We did a comprehensive MEDLINE search with the MeSH terms celiac disease and coeliac disease for articles published in English between January, 1997, and June, 2002. We also scrutinised reference lists of review articles on coeliac disease for extra articles.
SeminarCoeliac disease
Section snippets
Classification
The clinical classification of coeliac disease is based on the presence of gastrointestinal symptoms. Symptomatic, active, or classic coeliac disease refers to presentations with diarrhoea, with or without malabsorption; whereas in asymptomatic or silent coeliac disease, gastrointestinal symptoms are absent or not prominent even though the patient might report other non-intestinal symptoms. Latent coeliac disease is thought to be present in a person who will develop coeliac disease in the
Clinical significance
Symptomatic coeliac disease is associated with substantial morbidity caused by chronic gastrointestinal symptoms, weight loss, metabolic bone disease, anaemia, and general weakness. Implications of the disease in patients with silent coeliac disease is less clear. However, most patients with silent coeliac disease do have occult manifestations, including reduced bone density, iron or folate deficiencies,4, 5 and associated autoimmune diseases that are often of greater clinical significance than
Genetics
Coeliac disease is a multigenic disorder associated with HLA-DQ2 (DQA1*05/DQB1*02) or HLA-DQ8 (DQA1* 0301/DQB1*0302). HLA-DQ2 is expressed in more than 90% of people with coeliac disease. The expression of these HLA-DQ2 or HLA-DQ8 molecules is necessary, but not sufficient, to develop the disease. Results of studies in siblings (sib recurrence risk for coeliac disease is 10%)11 and identical twins (70% concordance)12 suggest that HLA genes are not the main causative factor in coeliac disease.
Epidemiology
On the basis of clinical frequency, coeliac disease was previously regarded as rare, occurring in 1 in 3345 people worldwide.16 However, serologic screening studies have shown the worldwide prevalence to be 1 in 266.16 Such a rate establishes coeliac disease as one of the most common genetically based diseases. Similar prevalence has been reported in most European countries, South America, and the USA.17, 18, 19 Reports from North Africa,20 Iran,21 and India22 indicate the widespread occurrence
Clinical presentation
Coeliac disease is a disorder of the proximal small intestine that can involve the entire small intestine in some individuals. This proximal location in the small intestine often results in malabsorption of iron, folic acid, calcium, and fat-soluble vitamins with resultant iron deficiency, folate deficiency, and reduced bone density. Diarrhoea, the hallmark of symptomatic coeliac disease, is mostly due to the progression of the disease into the distal small bowel.26 When only the proximal
Diagnosis
Coeliac disease can be diagnosed in the presence of characteristic changes in a small intestinal biopsy sample and improvements in clinical symptoms or histological tests on a gluten-free diet.49 Positive serological tests lend support to a diagnosis of coeliac disease, but they are not essential.
An intestinal biopsy might be done in several circumstances: if results of serological analysis are suggestive of coeliac disease; or if serological tests are negative, but clinical suspicion is high.
Serological tests
Selective IgA deficiency occurs in 1Ā·7%-2Ā·6% of patients with coeliac disease, a rate ten to 16-fold higher than that in the general population.56 Individuals with selective IgA deficiency and coeliac disease will not have IgA antibodies (endomysial antibodies, anti-tTG, and AGA [antigliadin antibodies] IgA), but usually have a raised concentration of IgG antibodies. To detect coeliac disease in selective IgA deficient individuals, total serum IgA needs to be included in the panel of tests.
Histological analysis
A major pitfall in the diagnosis of coeliac disease is in pathological interpretation of intestinal biopsies. An adequate number of biopsies needs to be taken because the disease is patchy and not all biopsy pieces will be adequately oriented for interpretation of the crypt to villous ratio. A poorly oriented biopsy, as shown by crypts cut tangentially, will falsely reduce the crypt to villous ratio.72 As a rule, at least three well oriented crypt to villous units need to be identified to
Pathogenesis and implications for innovative treatment
Coeliac disease is a T-cell mediated chronic inflammatory bowel disorder with an autoimmune component.3 Loss of tolerance to gluten is a possible cause. Although such loss of tolerance has been identified in people without the disease, as manifested by the presence of peripheral blood T cells that respond to gluten,73 the development of an anti-gluten T-cell response in the intestine is specific to people with coeliac disease.3 The reason for this occurrence is obscure; however, changes in
Poorly or non-responsive coeliac disease
Some patients have a poor clinical or histological response to a gluten-free diet. An important first step in the assessment of these patients is to confirm the diagnosis of coeliac disease by review of the original biopsy, preferably by an expert in gastrointestinal pathology72 (panel 7). However, the most common cause of a poor response is continued gluten ingestion, which might be intentional or unintentional. Therefore a consultation with an expert dietician is essential. Another reason for
Malignant disease
Malignant diseases that are more frequent in patients with coeliac disease include small bowel adenocarcinoma, oesophageal and oropharyngeal squamous carcinoma, and non-Hodgkin lymphoma.108 A gluten-free diet is thought to be protective against the development of malignant disease,109 although this might not be the case for the development of non-Hodgkin lymphoma.110
Patients with coeliac disease have a risk of small bowel adenocarcinoma that is about 80-fold greater than that of the general
Conclusion
Coeliac disease is a very common disorder and most people with the disease have the silent form. Many of these patients are identified through screening of at-risk groups. The effect of the disease on the health of those with silent coeliac disease is unclear; however, it might account for several chronic health issues including osteoporosis, infertility, autoimmune diseases, and the worsening of other serious medical conditions. Identification of genetic and environmental factors and the
Search strategy and selection criteria
References (142)
Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (āceliac sprueā)
Gastroenterology
(1992)- et al.
Significance of unsuspected celiac disease detected at endoscopy
Gastrointest Endosc
(2000) - et al.
Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure
Gastroenterology
(2002) - et al.
Mortality in celiac disease
Gastroenterology
(1989) - et al.
Mortality in patients with coeliac disease and their relatives: a cohort study
Lancet
(2001) - et al.
Genome search in celiac disease
Am J Hum Genet
(1998) - et al.
Genomewide linkage analysis of celiac disease in Finnish families
Am J Hum Genet
(2002) - et al.
Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum
Gastroenterology
(2001) - et al.
Prevalence of celiac disease among blood donors in Brazil
Am J Gastroenterol
(2000) - et al.
Why is coeliac disease endemic in the people of the Sahara?
Lancet
(1999)
Increasing incidence of celiac disease in India
Am J Gastroenterol
Breast-feeding protects against celiac disease
Am J Clin Nutr
Relation between cigarette smoking and celiac disease: evidence from a case-control study
Am J Gastroenterol
Characteristics of adult celiac disease in the USA: results of a national survey
Am J Gastroenterol
Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care
Lancet
Usefulness of videoduodenoscopy and vital dye staining as indicators of mucosal atrophy of celiac disease: assessment of interobserver agreement
Gastrointest Endosc
All that scallops is not celiac disease
Gastrointest Endosc
Ganglioside reactive antibodies in the neuropathy associated with celiac disease
J Neuroimmunol
Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia
Lancet
Prevalence of celiac disease in patients with juvenile chronic arthritis
J Pediatr
Duodenal histology in patients with celiac disease after treatment with a gluten-free diet
Gastrointest Endosc
Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease
Gastroenterology
Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease
Am J Gastroenterol
HLA-DQ typing in the diagnosis of celiac disease
Am J Gastroenterol
Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease
Am J Gastroenterol
Autoantibodies to tissue transglutaminase as predictors of celiac disease
Gastroenterology
Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice
Am J Gastroenterol
Serologic tests for celiac disease
Gastroenterology
Limitations of anti-guinea pig liver transglutaminase IgA in screening of celiac disease
Gastroenterology
Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease
Lancet
The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides
Gastroenterology
In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease
Gastroenterology
Selective expansion of intraepithelial lymphocytes expressing the HLA-E- specific natural killer receptor CD94 in celiac disease
Gastroenterology
Fatal leukemia in interleukin-15 transgenic mice
Blood Cells Mol Dis
A trial of oats in children with newly diagnosed celiac disease
J Pediatr
Health-related quality of life in children with celiac disease
J Pediatr
Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?
Hum Pathol
Autoimmune enteropathy and villous atrophy in adults
Lancet
Refractory celiac disease
Gastroenterology
Abnormal intestinal intraepithelial lymphocytes in refractory sprue
Gastroenterology
Azathioprine in refractory sprue
Am J Gastroenterol
Coeliac disease: dissecting a complex inflammatory disorder
Nat Rev Immunol
Prevalence and clinical presentation of subclinical/silent celiac disease in adults: an analysis on a 12-year observation
Hepatogastroenterology
Mortality and causes of death in celiac disease in a Mediterranean area
Dig Dis Sci
Coeliac disease-associated disorders and survival
Gut
Contribution of the MHC region to the familial risk of coeliac disease
J Med Genet
The first large population based twin study of coeliac disease
Gut
Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11
Eur J Hum Genet
The coeliac iceberg in Italy: a multicentre antigliadin antibodies screening for coeliac disease in school-age subjects
Acta Paediatr Suppl
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