Investigating coeliac disease in adults
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2176 (Published 17 June 2020) Cite this as: BMJ 2020;369:m2176
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Dear Editor
Ashton et al (1) highlight the need to remain on a gluten containing diet until diagnostic tests are complete for coeliac disease. Further, this instruction is covered in statement two of the NICE Quality Standard (2). However, this advice is not offered with sufficient weight by many referring clinicians. Consequently, some children and adults are already on a gluten free diet by the time they present for their diagnostic tests. This can lead to delayed diagnosis and unhappy patients. Worse, it can result in no diagnosis being formally confirmed when the patient refuses to be re-challenged with gluten ahead of their duodenal biopsy.
In order to rectify this recurring problem for Welsh children and to speed up the referral pathway, we worked with the Immunology Standing Specialist Advisory Group, to add a brief recommendation to the coeliac serology report. Soon, when the tissue transglutaminase IgA (TTG) lies outside the normal range, the report will state: “This child may have coeliac disease. Please recommend they must remain on a normal gluten containing diet until they are assessed by an expert and all diagnostic tests are complete. Please make an urgent paediatric outpatient referral stating “possible coeliac disease”.
Conversely, when the IgA TTG is within the normal range we offer: “To exclude coeliac disease with confidence this child must have a normal IgA level and must have been eating a normal gluten containing diet for at least 6-8 weeks prior to this blood test. If you still have concern please make a paediatric outpatient referral for expert advice.”
Working with physicians from the Welsh Association for Gastroenterology and Endoscopy (WAGE) and the Senedd Cymru Cross Party Group on coeliac disease, we hope that this innovation can be extended quickly to include all Welsh adults being investigated for coeliac disease as well.
1. Ashton et al Investigating Coeliac disease in adults BMJ 2020:369m2176
2. Coeliac disease Quality standard [QS134] October 2016 https://www.nice.org.uk/guidance/qs134
Competing interests: Ieuan Davies is a member of the Health Advisory Council of Coeliac UK and is a member of the Senedd Cymru Cross Party Group on coeliac disease. Richard Cousins is the Chair of the Immunology Standing Specialist Advisory Group (Wales)
Dear Editor,
The authors are absolutely correct in that normally a positive anti-tissue transglutaminase antibody result should always be followed up by a duodenal biopsy before embarking on a gluten-free diet in adults. However during the current limitations on availability of upper gastroscopy imposed by the SARS-CoV-2 pandemic, the British Society of Gastroenterology have endorsed temporality avoiding duodenal biopsy in those most likely to have coeliac disease, similar to the approach generally employed for children.
In those with a strongly positive anti-tissue transglutaminase antibody (> x 10 the upper limit of normal), it is recommended that a second positive confirmatory serological test, ideally endomysial antibody but a second anti-tissue transglutaminase if resources are limited, be obtained. In these patients, the gluten-free diet can be instigated without a duodenal biopsy. It seems in due course, reversion to the advocated "always biopsy before gluten-free diet" pathway will occur but in the short-term, endoscopy and biopsy will be avoided in selected patients.
Competing interests: No competing interests
Re: Investigating coeliac disease in adults
Dear Editor
Ashton and colleagues (BMJ 09 July 2020) are to be congratulated in bringing adult coeliac disease (CD) back to the limelight for GPs and secondary care clinicians in the Rational Testing series (1). The case and review highlight important issues, but unfortunately it is immediately out of date and statements about contemporary management could be misinterpreted. Ironically this review was published after the COVID-related British Society of Gastroenterology (BSG) coeliac advice went online in June 2020 (2). The review states all adults need to have a biopsy. As far back as 2008 in adults it was clear at ≥ 10 times upper limit of normal (ULN) anti-Tissue Transglutaminase (anti-TTG) / histology correlation was robust (3-8). Fuchs et al published their experience and from early 2019, having adopted no-biopsy, highlighting as many as a third of positive Finnish adults might avoid endoscopy (9).
ESPGHAN’s 2020 re-iteration of 2012 guidelines, following the ‘road-testing’ work in the ProCeDe study further embedded ‘no-biopsy’ practice in paediatrics (10-12). In 2015 NICE NG20 did not consider ‘no-biopsy’ as evidence was still evolving. (13) Despite a recent decision in 2019 not to update them, this surely needs to be urgently revisited especially in light of the pandemic (14).
The 29 year-old white female detailed in the review could and should now be safely diagnosed in secondary care without the need for biopsy due to her anti-TTG of over 10 times the ULN. This is not a condition exclusive to the Caucasian population: she could equally have been of Asian, Arabic or Latin origin or of mixed race (15).
With regard to small bowel biopsies, current BSG guidance specifically state that two D1 (bulb) biopsies and 4 D2 biopsies should be taken (16). This is especially important at low level anti -TTG positivity as D1 is often the only affected area (17,18) and is still not practiced in all centres, with potential missed diagnosis even after a long wait for upper endoscopy (Gillett P, data on file). Different serology strategies are present in UK practice e.g some do not include assessment of endomysial antibody. It is important for services to understand the predictive values (Negative and Positive) of their local tests, as not all assays are the same or have the same normal range (19).
The authors recommend anti-TTG at 6-12 months and then every 1-2 years for life. That’s a lot of unnecessary tests! Instead we should be targeting tests to the patient’s needs (eg. previous vitamin deficiency or onset of new symptoms) and look for secondary complications only where relevant (20). There is no evidence to recommend this testing frequency or in using serology alone to monitor adherence after normalisation. Gluten Immunogenic Peptide (GIP) is a promising test for monitoring adherence but still needs to find its specific niche (21). As with the case here, the young patient with no malabsorptive risk factors does not need a DEXA scan.
A mantra should always be challenged. Coeliac services need to make sure a patient’s symptoms and tests normalise, but we also need to focus on those who struggle with adherence and those with ongoing symptoms despite optimal adherence, and who have non-responsive or refractory CD (22). A UK no-biopsy strategy is now more important than ever to pursue as it will lead to fewer invasive investigations, quicker diagnosis for many and save NHS costs. We must more than ever look to ourselves and move to more pragmatic, effective and patient focused care whenever possible.
Refs
1.Ashton J, Smith R, Smith T, Beattie RM. Investigating coeliac disease in adults. BMJ 2020;369:m2176
2.https://www.bsg.org.uk/covid-19-advice/covid-19-specific-non-biopsy-prot... (Accessed online 18.08.20)
3.Hill PG, Holmes GK. Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther 2008; 27:572-7.
4.Sugai E, Moreno ML, Hwang HJ, et al. Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable? World J Gastroenterol 2010; 16:3144-52.
5.Zanini B, Magni A, Caselani F, et al. High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease. Dig Liver Dis 2012; 44:280-5.
6.Holmes GKT, Forsyth JM, Knowles S, et al. Coeliac disease: further evidence that biopsy is not always necessary for diagnosis. Eur J Gastroenterol Hepatol 2017 Jun; 29:640-645.
7.Holmes GKT, Hill PG. Coeliac disease: further evidence that biopsy is not always necessary for diagnosis. Author’s reply. Eur J Gastroenterol Hepatol 2017 ; 29:1189-1190.
8.Holmes G, Ciacci C. The serological diagnosis of coeliac disease - a step forward. Gastroenterol Hepatol Bed Bench 2018; 11:209-215.
9.Fuchs V, Kurppa K, Huhtala H, et al. Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities. Aliment Pharmacol Ther 2019; 49:277-284.
10.Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54 :136–160.
11.Werkstetter KJ, Korponay-Szabó IR, Popp A, et al. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice. Gastroenterology 2017; 153:924-935.
12.Husby S, Koletzko S, Korponay-Szabó I, Kurppa K, Mearin M, Ribes-Koninckx C, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr. 2020; 70:141-156.
13.NICE Coeliac disease: recognition, assessment and management (NG 20)
https://www.nice.org.uk/guidance/ng20 (Accessed online 18.08.2020)
14.2019 surveillance of coeliac disease: recognition, assessment and management (NICE guideline NG20) Surveillance report Published: 18 December 2019 https://www.nice.org.uk/guidance/ng20/resources/2019-surveillance-of-coe... (Accessed online 18.08.20)
15. https://www.worldgastroenterology.org/guidelines/global-guidelines/celia... disease-english (Accessed online 18.08.2020)
16.Ludvigsson J, Bai J, Biagi F, Card T, Ciacci C, Ciclitira P, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut. 2014; 63:1210-28.
17. Mooney PD, Kurien M, Evans KE, Rosario E, Cross SS, Vergani P, et al. Clinical and Immunologic Features of Ultra-Short Celiac Disease. Gastroenterology. 2016; 150:1125-34.
18. Holmes G. The Duodenal Bulb Comes of Age in the Diagnosis of Celiac Disease. Gastroenterology. 2016; 150:1071-3.
19. Paul SP, Harries SL, Basude D. Barriers to implementing the revised ESPGHAN guidelines for coeliac disease in children: a cross-sectional survey of coeliac screen reporting in laboratories in England. Arch Dis Child. 2017; 102:942-946.
20. Wessels M, van Veen I, Vriezinga S, Putter H, Rings E, Mearin M. Complementary Serologic Investigations in Children with Celiac Disease Is Unnecessary during Follow-Up. J Pediatr. 2016; 169:55-60.
21.Costa AF, Sugai E, Temprano MP, et al Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients. World J Gastroenterol. 2019; 25:1409-1420.
22. Penny HA, Baggus EMR, Rej A, et al. Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients. 2020; 12:216.
Competing interests: No competing interests