Paradoxical eruptions to targeted therapies in dermatology: A systematic review and analysis

Abstract

Background: Antibody-based therapies that inhibit proinflammatory cytokine signaling are commonly used in dermatology. Paradoxically, these medications may induce or exacerbate inflammatory disorders.

Objective: To summarize the spectrum of manifestations, incidence, timing, potential mechanisms of, and general management approaches to paradoxical cutaneous reactions induced by cytokine-targeted antibodies in dermatology.

Methods: We performed a systematic review and analysis of published cases of cutaneous paradoxical reactions (PRs) reported in association with tumor necrosis factor α, interleukin (IL) 12/23 (p40), IL-17A/17R, IL-23 (p19), and IL-4Rα inhibitors.

Results: We identified 313 articles reporting 2049 cases of PRs. Tumor necrosis factor α inhibitors resulted in 91.2% (1869/2049) of all cases, followed by IL-17/17R (3.5%), IL-4Rα (2.7%), IL-12/23 (2.4%), and IL-23 (0.01%) inhibitors. Psoriasiform and eczematous eruptions were the most commonly reported, but a wide spectrum of patterns were described. Phenotypically overlapping reaction patterns were common. Time to onset typically ranged from weeks to months but could occur more than a year later. Improvement or resolution upon discontinuation of the inciting drug was common.

Limitations: This was a retrospective analysis.

Conclusions: Familiarity with the clinical features of PRs from cytokine-blocking antibodies may facilitate efficient recognition and management.

Keywords: IL-17 inhibitor; IL-23 inhibitor; TNF-alpha inhibitor; dupilumab; lupus; paradoxical eruption; paradoxical psoriasis; psoriasis; sarcoidosis; ustekinumab.