A case of IgG4-related respiratory disease presenting as dupilumab-induced toxicity and severe asthma

Background IgG4-related disease (IgG4-RD) is a systemic immune-mediated disorder characterized by lymphoplasmacytic infiltration that can affect various organs, including lungs and bronchi. It may present as severe asthma with blood eosinophilia, which can delay the diagnosis. Case Presentation We report the case of a 60-year-old woman with a medical history of diabetes mellitus and a 10 pack-year smoking history. She was investigated for chronic cough, nasal polyposis and blood eosinophilia. Pulmonary function tests revealed a severe obstructive ventilatory defect, with an FEV₁/FVC ratio of 0.56 and an FEV₁ of 1.43 L (56% of the predicted value), reversible only after a course of oral corticosteroids. Eosinophilic granulomatosis with polyangiitis was ruled out based on a negative muscle biopsy and internal medicine evaluation. The patient subsequently developed severe asthma, for which biologics were required. After failure of anti-IL-5 therapies, dupilumab was initiated. One month later, she developed acute febrile respiratory failure with bronchocentric nodular opacities and peribronchovascular thickening on CT-scan. Bronchial biopsies showed dense IgG4⁺ plasma cell infiltration (IgG4⁺/IgG⁺ ≥40%). Serum IgG4 was elevated (5.18 g/L). Transparietal lung biopsy revealed a dupilumab-induced pulmonary vasculitis . In this context, this IgG4-RD with bronchial involvement was treated with high-dose corticosteroids, which led to rapid clinical improvement. Rituximab was introduced as a steroid-sparing agent, with favorable outcomes. Conclusions Severe eosinophilic asthma may be the initial manifestation of IgG4-RD involving the airways. This diagnosis should be considered in patients with corticosteroid-dependent asthma and abnormal chest imaging. Histopathological confirmation remains essential for the diagnosis and to guide treatment