Acquired eosinophilia can be classified into secondary (cytokine-driven reactive phenomenon), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories [
2]. In 1975 Chusid et al. described diagnostic criteria for idiopathic HES that remain in use today. These are blood eosinophilia of >1500 cells per microliter for more than six consecutive months, absence of an underlying cause of hypereosinophilia despite extensive diagnostic evaluation, and organ damage or dysfunction as a result of local release of the toxic contents of eosinophils [
1]. HES affects mostly men between 20 and 50 years of age, with a peak in the 4
th decade of life [
3,
4]. There are no published data regarding its incidence/prevalence, although the syndrome is considered rare in adults and very rare in children.
Clinical manifestations of HES are markedly heterogeneous as the disease can either be completely asymptomatic or involve multiple organs. In essence, any organ is vulnerable to eosinophilia-associated tissue damage. Thromboembolic disease involving the cardiac chambers and/or both the venous and arterial vessels is not infrequent [
2]. Cardiac involvement occurs in more than 75% of patients with HES and is the major cause of morbidity and mortality [
6]. Cardiac involvement in HES usually follows three stages. The first is an acute necrotic stage. This stage is usually neither recognized clinically nor diagnosed, like in our case. In this stage there is damage to the endocardium and infiltration of the myocardium with eosinophils and lymphocytes with histopathological evidence of myocardial necrosis and eosinophil degranulation and eosinophil micro abscesses [
3,
7]. The second stage concerns thrombosis with formation of thrombi along the damaged endocardium of either one or both ventricles and occasionally in the atrium. Outflow tracts near the aortic and pulmonic valves are usually spared, although rarely thrombus may involve these valves and thrombus may form on atrioventricular valve leaflets [
3,
8‐
10]. This stage is found in those with a mean 10-month duration of eosinophilia [
3]. In the third late fibrotic stage progressive scarring may lead to entrapment of chordae tendineae resulting in mitral and/or tricuspid valve regurgitation and endomyocardial fibrosis producing a restrictive cardiomyopathy [
3].
To diagnose HES and Löffler endocarditis, echocardiography enables sufficient detection of thickened endocardium and intraventricular thrombus. Nevertheless, acute necrotic stage can come along with absolute normal echocardiographic findings [
3]. Endomyocardial thickening is seen in 68% of patients on echocardiography and is progressive [
11]. Apical thrombus in the presence of normal apical contraction is one of the main clues in suspected Löffler’s endomyocarditis [
12]. There are three primary goals for the management of HES: 1) reduction of peripheral and tissue levels of eosinophils; 2) prevention of end-organ damage; and 3) prevention of thrombo-embolic events in patients at risk [
13,
14]. Patients without progressive organ system dysfunction typically do not require specific treatment, however, these patients should be monitored closely [
14]. Corticosteroids were initially the mainstay of HES treatment and are currently recommended as first-line therapy [
15,
16]. Cytotoxic agents like hydroxyurea are indicated in HES subsets with corticosteroid resistance or when corticosteroid tapering is necessary [
16]. Interferon-alpha is an immunomodulator that reduces Th2-mediated IL-5 production, synthesis of GM-CSF and release of eosinophil-specific neurotoxin and eosinophil cationic protein and indirectly inhibits eosinophil differentiation [
5,
13,
17]. It is recommended for use in HES patients with organ damage and corticosteroid/cytotoxic treatment failure [
17,
18]. Allogenic stem cell transplantation has also been reported to be a potentially curative therapy. It is the ultimate therapeutic measure in case of therapeutic refractoriness or intolerance to available therapies or in patients who present with progressive life-threatening end-organ damage. The optimal preparative regime is not well established and it is associated with major morbidity and even mortality [
19,
20]. Several therapies are currently under investigation as potential HES therapies, like Mepolizumab, a fully humanized monoclonal IgG anti-IL5 antibody. The secondary treatment should be directed at cardiac complications, e.g., heart failure and the presence of intracardial thrombus. In the view of subclinical progression of the cardiac involvement, especially in the primary stage of HES, our case suggests very early and aggressive anticoagulation, regardless of the initial (negative) cardiac evaluation. Occasionally, surgical therapies are needed for cardiovascular complications. Surgical experience of patients with valvular dysfunction secondary to HES is limited [
21]. Valve replacement is most often performed but the choice between a mechanical or biological prosthesis in this setting poses a difficult problem. Mechanical valves have a high incidence of recurrent obstructive thrombosis and therefor a bioprosthesis is recommended despite associated restrictive cardiomyopathy [
6].