A case of eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma

Abstract

Background:Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis in cases when there are no findings that clearly suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as severe asthma and refractory chronic rhinosinusitis. Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with severe asthma and chronic rhinosinusitis with nasal polyps after the administration of dupilumab, few studies have examined the development of EGPA.Case presentation:We report a case of 61-year-old woman treated with dupilumab for refractory eosinophilic chronic rhinosinusitis and eosinophilic otitis media complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis suggesting EGPA before the initiation of dupilumab therapy. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. Blood test showed an increase in the levels of eosinophils and re-elevation of MPO-ANCA levels after the administration of dupilumab therapy. Therefore, dupilumab therapy was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. Conclusion:To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, to measure MPO-ANCA in patients with multiple eosinophilic disorders prior to the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.