The Role of Screening for Coeliac Disease in Asymptomatic Individuals
R Kernan, S Hussey
Department of Paediatric Gastroenterology, Our Lady’s Children’s Hospital, Crumlin
Coeliac Disease (CD) is a genetically linked autoimmune disorder in which ingestion of gluten causes an immune-mediated reaction in the small intestine, leading to either gastrointestinal malabsorptive symptoms or non-gastrointestinal features including anaemia, Vitamin D deficiency, fatigue and growth failure in childhood. Ireland’s rising incidence of CD likely represents a true increase in disease, correlating with emerging epidemiological data from Scotland and North America1, 2.
A recent study by the US Preventive Services Task Force (USPSTF) reviewed the benefits and harms of screening for coeliac disease in asymptomatic adults, adolescents and children over three years of age3. The study addressed a predefined set of 7 key questions: What is the effectiveness of screening vs not screening for coeliac disease in asymptomatic adults, adolescents or children on morbidity, mortality or quality of life? What are the benefits of targeted vs universal screening in this cohort? How accurate are the results of screening tests? Does initiation of a gluten free diet in screen-detected coeliac disease improve morbidity, mortality or quality of life when compared against no treatment? Does treatment of asymptomatic coeliac disease lead to an improved health-related quality of life compared with treatment commenced after a clinical diagnosis? What harms come from screening, and what harms are associated with treatment? A well-structured literature search (3,036 citations) yielded just four articles (comprising of one systematic review of 55 studies, and three primary studies). The study could neither find sufficient evidence to guide clinicians’ decisions regarding CD screening in asymptomatic individuals, nor of the potential harms of doing so.
Current National Institute for Health and Care Excellence (NICE) Guidelines recommend coeliac screening of symptomatic patients (intestinal/extra-intestinal features); if a first degree relative has CD; for patients with Type 1 Diabetes, autoimmune (AI) thyroid disease; for patients with metabolic bone disorders, unexplained neurological symptoms, unexplained subfertility / miscarriages, raised liver function tests, dental enamel defects, Trisomy 21 and Turner syndrome. First-line investigations are anti-tissue transglutaminase IgA (tTG) testing, with the more specific anti-endomysial antibody IgA (EMA) performed if tTG is weakly positive. The European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines have broader CD screening criteria, including autoimmune liver disease, Williams syndrome and selective IgA deficiency. Their screening criteria recommend HLA testing of DQ 2 and DQ 8 as first line investigations prior to tTG IgA testing, with EMA IgA testing performed if tTG IgA results are less than 3 times the upper limit of normal4. Endoscopic duodenal biopsy is recommended for any positive screens in both guidelines, while patients remain on normal gluten containing diets.
A systematic review of accuracy of screening tests in symptomatic patients, when compared against duodenal biopsy as the reference standard, showed IgA tTG has a sensitivity and specificity of 92.8% and 97.9% respectively. EMA IgA testing had a lower sensitivity of 73% but a higher specificity of 99%5. The performance of these screening tests in asymptomatic individuals is more underwhelming. A Czech study of at risk children showed a reduction in diagnostic sensitivity and specificity to 67% and 83% respectively when combining both the presence of positive EMA antibodies and tTG > 10 times the upper limit of normal6.
The evidence for treatment of asymptomatic patients with screen detected coeliac disease in order to improve health and quality of life is limited. An adult study in Finland (n=40) showed small but significant improvements on Likert GI symptom Rating Scales and Psychological General Well Being Scales upon omission of dietary gluten. No significant differences were seen when compared against a control group in terms of haemoglobin levels, serum iron levels, BMI, body fat or lumbar/femoral bone neck densities. In addition, there was some disenchantment seen on social functioning scales associated with a gluten free diet7. There are no published studies of the effectiveness of treating screen-detected disease compared to symptomatic CD regarding morbidity, mortality or quality of life. Similarly, there are no studies of potential harms associated with the treatment of screen-detected coeliac disease.
The lack of evidence for coeliac screening in asymptomatic patients presents a challenge for clinicians. Clearly, there is a higher predisposition toward the development of coeliac disease in some conditions such as Type 1 diabetes and Trisomy 21, although the positive predictive value of a screening test decreases in the absence of symptoms. Equally, the nature of symptoms can be very subjective. Patients with subtle symptoms may not initially acknowledge them but may report improvement on a gluten free diet, whilst patients with ‘silent’ CD may have biopsy-proven disease and remain asymptomatic. Endoscopic small bowel biopsy is a safe, although invasive procedure. Whilst there is no evidence of harm described in the USPSTF report upon commencement of a gluten-free diet, it limits freedom of choice and potentially creates differences between school aged peers. It is difficult to advise on commencement of a gluten free diet in screen detected patients, when the natural history of untreated coeliac disease in asymptomatic patients remains largely unknown. A Dutch prospective study of asymptomatic toddlers with biopsy proven coeliac disease showed 20% remained symptom free at 10 years despite a full gluten diet8. However, disease manifestations may only become apparent decades later, with an adult population-based study suggesting an increased mortality in undiagnosed coeliac disease when associated with other comorbidities9. Furthermore, untreated asymptomatic coeliac disease has been shown to significantly increase the risk of premature delivery in women10. Long term untreated patients are at increased risk of malignancies such as small bowel lymphoma, although it is unclear as to whether this risk extends to asymptomatic patients.
From a research perspective this review helps to crystallise the current gaps in our knowledge base and challenges our research community to address them meaningfully.
Given the current lack of evidence that continued ingestion of gluten in asymptomatic patients with a positive coeliac screen is completely safe, confirmatory testing and subsequent adherence to a gluten-free diet in patients with histological confirmation is reasonable. Primum non nocere
Dr Robert Kernan, Paediatric Gastroenterology Department, Our Lady’s Children’s Hospital, Crumlin, Dublin 12
Phone: 01 4282776
Email: [email protected]
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