A systematic review and meta-analysis of cutaneous manifestations in late- versus early-onset systemic lupus erythematosus☆
Introduction
Systemic lupus erythematosus (SLE) most often occurs in women of reproductive-age. SLE onset in adults ≥50 years old is referred to as “late-onset SLE.” Previous studies report that late-onset SLE patients are more likely to include men and have a more insidious onset of disease [1], [2], [3], [4], [5], [6], [7]. Over one-third of the ACR SLE classification criteria reflect cutaneous manifestations, so it is not surprising that arthritis and cutaneous findings remain the most common presenting symptoms in both late-onset and early-onset SLE. Yet, previous literature suggested that these are less common in late-onset disease [3], [8], [9], [10], [11], [12]. Overall, the proportion of late-onset SLE among all SLE cases is relatively low, ranging from 4% to 20% [1], [3], [4], [8], [10], [13], [14]. However, due to a higher life expectancy and increasing awareness of the disease, the prevalence of late-onset SLE is expected to rise. Therefore, identifying the unique characteristics of this patient population is important. Conclusions drawn from previous studies including a 1989 meta-analysis of nine studies with 170 late-onset SLE patients [15] were limited by small sizes and heterogeneity of patient groups. To gain additional insight into the cutaneous manifestations of late-onset SLE, we conducted a systematic review and meta-analysis of published literature. We compared cutaneous manifestations in patients with early and late-onset SLE.
Section snippets
Methods
We performed a systematic review of the literature to identify articles comparing the cutaneous manifestations of patients with late versus early-onset lupus. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus was followed in the completion of this systematic review and meta-analysis [16]. With assistance from a professional medical librarian we electronically searched the literature in PubMed, CINAHL, Web of Science and Cochrane Library with MESH, and
Results
Literature searches yielded 1549 potential articles. After screening titles and abstracts, 95 full articles were retrieved for full-text evaluation. After application of exclusion criteria, 35 articles met criteria for final inclusion and level 3 review (Fig. 1), including 31 cohort studies and four case–control studies [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35],
Discussion
Our systematic review and meta-analysis of cutaneous manifestations in late-onset SLE shows that while cutaneous findings are still common, most cutaneous manifestations are less common in late compared to early-onset SLE (Table 2). In our pooled analysis of 1727 patients with late-onset SLE, malar rash, photosensitivity, alopecia, and Raynaud phenomenon occurred less frequently in late than in early-onset SLE patients. In more conservative random effects models for the meta-analysis of ACR
Conclusion
Our pooled analysis demonstrates that when SLE is diagnosed in older adults, most cutaneous manifestations are significantly less common. By contrast, sicca was significantly more prevalent in late-onset individuals. Future studies should examine differences in SLE manifestations in older versus younger-onset disease including investigating the roles of immune senescence in the skin and impact of gender and gene–environment interactions.
Acknowledgments
Authors would like to thank reference librarians at UW-School of Medicine and Public Health, Courtney Maxcy, Sarah Loring, and Becky Burton for help with article preparation.
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Bartels receives support from National Institutes of Health (NIH), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), United States (K23 #AR062381). The authors have no direct financial, consultant, or institutional conflict of interest pertaining to this article.