aspects of late-onset SLE observed in our study, that is, the higher prevalence of pulmonary involvement and of rheumatoid factor, 2 frequent features of primary Sjögren syndrome21, might have been influenced by the association of both diseases. Moreover, a 2004 study43 comparing SLE patients with and without associated Sjögren syndrome showed that the former were older; had a milder case of lupus; had a lower frequency of renal involvement, lymphadenopathy, and thrombocytopenia; and had a higher frequency of Raynaud phenomenon, rheumatoid factor, and anti-SSA and anti-SSB antibodies.
Thus, the peculiar features of late-onset SLE might be influenced by differences in gender, hormonal status, and prevalence of associated Sjögren syndrome.
Severity of Late-Onset SLE
Convincing data were found concerning severity of the disease and prevalence of renal involvement. In the late-onset group, proteinuria, renal insufficiency, and diffuse proliferative nephritis occurred less frequently, and treatment with high-dose steroids and immunosuppressive drugs was less frequently required. Diverse studies have emphasized that severity of SLE declines with age5,9,13,14,18,20,26,37,44,58,64. Cervera et al10 reported a decrease in prevalence of nephritis from 41% in early-onset to 22% in late-onset SLE patients. Wilson et al64, Ho et al26, Janwityanujit et al30, and Font et al19 also reported a negative influence of age on the occurrence of renal involvement.
Pooled Literature Data
The pooled analysis showed that the occurrences of nephritis (p = 2.10−10) and nephrotic syndrome (p = 0.015) were significantly lower in late-onset SLE (see Table 7). It should be noted that the criteria used for "nephritis" were different or not detailed in published studies; this was also true for the cutoff for proteinuria, which was <0.5 g/day3,6,15,19,22,30,57; <1 g/day (present report and references 5,13,64); <1.5 g/day18; and <3.5 g/day14. Similarly, renal failure was described as 30% decline of creatinine clearance (present report); creatinine clearance >50 mL/min41; and serum creatinine >1.4 mg/dL6, >1.5 mg/ dL5,64, or >2 mg/dL30. Histologic findings were rarely mentioned in the literature18,23,25,41, but our series provides detailed data demonstrating the rarity of severe proliferative nephritis in late-onset SLE. Finally, a lower prevalence of renal involvement has been reported not only in this particular setting, but also in SLE patients with either a positive rheumatoid factor10 or associated Sjögren syndrome43, 2 features shown to be more prevalent in late- versus early-onset SLE by our pooled analysis. A multivariate study is needed, therefore, to determine the major contributors to the reduced prevalence of renal involvement in late-onset SLE.
Outcome and Death
Dimant et al14 reported 5 deaths in older SLE patients, of which 2 were SLE-related, but the study was performed in 1966-1976 and azathioprine was the sole immunosuppressive drug used. Ward et al62, in a study performed between 1969 and 1983, observed that older patients tended to have a higher rate of SLE-related causes of death. This was not confirmed in further studies. Hashimoto et al25 reported 6 deaths, of which 3 were infections and 2 were perforated peptic ulcers. Antolin et al3 reported 11 deaths, mainly related to infectious diseases in 6 cases. None of our late-onset SLE patients died of SLE flare, and this agrees with the lower activity of SLE in the elderly. Our study was performed from 1980 to 2000, that is, during the cyclophosphamide era, and although we infrequently used immunosuppressive drugs in the elderly, this might explain the better control of the rare forms of severe SLE observed in this context. Causes of death according to treatment are rarely mentioned in literature. In a 2003 study, with a cohort of 1000 patients aged 37 ± 14 years when they entered the 10-year prospective study, Cervera et al11 found that causes of death were equally distributed between active SLE (26.5%), thrombosis within APS (26.5%), and infections (25%). In 2000, Pu et al50 reported the causes of death of elderly SLE patients between 1988 and 1998, but treatment was not detailed. In our series of late-onset SLE, infection caused death in 3 of 9 patients. Indeed, currently infection is the leading cause of death in SLE2,3,5,25, probably because improved management has reduced the role of uncontrolled disease. In the 2000 study by Pu et al50, this was true in all age-groups. Four of our patients died of neoplasia. Immunosuppressive drugs are known to increase the risk of neoplasia, but only 1 of these 4 patients had been treated with immunosuppressive agents. Some authors have suggested that neoplasia frequently occurs in the course of SLE, but these results have been disputed1. Moss et al49 reported a 20% malignancy-related death rate in all SLE age-groups. In contrast, the prevalence of neoplasia-related deaths was 6% in studies by Baker et al5 and Ward et al61. Cervera et al11 also mentioned a low prevalence of malignancies (2.3%). Following improvement in SLE management, the importance of cardiovascular diseases within causes of death has been highlighted. Aging; duration of exposure to classical vascular risk factors; and use of corticosteroids, associated with chronic inflammation and probably antiphospholipid antibodies, are responsible for an accelerated atherosclerotic process. Roman et al53 and Asanuma et al4 recently highlighted an accelerated atherosclerosis process in SLE. However, only 2 of our patients, both with APS, died of cardiovascular events. Because the study period started in 1980, antiphospholipid antibodies were not determined in all patients, and this is a clear limitation. Whether APS is more prevalent or severe with aging remains unknown, and is not confirmed in our report. The impact of APS on survival in SLE has been demonstrated by Drenkard et al16, especially for thrombocytopenia and arterial occlusion, but whether this impact is influenced by the age at SLE onset is unknown. Ward et al63 previously reported a premature cardiovascular morbidity in young women with SLE, but found no significant increase in hospitalization for acute myocardial infarction or stroke in women with SLE aged 65 years or older, compared with women who did not have SLE. Thus, the effect of APS on cardiovascular events in aged patients with SLE remains unclear.
In the late-onset SLE group, we observed a survival probability of 84% at 5 years from SLE onset, 71% at 10 years, and 59% at 15 years, versus 95% (p < 0.04), 95% (p < 0.001), and 92% (p < 0.001), respectively, in the early-onset group. The latter is in agreement with the prospective cohort reported by Cervera et al11. The difference became significant after 4 years of follow-up (see Figure 1). Age at SLE onset was previously reported as a risk factor for death42. The poorer prognosis of late-onset SLE contrasting with the lower severity of the disease might reflect only the consequences of aging. In a group of 25 late-onset SLE patients, Ballou et al6 reported a 5-year survival of 72%, not significantly different from that of younger patients (79%). In a series of 31 late-onset SLE patients studied between 1962 and 1977, Baker et al5 reported a 5- and 9-year survival of 92% and 83%, respectively. This fair result was observed despite a high prevalence of renal and pulmonary involvement (55% and 33%, respectively). However, it should be noted that 19% of the patients had only 3 ACR criteria and that immunosuppressive agents were not used. In the 1980s to 1990s, Studenski et al56 and Reveille et al51 found no significant differences in survival between younger versus older SLE patients.
The clinical pattern of late-onset SLE is characterized by a lower severity of disease especially with regard to renal involvement, leading to less frequent use of immunosuppressive drugs, and by the rarity of SLE flares among the causes of death. The reduced survival observed in comparison with younger SLE patients might reflect only the consequences of aging.
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