Studies presented at this year’s Digestive Disease Week addressed one current challenge regarding celiac disease: reliable, cost-effective detection.
- William F. Balistreri, MD, Digestive Disease Week (DDW) 2018 1
- To Screen or Not to Screen?
- Sex-Based Differences?
- The Role of HLA Testing in Stratification
- Point-of-Care Testing
- The Role of Biopsy
To Screen or Not to Screen?
The US Preventive Services Task Force recently concluded that “the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons.”
While the evidence may not support general population screening for CD, an important question is whether there is evidence to support or refute screening in selected populations, especially in children, given the long-term impact of untreated disease.
To help address this issue, Gallant and colleagues reported preliminary results of the Autoimmunity Screening for Kids (ASK) study, a study designed to screen 50,000 children for CD from the general population of the Denver metro area. They presented results from the initial screenings (approximately 4500 children).
Overall, 3% of the children were found to be positive for transglutaminase autoantibody (TGA); most screen-detected children were asymptomatic. Symptoms of potential CD were reported in about 30% of both TGA-positive and TGA-negative children.
The initial results of this ongoing mass-screening program indicate a high prevalence of undiagnosed celiac autoimmunity in the general pediatric population. We look forward to the full results of this study, which will include cost estimates and potential risks and benefits, to help inform evidence-based recommendations. This also will hopefully address the question of whether to target or prioritize specific populations.
The Role of HLA Testing in Stratification
To provide insight into prioritization strategies, Gallant and colleagues tested the hypothesis that the population frequency of human leukocyte antigen (HLA), a major genetic risk factor for CD, could be used to estimate the regional incidence.
Data obtained from annual screening of 6798 HLA-typed children followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) international study were used to determine cumulative risks. Sweden had the highest cumulative incidence of CD (2.1%) and celiac disease autoimmunity (CDA) (6.8%). Both Finland and Germany had a cumulative incidence of CD and CDA of 1.8% and 5.9%, respectively. In the United States, the cumulative incidence of CD and CDA was 1.8% and 5.0%, respectively, higher than past estimates. Homozygosity for HLA-DQ2 conferred the highest risk for CD and CDA.
These data may also help in the construction of a structured, stratified case-finding strategy.
Jansson-Knodell and colleagues explored sex-based differences via a large-scale, systematic review of available literature (MEDLINE, Embase, Cochrane, and Scopus databases) regarding epidemiologic studies of the relative incidence of undetected CD. They identified 88 articles that met inclusion criteria (290,969 subjects). Overall, the rate of undetected CD was higher in females than in males (the relative risk [RR] for women was 1.39). In children, undetected CD was higher in girls (RR 1.79).
While the biologic basis for this observed sex-based predominance of undetected CD was not defined, the finding could inform the strategies for screening, diagnosis, and management.
Newly developed point-of-care tests (POCTs) for CD may facilitate screening, especially in areas with limited access to laboratory-based testing. However, concern has been expressed regarding the reliability of these assays.
Singh and colleagues performed a systematic review and meta-analysis and concluded that the pooled sensitivity and specificity of currently available POCTs for diagnosing CD were both 94%. The pooled positive and negative likelihood ratios for POCTs were 17 and 0.06, respectively. These sensitivity estimates of POCTs were significantly lower than those of ELISA-based TGA tests.
Further research assessing the diagnostic accuracy and costs of POCTs is still needed before this strategy can be broadly recommended.
The Role of Biopsy
Guidelines recommend that individuals with symptoms suggestive of CD have histologic confirmation via duodenal biopsy, the gold standard for diagnosis. Failure to adhere to these guidelines, however, appears to be common. Does the absence of a biopsy-confirmed diagnosis of CD affect outcome? Specifically, would adherence to a gluten-free diet be as stringent if the diagnosis was not biopsy confirmed?
Joelson and colleagues explored these questions by seeking differences in adult patients in whom the diagnosis was based on biopsy confirmation versus those diagnosed by serology alone.
They analyzed data derived from a questionnaire distributed by the Celiac Disease Foundation to a patient-powered research network (iCureCeliac®). They identified 982 patients who met their criteria for inclusion; 79% were diagnosed by biopsy and 21% were diagnosed by serology alone. Patients diagnosed by serology were more likely to be diagnosed by healthcare practitioners other than those within the gastroenterology specialty, less likely to seek nutritional counseling for their disease, and more likely to take supplements to aid in the digestion of gluten, a treatment strategy that lacks evidence.