In the JournalsPerspective

Non-invasive test diagnoses celiac disease without biopsy in some patients

A non-invasive test can accurately diagnose celiac disease in some patients and could lead to a decreased need for endoscopic diagnostic tests in the population, according to research published in Alimentary Pharmacology & Therapeutics.

Kalle Kurppa, MD, PhD, of the University of Tampere in Finland, and colleagues wrote patients that fit a “triple criteria” — transglutaminase 2 antibodies more than 10 times the upper limit of normal, positive endomysium antibodies, and celiac genotype — can be diagnosed with a serology test regardless of their pre-test probability of celiac disease.

“There is increasing evidence to support the accuracy of these guidelines for pediatric celiac disease if applied meticulously,” they wrote. “Whether the non-biopsy approach could be applicable also in adult celiac disease remains controversial.”

To assess the reliability of the serology test, researchers recruited three study cohorts; adults with high-risk clinical celiac disease suspicion (n = 421), moderate-risk family members of patients with celiac disease (n = 2,357) and low-risk individuals from the general population. They collected serum samples to determine which patients fit the “triple criteria.”

Investigators diagnosed 274 patients with celiac disease using intestinal biopsy. Ninety patients (59 high-risk, 17 moderate-risk and 14 low-risk patients) fit the “triple criteria.” All were diagnosed with histologically proven disease, giving the serology test a predictive value of 100%.

Fuchs and colleagues wrote that the test worked well regardless of the presence of apparent symptoms, which could prove beneficial in a disease where recognizing symptoms can be difficult.

“Definition of symptoms and their association with celiac disease are challenging, as the clinical and histological presentation may not correlate and symptoms can fluctuate or not be recognized until their alleviation on a glutenfree diet,” they wrote. “Applying such serologybased approach would lead to substantially reduced number of endoscopies and subsequent health care savings without affecting the diagnostic accuracy.” – by Alex Young

Disclosures: The authors report no relevant financial disclosures.

A non-invasive test can accurately diagnose celiac disease in some patients and could lead to a decreased need for endoscopic diagnostic tests in the population, according to research published in Alimentary Pharmacology & Therapeutics.

Kalle Kurppa, MD, PhD, of the University of Tampere in Finland, and colleagues wrote patients that fit a “triple criteria” — transglutaminase 2 antibodies more than 10 times the upper limit of normal, positive endomysium antibodies, and celiac genotype — can be diagnosed with a serology test regardless of their pre-test probability of celiac disease.

“There is increasing evidence to support the accuracy of these guidelines for pediatric celiac disease if applied meticulously,” they wrote. “Whether the non-biopsy approach could be applicable also in adult celiac disease remains controversial.”

To assess the reliability of the serology test, researchers recruited three study cohorts; adults with high-risk clinical celiac disease suspicion (n = 421), moderate-risk family members of patients with celiac disease (n = 2,357) and low-risk individuals from the general population. They collected serum samples to determine which patients fit the “triple criteria.”

Investigators diagnosed 274 patients with celiac disease using intestinal biopsy. Ninety patients (59 high-risk, 17 moderate-risk and 14 low-risk patients) fit the “triple criteria.” All were diagnosed with histologically proven disease, giving the serology test a predictive value of 100%.

Fuchs and colleagues wrote that the test worked well regardless of the presence of apparent symptoms, which could prove beneficial in a disease where recognizing symptoms can be difficult.

“Definition of symptoms and their association with celiac disease are challenging, as the clinical and histological presentation may not correlate and symptoms can fluctuate or not be recognized until their alleviation on a glutenfree diet,” they wrote. “Applying such serologybased approach would lead to substantially reduced number of endoscopies and subsequent health care savings without affecting the diagnostic accuracy.” – by Alex Young

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Sheila Crowe

    Sheila Crowe

    Following the 2012 ESPGHAN guidelines for children with celiac disease in which an endoscopy with duodenal biopsies was not required to make a diagnosis in most children, there have been attempts to provide similar pathways for adult patients. In this study by Kurppa and colleagues, data indicated that celiac disease serology in adults could reduce the need for endoscopies in one-third of patients. They also established three risk categories; adult high risk, moderate risk (having family members with celiac disease), and low risk (the general population).

    The goal was to evaluate accuracy in serology-based criteria with variable pretest probabilities for celiac disease. Serological and clinical data were collected and “triple criteria” for celiac disease comprised tTG (TG2) IgA over 10 times the upper limit of normal; positive EMA assay; and HLA genetics if asymptomatic. Overall, 274 participants had celiac disease. Ninety of the 274 could have avoided a biopsy. While this study from Finland is interesting, my concern is that in the United States, there are more than one tTG/TG2 antibody detection assays available to clinicians. In my clinics over the past two decades, I have seen different tTG/TG2 assays with abnormal levels starting from 3, 5, 13, and 20 arbitrary units (AU). Compared with Finland, the population in the U.S. constitutes a much more diverse genetic basis. Additionally, Canadian and U.S. gastroenterologists reported soon after the ESPGHAN guidelines that some children being diagnosed for suspected celiac disease by not having an EGD had missed eosinophilic esophagitis and other diagnoses. I would be interested to see a similar study, as was done in Finland, in the U.S. before discarding the practice of endoscopy and biopsies for diagnosing adult patients with celiac disease.   

    Gidrewicz and colleagues studied 17,505 North American children aged 3.5 months to 18 years with serology performed. Overall, 775 children had positive tTG, 574 with negative tTG were biopsied, and 25 were IgA deficient. Gidrewicz and colleagues concluded that the tTG is a very sensitive screen for celiac disease, but positive predictive value improved with a positive EMA titer. However, the authors concluded that to apply the 2012 ESPGHAN guidelines, clinicians must understand the performance of their serology tests. That study also corroborates my concerns regarding the Finnish study with a less diverse population and well standardized tTG assays in Finland compared with the North American situation.

    Reference: Gidrewicz D, et al. Am J Gastroenterol. 2015; 110, 760-767.

    • Sheila Crowe, MD, FRCPC, FACP, FACG, AGAF
    • Professor of Medicine
      Director of Research, Division of Gastroenterology
      University of California, San Diego

    Disclosures: Crowe reports serving as a scientific advisory board member for the Celiac Disease Foundation.