The serology-based ‘no-biopsy’ approach recommended for diagnosis of paediatric coeliac disease can also be used in adults, an international study suggests.
Instead of relying on upper GI endoscopy to identify duodenal mucosal abnormalities, the diagnosis of CD can be confirmed by a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels, according to research published in Gut.
The study involving 1417 adult patients assessed in UK and international specialist CD centres found that almost all those with IgA tTG titres that were ten or more times the upper limit of normal (ULN) had small intestinal mucosal changes diagnostic of CD (Marsh 3 lesions) on duodenal biopsy.
Overall, 30% of patients had tTG titres of ≥10×ULN, of which 424 (98%) patients had Marsh 3 lesions on duodenal biopsy and were diagnosed with CD.
In a prospective cohort of 740 patients suspected of having CD and referred to a UK centre, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively.
For a second cohort of 532 patients with low suspicion and low prevalence (3.2%) of CD, the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively.
In a third cohort of 145 patients with suspected CD assessed in international centres, the predictive value of using a 10×ULN threshold at detecting individuals with Marsh 3 lesions was 95.2%.
The study investigators said their findings showed that tTG titres of ≥10×ULN were equally good at predicting Marsh 3 lesions in the setting of both low and high disease pretest probability and prevalence.
They noted that European Society for the Study of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines for the diagnosis of CD had challenged the necessity for duodenal biopsies in paediatric patients.
In 2012, ESPGHAN recommended that tTG titres of ≥10×ULN in combination with a positive EMA antibody test and compatible human leucocyte antigen (HLA) genotype was sufficient to support a diagnosis of CD in symptomatic individuals.
However the study authors cautioned that serology testing should not be seen as a screening tool for the general population or to be used by GPs to diagnose CD in adults.
A biopsy should still be performed in adults, particularly if there were ‘red flag’ signs/symptoms, such as persistent dyspepsia, weight loss and unexplained iron deficiency anaemia, they said.
“While these data support the use of the biopsy avoidance approach in adults, we still advocate that suspected cases with tTG titres exceeding the 10× threshold are referred to a gastroenterologist for assessment, rather than the diagnosis of CD being made in primary care,” they wrote.
“This study supports a no-biopsy strategy in adult gastroenterology services. This approach has implications in reducing the cost, risk and caseload associated with diagnostic endoscopy in adult CD,” they concluded.