The coexistence of pemphigus and systemic lupus erythematosus (SLE) had been reported anecdotally. Anti-desmoglein (Dsg)1 and anti-Dsg3 antibodies were detected concomitantly with antinuclear autoantibodies among blood donors. The aim of the current study was to study the association between pemphigus and SLE in Israeli patients and to synthesize existing data on this association in the current literature. The current study included two sections. Initially, a cross-sectional study was performed to compare pemphigus patients with age-, sex-, and ethnicity-matched control subjects regarding the prevalence of SLE using a real-life large-scale computerized database. Next, a systematic review and meta-analysis of similar observational studies in Medline, Embase, and Web of Science (1823–2017) was conducted. As for the cross-sectional study, a total of 1985 patients with pemphigus and 9874 controls were included in the study. The prevalence of SLE was slightly higher among patients with pemphigus as compared to controls (OR, 1.85; 95% CI, 0.89–3.82). In a sensitivity analysis that included patients who received pemphigus-related treatments, the association between pemphigus and SLE had been substantiated and was statistically significant (OR, 2.10; 95% CI, 1.00–4.48). In the meta-analysis section, three eligible studies, comprising 10,389 pemphigus patients met the eligibility criteria. The overall pooled multivariate OR was 2.50 (95% CI 1.54–4.07, I2 = 44.19%, P = 0.167) across all studies. In conclusion, the meta-analysis provides epidemiologic evidence that these B cell-driven diseases are significantly associated. Further research is required to elucidate the molecular mechanism underlying this association.
Pemphigus SLE Systemic lupus erythematosus Lupus Association Meta-analysis Systematic review
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
Conflict of interests
Prof. Arnon Cohen received research grants from Janssen, Novartis, AbbVie, Janssen, and Sanofi. Prof. Arnon Cohen served as a consultant, advisor, or speaker to AbbVie, Amgen, Boehringer Ingelheim, Dexcel pharma, Janssen, Kamedis, Lilly, Neopharm, Novartis, Perrigo, Pfizer, Rafa, Samsung Bioepis, Sanofi, Sirbal, and Taro. No funding was gained for the research.
Supplementary Figure 1Funnel plot for all the included studies. (DOCX 16 kb)
Malik M, Ahmed AR. Concurrence of systemic lupus erythematosus and pemphigus: coincidence or correlation? Dermatology. 2007;214:231–9.CrossRefGoogle Scholar
Parameswaran A, Attwood K, Sato R, Seiffert-Sinha K, Sinha AA. Identification of a new disease cluster of pemphigus vulgaris with autoimmune thyroid disease, rheumatoid arthritis and type I diabetes. Br J Dermatol. 2015;172:729–38.CrossRefGoogle Scholar
Chiu Y-W, Chen Y-D, Hua T-C, Wu C-H, Liu H-N, Chang Y-T. Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan. Eur J Dermatol. 2017;27:375–81.PubMedGoogle Scholar
Hsu DY, Brieva J, Sinha AA, Langan SM, Silverberg JI. Comorbidities and inpatient mortality for pemphigus in the U.S.A. Br J Dermatol. 2016;174:1290–8.CrossRefGoogle Scholar
Prüßmann J, Prüßmann W, Recke A, Rentzsch K, Juhl D, Henschler R, et al. Co-occurrence of autoantibodies in healthy blood donors. Exp Dermatol. 2014;23:519–21.CrossRefGoogle Scholar
Sezin T, Vorobyev A, Sadik CD, Zillikens D, Gupta Y, Ludwig RJ. Gene expression analysis reveals novel shared gene signatures and candidate molecular mechanisms between pemphigus and systemic lupus erythematosus in CD4+ T cells. Front Immunol. 2018;8:1992.CrossRefGoogle Scholar
Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Is there an association between pemphigus and hepatitis viruses? A population-based large-scale study. Immunol Res. 2017;65:1083–8.CrossRefGoogle Scholar
Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Association between pemphigus and neurologic diseases. JAMA Dermatol. 2018;154:281–5.CrossRefGoogle Scholar
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRefGoogle Scholar
Somers EC, Thomas SL, Smeeth L, Hall AJ. Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology. 2006;17:202–17.CrossRefGoogle Scholar
Szyper-Kravitz M, Marai I, Shoenfeld Y. Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity. Autoimmunity. 2005;38:247–55.CrossRefGoogle Scholar
McDonagh JE, Isenberg DA. Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus. Ann Rheum Dis BMJ Publishing Group. 2000;59:230–2.CrossRefGoogle Scholar
Ghandi N, Kamyab K, Attar SNG, Ghiasi M, Daneshpazhooh M, Karbakhsh M, et al. Antinuclear antibody in patients with pemphigus vulgaris: a case-control study. Br J Dermatol. 2012;167:107.Google Scholar
Blondin DA, Zhang ZH, Shideler KK, Hou HY, Fritzler MJ, Mydlarski PR. Prvalence of non-organ-specific autoantibodies in patients with pemphigus vulgaris. J Cutan Med Surg. 2009;13:82–7.CrossRefGoogle Scholar
Ippolito A, Wallace DJ, Gladman D, Fortin PR, Urowitz M, Werth V, et al. Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity. Lupus. 2011;20:250–5.CrossRefGoogle Scholar
Chan LS, Vanderlugt CJ, Hashimoto T, Nishikawa T, Zone JJ, Black MM, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. 1998;110:103–9.CrossRefGoogle Scholar