Idiopathic hypereosinophilic syndrome: causes, symptoms, diagnosis, treatment

Idiopathic hypereosinophilic syndrome (disseminated eosinophilic collagenosis; eosinophilic leukemia; Löffler's fibroplastic endocarditis with eosinophilia) is a condition defined by peripheral blood eosinophilia greater than 1500/μL continuously for 6 months with organ involvement or dysfunction directly related to the eosinophilia, in the absence of parasitic, allergic, or other causes of eosinophilia. Symptoms are variable and depend on which organs are dysfunctional. Treatment begins with prednisone and may include hydroxyurea, interferon a, and imatinib.

Only a few patients with prolonged eosinophilia develop hypereosinophilic syndrome. Although any organ may be involved, the heart, lungs, spleen, skin, and nervous system are commonly affected. Cardiac involvement is a common cause of cardiac pathology and death. A hybrid tyrosine kinase, FIP1L1-PDGFR, has recently been shown to be important in the pathophysiology of the process.

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Symptoms idiopathic hypereosinophilic syndrome.

The symptoms are varied and depend on which organs are dysfunctional. There are 2 main types of clinical manifestations. The first type resembles a myeloproliferative disorder with splenomegaly, thrombocytopenia, elevated serum vitamin B12 levels, _and hypogranulation and vacuolization of eosinophils. Patients with this type often develop endomyocardial fibrosis or (less commonly) leukemia. The second type has manifestations of a hypersensitivity disease with angioedema, hypergammaglobulinemia, elevated serum IgE, and circulating immune complexes. Patients with this type of hypereosinophilic syndrome are less likely to develop cardiac disease requiring therapy and have a good response to glucocorticoids.

Disorders in patients with idiopathic thrombocytopenic syndrome

System	Occurrence	Manifestations
Constitutional	50%	Weakness, fatigue, anorexia, fever, weight loss, myalgia
Cardiopulmonary	> 70%	Restrictive or infiltrative cardiomyopathy, or mitral or tricuspid regurgitation with cough, dyspnea, heart failure, arrhythmias, endomyocardial disease, pulmonary infiltrates, pleural effusions, and mural thrombi and emboli
Hematological	> 50%	Thromboembolic phenomenon, anemia, thrombocytopenia, lymphadenopathy, splenomegaly
Neurological	> 50%	Diffuse encephalopathy with behavioral, cognitive and spastic disorders, peripheral neuropathy, cerebral embolism with focal lesions
Dermatological	>50%	Dermographism, angioedema, rash, dermatitis
Gastrointestinal tract	>40%	Diarrhea, nausea, cramps
Immunological	50%	Increased immunoglobulins (especially IgE), circulating immune complexes in serum sickness

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Diagnostics idiopathic hypereosinophilic syndrome.

The diagnosis is suspected in patients with eosinophilia without an apparent cause and with symptoms suggesting organ dysfunction. Such patients should undergo a prednisolone test to exclude secondary eosinophilia. Echocardiography should be performed to determine myocardial involvement. A complete blood count and blood smear help to clarify which of the two types of eosinophilia is present. Thrombocytopenia is present in 1/3 of patients with both types of eosinophilia.

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Treatment idiopathic hypereosinophilic syndrome.

Treatment is not necessary until there are manifestations of organ dysfunction, for which the patient is examined every 2 months. Therapy is aimed at reducing the number of eosinophils, based on the premise that the manifestations of the disease are a consequence of tissue infiltration by eosinophils or the release of their contents. Complications from local organ damage may require specific aggressive treatment (for example, damage to the heart valves may require valve replacement).

Therapy is initiated with prednisolone 1 mg/kg until clinical improvement or normalization of the eosinophil count is achieved. Adequate duration of therapy should be 2 months or more. When remission is achieved, the dose is slowly reduced over the next 2 months to a dose of 0.5 mg/kg/day, then switched to 1 mg/kg every other day. Further reduction should be until the minimum dose that controls the disease is achieved. If prednisolone intake for 2 months or more is ineffective, higher doses of prednisolone are required. If the prednisone dose cannot be reduced without exacerbation of the disease, hydroxyurea 0.5 to 1.5 g orally per day is added. The therapeutic goal is an eosinophil count of 4000-10,000/μL.

Interferon can also be used in patients where prednisolone is ineffective, especially in cases of heart disease. The dose is 3 to 5 million units subcutaneously 3 times a week, depending on clinical efficacy and tolerance to side effects. Discontinuation of interferon therapy may lead to an exacerbation of the disease.

Imatinib, an oral protein kinase inhibitor, is a promising treatment for eosinophilia. The therapy has been shown to normalize eosinophil counts within 3 months in 9 of 11 treated patients.

Surgical and medical treatment is necessary for signs of cardiac involvement (eg, infiltrative cardiomyopathy, valvular disease, heart failure). Thrombotic complications may require antiplatelet agents (eg, aspirin, clopidogrel, ticlopidine); anticoagulants are indicated for left ventricular mural thrombosis or transient ischemic attacks that do not respond to aspirin.

Forecast

Hypereosinophilic syndrome has a poor prognosis, with death usually due to organ dysfunction. Chronic therapy may improve the prognosis.

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