Eosinophilic gastrointestinal disorders (EGID)

The spectrum of gastrointestinal inflammatory disorders involving eosinophils. Gastrointestinal eosinophils accumulate in a variety of disorders with variable dependence on IgE, ranging from predominant IgE dependence (food anaphylaxis) to non-IgE dependence (celiac disease), and IBD. Adapted with permission from Rothenberg et al.¹⁸

Eosinophil development and tissue localization. The eosinophil is formed in the bone marrow under the regulation of the transcription factors GATA-1, GATA-2, and c/EBP. With the influence of IL-5, adhesion molecules, and eotaxin 1, eosinophils subsequently relocate into the peripheral circulation and finally traffic to specific tissues, predominantly the gastrointestinal (GI) tract, thymus, hematopoietic organs, and mammary gland (during pubertal development).

Schematic diagram of an eosinophil and its pleiotropic effects. Eosinophils release their preformed secondary granule constituents, most notably 4 cytotoxic cationic proteins designated EPO, MBP, ECP, and EDN. ECP and EDN are also ribonucleases. Eosinophils also release a variety of cytokines and neuromediators and generate large amounts of lipid mediators. Lastly, eosinophils can be induced to express MHC class II and costimulatory (eg, B7) molecules and might be involved in propagating immune responses by presenting antigen to T cells.

Summary of pathogenesis and treatment strategies for EGIDs and HES. Pathologic increases in eosinophils, accompanied by marked increases of eosinophils in the blood, occur through a variety of mechanisms, including a chromosome 4 interstitial deletion that results in the generation of a fusion gene, FIP1L1-PDGFRA. Clinical intervention strategies that are currently being investigated for EGIDs include allergen avoidance and therapy with anti–IL-5 and anti–eotaxin 1 humanized antibodies, CCR3 antagonists, and imatinib mesylate.