The occurrence of drug-induced sarcoidosis secondary to dupilumab

SESSION TITLE: Diffuse Lung Disease Case Report Posters 13 SESSION TYPE: Case Report Posters PRESENTED ON: 10/09/2023 02:10 pm - 02:55 pm INTRODUCTION: Dupilumab is an IL-4α receptor monoclonal antibody used to treat a variety of Th-2 inflammatory disorders, including eosinophilic asthma. Rarely, dupilumab has been implicated in the development of erythema nodosum and recently with systemic sarcoidosis-like syndromes. Herein is described a case in which a patient developed EN and granulomatous lymphadenopathy consistent with a dupilumab-induced systemic sarcoidosis-like syndrome. CASE PRESENTATION: A 50-year-old female was evaluated for severe eosinophilic asthma and aspirin-exacerbated respiratory disease (AERD) with nasal polyps. Dupilumab therapy was initiated with improvement in AERD symptoms and nasal polyp size. One month after starting dupilumab, the patient reported intermittent blurry vision and tender erythematous nodules and plaques on the shins. Erythema nodosum (EN) was diagnosed by dermatology and dupilumab was discontinued with resolution of EN. Serologic evaluation for an alternate underlying trigger was unrevealing, and chest imaging revealed a peri-lymphatic pattern of lung nodules with hilar and mediastinal lymphadenopathy. Bronchoscopy with biopsy confirmed numerous noncaseating granulomata and multinucleated giant cells with negative GMS, AFB, and Fite staining, consistent with sarcoidosis. DISCUSSION: Drug-induced sarcoidosis-like reactions (DISRs) are systemic granulomatous syndromes that are clinically indistinguishable from sarcoidosis and temporally associated with a new medication. DISRs most frequently affect the lungs and skin, occurring 1-3 months after exposure to the offending agent. Numerous medications have been associated with DISR and it has been hypothesized that the immunomodulatory effect of dupilumab may result in a Th1-Th2 imbalance that can promote granuloma genesis and induce a sarcoidosis-like syndrome. While dupilumab is generally well tolerated, and adverse effects are most often injection site reactions and ocular symptoms, cases of EN and systemic granulomatous syndromes have been reported. This patient experienced a common ocular adverse effect, and simultaneously developed a new granulomatous lymphadenopathy and EN, after dupilumab initiation with clinical resolution of EN after medication cessation. The rapid development of an uncommon systemic granulomatous syndrome that is temporally associated with medication use with clinical improvement after drug cessation, and recent reports of similar pharmacopathologies, is highly suspicious for dupilumab-induced sarcoidosis or sarcoidosis-like reaction. CONCLUSIONS: Granulomatous syndromes temporally associated with new medication use should prompt consideration of drug-induced sarcoidosis. Dupilumab may trigger a drug-induced sarcoidosis-like reaction. REFERENCE #1: Mustin DE, Cole EF, Blalock TW, Kuruvilla ME, Stoff BK, Feldman RJ. Dupilumab-induced erythema nodosum. JAAD Case Rep. 2021;19:41-43. Published 2021 Nov 17. doi:10.1016/j.jdcr.2021.11.007 REFERENCE #2: Chopra A, Nautiyal A, Kalkanis A, Judson MA. Drug-Induced Sarcoidosis-Like Reactions. Chest. 2018;154(3):664-677. doi:10.1016/j.chest.2018.03.056 REFERENCE #3: Belhomme N, Gaignon T, Jouneau S, et al. Drug-induced granulomatosis: is dupilumab the new kid on the block?. J Eur Acad Dermatol Venereol. 2020;34(7):e312-e313. doi:10.1111/jdv.16218 DISCLOSURES: No relevant relationships by Maryssa Miller No relevant relationships by Ivana Milojevic No relevant relationships by Sowmya Swamy No relevant relationships by Christopher Walker