Chapter 123 Eosinophils
Eosinophils are distinguished from other leukocytes by their morphology, constituent products, and association with specific diseases. Eosinophils are nondividing fully-differentiated cells with a diameter of ≈8 µm and a bilobed nucleus. They differentiate from stem cell precursors in the bone marrow under the control of T cell–derived interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and, especially, IL-5. Their characteristic membrane-bound specific granules stain reddish brown with eosin and consist of a crystalline core made up of major basic protein (MBP) surrounded by a matrix containing the eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN). These basic proteins are cytotoxic for the larval stages of helminthic parasites such as Schistosoma mansoni and are also thought to contribute to much of the inflammation associated with asthma, causing sloughing of epithelial cells and contributing to clinical dysfunction (Chapter 138).
Eosinophil migration from the vasculature into the extracellular tissue is mediated by the binding of leukocyte adhesion receptors to their ligands or counterstructures on the postcapillary endothelium. Similar to neutrophils (see Fig. 121-2), transmigration begins as the eosinophil selectin receptor binds to the endothelial carbohydrate ligand in loose association, which promotes eosinophils rolling along the endothelial surface until they encounter a priming stimulus such as a chemotactic mediator. Eosinophils then establish a high-affinity bond between integrin receptors and their corresponding immunoglobulin-like ligand. Unlike neutrophils, which become flattened before transmigrating between the tight junctions of the endothelial cells, eosinophils can use unique integrins, known as VLA-4, to bind to vascular cell adhesion molecule (VCAM)-1, which enhances eosinophil adhesion and transmigration through endothelium. Eosinophils are recruited to tissues in inflammatory states by the chemokine eotaxin. These unique pathways account for selective accumulation of eosinophils in allergic and inflammatory disorders. Eosinophils normally dwell primarily in tissues, especially tissues with an epithelial interface with the environment, including the respiratory, gastrointestinal, and lower genitourinary tracts. The life span of eosinophils may extend for weeks within tissues.
Diseases Associated With Eosinophilia
Many diseases are associated with moderate (1,500-5,000 cells/µL) or severe (>5,000 cells/µL) eosinophilia (Table 123-1). Patients with sustained blood eosinophilia may develop organ damage, especially cardiac damage as found in the idiopathic hypereosinophilic syndrome, and should be monitored for evidence of cardiac disease. Many cases of moderately severe eosinophilia often have no clear etiology.
Table 123-1 CAUSES OF EOSINOPHILIA
ALLERGIC DISORDERS
INFECTIOUS DISEASES
Tissue-Invasive Helminth Infections
MALIGNANT DISORDERS
GASTROINTESTINAL DISORDERS
RHEUMATOLOGIC DISEASE
IMMUNODEFICIENCY DISEASE
MISCELLANEOUS
Infectious Diseases
In evaluating patients with unexplained eosinophilia, the dietary history and geographic or travel history may indicate potential exposures to helminthic parasites. It is frequently necessary to examine the stool for ova and larvae at least 3 times. Additionally, the diagnostic parasite stages of many of the helminthic parasites that cause eosinophilia never appear in feces. Thus, normal results of stool examinations do not absolutely preclude a helminthic cause of eosinophilia; diagnostic blood tests or tissue biopsy may be needed. Toxocara causes visceral larva migrans usually in toddlers with pica (Chapter 290). Most young children are asymptomatic, but some develop fever, pneumonitis, hepatomegaly, and hypergammaglobulinemia accompanied by severe eosinophilia. Isohemagglutinins are frequently elevated. Serology can establish the diagnosis.
Two fungal diseases may be associated with eosinophilia: aspergillosis in the form of allergic bronchopulmonary aspergillosis (Chapter 229.1) and coccidioidomycosis (Chapter 232) following primary infection, especially in conjunction with erythema nodosum.
Miscellaneous Diseases
Eosinophilia is observed in many patients with primary immunodeficiency syndromes, especially hyper-IgE syndrome (Chapter 116), Wiskott-Aldrich syndrome, and Omenn syndrome. Eosinophilia is also frequently present in the syndrome of thrombocytopenia with absent radii and in familial reticuloendotheliosis with eosinophilia. Mild eosinophilia is found in 20% of patients with Hodgkin disease and in gastrointestinal disorders including ulcerative colitis, Crohn disease during symptomatic phases, gastroenteritis that is associated with milk precipitins, and chronic hepatitis. Primary eosinophilic gastroenteritis usually involves the esophagus and stomach.
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