GLUTEN-SENSITIVE ENTEROPATHY
Section snippets
EPIDEMIOLOGY
A large multicenter study promoted by the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) involving 36 centers 22 countries has recently provided important information on the epidemiology of CD. The average incidence figure was found to be one case in every one thousand live births, with a range from 1 in 250 (observed in Sweden) to 1 in 4000 (observed in Denmark); 95% confidence intervals of observed rates in each region did not support the existence of significant
Family Studies
The strong genetic influence on the susceptibility to CD is suggested by the occurrence of multiple cases in families. In a large multicenter the prevalence of CD found among first-degree relatives is 8.7%, most of the newly recognized patients being completely asymptomatic.5 To further confirm the importance of genetic factors in CD, as many as 75% of monozygotic twins have been found to be concordant with the disease.76
HLA Genes
The major genetic association of CD is with genes and gene products of the
Abnormal Immune Response In Celiac Disease
It is now generally accepted that CD is an immunologically mediated small-intestinal enteropathy. In fact, the mucosal lesion shows features suggesting both humoral and cell-mediated immunologic overstimulation. Analogies with in vivo and in vitro models in which delayed-type hypersensitivity has been induced support the hypothesis that cell-mediated mechanisms have a key role in the induction of the mucosal damage. Flattening of the small intestinal mucosa occurs in vivo during the evolution
Clinical Presentation
Clinical features of CD differ considerably, most depending on the age at presentation. Intestinal symptoms are common in children diagnosed within the first 2 years of life. Failure to thrive, chronic diarrhea, abdominal distention, muscle wasting, anorexia, and irritability often are present. Vomiting may occur in one third of such presenting patients early. Clinical history reveals that growth has been normal in the first months of life, but within weeks or months since the introduction of
Tests for Malabsorption
Tests measuring intestinal absorption, such as xylose absorption, fecal fat excretion, and hematologic investigations, have been used in the past to select symptomatic patients for jejunal biopsy,54 the best of these traditional screening tests probably being the determination of red blood cell folate5 however, these tests are of some value only in children with a malabsorptive syndrome. None of them can be used alone even in classic cases of CD. Because normal results of any laboratory test
DIAGNOSIS
In 1969, the ESPGAN recommended three intestinal biopsies for the diagnosis of CD in childhood; one performed at the time of presentation, another after the patient has been on a gluten-free diet when the mucosa is expected to have returned to normal, and the final biopsy after the patient has been rechallenged with gluten, when villous atrophy is expected to have recurred.69
Twenty years later, a working group from the ESPGAN has reconsidered such diagnostic criteria.103 The two requirements
THERAPY
Since the identification of gluten as an etiologic factor in CD, a strict gluten-free diet (GFD) has become the cornerstone of the management of such patients. Their diet should exclude wheat, oats, rye, and barley; rice and maize are nontoxic and usually are used as wheat substitutes. In fact, the diet mainly should be based on natural food prepared with nontoxic cereals. The clinical response to withdrawal of gluten is often dramatic. A remarkable increase in growth velocity is observed soon
PROGNOSIS
Few studies of prognosis and survival of patients with CD are available. Recently, the overall mortality rate in celiac patients has been reported in Scotland to be 1.9-fold that of the general population.56 The excess mortality in celiac patients was not due to malabsorption but was accounted for by lymphoproliferative diseases and other malignancies. The greatly increased relative risk of lymphoma has long been recognized. More than 80% of lymphomas in celiac patients are intestinal in
SUMMARY
Gluten-sensitive enteropathy is induced by dietary wheat gliadin and related proteins in genetically susceptible individuals. Most evidence suggests that the mucosal lesion represents an immunologically mediated injury triggered by gluten in the context of a particular assortment of major histocompatibility complex genes. The amino acid residues of gliadin and related proteins responsible for toxicity have not been identified; in vitro systems are available, but definitive conclusions must rely
ACKNOWLEDGMENT
Giuseppe Ajello is gratefully acknowledged for assistance in typing the manuscript.
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Address reprint requests to Salvatore Auricchio, MD, PhD, Department of Pediatrics, via Sergio Pansini 5, I-80131 Naples, Italy
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From the Department of Pediatrics, University Federico II, Naples, Italy