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Eosinophilia

By

Jane Liesveld

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

Reviewed/Revised Jan 2024
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Topic Resources

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. Eosinophilia can be reactive (secondary) or the primary manifestation of a hematologic disorder. 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 ).

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).

Idiopathic 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 a parasitic or allergic disorder, a clonal disorder of hematopoiesis, or another cause of eosinophilia.

Etiology of Eosinophilia

Eosinophilia may be

The most common cause of eosinophilia in the United States 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 (amoeba) and noninvasive metazoa usually do not.

The pulmonary infiltrates that may occur with peripheral eosinophilia are part of a spectrum of clinical disorders, which can be infectious, autoimmune, or inflammatory in nature.

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) (2, 3 General references 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... read more General references ).

Table

General references

  • 1. Klion AD: Approach to the patient with suspected hypereosinophilic syndrome. Hematology Am Soc Hematol Educ Program 2022; 2022(1):47-54. doi: 10.1182/hematology.2022000367

  • 2. Wei BM, Fox LP, Kaffenberger BH, et al. Drug-induced Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms. Part I. Epidemiology, Pathogenesis, Clinicopathological Features, and Prognosis [published online ahead of print, 2023 Jul 27]. J Am Acad Dermatol 2023;S0190-9622(23)02402-7. doi:10.1016/j.jaad.2023.02.072

  • 3. Wei BM, Fox LP, Kaffenberger BH, et al. Drug-induced Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms. Part II. Diagnosis and Management [published online ahead of print, 2023 Jul 27]. J Am Acad Dermatol 2023;S0190-9622(23)02403-9. doi:10.1016/j.jaad.2023.02.073

  • 4. Muir A, Falk GW: Eosinophilic esophagitis: a review. JAMA 326: 1310–1318, 2021. doi: 10.1001/jama.2021.14920

Evaluation of Eosinophilia

Numerous conditions can cause eosinophilia. 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

  • Medication 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 medication cause is less likely, and a detailed evaluation for an infectious, neoplastic, systemic rheumatic disease, or other systemic disorder should be done. Other important parts of the history include family history of blood disorders and a complete review of systems, including symptoms of allergies and pulmonary, cardiac, gastrointestinal (GI), and neurologic dysfunction.

Physical examination

A 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

Eosinophilia is typically recognized when a complete blood count (CBC) is done for other reasons. Additional testing often includes the following (1 Evaluation 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... read more Evaluation reference ):

  • 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 systemic rheumatic diseases. 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 neoplasm Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow hematopoietic stem cells, which can manifest as an increased number of functionally normal platelets, red blood cells (RBCs)... read more , and a bone marrow aspirate and biopsy with cytogenetic studies may be helpful.

Evaluation reference

  • 1. Klion AD: Approach to the patient with suspected hypereosinophilic syndrome. Hematology Am Soc Hematol Educ Program 2022; 2022(1):47-54. doi: 10.1182/hematology.2022000367

Treatment of Eosinophilia

  • Sometimes corticosteroids

Medications 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 references 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... read more Treatment references ). Dupilumab, an IL-4/IL-13 inhibitor, may be used to treat chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillosis (2 Treatment references 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... read more Treatment references ).

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, systemic rheumatic disease, or parasitic infection) rather than primary. Such a trial is indicated if eosinophilia is persistent and progressive in the absence of a treatable cause. Because eosinophilia can involve multiple organ systems or may be a manifestation of a systemic disorder, multiple specialists may be needed for diagnostic and therapeutic input (3 Treatment references 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... read more Treatment references ).

Treatment references

  • 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;2018:4839230. doi:10.1155/2018/4839230

  • 2. Eldaabossi SAM, Awad A, Anshasi N: Meprolizumab and dupliumab as a replacement to systemic glucocorticoids for the treatment of chronic eosinophilic pneumonia and allergic bronchopulmonary aspergillus-Case series, Almoosa specialist hospital. Respir Med Case Rep 34:201520, 2021. doi: 10.1016/j.rmcr.2021.101520

  • 3. Thomsen GN, Christoffersen MN, Lindegaard HM, et al: The multidisciplinary approach to eosinophilia. Front Oncol 13:1193730, 2023. doi:10.3389/fonc.2023.1193730

Drugs Mentioned In This Article

Drug Name Select Trade
5-HTP, 5-HTP Maximum Strength
Entocort EC, Ortikos, Pulmicort, Pulmicort Flexhaler, Rhinocort, Rhinocort Aqua, Rhinocort Children's Allergy, TARPEYO, UCERIS, UCERIS Rectal
Nucala
CINQAIR
Fasenra
DUPIXENT
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