A systematic review and meta-analysis of cutaneous manifestations in late- versus early-onset systemic lupus erythematosus

https://doi.org/10.1016/j.semarthrit.2016.01.004Get rights and content

Abstract

Objectives

Although systemic lupus erythematosus (SLE) most commonly occurs in reproductive-age women, some are diagnosed after the age of 50. Recognizing that greater than one-third of SLE criteria are cutaneous, we undertook a systematic review and meta-analysis to evaluate differences in cutaneous manifestations in early- and late-onset SLE patients.

Methods

We searched the literature using PubMed, CINAHL, Web of Science, and Cochrane Library. We excluded studies that did not include ACR SLE classification criteria, early-onset controls, that defined late-onset SLE as <50 years of age, or were not written in English. Two authors rated study quality using the Newcastle Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% CI) of cutaneous manifestations by age. Study heterogeneity was assessed using I2.

Results

Overall, 35 studies, representing 11,189 early-onset and 1727 late-onset patients with SLE, met eligibility criteria. The female:male ratio was lower in the late-onset group (5:1 versus 8:1). Most cutaneous manifestations were less prevalent in the late-onset group. In particular, malar rash [OR = 0.43 (0.35, 0.52)], photosensitivity [OR = 0.72 (0.59, 0.88)], and livedo reticularis [OR = 0.33 (0.17, 0.64)] were less common in late-onset patients. In contrast, sicca symptoms were more common [OR = 2.45 (1.91, 3.14)]. The mean Newcastle Ottawa Quality Scale score was 6.3 ± 0.5 (scale: 0–9) with high inter-rater reliability for the score (0.96).

Conclusions

Overall, cutaneous manifestations are less common in late-onset SLE patients, except sicca symptoms. Future studies should investigate etiologies for this phenomenon including roles of immune senescence, environment, gender, and immunogenetics.

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.

References (46)

  • M. Yaar et al.

    Fifty years of skin aging

    J Investig Dermatol Symp Proc

    (2002)
  • J. Boddaert et al.

    Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in the literature

    Medicine

    (2004)
  • J. Dimant et al.

    Systemic lupus erythematosus in the older age group: computer analysis

    J Am Geriatr Soc

    (1979)
  • J. Font et al.

    Systemic lupus erythematosus in the elderly: clinical and immunological characteristics

    Ann Rheum Dis

    (1991)
  • H. Hashimoto et al.

    Differences in clinical and immunological findings of systemic lupus erythematosus related to age

    J Rheumatol

    (1987)
  • E. Karoubi Nordon et al.

    Late-onset systemic lupus erythematosus: a new approach

    Lupus

    (2007)
  • S.K. Shaikh et al.

    Late-onset systemic lupus erythematosus: clinical and immunological characteristics

    Med J Malaysia

    (1995)
  • J. Wang et al.

    Systemic lupus erythematosus: a genetic epidemiology study of 695 patients from China

    Arch Dermatol Res

    (2007)
  • J. Antolin et al.

    Systemic lupus erythematosus: clinical manifestations and immunological parameters in 194 patients. Subgroup classification of SLE

    Clin Rheumatol

    (1995)
  • R. Cervera et al.

    Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1000 patients. The European Working Party on Systemic Lupus Erythematosus

    Medicine

    (1993)
  • I. Domenech et al.

    Systemic lupus erythematosus in 50 year olds

    Postgrad Med J

    (1992)
  • C.T. Ho et al.

    Late onset systemic lupus erythematosus in southern Chinese

    Ann Rheum Dis

    (1998)
  • S. Janwityanujit et al.

    Age-related differences on clinical and immunological manifestations of SLE

    Asian Pac J Allergy Immunol

    (1995)
  • L.T. Costallat et al.

    Systemic lupus erythematosus: clinical and laboratory aspects related to age at disease onset

    Clin Exp Rheumatol

    (1994)
  • S. Jacobsen et al.

    A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets

    Clin Rheumatol

    (1998)
  • M.M. Ward et al.

    A meta-analysis of the clinical manifestations of older-onset systemic lupus erythematosus

    Arthritis Rheum

    (1989)
  • A. Liberati et al.

    The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

    Br Med J

    (2009)
  • M.C. Hochberg

    Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus

    Arthritis Rheum

    (1997)
  • Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for assessing the...
  • M.D. Alonso et al.

    Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review

    Lupus

    (2012)
  • S. Appenzeller et al.

    Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study

    Lupus

    (2008)
  • S. Cartella et al.

    Evaluation of mortality, disease activity, treatment, clinical and immunological features of adult and late onset systemic Lupus erythematosus

    Autoimmunity

    (2013)
  • Chen T-L, Wong C-H, Lee C-S, Loo J-H, Lin M. Systemic lupus erythematosus in the elderly. Int J Gerontol 3:...
  • Cited by (36)

    • Pulmonary manifestations in late versus early systemic lupus erythematosus: A systematic review and meta-analysis

      2018, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      Late-onset SLE is a distinct classification that begins in patients ≥50 years old. Prior meta-analyses report significant differences in the clinical manifestations between late- and early-onset SLE patients, including fewer cutaneous manifestations and more sicca symptoms [1,2]. A recent meta-analysis demonstrated increased pulmonary manifestations in adult-onset lupus patients compared to childhood-onset patients, suggesting a higher risk with increasing age [3].

    • Cells to Surgery Quiz: July 2018

      2018, Journal of Investigative Dermatology
      Citation Excerpt :

      Treatment is intramuscular penicillin administered daily for a minimum of 10 days (Chartier & Grosshans, 1990). Systemic lupus erythematosus (SLE) is an autoimmune disease that most commonly affects women of reproductive age and has many cutaneous manifestations include photosensitivity, mucosal ulcers, and bilateral malar rash (Medlin, et al, 2016). The image shows a unilateral facial rash, and the eruption is more lateral than the typical location of the rash associated with SLE.

    • Systemic Lupus Erythematosus for Primary Care

      2018, Primary Care - Clinics in Office Practice
      Citation Excerpt :

      Cutaneous manifestations occur in most patients with SLE and often occur early in the disease course.24,25 One meta-analysis concluded that cutaneous manifestations may be more common in early-onset SLE, with the exception of sicca symptoms.26 Cutaneous lupus erythematosus (CLE) can be classified under acute CLE (ACLE) (photosensitive malar and macular rash), subacute CLE (SCLE) (photosensitive papulosquamous or annular lesions), and chronic CLE (CCLE) (discoid lupus erythematosus, lupus profundus/panniculitis, chilblain lupus, and lupus tumidus).25,27

    • Overview and clinical presentation

      2018, Dubois' Lupus Erythematosus and Related Syndromes
    View all citing articles on Scopus

    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.

    View full text