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Eosinophilia is defined as a peripheral blood eosinophil count > 450/μL. Causes are myriad but often represent an allergic reaction or parasitic infection. Diagnosis involves selective testing directed at clinically suspected underlying causes. Treatment is directed at the underlying cause.

Eosinophilia has features of an immune response: an agent such as Trichinella spiralis invokes a primary response with relatively low levels of eosinophils, whereas repeated exposures result in an augmented or secondary eosinophilic response.

Factors that decrease the eosinophil count include β-blockers, corticosteroids, stress, and (sometimes) bacterial and viral infections. Several compounds released by mast cells and basophils induce IgE-mediated eosinophil production, eg, eosinophil chemotactic factor of anaphylaxis, leukotriene B4, complement complex (C5-C6-C7), and histamine (over a narrow range of concentration).

Eosinophilia may be primary (idiopathic) or secondary to numerous disorders (see Table 1: Eosinophilic Disorders: Important Causes of Secondary Eosinophilia). In the US, allergic or atopic diseases are the most common causes; the most common conditions are respiratory and skin diseases. Almost any parasitic invasion of tissues can elicit eosinophilia, but protozoa and noninvasive metazoa usually do not.

Table 1
Important Causes of Secondary Eosinophilia Cause Examples Allergic or atopic diseases Asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, occupational lung disease, urticaria, eczema, atopic dermatitis, milk-protein allergy, episodic angioedema with eosinophilia, drug reactions Parasitic infestations (especially tissue-invasive metazoans) Trichinosis, visceral larva migrans, trichuriasis, ascariasis, strongyloidiasis, hookworm infection, clonorchiasis, paragonimiasis, fascioliasis, cysticercosis (Taenia solium), echinococcosis, filariasis, schistosomiasis, Pneumocystis jiroveci (formerly P. carinii) infection Nonparasitic infections Aspergillosis, brucellosis, cat-scratch fever, infectious lymphocytosis, chlamydial pneumonia of infancy, acute coccidioidomycosis, infectious mononucleosis, mycobacterial disease, scarlet fever Tumors Carcinomas and sarcomas (lung, pancreas, colon, cervix, ovary), Hodgkin lymphoma (Hodgkin's disease), non-Hodgkin lymphomas, immunoblastic lymphadenopathy Myeloproliferative disorders Chronic myelocytic leukemia Syndromes of pulmonary infiltration with eosinophilia Simple pulmonary eosinophilia (Löffler's syndrome), chronic eosinophilic pneumonia, tropical pulmonary eosinophilia, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome Skin disorders Exfoliative dermatitis, dermatitis herpetiformis, psoriasis, pemphigus Connective tissue, vasculitic, or granulomatous disorders (especially those involving the lungs) Polyarteritis nodosa, RA, sarcoidosis, inflammatory bowel disease, SLE, scleroderma, eosinophilic fasciitis, Dressler's syndrome Immune disorders (often with eczema) Graft-vs-host disease, congenital immunodeficiency syndrome (eg, IgA deficiency, hyper-IgE syndrome, Wiskott-Aldrich syndrome) Endocrine disorders Adrenal hypofunction Miscellaneous Cirrhosis, radiation therapy, peritoneal dialysis, familial eosinophilia, use of l-tryptophan

Of the neoplastic diseases, Hodgkin lymphoma (Hodgkin's disease) may elicit marked eosinophilia, whereas eosinophilia is less common in non-Hodgkin lymphoma, chronic myelocytic leukemia, and acute lymphoblastic leukemia. Of solid tumors, ovarian cancer is the leading cause. The pulmonary infiltrates with eosinophilia syndrome comprises a spectrum of clinical manifestations characterized by peripheral eosinophilia and eosinophilic pulmonary infiltrates (see Interstitial Lung Diseases: Eosinophilic Pulmonary Diseases; see Histiocytic Syndromes: Langerhans' Cell Histiocytosis) but is usually of unknown cause. Patients with eosinophilic drug reactions may be asymptomatic or have a variety of syndromes, including interstitial nephritis, serum sickness, cholestatic jaundice, hypersensitivity vasculitis, and immunoblastic lymphadenopathy. Several hundred patients were reported to have developed an eosinophilia-myalgia syndrome after taking l-tryptophan for sedation or psychotropic support. This syndrome was probably caused by a contaminant rather than by l-tryptophan. The symptoms (severe muscle pain, tenosynovitis, muscle edema, skin rash) lasted weeks to months, and several deaths occurred.

Diagnosis and Treatment

When the CBC indicates eosinophilia, an absolute eosinophil count is rarely needed. A medical history, emphasizing travel, allergies, and drug use, is taken, and physical examination is performed. Specific diagnostic tests are determined by the clinical findings and may include chest x-ray, urinalysis, liver and kidney function tests, and serologic tests for parasitic and connective tissue diseases. Stool should be examined for ova and parasites, although negative findings do not rule out a parasitic cause (eg, trichinosis requires a muscle biopsy; visceral larva migrans and filarial infections require other tissue biopsies; duodenal aspirates may be needed to exclude specific parasites, eg, Strongyloides sp—see Nematodes (Roundworms): Strongyloidiasis). An elevated serum vitamin B₁₂ or low WBC alkaline phosphatase level or abnormalities on the peripheral smear suggest an underlying myeloproliferative disorder, in which case a bone marrow aspirate and biopsy with cytogenetic studies may be helpful.

If no underlying cause is detected, the patient is followed for complications. A brief trial with low-dose corticosteroids may lower the eosinophil count if eosinophilia is secondary (eg, to allergy or parasitic infestation) rather than malignant. Such a trial is indicated if eosinophilia is persistent and progressive in the absence of a treatable cause.

Idiopathic Hypereosinophilic Syndrome

(Disseminated Eosinophilic Collagen Disease; Eosinophilic Leukemia; Löffler's Fibroplastic Endocarditis with Eosinophilia)

Idiopathic hypereosinophilic syndrome is a condition defined by peripheral blood eosinophilia > 1500/μL persisting ≥ 6 mo with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the absence of parasitic, allergic, or other causes of eosinophilia. Symptoms are myriad, depending on which organs are dysfunctional. Treatment begins with prednisone and may include hydroxyurea, interferon-α, and imatinib.

Only some patients with prolonged eosinophilia develop idiopathic hypereosinophilic syndrome. Although any organ may be involved, the heart, lungs, spleen, skin, and nervous system are typically affected. Cardiac involvement often causes morbidity and mortality. A novel fusion tyrosine kinase, FIP1L1-PDGFR, has been recognized as contributing to the pathophysiology.

Symptoms, Signs, and Diagnosis

Symptoms are diverse and depend on which organs are dysfunctional (see Table 2: Eosinophilic Disorders: Abnormalities in Patients With Idiopathic Hypereosinophilic Syndrome). The clinical syndrome follows 2 broad patterns. The first pattern involves a myeloproliferative disorder with splenomegaly, thrombocytopenia, elevated serum vitamin B₁₂ levels, and hypogranular or vacuolated eosinophils. Patients with this pattern often develop endomyocardial fibrosis or (less commonly) frank leukemia. The second pattern involves a hypersensitivity-type illness with angioedema, hypergammaglobulinemia, elevated serum IgE, and circulating immune complexes. Patients with this pattern develop heart disease less often, usually require no therapy, and respond well to corticosteroids.

Table 2
Abnormalities in Patients With Idiopathic Hypereosinophilic Syndrome System Prevalence Manifestations Constitutional ≈ 50% Weakness, fatigue, anorexia, fever, weight loss, myalgias Cardiopulmonary > 70% Restrictive or infiltrative cardiomyopathy or mitral or tricuspid regurgitation with cough, dyspnea, heart failure, arrhythmias, endomyocardial disease, pulmonary infiltrates, and pleural effusions, and mural thrombi with emboli Hematologic > 50% Thromboembolic phenomena, anemia, thrombocytopenia, lymphadenopathy, splenomegaly Neurologic > 50% Diffuse encephalopathy with altered behavior and cognitive function and spasticity, peripheral neuropathy, and cerebral emboli with focal deficits Dermatologic > 50% Dermatographism, angioedema, rashes, pruritus GI > 40% Diarrhea, nausea, abdominal cramps Immunologic ≈ 40% Elevated immunoglobulins (especially IgE), circulating immune complexes with serum sickness

The diagnosis is suspected in patients with eosinophilia without an obvious cause and with symptoms suggesting organ dysfunction. Such patients should undergo testing as above to exclude any disorders causing eosinophilia secondarily. They should also undergo echocardiography to detect myocardial involvement. CBC and peripheral smear help determine which of the 2 broad patterns of disease exists. About ¹⁄₃ of patients with either of these patterns are thrombocytopenic at presentation.

Prognosis and Treatment

Hypereosinophilic syndrome used to have a poor prognosis, with death usually resulting from organ dysfunction. Current therapy has improved prognosis.

Treatment is not needed unless organ system dysfunction occurs; otherwise, the patient is evaluated q 3 to 6 mo. All therapy is designed to reduce the eosinophil count on the premise that disease manifestations result from tissue infiltration by eosinophils or the release of their contents. Focal organ system complications may need specific aggressive treatment (eg, valvular heart disease may mandate valve replacement).

Initial therapy is prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
1 mg/kg po once/day until clinical improvement and a normal eosinophil count are achieved; an adequate trial of prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
should last ≥ 2 mo. If remission occurs, the dose is tapered slowly over the next 2 mo to 0.5 mg/kg once/day and then switched to 1 mg/kg once every other day. Further tapering should be done slowly to the lowest dosage that controls the disease. If ≥ 2 mo of prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
is ineffective, if higher doses of prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
are required, or if the dose cannot be tapered without inducing exacerbation, then hydroxyurea Some Trade Names
HYDREA
Click for Drug Monograph
0.5 to 1.5 g po once/day is added; an eosinophil count of 4,000 to 10,000/μL is the therapeutic goal.

Interferon-α is also used for patients in whom prednisone Some Trade Names
DELTASONE
Click for Drug Monograph
is ineffective, particularly for those with cardiac lesions. The dose is 3 to 5 million units sc 3 times/wk, depending on clinical efficacy and tolerance to adverse effects. Stopping interferon-α may exacerbate the disease.

Imatinib Some Trade Names
GLEEVEC
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, an oral protein kinase inhibitor, is promising; it has been shown to normalize eosinophil counts for 3 mo in 9 of 11 patients treated.

Drug therapy and surgery may be required for cardiac manifestations (eg, infiltrative cardiomyopathy, valvular lesions, heart failure). Thrombotic complications may require the use of antiplatelet drugs (eg, aspirin Some Trade Names
BUFFERIN
ECOTRIN
GENACOTE
Click for Drug Monograph
, clopidogrel Some Trade Names
PLAVIX
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, ticlopidine Some Trade Names
TICLID
Click for Drug Monograph
); anticoagulation is indicated if a left ventricular mural thrombus is present or if transient ischemic attacks persist despite use of aspirin Some Trade Names
BUFFERIN
ECOTRIN
GENACOTE
Click for Drug Monograph
.

Last full review/revision November 2005

Content last modified November 2005