Current guidelines for detecting undiagnosed celiac disease (CD) are inadequate for widespread CD screening, according to results from a study published online January 13 in Pediatrics.
Current guidelines rely on asking children about disease symptoms, but in a population-based screening study, researchers found that questionnaire data on symptoms did not differ significantly between individuals ultimately diagnosed with CD and those without the disease.
"Several studies have presented active case-finding strategies and concluded that they are effective by showing an increased incidence of CD in the group subjected to the case-finding, both in the clinical setting and at a population-based level," write Anna Rosén, MD, PhD, from Umeå University, Sweden, and colleagues. "However, these earlier studies have limitations because control groups were lacking, and the sensitivity, specificity, and predictive values of the suggested strategies therefore remain to be evaluated."
Therefore, in the current study, the authors aimed, first, to describe the symptoms and conditions associated with CD among screening-detected CD cases and children without CD as reported before CD status was known, and second, to evaluate questionnaire-based case-findings targeting the general population.
The study included children from 5 regions across Sweden who were 12 years old and in the sixth grade.
In the population-based screening, 7054 (98%) of the children and 6294 (88%) of their parents completed questionnaires on the frequency of CD-associated symptoms and conditions, which included tiredness, poor appetite, nausea, stomachache, upset stomach, abdominal gas, bloating, hard stools, loose stools, and lactose intolerance.
Parents also reported on the presence of CD-associated disorders in their child. These included anemia, type 1 diabetes, thyroid disease, rheumatic disease, inflammatory bowel disease, vitiligo, alopecia areata, dermatitis herpetiformis, trisomy 21, and Turner syndrome, as well as the presence of CD among the child's first-degree relatives.
Of 7208 children tested for tissue transglutaminase–immunoglobulin A or tissue transglutaminase–immunoglobulin G, the investigators found 192 (2.7%) with elevated levels.
Of those, 153 (2.1% of the total sample) tested positive for CD in a confirmatory small-bowel biopsy.
However, when the investigators compared questionnaire responses from children with screen-detected CD and those without, they found no significant difference in frequency (2.1% vs 2.1%; P = .930). Similarly, they found no significant difference in the frequency of CD-associated conditions (3.6% vs 2.1%; P = .07).
"Case-finding by asking for CD-associated symptoms and/or conditions would have identified 52 cases (38% of all cases) at a cost of analyzing blood samples for 2282 children (37%) in the study population," they write.
The sensitivity of this case-finding questionnaire was 38%, the specificity was 63%, the positive predictive value was 2%, and the negative predictive value was 98%.
"Our findings indicate that a questionnaire concerning symptoms cannot be used to discriminate unrecognized CD children from their non-CD peers, which is in line with a recent CD screening study in adults in the United States," the authors write.
Meanwhile, using CD-associated conditions as a screening tool was no more effective. This method would have uncovered just 10% of cases and necessitated blood tests for 381 individuals. The sensitivity of the screening method in the current sample was 10%, specificity was 94%, positive predictive value was 3.7%, and negative predictive value was 98%.
"The large and carefully designed study by Rosen et al...calls into question the validity of using symptoms to identify children for screening," writes Susan S. Baker, MD, PhD, from the Department of Pediatrics at the University of Buffalo, New York, in an accompanying commentary.
"These results call into question the recommendations of the guidelines," she adds. "Importantly, they raise concern for the guideline that recommends a gluten-free diet may be initiated without a biopsy when signs or symptoms suggestive of CD and high anti-TG2 titers with levels >10 times [upper limit of normal] are present."
The new study raises many questions and adds a layer of complexity to identifying children with CD, according to Dr. Baker. For example, if symptoms cannot be used to identify candidates for screening, what can be used? "With the relatively high prevalence [of CD], should all children be screened? If so, at what age? Are repeat screenings necessary because CD can present at any age, and if so, at what intervals? Is it ever justifiable to place a child with gastrointestinal symptoms on a gluten-free diet without clearly making a diagnosis of CD?"
Dr. Baker emphases that this last question is important because some experts now advocate a trial of a gluten-free diet for children with gastrointestinal symptoms.
"This study...raises important questions, suggests recommendations for screening of CD be revisited, and further suggests that care be taken in prescribing a gluten-free diet when a diagnosis of CD has not been made," she concludes."
The study was funded by the European Union; the Swedish Research Council; the Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning; the Swedish Council For Working Life and Social Research; and the County Council of Västerbotten. The authors and Dr. Baker have disclosed no relevant financial relationships.
Pediatrics. Published online January 13, 2014.
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