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Eosinophilia

By

Jane Liesveld

, MD, James P. Wilmot Cancer Institute, University of Rochester Medical Center

Last full review/revision Jun 2020| Content last modified Jun 2020
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Eosinophilia is defined as a peripheral blood eosinophil count > 500/mcL (> 0.5 × 109/L). 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 Eosinophil Production and Function Eosinophils are granulocytes (white blood cells that contain granules in their cytoplasm) derived from the same progenitor cells as monocytes-macrophages, neutrophils, and basophils. They are... read more . 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/mcL (0.5 to 1.5 × 109/L)

  • Moderate: 1500 to 5000/mcL (1.5 to 5 × 109/L)

  • Severe: > 5000/mcL (> 5 × 109/L)

Mild eosinophilia itself does not cause symptoms, but levels ≥ 1500/mcL (> 1.5 × 109/L) may cause organ damage if they persist. 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 that 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 Abnormalities in Patients With Hypereosinophilic Syndrome Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the... read more ).

Occasionally, patients with very severe eosinophilia (eg, eosinophil counts of > 100,000/mcL [> 100 × 109/L]), 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 Hypereosinophilic Syndrome Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the... read more 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.

Etiology of Eosinophilia

Eosinophilia may be

The most common cause of eosinophilia in the US is

  • Allergic or atopic disorders (typically respiratory or dermatologic)

Other common causes of eosinophilia 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.

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).

Table
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Evaluation of Eosinophilia

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, gastrointestinal (GI), and neurologic dysfunction.

Physical examination

General physical examination should focus on the heart, skin, and neurologic and pulmonary systems. Certain physical findings may suggest causes or associated disorders. Examples include rash (allergic, dermatologic, or vasculitic disorders), abnormal lung findings (asthma, lung infections, or syndromes of pulmonary infiltration with eosinophilia), and generalized lymphadenopathy or splenomegaly (myeloproliferative disorders or cancer).

Testing

  • Stool ova and parasite testing

  • Other tests to detect organ damage or for specific causes based on clinical findings

Other specific diagnostic tests are determined by the clinical findings (particularly travel history) and may include chest x-ray, urinalysis, liver and kidney 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.

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 lactate dehydrogenase (LDH) and liver tests (suggesting liver damage or possibly a myeloproliferative neoplasm Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as an increased number of platelets, red blood cells (RBCs), or white blood cells (WBCs)... read more ), echocardiography, and pulmonary function tests. When hypereosinophilic syndrome is suspected, additional diagnostic evaluation Diagnosis Hypereosinophilic syndrome is a condition characterized by peripheral blood eosinophilia with manifestations of organ system involvement or dysfunction directly related to eosinophilia in the... read more may be needed. Once a specific cause has been determined, additional testing also may be needed.

Evaluation reference

  • 1. Larsen RL, Savage NM: How I investigate eosinophilia. Int J Lab Hematol 41:153–161, 2019. doi: 10.1111/ijlh.12955

Treatment of Eosinophilia

  • Sometimes corticosteroids

Drugs known to be associated with eosinophilia are stopped. Other identified causes are treated. Asthma mediated by eosinophils can sometimes be treated with antibodies against IL-5 (eg, mepolizumab, reslizumab) or with antibodies against the IL-5 receptor such as benralizumab (1 Treatment reference Eosinophilia is defined as a peripheral blood eosinophil count > 500/mcL (> 0.5 × 109/L). Causes and associated disorders are myriad but often represent an allergic reaction or a parasitic infection... read more Treatment reference ).

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.

Treatment reference

  • 1. Pelaia C, Calabrese C, Vatrell A, et al: Benralizumab: from the basic mechanism of action to the potential use in the biological therapy of severe eosinophilic asthma. Biomed Res Int 2018. doi doi.org/10.1155/2018/4839230

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Eosinophilia
Eosinophilia is defined as a peripheral blood eosinophil count of > 500/mcL. The most common causes of eosinophilia are allergic or atopic disorders. Other causes include solid or hematologic tumors. In which of the following hematologic tumors is eosinophilia most marked?
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