Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

Jennifer E Hundt,Khalaf Kridin,Dana Tzur Bitan,Ralf J Ludwig,Kyle T Amber,Arnon D Cohen

doi:10.1007/s00403-021-02211-4

Abstract

The association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

Highlights

Bullous pemphigoid (BP) is the most prevalent subepidermal autoimmune bullous disease worldwide [1]
In a stratified analyses by age, sex, and ethnicity, melanoma was observed to predict the diagnosis of BP in patients older 80 years of age, males, and individuals of Jewish ethnicity
The current large-scale population-based study revealed that patients with a preexisting diagnosis of melanoma are at a 1.5-fold increased risk of developing BP

Summary

Introduction

Bullous pemphigoid (BP) is the most prevalent subepidermal autoimmune bullous disease worldwide [1]. The disease is characterized by the presence of circulating IgG. Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel autoantibodies against BP180 and BP230, hemidesmosomal proteins promoting dermal-epidermal cohesion [2, 3]. Binding of these autoantibodies initiates blister formation via dermal-epidermal separation, which has been shown to be directly pathogenic [4]. The disease is clinically characterized by tense bullae, often in conjunction with urticarial plaques, and characteristically affects elderly individuals aged over 70 years. The past few years yielded a prominent advance in elucidating the comorbidity profile of patients with BP owing to an increasing number of well-designed controlled observational studies [1, 6]

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