Granulomatous Dermatoses and Sarcoidosis/Sarcoid‐Like Disease During Dupilumab Therapy: A Phenotype‐Based Case‐Level Review

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Background Dupilumab, an interleukin‐4 receptor alpha antagonist, is widely used across Type 2 inflammatory diseases. Case reports have described granulomatous inflammation arising or worsening during treatment, but the reported phenotypes are scattered across dermatology, respiratory and allergy literature. Objective To characterise the clinical, histological and outcome spectrum of granulomatous dermatoses and sarcoidosis/sarcoid‐like disease reported during dupilumab therapy. Methods PubMed and Embase were searched from inception to 26 April 2026 using dupilumab and its brand/development names (Dupixent, REGN668 and SAR231893) combined with terms for sarcoidosis, sarcoid‐like reaction, drug‐induced sarcoidosis‐like reaction, granuloma, granuloma annulare, lichenoid‐granulomatous dermatitis, interstitial granulomatous dermatitis, granulomatous rosacea‐like reaction and noncaseating/non‐necrotising granuloma. Eligible reports, including conference abstracts with sufficient case‐level detail, described granulomatous dermatoses or sarcoidosis/sarcoid‐like disease arising or worsening during dupilumab therapy and provided patient‐level clinical, histological, radiological or outcome information. Results Seventeen reports (12 full publications and 5 conference abstracts) representing 18 patient‐level cases met the inclusion criteria. Six phenotype groups were identified: sarcoidosis/sarcoid‐like disease (11 cases), granuloma annulare (2), lichenoid‐granulomatous drug eruption (2 cases from 1 report), interstitial granulomatous dermatitis (1), granulomatous rosacea‐like reaction (1) and tattoo‐associated granulomatous dermatitis exacerbation (1). Biopsy or tissue sampling demonstrated granulomatous inflammation or a granulomatous‐pattern dermatosis in 15 of 18 cases. Latency ranged from approximately 1 month to 3 years. Positive rechallenge, the strongest attribution signal, was documented in two cases: sarcoid‐like disease and granulomatous rosacea‐like reaction. Conclusion Granulomatous inflammation during dupilumab therapy is a heterogeneous, postmarketing, case‐level phenomenon spanning six clinicopathological phenotypes. Recognition should prompt biopsy where feasible, exclusion of infection and mimics and careful assessment of attribution signals rather than reflexive drug discontinuation or premature causal labelling. Prospective pharmacovigilance and registry data are needed to clarify incidence, risk factors and mechanisms.

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