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Discrepancies between histology and serology for the diagnosis of coeliac disease (1)

Devasenan Devendra, Chukwuma Uduku, Edwin Liu and Yannoulla Wilson
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DOI: https://doi.org/10.7861/clinmedicine.10-1-98
Clin Med February 2010
Devasenan Devendra
NHS Brent, Central Middlesex Hospital and Imperial College, London
Roles: Consultant physician and honorary senior lecturer
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Chukwuma Uduku
Department of Investigative Sciences, Imperial College, London
Roles: Research assistant and 6th year medical student
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Edwin Liu
Section of Gastroenterology, Hepatology and Nutrition The Children's Hospital, University of Colorado at Denver
Roles: Associate professor, pediatrics
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Yannoulla Wilson
Northwest London Hospitals NHS Trust
Roles: Laboratory manager, Autoimmune Serology
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Editor – Sweis and colleagues showed discrepancies between histology and serology in the diagnosis of coeliac disease (CD) (Clin Med August 2009 pp 346–8), and suggest we reduce our reliance on serology testing in diagnosing and excluding CD. However, we feel there are major reasons to reconsider this.

The numbers reported here must be interpreted carefully: 10 out of 26 CD patients who received serologic testing were seronegative. This 38.5% occurrence of seronegative CD is misleading. In the spirit of Bayes theorem, the more common the condition we are testing, the greater the percentage of false negative results.1 In this case, all 26 patients were selected due to the diagnosis of CD, meaning the prevalence in this group was already 100%. Therefore, this group is bound to have a high number of false negative tests. The authors correctly state that a small number of cases of CD will be missed by relying on serology alone, but the true prevalence is unknown, and this number is likely to be much lower than 38.5%.

In addition, the predictive value of using an ELISA-based method to detect tissue transglutaminase autoantibody (tTG) remains open to discussion. There are currently numerous tTG assays available, all with varying performances. The International tTG Workshop for CD performed head-to-head comparisons of various commercial and laboratory-based tTG assays. For this workshop, assays reported sensitivities ranging from 82% to 93%, underscoring the marked variability in assay performance.2 Given these findings, the lack of positive serology in a proportion of their biopsy-proven coeliacs could be assay dependent.

Finally, even though intestinal biopsy is the gold standard method to diagnose CD, it is not without its short comings. The sensitivity of histology is largely dependent on the site and number of biopsy samples taken.3,4 Negative histology often excludes a diagnosis of CD. However, a proportion of these patients have CD-like gastrointestinal symptoms, which might be attributed to the subtle changes seen in microscopic enteritis that could go undetected.5

In all, we agree that it is important not to rely on serology alone for the diagnosis of CD, but to allow serology to increase or decrease your estimation of risk of disease. However, considering the lifelong implications of a diagnosis of CD, one should still maintain a degree of suspicion and also take great care in interpreting villous atrophy in the absence of autoantibodies in any patient.

Footnotes

  • Please submit letters for the Editor's consideration within three weeks of receipt of the Journal. Letters should ideally be limited to 350 words, and sent by email to: Clinicalmedicine{at}rcplondon.ac.uk

  • © 2010 Royal College of Physicians

References

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    1. Shapiro D
    . The interpretation of diagnostic tests. Stat Methods Med Res 1999; 8 [2]:113–34.doi:10.1191/096228099666928387
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    1. Li M
    .Yu L.Tiberti C, et al. A report on the International Transglutaminase Autoantibody Workshop for Celiac Disease. Am J Gastroenterol 2009; 104: 154–63.doi:10.1038/ajg.2008.8
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    1. Bonamico M
    .Mariani P.Thanasi E, et al. Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr 2004; 38: 204–7.doi:10.1097/00005176-200402000-00019
    OpenUrlPubMed
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    1. Pais W
    .Duerken D.Pettigrew N, et al. How many duodenal biopsy specimens are required to make a diagnosis of celiac disease? Gastrointest Endosc 2008; 67: 1082–7.doi:10.1016/j.gie.2007.10.015
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  5. ↵
    1. Rostami K
    .Villanacci V. Microscopic enteritis: novel prospect in coeliac disease clinical and immuno-histogenesis. Evolution in diagnostic and treatment strategies. Dig Liver Dis 2009; 41: 245–52.doi:10.1016/j.dld.2008.06.008
    OpenUrlCrossRefPubMed
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Discrepancies between histology and serology for the diagnosis of coeliac disease (1)
Devasenan Devendra, Chukwuma Uduku, Edwin Liu, Yannoulla Wilson
Clinical Medicine Feb 2010, 10 (1) 98; DOI: 10.7861/clinmedicine.10-1-98

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Discrepancies between histology and serology for the diagnosis of coeliac disease (1)
Devasenan Devendra, Chukwuma Uduku, Edwin Liu, Yannoulla Wilson
Clinical Medicine Feb 2010, 10 (1) 98; DOI: 10.7861/clinmedicine.10-1-98
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