Two Cases of Peculiar Hypereosinophilic Syndrome Treated with Mepolizumab

Hypereosinophilic syndromes (HES) are challenging heterogeneous disorders. We describe two cases of uncommon HES, treated with the monoclonal anti-IL-5 antibody mepolizumab. Patient 1, a 34-year-old man, and patient 2, a 57-year-old woman, referred to our Center complaining about recurrent episodes of edema of the extremities, with significant weight gain, partial functional defect and severe weakness. Marked hypereosinophilia was repeatedly detected. The autoimmunity panel, IgE, C4 resulted normal. The evaluation for hematologic, allergic, infectious diseases including bone marrow biopsy with cytogenetic analysis-immunophenotyping,viral panel, prick/patch tests and imaging provided inconclusive results. Interestingly, the exams of patient 1 showed hyper-IgM, IgM monoclonal components and IgM-cryoglobulinemia. The diagnosis of Gleich syndrome was suggested. In both cases IL-5 and eosinophil cationic protein (ECP) were elevated: IL-5 264.2 and 84.10 pg/ml, nv < 7.8; ECP 192 and 171 mcg/l, nv < 15 respectively. Off label mepolizumab was started, with subcutaneous administrations twice a month. Both patients initially showed clinical-laboratory improvement (from 27970/mm3 to 10171/mm3 eosinophils in patient 1, from 6340/mm3 to 850/mm3 eosinophils in patient 2). Steroids were tapered, mepolizumab dose was increased (200 mg in patient 1, 300 mg in patient 2 twice a month). Patient 1 experienced minor recurrences and, also due to the lack of compliance, mepolizumab was withdrawn. Patient 2 developed mild erythematous lesions. Punch biopsy revealed a diffuse eosinophilic inflammatory infiltration. Biologicals targeted to eosinophilic growth factors open a new area of intervention for HES, potentially allowing steroid sparing strategies. Further investigation is needed to evaluate the correct treatment regimens.