Study: One-Third of Pemphigus Cases Deviate From Classic Desmoglein Compensation Model
Key Takeaways
- Nearly one-third of patients with pemphigus demonstrated clinical, serologic, or histopathologic findings that did not align with the desmoglein compensation hypothesis (DCH).
- Concordance with DCH was highest in mucocutaneous pemphigus vulgaris, while mucosal-only disease frequently showed discordant anti-desmoglein antibody profiles.
- The findings suggest that additional pathogenic mechanisms beyond anti-desmoglein antibodies may influence disease phenotype.
New research published in the International Journal of Dermatology suggests that while the desmoglein compensation hypothesis (DCH) explains many classic presentations of pemphigus, nearly one-third of patients exhibit clinical, serologic, or histopathologic features that fall outside the traditional model.
Investigators conducted a bicentric retrospective study of 106 patients with confirmed pemphigus, including 93 with pemphigus vulgaris (PV) and 13 with pemphigus foliaceus (PF), evaluating relationships among clinical phenotype, histopathologic split level, and anti-desmoglein (Dsg)1 and Dsg3 IgG antibody profiles.
Study Finds Frequent Exceptions to Classic Pemphigus Model
Among patients with PF, 61.5% demonstrated isolated anti-Dsg1 IgG positivity consistent with DCH, although histopathologic findings varied, with subcorneal, suprabasal, and dual-level splits observed. In PV, suprabasal acantholysis remained the predominant histopathologic finding, occurring in 80.6% of patients.
The greatest agreement with DCH occurred in mucocutaneous PV, where 74.7% of patients demonstrated dual anti-Dsg1 and anti-Dsg3 positivity. However, discordance was common in mucosal PV. Only 37.5% of patients with mucosal-only disease exhibited the expected isolated anti-Dsg3 antibody profile. Investigators also identified patients with cutaneous-only PV who demonstrated dual antibody positivity despite suprabasal histopathologic splits.
"While DCH explains many classic presentations, nearly one-third of patients in our cohort exhibited discordant clinical, serologic, or histologic features," the authors wrote. "These findings highlight the need for more comprehensive models of pemphigus pathogenesis that incorporate antibody titers, affinity, subclass, and non-desmoglein targets."
The authors note that additional immunologic factors beyond anti-Dsg1 and anti-Dsg3 antibodies may better explain disease heterogeneity and warrant further investigation.
Source
De D, Chatterjee D, Mehta H, et al. International Journal Dermatology. Published online July 1, 2026. Doi:10.1111/ijd.70549