Hypereosinophilic Syndrome (HES)

At a glance

HES is a myeloproliferative disorder characterized by the simultaneous existence of (1) eosinophil count greater than 1500/mm³ for more than 6 months, (2) absence of any known cause of eosinophilia, and (3) with involvement of the heart, nervous system, and bone marrow (benign eosinophilia is excluded). Patients without symptoms of chronic heart failure and responding well to prednisone have a good prognosis. However, the mortality rate rises in patients with anemia.

Synonym

Idiopathic Hypereosinophilic Syndrome.

History

Leukoproliferative disorder of unknown origin characterized by overproduction of eosinophils that result in multiple organ damage. First described by Hardy and Anderson in 1968.

Classification

In the heart, there are two forms of the Hypereosinophilic Syndrome:

• Endomyocardial Fibrosis (Davies Disease): Mostly observed in tropical areas.

• Löffler’s Endocarditis: Does not have any geographic predisposition.

Incidence

The estimated prevalence of HES is 1.9:100,000 people. No racial predilection is reported, but male-to-female ratio is 9:1 (male predominance). Individual affected are aged between 20 and 50 years. Survival rate is 80% at 5 years and 42% at 10 years.

Genetic inheritance

None.

Pathophysiology

The etiology of this syndrome is unknown, but it is characterized by proliferation of eosinophils. These cells damage tissue, especially cardiac and neural tissue, by release of peroxidase and neurotoxin. The production of eosinophil is regulated by several cytokines (IL-3, GM-CSF, IL-5). Usually, eosinophils reach areas of inflammation and quickly undergo apoptosis after degranulation. In HES, eosinophils survive longer in the tissues, thus increasing the amount of damage they can inflict because they store (and release) toxic cationic proteins, which are the primary mediators of tissue damage. The most serious complication of HES is cardiac involvement (myocardial fibrosis and congestive heart failure); however, hypereosinophilia alone is insufficient to cause cardiac damage.

Diagnosis

Leukocytosis with eosinophilia. Bone marrow examination is required to rule out eosinophilic leukemia. Treatable parasitic infections must be sought. Some cases previously diagnosed as HES involved malignant transformation of eosinophils, but these constitute a minority and malignant evolution and are not a feature of HES. Pulmonary chest radiograph must be obtained to confirm the presence of lung eosinophilic infiltration.

Clinical aspects

HES is a heterogenous disease process. Multiple clinical manifestations may occur simultaneously or individually. Central nervous system (CNS) dysfunction (confusion, delirium, coma, dementia), congestive heart failure, arrhythmias, pulmonary infiltrates/effusion, nonproductive cough, hepatosplenomegaly, anemia and/or thrombocytopenia, anorexia, weight loss, fatigue, nausea, abdominal pain, diarrhea, pruritic rash, fever, night sweats, hepatosplenomegaly, peripheral neuritis, and venous thrombosis. Most commonly diagnosed between 20 and 50 years of age. It is rare in children.