This page has moved. Click here to view. Celiac diseaseThe cereals that are toxic for patients with celiac disease are wheat, rye, and barley. The toxicity of oats is still controversial celiac disease, sprue, gluten, gluten free. The use of oats as part of a gluten-free diet had no unfavorable effects on adult patients in remission and did not prevent mucosal healing in patients with newly diagnosed disease. Nevertheless, the fact that oat prolamins (avenins) seem to be able to activate mucosal cell-mediated immunity in in vitro cultured celiac biopsy specimens, coupled with the fear that small amounts of gliadin could contaminate oats, suggests caution before advocating the inclusion of oats in the diet of Wheat toxicity results from the gliadin protein fraction; the toxicity of other cereals is most likely associated with inherent prolamin fractions equivalent to gliadin. The amino acid sequence(s) responsible for the disease have not been fully elucidated. Studies from in vitro organ culture systems suggest that 31 to 43 and 44 to 55 sequences of the A-gliadin molecule seem to be However, in vitro methods must be paralleled by in vivo challenge studies. In fact, histologic changes have been shown to occur in the celiac intestinal mucosa after challenge with 200 mg of a synthetic peptide encompassing the 31 to 49 sequence of A-gliadin. The PQQP (present in the 31 to 43 and 31 to 49 sequences) and the PSQQP (present in the 44 to 55 sequence) motifs have been proposed to be the most active moieties to account for immunogenicity. However, it is now becoming clear that more than primary sequences, studies of antigenic surfaces by molecular modeling are important, because they can help in EpidemiologyA large multicenter study promoted by the European Society for Paediatric Gastroenterology and Nutrition involving 36 centers from 22 countries has recently determined that the average incidence of CD in Europe is 1 case in every 1000 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 In the 1970s a sudden and pronounced decline in the incidence of CD was reported in Britain and in other parts of Europe. At present, it is still not clear whether the decreased frequency of at least classical CD represents a real reduction in prevalence of the disease or a delay in onset. There are environmental factors that might affect the prevalence of CD or change the age of onset. A more attractive explanation is an alteration in the pattern of infant feeding: prolonged duration of breast-feeding has been found to be associated with a reduced risk of the development of celiac symptoms. The infective factors must also be considered. Adenovirus serotype 12 is particular interesting, because one of its proteins (Elb protein) shows significant amino acid sequence homology with an antigenically active gluten peptide. Viral infection and subsequent exposure to gliadin could PathogenesisIt is now generally accepted that CD is an immunologically mediated small intestinal enteropathy; in fact, the mucosal lesion shows features suggesting both cell-mediated and humoral immunologic overstimulation. Most favor the hypothesis that the activation of lamina propria T cells by class II HLA-restricted antigen-presenting cells is one of the first events driven by gliadin. Antigen recognition leads to upregulation of interleukin-2 receptor expression and production of cytokines. In the untreated celiac mucosa a significant increase in the percentage of mononuclear cells expressing the IL2 receptor (CD25+ cells) has been noted "Classical" FormsThe clinical features of CD may occur early in life or may be delayed for years or even decades. The typical early presentation of CD occurs during the first 2 years of life, manifest as diarrhea and failure to thrive. Anorexia, apathy, and irritability are common. Vomiting may be the dominant symptom. Constipation, pseudoobstruction-like syndrome, and intussusception have also Extraintestinal Manifestations and "Atypical Forms"Growth retardation can be the only presenting symptom. Endocrine abnormalities can occur in CD; secondary hypopituitarism probably is caused by severe malnutrition mainly found in long-standing disease. Untreated female patients sometimes report Associated DisordersIt is clearly established that a high proportion of patients with dermatitis herpetiformis have an abnormal intestinal mucosa consistent with CD. Some diseases, many with an autoimmune pathogenesis, are found with a higher than normal frequency in patients with CD; these include thyroid diseases, Addison disease, pernicious anemia, autoimmune thrombocytopenia, sarcoidosis, insulin-dependent diabetes mellitus, and alopecia. These associations may be a consequence of the shared identical HLA haplotypes (ie, B8, DR3). Nevertheless, the relation between CD and autoimmunity is more complex. The risk of autoimmune diseases developing in patients with CD may be directly correlated to the duration of Among other conditions an increased incidence of Down syndrome has been found in patients with CD compared with the general population. Selective IgA deficiency is also associated with CD: screening tests alternative to those based on the PrognosisThere is an increased risk of malignant lymphoma associated with CD in the order of 25- to 120-fold. The risk of malignancy is increased only in patients ingesting a normal diet. For patients who have followed a GFD for 5 years or more, the risk of having malignancies (all sites) is not increased when compared with the general population. The judicious approach is to Laboratory TestsAmong noninvasive screening tests the measurement of serum antigliadin antibodies has found great application. IgA class antiendomysial antibodies were reported as very sensitive and specific tests for CD, but in our experience the sensitivity and specificity of EmA (IgA type) are not 100%. One should always keep in mind that a patient with IgA deficiency might have a DiagnosisIn 1989 a working group from the European Society for Paediatric Gastroenterology and Nutrition reconsidered the original diagnostic criteria. The two requirements mandatory for the diagnosis of CD remain: (1) the finding of characteristic mucosa while the patient is eating an adequate amount of gluten and (2) a full clinical remission after gluten is withdrawn from the diet. The finding of circulating IgA antibodies to gliadin, reticulin, and endomysium at the time of diagnosis and their disappearance on a Gluten challenge is not considered mandatory but is used under certain circumstances such as doubt about the initial diagnosis. The diagnostic challenge is necessary to exclude other causes that could be responsible for the flat mucosa. Because most of The challenge should be discouraged before the age of 6 years and during the pubertal spurt. Gluten challenge should always be performed under strict medical supervision. The postchallenge biopsy is taken when there is a noticeable clinical relapse or in any event after 3 to 6 months. Serologic tests can be helpful in assessing the optimal timing of the biopsy to shorten the duration of TreatmentThe treatment of patients with CD consists of complete withdrawal of any food containing gluten; rice, potato, and maize, which are nontoxic, can be used as wheat substitutes. Other dietary measures are rarely needed. Secondary lactase deficiency resolves rapidly after the institution of a GFD, and milk can usually be tolerated after 2 to 4 weeks of Corticosteroids should be reserved for the life-threatening situations of celiac crisis. The clinical response to withdrawal of gluten is usually dramatic; an increase in growth velocity is observed. The GFD is recommended for patients with CD both with and Normalization of the jejunal histology occurs after ~6 months. The most likely cause of lack of response is failure to adhere strictly to the diet, but the possibility of sensitivity to other dietary proteins, lymphoma, and immune deficiency should also be considered. Conclusions and RecommendationsIt is our conviction that CD is much more common than the current rate of diagnosis indicates. A great proportion of individuals have clinically silent disease; others have a minor form of the enteropathy. The spectrum of gluten sensitivity extends beyond the severe damage of During the last few years the clinical presentation has dramatically changed, with extraintestinal autoimmune symptoms increasingly being recognized. Tests based on the measurement of antigliadin or EmA may be useful in mass screening for silent CD. However, the diagnosis is still based on the finding of a severe histologic lesion of the jejunum while the patient is receiving a gluten-containing diet and on its disappearance once the gluten is excluded from the diet. A lifelong strict gluten-free diet is |