Population-level analysis reveals increased odds of hypertrophic/keloidal scarring in pemphigus

Summary: Abstract Body: The existence of a hypertrophic form of pemphigus, Pemphigus vegetans, has been long appreciated. Moreover, multiple case reports spanning nearly three decades have documented instances of hypertrophic and/or keloidal scarring (“excessive scarring”) in individuals with pemphigus. Emerging evidence has implicated the Th2 pathway—long linked to pemphigus pathogenesis—in the development of excessive scarring. Despite these suggestive links, population-level evidence on an association between pemphigus and excessive scarring is lacking. To address this, we conducted a retrospective cohort study using TriNetX’s Global Collaborative Network. Our pemphigus cohort was compared to control cohorts identified by the absence of ICD-10 codes for pemphigus and the presence of psoriasis (a non-Th2 disease), atopic dermatitis (AD) (a Th2-mediated disease), or healthy individuals. Comparisons were propensity score-matched for age, gender, race, and ethnicity. The outcome of interest was the ICD-10 code for excessive scarring. Among >12,000 pemphigus patients and >36,000 matched controls, pemphigus patients consistently showed significantly increased odds of excessive scarring when compared to psoriasis (OR=1.645, 95% CI 1.213–2.231), and AD (OR=1.506, 95% CI 1.119–2.026). Compared to healthy controls, pemphigus patients demonstrated a threefold increased odds (OR=3.172, 95% CI 2.155–4.67), suggesting that excessive risk is even higher in pemphigus than other immune-mediated diseases compared to healthy controls. Given that excessive scarring is more frequent among individuals with skin of color (SoC), we stratified our comparison between pemphigus and healthy cohorts by ancestry. We did not find a significant difference (p=0.528) between ancestry-stratified cohorts, however, point estimates modestly preferred elevated risk in SoC patients. Our results underscore a novel, race-independent, link between pemphigus and excessive scarring. Justin Baroukhian¹, Kristina Seiffert-Sinha¹, Animesh A. Sinha¹ 1. Dermatology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States. Clinical Research: Epidemiology and Observational Research