Myeloproliferative Hypereosinophilic Syndrome with Concomitant Ischemic Events
Authors: Aleman Roxanne T , Deleveaux Spencer , Pandya Mauna B 
Published: November 2021

Abstract

Background:
Eosinophils are versatile reactionary cells that play a key role in the inflammatory response. Excessive proliferation and aggregation of eosinophils have been implicated in the pathogenesis of ischemic neurologic and cardiac events. We present a rare case of hypereosinophilic syndrome (HES) in a patient hospitalized for simultaneous acute cerebrovascular accident (CVA) and acute coronary syndrome.
Case:
A 53-year-old male with past medical history of hypertension and diabetes mellitus presented with new onset bifrontal headache, right arm numbness and apraxia, and concurrent typical angina. On physical examination, he had small non-tender raised nodules on the bilateral upper and lower limbs. MRI of the brain demonstrated multifocal infarcts in a watershed distribution. Biochemical investigation revealed rising troponins. Splenomegaly of 16.4 cm was found on CT imaging. He was admitted for management of acute CVA and non-ST segment elevation myocardial infarction (NSTEMI). Complete blood count (CBC) revealed leukocytosis (34.4 K/mcL) with an eosinophilia of 85% and an absolute eosinophil count (AEC) of 29.2 x 10 3 eosinophils/µL. Serum tryptase was 29.2 µg/L. The patient was started on a high dose steroid with subsequent resolution of his neurologic and cardiac symptoms. Due to high suspicion for HES, FISH panel and bone marrow biopsy were performed. A small focus of marrow on his biopsy showed abundant eosinophils and bland spindle cells (&gt;15 mast cells in aggregate). FISH panel was positive for 4q12 rearrangement, consistent with a FIP1L1/PDGFRA fusion mutation. Skin biopsy of his lesions demonstrated superficial and deep inflammation with eosinophils. He was diagnosed with myeloproliferative HES with features of mastocytosis and started on imatinib.
Discussion:
The defining features of HES consist of eosinophilia greater than 1500/µL for greater than 6 months with evidence of eosinophil induced tissue infiltration and injury. The ability of eosinophils to induce pathologic outcomes is influenced by a variety of parameters, including the number of eosinophils present, their location, and the degree of activation. Published data suggests that neurologic and cardiac ischemic events occur in HES patients with a higher leukocyte count and AEC than what we present with in this case. Our patient meets the main lab criteria of HES and our case highlights that simultaneous clinical manifestations can occur in the absence of markedly elevated peripheral eosinophilia. As with most cases involving unexplained hypereosinophilia, a wide range of diagnostic testing was necessary. The presence of a PDGFRA fusion mutation established a clonal disorder, supporting the diagnosis of myeloproliferative HES variant. The presence of eosinophils and the lack of mast cells on skin biopsy further supports myeloproliferative HES variant rather than a true systemic mastocytosis. Despite recent advances in molecular and immunologic therapies, treatment for HES remains challenging due to the wide variety of etiological classifications necessitating targeted treatments. At the time of submission, KIT mutation analysis is pending. Identification of a KIT D816V mutation would support use of midostaurin or the recently approved avapritinib for treatment of overlap syndrome.

Disclosures
No relevant conflicts of interest to declare.