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Celiac disease

The 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.

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.

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.

Epidemiology

A 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 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.

Pathogenesis

It 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" Forms

The 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.

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.

Associated Disorders

It 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.

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.

Prognosis

There 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.

Laboratory Tests

Among 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.

Diagnosis

In 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.

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.

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.

Treatment

The 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.