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October 25, 2017
Coeliac Disease
October 25, 2017
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Coeliac Disease

(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, which can lead to malabsorption of nutrients. Gluten is a protein found in wheat, rye and barley.

Histology

It is a multi genetic 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.

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.

Prevalence of Coeliac Disease

Prevalence is approximately 1 in 1000 However, only 10-20% will have been diagnosed as having CD. Coeliac disease affects all ethnic groups.

Appearance

It may appear at any age. CD can be difficult to recognise because of the wide variation in symptoms and signs. Many cases may be asymptomatic. There may be a very long delay from the onset of symptoms until the diagnosis is made.

It is recommends that serological testing for CD should be offered for people:

With severe or persistent mouth ulcers

With prolonged fatigue.

With autoimmune thyroid disease (at the time of diagnosis).

Who have persistent unexplained abdominal or gastrointestinal symptoms.

Who have faltering growth.

With unexpected weight loss.

With type 1 diabetes (at the time of diagnosis).

Who are first-degree relatives of people with coeliac disease.

Who have unexplained iron, vitamin B12 or folate deficiency.

With Irritable bowel syndrome (IBS) – in adults.

Serological testing for coeliac disease can also be recommended for people with any of the following:

Dental enamel defects.

Unexplained sub fertility or recurrent miscarriage.

Turner syndrome.

Metabolic bone disorder (reduced bone mineral density or osteomalacia).

Persistently raised liver enzymes with unknown cause.

Unexplained neurological symptoms (particularly peripheral neuropathy or ataxia).

Down’s syndrome.

Dermatitis Herpitiformis (a chronic, polymorphic, pruritic skin disease) 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.

Neurological appearances

CD is associated with neurological and psychiatric disorders including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia and depression. It is also considered that a broader spectrum of neurological syndromes may be the initial presentation of gluten sensitivity with or without intestinal pathology. These include migraine, encephalopathy, chorea, brainstem dysfunction, myelopathy, mononeuritis multiplex, Guillain-Barré-like syndrome and neuropathy with positive antiganglioside antibodies.

Probes

Any test for CD is accurate only if a gluten-containing diet is eaten during the diagnostic process. The person should not start a gluten-free diet until diagnosis is confirmed by a specialist, even if the results of a serological test are positive. For people who have restricted their gluten intake or excluded gluten from their diet and are reluctant or unable to re-introduce gluten into their diet before testing, refer to a gastrointestinal specialist but explain that it may be difficult to confirm their diagnosis by intestinal biopsy. Serological testing for CD should not be offered in infants before gluten has been introduced into the diet.

Always have a low threshold for re-testing people if they develop any symptoms consistent with CD.

Related 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.

Recommendations:

For suspected CD in young people and adults:

Total immunoglobulin A (IgA) and IgA tissue transglutaminase (tTG) as the first choice. IgA EMAs if IgA tTG is weakly positive.

For suspected CD in children:

Total IgA and IgA tTG as the first choice.

Consider using IgG EMA, IgG DGP or IgG tTG if IgA is deficient.

HLA DQ2 (DQ2.2 and DQ2.5)/DQ8 testing should only be used in the diagnosis of CD in specialist settings (eg, children who are not having a biopsy, or people who already have limited gluten ingestion and choose not to have a gluten challenge).

Some more probes

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.

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.

Biopsy confirmation

A biopsy is still needed to diagnose CD. 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 EMAs 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 conditions with similar symptoms

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

Exception (coeliac gluten sensitivity)

This is an umbrella term and may incorporate a wide range of possible clinical features. Some people report gluten-related symptoms but without evidence of CD. There is evidence suggesting that, even in the absence of CD, gluten-based products can induce abdominal symptoms which may appear as IBS. The spectrum of gluten-related disorders includes CD, wheat allergy and non-coeliac gluten sensitivity. In all three conditions symptoms improve on the withdrawal of gluten.

Controlling Effectively

Treatment with a lifelong strict gluten-free diet (GFD) is currently the only treatment of known effectiveness.

Starting a 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).

Creating awareness and providing support

People who are thought to be at risk of CD should be explained that a delayed diagnosis, or undiagnosed CD, can result in continuing ill health and serious long-term complications.

Sources of information on the disease, including national and local specialist coeliac groups and dieticians with a specialist knowledge of CD should be provided.

A healthcare professional with a specialist knowledge of CD should explain the importance of a GFD 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. All allergens (eg, wheat, rye, barley and oats) must be emphasised in the list of ingredients.

Information sources about GFDs, 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.

Counsel on food intake

Explain to people with CD (and their family members or carers, where appropriate):

That they should seek advice from a member of their healthcare team if they are thinking about taking over-the-counter vitamin or mineral supplements.

That they may need to take specific supplements such as calcium or vitamin D if their dietary intake is insufficient.

That they can choose to include gluten-free oats in their diet at any stage and they will be advised whether to continue eating gluten-free oats depending on their immunological, clinical or histological response.

Surveillance

Consider referring people with CD 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.

Serological testing alone to determine whether gluten has been excluded from the person’s diet may not be helpful.

Annual Follow up:

Specialist dietetic and nutritional advice

Measure weight and height.

Assessment of diet and adherence to the GFD.

Need for a dual-energy X-ray absorptiometry (DEXA) scan or active treatment of bone disease.

Need for specific blood tests, the risk of long-term complications and comorbidities and the need for specialist referral.

Blood tests that may need to be considered include FBC, LFTs, calcium and albumin, B12, folate, serum ferritin. Low haemoglobin, red cell folate and serum ferritin may suggest persisting malabsorption warranting further assessment.

Insusceptible coeliac disease

For people with CD who have persistent symptoms despite advice to exclude gluten from their diet:

Review the certainty of the original diagnosis.

Refer the person to a specialist dietician to investigate continued exposure to gluten. Investigate potential complications or co-existing conditions which may be causing persistent symptoms, such as IBS, lactose intolerance, bacterial overgrowth, microscopic colitis or inflammatory colitis.

Complexities

Delayed diagnosis of CD may result in continuing ill health and may lead to –

1)miscarriage

2) Osteoporosis,

3) growth failure, delayed puberty

4) dental problems (in children).

5) Nutrient deficiencies – eg, vitamin D and iron.

6) 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. [ Intestinal lymphoma usually presents with the return of bowel symptoms, although it usually responds poorly to treatment.

7) Ulcerative jejunitis.

8) Functional hyposplenism: some degree of splenic atrophy is present in most patients with CD.

9)People with CD may experience anxiety and depression.

10)Untreated CD is associated with infertility in men and women but this resolves on a GFD.

11) Poor fetal outcome in pregnant women with undiagnosed CD but not in diagnosed CD.

Patients often find it difficult to be fully compliant with a GFD, particularly adolescents.The long-term health risks for patients who comply poorly with a GFD include nutritional deficiency and reduced bone mineral density. Many coeliac patients have an inadequate energy intake. Poor absorption often leads to inadequate intake of calcium and vitamin B6 and vitamin D. 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.