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Eosinophil-Associated

Gastrointestinal Disorders

Alex Straumann

The human gastrointestinal (GI) tract is the largest host- eosinophil-predominant tissue infiltration. Moreover, it is likely
environment interface of the body, where the epithelial surface that eosinophils play a crucial role in the pathogenesis of these
is exposed to an overwhelming load of diverse microorganisms disorders. However, each of these conditions has different proper-
as well as to dietary products. Commensal microorganisms, the ties and probably has its own pathogenesis; to subsume them
so-called “intestinal microbiota,” are currently regarded as an into one single category is quite arbitrary and based exclusively
integrated part of the body involved in the regulation of several on descriptive features. EoE is definitely an esophageal-restricted
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physiological functions (Chapter 14). In contrast, potentially disease with a benign long-term prognosis. In patients with
pathogenic microorganisms of the luminal content must be EGE, the inflammatory process can involve several segments of
recognized and, if possible, eliminated by the mucosal immune the GI tract; nevertheless, in clinical terms this chronic inflam-
5
system. Several mechanisms are involved in maintaining a physical mation is also a benign disorder. In contrast, HES is a multisystem
and functional barrier to stabilize body homeostasis. Besides the disorder that may involve several organ systems, including the
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physical barriers, the mucosal immune system is of particular digestive tract, sometimes with a fatal outcome. Despite these
importance, with the evolutionarily ancient “innate” and the differences, all three conditions share the common features of
more specific and more diverse “adaptive” immunity (Chapter being idiopathic, chronic, and eosinophilic, and although our
20). Its task is to initiate an inflammatory response against understanding of the underlying mechanisms remains fragmen-
invading microorganisms while maintaining a state of nonre- tary, we may take the liberty of classifying them into one single
sponsiveness or tolerance to innocuous substances such as category.
commensal bacteria or food antigens. EoE is by far the most common eosinophil gastrointestinal
Each system of immunity relies on different cell types and disorder (EGID). Because of its clinical relevance, EoE is discussed
gene products with characteristic modes of action. Eosinophils— in greater depth here than the other two eosinophil-associated
part of the innate immune system—are present in the peripheral disorders.
blood of healthy individuals and account for approximately 1–3%
of peripheral leukocytes with an upper limit of the normal range EOSINOPHILIC ESOPHAGITIS
1
of 350 cells per cubic millimeter of blood. Tissue-dwelling
eosinophils reside in the hematopoietic and lymphatic organs, Definition
such as the bone marrow, spleen, lymph nodes, and thymus. In the latest consensus recommendations, the following conceptual
However, based on a comprehensive analysis of normal human definition was published: EoE represents a chronic, immune/
tissues from almost all body organs, we know that the GI tract antigen-mediated esophageal disease, characterized clinically by
is the only nonhematopoietic organ showing significant numbers symptoms related to esophageal dysfunction and histologically
2
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of tissue-dwelling eosinophils under healthy conditions. The by an eosinophil-predominant inflammation. This definition
distribution of eosinophils is not homogeneous throughout the shows that the diagnosis of EoE is based on clinical and on
digestive tract, with the highest density of cells in the cecal and histopathological findings.
2
appendiceal region. Under physiological conditions, the esopha-
gus is the only segment of the digestive tract that lacks tissue- Epidemiology
2,3
dwelling eosinophils. Besides the resident eosinophils, a marked Epidemiological information is essential to determine the clinical
accumulation of eosinophils in the digestive tract can be seen and socioeconomic impact of a disease. Therefore knowledge
under inflammatory conditions. Because eosinophils are non- of the epidemiological parameters of a disease is crucial for
specific late-phase inflammatory cells, infiltration can occur in identifying risk factors as well as pathogenetic mechanisms, for
the context of any type of inflammation—e.g., bacterial and planning preventive measures, and for determining optimal
parasitic infections, celiac disease, Crohn disease, and ulcerative treatment approaches.
colitis—independently of its cause. 1
This chapter focuses on three idiopathic eosinophil-associated Demographic Cornerstones
GI disorders, in particular idiopathic eosinophilic esophagitis Cases of EoE have been reported worldwide and identified in
(EoE), idiopathic eosinophilic gastroenteritis (EGE), and idio- those with a variety of ethnic backgrounds, including Caucasians,
pathic hypereosinophilic syndromes (HESs) with GI manifestation African Americans, Hispanics, and Asians. However, as there are
(Table 46.1). The term “eosinophil-associated” denotes that the no controlled data about geographical variations of prevalence,
histological inflammatory response is characterized by an it remains unclear whether EoE is associated with any particular

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