Genetics and environment
Nice quality standards



Coeliac disease is an autoimmune condition associated with chronic inflammation of the small intestine, which can lead to malabsorption of nutrients. It is a common condition and population screening studies suggest that in the UK, one in 100 people are affected.1 But, only 24% who have the condition have been diagnosed, which means there are currently nearly half a million people who have coeliac disease but don’t yet know.2 If a first degree family member has the condition then the chances of having it increase to one in 10.

People with conditions such as type 1 diabetes, autoimmune thyroid disease, Down’s syndrome and Turner syndrome are at a higher risk than the general population of having coeliac disease. First described by Dr Samuel Gee in 1888,3 the highest prevalence is in Ireland, Finland and countries to which Europeans have emigrated such as North America and Australia.

Coeliac disease diagnosis can be delayed when people present in primary care and other nonspecialist settings, which can lead to possible long‑term complications.1


Genetics and environment

Coeliac disease is caused by both genetic and environmental facto rs; namely gluten. Proteins in wheat, rye and barley are collectively termed gluten. Wheat contains gliadins and glutenins. Barley and rye have hordeins and secalins that activate disease. The high glutamine and proline content in these proteins may play a key part in disease pathogenesis.4

Contrary to common belief, gluten enteropathy is a systemic disease rather than merely an ailment of the alimentary tract. Genetically susceptible persons develop autoimmune injury to the gut, skin, liver, joints, uterus, brain, heart, and other organs.4 Genetic susceptibility is suggested by an approximately 70% concordance between monozygotic twins5 and an association with certain type II human leukocyte antigens (HLA). More than 95% of affected patients have DQ2 (HLADQA1* 05-DQB1*02) or DQ8 (HLADQA1*03- DQB1*0302), compared with 40% in the general population.6,7,8

More recent evidence suggests that the presence of auto‐antibodies to a connective tissue element surrounding smooth muscle called endomysium is highly specific for coeliac disease. The target of this autoantibody is now known to be an enzyme called tissue transglutaminase (tTG). This enzyme may play a prominent role in the pathogenesis of coeliac disease by modifying gliadin, resulting in a greater proliferative response of gliadin specific T‐cells, which contributes to mucosal inflammation and further B‐cell activation.9,10



The classical definition of coeliac disease includes gastrointestinal manifestations such as chronic diarrhoea, failure to grow, weight loss, vomiting, abdominal pain, bloating, distention, and constipation.

The presence of obesity does not exclude the diagnosis. Extra-intestinal manifestations are also common, sometimes with little or no gastrointestinal symptoms. One example is dermatitis herpetiformis, which is the skin manifestation of coeliac disease that occurs as a rash that commonly occurs on the elbows, knees, shoulders, buttocks and face, with red, raised patches often with blisters. It affects around one in 3,300 people.

Iron deficiency anaemia is also common and may be the only presenting sign. Other presentations are unexplained short stature, osteoporosis, vitamin deficiencies, fatigue, protein calorie malnutrition, recurrent aphthous stomatitis, elevated transaminases, and dental enamel hypoplasia.

Coeliac disease may also be associated with an autoimmune endocrinologic disorder such as thyroiditis. In addition, a variety of neuropsychiatric conditions such as depression, anxiety, peripheral neuropathy, ataxia, epilepsy with or without cerebral calcifications, and migraine headaches have been reported in individuals with coeliac disease.11



There is no one test that can definitively diagnose or exclude coeliac disease in every individual. Just as there is a clinical spectrum of coeliac disease, there is also a continuum of laboratory and histopathologic results. The combination of clinical and laboratory features may result in a diagnosis of coeliac disease.11

All diagnostic tests need to be performed while the patient is on a gluten-containing diet. The diagnosis of coeliac disease in adults is classically made on the basis of clinical suspicion and by recognising atypical presentations such as isolated iron deficiency, combined iron and folate deficiency, and osteoporosis. It is confirmed by a small bowel biopsy (SBB) with findings of villous atrophy, crypt hyperplasia, and normalisation of the villous architecture in response to a gluten-free diet.

Several serologic markers have become available that have altered the classic diagnostic pathway. Based on very high sensitivities and specificities, the best available tests are the IgA antihuman tissue transglutaminase (TTG) and IgA endomysial antibody immunofluorescence (EMA) tests that appear to have equivalent diagnostic accuracy. Antigliadin antibody (AGA) tests are no longer routinely recommended because of their lower sensitivity and specificity.11

The sensitivity of IgA anti‐gliadin antibodies (AGA) is reported to range from 70 to 85%, whereas the specificity ranges from 70 to 90%. IgA antiendomysial (EMA) and anti‐tissue transglutaminase (tTG) antibodies have sensitivities in excess of 90% and specificities of over 95%.12

NICE guidance suggests offering serological testing for coeliac disease to people with any of the following:

  • Persistent unexplained abdominal or gastrointestinal symptoms
  • Faltering growth nnProlonged 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.13



The management of coeliac disease is a gluten-free diet for life. A gluten-free diet is defined as one that excludes wheat, rye, and barley.

The NIH consensus statement lists six key elements in the management of coeliac disease, similar to the NICE guidelines. They can be summarised as CELIAC (Consultation with a skilled dietitian, Education, Lifelong adherence to gluten-free diet, Identification and treatment of nutritional deficiencies, Access to an advocacy group, Continuous long-term follow-up).

Following initial diagnosis and treatment, individuals should return for periodic visits with the physician and dietitian to assess symptoms and dietary adherence and monitor for complications.11

NICE suggest this should by an annual review. During the review: weight and height should be measured and symptoms reviewed. Healthcare physicians should also consider the need for assessment of diet and adherence to the gluten‑free diet and consider the need for specialist dietetic and nutritional advice.13

It also adds that a healthcare professional with a specialist knowledge of coeliac disease should tell people with a confirmed diagnosis of coeliac disease (and their family members or carers, where appropriate) about the importance of a gluten‑free diet and give them information to help them follow it. This should include:

  • Information on which types of food contain gluten and suitable alternatives, including gluten‑free substitutes
  • Explanations of food labelling
  • Information sources about gluten‑free diets, recipe ideas and cookbooks
  • How to manage social situations, eating out and travelling away from home, including travel abroad
  • Avoiding cross contamination in the home and minimising the risk of accidental gluten intake when eating out
  • The role of national and local coeliac support groups.


Arrange annual review of a person with confirmed coeliac disease and ensure the following is covered:
  • Ensure the person has received adequate advice and information on coeliac disease and gluten-free diets.
    • Assess the person’s adherence to a nutritious, varied, gluten-free diet.
    • Review the type and quantity of gluten-free foods that have been prescribed, and adjust the prescription accordingly.

      Do not routinely recommend nutritional supplements to prevent nutritional deficiencies.

    Some people may require specific supplements such as calcium and vitamin D if their dietary intake is insufficient.
    • Assess for symptoms and signs of coeliac disease, its complications and associated conditions.
    • Ask about gastrointestinal symptoms such as diarrhoea, abdominal pain, and blood in the stools.

      Measure body weight, height, and body mass index (BMI) to assess for signs of malnutrition (indicated by weight loss in adults).

    Assess and manage osteoporosis risk.
    • Consider annual blood testing, including:
    • Coeliac serology to help assess adherence to a gluten-free diet.

      Full blood count and ferritin — to screen for anaemia.

      Thyroid function tests — to screen for autoimmune thyroiditis.

      Liver function tests — to screen for autoimmune hepatitis.

      Vitamin D, vitamin B12, red cell folate, and serum calcium — to assess for deficiency.

    Electrolytes — to assess for Addison’s disease.
  • If malabsorption, diarrhoea, or other symptoms recur or persist despite strictly adhering to a gluten-free diet, exclude, diagnose, and/or manage alternative conditions, complications, and specific deficiencies.
    • Refer the person to a gastroenterologist if there is:
    • Symptoms and signs suggestive of gastrointestinal cancer such as unexplained blood in the stool — refer under the two-week wait rule.

    Complications, or persistent symptoms or signs of coeliac disease despite adherence to a gluten-free diet.
    • Consider referring the person to a dietitian if:
    • There is difficulty in assessing adherence to a gluten-free diet.

    Poor adherence to a gluten-free diet is suspected.
  • Offer immunisations, if indicated, for example for people with splenic dysfunction.
  • Offer more frequent review if problems arise or if there is a change in clinical needs


NICE quality standards

Recently NICE also published a series of quality standards. These were:

  • Statement 1. People at increased risk or with symptoms of coeliac disease are offered a serological test for coeliac disease. Offering serological testing when there is a new diagnosis for a condition that increases the risk of having coeliac disease or at presentation of symptoms of coeliac disease will improve detection and diagnosis, thereby enabling people to begin treatment.
  • Statement 2. People with a positive serological test for coeliac disease are referred to a specialist and advised to continue with a gluten‑containing diet until diagnosis is confirmed. As a positive serological result for coeliac disease is not sufficient to confirm diagnosis, people should be referred to a specialist for assessment and further investigation. Confirming diagnosis will ensure that people with coeliac disease can get support to help them manage their condition.
  • Statement 3. People referred to a specialist who need an endoscopic intestinal biopsy to diagnose coeliac disease have it within six weeks of referral. A long wait for an endoscopic intestinal biopsy can mean that some people will start a gluten-free diet to relieve symptoms and will therefore not be able to complete the diagnosis process.
  • Statement 4. People newly diagnosed with coeliac disease discuss how to follow a gluten‑free diet with a healthcare professional with specialist knowledge of coeliac disease. Personalised information and advice about a gluten‑free diet from a healthcare professional with specialist knowledge of coeliac disease will help people to understand and self‑manage their condition.
  • Statement 5. People with coeliac disease are offered an annual review. Annual reviews provide the opportunity to identify people with refractory coeliac disease that does not improve with a gluten‑free diet and to monitor any emerging long‑term complications of coeliac disease.1


  • Coeliac disease is a lifelong autoimmune disease caused by a reaction to gluten
  • 1 in 100 people have the condition
  • Symptoms include bloating, diarrhoea, nausea, wind, constipation, tiredness, sudden or unexpected weight loss (but not in all cases), hair loss and anaemia
  • Once diagnosed, it is treated by following a gluten-free diet for life
  • Dermatitis herpetiformis is the skin manifestation of coeliac disease.



The complications of coeliac disease (which may or may not be present at diagnosis) can include osteoporosis, ulcerative jejunitis, malignancy (intestinal lymphoma), functional hyposplenism, vitamin D deficiency and iron deficiency.1

Refractory coeliac disease refers to persistence of symptoms and intestinal inflammation despite a gluten-free diet. This may occur in the context of ulcerative jejunitis, or it may be an early manifestation of intestinal lymphoma.11

There is an increased risk of adenocarcinoma of the small intestine and some evidence that there may be an increased risk of carcinoma elsewhere in the gastrointestinal tract. All-cause mortality among those with clinically diagnosed coeliac disease is about twice that of control populations.11

Symptoms of refractory coeliac disease include: ongoing severe diarrhoea, stomach pain and sudden unexpected weight loss. Refractory coeliac disease is estimated to affect around 2-5%of people with coeliac disease. In most cases, refractory coeliac disease is diagnosed in people over the age of 50 years. Diagnosis of this should be conducted in a specialist centre where further tests will be conducted.

Further endoscopy investigations may be necessary. In people with refractory coeliac disease, the lining of the gut remains damaged and little or no improvement is seen from the start of the diet.15

Refractory coeliac disease is associated with a higher risk of complications and is associated with a poorer prognosis. There are two types of refractory coeliac disease: type 1 and type 2. People with type 2 refractory coeliac disease are at an increased risk of developing certain types of gut cancer



The symptoms of coeliac disease vary from person to person and can range from very mild to severe. Symptoms of eating gluten include diarrhoea, stomach pains and lethargy. The reaction is not the same as an allergic reaction and does not cause anaphylactic shock. The symptoms may last from a few hours to a few days. The only treatment for coeliac disease is a gluten-free diet for life. Once on the gluten-free diet, symptoms should improve, but the time it takes for the gut to heal varies from person to person.


Alison Bloomer, Managing Editor, BJFM

Conflict of interest: none declared.



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