Clinical and Serologic Predictors of Relapse in Pemphigus Clinical and Experimental Dermatology

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• A total of 143 patients with a diagnosis of pemphigus vulgaris or pemphigus foliaceus and at least 36 months of follow-up were included in this study. A body surface area (BSA) of 15% or more was associated with a greater chance of relapse compared with BSA less than 15% (OR, 3.30; P = .02). Additionally, anti-desmoglein (Dsg) 1 positivity or anti-Dsg3 positivity at the time of remission versus both being negative at the time of remission was predictive of a greater risk of relapse (OR, 2.42; P = .01). Clinical findings such as patient age, sex, pemphigus subtype, cutaneous and mucosal involvement, and ocular involvement were not associated with relapse risk in this cohort.

• This study highlights the involvement of BSA and Dsg positivity at remission as two important predictors of pemphigus relapse. Interestingly, pemphigus subtype was not associated with a greater risk of relapse.

–  Alex Noble, MD

Written by



Mohsen Afarideh MD, MPH

Written by



Victoria P. Werth MD

Pemphigus is a life-threatening autoimmune blistering disease of the skin and mucosa. Almost 50% of patients do not achieve complete remission off therapy, and many experience relapse. Multiple relapses can occur over time with pemphigus. In this article, the authors discuss the significance of serologic and clinical factors to prognosticate first-episode relapses of pemphigus.

Their serologic subsetting of patients at diagnosis creates three homogeneous immunopathological categories (ie, anti–Dsg1-positive/ anti–Dsg3-positive, anti–Dsg1-positive/ anti–Dsg3-negative, and anti–Dsg1-negative/ anti–Dsg3-positive). Accordingly, failure to achieve anti-Dsg1 titer negativity at remission (on minimal to no therapy) predicted relapse in patients with positive titers of both anti-Dsg1 and anti-Dsg3, but not among those with exclusively positive anti-Dsg1 titers (ie, anti–Dsg1-positive/ anti–Dsg3-negative). By comparison, failure to achieve anti-Dsg3 titer negativity at remission predicted relapse in patients with exclusively positive anti-Dsg3 titers at diagnosis (ie, anti–Dsg3-positive/ anti–Dsg1-negative). Conversely, neither anti-Dsg1 nor anti-Dsg3 titer positivity at diagnosis or remission (when considered separately) were a significant predictor of relapse in the entire cohort. Of note, demographics (age, gender), pemphigus subtype (mucosal, cutaneous, mucocutaneous, foliaceous), the percentage of oral surface area involved, body site affected (nasal and laryngeal, anogenital, ocular), nor the use of induction adjuvant immunosuppressants predicted relapse across the three homogeneous serological subsets.

Body surface area (BSA) >15% was the only clinical correlate found to predict pemphigus relapse. However, BSA may be difficult to determine in patients with minimal surface area involvement. It is unclear if treatment with rituximab would affect serologic prediction of relapse (ie, more anti–Dsg1/3-negative patients at remission whose B cells would repopulate prior to relapse) as those patients were excluded. Considering the limited sample size, the role of clinical subtype in relapse prediction could not be established. In addition, multiple episodes of relapse were not taken into consideration. Searching for sensitive clinical/serologic markers of relapse in the anti–Dsg1-positive/ anti–Dsg3-negative group remains of high clinical interest.

Abstract

BACKGROUND

Pemphigus is an autoimmune bullous disease mediated by autoantibodies targeting epithelial cell-cell adhesion molecules. Predictors of relapse have not yet been clearly identified.

AIMS

To identify factors at diagnosis and during follow-up that could be predictors of relapse.

METHODS

Clinical and immunopathological data at diagnosis, clinical remission and first relapse from patients with pemphigus vulgaris or foliaceus and at least a 36-month follow-up were collected retrospectively. Based on the autoantibody profile at diagnosis, three serological patient subsets were devised: (i) anti-desmoglein (Dsg)1-positive and anti-Dsg3-negative; (iii) anti-Dsg1-negative and anti-Dsg3-positive; and (iii) anti-Dsg1-positive and anti-Dsg3-positive.

RESULTS

Data from 143 patients were collected. No significant differences were found between relapsers (n = 90) and nonrelapsers (n = 53) for time to remission or for anti-Dsg1 and anti-Dsg3 titres at diagnosis and remission. In the analysis of all patients, a higher risk of relapse was found for a body surface area (BSA) score of 3 compared with BSA < 3 (OR = 3.30, 95% CI 1.17-9.28; P = 0.02) and for a positive titre of either anti-Dsg1 or anti-Dsg3 autoantibodies at remission compared with both being negative (OR = 2.42, 95% CI 1.21-4.85, P = 0.01). In patients who were anti-Dsg3-positive and anti-Dsg1-negative at diagnosis, failure to achieve anti-Dsg3 negativity at clinical remission was a significant predictor of relapse (OR = 7.89, 95% CI 2.06-30.21; P < 0.01). Similarly, failure to achieve anti-Dsg1 negativity at clinical remission was a significant predictor of relapse in patients with both anti-Dsg1 and anti-Dsg3 positivity at diagnosis (OR = 5.74, 95% CI 1.15-28.61; P = 0.03), but not in those who were anti-Dsg1-positive/anti-Dsg3-negative at diagnosis (OR = 1.08, 95% CI 0.27-4.30; P = 0.91).

CONCLUSION

Regardless of pemphigus subtype, autoantibody titre negativity at clinical remission in patients classified based on their anti-Dsg1 and anti-Dsg3 profile at diagnosis and BSA were useful tools in predicting relapse.

Clinical and Experimental Dermatology

Clinical and serological predictors of relapse in pemphigus: a study of 143 patients

Clin Exp Dermatol 2021 Jul 20;[EPub Ahead of Print], G Genovese, CA Maronese, G Casazza, L Corti, L Venegoni, S Muratori, E Berti, D Fanoni, AV Marzano