• Coeliac Disease
• Gluten-free diet
• Diagnosis
• Historical
• Cause

Coeliac disease. The top 2 photos show a normal small bowel and the bottom 2 photos show coeliac disease - with loss of villi

How common is coeliac disease?

• Previous estimates - based on clinical detection - suggested that around 1:2000 people had coeliac disease.
• In contrast, a population screening study from Christchurch (screening using a blood test) showed that 1:85 had coeliac disease.
• This is a major difference!!

What is the benefit of diagnosing the mild cases of coeliac disease?

• Other population studies have had more mixed results.
  • In a large UK health survey of individuals aged 45-75 years 1.2% had positive endomysial antibodies i.e a diagnosis of coeliac disease.
    • This is a similar proportion of the population (compared with the Christchurch study).
    • There was no difference between subjects who were antibody positive or antibody negative for a wide range of indicators that were used to measure health and general well-being.
    • The only significant difference was a higher proportion of antibody positive subjects who had anaemia (16% compared with 4%).
    • There was a non-significant trend towards lower bone density in antibody positive subjects.
  • This study confirms the importance of checking for coeliac disease if there is iron deficiency (+/- anaemia) without any other obvious cause.
• It is perhaps helpful to use an “iceberg” analogy for coeliac disease with overt severe disease at the top and mild or silent disease forming the majority below sea level.
  • We are diagnosing a lot more people with mild coeliac disease.  Also some with "silent" disease.
  • The advice for this larger group beneath the surface may be different from those with severe disease.

Treatment of coeliac disease

• The only treatment is a gluten-free diet.
  • There is usually a rapid improvement in symptoms over a few weeks.
  • Continued improvement can occur over the first 6-12 months.
• If there is not any improvement specialist review is required.
  • Adherence to a gluten-free diet is easier when there is a clear correlation between gluten exposure and abdominal symptoms.
    • This is not always the case. Some people do not observe any direct relationship of inadvertent gluten exposure an symptoms.
  • Adherence to the diet has become easier because of a wide range of commercially available gluten-free foods and the mandatory labelling of foods for gluten content.
  • A list of manufactured foods that are gluten free is maintained on the website listed below.
• Helpful advice is available thorough dieticians and through the Coeliac Society of NZ.
  • There is a lot of good information on websites. Some examples are given below.
  • Dietary supplements are not usually required except during the first 6-12 months if significant nutritional deficiencies are identified.
  • Prompt replacement of vitamin D (if low serum vitamin D) is appropriate.

What are the advantages of gluten-free diet when there are no or few abdominal symptoms?

• You may be surprised by how much better you feel!!
  • That is, there has been an acceptance of a decreased level of well-being and energy levels as part of normality.
  • It is also common to have accepted abdominal bloating and flatulence as normal.
  • Any nutritional deficiency is highly likely to correct on a gluten-free diet without the need for supplements.
    • This includes nutrients that are easily measured (iron, folate, B12, calcium, vitamin D).
    • AND also other nutrients that may be important for well being (but are not easily measured).
• Osteoporosis is a definite risk with untreated coeliac disease although the fracture risk may not be that large.
  • Bone density does improve significantly on a gluten-free diet.>
• There is an increased risk of some cancers with untreated coeliac disease.
  • This includes two rare cancers - small bowel lymphoma and small bowel adenocarcinoma.
  • This also includes a slightly increased risk for other more common abdominal cancers (stomach / oesophagus / pancreas /bowel).
    • However, the overall cancer risk may not be different (or only marginally elevated).
    • For example some studies show that risk of breast cancer is reduced in coeliac disease (so there are "swings and roundabouts").
  • The risk is most apparent with more severe disease(ie. significant gastrointestinal symptoms) and with later age of diagnosis (more than 50 years).
  • The important fact is that the risk is virtually eliminated with a gluten-free diet.
• There is an increased risk of auto-immune diseases (type 1 diabetes, thyroid disease, Sjogrens disease).
  • It is not known if a gluten-free diet protects against getting an auto-immune disease but in theory this is a likely effect if the disease is diagnosed as a young adult.
  • There is a skin disease associated with coeliac disease called dermatitis herpatiformis.
    • Itchy raised red spots on the back, buttock and thighs - sometimes small blisters.
    • This responds to a gluten-free diet.
    • May take several months or even years to completely respond.
    • A skin biopsy can be useful to accurately diagnose the problem.

Bread made from wheat flour needs to be excluded. Gluten-free breads are made from a combination of cornflour, rice flour, soy flour and many other options - e.g tapioca, millet


The gluten-free needs to exclude wheat, barley and rye

What is a gluten-free diet?
 

It is universally agreed that subjects with coeliac disease have an intolerance to proteins fractions in wheat, rye and barley.

It is clear that corn and rice are harmless.

1. There remains a debate about oats. There is much scientific data that is reassuring. A large study from Finland showed that pure oats 40-50g per day given for a year had no effect on a group of coeliac who had been established a gluten-free diet.
   
2. Oats can provide a good source of fibre. There is still some resistance amongst some dietitians and coeliac societies to accept oats. Part of the concern is limited data on the purity of the source of oats. There could be some contamination with wheat. Some longer term follow-up studies on coeliacs given oats over several years are still awaited.
   
3. Several other grains such as quinoa, millet, sorghum, buckwheat, amaranth are now more widely available and form the basis for many gluten-free flours. There is not complete data on all these sources but plant taxonomy would suggest that they are safe.

Natural food sources are likely to be OK (apart from cereals). i.e meat, fish, vegetables, fruit.

Including fibre in a gluten-free diet can be difficult.

1. Constipation is a reported problem with a gluten-free diet. Cornflakes and rice bubbles are good standards for breakfast.
   
2. Higher fibre alternatives include rolled rice flakes, brown rice flakes, rice bran, puffed brown rice, puffed buckwheat, puffed millet. A museli can be made from a combination of these ingredients (with added dried fruit and nuts).
3. Rice porridge can be made from rolled rice flakes. For biscuits, try buckwheat crispbreads. For evening meals, brown rice or wild rice gives a different taste.
   
4. Buckwheat can be used for pancakes or in cake and muffin recipes.

Risk of osteoporosis

1. Osteoporosis does improve significantly with a gluten-free diet.
2. Other sensible measures will be a diet high in calcium perhaps with some calcium tablets.
3.  Vitamin D levels need to be checked in case there is a problem with absorption of this vitamin and vitamin D supplements may be required
4. Bone mineral density (measured by bone scans) continued to improve for up to 3 years after starting a gluten-free diet.

Is there a safe level of gluten exposure?

• The amount of gluten that can be safely taken in coeliac disease is not known.
• Many people with coeliac disease have ingested small amounts of gluten over the years with no apparent problems.
• The reaction of a patient on a strict gluten-free diet to inadvertent small amounts of gluten is highly variable. Most people do not develop immediate symptoms.
• It is important to realize that there is some debate and variation in advice (varying from country to country).

The labelling of foods has changed.

•  Previously food containing < 0.02% gluten was labelled as gluten-free.
• Now to gain this label there has to be “zero gluten”. This change may be an advance for patients who develop gastro-intestinal symptoms with inadvertent exposure to very small amounts of gluten.
• However this does impose more dietary limitations on the increasing numbers of patients with no gastrointestinal symptoms prior to starting the gluten-free diet.
• Reasonable advice for most people with coeliac disease is to say that low gluten foods are acceptable.

Absence of small bowel villi


The appearance of the duodenum at gastroscopy may be diagnostic (as here) - a nodular appearance - but usually biopsies are required


Normal small bowel villi

How does the condition present?

1. Abdominal bloating and/or abdominal discomfort.
2. Diarrhoea(with or without a history of aggravation by wheat/breads).
   
3. The finding of iron deficiency with or without anaemia (particularly in a younger person with no symptoms and no other obvious cause) is suggestive of coeliac disease.

Blood tests for coeliac disease (antibody tests)

Other possible indications for screening are

1. Screening of relatives is an effective means of picking up more people with coeliac disease. 1:10 first degree relatives will be positive. >1:35 second degree relatives. The proportion will be higher if there are suggestive symptoms.
2. Currently, up to 25% of people with coeliac disease are identified by this method. Less than 50% of people diagnosed with coeliac disease today have abdominal symptoms.
   
3. In a typical NZ general practice (with 2000 patients) there should be 20 people with coeliac disease (according to the Christchurch population survey).
4. Using the clinical criteria of diarrhoea and weight loss only 2-3 patients will be identified. Testing people who present with anaemia (or with a past history of unexplained anaemia) will identify another 5. Testing of 1st degree relatives will identify another 2-3.  Some will be hard to find!

Making the diagnosis.

1. The initial test will usually be a blood test - endomysial antibody or tissue transglutaminase antibody.
   
2. Some people are diagnosed initially by duodenal biopsy directly because of a high index of suspicion at the time of the procedure (gastroscopy).
3. The endomysial antibody was the first accurate antibody test to be developed. The endomysial antibody is absent with IgA deficiency (found in 2% of coeliacs). Most labaoratories will routinely check the IgA level.  The test may be falsely negative if low Ig A levels
   
4. The transglutaminase antibody (tTGA) is also an IgA test. This is a simple test that is automated and quantitative (i.e will give a number for the level of antibody). The two tests give highly similar but not identical results. Currently most laboratories are able to offer both tests. Probably this is preferable as up to 20% of people with coeliac disease will have only one test positive.

Follow-up testing

1. It is not adequate to use the response to a gluten-free diet as evidence of coeliac disease. patients with irritable bowel syndrome often improve with exclusion of bread from the diet. This may be related to a decrease in wind from the fermentation of wheat.
2. There is no need for another biopsy after gluten re-exposure if there was a good clinical response to a gluten-free diet.
3.  The transglutaminase antibody can be used to monitor progress. It is to some extent a surrogate marker of villous atrophy although villous atrophy may be present with a negative antibody test. The antibody levels should gradually fall into the normal range within 12-18 months.

Historical perspective

• Coeliac disease is a condition where there is an abnormal lining of the small bowel that improves after excluding wheat from the diet.
  
• The link with wheat was only recognised after the end of WWII when children who had been deprived of wheat during the war years started eating wheat again.
• In the past the diagnosis was only made when there was significant weight loss and multiple problems with absorption of nutrients (vitamins). The diagnosis was confirmed by a small bowel biopsy - this was a difficult and cumbersome test.
• The simple realisation that a duodenal biopsy - obtained at the time of a gastroscopy - was as accurate led to more frequent diagnosis of the condition.
• Blood tests - gliadin antibody tests - have been available for many years - but there were problems with false positive and false negative tests.
  
• In the last 10 years more accurate antibody tests have become available.

There is a strong genetic component to the disease.

• • About 1:10 1st degree relatives will have coeliac disease (positive antibodies and abnormal duodenal biopsies).
  • One major gene has been identified. There may be several others.
  • There is now a genetic test.
  • The gene is called HLA DQ2 (90%) or DQ8 (10%).
    • If you have the gene, coeliac disease is more likely.
    • If you do not have the gene, then coeliac disease is excluded.
    • There is limited availability of this test in NZ; the test is used more frequently in some countries.
• The risk of having coeliac disease varies around the world.
  • It is common in people with Northern European ancestry.
  • Populations without HLA DQ2 (e.g Japanese and Chinese) do not develop coeliac disease.
  • The disease may be as common in some Indian populations.

• How does the damage to the small bowel occur?

  • Immune cells, called antigen-presenting cells (APC) combine with HLA receptors (on the surface of cells), then become activated by the gliadin protein that is found in wheat.
  • The resulting tissue damage leads to the release of the enzyme - tissue transglutaminase.
  • This enzyme alters an important section of the gliadin protein.
  • This changes a critical portion in the gliadin molecule that then activates lymphocytes.
  • Tissue damage in the duodenum and further down the small bowel in the jejunum is caused by activated lymphocytes (immune cells).
  • There are antibodies against the enzyme transglutaminase in the blood. However, these antibodies are not doing the damage. They are a by-product of the inflammation and damage caused by activated immune cells.
  • The bowel tries very hard to replace the damaged villi (frond-like projections in the liming of the bowel) but cannot keep up with the tissue damage from the activated immune cells.