Eosinophilic myocarditis in hypereosinophilic syndrome

Abstract

A 49-year-old woman presented with cough, fatigue, stomach pain, and fevers to 38.0 °C. An echocardiogram showed a mildly reduced left ventricular ejection fraction and global hypokinesis. A CBC was remarkable for a leukocyte count of 21.4 × 103 μL−1 with a relative and absolute eosinophil count of 67% and 14.4 × 103 μL−1, respectively. The serum IgE concentration was 290 IU/mL (normal, 0–150 IU/mL). An endomyocardial biopsy of the right ventricle revealed abundant, focally degranulating eosinophils infiltrating the myocardium in both perivascular and interstitial patterns (Image 1A, H&E stain, 600×). There was associated multifocal myocyte damage and drop-out, compensatory myocyte hypertrophy, and significant interstitial and replacement fibrosis, as highlighted by expanded blue areas on a trichrome stain (Image 1B, 200×). The myocardium also showed scattered CD4+ T cells but virtually no CD8+ T cells or CD20+ B cells. A bone marrow biopsy revealed a hypercellular marrow with trilineage maturation and a prominent component of mature-appearing eosinophils comprising 60–70% of total cellularity (Image 1C, H&E stain, 600×). Cytogenetic analysis revealed a normal 46,XX karyotype. FISH testing was negative for BCR-ABL1, PDGFRA, and PDGFRB rearrangements. Because of documented cardiac tissue damage, a diagnosis of idiopathic hypereosinophilic syndrome (HES) was deemed most appropriate [1]. Our patient was treated with 60 mg of oral prednisone per day starting on hospital day 8 (Image 1D, arrow), achieving a near-normal eosinophil count on day 18 (dashed line, upper limit of normal). Response to steroids is thought to indicate an overall better prognosis. Approximately one third of patients, however, will not respond to steroids. Hydroxyurea and interferon alpha are currently second-line drugs of choice and can be complemented by attempts of high dose imatinib, monoclonal antibodies against IL-5 (mepolizumab) or CD52 (alemtuzumab), or hematopoietic stem cell transplantation [2]. Myocardial involvement is a common and serious complication of HES, potentially resulting in death due to cardiac fibrosis, congestive heart failure, and arrhythmia [3]. A fraction of patients with idiopathic HES likely represent neoplastic processes that are not recognized by currently available standard molecular assays. Genomic approaches to personalized pathology, such as high- resolution arrays or whole genome sequencing, will undoubtedly uncover many of these aberrations in the near future.