Ninety Percent of Celiac Disease Is Being Missed : Journal of Pediatric Gastroenterology and Nutrition

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Ninety Percent of Celiac Disease Is Being Missed

Ravikumara, M; Nootigattu, VKT; Sandhu, BK

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Journal of Pediatric Gastroenterology and Nutrition: October 2007 - Volume 45 - Issue 4 - p 497-499
doi: 10.1097/MPG.0b013e31812e5710
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Celiac disease (CD) is an immune-mediated enteropathy, induced by dietary gluten in genetically susceptible individuals. It has diverse manifestations, including being completely asymptomatic. Untreated, CD has the potential to result in various health problems ranging from malabsorption leading to various nutrient deficiencies, anemia, and osteoporosis to autoimmune problems and malignancies (1–4). With the advent of highly sensitive and specific serological markers like anti-tissue transglutaminase and anti-endomysial antibodies (EMA) and awareness of specific high-risk patient/population groups, the ability for early recognition and diagnosis of CD has increased. Although the available serological tests are highly sensitive and specific, they are not definitive. Confirmation of CD requires demonstration of enteropathy in small intestinal biopsy specimens (5).

Despite these advances in our understanding of CD, increased public and professional awareness and the availability of reliable serological testing, CD may be underdiagnosed in clinical practice. Serological screening of 5470 children, randomly selected from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of 13,971 resulted in 1% testing positive for IgA-EMA (6). ALSPAC is an anonymous study, and hence these children could not be individually identified and referred for intestinal biopsy. However, all of the children within the study who are suspected of having CD are referred to just 1 center for biopsy confirmation of CD before being given a gluten-free diet.

The aim of this study was to identify the children who were likely to be part of the ALSPAC cohort and had histologically confirmed CD to determine the magnitude of discrepancy between the number of children who had biopsy-confirmed CD and the number expected to have CD based on serological testing.


ALSPAC is a population-based study designed specifically to determine ways in which the individual's genotype combines with environmental factors to influence health, behaviour, and development (7). Enrollment was in early pregnancy, and a total of 14,541 pregnancies (expected date of delivery April 1, 1991—December 31, 1992) were enrolled, representing about 85% of the eligible population. A total of 13,971 children were participating in the study at the age of 12 months, and they have continued to be followed up with questionnaires and annual clinic visits. (7,8). From this cohort, 5470 children were randomly selected at 7.5 years of age and screened for CD by use of anti-tissue transglutaminase with further testing of samples that were positive for IgA-EMA. Of those, 54 had positive results for IgA-EMA, suggesting that 1% of children are likely to have CD (6). Inasmuch as ALSPAC is an observational study based on analysis of anonymous samples, these children could not be individually identified and referred for confirmatory biopsy and treatment.

The Department of Paediatric Gastroenterology at Bristol Children's Hospital is the only center for pediatric endoscopy service for Avon and for the rest of the southwestern region of the UK. All of the children within Avon suspected to have CD are referred to the department for endoscopic small intestinal biopsy for confirmation of CD before they are given a gluten-free diet. From 1990 onward, the department has been prospectively collecting data from all children undergoing small bowel biopsy and receiving diagnoses of CD. These data were analyzed to identify biopsy-confirmed CD patients from the Avon postal code whose dates of birth were between April 1, 1991, and December 31, 1992. To ensure complete coverage and accuracy, the data were cross-checked with central computer records, dietetic records, and records from 3 other hospitals in the area.


The study identified 12 children, 9 boys and 3 girls, who had biopsy-confirmed diagnoses of CD and whose details were concordant with the ALSPAC cohort. Of those, 6 were referred by general practitioners and 6 by consultant pediatricians for further investigation and treatment of various symptoms. At diagnosis, all were older than 2 years of age, and 4 children had positive family histories for CD. Diarrhea was present in 7 children, abdominal pain in 5, weight loss in 5, and vomiting in 2. One child had constipation.

On the basis of serological screening at age 7.5 years, at least 140 children from the ALSPAC cohort would be expected to have CD (ie, 1% of 13,971 children in the ALSPAC cohort). However, under current clinical practice and until December 2005, CD was diagnosed in only 12 children, now 13 to 14 years old. This study confirms that under the current clinical practice, despite the fact that there is a national health service in the United Kingdom, >90% of childhood CD remains undiagnosed.


Serological screening of 5470 children from a cohort of 13,971 at the age of 7.5 years identified 54 as having positive anti-EMA (6). According to these data, the ALSPAC cohort of 13,971 children should contain at least 140 children in whom CD would be expected to develop. In the current clinical practice, by the age of 14, only 12 children from the cohort have received formal diagnoses of CD and treated with a gluten-free diet, giving the incidence of diagnosed CD as 1 in 1164. Some of the seropositive children will continue to present and subsequently receive diagnoses of CD, but this is likely to be only a small minority. Another possible bias may be that families move out of the region and the diagnoses are made elsewhere. This is unlikely because ALSPAC is a stable population. Although families move within Avon, few families move out of Avon. (This is known to be <5% over the study period). The study suggests that in >90% of children with probable CD, the condition was not being clinically suspected and hence not formally diagnosed, and the children given a gluten-free diet. These children may be at risk of complications associated with untreated CD.

The findings of this study add weight to the evidence that clinically suspected cases of CD account only for a minority of patients and that a majority of cases remain undiagnosed (9–11). There may be a lack of awareness of the increasingly diverse manifestations of CD. The presenting features of childhood CD seem to have changed over the years, with many children being completely asymptomatic (12). Among the children in the ALSPAC cohort (n = 5470), there seem to be no significant differences in gastrointestinal symptoms in IgA-EMA positive children compared with IgA-EMA negative children (6). However, IgA-EMA positive children at the age of 7.5 years were shorter and lighter, equivalent to about 9 months' growth deficit, suggesting a significant impact on optimal health potential.

The potential health hazards of untreated CD are many. It has been reported that early diagnosis and initiation of a gluten-free diet not only relieves symptoms but also may prevent severe complications of untreated CD, including autoimmune diseases and malignancies (13–15). Some evidence suggests the benefits of a gluten-free diet in terms of reduction of long-term morbidity and mortality in asymptomatic people with screening-detected CD (16,17). The availability of highly sensitive and specific serological markers for CD in such a context raises the question of population screening. CD satisfies all 5 of the World Health Organization criteria for mass screening: the disease is common, early detection of the disease is difficult, screening tests are highly sensitive and specific, effective treatment is available, and if not recognized the disease could result in severe complications, which are difficult to treat (18). Controversies exist around various issues, including the cost–benefit ratio of mass screening, the benefit of a gluten-free diet in asymptomatic individuals, compliance with a gluten-free diet in asymptomatic individuals, and appropriate age for screening. The ALSPAC data suggest that screening at 7.5 years of age will detect most cases of probable CD (ie, in 1% of the population). A recent study of Italian school children ages 6 to 12 years also gave a prevalence of about 1% with mass screening. This study was not anonymous, and the children were offered formal diagnosis with small bowel biopsy and then given a gluten-free diet. Dietary compliance was good at 24 months follow-up, even in asymptomatic children (19). An assessment of the cost–benefit ratio was made. Without screening, the cost to the Italian health service of delayed/complicated diagnosis of CD was estimated to be approximately €8700/case. In addition, there is a personal cost related to morbidity.

In conclusion, this large population-based study from the UK suggests that under current clinical practice, 90% of CD in children remains undiagnosed. With evidence that seropositivity at 7 years of age is similar to that seen in the general population (6) and that there is good dietary compliance even in asymptomatic children with screening-detected CD (19), the study findings add further evidence to the debate that serious consideration should be given to screening all children for CD. This could be safely done at 7 years of age, but by this age, there already seems to be an impact on growth. Further studies may be needed to establish the earliest optimal age for screening.


The authors thank Prof J. Golding and the ALSPAC team and their pediatric and dietetic colleagues for their help and support.


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Celiac disease; Screening; ALSPAC; Incidence

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