デュピルマブ初回投与後に発症した好酸球性多発血管炎性肉芽腫症例

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory rhinosinusitis characterized by elevated peripheral blood eosinophil counts, nasal polyps, and bronchial asthma. In recent years, anti-human IL-4/13 receptor monoclonal antibody (dupilumab) has become available as a new treatment option for patients with ECRS who are poorly controlled by existing treatments, such as surgery and steroid treatment. On the other hand, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis syndrome characterized by peripheral blood eosinophilia, peripheral neuritis, purpura, muscle and joint pain, heart disorder, gastrointestinal disorder, etc. Since patients with EGPA often exhibit symptoms of bronchial asthma and rhinosinusitis prior to manifesting vasculitis symptoms, it is difficult to distinguish patients with the early phase of EGPA from those with ECRS. We encountered a patient of ECRS who developed EGPA after the initial administration of dupilumab. The patient was a 55-year-old woman who presented with the chief complaints of nasal obstruction and olfactory disturbance. She was diagnosed as having severe ECRS with asthma and endoscopic sinus surgery was performed, but the nasal symptoms and polyps recurred. The nasal polyps shrank with the administration of oral steroids, but quickly enlarged upon discontinuation of the steroids. Because the manifestations of ECRS were poorly controlled with the existing treatments, we started the patient on treatment with dupilumab. However, the day after the first administration of dupilumab, the patient developed weakness and numbness in both legs. Blood tests showed an increase in the percentage of eosinophils in the peripheral blood from 28% to 55%, and serology for MPO-ANCA was positive. A nerve conduction study revealed evidence of mononeuritis multiplex, and the patient was diagnosed as having EGPA. Dupilumab was discontinued and steroid pulse therapy was administered, which led to improvement of the weakness and numbness in both legs, although both the symptoms persisted. Since serology for MPO-ANCA was also positive in stored blood prior to the dupilumab administration, it is suggested that dupilumab administration induced peripheral blood eosinophilia, leading to the onset of mononeuritis multiplex in the patient with EGPA.