Celiac diagnosis without biopsy may be valid in asymptomatic children

Last Updated: 2015-10-14

By Will Boggs MD

NEW YORK (Reuters Health) - A new biopsy-sparing protocol for diagnosing celiac disease in symptomatic children with high anti-transglutaminase (anti-tTG) antibody levels might also be safe in asymptomatic children with elevated anti-tTG, researchers from Italy suggest.

"If confirmed in large multicenter prospective studies, the 'biopsy-sparing' protocol might be recommended in future to both symptomatic and asymptomatic patients with anti-tTG antibody titer (at least) 10 times the upper limit of normal (ULN) and anti-endomysial antibodies (EMA) and HLA-DQ2/DQ8 positive," Dr. Francesco Valitutti from Sapienza University of Rome told Reuters Health by email.

In 2012, the European Society of Pediatric Gastroenterology, Hematology, and Nutrition (ESPGHAN) published guidelines that said biopsies could be omitted in children and adolescents with signs and symptoms of celiac disease if they met the criteria just noted by Dr. Valitutti. The guidelines maintained the requirement for biopsy in asymptomatic patients and in patients with anti-tTG antibodies below 10 times ULN.

Dr. Valitutti's team assessed the accuracy of serological tests to diagnose celiac disease in asymptomatic patients in a retrospective review of 286 children and adolescents who had received a celiac disease diagnosis.

Among 196 patients with anti-tTG antibodies at least 10 times ULN and EMA positive, 156 had symptoms and 40 were asymptomatic. More than 90% of the symptomatic children (142/156, 91%) showed severe lesion degree on biopsy, and an even higher percentage of asymptomatic patients (37/40, 92.5%) had severe lesions.

Histological damage did not differ significantly between the "high-titer" symptomatic and asymptomatic children, according to the September 15th online report in The American Journal of Gastroenterology.

Among the children with lower titers of anti-tTG antibodies (still EMA positive), 70% of symptomatic children and 81% of asymptomatic children showed severe lesions.

"In relation to our results, we confirm that the most important predictor factor for intestinal damage is the titer of anti-tTG antibodies," the researchers note. "According to our data, extending the biopsy sparing protocol to 'high-titer' asymptomatic children would reduce the cost and the burden of biopsy and anesthesia."

"Asymptomatic patients should be (managed) with gluten-free diet as strictly as symptomatic ones, in order to prevent other autoimmune diseases and enteropathy-associated T-cell lymphoma," the investigators conclude.

Dr. Valitutti added that "it is essential to remember that in all cases the new diagnostic protocol must be handled by referral centers only and cannot be used indiscriminately in the primary care, in order to ensure the appropriateness of diagnosis and then the correct follow-up."

Dr. Farid Mahmud from Hospital for Sick Children, Toronto, Ontario, Canada told Reuters Health, "For any test a physician may order, we have to be aware of the clinical rationale for ordering it and the potential consequences; it the case of celiac disease (CD), this is a lifelong gluten-free diet which can be challenging for many patients. If there is a strong clinical suspicion for CD that includes weight loss, abdominal symptoms, poor growth, etc. or those at high risk of CD, then use of a CD testing strategy with elevated TTG levels is highly predictive for CD and biopsies may not be warranted in these patients."

"The caution relates to dissemination of the wrong message that TTG serology using a single cut-off (>10 ULN) for all TTG assays (as these differ widely in quality), in the absence of clinical judgment, is good enough to diagnose and treat celiac disease in all children," Dr. Mahmud said. "The ESPGHAN guidelines are nuanced to include multiple serologic testing strategies (TTG and EMA) plus HLA and exercise caution in young children (less than 2 years)."

"An increasing number of patients are asymptomatic, and in these patients with low TTG titers we need more evidence as to optimal testing strategy that may be effective in replacing biopsies, but we are not there yet," Dr. Mahmud said.

He added, "I think the issue that remains unclear relates to adherence with diet in asymptomatic patients who do not have biopsies: will they be as adherent?"

Dr. Dominica Gidrewicz from the University of Calgary, Alberta, Canada, who has previously reported on the effects of the 2012 guideline in children, told Reuters Health by email, "We agree that appropriate asymptomatic patients, who fulfill select criteria, can be offered a 'non biopsy' diagnosis."

At her center, she said, these criteria include:

1. Patient and family agreement and knowledge about celiac disease,

2. TTG > 10 times ULN,

3. An EMA of at least 1:80 (not just a positive EMA),

4. A positive repeat serology to exclude laboratory error,

5. HLA-DQ2 and/or -8 positivity, and

6. A serological response to a gluten-free diet.

She added, "These patients must be serially followed to evaluate serological response and ongoing compliance with a gluten-free diet. By using these criteria, we had a positive predictive value of 100% to diagnose celiac disease in symptomatic and asymptomatic patients."

"Low-titer children should all continue to have an intestinal biopsy to diagnosis celiac disease," Dr. Gidrewicz said. "Too many of them did not have significant diagnostic findings of celiac disease. The gluten-free diet is difficult to manage, expensive, and must be followed for life. To use it in 20-30% of patients who do not have celiac disease is equivalent to prescribing a drug for life in patients who do not need it."

SOURCE: http://bit.ly/1ZDqHcz

Am J Gastroenterol 2015.