Eosinophilia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: George Leef MD
Overview
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. Most patients with eosinophilia do not have a hypereosinophilic syndrome.
Historical Perspective
- 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 [1] 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. [2]
Classification
- Major disease categories that can cause eosinophilia: [2]
- 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
Pathophysiology
- 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.
Causes
- Eosinophilia can be caused by numerous different processes listed above.
Differentiating eosinophilia from other Diseases
- If the eosinophil count is elevated, eosinophilia is present by definition. Care should be taken to discover the correct cause for the eosinophilia.
Epidemiology and Demographics
- Eosinophilia is not a specific disease entity, epidemiologic numbers are availble for major causes of eosinophilia
- Hypereosinophilic syndromes are extremely rare
Risk Factors
- 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.
Natural History, Complications and Prognosis
- 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
Diagnosis
Diagnostic Criteria
- 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 [3].
Symptoms
- 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. [2][3] Symptoms attributable to the elevated eosinophil count include:
- Dermatologic manifestations insluding rash, urticaria
- 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 Examination
- 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
Laboratory Findings
- 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. [3]
Imaging Findings
- There are no imaging findings associated with eosinophilia unless it is secondary to a disease process that causes imaging findings.
Treatment
Medical Therapy
- 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. [3] [4]
- Corticosteroids are commonly used as first line therapy. They are able to produce a rapid decrease in eosinophil counts, which is valuable if there is already evidence of organ dysfunction related to high eosinophil levels. [3]
- 0.5-1mg/kg/kday of prednisone (or the equivalent dose of another steroids) is the recommneded starting dose. Patients with non-severe disease manifestations can start with lower doses [3]
- Steroids are tapered over time, with second line agents added if needed to maintain control.
- In one study, corticosteroids were able to induce remission in 85% of patients at 1 month [4]
- Hydroxyurea is the most commonly used second-line agent for hypereosinophilic syndrome. Typical dose range is 500mg-2g per day. Hydroxyurea acts at the level of the bone marrow to reduce production of new eosinophilis. [3] As such it is not suitable if a rapid lowering in eosinophil levels is needed. Hydroxyurea is not usually used alone, it is most often used as an additional steroid-sparing agents.
- Interferon-alpha is also a second-line, steroid sparing agent. Use of this agent is limited by its toxicities. Interferon-alpha also has activity on lymphocytes, so it may be particularly effective in eosinophilia secondary to lymphocytic malignancies. [3]
- Imatinib and related TKIs have shown promise in treating chronic eosinophilic leukemia due to similar molecular re-arrangements as CML. [3][5] This family of TKIs is very well tolerated. These drugs are most effective in patients who have the FIP1L1-PDGFRA rearrangement driving a clonal expansion in the bone marrow. [4]
- Anti-IL5 antibody mepolizumab has shown potential to rapidly reduce eosinophil counts in trials and reduce the need for corticosteroids, however this agent is still investigational. [6]
- Other cytotoxic agents have been used in isolated cases, but lack strong evidence
- In severe cases refractory to other therapy, stem cell transplant may be considered if the cause of the eosinophilia is a primary bone marrow process.
Surgery
- 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.
Prevention
- There are no primary preventive measures available for eosinophilia.
- Primary prevention should be targeted as specific disease entities.
References
- ↑ Kay AB. The early history of the eosinophil. Clin Exp Allergy. 2015 Mar;45(3):575-82.
- ↑ 2.0 2.1 2.2 Brito-Babapulle. The Eosinophilias including the Hypereosinophilic Syndrome. British Journal of Hematology (2003) 121(3):203-223.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Cogan and Roufosse. Clinical Management of the Hypereosinophilic Syndromes. Expert Reviews in Hematology 5(3) 275-290 (2012).
- ↑ 4.0 4.1 4.2 Ogbogu et al. Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy. Journal of Allergy and Clinical Immunology (2009) 124(6):1319–1325
- ↑ Pardanani et al. Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders. Blood 2003 101:3391-3397.
- ↑ Rothenberg et al. Treatment of Patients with the Hypereosinophilic Syndrome with Mepolizumab. NEJM 2008; 358:1215-1228