Cutaneous Adverse Reactions to IL-17 and IL-23 Inhibitors: A Clinical Review of Reaction Patterns.

Abstract

Introduction: IL-17 and IL-23 inhibitors have transformed the management of moderate-to-severe psoriasis and other inflammatory diseases through targeted immune modulation. Although generally well tolerated, an expanding spectrum of cutaneous adverse reactions has been reported, ranging from common paradoxical eruptions to rare immune-mediated dermatoses that may mimic primary inflammatory or autoimmune conditions.

Objectives: We present a narrative review of cutaneous adverse reactions associated with IL-17 and IL-23 inhibitors. This review aims to summarize reported reaction patterns, proposed mechanisms, clinical and histopathologic features, and current diagnostic and therapeutic considerations to support clinical decision-making.

Methods: We performed a narrative review of English-language literature describing cutaneous adverse reactions associated with IL-17, IL-23, and IL-12/23 inhibitors indexed in PubMed, Google Scholar, and Web of Science from database inception through August 2025. Clinical trials, observational studies, case series, case reports, and reviews were evaluated, and findings were synthesized according to reaction phenotype.

Results: Psoriasiform and eczematous eruptions represent the most frequently reported cutaneous adverse reactions and may be clinically and histologically indistinguishable from idiopathic dermatoses. Less commonly reported reactions include lupus-like syndromes, bullous pemphigoid, lichenoid drug reactions, granulomatous eruptions, and vasculitic presentations, including IgA vasculitis. Proposed mechanisms involve paradoxical alterations in immune signaling following cytokine blockade rather than direct drug toxicity, although definitive pathways remain incompletely understood. Management strategies vary according to severity and phenotype, ranging from topical therapies and continued biologic use to discontinuation of the offending agent and systemic immunosuppression.

Conclusions: IL-17 and IL-23 inhibitors are associated with a diverse spectrum of cutaneous adverse reactions that require recognition due to their potential overlap with primary dermatologic diseases. A structured approach to diagnosis and management may facilitate timely intervention. Further studies are needed to clarify incidence, risk factors, mechanisms, and evidence-based treatment strategies.