Introduction

Coeliac (celiac) disease is a life-long inflammatory disease of the upper small intestine caused by intolerance to the gluten affecting many genetically susceptible individuals worldwide. Gluten is a protein found in wheat, and other similar proteins found in rye, barley and oats. These proteins damage the small finger-like projections (villi) that line the small intestine (see Figure 1), resembling a pile in a carpet, and play a significant role in digestion. When damaged and inflamed, the villi are unable to absorb water and nutrients such as vitamins, folic acid, iron and calcium. This causes the coeliac to be susceptible to a variety of other conditions related to malabsorption, including lactose intolerance. Clinical and mucosal recovery after institution of a gluten free diet is objective evidence that the enteropathy is gluten induced.

Causes & Mechanism

Causes

The causes are presently presumed to be:

• Genetic susceptibility to the illness.
• A trigger, which could be one of:
  - An environmental agent, probably a virus or other infection
  - Stress
  - Pregnancy
• Possible exposure to gluten as a young baby before the gut barrier has developed fully. This association is currently under investigation.

The timing of the first exposure to gluten is also thought to be important. Babies who were introduced to wheat, barley, or rye at any time in the first three months had five times the risk of developing coeliac over those exposed at 4 to 6 months. Those exposed later had a slightly increased risk relative to those exposed at 4-6 months.

Mechanism

Gluten is a mixture of two proteins, gliadin and glutenin which when mixed with water it becomes sticky and so forms the familiar texture of dough made from wheat and rye flour.

Figure 1: Healthy villi of the small intestine seen under the microscope.

Figure 2: Damaged villi of the small intestine.

Figure 3: Villi completely destroyed by the immune system. All pictures from netdoctor.com, courtesy of Prof PJ Ciclitira.

As gluten is ingested and comes into contact with the villi covering the lining of the small intestine the immune system mistakenly attacks the villi by antibody production as if it was a 'foreign' organism. Antibodies are important defence proteins that have the ability to attach themselves to unfamiliar antigens, the enemy, such as bacteria or cancerous cells and trigger other reactions in order to destroy the offending organism or cell. In this case and in all other autoimmune diseases, a 'friendly fire' occurs the immune system fails to recognise the villi. Figure 1 shows a microscopic view of healthy villi attached to the lining of the small intestine. The antibodies are so potent that with immediate effect damage occurs (see Figure 2) and unless gluten is removed from the diet they are eventually destroyed (see Figure 3).

Apart from the inability to absorb nutrients, damaged lining to the small intestine has other negative results. It is unable to produce sufficient digestive enzymes essential to break down foods for complete digestion and absorption, such as lactose and carbohydrates. Large components of foods remain in the digestive tracts unabsorbed which are in turn fermented by bacteria living naturally in our digestive tract and ideal conditions causing cramps, gas, bloating, flatulence and diarrhoea. See related Food Intolerance pages for more information and how to supplement your diet with enzymes to avoid these symptoms. More symptoms explained below.

Symptoms & Signs

 Coeliac disease has many and varied symptoms, and adult symptoms are different from those of children. A range of symptoms and signs may be associated with untreated coeliac disease. Diarrhoea is one of the most common symptoms to affect people of all ages with coeliac disease. Children may not gain weight or grow properly, while adults may find they lose weight. Malabsorption may also leave people tired and weak, because of anaemia caused by iron or folate deficiency.

Babies:

• chronic diarrhoea
• abdominal distension
• poor feeding
• poor weight gain
• muscle wasting.

Children:

• chronic diarrhoea or constipation
• vomiting
• poor weight gain or growth
• poor feeding
• irritability
• muscle wasting.

Adults:

• chronic diarrhea
• weight loss
• anaemia
• weakness
• fatigue

Other notes:

Rather than suffering from bowel problems, half of coeliac sufferers approach their doctor because of extreme tiredness and psychological problems such as depression, bone pain and sometimes even fractures (due to thinning of the bones), ulcers in the mouth or a blistering, itchy skin rash mostly on the elbows and knees (called dermatitis herpetiformis).

Coeliac disease may be the cause for some women having difficulty getting pregnant. Recurrent miscarriage (spontaneous loss of a pregnancy) may also be attributed to coeliac disease.

Women with coeliac disease may become diagnosed during pregnancy because their bowel cannot absorb enough iron and vitamins to keep up with the demand of being pregnant, making them severely anaemic. Babies who are small for their age in the womb (intrauterine growth retardation) are more frequently born to mothers with coeliac disease.

Prevalence

Coeliac disease is reported to be most common in Ireland at a rate of 1 in 100 people. Reviews about the rate in UK vary from 1 in 100 persons to 1 in 300. With a diagnosis of 1 in 250, Italy also has a high rate. Reports about the incidence in US vary as well, ranging from 1 per 133 to 1 per 500. However, it is more likely to be similar to the rage of the UK. Some researchers have suggested that up to 10-15% of persons may have some form of gluten intolerance but most of them either have no digestive-tract symptoms at all or they are so minor that go unnoticed. A large number of these can be Non Coeliac Gluten Intolerant.

Another problem is that many can go misdiagnosed because persons going for coeliac blood tests present themselves on a gluten free diet, hence antibodies are not present in their blood and tests prove false negative.

It's also known that the condition runs in families and was once thought to affect only children. However, many adults are now being diagnosed with the disease. It's particularly common between the ages of 30 and 45; men and women seem to be affected equally.

Coeliac disease is sometimes associated with other conditions including type 1 (insulin-dependent) diabetes, autoimmune thyroid disease and ulcerative colitis. Some reports claim that people from the west of Ireland are more often affected, as are those from the Punjab region of India, Pakistan, the Middle East and North Africa.

Prevention

Breastfeeding and delaying the introduction of foods containing gluten until after four months is suggested to prevent children from developing coeliac disease. This would avoid exposure to gluten as a young baby before the gut barrier has developed fully. This association is currently under investigation and a definitive way to stop the disease from developing is not known yet.

Treatment

Coeliac disease comes in a variation of strengths, where some people are more severely affected than others. Presently the only treatment is a life-long gluten-free diet. In the vast majority of patients, a strict gluten-free diet will relieve the symptoms. A tiny minority of patients suffer from refractory sprue, which means they do not improve on a gluten-free diet. This may be because the disease has been present for so long that the intestines are no longer able to heal. In other patients, the intestinal damage of coeliac disease may have been aggravated by other problems, such as intolerance to the dietary proteins found in eggs, milk, or soy.

Clinical trials are underway for a medication that can be taken by Coeliacs before eating gluten that will protect against an auto-immune reaction, and hence prevent intestinal damage (read article) Phase II trials are expected to begin as early as the summer of 2006. Recently in the U.S. researchers developed an enzyme that is able to break down the protein associated with gluten intolerance and inflammation of the upper digestive tract, causing damage to the villi.

On a better note, for several years Glutenzyme has been available in the UK. It is an enzyme protease produced from natural resources (suitable for vegans) that is able to break down the gluten protein, hence limiting or eliminating the damage that gluten causes to many coeliac sufferers. Persons with severe Coeliac disease are recommended to take Glutenzyme especially when eating out to avoid any damage caused by hidden gluten. Persons who do not suffer from severe symptoms and are able to tolerate some gluten may find that Glutenzyme may help them to move onto a normal diet. See products page for Coeliac disease. Find out more about Glutenzyme.

Tests & Diagnoses

Although the doctor may request a coeliac screen, which involves blood serum investigations, these tests are not definitely diagnostic of celiac disease. Blood serum antibody tests (endomysial, reticulin (IgA), and gliadin (IgG and IgA) are used to measure levels of antibodies to gluten. If the antibodies in the blood are higher than normal then a biopsy of the small intestine is recommended.

A biopsy of the lining of the small intestine checks for damage to the villi. If the villi appear damaged then a gluten-free diet is introduced. Another biopsy is done after 6 months or more of dieting.

Relief of symptoms or reversion of an abnormal intestinal biopsy is the most convincing evidence that an individual has celiac disease or gluten sensitivity.

A thorough workup includes four tests:

• Anti-tissue transglutaminase Antibody (tTG), IgA. This test is sometimes used alone. If this test is positive it is highly likely that the patient has coeliac disease. tTG test is not reliable in children before the age of 2.
• Anti-gliadin antibodies (AGA), IgG and IgA. These tests are often useful when testing young symptomatic children, but they are found in fewer Coeliacs than Anti-tTG, and their presence does not automatically indicate coeliac disease because they are found in some other disorders. Some people have an IgA deficiency. They are unable to mount an IgA response to any antigen and will have false negative tests for the IgA type coeliac tests. Yet IgA deficiency is associated with coeliac disease and a tenfold risk of coeliac disease has been documented in selective IgA deficiency.
• Anti-endomysial antibodies (EMA), IgA. This test is being replaced by the anti-tTG test because both tests measure the autoantibodies that cause the tissue damage associated with coeliac disease. Many physicians still order this test. This test as tTG test is also not reliable in children before the age of 2.
• An older test, the anti-reticulin antibodies (ARA), IgA. IgA Anti-ARA is not ordered as frequently as it once was, because it is less sensitive and less specific than the other tests. It is found in about 60% of people with coeliac disease and 25% of those with dermatitis herpetiformis.

Other routine tests are usually requested to assist in the diagnosis, including full blood count to check for anaemia, electrolytes, renal function and liver enzymes.

Testing Negative but still feeling sensitive to gluten.

Many people contact me after they are sure to suffer from gluten intolerance but tests conclude negative. In a particular email, a 28 year old woman writes how much she suffered from coeliac like symptoms, mainly bloating and cramps followed by diarrhoea after having food containing gluten. Her doctor requested a coeliac screen and when she went back for her results, the doctor told her to go home and make herself a nice cup of tea and a sandwich because the results were negative.

She was happy at the news, and indeed she went home making herself a cup of tea and a nice sandwich which she has not had for many weeks. However, moments later the dreaded symptoms came back and was ill for two days missing her work!

So what did go wrong?

For three years, between 2001 and 2004 I worked in the immunology department of one of London's University Hospitals. Weekly we performed coeliac screening on around 80 patients referred to us by their doctor following a protocol to narrow down the patients with possible gluten intolerance.

Surprisingly it was only 1-2% of them tested positive, this despite these patients experience coeliac like symptoms! So how could this be?

A false negative result is possible to occur after the patient testing for the screen had gone for several days on a gluten free diet. This causes the immune system to slow its antibodies production down to normal levels. Since the tests rely on antibody detection the end result will be that or 'normal levels', hence classified as negative.

Avoiding a false negative result.

To obtain the real status of the condition it is necessary to consume food that contains gluten for a week before blood is being taken for the test. This way, if truly having Coeliac Disease there will be enough time for the immune system to produce antibodies. The presence of these antibodies determines the diagnosis of the disease. Abstaining from food containing gluten will stop the immune system producing the antibodies needed for detection in the test, and people intolerant to gluten will end up as being told to be negative.

Unfortunately this may be a painful solution, but it is recommended for accurate diagnosis. One must take care in the quantities of gluten taken not to cause excessive symptoms but this varies from person to person. More importantly is not to subject children to aggressive consumption of foods with gluten and it is vital to to speak to the doctor about it first. If the test is negative, then it would be understandable to declare being free from Coeliac Disease.

The same thing applies to those who are heading for a biopsy to confirm Coeliac disease. If gluten had been out of the system for even a short time, the villi of the small intestines regenerate readily and hence, the biopsy will only reveal healthy villi. Once again a false negative result.

Non Coeliac Gluten Intolerance

Many times when a person is screened for coeliac, despite taking all precautions mentioned above, tests still indicate that the disease is not present. This despite that these persons suffer from symptoms upon digesting food containing gluten. This is very interesting or perhaps confusing to many. But put simply , this person may be Non Coeliac Gluten Intolerant (NCGI). It is estimated that around 15% of the world population is NCGI as opposed to less than 1% of Coeliacs. Gluten consists of many long elastic chains of proteins (gives it the characteristics of a dough) lined along each other. Not all of them cause Coeliac disease, but some can cause irritation to the small intestine, enough to hinder the cells of the small intestine to produce digestive enzymes to break down foods. Symptoms are similar to food intolerance and more details can be found in the food intolerance pages. To confirm if you are NCGI do an elimination test. Avoid all gluten food for at least two weeks and then introduce it. If symptoms return, and previous tests were negative or inconclusive then you know that you are NCGI. NCGI persons suffer from similar symptoms of food intolerance and Glutenzyme that is capable to breaking down gluten proteins can be the solution for a normal diet reducing or eliminating symptoms associated with NCGI.

Other Names For Coeliac Disease

Listed below are the names associated with Celiac Disease. All the names refer to the inability to tolerate gluten.

• Coeliac or Celiac Sprue
• Coeliacs or Celiacs
• Coeliac or Celiac Disease
• Gee-Herter's syndrome
• Gluten Intolerance
• Gluten Sensitive Enteropathy
• Gluten Sensitivity
• Idiopathic Steatorrhea
• Intestinal Infantilism
• Malabsorption Syndrome
• Nontropical Sprue
• The Coeliac Syndrome

Related Disorders

Celiac Disease is linked to many immune related disorders. The best established connection is with Type I diabetes (mellitus).

Some other illnesses related to Celiac Disease are chronic active hepatitis, chronic fatigue syndrome, and inflammatory bowel disease. Some researchers believe that gluten intolerance can impair mental functioning in some individuals.

Since gluten can damage the villi, it is common for Coeliacs to have problems with food intolerance, especially lactose intolerance.

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