Studies rebut common theories about pediatric celiac disease

May 07, 2016

Celiac disease (CD) is an immune-based reaction to gluten — a protein in wheat, rye and barley — that results in damage to the small intestine mucosa. It occurs in genetically predisposed children and adults and usually responds to a gluten-free diet.

CD is one of the most common causes of malabsorption; progressive villous atrophy limits both production of digestive enzymes and absorption of iron and some vitamins, especially fat-soluble vitamins such as A, D, E and K. Although adults with CD tend to show low levels of these and other micronutrients, a retrospective study published in the Journal of Pediatric Gastroenterology and Nutrition in 2014 found little evidence of vitamin deficiencies in newly diagnosed children.

The study examined the records of pediatric patients at Mayo Clinic between 1994 and 2012 who had vitamin levels checked at the time of CD diagnosis. Of 83 patients, all had normal levels of vitamin A and only two, both with complete villous atrophy, had low levels of vitamin E. Thirty-one patients had insufficient 25-hydroxy vitamin D — less than the frequency of vitamin D deficiency in the general pediatric population in the U.S. in 2004. The low levels quickly corrected with vitamin supplements and a gluten-free diet.

Imad Absah, M.D., a pediatric gastroenterologist at Mayo Clinic's campus in Rochester, Minnesota, and the study's senior author, says the near-normal vitamin levels in these patients may be the result of earlier diagnosis due to sensitive serologic markers and increased awareness or changes in the disease itself.

"We don't see as many children who have classic malabsorptive syndrome with chronic diarrhea, steatorrhea, weight loss and multiple deficiencies," he says. "They are more likely to be asymptomatic or monosymptomatic, with, for example, abdominal pain, recurrent oral ulcers, poor tooth enamel, skin rash or celiac hepatitis.

"About 1 in 5 children with celiac disease has constipation, so patients with constipation outside the range of what is physiologically normal should be screened. Kids with iron deficiency anemia that's not responding to treatment should be tested, and any concern about growth should be checked.

"We are doing better at screening because of the vigilance of providers, but it can still be seven or eight years before some children are diagnosed."

Poorer healing

Treated patients also have lower rates of complete mucosal healing than expected, according to a study published in 2014 in the same issue of the Journal of Pediatric Gastroenterology and Nutrition. In that study, Dr. Absah and colleagues retrospectively reviewed the records of 40 children with CD who underwent a second small bowel biopsy at Mayo Clinic's Minnesota campus between 1997 and 2013. The most common indication for the second biopsy was abdominal pain, followed by diarrhea and constipation. The average time between biopsies was two years.

The investigators found a total of six patients — two with persistent abdominal pain and one with diarrhea — who had partial or complete villous atrophy. Dr. Absah says it is important to note, however, that these children had persistent symptoms as an indication for repeating endoscopy, making it hard to generalize the data to all children with treated CD.

The study did not look at why healing was impaired, but another 2014 study, published in Alimentary Pharmacology & Therapeutics, did. In that study, researchers at the Karolinska Institutet in Stockholm identified over 7,000 patients with diagnosed CD who underwent follow-up biopsies between 1969 and 2008. Of these, nearly half had persistent villous atrophy, which the investigators suggest was associated with a lack of access to or poor understanding of a gluten-free diet.

Children and the gluten-free diet

Clinical response to a gluten-free diet is faster in children than adults; the mean time to symptom relief is four to eight weeks, and serologies often improve within six months and normalize within 12 to 18 months. Yet the diet is challenging to follow, especially for older children and teens, Dr. Absah says.

"Compliance studies have shown that preschool-age children have an easier time transitioning to a gluten-free diet because they don't have established food preferences. It's also easier if family members switch to the diet at home, at least for the first few weeks. When everyone is eating the same meal, the risk of cross-contamination is much lower, and kids don't feel as different.

"Normalization is one of the most important things. This is a lifelong diagnosis, so we want to give kids as much normalcy as possible," he explains.

Teens, on the other hand, have established food preferences and are usually involved in school and social activities, where they are likely to be offered meals that aren't gluten-free.

"We schedule follow-up visits at three and six months to reinforce the importance of adhering to the diet," Dr. Absah says. "We may offer a full visit or repeat bloodwork to see if serologies are trending down; if they are trending down at six months, we are reassured, and patients are praised for being compliant with the diet, which helps them stick with it."

The greatest challenge, he says, comes from patients who were screened but are asymptomatic. "We bring them back for follow-up, and they meet with an experienced dietitian one more time to assess the risk of cross-contamination and to make sure they understand how to determine if a food or over-the-counter supplement or medication is gluten-free," he explains.

Clinical trial recruitment

Dr. Absah is currently recruiting patients for an observational clinical trial to assess the effect of gluten on gut barrier function using a new gut permeability test developed at Mayo Clinic. The study will look at gut permeability in three groups:

  • Children with siblings who have celiac disease
  • Children with self-diagnosed non-celiac gluten sensitivity
  • Age- and sex-matched healthy controls

Participants will undergo celiac serologic and genetic testing before the gut permeability test.

To refer patients for the study, NCT02690532, contact James D. Allen or Michelle M. Burtis, CCRP.

For more information

Imam MH, et al. Is it necessary to assess for fat-soluble vitamin deficiencies in pediatric patients with newly diagnosed celiac disease? Journal of Pediatric Gastroenterology and Nutrition. 2014;59:225.

Ghazzawi Y, et al. Mucosal healing in children with treated celiac disease. Journal of Pediatric Gastroenterology and Hepatology. 2014;59:229.

Lebwohl B, et al. Predictors of persistent villous atrophy in coeliac disease: A population-based study. Alimentary Pharmacology & Therapeutics. 2014;39:488.

Mayo Clinic. Gut permeability assessment in celiac and gluten sensitive children.