Dr Tanay Sheth discusses updated NICE guidance on coeliac disease and the importance of diagnosis and treatment through adherence to a gluten-free diet

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Read this article to learn more about:

  • the prevalence of coeliac disease
  • the tests required for diagnosis of this condition
  • recommended dietary advice for patients and carers.

Key points

CP commissioning messages

C oeliac disease (CD) is an immune-mediated enteropathy that is triggered by dietary gluten (present in wheat, barley, and rye) in genetically predisposed individuals, resulting in chronic small intestinal inflammation and malabsorption.1,2 It is strongly associated with the human leukocyte antigen (HLA) variants HLA-DQ2.5 (≥90%) and HLA-DQ8 (most of the remainder).2

Coeliac disease is common, with a prevalence of about 1% in the UK.1 It may present at any age and with a diverse range of clinical features—both gastrointestinal and non-gastrointestinal. The 'classic' CD picture of diarrhoea, steatorrhoea, weight loss, and failure to thrive is no longer the dominant presentation. Up to 80% of cases of CD remain clinically undetected.1,3 Although some individuals may have few or no symptoms, at least initially, many experience very long delays (>10 years) from onset of symptoms to diagnosis.3

Patients with a number of autoimmune and chromosomal conditions, including type 1 diabetes mellitus, autoimmune thyroid disease, and Down's syndrome, are at higher risk of CD.1 First-degree relatives of patients with CD have a 10% risk of being affected.2 Complications of CD include vitamin D deficiency, iron deficiency, osteoporosis, ulcerative jejunitis, hyposplenism, subfertility, miscarriage, and a small risk of malignancy (including intestinal lymphoma).1,2 A lifelong gluten-free diet (GFD), which reduces symptoms and seems to reduce the risk of complications in symptomatic patients, is the only treatment available.12

Box 1: NICE Accreditation Mark

NICE accreditation logo

NICE Guideline 20 on Coeliac disease: recognition, assessment and management has been awarded the NICE Accreditation Mark. This Mark identifies the most robustly produced guidance available.

See evidence.nhs.uk/accreditation for further details. 

This article reviews how to recognise, assess, and manage CD, with particular reference to the updated NICE Guideline 20 (NG20).1

Box 2: NICE Pathways

NICE pathways logo

This NICE guideline is part of the NICE coeliac disease pathway, available at: pathways.nice.org.uk/pathways/coeliac-disease

See here for more information on NICE pathways.

Recognition

Considering the possibility of CD, with its wide range of presentations (see Box 3, below), is key to recognising the condition.

Advise patients that any test (serology or duodenal biopsy) is accurate only if they continue to eat gluten during the diagnostic process, and so they should not start a GFD until the diagnosis has been confirmed by a specialist (even if serology is positive).2 Gluten in more than one meal every day for at least 6 weeks prior to testing is advised.1 If patients have already restricted or excluded dietary gluten and are unwilling or unable to reintroduce it, refer them to a specialist, explaining that it may be difficult to confirm the diagnosis by intestinal biopsy. If initial testing is negative in at-risk groups (particularly first-degree relatives and those with type 1 diabetes), have a low threshold for re-testing if any of the symptoms in Box 3 (below) develop and advise patients to make a return appointment.

Do not offer serological testing for infants before gluten has been introduced to the diet.1

Box 3: Recognition of coeliac disease1

  • Offer serological testing for coeliac disease to:
    • people with any of the following:
      • persistent unexplained abdominal or gastrointestinal symptoms
      • faltering growth
      • prolonged fatigue
      • unexpected weight loss
      • severe or persistent mouth ulcers
      • unexplained iron, vitamin B12, or folate deficiency
      • type 1 diabetes, at diagnosis
      • autoimmune thyroid disease, at diagnosis
      • irritable bowel syndrome (in adults)
    • first-degree relatives of people with coeliac disease.
  • Consider serological testing for coeliac disease in people with any of the following:
    • metabolic bone disorder (reduced bone mineral density or osteomalacia)
    • unexplained neurological symptoms (particularly peripheral neuropathy or ataxia)
    • unexplained subfertility or recurrent miscarriage
    • persistently raised liver enzymes with unknown cause
    • dental enamel defects
    • Down's syndrome
    • Turner syndrome.

NICE (NG20). Coeliac disease: recognition, assessment and management. NICE, 2015. Available at: www.nice.org.uk/guidance/ng20
Reproduced with permission

 

Serological testing

Total immunoglobulin A (IgA) and IgA tissue transglutaminase (tTG) are the first-choice tests in adults and children.1 If IgA tTG is weakly positive in adults, IgA endomysial antibodies (EMA) should be assayed. If IgA is deficient (<0.07 mg/l) in adults or children, consider assaying IgG EMA, IgG deamidated gliadin peptide (DGP), or IgG tTG. Serological testing should be undertaken in laboratories with clinical pathology accreditation (CPA) or ISO15189 accreditation, and a specific assay should be used for total IgA. Laboratories should clearly communicate their interpretation of the results and make recommendations to requesting healthcare professionals.1

Testing for HLA-DQ2 (DQ2.2 and DQ2.5) and HLA-DQ8 to rule out CD should be considered only in specialist settings—for example, in children who are not having a biopsy or patients who have restricted their gluten ingestion and choose not to have a gluten challenge.1

Referral

Box 4 (Below) details which patients should be referred.

Box 4: When to refer1,4

 

Referral of people with suspected coeliac disease1
  • Refer young people and adults with positive serological test results* to a gastrointestinal specialist for endoscopic intestinal biopsy to confirm or exclude coeliac disease
  • Refer children with positive serological test results to a paediatric gastroenterologist or paediatrician with a specialist interest in gastroenterology for further investigation for coeliac disease
  • Refer people with negative serological test results to a gastrointestinal specialist for further assessment if coeliac disease is still clinically suspected.
Monitoring in people with coeliac disease1
  • Consider referring people with coeliac disease for endoscopic intestinal biopsy if continued exposure to gluten has been excluded and:
    • serological titres are persistently high and show little or no change after 12 months or
    • they have persistent symptoms, including diarrhoea, abdominal pain, weight loss, fatigue or unexplained anaemia.
Suspected cancer4
  • Refer patients with symptoms suggestive of cancer in line with NICE Guideline 12 on suspected cancer.

* In young people and adults, a positive serological test result is defined as unambiguously positive IgA tTG alone, or weakly positive IgA tTG and a positive IgA EMA test result. Note: In people who have IgA deficiency, a serologically positive result can be derived from any one of the IgG antibodies

Further investigation may include, but is not limited to, one or more of the following: an IgA EMA test to confirm serological positivity, HLA genetic testing, an endoscopic biopsy

IgA=immunoglobulin A; tTG= tissue transglutaminase; EMA=endomysial antibodies;
IgG=immunoglobulin G; HLA=human leucocyte antigen

Taken from:
NICE (NG20). Coeliac disease: recognition, assessment and management. NICE, 2015. Available at: www.nice.org.uk/guidance/ng20
NICE (NG12). Suspected cancer: recognition and referral. NICE Guideline 12. London: NICE, 2015. Available at: www.nice.org.uk/guidance/ng12
Reproduced with permission

Information and support

Explain to those people who are thought to be at risk of CD that delayed diagnosis—or undiagnosed CD—can result in continuing ill health and serious long-term complications. Provide sources of information on CD, including signposting to national and local specialist coeliac groups and specialist dietitians.1 At diagnosis, encourage patients to join Coeliac UK (www.coeliac.org.uk)—the UK's leading charity for CD, which provides information and support for patients and their families and carers; patients, particularly adolescents, often find it difficult to adhere fully to a GFD and need encouragement and motivation. Patients with CD may experience anxiety or depression, which should be managed in line with the relevant NICE guidelines (CG28, CG91, CG113, and CG159).1,5 -8

Dietary advice

A dietitian or other healthcare professional with a specialist knowledge of CD should explain the importance of a GFD and provide information to help patients follow it. This should include:1

  • information on types of food that contain gluten and suitable alternatives, including gluten-free substitutes—gluten-free foods available on prescription are found in Appendix 2 (Borderline substances) of the British National Formulary (BNF)9 and the BNF for Children10
  • explanations of food labelling—the Food Information Regulations (2014) require emphasis on regulated allergen ingredients (including wheat, rye, barley, and oats)
  • information sources for GFDs, recipe ideas, and cookbooks
  • advice on avoiding cross-contamination in the home and minimising the risk of accidental gluten intake when eating out
  • advice on managing social situations, eating out, and travelling away from home, including travel abroad
  • information about the role of national and local coeliac support groups, including Coeliac UK.

Patients (and their family members or carers, as appropriate) should be advised:1

  • to seek advice if they are considering over-the-counter vitamin or mineral supplements
  • that they may need calcium or vitamin D supplements if their dietary intake is insufficient (adult patients should have a calcium intake of ≥1000 mg per day)2
  • that they may take gluten-free oats at any stage and that they will be advised whether to continue depending on their clinical, immunological, or histological response.

A GFD may provide no health benefits in individuals who are truly asymptomatic.2

Monitoring

Patients should be offered an annual review, which may be delivered in primary care by a GP or a dietitian with specialist knowledge of coeliac disease. During the review, the following should be assessed:1

  • symptoms
  • weight and height
  • need for further assessment of diet and adherence with GFD and/or specialist dietetic and nutritional advice.

If concerns are raised by the review, refer the patient to a GP or consultant, who should assess:1

  • the need for specific blood tests—the British Society for Gastroenterology (BSG) advises annual blood profiles, including full blood count, ferritin, serum folate, vitamin B12, calcium, liver enzymes, thyroid function tests, serum glucose, and tTG (or EMA/DGP)2
  • the need for dual-energy x-ray absorptiometry (DEXA) (in line with NICE CG146 on assessing the risk of fragility fracture in osteoporosis11) or active treatment of bone disease
  • the risk of long-term comorbidities and complications (e.g. osteoporosis and small bowel malignancy)
  • the need for specialist referral.

Newly diagnosed patients should be offered pneumococcal vaccination in view of the risk of hyposplenism.2

Serological testing alone should not be used to determine adherence with a GFD. This is best achieved by a stepwise combination of symptom assessment, dietetic review, serology, and duodenal biopsy.2

Non-responsive and refractory coeliac disease

Non-responsive CD occurs in patients who report persistent symptoms despite advice on following a GFD (5–30% of patients with CD1). The original diagnosis should be confirmed in such patients, who should then be referred to a specialist dietitian so that their adherence with a GFD can be assessed. Inadvertent or deliberate exposure to gluten is the most frequent cause.2 They should then be referred for duodenal biopsy and consideration of co-existing conditions (e.g. irritable bowel syndrome, lactose intolerance, bacterial overgrowth, microscopic colitis, and inflammatory colitis).1,2

Refractory CD is diagnosed in patients with persistent symptoms, in whom the original diagnosis of CD has been confirmed, exposure to gluten has been excluded, and any coexisting conditions have been excluded as the cause (10% of patients with non-responsive CD1). Such patients should be referred to a specialist centre for further investigation. Prednisolone may be considered for initial management of symptoms in adults while awaiting specialist advice.1

Implementation and conclusions

NICE NG20 sets out evidence-based good practice on the recognition, assessment, and management of CD. Coeliac disease is common and has a wide range of presentations. Many patients continue to experience long periods of ill health before diagnosis. Primary care is best placed for active case finding. More widespread testing will improve detection rates, and successful treatment will improve symptoms and may help reduce complications. Many laboratories currently offer only one coeliac serological test (usually tTG), and laboratories often report results as numbers without interpretation or recommendation, but this should improve with implementation of NICE NG20. The only available treatment is lifelong GFD. Specific information, support, and dietary advice may increase the likelihood of adherence and the best prognosis but access to specialist dietitians is currently patchy. Patients may be monitored in primary care once stable, although they should have ready access to secondary care in case of problems.

Key points

  • Clinicians should have a low threshold for case finding (see Box 3, above)
  • Prior to testing, clinicians should encourage patients to eat gluten in more than one meal every day for ≥6 weeks (and to continue until the diagnosis has been confirmed)
  • Total IgA and IgA tTG are the first-choice serological tests in adults and children
  • Patients should be encouraged to join Coeliac UK (www.coeliac.org.uk)
  • A specialist dietitian (or other healthcare professional) should tell patients about the importance of a gluten-free diet and give them information to help them follow it
  • Clinicians should offer an annual review
  • In patients with non-responsive coeliac disease, the original diagnosis should be confirmed and they should be referred to a specialist dietitian for assessment of their adherence with a gluten-free diet in the first instance.

IgA=immunoglobulin A; tTG=tissue transglutaminase.

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GP commissioning messages

written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead

  • Coeliac disease is common and initial diagnosis is often delayed due to a wide variation in presenting symptoms
  • Commissioners with local specialist providers and coeliac charities should consider creating patient-targeted awareness campaigns (possibly through pharmacies and general practices), supported by education programmes for healthcare professionals
  • There should be agreed local pathways for referral for diagnosis and dietary advice, and it should be clearly defined who is to be responsible for conducting a patient’s annual review and associated blood tests:
    • These pathways should also include other initial investigations that should follow immediately after diagnosis (e.g. DEXA scanning in adults)
  • Local medicines optimisation teams should establish local formularies for gluten-free products and decide which products will be supported and prescribed and which (e.g. non-healthy foods like biscuits) will not.

DEXA=dual-energy X-ray absorptiometry

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g logo gls turquoise

Read the Guidelines summary of NG20 on Coeliac disease: recognition, assessment and management for more recommendations on identifying and managing coeliac disease

References

  1. Internal Clinical Guidelines Team. Coeliac disease: recognition, assessment and management. Clinical Guideline NG20. Methods, evidence and recommendations. Manchester: NICE, 2015. Available at: www.nice.org.uk/guidance/ng20/evidence
  2. British Society of Gastroenterology. Guidelines on the diagnosis and management of adult coeliac disease. London: BSG, 2014. Available at: www.bsg.org.uk/clinical-guidelines/small-bowel-nutrition/guidelines-on-the-diagnosis-and-management-of-adult-coeliac-disease.html
  3. Coeliac UK. Coeliac UK fact sheet. Coeliac UK, 2013. Available at: https://www.coeliac.org.uk/document-library/25-key-facts-and-stats/
  4. NICE. Suspected cancer: recognition and referral. NICE Guideline 12. London: NICE, 2015. Available at: www.nice.org.uk/guidance/ng12
  5. NICE. Depression in children and young people: identification and management. Clinical Guideline 28. London: NICE, 2005. Available at: www.nice.org.uk/guidance/cg28
  6. NICE. Depression in adults with chronic physical health problem: recognition and management. Clinical Guideline 91. London: NICE, 2009. Available at: www.nice.org.uk/guidance/cg91
  7. NICE. Generalised anxiety disorder and panic disorder in adults: management. Clinical Guideline 113. London: NICE, 2011. Available at: www.nice.org.uk/guidance/cg113
  8. NICE. Social anxiety disorder: recognition, assessment and treatment. Clinical Guideline 159. London: NICE, 2013. Available at: www.nice.org.uk/guidance/cg159
  9. Joint Formulary Committee. British National Formulary. 70th ed. London: British Medical Association and Royal Pharmaceutical Society, 2015.
  10. Paediatric Formulary Committee. BNF for Children 2015–2016. London: British Medical Association and Royal Pharmaceutical Society, 2015.
  11. NICE. Osteoporosis: assessing the risk of fragility fracture. Clinical Guideline 146. London: NICE, 2012. Available at: www.nice.org.uk/guidance/cg146G