Eosinophils

Eosinophils serve many functions in the body, including mediation of allergic responses, eradication of parasitic infections, and down-regulation of the inflammatory response. Eosinophilia is defined as the presence of an absolute eosinophil count of more than 500 per microliter of blood. Absolute eosinophil count refers to the number of circulating eosinophils in the peripheral blood expressed as cells per uL. Eosinophilia can be classified as mild (500-1500 eosinophils/μL), moderate (1500-5000 eosinophils/μL), or severe (>5000 eosinophils/μL).

Two terms commonly used to describe eosinophilia. Hypereosinophilia is defined as an absolute eosinophil count greater than 1500 eosinophils/μL on at least 2 occasions separated by at least 2 weeks. Patients with hypereosinophilia may have tissue infiltration by eosinophils which can cause inflammation, tissue damage, fibrosis, and thrombosis. The most commonly affected organs are the heart, lungs, gastrointestinal tract, and skin. 

The hypereosinophilic syndrome (HES) is defined by hypereosinophilia, eosinophil-mediated organ damage, and absence of alternative explanations for hypereosinophilia. HES is typically diagnosed at approximately 45 years of age and frequently affects the heart, lungs, bone marrow, skin, liver, and lymph nodes. Approximately one-fifth of patients develop venous or arterial thrombosis. 

HES is considered to be primary if it is caused by a stem cell, myeloid, or eosinophil neoplasm. Patient with primary HES often have mutations in genes PDGFRA, FDGFRB, and FGFR1. Secondary HES includes lymphoid variants, eosinophilic granulomatosis, and IgG4-related disease. 

Absolute eosinophilia also occurs in benign conditions such as allergic reactions and infectious diseases as well as neoplastic disorders such as myeloproliferative and lymphoproliferative diseases. Exposure history including occupation, recreational activities, medications, supplements and food consumption is an important aspect of the initial evaluation. Examples include a risk of; strongyloides infection in miners, ascariasis in slaughterhouse workers, and schistosomiasis in river rafters. 

Drug reactions to penicillin, cephalosporin, fluoroquinolones, NSAIDs, proton pump inhibitors, allopurinol, aspirin, hydrochlorthiazide, carbamazepine, phenytoin, and statins may be associated with eosinophilia. Manifestations of drug-induced eosinophilia can range from an asymptomatic eosinophilia to clinically significant end-organ involvement, such as the drug reaction with eosinophilia and systemic symptoms syndrome (DRESS). Symptoms of DRESS syndrome often develop 2 to 8 weeks after initiation of a new drug. 

The following laboratory tests should be included in the initial workup of eosinophilia:

• CBC with differential and peripheral blood smear review to detect abnormalities in other cell lines and dysplasia 
• Serum creatinine and urinalysis for renal insufficiency
• Serum vitamin B12 level which is often elevated in myeloproliferative disorders
• Serologic testing for parasites especially for immigrants, patients with a history of travel or consumption of raw or incompletely cooked food. Possibilities include Strongyloides, Toxocara, Trichinella, Schistosomiasis, Ancylostomiasis, Ascariasis and Filariasis
• Stool studies for ova and parasites
• Liver function tests to assess hepatic involvement
• Troponin levels to assess cardiac involvement
• Flow cytometric analysis for lymphocyte subsets to detect lymphoproliferative disorders

The primary goal of the initial evaluation is to identify disorders requiring specific treatments such as parasitic infection, drug-hypersensitivity, or leukemia.

References

Valent P, et al. Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes. Allergy. 2023;78:47-59.

Requena G, et al. Clinical profile and treatment in hypereosinophilic syndrome variants: a pragmatic review. Clin immunol Pract. 2022; 10:2125-2134.