Celiac Disease and Anorexia Nervosa Linked, Study Shows

Ricki Lewis, PhD

April 03, 2017

Anorexia nervosa (AN) is associated with celiac disease (CD) both before and after CD diagnosis, a study published online April 3 in Pediatrics found.

"The bidirectional association between diagnosis of AN and CD warrants attention in the initial assessment and the follow-up of women with these illnesses," the researchers write. "This is important because the presentation of these conditions may mimic each other and the misdiagnosis of either disorder likely causes protracted and unnecessary morbidity."

Differentiating between the two can be difficult because CD and AN share some symptoms, including abdominal pain, bloating, diarrhea, and underweight. Because previous data linking the two conditions are mostly case reports, Karl Mårild, MD, PhD, from the Barbara Davis Center, University of Colorado, Aurora, and colleagues conducted a cohort and case-control investigation probing association between CD and timing of diagnosis of AN.

The researchers accessed records from Sweden's 28 pathology departments for 17,959 cases of small intestinal biopsy-verified CD in women from 1969 through 2008 and 89,379 sex- and age-matched population-based controls. The researchers identified AN cases through inpatient and hospital-based outpatient records.

The researchers also considered individuals undergoing biopsy who had small intestinal inflammation or normal mucosa but were positive for CD-related autoantibodies. They noted educational level, socioeconomic status, and type 1 diabetes status.

The hazard ratio for developing AN subsequent to CD diagnosis was 1.46 (95% confidence interval [CI], 1.08 - 1.98), and 1.31 beyond the first year after CD diagnosis (95% CI, 0.95 - 1.81). The odds ratio for association of previous AN diagnosis with diagnosis of CD was 2.18 (95% CI, 1.45 - 3.29). Adjustments for type 1 diabetes status and socioeconomic level did not alter the findings.

Women who had positive CD serology but without evidence of villous atrophy were also more likely to have AN diagnoses before or after CD diagnosis.

The researchers hypothesize three possible explanations for the bidirectional findings:

  • CD may have been misdiagnosed earlier as AN, or vice versa;

  • closer scrutiny of patients diagnosed with one condition may have led to a surveillance bias in detecting the second condition; and

  • a shared genetic susceptibility may have increased the risk of developing both conditions.

Whatever the reason behind the association, the ties between the two conditions are complex. "This bidirectional association should encourage physicians to closely monitor these patients and calls for heightened understanding of factors that contribute to their co-occurrence," the researchers conclude.

The investigators also point out how the conditions can exacerbate each other. People who know they have AN may find that eating foods with gluten may accelerate weight loss through diarrhea and consume more of them, whereas most people who know that they have CD may eat less to avoid the painful symptoms.

Limitations of the study include not considering people with undiagnosed or milder manifestations of either condition or clinical subtypes, or accounting for initial misdiagnoses of one disorder for the other.

"Although the vast majority of AN occurs in women, this disease can also occur in men," the researchers write. "Although we found no significant association between AN and CD in men, this does not mean that the risk of CD is different in women and men with AN. Our male-restricted analysis had low statistical power, and we urge caution when interpreting those findings."

In an accompanying commentary, Neville H. Golden, MD, and K.T. Park, MD, from the Department of Pediatrics, Stanford University School of Medicine, California, broaden the interpretation of the study in light of the popularity of gluten-free diets, even without diagnosis of CD, especially among young females. They write that the "interaction between gluten-free diets and eating disorders is an even larger issue. This important study only addresses the tip of the iceberg."

The editorialists hypothesize an underlying mechanism that combines the suggestions of the researchers: "The present study suggests that excessive focus on diet in patients with CD may lead to development of AN in susceptible individuals."

One coauthor reports receiving a grant from and consulting for Shire. The other authors and the commentators have disclosed no relevant financial relationships.

Pediatrics. Published online April 3, 2017. Article abstract, Commentary extract

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