The clinical challenges of celiac disease go beyond identifying the condition and helping families adjust to a child’s gluten-free diet. Behavioral problems and/or an eating disorder may predate celiac disease, according to Alex R. Kemper, MD, MPH, division chief of ambulatory pediatrics at Nationwide Children’s Hospital, Columbus, Ohio, and deputy editor of Pediatrics.

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Also, a 2017 study discovered a bidirectional relationship between celiac disease and anorexia nervosa.

“We are learning more and more about celiac disease. The presentation and implication of celiac disease can involve more than the gastrointestinal tract,” Dr. Kemper noted. “Figuring out who to screen for celiac disease and how best to do so is complex, and we are always learning more about the best way to provide care after celiac disease is diagnosed.”

Impact of undiagnosed celiac disease on behavior

At the 2017 annual meeting of the American Academy of Pediatrics and, in a later interview, Dr. Kemper discussed a study that explored how behavior and celiac disease might be interrelated, particularly among children whose families don’t yet know their child has the condition.

“It’s challenging to assess the psychological impact of celiac disease autoimmunity when families aren’t aware a child has it, because prospective studies are difficult to do and recall bias can distort findings,” he noted.

“There have been reports of psychological problems in young children with celiac disease, but there have been questions about the type and degree of problems, and whether the problems might be caused by the celiac disease or be affected by the treatment,” Dr. Kemper said in an interview.

Smith et al. used data from a prospective international study, The Environment Determinants of Diabetes in the Young (TEDDY), designed to learn about factors associated with type 1 diabetes and celiac disease over a 15-year follow-up period (Pediatrics. 2017 Mar. doi: 10.1542/peds.2016-2848).

TEDDY tracked 8,676 infants deemed at high risk for celiac autoimmunity based on their human leukocyte antigen (HLA) antigen status at birth. The investigators regularly measured celiac disease autoimmunity based on tissue transglutaminase antibodies (tTGA), beginning at age 2 years. They assessed the children’s behavior at ages 3.5 years and 4.5 years using the Achenbach System of Empirically Based Assessment. If a child was found to have celiac disease, the researchers revisited the earlier behavior scores reported by their mothers before their children’s status were known.

When the children were 3.5 years old, 66 had celiac disease that their mothers were not yet aware of and 440 children had diagnosed celiac disease. The 66 mothers unaware of their child’s condition reported more anxiety, depression, aggression, and sleep problems in their children than did the 440 mothers who knew their child’s diagnosis or the 3,651 mothers of children without celiac disease. The differences were subclinical but statistically significant.

“It is important to recognize that the magnitude of the psychological problems in the 3.5 year olds was small,” Dr. Kemper said in an interview. “Parents might not recognize these symptoms.”

When the researchers looked at child behavior reports only among the mothers who knew their children had celiac disease, no differences existed regardless of the children’s tTGA levels or whether they were following a gluten-free diet. Then, when the children were 4.5 years old and all mothers were aware of their child’s status, no significant differences in mothers’ reporting of child behavior existed across any of the groups.

“Perhaps the knowledge of the child’s celiac disease autoimmunity increases a parent’s sensitivity to physical discomforts of their child while providing an alternative explanation for any psychological symptoms the child exhibits,” the researchers offered.

“Pediatricians should be aware of this association and consider testing young children with a family history of celiac disease if there are concerns,” Dr. Kemper said in an interview. “Because the magnitude of change was subclinical, this study does not suggest the need for more extensive screening of all children.”

Link between celiac disease and anorexia nervosa

The eating disorders study Dr. Kemper discussed examined possible associations between celiac disease and anorexia nervosa (Pediatrics. 2017. doi: 10.1542/peds.2016-4367). Researchers compared 17,959 Swedish females diagnosed with celiac disease between 1969 and 2008, at a median 28 years old, to 89,379 controls matched by sex and age.

Anorexia occurred more often among those with celiac disease than those without: a rate of 27 girls per 100,000 with celiac disease developed anorexia per year, compared with 18 of 100,000 without celiac disease, for a hazard ratio for an anorexia nervosa diagnosis of 1.46 (95% confidence interval, 1.08-1.98). In addition, girls whose celiac disease had not yet been identified had more than double the odds of developing anorexia before diagnosis than did those without celiac disease (odds ratio, 2.13).

Females with celiac disease therefore were more likely to have anorexia both before and after their celiac diagnosis, although the authors noted that surveillance bias may have made it more likely for either of the patients’ conditions to be identified after the first was. Another possible explanation is shared genetic risk factors, the authors wrote.

Dr. Kemper also offered possible reasons, including one related to the child behavior study.

“It could be that girls with celiac disease might develop anorexia because of the need to focus on their diet,” he said in an interview. “Celiac disease has been associated with psychological problems, and so that could contribute.”

Until further research can shed light on the reasons for the associations, physicians simply should be aware of the study’s clinical implications.

“Pediatricians should be aware of the bidirectional association between celiac disease and anorexia nervosa in teens and young adult women, and be prepared to evaluate for celiac disease or treat anorexia,” Dr. Kemper said.

He noted the need for more research to learn “what pediatricians can do to help to either prevent these problems from developing in the first place, or identify and treat celiac disease or anorexia nervosa early to prevent long-term complications.”

Dr. Kemper reported having no relevant financial disclosures and no external funding. Ketil Stordal, MD, PhD, of the anorexia study received funding from the OAK foundation in Switzerland, and Cynthia M. Bulik, PhD, from the same study received funding from the Swedish Research Council, and has consulted for and received a grant from Shire. The remaining authors of the anorexia study had no relevant financial disclosures. The behavioral study was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Centers for Disease Control and Prevention. The authors from the behavioral study had no relevant financial disclosures.

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Behavioral issues, anorexia may presage celiac disease