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.