Looking for coeliac disease hiding in the family

Coeliac disease is an immune‐mediated enteropathy, triggered in genetically susceptible people by dietary gluten.1 Diagnosis has historically been based on positive serological test results (such as elevated anti‐tissue transglutaminase [tTG] or endomysial antibody levels) together with characteristic histological features identified by small bowel biopsy in people with typical symptoms. However, serological diagnosis (without small bowel biopsy) may be considered in children.2 In Australia, an estimated 1.2% of men and 1.9% of women have coeliac disease,3 while an electoral roll‐based study determined a rate of 1.2% in Christchurch, New Zealand.4 Both figures are consistent with the estimated pooled global prevalence of 1.4%.5

Some people are at significantly greater risk of developing coeliac disease, including those with certain autoimmune conditions (including type 1 diabetes mellitus) and, in particular, people with first degree relatives diagnosed with coeliac disease.6 Consequently, many medical practitioners actively screen individuals in these risk groups, regardless of the presence of symptoms. The prevalence of coeliac disease among first degree relatives of Australians diagnosed with the disorder is likely to be similar to rates reported overseas (at least 7.5%).6,7,8

In this issue of the MJA, Muir and colleagues report the results of their focused screening of 202 first degree relatives of 134 people diagnosed with coeliac disease in Brisbane.9 In their cross‐sectional observational study, the participants were assessed using standard serological tests (anti‐tTG IgA, anti‐deamidated gliadin peptide IgG) and screened for coeliac disease risk alleles (HLA‐DQ2/8/7 genotyping). Endoscopic assessment for definitive histological evidence of coeliac disease was recommended for participants with positive serological screening results.

Coeliac disease susceptibility haplotypes were identified in 173 first degree relatives (86%), for sixteen of whom (9%) serological tests were positive. Ten people in this group underwent endoscopy; nine met the histological criteria for the diagnosis of coeliac disease, including all seven children and two of the three adults from whom small bowel biopsies were collected. Participants with positive serology results who did not proceed to endoscopy generally had low anti‐tTG IgA levels. Muir and colleagues noted that their estimated rates of coeliac disease in this group of first degree relatives (children, 11%; adults, at least 1.4%) were similar to those reported by other investigations.9

Studies of focused screening of first degree relatives or other groups of people at high risk have found that many of those diagnosed with coeliac disease had no symptoms and may consequently not have been diagnosed otherwise.6,7,8 Muir and his colleagues did not report whether the first degree relatives in their study had symptoms or signs suggestive of coeliac disease.9

The authors of a meta‐analysis estimated that the pooled prevalence of coeliac disease in first degree relatives was 7.5%.7 The rate was higher among female (8.4%) than male relatives (5.2%) and higher among siblings (8.9%) than parents (3.0%) of people with coeliac disease; it also varied by geographic location (highest in North America, lowest in South America).7 A more recent report found that 11% of siblings of children diagnosed with coeliac disease had the disorder.8

The study by Muir and colleagues included a relatively small number of participants (mostly adults) from just one region of Australia; their findings may not be generalisable across Australia. As participants were assessed only once and some people with positive serology results did not undergo endoscopic assessment, coeliac disease rates may have been underestimated; further, some participants who are currently disease‐free may nevertheless be at risk of developing coeliac disease in the future.10

While it is estimated that 1–2% of Australians have coeliac disease,3 it is likely that many people with the disorder are not diagnosed in a timely fashion, if at all. Actively looking for coeliac disease in groups at greater risk may help identify these people earlier and avert disease‐related complications, regardless of the presence or absence of symptoms. The study by Muir and his colleagues highlights the importance of active searching among first degree relatives, and further focused screening could build upon their findings.