Coeliac disease

Synonyms: gluten-sensitive enteropathy, celiac disease, celiac sprue

This is a genetically-determined chronic inflammatory intestinal disorder of the proximal bowel. It is induced by gluten, a protein found in wheat, rye and barley. 1

Epidemiology

Prevalence is approximately 1 in 100 people in the UK.2 Prospective birth cohort studies suggest 1% of children have immunoglobulin A (IgA) endomysial antibodies by 7 years of age,3,4 although only 1:2,500 will have been diagnosed as having coeliac disease (CD) at that time.5,6 This demonstrates that there must be a large number of undiagnosed coeliac patients in the community, which presents a large diagnostic challenge to primary care.

Delayed diagnosis of CD may result in continuing ill health, osteoporosis, miscarriage and a modest, increased risk of intestinal malignancy (in adults); also, growth failure, delayed puberty and dental problems (in children).4

It is a multigenetic disorder, associated with HLA types HLA-DQ2 (90%) or HLA-DQ8, plus other genetic or environmental factors. There is a familial tendency (10-15% of first-degree relatives will also be affected), and identical twins' concordance is 70%. It is theoretically possible, by HLA testing, to provide more accurate information to parents with a child with CD about the real risk for another child having the disease, including an antenatal assessment.7 HLA typing indicating lack of DQ2 or DQ8 has a high negative predictive value for - which may be useful if trying to exclude coeliac disease.1

2-8% of patients with type 1 diabetes mellitus also have CD,8 and it also occurs with increased frequency in patients with Down's Syndrome, Hashimoto's thyroiditis,9 irritable bowel syndrome (IBS), and in the people with Irish, Punjabi and other South Asian ethnic backgrounds.

Presentation10,11

It may present at any age - presentation in childhood is now less common (9%), and increasingly being recognised in adults (the average age at diagnosis is now 40-60 years).1

  • Babies and young children present any time after weaning (peak 9 months to 3 years). Malabsorption generally presents with diarrhoea (frequent paler stools), weight loss and failure to thrive. Vomiting, anorexia, irritability, and constipation are also common. The abdomen may protrude, with eversion of the umbilicus.
  • Older children and adults may present with anaemia (folate or iron deficiency) nonspecific symptoms of abdominal discomfort, arthralgia, anaemia, fatigue and malaise, as well as diarrhoea, steatorrhoea and malabsorption. Mouth ulcers and angular stomatitis are common (85% have asymptomatic iron/folate deficiency, 15-30% have vitamin D deficiency and 10% vitamin K deficiency); deficiencies of vitamin E also occur. B12 deficiency can also occur (mechanism unknown).
    Some coeliac disease (CD) patients are identified at infertility clinics. CD is associated with subfertility in both men and women, miscarriage, low-birthweight children and increased infant mortality.12,13

Dermatitis herpetiformis is the classic skin manifestation of CD - almost all patients with the rash have either detectable villous atrophy (~75%) or minor mucosal changes. Acquired ichthyosis has been reported.14

Investigations

Target case finding for serological testing

Because coeliac disease (CD) is considerably underdiagnosed in primary care, a targeted case-finding exercise is recommended.1,11
Consider the diagnosis and perform serological testing in all patients who present with:4

  • Chronic or intermittent diarrhoea.
  • Failure to thrive or faltering growth in children (including short stature and delayed puberty).15
  • Persistent or unexplained gastrointestinal (GI) symptoms, including nausea and vomiting.
  • Prolonged fatigue ('tired all the time').
  • Recurrent abdominal pain, cramping or distension.
  • Sudden or unexpected weight loss.
  • Unexplained iron-deficiency anaemia, or other unspecified anaemia.

Also offer testing to patients with:4

The National Institute for Health and Clinical Excellence (NICE) also suggests considering serological testing in patients with:4 Addison's disease, amenorrhoea, aphthous stomatitis (mouth ulcers), autoimmune liver conditions, autoimmune myocarditis, chronic thrombocytopenia purpura, dental enamel defects, depression or bipolar disorder, Down's syndrome, epilepsy, lymphoma, metabolic bone disease (such as rickets or osteomalacia), microscopic colitis, persistent or unexplained constipation, persistently raised liver enzymes with unknown cause, polyneuropathy, recurrent miscarriage, reduced bone mineral density and/or low-trauma fracture, sarcoidosis, Sjögren's syndrome, Turner's syndrome, unexplained alopecia, and unexplained subfertility.

Screening

Coeliac disease (CD) appears to be underdiagnosed in primary care.5

  • In order to uncover the 'iceberg', GPs need to screen for CD - especially patients with autoimmune disease, unexplained anaemia,18 unexplained osteoporosis,19 chronic abdominal pain or other bowel symptoms (e.g. IBS), or family history of CD.20
  • Patients having upper GI endoscopy for iron deficiency or macrocytic anaemia may be suitable for screening with distal duodenal biopsies (but it may be better to perform CD serology first and follow algorithm).21 The case for childhood screening is currently being considered.

Serological testing

Serological testing identifies patients who need further testing for CD. It should only be done when a patient is on a diet containing gluten (check patients have not already been on a gluten-free diet (GFD) prior to test). Arrange a serology test if a patient has been on a gluten-containing diet (e.g. normal bread, chapatis, pasta, biscuits, or cakes) in more than one meal every day for a minimum of 6 weeks before testing.4
  •  IgA anti-tissue transglutaminase antibodies (tTGAs) is the preferred investigation. Endomysial antibodies (EMAs) are used if the tTGA test is not available or equivocal. The tTGA is a newer test (tTGA is the autoantigen of EMA) and is gradually replacing the latter, but both are highly specific and sensitive for untreated CD, provided the patient is still on gluten.10
  • False negatives occur if the patient has selective IgA deficiency, as occurs in ~0.4% of the general population21 and in 2.6% of patients with CD (laboratories should test for IgA deficiency on negative samples). Use IgG tTGA and/or IgG EMA serological tests for people with confirmed IgA deficiency.
  • Antibodies frequently become undetectable after 6-12 months of a GFD and thus can be used to monitor the disease.

Antigliadin antibodies (AGAs) are no longer recommended - they are less specific, but can be either IgA or IgG. They can be positive in other GI conditions, such as Crohn's disease.

Biopsy confirmation

Patients with positive serological tests should be offered referral to a local gastroenterologist for endoscopic or enteroscopic distal duodenal or jejunal biopsy to confirm diagnosis.4,17,21 They need to stay on gluten until after the biopsy. Referral should also be made where the serology is negative but there is still clinical suspicion of CD.

  • The diagnosis of CD is made when biopsy shows villous atrophy while the patient is eating adequate amounts of gluten, followed by full clinical remission on excluding gluten.
  • Under these circumstances, tTGA or EMA antibodies found at the time of diagnosis and their disappearance after gluten exclusion, means that it is only necessary to perform a further biopsy (and even a further gluten challenge and more biopsies) if there are still doubts. The further gluten challenge should always be performed if CD is diagnosed in children less than 2 years of age because of a high incidence of other causes of flat mucosa.19

Other investigations

  • FBC shows anaemia in 50%; iron and folate deficiency are both common (microcytes and macrocytes), hypersegmented leukocytes and Howell-Jolly bodies (splenic atrophy). Also check B12, folate, ferritin, LFTs, calcium and albumin.
  • LFTs may show elevated transaminases which should return to normal on a GFD. If they don't, consider associated autoimmune disease, i.e. primary biliary cirrhosis, autoimmune hepatitis or primary sclerosing cholangitis.
  • Small bowel barium studies are occasionally needed to exclude other causes of malabsorption and diarrhoea, and to diagnose rare complications such as obstruction or lymphoma.

Histopathology

Histological examination of the mucosa which has been exposed to gluten classically shows 'subtotal villous atrophy' and results in malabsorption - however mucosa is of normal thickness, the villous atrophy is compensated by crypt hyperplasia. There may be a range of abnormality, from a normal villous architecture with epithelial lymphocytosis, to total villous atrophy.10

Differential diagnosis

IBS,22 lactose or other food intolerances, colitis (including inflammatory bowel disease), and other causes of malabsorption.

Associated conditions

The following occurring with increased frequency in coeliac disease (CD) include osteoporosis, subfertility, Down's Syndrome and various autoimmune diseases (especially Hashimoto's thyroiditis and type 1 diabetes mellitus; however, it is probably also true of Sjögren's syndrome and primary biliary cirrhosis), and IgA deficiency. Always consider CD in patients thought to have IBS.22

Management17,23

Starting a gluten-free diet (GFD) rapidly induces clinical improvement, which is mirrored by the mucosa. The diet consists of no wheat, barley, rye, or any food containing them (e.g. bread, cake, pies). Moderate quantities of oats (free from other contaminating cereals) can be consumed, as studies suggest that they do not damage the intestinal mucosa in most coeliac patients,24 although a small number of patients remain unwell if oats are included in the diet. British Society of Gastroenterology (BSG) guidelines suggest oats be excluded at least for the first year while patients get used to a GFD but then can be cautiously introduced. Rice, maize, soya, potatoes, sugar, jam, syrup and treacle are all allowed. Gluten-free biscuits, flour, bread and pasta are NHS prescribable. There is a gluten-free food prescribing guide available for health professionals and Coeliac UK produces a prescribable product list.25,26

Arrange a dietitian appointment (with regular reviews). Even minor dietary lapses may cause recurrence. A GFD should be lifelong, as relaxation of diet generally brings a return of symptoms and increased incidence of complications. Add supplements as necessary (e.g. fibre, folic acid, iron, calcium and vitamin D).
Serial tTGA or EMA antibodies can be used to monitor response to diet.

Oral proteases are being developed (which digest gluten) and these may offer therapeutic options in the future.27

Why follow up patients with CD?17

  • Patient compliance with a GFD is poor, ranging from 45-87%. The long-term health risks for patients who comply poorly with a GFD include nutritional deficiency and reduced bone mineral density. About a quarter of patients with CD have osteoporosis of the lumbar spine compared with 5% of matched controls. Bone mineral density improves significantly with a GFD.
  • Dietary compliance positively correlates with regular follow-up and knowledge of the condition.
  • Half of all coeliac patients have an inadequate energy intake, and 10% have inadequate intake of calcium and vitamin B6. 80% of elderly patients have inadequate intake of vitamin D.
  • GPs are responsible for the appropriate prescription of gluten-free products.26
  • Regular follow-up is an opportunity to provide patient-centred care that is sensitive to the individual's life circumstances.

How often should patients be reviewed?

  • Patients should be followed up throughout their lifetime.
  • After diagnosis, the patient should be reviewed at the gastroenterology clinic after 3 months and 6 months to ensure they are making satisfactory progress and managing the diet.
  • If well, they should be reviewed annually or sooner if problems arise - follow-up assessments are currently being carried out by dietitians, nurses, general practitioners and gastroenterologists in primary and secondary care.

What should be done at annual assessments?1,17

Disease status

  • General: weight, height, and BMI.
  • Symptom assessment: bowel function (stool frequency, stool consistency, blood in stool) abdominal pain.

Investigations

  • FBC, LFTs, calcium and albumin, B12, folate, serum ferritin. Patients with coeliac disease (CD) who adhere to a gluten-free diet (GFD) often eat inadequate intakes of folic acid and iron. Low haemoglobin, red cell folate, and serum ferritin may suggest persisting malabsorption warranting further assessment.
  • Antibody tests can be used to monitor significant dietary gluten ingestion.

Complication prevention

  • Osteoporosis risk assessment and management:
    • Consider measuring bone mineral density with a dual energy X-ray absorptiometry (DEXA) scan at the time of diagnosis (depending on age), and the test should then be repeated:17
      • After 3 years on a GFD (only if the baseline DEXA is abnormal).1
      • At the menopause for all women.
      • At the age of 55 years for all men.
      • At any age if a fragility fracture is suspected (follow osteoporosis guidelines).
      Some have doubted the yield of screening with DEXA at diagnosis.17
    • Advise regular physical activity, reduce smoking and alcohol consumption.
    • Calcium and/or vitamin D supplements can be prescribed if dietary intake is inadequate (<1,500 mg/day) or the patient is housebound. Checking Vitamin D levels and PTH levels may be appropriate in at-risk individuals.1
    • Bisphosphonates or strontium, etc. should be considered if the patient is osteoporotic - again follow osteoporosis guidelines.
  • Hyposplenism- some degree of splenic atrophy is present in most patients with CD, and is sufficiently severe to cause peripheral blood changes in about a quarter (Howell-Jolly bodies, target cells and elevated platelet count). Patients should be considered for:
    • Vaccination against pneumococcus and Haemophilus influenzae type b.
    • Vaccination against influenza.
    • Guidance about the increased risks attached to tropical infections, e.g. malaria.
    Lifelong prophylactic antibiotics are not recommended.

Management of disease and associated medical problems

  • Discussion of familial risk if required. First-degree relatives of people with CD have a 1 in 10 chance of developing the disease, and should be screened.
  • Review prescription items - prescribing guidelines suggest minimum monthly prescription requirements, so discuss prescribable items with any patients using fewer than these recommendations.26
  • Self-care:
    • Discuss GFD compliance and advice.
    • Discuss membership of the Coeliac Society.
    • Discuss use of the Coeliac Society's Gluten-free Food and Drink directory.
    • Provide dietary advice on weight, macronutrients, calcium, vitamin D, iron and fibre intake as required.

When should the patient be under specialist care?

You should consider specialist referral if:

  • There is poor response to a GFD.
  • There is weight loss on a GFD.
  • There is blood in stools.
  • There is onset of unexplained abdominal pain.
  • There are other clinical concerns.

Complications

  • Osteoporosis (see box above).28
  • Cancer risk - there is conflicting research on this subject. Some research fails to show any increased risk,29 whilst other papers have shown a very modest increase in overall risks of developing malignancy, e.g. GI cancers and several types of lymphoma (risk is greatest in the first year after coeliac disease (CD) diagnosis).30,31 Interestingly, CD patients may have a reduced incidence of breast and lung cancers (reasons are unclear).
    Intestinal lymphoma usually presents with the return of bowel symptoms, although it usually responds poorly to treatment.


Document references

  1. The Management of Adults with Coeliac Disease, British Society of Gastroenterology (2010)
  2. Clinic Consultation: Coeliac Disease. Short video from 'Embarrassing bodies - Kids' (2010)
  3. http://www.coeliac.org.uk/coeliac-disease/case-studies Case studies: Coeliac UK website
  4. West J, Logan RF, Hill PG, et al; Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut. 2003 Jul;52(7):960-5. [abstract]
  5. Bingley PJ, Williams AJ, Norcross AJ, et al; Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. BMJ. 2004 Feb 7;328(7435):322-3.
  6. Coeliac disease, NICE Clinical Guideline (May 2009); Recognition and assessment of coeliac disease
  7. Hawkes ND, Swift GL, Smith PM, et al; Incidence and presentation of coeliac disease in South Glamorgan. Eur J Gastroenterol Hepatol. 2000 Mar;12(3):345-9. [abstract]
  8. Tommasini A, Not T, Kiren V, et al; Mass screening for coeliac disease using antihuman transglutaminase antibody assay. Arch Dis Child. 2004 Jun;89(6):512-5. [abstract]
  9. Bourgey M, Calcagno G, Tinto N, et al; HLA related genetic risk for coeliac disease. Gut. 2007 Aug;56(8):1054-9. Epub 2007 Mar 7. [abstract]
  10. NIH Consensus and State-of-the-Science Statements; NIH Consensus Statement on Celiac Disease; Volume 21, Number 1 June 28?30, 2004
  11. Hadithi M, de Boer H, Meijer JW, et al; Coeliac disease in Dutch patients with Hashimoto's thyroiditis and vice versa. World J Gastroenterol. 2007 Mar 21;13(11):1715-22. [abstract]
  12. Green PH, Jabri B; Coeliac disease. Lancet. 2003 Aug 2;362(9381):383-91. [abstract]
  13. Hin H, Bird G, Fisher P, et al; Coeliac disease in primary care: case finding study. BMJ. 1999 Jan 16;318(7177):164-7. [abstract]
  14. Sher KS, Mayberry JF. Female fertility, obstetric and gynaecological history in coeliac disease. A case control study. Digestion 1994; 55(4):243-6.
  15. Sher KS, Jayanthi V, Probert CS et al. Infertility, obstetric and gynaecological problems in coeliac sprue. Dig Dis 1994;12(3):186-90
  16. Menni S, Boccardi D, Brusasco A; Ichthyosis revealing coeliac disease. Eur J Dermatol. 2000 Jul-Aug;10(5):398-9. [abstract]
  17. Di Sabatino A, Corazza GR; Coeliac disease. Lancet. 2009 Apr 25;373(9673):1480-93. [abstract]
  18. Mein SM, Ladabaum U; Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost-effectiveness analysis. Aliment Pharmacol Ther. 2004 Jun 1;19(11):1199-210. [abstract]
  19. The management of adults with coeliac disease in primary care, Primary Care Society for Gastroenterology (May 2006)
  20. Farrell RJ, LaMont JT; Rational approach to iron-deficiency anaemia in premenopausal women. Lancet. 1998 Dec 19-26;352(9145):1953-4.
  21. Feighery C; Fortnightly review: coeliac disease. BMJ. 1999 Jul 24;319(7204):236-9.
  22. Fraser JS, King AL, Ellis HJ, et al; An algorithm for family screening for coeliac disease. World J Gastroenterol. 2006 Dec 28;12(48):7805-9. [abstract]
  23. Hopper AD, Cross SS, Hurlstone DP, et al; Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool. BMJ. 2007 Apr 7;334(7596):729. Epub 2007 Mar 23. [abstract]
  24. Sanders DS, Carter MJ, Hurlstone DP, et al; Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. Lancet. 2001 Nov 3;358(9292):1504-8. [abstract]
  25. van Heel DA, West J; Recent advances in coeliac disease. Gut. 2006 Jul;55(7):1037-46.
  26. Diagnosis and management of type 1 diabetes in children, young people and adults, NICE Clinical Guideline (July 2004)
  27. Prescribable Product List, Coeliac UK
  28. Coeliac UK, Prescribing Guide (Gluten-free Foods)
  29. Cerf-Bensussan N, Matysiak-Budnik T, Cellier C, et al; Oral proteases: a new approach to managing coeliac disease. Gut. 2007 Feb;56(2):157-60. Epub 2006 Sep 1. [abstract]
  30. Guidelines for Osteoporosis in Inflammatory Bowel Disease and Coeliac Disease, British Society of Gastroenterology (2007)
  31. Viljamaa M, Kaukinen K, Pukkala E, et al; Malignancies and mortality in patients with coeliac disease and dermatitis herpetiformis: 30-year population-based study. Dig Liver Dis. 2006 Jun;38(6):374-80. Epub 2006 Apr 14. [abstract]
  32. West J, Logan RF, Smith CJ, et al; Malignancy and mortality in people with coeliac disease: population based cohort study. BMJ. 2004 Sep 25;329(7468):716-9. Epub 2004 Jul 21. [abstract]
  33. Smedby KE, Akerman M, Hildebrand H, et al; Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. 2005 Jan;54(1):54-9. [abstract]

Internet and further reading

  • Coeliac disease, NICE Clinical Guideline (May 2009); Recognition and assessment of coeliac disease
  • Coeliac UK, Charity for coeliac disease and dermatitis herpetiformis
  • Di Sabatino A, Corazza GR; Coeliac disease. Lancet. 2009 Apr 25;373(9673):1480-93. [abstract]
The clinicians responsible for the production of this document are:
Original Author: Dr Huw Thomas
Last Checked: 22 Feb 2011
Current Version: Dr Huw Thomas
Document ID: 1975  Version: 24
Peer Reviewer: Dr Paul Scott
© EMIS 2011
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