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

BACKGROUND Antibody-based therapies that inhibit pro-inflammatory 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, 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 reported in association with TNF-α, IL-12/23 (p40), IL-17A/17R, IL-23 (p19), and IL-4Rα inhibitors. RESULTS We identified 313 articles reporting 2049 cases of paradoxical reactions. TNF-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 are described. Phenotypically overlapping reaction patterns were common. Time to onset typically ranges from weeks to months, but can occur up to 1-2 years later. Improvement or resolution upon discontinuation of the inciting drug is common. LIMITATIONS This is a retrospective analysis. CONCLUSIONS Dermatologists should be familiar with the clinical features of paradoxical reactions from cytokine blocking antibodies to facilitate efficient recognition and management.