Coeliac Disease
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Introduction

Coeliac disease is a common but often under diagnosed gastrointestinal disorder. Its presentation is often vague and a low level of suspicion should be applied to anybody who presents with non-specific abdominal symptoms, and particularly in those with a family history of the disease.

It is a chronic, auto-immune like illness that occurs in genetically susceptible individuals. It is caused by an abnormal inflammatory response to the presence of gluten in the diet. This small bowel inflammation disappears when gluten is removed from the diet, and reappears if gluten is eaten again.

In susceptible individuals, exposure to gluten can lead to damage of the proximal small bowel. In serious cases, it can affect the whole bowel. Wheat, rye and barley all contain gluten – these are collectively referred to as prolamin.

Coeliac disease is a major cause of GI malabsorption.However, coeliac disease is not just a gastrointestinal disorder. It is also associated with other organ effects, such as dermatitis herpetiformis (a rash that is herpes-like in appearance and occurs in a about 10-25% of all coeliac patients), ataxia, and immune dysfunction – particularly affecting the spleen.

Treatment involves a life-long gluten-free diet.

Epidemiology

  • The prevalence of coeliac disease is about 1 in 50 to 1 in 100. However it is thought that less than half of cases are actually diagnosed
  • Most common incidence is in children, and in those over 60, although it can occur at any age
  • Slightly more common in women over 60 than in men over 60
  • 30% risk for sibling, and 10% risk for first degree relatives, indicating an element of genetic susceptibility
  • Associated with other autoimmune diseases

Pathology

Gluten is a protein, found in many grass-type foods. It gives starchy foods their chewy bread-like texture. In the intestine, gluten is broken down by tissue transglutaminases (tTG) into smaller constituents called gliadins. Antibodies against tTG and other substances are hallmarks of coeliac disease.

  • Coeliac disease is a T-cell mediated auto-immune disease whereby a reaction against gluten eventually becomes an auto-immune reaction against the small intestinal mucosa.
  • The cause of the initial reaction is unknown. However, it may be mediated by a viral infection, for example, the adenovirus 12 shows homology with gliadin.
  • Gluten is a large molecule, that is broken down to smaller ones in the gut, and it is the breakdown products that are toxic (gliadins). The main toxic peptide is α-Gliadin.
  • In coeliac disease there is production of two antibodies – anti-gliadin, and anti-endomysial. Anti endomysial antibody attacks tTG (tissue transglutaminase) which is the enzyme responsible for gluten breakdown.
  • There is hypertrophy of crypts, and atrophy of the villi thus the overall wall thickness remains stable, but the surface of the bowel becomes flattened, and the surface area for absorption becomes greatly reduced
  • Increase in the number of inflammatory cells in the lamina propria
  • The proximal small intestine is most affected – due to the higher concentration of gluten products in this area (they get more broken down the further along the intestine they travel)
Left - normal histology of the small bowel. Right: Histology of the mucosa in Coeliac disease. Note the hypertrophy of the pits, and atrophy of the villi to create an almost flat mucosal surface, vastly reducing the surface area
Left – normal histology of the small bowel. Right: Histology of the mucosa in Coeliac disease. Note the hypertrophy of the pits, and atrophy of the villi to create an almost flat mucosal surface, vastly reducing the surface area

Symptoms

About 50% of cases exhibit no gastrointestinal symptoms. When present, gastrointestinal symptoms may be vague, which means coeliac disease can be easily mistaken for irritable bowel syndrome (IBS). 
  • About 25% of coeliac disease patients are initially diagnosed with IBS
  • The mean time from presumed disease onset to diagnosis is about 10 years

Gastrointestinal symptoms

  • General malaise / tiredness – often as a result of iron deficiency anaemia due to malabsorption
  • Diarrhoea – due to malabsorption
  • Nausea / vomiting
  • Bloating
  • Angular stomatitis – anaemia
  • Weight loss
  • Oral ulceration
  • Osteomalacia

Non-GI manifestations

  • Dermatitis Herpetiformis
    • About 20% patients will develop this rash. The rash tends to be very itchy and it found on the extensor surfaces of elbows and knees or on the trunk. The rash has a ‘herpetic’ appearance – looking like small vesicles, however in a truly heretic rash (as see in shingles, or HSV1 or 2 infection) the rash is often painful, and not itchy, as opposed to dermatitis herpetiformis which tends to be painless and itchy.
  • Ataxia
    • About 50% of all “ataxia of unknown origin” patients are subsequently discovered to have coeliac disease. These symptoms are more likely to be permanent than other manifestations of coeliac disease

Children – The disease may present with weaning onto cereals. Symptoms will include diarrhoea (steatorrhea), malabsorption and failure to thrive.

Adults – In older children and adults it may present with more non-specific symptoms, such as failure to grow properly, or more vague symptoms, such as fatigue, abdominal pain, abdominal distension, iron-deficiency anaemia, (angular stomatitis), weight loss, and oral ulceration.

  • Often the only sign is iron-deficiency anaemia.
  • 1/3 of patients are asymptomatic.
  • Skin rash – There is a very specific skin rash linked to coeliac disease.  It is called Dermatitis herpetiformis.

Investigations

Knowing whom to test for coeliac disease is a diagnostic challenge.

NICE recommends testing  patients (adults and children) with any of the following:

  • Diarrhoea – chronic or intermittent
  • Failure to thrive
  • Irritable bowel syndrome
  • Persistent, recurrent or unexplained nausea, vomiting, abdominal pain or bloating
  • Sudden or unexpected weight loss
  • Unexplained iron-deficiency  (or other) anaemia
  • Autoimmune thyroid disease
  • Type 1 diabetes
  • Dermatitis herpetiformis
  • First-degree relative with CD
A higher index of suspicion should be applied when:
  • Diarrhoea is present
  • Iron deficiency is present
  • Other autoimmune diseases are present
  • There is a family history of coeliac disease

The tests

  • Blood Test for tissue Transglutaminase (tTG) IgA (anti-tTG).
    • Patients need to eat a diet containing gluten to return a positive tTG result. If they have been trialling a gluten free diet, they will need to eat at least 3g of gluten (approximately equivalent to 2 slices of bread) per day for at least two weeks to generate an inflammatory response in the small intestine, and at least 4 weeks for a positive blood result.
    • Anti-tTg is a type of IgA. 3% of patients with coeliac disease also have IgA deficiency and will return a false negative. If total IgA is low (usually the lab will perform this as well as the tTG) then testing deaminated gliadin peptide (DGP) can be tested to confirm the suspicion of serology evidence of coeliac disease
    • If positive tTG-IgA or DGP then refer to gastroenterology for duodenal biopsy to confirm that diagnosis
  • HLA-DQ2/8 gene testing can be useful in certain circumstances.
    • About half the general population carry this gene variant
    • A positive test therefore is NOT diagnostic
    • However, a negative test has a strong negative predictive value (<1% of patients with negative test will have coeliac disease)
  • Endoscopy to take a duodenal biopsy for histological examination (>4 samples should be taken) is required to confirm the diagnosis. 50% of those with positive antibody test may not have histological changes.
    • Serology alone is not enough to diagnose coeliac disease – confirmatory biopsy is required
  • Histological findings typically involve: hypertrophy of the crypts, and atrophy of the villi, giving the mucosa a flattened appearance. The overall thickness of the mucosa is not changed. There must also be an increase in the number of inflammatory cells in the lamina propria for a diagnosis to be made. Also the receptors on T cells are different. Normally , they are of the Îł δ type, but in coealic’s they become α β. This is specific to coeliacs, and is irreversible.
    • The changes seen in coeliacs are measured in the Marsh scale. This has 4 levels (I-IV, IV being the most severe), with most coeliacs patients being level III. Marsh type IV is associated with a non-response to a gluten-free diet, and thus has a much greater risk of complications.

Diagnosis

There are no set criteria for the diagnosis of coeliac disease, but typically you will need:

  • Evidence of malabsorption (steatorrhoea, vitamin / nutritient deficiency)
  • Villous atrophy on duodenal biopsy (this is the most specific diagnostic test)
  • Weight loss
  • Features resolve upon adoption of gluten free diet

Screening

There is a 10% risk of first degree relatives being affected (thought to be as high as 30% for siblings) and any symptomatic first degree relatives should be screened once other family members have been diagnosed.

Complications

  • Nutritional deficiency due to malabsorption – particularly iron, B12 and folate
  • Increase risk of some cancer – particularly lymphoma. Risk is less than previously thought. Those who have been following a gluten free diet for 3-5 years have same risk as the general population
  • Reduced fertility (possibly) and increased risk of complications in pregnancy
  • Osteopaenia – reduction in bone density – due to lack of calcium absorption. 
    • Consider early, and regular DEXA (bone density) scanning. Patients as young as 20 may have osteopenia. Scan within the first year of diagnosis and treat accordingly
  • Osteoporosis – due to prolonged lack of calcium absorption
  • Osteomalacia– due to vitamin D / calcium malabsorption
  • Cerebellar disorders – due to problems with calcium metabolism
  • Neurological disorders – e.g. parasthesia and muscle weakness
  • Increased incidence of atopy other auto-immune conditions – particularly thyroid disease, type-1 diabetes etc.
  • Increased risk of malignancy – GI lymphoma (rare) or can be oesophageal, gastric, brain or breast (these are even rarer). Also increased risk of T-cell lymphoma and MALT, although this is still rare.

Management

This is life-long gluten free diet.
On diagnosis patients should be referred to an experienced dietician. Encourage them to learn about gluten free cooking.
Gluten is contained in: wheat, barley and rye. A wheat-free diet is not sufficiently gluten free and is not equivalent to a gluten free diet. Foods containing these products include:
  • Pasta
  • Bread
  • Cereals
  • Biscuits
  • Pastries / pies
  • Crumbed foods
  • Pizza
  • Oats* <30g / day
    • many patients choose the avoid oats altogether
  • Beware of additives – e.g. wheat based thickeners
There are gluten free versions of most of these foods and these are available on prescription.
*Oats do not actually cause the disease but are often prepared in factories where gluten has been used, thus these should be restricted to <30g/day
Problems with adherence are often because people do not realise some products contain gluten.
Very small amounts of gluten, with repeated exposure over prolonged periods can cause intestinal inflammation in some patients (as low as 50mg daily – equivalent to just a few bread crumbs). Encourage patients to check the labels of processed foods to determine if it may contain gluten.
Naturally gluten free foods include:
  • Rice
  • Corn
  • Meat
  • Dairy products
  • Fruit
  • Vegetables

Many processed gluten free foods contain increased amounts of sugar and fat.

Symptoms start to resolves within weeks to months of a gluten free diet.

Weight gain and constipation are common in those adhering to a gluten free diet.

You need to re-check anti-tTG levels to check control of the disease – typically at around 3-6 months to ensure the levels are falling.
You  should also investigate for and treat individual food deficiencies, such as vitamins (particularly B12 and folate), calcium and iron. Once inflammation of the bowel settles, long-term nutrient replacement is not usually required.
Re-testing
The goal of treatment is to reduce intestinal inflammation. Consider re-testing tTG every 3 months in the fist year after diagnosis to assess the effectiveness of treatment. This can cease once the patient is symptom free and well controlled.

If symptoms remain at 18-24 months consider repeat endoscopy for a re-biopsy.

References

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) currently works as a GP Registrar and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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