Coeliac disease damages the upper small intestine and prevents proper absorption of nutrients such as iron, calcium, vitamins such as folic acid, proteins, fats and carbohydrates. Coeliac disease is associated with anaemia, osteoporosis, diarrhoea and loss of weight and often there are vague symptoms such as tiredness all the time, fractures due to osteoporosis and even infertility. It occurs in about 1 in 160 of individuals with about one-third being diagnosed during childhood and two-thirds diagnosed as adults. Often it takes some time to associate symptoms with the possible diagnosis of coeliac disease especially if symptoms are not typical. Treatment consists of total and lifelong exclusion of wheat, rye and barley from the diet. Coeliac disease runs in families, as about 1 in 10 family members of a known coeliac sufferer will have coeliac disease.
To diagnose Coeliac disease doctors will use an endoscopy from the lining of the upper small intestine to determine the level of intestinal damage.
It is very important that a gluten-free diet is not started before endoscopy as this makes the diagnosis more difficult if not impossible. Because of the absolute need for a strict and lifelong diet and the genetic implications for the family, it is important that coeliac disease be properly diagnosed. There is only one opportunity to diagnose coeliac disease properly and that is before starting a gluten-free diet.
Patients are selected for endoscopy by the pattern and severity of their symptoms, by a positive coeliac blood test, and by a family history of coeliac disease.
Four out of five rule for diagnosis-not just a blood test!
A recent American study however has advocated the 4 out of 5 rule which says that coeliac disease may be diagnosed when four of the following five criteria are present:
1) Typical symptoms (eg diarrhoea and loss of weight)
2) Strongly positive coeliac blood test
3) Presence of HLA DQ2 gene which 90% of coeliac subjects will have but only 20 to 30% of the healthy population
4) Abnormal intestinal biopsy
5) Response to the gluten-free diet
Another recent article has suggested that coeliac disease is being overdiagnosed based on just the blood test alone, although we believe that many people with coeliac disease remain undiagnosed.
The detailed cause of coeliac disease is unknown but it involves an abnormal immune response to gluten (the protein in wheat). Normally the immune system should not react to food proteins, otherwise we all would get diarrhoea after we eat, however sufferers of coeliac disease often have these issues. Coeliac disease is predisposed by a combination of multiple genetic factors and environmental factors.
There seems to be a critical time during infancy at about 2 to 6 months of age when the immune system of the small intestine becomes tolerant to gluten and to other foods as well as to the healthy bacteria in their intestines. This process of ‘oral tolerance’ might be interrupted by repeated viral infections. Recent evidence suggests that it is better for infants to have small amounts of wheat cereal before 6 months of age while still being breast-fed. Breast feeding is known to reduce the risk of coeliac disease. It is still unclear in the case of adults diagnosed with coeliac disease if they had coeliac disease from childhood but just did not have obvious symptoms, or whether they lose oral tolerance later in life. It has been observed that teenagers with coeliac disease diagnosed in earlier in childhood may not develop their previous symptoms if they do have gluten suggesting their intestine can compensate for some time, although it remains damaged. This compensation might explain the delay in presentation of coeliac disease in adults but needs to be confirmed through research.
The mainstay of treatment consists is a strict gluten-free diet for life. At the start, some people may need specific mineral or vitamin deficiencies treated such as iron or folate deficiency. One in 25 coeliac sufferers develop the complication of ‘refractory sprue’ in which the gluten-free diet no longer is sufficient to improve the damaged intestine and the overactive intestinal immune system needs to be suppressed by drug treatment with steroids such as prednisolone or methotrexate (an immunosuppressive drug). This scenario often suggests the development of cancer of the immune cells called ‘enteropathy-T cell lymphoma’. This is often extremely difficult to diagnose and involves testing the biopsies in a special test called flow cytometry which counts the number of immune cells with abnormal changes. After 5 years of a gluten-free diet, the risk of enteropathy-associated T cell lymphoma falls to that of the normal healthy non-coeliac population. There is no effective long-term treatment for this problem and death occurs after a few months to a few years. Generally, this occurs in coeliac patients over 40 years of age and unfortunately about half the patients with enteropathy-associated T cell lymphoma do not know they had coeliac disease.
1) The Department of Gastroenterology & Hepatology has been studying what happens to the intestinal immune system during weaning for many years. Although the immune system is commonly thought to be ‘immature’ at this age, studies have shown that the immune system of the intestine is strongly activated from 2 to 4 months of age in healthy humans, which is when an infant starts to ingest small amounts of food. It has been shown in both animals and humans that this enormous peak of immune activity drives development and maturation of the small intestine. These studies have shown that ‘physiological inflammation’ in the intestine decreases after 6 months of age even in site of increasing diversity of food intake. This strongly suggests that oral tolerance is a lifelong active process that normally suppresses immune reactivity to foods after this age.
2) Another study has investigated how well the intestine returns to normal after intervals of a gluten-free diet. We are presently extending a study of how well the intestine responds after 8 years of the gluten-free diet. We found that a biopsy only returns to about 50% of normal area after 6 to 12 months and remains so up to 4 years of a gluten-free diet
3) We have recently found that coeliac disease is only present in certain countries in South East Asia such as Iran, Iraq, Northern India. Pakistan, possibly Western China along the silk route, New Zealand and Australia but not in Japan. These represent either ancient migration patterns out of Mesopotamia over the last 10,000 years or colonisation by European countries from 1640 to 1890s. The common factor is the HLA DQ2 gene that was present in hunter gather humans who settled and harvested wild grasses that developed as hybrids into today’s cereals.
4) We have found that 25% of adults with newly diagnosed coeliac disease in Adelaide have osteoporosis. Only a few cases were due to vitamin D deficiency and most are due to persistent intestinal damage in coeliac disease
5) We have recently demonstrated using the PillCAM (a minute TV camera in a pill that is swallowed) could be used to reliably diagnose coeliac disease by finding the extent of intestinal damage down the small intestine. ‘Small’ in ‘small intestine’ refers to the smaller diameter as compared to the large intestine and not to the length which is longer at 4 to 6 metres in the small intestine compared to 0.9 to 1.5 metres length of the large intestine. The severity of intestinal damage was measured by the length of small intestine involved.
Present and Future Research
1) We would like to record how well coeliac subjects comply to a gluten-free diet by comparing assessment by an expert dietitian, by using self assessment of a coeliac subject, by using a validated dietary questionnaire and by using a food dietary program on an iPad.
2) We are presently assessing how many cytokine chemicals are produced by immune cells that are present in intestinal biopsies. Some of these are known from other diseases to be pro-inflammatory and cause damage and while others are immunosuppressive and protect the intestine. In the past, only a few cytokines have been examined concurrently. There are 35 cytokines described at present. The technique use a multi array real time PCR card which costs $500. Each one can analyse 48 genes of eight individuals
3) We are assessing how certain of these cytokines change the permeability of the small intestine in coeliac disease.
Coeliac Society of South Australia: http://www.coeliacsociety.com.au/southaustralia/homepage.html
Coeliac Society of Australia: www.coeliacsociety.com.au/
Note that a gluten-free ingredient list complied by the Coeliac Society is also available for the iPhone at the App Store.