Citations

Abstract Background Immune checkpoint inhibitors (ICIs) directed against PD-1, PD-L1, and CTLA-4 augment antitumor immune responses but may also induce unintended immune activation, resulting in immune-related adverse events (irAEs). Cutaneous manifestations of irAEs are among the most common, ranging from mild eruptions to severe autoimmune blistering disorders (AIBDs). Although bullous pemphigoid (BP) is the most reported ICI-related autoimmune bullous disorder (irAIBD), data on the spectrum, and management of other ICI-associated AIBDs remain limited. Understanding these reactions is crucial to managing treatment interruptions and influencing oncologic outcomes. Objective This study aims to comprehensively characterize ICI-associated irAIBDs by examining demographics, clinical presentation, disease severity, therapeutic approaches, treatment responses, clinical outcomes, and mortality. Methods A single-institution retrospective chart review was conducted, using a text-based database search from 2011–2023. Adult patients (≥18 years) with biopsy-confirmed AIBDs attributed to ICIs were included. Demographic, oncologic, and immunotherapy details, as well as clinical, histopathologic, and immunofluorescence characteristics of AIBDs, were reviewed. Treatment approaches, outcomes, and mortality data were analyzed. Results Forty-four patients with irAIBDs were identified, predominantly representing males (29, 65.9%) with a mean age of 70.4 years (range: 62-80 years). Lung carcinoma (12, 27.2%) and melanoma (9, 20.4%) were the most frequent underlying malignancies, and pembrolizumab (25, 56.8%) was the most common agent. Bullous pemphigoid (BP) accounted for most cases (36, 81.8%), followed by lichen planus pemphigoides (LPP) (6, 13.6%), with one case each of mucous membrane pemphigoid (MMP) and linear IgA bullous dermatosis (LABD). Pruritus was reported in most (42, 9%) patients, and upper (36, 81.8%), lower (32, 72.2%) extremities and the chest (34, 77.2%) were most often involved. Eosinophilic infiltration was present in most (23, 81.8%) of BP cases, and linear IgG and C3 deposition were the predominant immunofluorescence patterns in BP. Most patients received topical (34, 77.2%) and/or systemic corticosteroids (32, 72.7%), while 16 required at least temporary ICI discontinuation. Four BP (4, 9.1%) patients were treated with dupilumab. Other systemic agents used included doxycycline (22, 50%), intravenous immunoglobulin (IVIG) (5, 11.3%), rituximab (6, 13.6%), dapsone (1, 2.2%), mycophenolate mofetil (1, 2.2%), methotrexate (1, 2.2%), and colchicine (1, 2.2%). Three cases with Grade 3 severity necessitated permanent ICI discontinuation. Clinical stabilization (24, 54.5%) or remission of the irAIBD (16, 36.3%) was achieved in most cases. One death (2.2%) was attributed to sepsis in a patient with severe irAIBD. Conclusion ICI-associated AIBDs are uncommon but clinically significant complications. Most patients in our cohort continued ICI therapy during management of their irAIBD, while others required temporary or permanent interruption. These findings highlight the importance of prompt recognition and multidisciplinary management of these uncommon toxicities.

This article describes clinical, serologic, and histopathologic features of the first North American cohort of patients with positive anti-p200 serology identified at Mayo Clinic, Rochester, Minnesota, USA and Beutner Laboratories, Buffalo, New York, USA. Forty-seven patients were identified with positive p200 laminin beta 4 autoantibodies, detected with either immunoglobulin (Ig)G or IgG4 modified indirect immunofluorescence on HEK293 cells transfected with recombinant laminin beta.

Abstract Darier disease (DD) is a rare autosomal dominant genodermatosis. This comprehensive review, developed by the Darier Disease International Task Force (DDITF), consolidates current knowledge on the genetic basis, molecular pathophysiology, clinical presentation, diagnosis and management of DD, offering a global perspective that unites shared expertise. The disease arises from pathogenic variants in the ATP2A2 gene, which encodes sarco/endoplasmic reticulum Ca 2+ ‐ATPase isoform 2 (SERCA2), leading to disrupted calcium homeostasis and impaired desmosomal integrity. Clinically, DD is classified based on lesion type (classic vs. non‐classic) and is often accompanied by significant extracutaneous manifestations. Management remains challenging and requires a multifaceted approach, including topical therapies, systemic retinoids and lifestyle modifications. Emerging treatments that target the underlying molecular mechanisms offer promise for improved outcomes. This review aims to provide an updated reference and practical guidance for clinicians involved in the care and study of DD.

Abstract Cutaneous IgM/IgG immune complex vasculitis is a newly recognized provisional subtype of single-organ vasculitis that is clinically indistinguishable from IgA vasculitis. This retrospective case series evaluated the presence, clinicopathological characteristics and outcomes of patients with IgM and/or IgG dominance or codominance on direct immunofluorescence testing (2010–23). This review represents only the second study to date to characterize this population. Early analysis of 14 patients revealed that cutaneous IgM/IgG immune complex vasculitis was mainly skin limited, and treatment with topical and oral corticosteroids typically resulted in complete resolution without recurrence. Additionally, this study demonstrated that nearly two-thirds (64%) of patients with cutaneous small-vessel vasculitis with IgM and/or IgG dominance or codominance on direct immunofluorescence were ultimately found to have an underlying autoimmune connective tissue disease, cryoglobulinaemia, antineutrophil cytoplasmic antibody-associated vasculitis, infection or a drug-related cause. Therefore, it is imperative that clinicians perform a thorough investigation of this unique population to evaluate for potential underlying diseases and/or triggers.

The focus of this review is the clinical and pathologic presentations of hereditary cancer syndromes with cutaneous manifestations, with the goal of providing a reference for the multidisciplinary care teams involved in the diagnosis and management of these conditions. Advancements in genomics have led to newly recognized syndromes and a deeper understanding of established syndromes. We focus on those with the most relevant cutaneous manifestations. Clinical and histopathologic images provide visual context for these findings, many of which are rare. We summarize the established literature and incorporate new research and noteworthy case reports.

Patzelt et al. previously characterized dermal-binding autoantibodies using an indirect immunofluorescence (IIF) mosaic assay with cells transfected with p200-laminin β4, laminin-332 or collagen VII subunits among specimens showing a dermal pattern on IIF using salt-split skin (IIF-SSS) and IgG. This study expanded testing to include specimens with either a dermal or mixed pattern on IIF-SSS and demonstrated improved test sensitivity with modified testing methods.