Pemphigus and rheumatoid arthritis: A systematic review and meta‐analysis

Abstract

Dear Editor, Pemphigus is a group of rare autoimmune bullous dermatosis of stratified squamous epithelia characterized by the presence of IgG autoantibodies directed against epithelial desmosomal adhesion molecules. This leads to the disruption of the cell to cell adhesion, resulting in acantholysis and intraepidermal blisters of the skin and mucosal surfaces. It has been noted anecdotally in several case reports that the prevalence of rheumatoid arthritis (RA) and pemphigus may be coexisted, however, the significance of the association remains elusive. We conducted a systematic review and meta-analysis to assess the association between pemphigus and RA. The systematic review and meta-analysis were conducted and reported in accordance with the recommended PRISMA guidelines, using Ovid Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club, Database of Abstracts of Review of Effectiveness (DARE) and EMBASE from their dates of inception to 12th October 2020. We combined the terms “pemphigus foliaceus”, “pemphigus vulgaris”, or “pemphigus” combined with “rheumatoid arthritis”, “acantholysis”, as either key words or MeSH terms. Eligible studies were those comparing RA cases in pemphigus vs controls. Pemphigus cases included pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, and drug-induced pemphigus identified by clinical diagnosis with either direct or indirect immunofluorescence staining or enzyme-linked immunosorbent assay. Abstracts, conference presentations, case reports, reviews and studies without controls were excluded. Odds ratio (OR) was used in statistical analysis for this study. In view of the limited studies with small sample sizes and anticipated variances, a random effect model was utilized to decrease the heterogeneity between studies. Analyses were performed using Review Manager Version 5.3 (Cochrane Collaboration, Oxford, United Kingdom). The Newcastle-Ottawa Scale was used to evaluate the quality of the studies (NOS). Sensitivity analysis based on case-controlled studies were conducted to eliminate the selection bias of cross-sectional studies. A total of 897 articles were identified through the search strategy. Applying inclusion and exclusion criteria, five studies were included in the quantitative meta-analysis (Table 1). Our result demonstrated a significant association between pemphigus and RA (OR 1.56, 95% CI 1.04-2.33, P = .03) in adult patients. The majority weightage was contributed by Narla et al (55.1%) followed by Parameswaran et al (19.8%) and Chiu et al (11.7%) (Figure 1). In the risk of bias assessment, three (Narla et al, Chiu et al, Hsu et al) out of five studies were assessed low risk of bias (Table 1). However, our sensitivity analysis based on case-controlled studies reported no significant association between pemphigus and RA (studies = 3; OR 1.24, 95% Cl 0.70-2.20, P = .03, I = 44%) (Figure 2). Substantial heterogeneity across the studies may introduce variance to the finding.