GLUTEN-SENSITIVE ENTEROPATHY

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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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References (106)

  • KettK. et al.

    Secretory immunity in celiac disease: Cellular expression of immunoglobulin A subclass and joining chain

    Gastroenterology

    (1990)
  • LoganR.F.A. et al.

    Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland

    Gastroenterology

    (1986)
  • LoganR.F.A. et al.

    Mortality in celiac disease

    Gastroenterology

    (1989)
  • MakiM. et al.

    Evaluation of serum IgA-class reticulin antibody test for the detection of childhood coeliac disease

    J Pediatr

    (1984)
  • MakiM. et al.

    Reaction of human non-collagenous polypeptides with coeliac disease autoantibodies

    Lancet

    (1991)
  • MarshM.N.

    Gluten, major histocompatibility complex, and the small intestine: A molecular and immunobiologic approach to the spectrum of gluten sensitivity

    ("Celiac Sprue") Gastroenterology

    (1992)
  • O'MahonyS. et al.

    Similarities in intestinal humoral immunity in dermatitis herpetiformis without enteropathy and in coeliac disease

    Lancet

    (1990)
  • RoschmannE. et al.

    T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study

    Gastroenterology

    (1993)
  • SavilahtiE. et al.

    Coeliac disease in insulin-dependent diabetes mellitus

    J Pediatr

    (1986)
  • SpurklandA. et al.

    HLA-DR and DQ genotypes of celiac disease patients seriologically typed to be non DR3 or non DR5/7

    Human Immunol

    (1992)
  • SturgessR. et al.

    Wheat peptide challenge in coeliac disease

    Lancet

    (1994)
  • TosiR. et al.

    Evidence that celiac disease is primarily associated with a DC locus allelic specificity

    Clin Immunol Immunopathol

    (1983)
  • TronconeR. et al.

    A sandwich enzyme immunoassay for wheat gliadin

    J Immunol Meth

    (1986)
  • AineL. et al.

    Dental enamel defects in coeliac disease

    J Oral Pathol Med

    (1990)
  • Amil DiasJ. et al.

    Down's syndrome and coeliac disease

    J Pediatr Gastroenterol Nutr

    (1990)
  • AuricchioS. et al.

    Working hypothesis. Does breast feeding protect against the development of clinical symptoms of celiac disease in children? I

    Pediatr Gastroenterol Nutr

    (1983)
  • AuricchioS. et al.

    Coeliac disease as a familial condition: Identification of asymptomatic coeliac patients within family groups

    Gastroenterol Int

    (1988)
  • AuricchioS. et al.

    Effects of small amounts of gluten in the diet of coeliac patients

    Panminerva Med

    (1991)
  • BoudraaA. et al.

    Epidemiology of Gluten Intolerance in North Africa: Analysis of the Case Reports from West Algeria and North-West Tunis

    Dyn Nutr Res

    (1992)
  • Burgin-WolffA. et al.

    Antigliadin and antiendomysium antibody determination for coeliac disease

    Arch Dis Child

    (1991)
  • CatassiC. et al.

    Dose-dependent effects of protracted ingestion of small amounts of gliadin in children with coeliac disease: A clinical and jejunal morphometric study

    Gut

    (1993)
  • ChanK.N. et al.

    Endomysial antibody screening in children

    J Pediatr Gastroenterol Nutr

    (1994)
  • ChorzelskiT.P. et al.

    IgA anti-endomysial antibody: A new immunological marker of dermatitis herpetiformis and coeliac disease

    Br J Dermatol

    (1984)
  • CiclitiraP.J. et al.

    Evaluation of a gliadin-containing gluten-free product in coeliac patients

    Hum Nutr Clin Nutr

    (1985)
  • Clerget-DarpouxF. et al.

    High risk genotypes for celiac disease: Genotypes risque lev pour la maladie coeliaque

    CR Acad Sci Paris, Life Sciences

    (1994)
  • CollinP. et al.

    Follow-up of patients positive in reticulin and gliadin antibody tests with normal small-bowel biopsy findings

    Scand J Gastroenterol

    (1993)
  • ColonnaM. et al.

    Allelic variants of the human putative peptide transporter involved in antigen processing

    Proc Nat Acad Sci USA

    (1992)
  • Congia M, Cucca F, Frau F, et al: A gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the...
  • DouglasJ.D. et al.

    Sarcoidosis and coeliac disease: An association

    Lancet

    (1984)
  • Duff GW: Cytokines as genetic factors in inflammatory diseases: 2nd Annual Congress of the British Society for...
  • Ejederhamn J, Veress M, Strandvik B: The long-term effect of continual ingestion of wheat starch-containing gluten-free...
  • FaisS. et al.

    Gliadin-induced changes in the expression of MHC-class II antigens by human small intestinal epithelium. Organ culture studies with celiac disease mucosa

    Gut

    (1992)
  • FergusonA. et al.

    Effect of additional dietary gluten on the small intestinal mucosa of volunteers and of patients with dermatitis herpetiformis

    Scand J Gastroenterol

    (1987)
  • FergusonA.

    Models of immunologically-driven small intestinal damage

  • FergusonA. et al.

    Clinical and pathological spectrum of coeliac disease-active, silent, latent, potential

    Gut

    (1993)
  • Fernandez-CalleP. et al.

    Is an intestinal permeability test a valid marker for slight dietary transgressions in adolescents with coeliac disease?

    Gut

    (1993)
  • FerreiraM. et al.

    Endomysial antibody: Is it the best screening test for coeliac disease?

    Gut

    (1992)
  • GobbiG. et al.

    Coeliac disease, epilepsy, and cerebral calcifications

    Lancet

    (1992)
  • GrecoL. et al.

    Catch-up growth in coeliac children: A longitudinal study

  • GrecoL. et al.

    Epidemiology of coeliac disease in Europe and the Mediterranean area. A summary report on the multicentre study by the European Society of Pediatric Gastroenterology and Nutrition

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    Address reprint requests to Salvatore Auricchio, MD, PhD, Department of Pediatrics, via Sergio Pansini 5, I-80131 Naples, Italy

    *

    From the Department of Pediatrics, University Federico II, Naples, Italy

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