Page 664 - Clinical Immunology_ Principles and Practice ( PDFDrive )

638 Part five Allergic Diseases

published large series suggest this risk is not as great as originally responses to a variety of agents, including corticosteroids, PPIs,
thought. 7,8 mast cell stabilizers, antihistamines, and leukotriene antagonists
as well as surgical resection of strictured segments. 5,20
IDIOPATHIC EOSINOPHILIC GASTROENTERITIS Patients with the serosal type typically respond to steroid
therapy; however, optimal treatment is not yet defined for other
Definition and Classification forms of EGE. Based on these limited data, initial treatment
EGE is a rare, heterogeneous, and poorly defined condition. It should be with PPIs, with a switch to systemic corticosteroids
is characterized by chronic-recurrent tissue infiltration of the in the case of nonresponse. Unfortunately, the relapsing nature
5
GI tract with eosinophils. The diagnosis is based on the following of the disease means long-term treatment may be needed with
three criteria: 1) nonspecific GI symptoms; 2) eosinophilic infiltration oral corticosteroids, with the inevitable risk of side effects.
of one or more areas of the GI tract; and 3) exclusion of other Leukotriene inhibitors should be evaluated in patients with
5
causes for the intestinal eosinophilia. No consensus has yet been frequent flare-ups.
reached regarding the histological criteria for diagnosing EGE.
This may be related to the fact that healthy gastric and intestinal
mucosa harbors eosinophils under physiological conditions and HYPEREOSINOPHILIC SYNDROMES WITH
so it is difficult to establish “normal” cell numbers. GASTROINTESTINAL INVOLVEMENT
EGE can be subclassified either according to the segments of
the GI tract affected by the process or according to the depth Definition and Classification
5
of the eosinophilic infiltration. The latter (or Klein) classification The HESs are a heterogeneous group of rare disorders character-
system distinguishes between mucosal, muscular, and serosal ized by 1) persistent peripheral blood eosinophilia with more
5
3
forms of EGE. Parasitic infections, inflammatory bowel disease, than 1500 cells/mm for a period of >6 months; 2) no known
connective tissue diseases, side effects of drugs, and lympho- cause of eosinophilia; and 3) signs and symptoms of organ
6,21
proliferative malignancies must be ruled out before a diagnosis involvement. Recent efforts have led to reclassification of these
of EGE can be established. 5 disorders according to the recognition of several clinical subtypes
and new biomarkers. Currently recognized subtypes include
Epidemiology and Natural History fip1-like1/platelet-derived growth factor receptor α (FIP1L1-
EGE predominantly affects male children and adults. In contrast PDGFRA)-associated HESs, lymphocytic variant HESs, chronic
to EoE, EGE is a very rare disease. During the 70 years since it eosinophilic leukemia, and familial eosinophilia. 22,23 Independent
19a
was first described by Kaijser in 1937, approximately 200 cases of this subclassification, the eosinophilic infiltration can affect
have been reported in the literature. Although EGE is likely a the cardiovascular system (90%), the peripheral and central
chronic disorder, its natural course is still poorly defined. nervous systems (90%) including the retina, the coagulation
system (80%), the skin (55%), the respiratory system (50%), the
Clinical Presentation liver and spleen (35%), and the GI tract (25%).
The clinical manifestation of EGE depends on its location within
the GI tract and on its depth of infiltration of the intestinal wall. Epidemiology and Natural History
Mucosal involvement is typically associated with vomiting, HESs, similar to the other idiopathic eosinophilic disorders,
diarrhea, abdominal pain, weight loss, failure to thrive, and either predominantly affect middle-aged males, with a male-to-female
occult or frank bleeding. Involvement of the muscular layers ratio of 3 : 1. Onset of the disease is commonly between 20 and
may lead to signs and symptoms of intestinal obstruction, whereas 50 years of age. Data about its prevalence or incidence are not
patients with serosal involvement typically complain of bloating available. 6,21
and can present with ascites. Peripheral blood eosinophilia is
observed in approximately two-thirds of EGE patients. 5 Clinical Presentation
HES has a gradual onset, presenting initially with general
Diagnostic Measures symptoms such as anorexia, fatigue, weight loss, fever, abdominal
The mucosal form of the disease can be visualized by endoscopy. pain, and night sweats. Throughout the course of the disease,
The findings are usually not spectacular and include thickening the clinical manifestations vary according to which organs are
of the intestinal folds with deformation of the luminal configura- involved. With GI involvement, abdominal pain and diarrhea
tion, diminished peristalsis, and an erythematous and friable with malabsorption have been reported, but the leading sign is
mucosa. Moreover, endoscopy enables representative biopsy samples hepatosplenomegaly, either due to eosinophilic infiltration or
5
to be taken for histological confirmation of the diagnosis. Patients secondary to congestive heart failure. During its long-term course,
with suspected serosal disease should be evaluated by laparoscopy; extraintestinal manifestations or lymphoproliferative conditions
findings for this form of EGE include ascites, whitish nodules, may occur and facilitate the definite diagnosis. The ultimate
and thickening of the parietal and visceral peritoneum. 5 prognosis depends on the extent of end organ damage. Intestinal
The muscular form of EGE can be detected by CT scan or manifestations and cardiac involvement are associated with poor
conventional radiological examinations. Diagnostic confirmation prognosis and risk of fatal outcome, whereas patients with skin
is hampered by the difficulty in obtaining histological samples. Most disease generally have a milder course. 6,21
reported cases of muscular EGE have been diagnosed after surgical
resection of an intestinal obstruction or suspected malignancy. Immunopathogenesis
HESs encompass several disease processes with different patho-
Treatment genic mechanisms. One form is characterized by a significant
EGE is an uncommon disease, and therefore no therapeutic trials elevation of the eosinophilopoietic cytokine IL-5 in serum.
have been done. Case reports and small case series have reported Recently an IL-5–independent form of HES has been described