THE DISEASE

The effectiveness of a screening programme is closely related to the characteristics of the disease for which screening is proposed. CD is an important health problem as it is common, affecting 1 in 120–300 people in Europe,⁵ and its associated morbidity and excess mortality are well recognised.^6,7 However, the natural history of asymptomatic CD is less well understood, although some patients with unrecognised disease have extra-intestinal manifestations such as growth restriction⁸ or associated autoimmune disease.⁶ The prevalence of associated autoimmune disorders in CD is related to the duration of exposure to gluten,⁹ providing a strong imperative for screening and early treatment.

THE TEST

As with type 2 diabetes screening, there is considerable debate around the relative merits of different screening modalities for CD. The performance of a potential screening test is dependent on diagnostic thresholds for the disease and the availability of a simple, precise, and validated test that is acceptable to the population. Serological tests are easy to administer and have an important role in screening for CD. A number of highly sensitive and specific markers are available.^5,6 In this issue, Alberto and colleagues show the high positive predictive value of one autoantibody, serum anti-h-tTG-ab.³ For any screening test, there should be an agreed policy on the further diagnostic investigation of individuals with a positive test result. In this instance, individuals with a positive antibody result underwent the gold standard diagnostic test of small intestine biopsy. Screen negative children were not investigated further. However, without biopsying screen negative children the sensitivity or specificity of the test cannot be established.

THE TREATMENT

A key issue in evaluating any screening test is to consider whether screening and subsequent treatment result in health gain. For patients with symptom detected CD, delay in diagnosis unfavourably affects patients’ prognosis.⁷ Treatment with a gluten-free diet for life provides good relief of symptoms and is effective in reversing abnormal gut pathology. Prompt treatment also decreases mortality.⁷ For adults, quality of life is improved on a gluten-free diet.¹⁰ Children develop normally and report a quality of life similar to that of children in the general population.¹¹ However, not all adults with CD attain the same degree of subjective health as the general population.¹² Provided that patients with CD adhere to a strict diet, the prognosis is excellent and there are no data to suggest that there is an excess mortality in this group.

Yet the benefits of early detection and treatment of screen detected asymptomatic CD have not been proved. With treatment, quality of life improves for those whose disease was screen detected.¹³ The impact of treatment on mortality and morbidity for asymptomatic individuals is less clear. Asymptomatic CD is often associated with other pathology including reduced bone density, and iron and folate deficiencies, which if left untreated would account for a number of chronic health issues. Silent disease may also account for the worsening of other serious medical conditions,¹⁴ although this link is by no means established.

It is the evaluation of evidence concerning the costs and benefits of treatment for individuals with screen detected disease that is often lacking. One cannot necessarily translate results from treatment trials in people with established disease and apply the evidence to the population with screen detected, possibly asymptomatic, disease. In type 2 diabetes even though patients may believe their illness to be serious, many can reconcile such beliefs with poor adherence to medical advice about lifestyle.¹⁵ Many patients assume that the presence of symptoms is a necessary precursor of complications and equate freedom from symptoms with freedom from risk. This is highly relevant to CD, since screening would result in asymptomatic individuals being advised a lifelong gluten-free diet. Although the diet may be efficacious, its effectiveness in real life is a function of the degree to which patients adhere to advice.

THE SCREENING PROGRAMME

Population screening is always a major undertaking, and the merits of universal population screening must be weighed up against targeting high risk subgroups. The health benefits of mass screening for CD are not known, and in particular no good trial evidence exists to indicate that screening for CD would achieve significant health gain or that it would outweigh the disbenefits of screening. Ideally, evidence of effectiveness in reducing mortality and morbidity should come from randomised trials. A trial would also make it possible to calculate more accurately the costs of screening.

IMPLICATIONS

In the case of type 2 diabetes, the argument surrounding the benefits of screening has continued since the 1960s. Although the disease and the test criteria are easily met, as with CD the major uncertainties concern the benefits and disbenefits of early detection and treatment. It becomes increasingly difficult to undertake a randomised controlled trial of screening as evidence mounts, and there is probably a window of opportunity in which people are sufficiently uncertain to tolerate randomisation. The lesson for researchers into disorders such as CD is not to miss that window, otherwise the debate about whether or not to screen may run for decades.