The accuracy of diagnostic indicators for coeliac disease: A systematic review and meta-analysis

Abstract

Background: The prevalence of coeliac disease (CD) is around 1%, but diagnosis is challenged by varied presentation and non-specific symptoms and signs. This study aimed to identify diagnostic indicators that may help identify patients at a higher risk of CD in whom further testing is warranted.

Methods: International guidance for systematic review methods were followed and the review was registered at PROSPERO (CRD42020170766). Six databases were searched until April 2021. Studies investigating diagnostic indicators, such as symptoms or risk conditions, in people with and without CD were eligible for inclusion. Risk of bias was assessed using the QUADAS-2 tool. Summary sensitivity, specificity, and positive predictive values were estimated for each diagnostic indicator by fitting bivariate random effects meta-analyses.

Findings: 191 studies reporting on 26 diagnostic indicators were included in the meta-analyses. We found large variation in diagnostic accuracy estimates between studies and most studies were at high risk of bias. We found strong evidence that people with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease are more likely than the general population to have CD. Symptoms, psoriasis, epilepsy, inflammatory bowel disease, systemic lupus erythematosus, fractures, type 2 diabetes, and multiple sclerosis showed poor diagnostic ability. A sensitivity analysis revealed a 3-fold higher risk of CD in first-degree relatives of CD patients.

Conclusions: Targeted testing of individuals with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease could improve case-finding for CD, therefore expediting appropriate treatment and reducing adverse consequences. Migraine and chronic liver disease are not yet included as a risk factor in all CD guidelines, but it may be appropriate for these to be added. Future research should establish the diagnostic value of combining indicators.

Fig 1. PRISMA flow diagram.

Abbreviations: BSG: Guidelines from the British Society of Gastroenterology [9]; NICE: National Institute for Health and Care Excellence; ESsCD: European Society for the Study of Coeliac Disease guideline [8]; ESPGHAN: European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines [7].

Fig 2. Summary graph of risk of bias.

Fig 3. Sensitivity, specificity, and positive predictive values.

Meta-analysis results are shown per diagnostic indicator. Positive predictive values (PPVs) were calculated for a population with a CD prevalence of 1% (red dotted line) using the estimated sensitivities and specificities from the meta-analyses. Diagnostic indicators are ordered from high to low PPV per diagnostic indicator group. The area of the box size is proportional to the total number of participants.

Fig 4. Subgroup analysis stratified by age group and CD diagnosis.

Stratified meta-analysis results are shown per diagnostic indicator. Positive predictive values (PPVs) were calculated for a population with a CD prevalence of 1% (red dotted line) using the estimated sensitivities and specificities from the meta-analyses. The area of the box size is proportional to the total number of participants.

Fig 5. Sensitivity analysis restricting to cohort studies.

Sensitivity meta-analysis on study design. Positive predictive values (PPVs) were calculated for a population with a CD prevalence of 1% (red dotted line) using the estimated sensitivities and specificities from the meta-analyses. The area of the box size is proportional to the total number of participants.