Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease.

Athena L Sheppard,Martha M C Elwenspoek,Hayley E Jones,Hazel Everitt,Jessica Watson,Peter M Gillett,Alastair D Hay,Susan Mallett,Victoria Corfield,Penny F Whiting,Lauren J Scott

doi:10.1111/apt.16729

Abstract

SummaryBackgroundThere is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead.AimsTo assess the diagnostic accuracy of serological tests for coeliac disease in adults and children.MethodsSeven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS‐2. Bivariate random‐effects meta‐analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds.Results113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta‐analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti‐tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies).ConclusionsAnti‐tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting.

Highlights

Coeliac disease is a chronic small intestinal immune-mediated enteropathy triggered by the ingestion of gluten, a protein found in wheat, rye and barley.[1]
Coeliac disease is estimated to affect around 1% of people in the UK,[2] only 24% of those with coeliac disease are thought to be diagnosed.[3]. These large numbers of undiagnosed patients—known as the “coeliac iceberg”—are thought to be a consequence of the non- specific nature of coeliac disease symptoms and variation in clinical presentation, from none to a broad spectrum of symptoms.[1]
We present the summary receiver operating characteristic (ROC) curve, which represents the trade-off between sensitivity and specificity across thresholds

Summary

Introduction

Coeliac disease is a chronic small intestinal immune-mediated enteropathy triggered by the ingestion of gluten, a protein found in wheat, rye and barley.[1]. People with certain health conditions, such as type I diabetes, autoimmune thyroid disease or Down syndrome, as well as first-degree relatives of people with coeliac disease, are at higher risk of developing coeliac disease than the general population and are more likely to present without classical symptoms.[4]

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