Clinical features, serological findings, and survival rate comparison between early versus late-onset systemic lupus erythematosus from 2000 to 2010, two centers experience

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from chronic and recurrent activation of the immune system contributing to inflammation and tissue destruction involving different organs. It frequently occurs in reproductive-age women and the onset of SLE after 50 years occurs in only 3–18% of patients.^[1] Late-onset SLE (age ≥50 years at diagnosis) has a strong modifying effect on the clinical presentation, disease course, response to treatment, and prognosis of SLE.^[2,3] In comparison with Early-onset SLE (age <50 years at diagnosis), late-onset SLE has a more insidious onset of the disease and a lower prevalence of severe manifestations.^[4,5] The diagnosis of late-onset SLE is often delayed and only established after more extensive investigations. Late-onset SLE has a higher mortality rate compared to early-onset SLE; probably due to the negative impact of age and associated comorbidities, and the specific effect of lupus in these patients.^[5-9] There are also variations in clinical features, organ involvement, and differences in laboratory findings of SLE in the different age groups. Just more than one third (35%) of mortality in SLE is caused by the active disease in young patients compared to the elderly.^{[3, 10-12]} Comparative studies reported variable conclusions, while one study reporting similar clinical features and prognosis in all age groups; the others indicated that cutaneous, renal, and hematological manifestations are more prevalent in early-onset SLE, in addition, late-onset SLE patients had a poor prognosis due to higher comorbidities and risks of cardiovascular diseases.^{[8, 13-15]} The aim of this study is to compare clinical features, laboratory findings, and survival rates between early and late-onset SLE groups in the Saudi Arabian population.

Materials and Methods

This was a retrospective cohort study of patients diagnosed with SLE at King Abdulaziz Medical City (KAMC) and King Faisal Hospital and Research Center (KFH and RC) in Riyadh, Saudi Arabia, from January 2000 to December 2010. Ethical approval was obtained from the Institutional Review Board of King Abdullah International Medical Research Center and KFH and RC, Riyadh, Saudi Arabia. The diagnosis was based on the presence of at least four of the revised American College of Rheumatology (ACR) criteria. Clinical presentation, laboratory findings, organ involvement, and the European Consensus Lupus Activity Measurement (ECLAM) score based on the available data at the time of diagnosis were collected. The patient data were collected from the time of diagnosis to the latest documented visit to the hospital and entered in an excel sheet for analysis.

Results

Discussion

The age at disease onset plays a fundamental role in the expression and course of SLE. Early-onset SLE patients differ from late-onset SLE patients in the severity of the disease, clinical presentation, prognosis, and pattern of organ involvement. There could also be inter-ethnic differences in some of these clinical features.^[5-7,17] Therefore, the study aimed to compare the differences in patients diagnosed with early versus late-onset SLE in terms of clinical features, disease activity, laboratory findings, and the 5-year survival rate.

In the current study, the prevalence of late-onset SLE was lower than the early-onset SLE. Similar results have been reported in literature.^[18-20] In terms of gender, the majority was female (91.1% in early-onset SLE and 72.5% in Late-onset SLE). The study of Boddaert et al. supported the finding reporting that 93% of the early-onset SLE group and 72.3% of the late-onset SLE group was female.^[4] Mohamed et al. reported a female:male ratio of adult SLE as 10:1.^[21] The Das Chagas Medeiros et al. study also reported 93.5% female, but this high ratio could be because 81% of their sample was adult-onset SLE.^[15] The finding was expected as SLE affects women predominantly young women (childbearing age) 9 times more frequently than men, with the frequent exacerbations during pregnancy, indicating a role of estrogens as a precipitating factor.^[17] In addition, the cultural requirement for women to cover-up caused a high prevalence of Vitamin D deficiency, which could play an additional role in autoimmune diseases.^[21] Based on the current results, the female-to-male ratio declines in Late-onset SLE, as supported in literature.^{[4, 18, 22]} Menopause and the reduced production of estrogen may explain the decrease of both the SLE incidence and the gender ratio with aging.^[4] In contrast, Aljohani et al. reported that the female-to-male ratio was the same in early and late-onset SLE.^[6]

Regarding the comorbidities associated with SLE, the current study found that diabetes mellitus and hypertension were more prevalent in late-onset SLE compared to early-onset SLE. Das Chagas Medeiros et al. reported similar results in their study in Brazil and Sonia et al. in Tunis.^[15,18] The higher frequency of SLE comorbidities in older individuals could be due to aging, longer exposure to classical risk factors, and use of corticosteroids.^[18] In the present study, there was a significant increase in the number of patients with Sjögren syndrome in the late-onset SLE group; this finding is also supported in literature, but contrasted by Sonia et al. who found no significant difference in the frequency of Sjögren’s syndrome between the two groups.^{[18, 23, 24]} The symptoms of Sjögren syndrome may be associated with other frequent causes of mucosal dryness in an elderly population, such as polypharmacy, chronic debilitating diseases, and senile salivary gland atrophy.^[18]

Regarding clinical presentation, arthritis was the most frequent clinical presentation for both groups, a similar finding is also reported by Budhoo et al.^[25] In the current study, the late-onset group had a slightly higher prevalence (85% vs. 81.4%). In contrast, several studies reported arthritis to be less frequent in late-onset SLE patients.^{[4, 26, 27]} In the present study, the frequency of malar rash was higher in the early-onset SLE group which is in contrast to Tomic-Lucic et al. and Appenzeller et al. who reported an increase in the frequency of malar rash in the late-onset SLE group.^[13,26] Similarly, anemia was more frequent in the early-onset SLE group (82.1%) in contrast with Tomic-Lucic et al. reporting hematological abnormalities equal in the two groups and Appenzeller et al. who reported that hemolytic anemia and thrombocytopenia were more frequently in the Late-onset SLE group.^[13,26]

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Figure 1:

Five year (60 months) overall survival. Group I = Early-onset SLE, Group II = Late-onset SLE

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Serological findings in the current study reported all patients positive for ANA with anti-dsDNA positivity and anti-SM higher in the early-onset SLE group. These results were confirmed by Tomic-Lucic et al., who reported a lower prevalence of anti-dsDNA and anti-SM antibodies in the late-onset SLE group but in contrast to Sonia et al. who found the same results higher in the early-onset SLE group.^[13,18] The effect of SLE on the organs of patients differed in the two groups. In the current study, proteinuria was higher in the early-onset SLE group (46.4%). Proteinuria identifies patients with renal damage, those at risk for deteriorating renal disease and increased cardiovascular morbidity. The finding is consistent with Tomic-Lucic et al. and Aljohani et al., reporting a lower prevalence of nephritis in the late-onset SLE group.^[6,13] Pulmonary hypertension, interstitial lung disease, and hepatitis had a higher frequency in the late-onset SLE group (current study), because the degree of cumulative organ damage correlates directly with the age of onset, increasing with age.^[13]

This study used the ECLAM score to assess disease activity and the difference in disease activity in both groups was not statistically significant. Using the cox proportional model and reporting the results as a hazard ratio, the overall 5-year survival analysis was probably lower in the late-onset SLE group compared to the early-onset SLE group. Literature consistently reports a higher mortality rate in the late-onset SLE group, possibly due to aging, the lack of efficiency of the body organs as a result of aging and SLE, as well as complications due to comorbidities, and an increased risk of toxicities from immunosuppressive drugs.^[6,8,18,26]

Conclusion

This study conducted on Saudi patients suffering from SLE highlighted differences in between the early-onset and late-onset SLE. Compared with the early-onset SLE group, the late-onset SLE group exhibited a higher frequency of medical comorbidities such as diabetes mellitus and hypertension. The early-onset SLE had a higher frequency of ACR criteria and other clinical presentations such as malar rash. Hematological abnormalities, specifically anemia, renal impairment due to lupus nephritis, and thromboembolic events, had a significantly higher frequency in the early-onset SLE group. More patients with late-onset SLE presented with respiratory and gastrointestinal involvement. An analysis of the estimated 5-year survival rate was lower in the late-onset SLE group; however, it was not significant. It is important for the health-care practitioner treating a patient with late-onset SLE to manage the medical comorbidities and use preventive medicine to achieve a better patient outcome.