Eosinophilia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: George Leef MD

Eosinophilia refers to elevated eosinophils in the peripheral blood. It is important to remember that eosinophilia is a symptom, not a disease. Eosinophilia can be a manifestation of a variety of different disease processes, including neoplastic, infectious, allergic, and idiopathic processes.

When the eosinophil count is markedly elevated and the patient has symptoms attributable to the eosinophils (and not explained by the underlying condition, if any), it is referred to as a hypereosinophilic syndrome. ^[1] Most patients with eosinophilia do not have a hypereosinophilic syndrome.

• As mentioned above, eosinophilia is not a unified disease entity, but rather a manifestation of many different disease processes.
• The eosinophil itself was discovered in 1879 ^[2] as a granulocytic cell that stained with the red dye eosin. Granulocytes in general were described several decades earlier.
• The hypereosinophilic syndrome was first described in 1968. ^[3]

• Major disease categories that can cause eosinophilia: ^[3]
• Allergy/Atopy
• Infections
  • Parasitic: particularly associated with helminths, most protozoan parasites do not cause eosinophilia (Toxoplasma is an exception)
  • Certain fungal organisms: Coccidiomycosis
  • Viral (HIV, HTLV, Herpes)
• Malignancies
  • Hematologic: primary eosinophil neoplasia, B and T cell lymphomas, CML, Hodgkin’s Lymphoma
  • Solid tumors: breast, lung
• Myelodysplastic and myeloproliferative disorders
• Systemic Mastocytosis
• Addison’s Disease
• Drug Reactions (DRESS)
• Vasculitis (Churg-Strauss)
• Idiopathic

• Eosinophilia is defined by blood eosinophil count > 500/microL.
• The pathogenesis is variable. Eosinophila can be caused by a proliferative neoplasm (as in eosinophilic leukemia), or as a reaction to another process (parasitic infection, drug reaction, solid tumor) that causes elevated levels in cytokines that promote eosinophil maturation in the bone marrow, or it may be idiopathic.

• Eosinophilia can be caused by numerous different processes listed above.

• If the eosinophil count is elevated, eosinophilia is present by definition. Care should be taken to discover the correct cause for the eosinophilia.

• Eosinophilia is not a specific disease entity, epidemiologic numbers are availble for major causes of eosinophilia
• Hypereosinophilic syndromes are extremely rare, estimated at 0.36 to 6.3 people per 100000 in the US. ^[1] Adults are most commonly affected, however children and the elderly can be affected as well.

• Common risk factors in the development of eosinophilia are allergies and parasitic infections. Eosinophilia is most commonly associated with allergic processes in developed countries and with parasitic infections in developing countries.

• Highly variable based on the underlying etiology.
• The diseases eosinophilia can be associated with have a wide range of natural histories and prognoses.
• An asthmatic patient with eosinophilia has a very different prognosis than a cancer patient with eosinophilia
• Hypereosinophilic syndromes have a poor prognosis and high mortality, mostly from the cardiac effects of hypereosinophilia

• The diagnosis of eosinophilia is made when the peripheral blood eosinophil count is greater than 500 cells/microL.
• Hypereosinophilic syndrome usually has eosinphil counts greater than 1500 cells/microL. Hypereosinophilic syndrome also requires the presence of organ dysfunction that is caused by the eosinophils and cannot be explained by another disease process ^[1][4].

• Symptoms seen in eosinophilia are highly variable and reflect the underlying disease.
• Hypereosinophilia can cause symptoms due to the release of destructive compounds from eosinophils. ^[1][3][4] Symptoms attributable to the elevated eosinophil count include:
  • Dermatologic manifestations insluding rash, urticaria
  • Muscle and joint pains
  • Heart failure and endocardial fibrosis
  • Cough and shortness of breath
  • Thrombotic and embolic events
  • Encephalopathy or neuropsychiatric disturbances
  • Peripheral neuropathies
  • Abdominal pain, nausea/vomiting, diarrhea, weight loss
  • Any organ can be affected by hypereosinophilia and manifestations are variable

• Physical exam findings in eosinophilia are highly variable and reflect the underlying disease.
• Physical exam findings in a hypereosinophilic syndrome are also highly variable, since the disease can affect any organ system. Possible manifestations include:
  • Signs of volume overload related to heart failure: peripheral edema, pulmonary edema, engorged neck veins, etc.
  • Rash, skin ulcerations, lichenification
  • Altered mental status
  • Respiratory distress

• There are no specific laboratory findings associated with eosinophilia aside from the elevated eosinophil count.
• Anemia and thrombocytopenia or thrombocytosis may be seen if the eosinophilia is related to a clonal proliferative process in the bone marrow. ^[4]

• There are no imaging findings associated with eosinophilia unless it is secondary to a disease process that causes imaging findings.

• Medical treatment for eosinophilia should be directed at the underlying cause (for example treating parasitic infection or malignancy).
• Eosinophilia without evidence of organ dysfunction may be observed with monitoring for evidence of organ involvement.
• Treatment of hypereosinophilic syndrome has a number of options including corticosteroids, hydroxyurea, interferon-alpha, imatinib and other tyrosine kinase inhibitors, IL-5 antibodies, and other cytotoxic and immunomodulatory agents. ^{[1][4] [5]}

• Surgery may be part of the treatment for certain causes of eosinophilia, such as solid organ malignancies. However most conditions associated with eosinophilia are not treated surgically.

• There are no primary preventive measures available for eosinophilia.

• Primary prevention should be targeted as specific disease entities.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

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Eosinophilia is a laboratory finding rather than a diagnosis, and can arise from different pathologic processes. Causes of eosinophilia fall into three general groups: primary eosinophilia (caused by a proliferative neoplasm in the bone marrow), reactive eosinophilia (another disease process creates high levels of cytokines that induce the bone marrow to produce eosinophils), and idiopathic.

Primary Eosinophilia: eosinophils are a type of granulocytic white blood cell produced in the bone marrow from myeloid precursors. A neoplasm of these bone marrow cells can lead to massive overproduction of eosinophils. Such neoplasia include acute and chronic eosinophilic leukemia, as well as some myelofibrotic or myelodysplastic syndromes. These are primary causes of eosinophilia since the bone marrow itself it dysregulated.

Reactive Eosinophilia: the eosinophil precursor cells in the bone marrow are responsive to various molecular signals, including IL-3 and IL-5. When these signals are present at high levels, the bone marrow can respond by increasing production of eosinophils to abnormally high levels. Reactive eosinophilia can be caused by a wide variety of causes, including helminthic infections, hematologic and solid organ malignancies, etc. Eosinophilia in these cases is “reactive” because the bone marrow is responding appropriately to elevated levels of cytokines caused by another process.

Idiopathic: no caused for the elevated eosinophil count can be discovered

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

• Adrenal insufficiency
• Asthma
• Atheroembolic disease
• Atopic dermatitis
• Fungal infections
• Hypereosinophilic syndromes
• Immunodeficiency states
• Leukemia
• Lymphoma
• Mastocytosis
• Medication-related eosinophilia
• Parasitic infections
• Rhinitis syndromes
• Vasculitis

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The natural history and prognosis of eosinophilia are highly variable and driven by the underlying disease process.

Natural history is highly variable and dependent on the disease process causing the eosinophilia.

Complications to monitor for are dictated by the underlying disease process. Since eosinophilia can accompany a wide variety of disease states, no single comprehensive list of complications can be given.

Again, no single prognosis can be given for eosinophilia. Eosinophilia may accompany allergies, which have an excellent prognosis, but it may also accompany a variety of malignancies with poor prognosis. Other causes of eosinophilia fall somewhere in the middle, such as Addison’s disease, which may be fatal if left untreated but has a good prognosis if recognized and treated.

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