Coeliac disease, or gluten-sensitive enteropathy, occurs in about 1% of the UK population and is a condition that all GPs can expect to encounter. It may cause digestive symptoms and is also responsible for a range of non-gastrointestinal problems and lifelong ill health.

Presentation

Nowadays, most new cases of coeliac disease do not match the classical description by Samuel Gee in 1888, of children with obvious malabsorption, fatty stools, abdominal bloating and failure to thrive.

It is important to consider the diagnosis in all ages; the average age of diagnosis is now over 50 and patients have been diagnosed in their 80s or later.

The most common mode of presentation is anaemia, and coeliac disease is often diagnosed by gastroenterologists in patients referred with suspected gastrointestinal cancer. Fatigue is common, as are symptoms compatible with irritable bowel syndrome.

Not all patients have diarrhoea or are underweight; many are actually overweight.

The majority of patients with coeliac disease remain undiagnosed. This is the so-called "coeliac iceberg" - only 10% of cases have been recognised.

This figure comes from population studies using specific antibodies. Several case-finding studies have been carried out in general practice. One study, in Central England, found 30 new cases in the first 1,000 adult patients with possible presentations that could be due to undiagnosed coeliac disease who were screened.¹ Of these newly diagnosed patients, 50% had a history of anaemia and most had non-gastrointestinal symptoms, such as feeling "tired all the time".

Another cross-sectional study, from Yorkshire,² found an overall prevalence of 1%, with higher prevalences in patients with iron-deficiency anaemia, irritable bowel syndrome and fatigue. A similar prevalence was found in a large Cambridge general practice survey.³

People with occult undiagnosed coeliac disease detected in large population studies show lower values for haemoglobin, hip bone mineral density, body mass index and cholesterol.⁴

Children aged seven with undiagnosed coeliac disease are shorter, weigh less and are more likely to have had diarrhoea. The prevalence in this age group is about 1%, indicating that the condition begins earlier in life.⁵

Dermatitis herpetiformis, a characteristic itchy rash on the upper body, is usually associated with coeliac disease. Mouth ulcers are also more common.

Mild abnormalities in liver function tests are often found in patients with coeliac disease and occasionally patients will present with disorders of mineral metabolism. Coeliac disease is also prevalent in patients with a number of other conditions, especially other autoimmune disorders such as type 1 diabetes and thyroid disease, presenting as either hyper- or hypothyroidism (see table 1,attached).

Coeliac disease has a strong genetic component. About 10% of first-degree relatives of a patient with coeliac disease will also have the condition. Testing should be performed routinely if coeliac disease is suspected in a patient with a family member who has the condition.

Diagnosis

The initial diagnosis of coeliac disease can now be made easily with simple blood tests. Patients should be tested for tissue transglutaminase (tTG) antibodies and endomysial antibodies whenever there is even a remote chance of coeliac disease.

• tTG is an enzyme involved in healing, which also reacts with peptides in gluten. In coeliac disease, IgA antibodies are produced to tTG, which can be detected by ELISA tests. The use of recombinant human tTG provides the greatest specificity and sensitivity.

•The presence of endomysial antibodies, detected by immunohistochemistry, is used to confirm positive tTG tests.

Both antibodies are highly specific and sensitive, unlike gliadin antibodies. High levels are found only in patients with coeliac disease, although borderline levels are less specific.

The main cause of a false-negative result is comorbid selective IgA deficiency. This is found in 1-2% of the UK population and does not produce any other significant abnormality. Measurement of total IgA levels will detect this condition; IgG class tTG and endomysial antibodies will then usually be found if the patient has coeliac disease.

Referral to a gastroenterologist is essential in patients with a positive antibody test, or when coeliac disease is strongly suspected from symptoms and the serology is negative.

Endoscopic duodenal biopsy is required to confirm the diagnosis, particularly in view of the lifelong nature of the condition and the significant dietary changes that are needed.

Multiple biopsies from the proximal duodenum are taken. The classical finding in patients with coeliac disease is villous atrophy (see figure 1), which can range from subtotal to minor degrees of partial villous atrophy. Hyperplasia of the intestinal crypts is found, together with an increase in the number of intraepithelial lymphocytes.

The magnitude of the changes can be described according to the Marsh classification. An algorithm has been developed for endoscopists, which has been shown to be 100% sensitive in diagnosing new cases of coeliac disease when there is a positive tTG antibody test combined with biopsy in those with high-risk symptoms: diarrhoea, weight loss or anaemia.⁶

If a patient has already begun dietary treatment it can be difficult to confirm the diagnosis, so a normal diet should be continued after a positive tTG blood test until endoscopy.

Some patients may not have had the diagnosis fully established in the past but have been started on a gluten-free diet, which they are reluctant to give up. In these patients, and in patients with discordant serology and biopsy findings, HLA class II testing is helpful to exclude a diagnosis of coeliac disease. As all patients with coeliac disease have either the HLA-DQ2 (more than 90%) or HLA-DQ8 (5-10%) genes, the absence of these genes makes the diagnosis most unlikely.

Treatment

The only treatment for coeliac disease is a lifelong gluten-free diet. This involves exclusion of all foods containing wheat, barley and rye; normal bread, cakes, biscuits, pies and pasta cannot be eaten. Most processed foods contain gluten, and it is found unexpectedly in many foods, such as confectionery and potato crisps.

Pure potato, rice and corn cause no problems and provide excellent sources of carbohydrates and calories. The role of oat products is less clear, as most oats are contaminated with wheat, and probably best avoided.

Referral to a specialist dietitian to help patients adapt their diet is essential. Patients will initially need several appointments with an experienced gastrointestinal dietitian, and long-term follow-up to ensure they keep up to date with changes in gluten-free products. For instance, it has recently become apparent that most sources of cornflakes contain sufficient gluten to be a problem for patients with coeliac disease.

The support group Coeliac UK is a valuable resource for information about diet (and other concerns) for patients with coeliac disease, and all patients should be encouraged to join. Coeliac UK provides dietary updates and publishes an annual guide to which foods are gluten-free.

Gluten-free substitute foods, such as bread loaves, rolls, crispbreads, crackers, pasta, pizza bases, biscuits, flour and cake mixes, are all available and can be prescribed as approved by the Advisory Committee on Borderline Substances. Although patients can also buy many gluten-free products these are more expensive and prescription of appropriate foods helps ensure compliance, particularly when the disease is newly diagnosed.

Problems with adherence to a gluten-free diet should not be underestimated: eating out, hotel stays, visiting friends, peer pressure and inadvertent contamination are frequent concerns, particularly if they cause digestive symptoms. Experienced dietitians and Coeliac UK can provide crucial help. See table 2, attached, for key factors in the management of patients with coeliac disease.

Complications

Follow-up by specialists will provide advice on managing the disease and avoiding the long-term complications. The extent of any malabsorption needs to be defined, particularly when the condition is diagnosed, so that, as well as appropriate dietary advice, supplements can be prescribed.

Folic acid and iron deficiency are frequent and patients often need supplements. B₁₂ deficiency requires replacement therapy. Fibre supplements (gluten-free) may be required if constipation becomes a problem when diarrhoea is no longer an issue. Weight gain may be excessive when the malabsorption is controlled.

Awareness of impaired calcium absorption is important for long-term bone health. Patients with coeliac disease are often vitamin D deficient and have secondary hyperparathyroidism. Dietary calcium intake can be low, so calcium and vitamin D supplements are often necessary.

In newly diagnosed patients, osteopaenia is common. Bone mineral density improves in patients on a gluten-free diet.

Fractures are significantly more frequent in patients with coeliac disease,⁷ and referral for DEXA scanning to identify those with osteopaenia is justified. Based on these results, patients may need help to improve their compliance with a gluten-free diet, and to be prescribed calcium and vitamin D supplements or other medication such as bisphosphonates. Guidelines for managing osteoporosis in coeliac disease have been published by the BSG (see table 3, attached).⁸

The tTG antibody level will normalise with a strict gluten-free diet, but further duodenal biopsy may be needed to confirm healing of the intestine.

Persistent digestive symptoms have a variety of causes, including microscopic colitis, lactose intolerance, visceral hypersensitivity, pancreatic insufficiency and many others, but usually result from inadvertent gluten ingestion. Refractory coeliac disease is rare and needs further investigation by a gastroenterologist.

The most serious long-term complications are small intestinal malignancies. Lymphomas and adenocarcinomas are both significantly more common in patients with coeliac disease, but fortunately are rare. The combined increase in incidence is only about 1 per 1,000 patient-years following the first year after the diagnosis of coeliac diagnosis is made.⁹ The increase in these malignancies is most frequently seen when coeliac disease is first recognised and they have a poor prognosis.

Other aspects of long-term care include looking for associated hypothyroidism and advice about pneumococcal and other vaccinations in patients who may have hyposplenism.

Patients may be concerned about fertility and inheritance, and new parents may ask about the best practices in weaning to avoid their children having the same condition. Introduction of gluten before three months of age or after seven months of age should probably be avoided and only small amounts given.

More evidence is needed to understand fully the combination of genetic and environmental conditions that produce this common disease. GPs have an important role in recognising this condition and its ongoing management.