Hypereosinophilic syndrome (HES) is characterized by a persistently elevated eosinophil count associated with eosinophil-related end-organ damage and thromboembolic events, in the absence of an identifiable cause. We present a case of idiopathic HES with evidence of peripheral and tissue eosinophilia while on high dose prednisone, associated with muscle tension dysphonia, colitis, and jackhammer esophagus. The patient was treated with the interleukin-5 inhibitor, Mepolizumab, with resolution of symptoms including dyspnea, diarrhea and dysphonia.