Published 17 September 2009, doi:10.1136/bmj.b3674
Cite this as: BMJ 2009;339:b3674

Head to Head

Should we screen for coeliac disease? No

¹ Department of Gastroenterology, Sheffield Teaching Hospitals Trust, Sheffield S10 2JF

Coeliac disease often goes undiagnosed. Alessio Fasano (doi:10.1136/bmj.b3592) argues that screening would prevent considerable morbidity, but Kate Evans and colleagues think we do not know enough about the effects on people without symptoms

Coeliac disease is common, can be detected by a cheap accurate test, and there is an effective treatment that can reduce morbidity and severe complications. So of course we should screen for it. Or should we? Controversies of diagnosis, a poor understanding of the natural course of coeliac disease, difficulties with adherence to a gluten-free diet, and a lack of cost effectiveness all suggest caution before we implement population screening.

Diagnosis

Coeliac disease is detected using tests for tissue transglutaminase or endomysial antibodies. In combination these antibodies have a positive predictive value above 90% in selected groups,^{1 2} although it falls to around 70% in the general population.³ Furthermore, serological positivity can be transient or fluctuating. Simell and colleagues showed that seropositive children carrying the genetic risk of coeliac disease could become seronegative spontaneously—a concept labelled as immune tolerance.⁴

Additional logistical problems were highlighted in a recent screening study that identified 26/1868 adults with positive coeliac serology.⁵ Six of the 26 had villous atrophy on biopsy and had coeliac disease diagnosed. Of the remainder, five refused biopsy and the rest had lesser degrees of enteropathy or a normal small bowel. These patients, and their doctors, face the unenviable quandaries of a "not quite" diagnosis. Should they have repeat serology or biopsies? How often? Should they follow a gluten-free diet, and are they at risk of complications of coeliac disease? We do not have the answers to these questions.

One of the key principles for screening is that we understand the natural course of the condition. This is not the case with coeliac disease. The disease may follow a more indolent course in people identified by screening than in those presenting with overt disease.

Benefits of early diagnosis

Patients with coeliac disease are advised to follow a gluten-free diet to reduce symptoms and complications. Only 50-70% adhere to the diet because of cost, poor palatability, and social difficulties.⁶ Weight gain, depression, and anxieties about socialising with friends are common complaints about the diet. Women perceive greater disease burden than men, reporting significantly poorer subjective health and quality of life.⁷ Although a gluten-free diet can produce a rapid improvement in adults and children with symptoms, those with screen detected subclinical or silent disease have a quality of life similar to that of the general public and therefore cannot derive such benefits.^{8 9}

We do not know the risk of complications in subclinical disease or whether this can be modified by a gluten-free diet. One study with a 20 year follow-up found no increased risk of malignancy in seropositive individuals (who did not have a confirmatory biopsy but are likely to have untreated coeliac disease) not following a gluten-free diet.¹⁰

Contemporary population studies of coeliac disease show only a modest risk of malignancy and death. The overall hazard ratio for death in coeliac disease is reported to be as low as 1.3.¹¹ And although the relative risk of lymphoma in coeliac disease is high, the absolute risk remains small.

Similar uncertainties exist about bone mineral density.¹² Interestingly, hypertension and hypercholesterolaemia are reportedly less prevalent in adults with undetected coeliac disease than in the general population,¹³ so undetected coeliac disease may even confer benefit in a society with an obesity epidemic.

Case finding versus mass screening

Although the investigational processes for population screening and case finding are the same, there is an important ethical difference between them. If a patient seeks medical help—for example, for symptoms of irritable bowel syndrome—the doctor is attempting to diagnose the underlying condition. This would be classified as case finding, and clearly the patient has initiated the consultation and in some sense is consenting to investigation. Conversely, individuals found to have coeliac disease through screening programmes may have considered themselves as well, and it is the doctor or healthcare system that is identifying them as potentially ill. There may be negative ramifications for insurance, other family members, and quality of life.

A high index of suspicion should enable astute doctors to diagnose coeliac disease. In a recent screening study 27 out of 32 patients with screen detected coeliac disease who were initially assessed as well were later proved to have common clinical problems such as anaemia, other autoimmune diseases, thyroid disease, or being underweight.¹⁴

Cost effectiveness

Screening has been calculated to be cost effective in a population with a relatively high prevalence of coeliac disease or when the standardised mortality ratio for untreated disease is greater than 1.5.¹⁵ However, contemporary data give a standardised mortality ratio of 1.3.¹¹

A case finding approach may be more financially viable. Serological testing of patients with irritable bowel syndrome has been shown to be cost effective.^{16 17}

We need a large, European, prospective, multicentre study to assess the benefits of mass screening longitudinally. We must determine the optimum screening strategy and clarify the approach to milder degrees of enteropathy. Screen detected individuals can then be assessed for adherence to and benefit from a gluten-free diet, quality of life, and health outcomes. Until then, we favour case finding over mass screening.

Cite this as: BMJ 2009;339:b3674

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Competing interests: DSS is an associate medical adviser for Coeliac UK (National Medical Charity), an honorary reader in gastroenterology at the University of Sheffield, and chairman of the small bowel and nutrition committee of the British Society of Gastroenterology. These are honorary posts with no financial benefits.

References

1. Hopper AD, Cross SS, Hurlstone DP, McAlindon ME, Lobo AJ, Hadjivassiliou M, et al. Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. BMJ 2007;334:729.[Abstract/Free Full Text]
2. National Institute for Health and Clinical Excellence. Coeliac disease: recognition and assessment of coeliac disease. NICE clinical guideline 86. London: NICE, 2009.
3. Hopper AD, Hadjivassiliou M, Hurlstone DP, Lobo AJ, MaAlindon ME, Egner W, et al. What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol 2008;6:314-20.[CrossRef][Web of Science][Medline]
4. Simell S, Hoppu S, Hekkala A, Simell T, Stahlberg MR, Viander M, et al. Fate of five celiac disease-associated antibodies during normal diet in genetically at-risk children observed from birth in a natural history study. Am J Gastroenterol 2007;102:2026-35.[CrossRef][Web of Science][Medline]
5. Marine M, Fernandez-Banares F, Alsina M, Farre C, Cortijo M, Santaolalla R, et al. Impact of mass screening for gluten-sensitive enteropathy in working population. World J Gastroenterol 2009;15:1331-8.[CrossRef][Web of Science][Medline]
6. Leffler DA, Edwards-George J, Dennis M, Schuppan D, Cook F, Franko DL, et al. Factors that influence adherence to a gluten-free diet in adults with celiac disease. Dig Dis Sci 2008;53:1573-81.[CrossRef][Web of Science][Medline]
7. Hallert C, Grännö C, Hultén S, Midhagen G, Ström M, Svensson H, et al. Living with coeliac disease: controlled study of the burden of illness. Scand J Gastroenterol 2002;37:39-42.[CrossRef][Web of Science][Medline]
8. Nachman F, Maurino E, Vazquez H, Sfoggia C, Gonzalez A, Gonzalez V, et al. Quality of life in celiac patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig Liver Dis 2009;41:15-25.[CrossRef][Web of Science][Medline]
9. Fabiani E, Taccari LM, Ratsch IM, Di Giuseppe S, Coppa GV, Catassi C. Compliance with gluten-free diet in adolescents with screening-detected celiac disease: a 5-year follow-up study. J Pediatr 2000;136:841-3.[CrossRef][Web of Science][Medline]
10. Lohi S, Maki M, Montonen J, Knekt P, Pukkala E, Reunanen A. Malignancies in cases with screening-identified evidence of coeliac disease: a long-term population-based cohort study. Gut 2009;58:643-7.[Abstract/Free Full Text]
11. West J, Logan RFA, Smith CJ, Hubbard RB, Card TR. Malignancy and mortality in people with coeliac disease: population based cohort study. BMJ 2004;329:716-9.[Abstract/Free Full Text]
12. Corazza GR, Di Sario A, Cecchelti L, Jorizzo RA, Di Stefano M, Minguzzi L, et al. Influence of pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease. Bone 1996;18:525-30.[CrossRef][Web of Science][Medline]
13. West J, Logan RF, Card TR, Smith C, Hubbard R. Risk of vascular disease in adults with diagnosed celiac disease: a population-based study. Aliment Pharmacol Ther 2004;20:73-9.[CrossRef][Web of Science][Medline]
14. Korponay-Szabo IR, Szabados K, Pusztai J, Uhrin K, Ludmany E, Nemes E. Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: diagnostic accuracy and feasibility study. BMJ 2007;335:1244-7.[Abstract/Free Full Text]
15. Shamir R, Hernell O, Leshno M. Cost-effectiveness analysis of screening for celiac disease in the adult population. Med Decis Making 2006;26:282-93.[Abstract/Free Full Text]
16. Mein SM, Ladabaum U. Serological testing for celiac disease in patients with symptoms of irritable bowel syndrome: a cost-effectiveness analysis. Aliment Pharmacol Ther 2004;19:1199-210.[CrossRef][Web of Science][Medline]
17. National Institute for Health and Clinical Excellence. Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome in primary care. NICE clinical guideline 61. London: NICE, 2008.

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