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What Happens to Patients With Markers of Celiac Disease but no Symptoms?

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A 3-year study of adults with potential celiac disease found most to have symptoms, and that these adults improve after gluten withdrawal, as reported in the May issue of Clinical Gastroenterology and Hepatology. The study also shows that patients without symptoms should not go on gluten-free diets, because they are unlikely to develop villous atrophy.

Celiac disease is an immune-mediated gluten-dependent systemic disorder characterized by serologic and genetic factors and villous atrophy in the small intestine. Although some people test positive for antibodies and carry genetic alleles associated with celiac disease, they have relatively normal or slightly inflamed intestinal mucosa, with no or mild enteropathy. These patients are considered to have potential celiac disease (defined as increased serum levels of antibodies against tissue transglutaminase [tTG] without villous atrophy). They can have gastrointestinal and extra-intestinal symptoms or be completely asymptomatic.

It is not clear whether gluten-containing diets will lead to overt enteropathy over time, or whether these patients should be placed on a gluten-free diet.

To learn more about progression of potential celiac disease, Umberto Volta et al performed a prospective study to track clinical, serologic, and histologic features of 77 patients. The subjects had normal or slight inflammation of the small intestinal mucosa and were followed for 3 years.

Sixty-one patients had intestinal and extra-intestinal symptoms and 16 were completely asymptomatic at diagnosis. All subjects tested positive for IgA endomysial and tTG antibodies, except for 1 patient with IgA deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1.

IgA anti-TG2 intestinal deposits (A, arrowheads), along with histologic (B) and immunohistochemical (C) analyses of intestinal tissue from a patient with potential celiac disease. Note the dense immunostaining for CD3, indicating abundant lymphocytic infiltrate and increased numbers of intraepithelial lymphocytes. Bar = 25 μm
Anti-transglutaminase 2 deposits (A, arrowheads), along with histologic (B) and immunohistochemical (C) analyses of intestinal tissue from a patient with potential celiac disease. The dense immunostaining for CD3 indicates infiltration of lymphocytes and increased numbers of intraepithelial lymphocytes.
Bar = 25 μm

Patients with symptoms were placed on a gluten-free diet and followed to assess their clinical and serologic features. Patients without symptoms were left on a gluten-containing diet and followed for 2 years with histologic evaluation.

Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients.

Of the 16 asymptomatic patients, who were left on the gluten-containing diets, only 1 developed mucosal flattening; levels of anti-endomysial and tTG antibodies fluctuated in 5 of these patients or became undetectable.

A significantly higher proportion of symptomatic patients had autoimmune disorders (36%) compared with asymptomatic patients (5%).

Volta et al recommend using caution in placing asymptomatic patients on gluten-free diets, based on the spontaneous loss and fluctuations in serologic markers of celiac disease while they are on gluten-containing diets. They recommend gluten-free diets for symptomatic adults, but say that asymptomatic patients should continue their gluten-containing diets under strict clinical, serologic, and histologic surveillance. They believed that only a small proportion of asymptomatic adults will develop active disease over time.

In an editorial that accompanies the article, Jocelyn A. Silvester and Ciarán P. Kelly point out that the asymptomatic patients were generally younger (median 21 years vs 36 years for those who were symptomatic), so symptomatic celiac disease might develop with more time.

A guideline from the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition allows for diagnosis of celiac disease without evaluation of small intestinal histology under certain circumstances.

Silvester and Kelly say the findings of Volta et al are consistent with this guideline, in that symptomatic patients were HLA DQ2- or HLA DQ8-positive and responded to a gluten-free diet, even if they did not have villous atrophy. Biopsy findings were therefore not required for management and did not seem to predict response to the gluten-free diet. The findings suggest that a gluten-free diet is worth trying in symptomatic patients with potential celiac disease.

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Kristine Novak

Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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