Coeliac Disease

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oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

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

This is an immune-mediated, inflammatory systemic disorder provoked by gluten and related prolamines in genetically susceptible individuals.[1] Gluten is a protein found in wheat, rye and barley.

It is a multigenetic disorder, associated with HLA types HLA-DQ2 (90%) or HLA-DQ8, plus other genetic or environmental factors. HLA typing indicating lack of DQ2 or DQ8 has a high negative predictive value, which may be useful if trying to exclude coeliac disease.[2]

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 coeliac disease (CD) about the real risk for another child having the disease, including an antenatal assessment.[3]

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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.[4] However, only 10-20% will have been diagnosed as having coeliac disease (CD).[5]

The disorder is thought to be rare in central Africa and East Asia.[6]

It may present at any age.[1][2] Coeliac disease (CD) can be difficult to recognise because of the wide variation in symptoms and signs. Many cases may be asymptomatic.

  • 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.
    • 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 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.[7]

Dermatitis herpetiformis is the classic skin manifestation of CD - almost all patients with the rash have either detectable villous atrophy (approximately 75%) or minor mucosal changes. Lamellar ichthyosis has also been reported in association with CD.[8]

Specific auto-antibodies

CD-specific antibodies include auto-antibodies against tissue transglutaminase type 2 (tTGA2), including endomysial antibodies (EMAs), and antibodies against deamidated forms of gliadin peptides (DGPs). These are measured in blood.

  • IgA anti-tissue transglutaminase antibodies (tTGAs) is the preferred investigation. EMAs are used if the tTGA test is not available or equivocal. The tTGA is a newer test (tTGA is the auto-antigen 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. tTGA should not be performed on children younger than 2 years.[1]
  • False negatives occur if the patient has selective IgA deficiency, as occurs in approximately 0.4% of the general population 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 gluten-free diet (GFD) and thus can be used to monitor the disease.

Positive antibodies should prompt a referral to a gastroenterologist. In children and adolescents with signs or symptoms suggestive of CD and high anti-tTGA titres (levels ≥10 times the upper limit of normal), the likelihood for villous atrophy is high. The paediatric gastroenterologist may discuss with the parents and patient (as appropriate for age) the option of performing further laboratory testing (EMA, HLA) to make the diagnosis of CD without biopsies.

Referral should also be made where the serology is negative, but there is strong clinical suspicion of CD.

HLA-DQ2 and HLA-DQ8 typing

A negative result for these makes a diagnosis of coeliac disease (CD) highly unlikely. If available, it can be offered to:

  • Patients with an equivocal diagnosis of CD.
  • Asymptomatic patients - as a screening tool for, for example, first-degree relatives, patients with Down's syndrome or known associated autoimmune or other conditions.

In the community for example, a GP may request HLA testing in a young patient with Down's syndrome, to obviate the need for annual screening.

Biopsy confirmation

Patients will need to stay on gluten until after the biopsy. The biopsy is obtained by upper gastrointestinal endoscopy or by suction capsule.

  • Histological examination of the mucosa classically shows 'subtotal villous atrophy' and results in malabsorption - however, mucosa is of normal thickness, the villous atrophy is compensated by crypt hyperplasia. There should be full clinical remission on excluding gluten from the diet.
  • 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.

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, ie 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.

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).[6]
  • Persistent or unexplained gastrointestinal 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 known associated conditions:[4]

  • Autoimmune thyroid disease.
  • Dermatitis herpetiformis.
  • Irritable bowel syndrome (IBS).[9]
  • Type 1 diabetes (3-12% have coeliac disease (CD))[6] - screen children every 2-3 years until adulthood, and subsequently if adults have a low body mass index (BMI) or develop unexplained weight loss.[1]
  • First-degree relative (parents, siblings or children) with CD.

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 syndrome, unexplained alopecia and unexplained subfertility.

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

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 (eg bread, cake, pies).[2] 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, 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 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.[10] GPs are responsible for the appropriate prescription of gluten-free products.

Arrange a dietitian appointment (with regular reviews).[2] 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 (eg fibre, folic acid, iron, calcium and vitamin D). Serial tTGA or EMA antibodies can be used to monitor response to diet.

Research is looking at how gluten could be detoxified in the intestine by oral endopeptidases. They are enzymes that break the gluten peptides into small chunks with fewer adverse effects.[6]

  • Patient compliance with a gluten-free diet (GFD) is poor, particularly in adolescents.[6] 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 coeliac disease (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.
  • Many coeliac patients have an inadequate energy intake. Poor absorption often leads to inadequate intake of calcium and vitamin B6 and vitamin D.
  • 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 three months and six 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.

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:
      • After three years on a GFD (only if the baseline DEXA is abnormal).[2]
      • 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).
    • 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 parathyroid hormone levels may be appropriate in at-risk individuals.[2]
  • 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, eg 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.
  • 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.

You should consider specialist referral if:

  • There is poor response to a gluten-free diet (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.

Delayed diagnosis of coeliac disease (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]

  • Osteoporosis.[11]
  • Cancer risk - there is conflicting research on this subject. Some research shows a small increase in overall risks of developing malignancy, eg gastrointestinal cancers and some types of lymphoma.[6] Intestinal lymphoma usually presents with the return of bowel symptoms, although it usually responds poorly to treatment.

Further reading & references

  1. Guidelines for the Diagnosis of Coeliac Disease, European Society for Pediatric Gastroenterology Hepatology and Nutrition (January 2012)
  2. The Management of Adults with Coeliac Disease; British Society of Gastroenterology (2010)
  3. 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.
  4. Coeliac disease; NICE Clinical Guideline (May 2009)
  5. Steele R; Diagnosis and management of coeliac disease in children. Postgrad Med J. 2011 Jan;87(1023):19-25. Epub 2010 Dec 3.
  6. Di Sabatino A, Corazza GR; Coeliac disease. Lancet. 2009 Apr 25;373(9673):1480-93.
  7. Pellicano R, Astegiano M, Bruno M, et al; Women and celiac disease: association with unexplained infertility. Minerva Med. 2007 Jun;98(3):217-9.
  8. Nenna R, D'Eufemia P, Celli M, et al; Celiac disease and lamellar ichthyosis. Case study analysis and review of the Acta Dermatovenerol Croat. 2011 Dec;19(4):268-70.
  9. Ford AC, Chey WD, Talley NJ, et al; Yield of diagnostic tests for celiac disease in individuals with symptoms Arch Intern Med. 2009 Apr 13;169(7):651-8.
  10. Prescribable Product List, Coeliac UK
  11. Guidelines for Osteoporosis in Inflammatory Bowel Disease and Coeliac Disease; British Society of Gastroenterology (2007)

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Huw Thomas
Current Version:
Peer Reviewer:
Dr Helen Huins
Document ID:
1975 (v25)
Last Checked:
13/06/2012
Next Review:
12/06/2017