Eosinophilia

By Jane Liesveld, MD, University of Rochester ; Patrick Reagan, MD, University of Rochester Medical Center

NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

Eosinophilic Disorders
Eosinophil Production and Function
Eosinophilia
Hypereosinophilic Syndrome

Eosinophilia is defined as a peripheral blood eosinophil count > 500/μL. Causes and associated disorders are myriad but often represent an allergic reaction or a parasitic infection. Diagnosis involves selective testing directed at clinically suspected causes. Treatment is directed at the 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. Several compounds released by mast cells and basophils induce IgE-mediated eosinophil production. Such substances include eosinophil chemotactic factor of anaphylaxis, leukotriene B4, complement complex (C5-C6-C7), and histamine (over a narrow range of concentration).

Peripheral eosinophilia is characterized as

Mild: 500 to 1500/μL
Moderate: 1500 to 5000/μL
Severe: > 5000/μL

Mild eosinophilia itself does not cause symptoms, but levels ≥1500/μL may cause organ damage. Organ damage typically occurs because of tissue inflammation and reaction to the cytokines and chemokines released by the eosinophils as well as to immune cells which are recruited to the tissues. Although any organ may be involved, the heart, lungs, spleen, skin, and nervous system are typically affected (for manifestations see Table: Abnormalities in Patients With Hypereosinophilic Syndrome). Occasionally, patients with very severe eosinophilia (eg, eosinophil counts of >100,000/μL), usually with eosinophilic leukemia, develop complications when eosinophils form aggregates that occlude small blood vessels, causing tissue ischemia and microinfarctions. Manifestations typically include those of brain or lung hypoxia (eg, encephalopathy, dyspnea, respiratory failure).

Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in patients who do not have parasitic, allergic, or other causes of eosinophilia.

Clinical Calculator: Absolute Eosinophil Count

Etiology

Eosinophilia may be

Primary: A clonal proliferation of eosinophils associated with hematologic disorders such as leukemias and myeloproliferative disorders
Secondary: Caused by or associated with nonhematologic disorders (see Table: Important Disorders and Treatments Associated With Eosinophilia)
Idiopathic: Causes cannot be identified

The most common cause in the US is

Allergic or atopic disorders (typically respiratory or dermatologic)

Other common causes include

Infections (typically parasitic)
Certain tumors (hematologic or solid, benign or malignant)

Almost any parasitic invasion of tissues can elicit eosinophilia, but protozoa and noninvasive metazoa usually do not.

Of hematologic tumors, Hodgkin lymphoma may elicit marked eosinophilia, whereas eosinophilia is less common in non-Hodgkin lymphoma, chronic myelogenous leukemia, and acute lymphocytic leukemia.

The pulmonary infiltrates with eosinophilic syndrome comprise a spectrum of clinical manifestations characterized by peripheral eosinophilia and eosinophilic pulmonary infiltrates but is usually of unknown cause.

Patients with eosinophilic drug reactions may be asymptomatic or have various syndromes, including interstitial nephritis, serum sickness, cholestatic jaundice, hypersensitivity vasculitis , and immunoblastic lymphadenopathy.

Eosinophilia-myalgia syndrome is rare; the cause is unknown. However, in 1989, several hundred patients were reported to have developed this 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, including severe muscle pain, tenosynovitis, muscle edema, and rash, lasted weeks to months, and several deaths occurred.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare syndrome characterized by fever, rash, eosinophilia, atypical lymphocytosis, lymphadenopathy, and signs and symptoms related to end-organ involvement (typically, heart, lungs, spleen, skin, nervous system).

Important Disorders and Treatments Associated With Eosinophilia

Cause or Associated Disorder	Examples
Allergic or atopic disorders	Asthma Allergic bronchopulmonary aspergillosis Allergic rhinitis Atopic dermatitis Drug reactions (eg, to antibiotics or NSAIDs) Episodic angioedema with eosinophilia Milk-protein allergy Occupational lung disease Urticaria
Connective tissue, vasculitic, or granulomatous disorders (especially those involving the lungs)	Eosinophilic fasciitis Idiopathic eosinophilic synovitis Inflammatory bowel disease Polyarteritis nodosa Post myocardial infarction syndrome (Dressler syndrome) Progressive systemic sclerosis (scleroderma) Rheumatoid arthritis Sarcoidosis Sjögren syndrome SLE
Endocrine disorders	Adrenal hypofunction
Immune disorders (often with eczema)	Congenital immunodeficiency syndrome (eg, IgA deficiency, hyper-IgE syndrome, Wiskott-Aldrich syndrome) Graft-vs-host disease
Myeloproliferative disorders	Acute or chronic eosinophilic leukemia Acute lymphocytic leukemia (certain types) Chronic myelogenous leukemia Hypereosinophilic syndrome
Nonparasitic infections	Aspergillosis Brucellosis Cat-scratch disease Chlamydial pneumonia of infancy Coccidioidomycosis (acute) Infectious lymphocytosis Infectious mononucleosis Mycobacterial disease Scarlet fever
Parasitic infections (especially due to tissue-invasive metazoans)	Ascariasis Clonorchiasis Cysticercosis (caused by Taenia solium) Echinococcosis Fascioliasis Filariasis Hookworm infection Paragonimiasis Pneumocystis jirovecii infection Schistosomiasis Strongyloidiasis Toxocariasis Trichinosis Trichuriasis
Skin disorders	Dermatitis herpetiformis Exfoliative dermatitis Pemphigus Psoriasis
Syndromes of pulmonary infiltration with eosinophilia	Allergic bronchopulmonary aspergillosis Chronic eosinophilic pneumonia Eosinophilic granulomatosis with polyangiitis Löffler syndrome Tropical pulmonary eosinophilia
Tumors	Angioimmunoblastic T-cell lymphoma (previously known as angioimmunoblastic lymphadenopathy with dysproteinemia or AILD) in association with systemic symptoms and autoimmune hemolytic anemia Carcinomas and sarcomas of the lung, pancreas, colon, cervix, or ovary Hodgkin lymphoma Non-Hodgkin lymphomas
Miscellaneous	Cirrhosis Familial eosinophilia Peritoneal dialysis Radiation therapy

Evaluation

The number of possible causes and associated disorders is very large. Common causes (eg, allergic, infectious, or neoplastic disorders) should be considered first, but even they are often difficult to identify, so a thorough history and physical examination are always required.

History

The questions most likely to be helpful pertain to the following:

Travel (suggesting possible parasite exposure)
Allergies
Drug use
Use of herbal products and dietary supplements, including l-tryptophan
Systemic symptoms (eg, fever, weight loss, myalgias, arthralgias, rashes, lymphadenopathy)

Systemic symptoms suggest that a minor allergic or drug cause is less likely, and a detailed evaluation for an infectious, neoplastic, connective tissue, or other systemic disorder should be done. Other important parts of the history include family history of blood dyscrasias and a complete review of systems, including symptoms of allergies and pulmonary, cardiac, GI, and neurologic dysfunction.

Testing

Eosinophilia is typically recognized when CBC is done for other reasons. Additional testing often includes the following:

Stool ova and parasite testing
Other tests to detect organ damage or for specific causes based on clinical findings

In general, if a drug or allergic cause is not suspected based on clinical findings, 3 stool specimens should be examined for ova and parasites; however, 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).

Other specific diagnostic tests are determined by the clinical findings (particularly travel history) and may include chest x-ray, urinalysis, liver and kidney function tests, and serologic tests for parasitic and connective tissue disorders. If patients have generalized lymphadenopathy, splenomegaly, or systemic symptoms, blood tests are done. An elevated serum vitamin B₁₂ level or abnormalities on the peripheral blood smear suggest an underlying myeloproliferative disorder, and a bone marrow aspirate and biopsy with cytogenetic studies may be helpful. Also, if routine evaluation does not reveal a cause, tests are done to detect organ damage. Testing can include some of the tests previously mentioned as well as LDH and liver function tests (suggesting liver damage or possibly a myeloproliferative disorder), echocardiography, and pulmonary function tests. Once a specific cause has been determined, additional testing may be needed.

Treatment

Sometimes corticosteroids

For corticosteroid treatment of hypereosinophilic syndrome, see Hypereosinophilic Syndrome : Immediate therapy.

Drugs known to be associated with eosinophilia are stopped. Other identified causes are treated.

If no 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, connective tissue disorders, or parasitic infection) rather than primary. Such a trial is indicated if eosinophilia is persistent and progressive in the absence of a treatable cause.

Last full review/revision November 2016 by Jane Liesveld, MD; Patrick Reagan, MD