D1.106 - Dupilumab-Induced Systemic Eosinophilic Immune Activation Mimicking an EGPA-Like Prodrome: A Case Report

Background: Dupilumab, an IL-4Rα–blocking monoclonal antibody, blocks IL-4 and IL-13 signaling and is widely used in the management of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis, eosinophilic esophagitis, and others. Although usually well tolerated, there is an emerging body of evidence that dupilumab may cause systemic eosinophilia, eosinophilic pneumonia, autoimmune activation, and EGPA-like inflammatory syndromes. The proposed mechanisms include impairment of eosinophil trafficking secondary to decreased VCAM-1/ICAM-1 expression, the presence of an “IL-5–unopposed” state, and immune disequilibrium with Th1/Th17 upregulation.

Case Presentation: We describe the case of a 35-year-old female with asthma and recurrent CRSwNP who developed a severe systemic eosinophilic inflammatory reaction shortly after her first dose of dupilumab. The initial symptoms of erythematous rash, fever, arthralgia, and cervical lymphadenopathy progressed to hypereosinophilia (figure 1), pleuritic chest pain, microscopic hematuria, and bilateral pulmonary infiltrates. High-resolution CT showed findings suggestive of organizing pneumonia (figure 2). Extensive microbiologic and autoimmune evaluation, including ANCA, complements, anti-GBM, and lymph node biopsy, did not reveal any evidence of infection, granulomatous disease, or vasculitis; however, ANA was strongly positive. Her clinical course closely followed corticosteroid exposure: rapid improvement on steroids, deterioration after steroid withdrawal, and prompt recovery after re-initiation. Evaluation by pulmonology, rheumatology, and nephrology collectively favored dupilumab-induced eosinophilic immune activation with EGPA-like prodromal features.

Conclusion: This case demonstrates how dupilumab can cause severe eosinophilic immune dysregulation, closely mimicking early-phase EGPA. The use of IL-4/IL-13 pathway inhibitors is on the rise; hence clinicians must be vigilant for early systemic eosinophilic complications. Early recognition, prompt corticosteroid treatment, and longitudinal follow-up of eosinophils and organ involvement are crucial.