A previously healthy 7-year-old male presented with acute onset of painful cyanosis of his fingers and toes. His eosinophil count was found to be markedly elevated at 17 k/μL. He had no known drug exposures and no history of respiratory or atopic disease. Workup for malignancy and parasitic infection was negative. A skin biopsy revealed eosinophilic vasculitis, and the patient was found to be c-ANCA positive.
Hypereosinophilic syndrome (HES) is a rare disorder characterized by marked peripheral hypereosinophilia (absolute eosinophil count > 1.5 k/μL) causing end-organ dysfunction. Once clonal disorders, parasitic infection, drug exposures, and other more frequent causes of eosinophilia have been excluded, other subtypes of HES should be considered, including eosinophilic granulomatosis with polyangiitis (EGPA) and idiopathic HES (I-HES).
EGPA is one of the ANCA-associated vasculitides classically characterized by asthma, eosinophilia, and vasculitis. Given the patient’s degree of eosinophilia and ANCA positivity, a diagnosis of EGPA was considered, however, the patient did not fulfill full diagnostic criteria owing to his lack of respiratory involvement. I-HES, which is a diagnosis of exclusion once other causes of eosinophilia have been ruled out, was thus also considered, though it does not classically present with ANCA positivity nor vasculitic complications.
The patient started on pulse steroids with successful lowering of eosinophil counts and improvement in ischemia. Quickly into the steroid taper, however, his eosinophils again rose and ischemia returned, necessitating the use of a steroid-sparing agent. Given the patient’s overlapping I-HES and EGPA features, mepolizumab was chosen, as it has been shown to effectively treat both conditions, albeit in older patients. Mepolizumab is an antibody directed against IL-5, a known driver of eosinophilia. The patient was given 100 mg of subcutaneous mepolizumab, after which eosinophil count reached zero and ischemia resolved. Although an off-label use given his age, he continues on monthly mepolizumab, and eosinophils have remained suppressed. Read the entire case.