DISCUSSION
The hypereosinophilic syndrome (HES) constitutes a rare hematological group of disorders defined by the association of hypereosinophilia (absolute eosinophil count >1.5 x 109/L) with eosinophil mediated organ damage and/or dysfunction in the absence of other etiologies of eosinophilia including parasitic infection and allergies4.
The incidence and prevalence of HES are not well characterized. The Surveillance, Epidemiology and End Result (SEER) database recorded a crude incidence of ~0.035 per 100 000 over a five year period (2001-2005). The syndrome is more common in men than women (male: female ratio 1.47) and rates increased with age to a peak in the range of 65 to 74 years. As seen in this case, the HES may result from the novel fusion of tyrosine kinase FIP1L1-PDGRA genes as a result of chromosomal deletion on 4q12 which has more frequently been detected in males2.
The varied clinical presentations of HES reflect the heterogeneous nature of the disease. Essentially, all organs may be susceptible to the effects of sustained eosinophilia and the heart is no exception. Cardiac disease (unrelated to hypertension, Rheumatic heart disease and atherosclerosis) was identified in 20% of patients (37/188) of patients in a clinical analysis of data taken from 2001-20061.
Essentially, the cardiac pathology of HES has been divided into three stages: acute necrosis, thrombosis, and fibrosis. The acute necrotic stage is characterized by eosinophilic infiltration into the myocardium and degradation with release of toxic cationic proteins leading to myocardial necrosis5. The stimulus for thrombosis in the second stage is ventricular wall vascular damage leading to exposure of von Willebrand factor, collagen, and tissue factor (TF) that ultimately lead to generation of a fibrin thrombus6. The majority of patients who have HES may not be diagnosed with cardiac involvement until the final pathological stage where they present with scarring of the chordae tendinae and endocardium leading to a restrictive or dilated cardiomyopathy and progressive valvular incompetence most commonly from regurgitant atrioventricular valves7.
Eosinophilic myocarditis may present in many different ways, ranging from asymptomatic cases to life-threatening conditions such as cardiogenic shock or sudden cardiac death due to malignant ventricular arrhythmias. In this case, our patient presented with eosinophilic myocarditis which an uncommon initial presentation. However, there was high clinical suspicion in the setting of his febrile illness, pleuritic chest pain and elevated cardiac biomarkers. Elevations in serum troponin levels can be sensitive indicators of early and ongoing eosinophil-associated myocardial damage in forms of HES8. Additionally, peripheral hypereosinophilia remained the only initial clinical clue to suggest eosinophilic myocarditis in this patient. However, there are cases reported where peripheral hypereosinophilia is not present initially and found solely on endomyocardial biopsy9. It is also recommended to assess serum tryptase and Vitamin B12 levels since increased concentrations support a diagnosis of myeloproliferative disorder. Although EKG and ECHO are both non-specific for the diagnosis of eosinophilic myocarditis, it was done to rule out other sinister causes of chest pain.
In the acutely ill patient, endomyocardial biopsy is the gold standard but can lead to significant complications such as ventricular perforation, arrhythmia or conduction abnormalities10. Additionally, patchy or focal myocarditis can lead to significant sampling error which limits its effectiveness. As such, there is now an emerging role for cardiac magnetic imaging for diagnosing eosinophilic myocarditis11. However, its use is constrained by high expense and limited availability. In this case, given that our patient had a positive tissue biopsy showing showed chronic myeloproliferative neoplasm with hypereosinophilia, we opted to initiate treatment based on the clinical diagnosis.
Corticosteroids have long been the standard treatment for HES and EM. The goal of corticosteroid therapy is to prevent or reduce eosinophil-mediated organ damage12. Additionally, the early initiation of steroid therapy can achieve substantial improvements in clinical outcomes, prognosis and long-term survival. However, as seen in this case, it may not always be clinically feasible to do so when there is need to rule out other credible etiologies of chest pain such as acute coronary syndrome. Our patient had significant improvement of symptoms with prednisone dosed at 1mg/kg/day. Additionally, there was a substantial decrease in peripheral eosinophilia with initiation of Imatinib in the outpatient setting.
In conclusion, eosinophilic myocarditis is a rare initial presentation of hypereosinophilic syndrome. Peripheral eosinophilia is a valuable clue to point clinicians in the direction of eosinophilic myocarditis as a possible diagnosis. In patients with high clinical suspicion for acute myocarditis and confirmed peripheral eosinophilia, timely diagnosis and treatment is imperative to avoid the catastrophic consequence of irreversible fibrotic changes to the cardiac tissue.