Eosinofilia

The Ne w E n g l a nd Jou r n a l of Me d ic i ne

Review Articles

Mechanisms of Disease
F R A N K L I N H . E P S T E I N , M. D. , Editor

E OSINOPHILIA
MARC E. ROTHENBERG, M.D., PH.D.

MARKED accumulation of eosinophils occurs in several important disorders, such as allergic diseases, parasitic infections, and cancer.1 The level of eosinophils in the body is normally tightlyregulated. In normal subjects, eosinophils account for only a small minority of peripheral-blood leukocytes, and their presence in tissues is primarily limited to the gastrointestinal mucosa.2 In certain disease states, however, eosinophils can selectively accumulate in the peripheral blood or any tissue in the body. Any perturbation that results in eosinophilia, defined here as an abnormal accumulationof eosinophils in blood or tissue, can have profound clinical effects. Eosinophilia may be harmful, because of the proinflammatory effects of eosinophils,3 or it may be helpful, because of the antiparasitic effects of these cells.4 This article focuses on recent advances in our understanding of the accumulation of eosinophils, as well as treatment approaches and the development of new therapeuticagents.
CLINICAL ASPECTS OF EOSINOPHILIA

A

Eosinophils normally account for only 1 to 3 percent of peripheral-blood leukocytes, and the upper limit of the normal range is 350 cells per cubic millimeter of blood. Eosinophilia occurs in a variety of disorders (Table 1)5 and is arbitrarily classified as mild (351 to 1500 cells per cubic millimeter), moderate (>1500 to 5000 cells per cubicmillimeter), or severe (>5000 cells per cubic millimeter). The most common cause of eosinophilia worldwide is helminthic infections, and the most common cause in industrialized nations is atopic disease. The differential diagnosis of eosinophilia requires

From the Department of Pediatrics, Children’s Hospital Medical Center, University of Cincinnati, 3333 Burnet Ave., Cincinnati, OH 45229, wherereprint requests should be addressed to Dr. Rothenberg. ©1998, Massachusetts Medical Society.

a review of the patient’s history, which may reveal wheezing, rhinitis, or eczema (indicating atopic causes); travel to areas where helminthic infections (e.g., schistosomiasis) are endemic; the presence of a pet dog (indicating possible infection with Toxocara canis); symptoms of cancer; or drugingestion (indicating a possible hypersensitivity reaction). Eosinophilia caused by drugs is usually benign but can sometimes be accompanied by tissue damage, as in hypersensitivity pneumonitis. In most cases, the eosinophilia resolves once the drug is withdrawn, but in some cases, such as the eosinophilia–myalgia syndrome due to the ingestion of contaminated tryptophan, the disease can persist despitewithdrawal of the drug.6 Abnormal morphologic features of eosinophils, an increase in immature cells in the bone marrow or blood, or a karyotypic abnormality indicates the presence of eosinophilic leukemia. An accumulation of eosinophils that is limited to specific organs is characteristic of particular diseases, such as eosinophilic cellulitis (Well’s syndrome), eosinophilic pneumonias (e.g.,Löffler’s syndrome), and eosinophilic fasciitis (Shulman’s syndrome). The association of eosinophilia with vasculitis, neuropathy, and a history of asthma indicates the presence of the Churg–Strauss syndrome. In the absence of an identifiable cause of moderate-to-severe eosinophilia and in the presence of end-organ involvement, the diagnosis of the idiopathic hypereosinophilic syndrome should beconsidered. This disorder occurs predominantly in men and is usually a progressive, fatal disease in the absence of effective medical management.7 Diagnostic studies that should be performed in patients with moderate-to-severe eosinophilia and should be considered in patients with persistent mild eosinophilia include morphologic examination of a blood smear, urinalysis, and serial stool examinations...