Clinical Information

Eosinophils are a type of white blood cell (WBC) that derives from myeloid progenitor cells.(1) They are a critical part of the immune response to helminth and other infections and play a significant role in allergic diseases. Eosinophils are characterized by their cytoplasmic granules, which appear dark red when stained with eosin. These cytoplasmic granules contain a number of cytotoxic proteins, including major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin (EDN). Upon activation, eosinophils degranulate, with subsequent release of these proteins into the extracellular space. These proteins exhibit a variety of activities, with EDN being a ribonuclease having antiviral activity.

Eosinophils generally comprise less than 5% of the total WBC count. Eosinophilia, or elevated numbers of eosinophils in the peripheral blood, can be defined as mild (up to 1500/mcL), moderate (1500-5000/mcL), or severe (>5000/mcL).(2) Hypereosinophilia (HE) identifies a situation in which peripheral eosinophils >1500/mcL are detected at least 2 occasions at least 4 weeks apart. Causes of HE can be classified as secondary (reactive), primary (neoplastic) or idiopathic. Some secondary (reactive) causes of HE include allergy, parasite infection, and autoimmunity. Additionally, secondary (reactive) HE can occur in the context of a malignancy (paraneoplastic), such as solid-organ cancer, T-cell lymphoma/leukemia, and Hodgkin lymphoma. In contrast, primary (neoplastic) HE occurs in situations of clonal myeloid/lymphoid stem cells; in this case, the eosinophils originate from the malignant clone. Lastly, idiopathic HE is reserved for cases where no underlying cause can be identified.

In some cases, peripheral HE leads to infiltration of tissues by the eosinophils. Hypereosinophilic syndrome (HES) identifies patients in whom organ damage occurs and is caused by degranulation of eosinophils within the target organ. The most commonly involved organ systems in HES are the skin, lungs, and gastrointestinal tract.(2) Evaluation of patients with peripheral HE begins with screening for second causes (infection, allergy, etc) and assessing for organ damage though imaging, functional testing, and tissue pathology.(3) Although peripheral blood eosinophil counts are used to identify patients with HE, they may not always accurately reflect elevated numbers of eosinophils found in tissues. In addition, absolute counts also do not indicate the level of eosinophil activation and degranulation. EDN concentrations have been shown to correlate with peripheral blood eosinophil counts and may provide additional information related to activation status.(4,5)