Steroid-Refractory Idiopathic Hypereosinophilic Syndrome with Prolonged Respiratory Failure Responsive to Mepolizumab

Background and Literature ReviewHypereosinophilic syndrome (HES) is a rare, heterogeneous group of disorders defined by persistent hypereosinophilia (>1,500 cells/µL) with eosinophil-mediated end-organ damage. Its estimated prevalence ranges from 0.36 to 6.3 per 100,000 individuals. Pulmonary involvement occurs in 40–60% of cases and most commonly presents as chronic cough or dyspnea. Acute respiratory failure requiring mechanical ventilation is uncommon and represents a severe manifestation. Glucocorticoids remain the first-line therapy and induce remission in approximately 85% of patients. However, nearly 15% demonstrate steroid-refractory or steroid-dependent disease. Mepolizumab, an anti–IL-5 monoclonal antibody, reduces eosinophil production and survival and has shown efficacy in decreasing disease flares and corticosteroid dependence, with reported remission rates of 57–76%. It is currently used as rescue therapy in steroid-refractory HES.Case SummaryA 73-year-old man presented with six weeks of progressive dyspnea and nonproductive cough. His medical history included coronary artery disease, stage 3 chronic kidney disease, and alcohol use disorder. Evaluation revealed a small pulmonary embolism, diffuse bilateral pulmonary opacities, lymphadenopathy, and marked eosinophilia peaking at 5,730/µL. His condition rapidly deteriorated, requiring intubation and intensive care unit (ICU) admission. He received pulse-dose methylprednisolone followed by high-dose oral prednisone.Despite aggressive steroid therapy, eosinophil counts rebounded to 3,470/µL by hospital day eight, and he experienced repeated failures to wean from mechanical ventilation. A tracheostomy was performed on day 21. Persistent eosinophilia despite steroids prompted initiation of mepolizumab 300 mg on day 24 after exclusion of secondary causes. Following treatment, eosinophil counts stabilized, and respiratory status improved. By day 41, he was successfully transitioned to a tracheostomy collar.ConclusionThis case illustrates a rare presentation of steroid-refractory idiopathic HES causing life-threatening respiratory failure. Mepolizumab resulted in hematologic stabilization and meaningful respiratory recovery. Early recognition of steroid resistance and timely initiation of biologic therapy may reduce morbidity and improve outcomes in severe HES.Figure 1.Eosinophil count of the patient throughout the hospital course. Stress dose steroids administered 11/10-11/15. Mepolizumab was administered 11/30.