2012-03-26 14:44:51 UTC

The Case Against Screening for Celiac Disease

March 26, 2012


Ciarán P. Kelly, MD

Professor of Medicine, Harvard Medical School; Gastroenterology Fellowship Training Director, Beth Israel Deaconess Medical Center, Boston, MA

Screening for celiac disease is not justified because of inadequate information on the possible benefits of diagnosing and treating subclinical or silent celiac disease. We do not know enough about the natural history of subclinical celiac disease. We do not know the health consequences of identifying and treating silent celiac disease compared to leaving it undiagnosed. Without this information, it is impossible to gauge the theoretical benefits of screening against the all-too-concrete financial and personal costs of diagnosis and treatment.

Before discussing costs and benefits, let me clarify what is meant by screening. Screening means offering testing for celiac disease to individuals with no evident signs or symptoms of the disorder. This may be universal screening where an entire population group is offered testing, or case finding where testing is offered to individuals at higher risk. Screening is very different from early diagnosis, which refers to prompt testing of those with possible symptoms or signs of celiac disease.

The value and wisdom of screening for celiac disease is controversial. Conversely, there is little or no disagreement regarding early diagnosis, which is widely advocated and encouraged. Why this distinction? When a patient presents seeking help in understanding and managing the symptoms or signs of a possible underlying disease, the onus is on the health-care provider to work with the patient to seek an explanation and determine the best line of treatment. In screening the situation is reversed, as the initiative is taken by the health-care community. Many individuals who are healthy will be approached and tested with the goal of identifying a small number with latent or silent disease. The final result is that most individuals are needlessly inconvenienced and some are “given” a disease. There needs to be a very high degree of certainty of ultimate overall benefit to justify these incursions into the everyday lives of the screened population.

Currently there is very little certainty of ultimate overall benefit in the case of screen-detected, silent celiac disease, as none of the potentially positive outcomes have been tested rigorously or demonstrated convincingly. A substantial improvement in overall health and well-being is difficult, or impossible, to achieve in a group that is without symptoms to begin with. Nutritional deficiencies that are associated with celiac disease can be detected, if and when they arise, during routine medical care and prompt testing for celiac disease performed at that time. In one longitudinal study of more than 11,000 patients with clinically evident celiac disease, 2.3 percent developed a malignancy compared to an expected 1.8 percent in the general population (standardized incidence ratio 1.3).1 Thus, the increased risk of malignancy in untreated overt celiac disease is real but modest. It seems probable, but not certain, that treatment with a gluten-free diet (GFD) may reduce this risk. However, it is not known whether or not silent celiac disease is also associated with an increased risk for malignancy; the effect, if any, of a GFD on this unknown risk has not been studied. To the contrary, one study found no increased risk for malignancy during almost 20 years of follow-up in individuals found to have a positive celiac serology.2 The possible benefits of screening for subclinical celiac disease are theoretical rather than evidence-based. Not so for the risks and costs of screening.

The most obvious costs are the financial costs of the screening program. Additional financial costs are incurred in further testing of those who yield a positive result on the initial screening test. Testing approaches may vary, but it is likely that many of those who test positive would be offered endoscopy with small intestinal biopsy. This is costly, invasive and carries risk. Many who would undergo biopsy would be found not to have intestinal changes of celiac disease. Thus, the entire workup would prove to be unnecessary. Others would have equivocal or non-specific findings, such as an increase in intraepithelial lymphocytes. Should a GFD be advocated for those individuals or only for those with more advanced pathology, including villous atrophy? Even a negative screening result is not without risk; a false negative screening test result may lead to a delay or failure of celiac disease diagnosis due to misplaced trust in the negative findings of the screening assay.

The potential costs and risk for harm in screening for celiac disease is greatest in those who test positive and are confirmed to have silent celiac disease. In addition to the medical costs of diagnosis and long-term management, there is clear and consistent evidence that adherence to a GFD is inconvenient, time-consuming, expensive and can be a social liability. These disadvantages might be considered minor if the duration of treatment was measured in days, but over many years and decades of treatment, the costs become enormous. Some baulk at the dietary and lifestyle changes involved, and resent the intrusion and the restrictions that it imposes. This problem is compounded by the fact that, in screening symptomless individuals, one cannot expect substantial immediate benefit from adhering to the diet. Compliance with dietary therapy for diabetes mellitus and hypercholesterolemia is generally incomplete despite the fact that the benefits are well established and the dietary regimens less challenging than a strict GFD. Therefore, it is probable that many individuals with screen-detected celiac disease will opt not to adhere to the diet. In that instance, the goal of the screening program is not achieved and the individual is left feeling guilty, anxious or both.

There is another line of reasoning against screening for celiac disease that is based on unproven theories: silent celiac disease is not only common and generally carries low morbidity and so can be ignored, but in some circumstances it may even be beneficial. Celiac disease is associated with a reduction in hypertension and hyperlipidemia, whereas treatment with a GFD may lead to increased body mass index and obesity.3,4 Given the enormous increases in obesity-related morbidity and mortality, these phenomena have the potential to offset some or all of the unproven risks of undiagnosed silent celiac disease.

In 2004, the NIH Consensus Conference on Celiac Disease also considered this question and concluded: “At this time, there are insufficient data to recommend screening of the general population for celiac disease.” In my opinion, their conclusion still holds good today.5 In order to fill the substantial knowledge gaps regarding the potential value of screening for celiac disease, we need to “conduct a cohort study to determine the natural history of untreated celiac disease, especially ‘silent’ celiac disease.”5 On the other hand, I strongly endorse efforts to advance the early diagnosis of celiac disease, as this is a highly feasible and worthwhile goal.5

Dr. Kelly is a scientific and clinical consultant for Alba and ImmusanT, and is a scientific advisory board member of Alba, Alvine and ImmusanT. He also received research support from Alba, Alvine, Shire and SQI Diagnostics.


1. Askling J, Linet M, Gridley G, Halstensen TS, Ekstrom K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology 2002;123(5):1428-35.

2. Lohi S, Maki M, Montonen J, Knekt P, Pukkala E, Reunanen A, et al. Malignancies in cases with screening-identified evidence of coeliac disease: a long-term population-based cohort study. Gut 2009;58(5):643-7.

3. West J, Logan RF, Card TR, Smith C, Hubbard R. Risk of vascular disease in adults with diagnosed coeliac disease: a population-based study. Aliment Pharmacol Ther 2004;20(1):73-9.

4. Goldberg A, Kabbani T, Leffler DA, Pallav K, Tariq S, Peer A, Hansen J, Dennis M, Kelly CP. Body Mass Index and Risk of Obesity in Celiac Disease treated with the Gluten Free Diet [in press].

5. National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004. Gastroenterology 2005;128(4 Suppl 1):S1-9.

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