Celtnet Coeliac Disease Infromation Page

Coeliac disease (also known as celiac disease, cœliac disease, c(o)eliac sprue, non-tropical sprue, endemic sprue, gluten enteropathy or gluten-sensitive enteropathy, and gluten intolerance) is an autoimmune disorder caused by a reaction to gliadin, a gluten protein found in wheat (along with similar proteins found in the crops of the tribe Triticeae (which includes other common grains such as barley and rye). Upon exposure to glandins (in actual fact three peptides found in prolamins) a natural enzyme in the gut, tissue transglutaminase modifies the protein, and the immune system cross-reacts with the small-bowel tissue, causing an inflammatory reaction. That leads to a truncating of the villi lining the small intestine (called villous atrophy). In turn, this interferes with the absorption of nutrients, because the intestinal villi are responsible for absorption. The only known cure, to date, is for the person affected to maintain a gluten-free diet for the remainder of their lives.

To show the effects of the disease, the image show here gives a cross section of normal villi from the small intestine (A, left) compared with a cross section of the villi from a sufferer of coeliac disease (B, righ). You can see that the villi on the right are truncated and squared off and that the crypts (the pits where food is absorbed) are blocked off and inacessible in the right-hand image.

Severe coeliac disease is typically exemplified by pale, loose and greasy stool (steatorrhoea), and weight loss or failure to gain weight (in young children). Those with milder coeliac disease may have symptoms that are much more subtle and occur in other organs rather than the bowel itself. It should be noted, however, that it's also to have coeliac disease without any symptoms whatsoever. Indeed, many adults with subtle symptoms of coeliac disease may only show mild fatigue or anaemia.

the diarrhoea that is characteristic of coeliac disease tends to be pale, voluminous and malodorous. This is often accompanied by abdominal pain, and cramping, bloatedness with abdominal distension (which is typically the result of fermentation in the bowel producing gas) and mouth ulcers. As more damage occurs in the small intestine, a degree of lactose intolerance may also develop. Coeliac disease also leads to an increased risk of adenocarcinoma (small intestine cancer) and lymphoma of the small bowel (enteropathy-associated T-cell lymphoma or EATL), though this risk reduces to the same as that of the general population with a gluten-free diet. If left untreated, coeliac disease may also result in ulcerative jejunitis (ulcer formation of the small bowel) and scarring of the small intestine.

Quite frequently, the symptoms of coeliac disease are initially ascribed to irritable bowel syndrome (IBS), only later to be recognised as coeliac disease; a small proportion of patients with symptoms of IBS have underlying coeliac disease, and screening for coeliac disease is recommended for those with IBS symptoms.

It should be noted that the changes to the small intestine associated with coeliac disease make it less able to absorb nutrients, minerals and the fat-soluble vitamins A, D, E, and K. The inability to absorb carbohydrates and fats may also cause weight loss, fatigue and loss of energy. Anaemia may develop in several ways: iron malabsorption may cause iron deficiency anaemia, and folic acid and vitamin B12 malabsorption may give rise to megaloblastic anaemia. Coeliac disease can also be associated with bacterial overgrowth of the small intestine, which can worsen malabsorption or cause malabsorption even if the sufferer is on a gluten-free diet.

Coeliac disease is both polyfactorial, in that more than one genetic factor can cause the disease and that more than one factor is necessary for the disease to manifest in a patient and multi-symptomatic in that patients present with a range of symptoms. At a genetic level, almost all coeliac disease patients have a variant in their HLA-DQ2 allele (see below). Though posessing this variant does not necessarily mean that you have coeliac disease (indeed about 20–30% of people without coeliac disease have inherited an HLA-DQ2 allele). This strongly suggests that additional factors must be present for coeliac disease to be present. It should be noted that about 5% of those people who do develop coeliac disease do not have the DQ2 gene.

• 2.3% of coeliac disease sufferers present with IgA deficiency, and run an increased risk of infections and autoimmune diseases.
• Dermatitis herpetiformis, which is an itchy cutaneous condition that has been linked to a transglutaminase enzyme in the skin, features small-bowel changes identical to those in coeliac disease, and may respond to gluten withdrawal even if there are no gastrointestinal symptoms.
• Growth failure and pubertal delay. In childred with coeliac diseas, the changes to the small intestine leading to malabsorption of food can lead to these conditions.
• Recurrent miscarriage and infertility.
• Hyposplenism: in about a third of cases the patient may have a small or underactive spleen, which may pre-dispose to infection.
• Other conditions: Coeliac disease is also associated with autoimmune disorders: diabetes mellitus type 1, autoimmune thyroiditis, primary biliary cirrhosis, and microscopic colitis.

Contrary to common belief, it is not just wheat that contains the glutens to which sufferers of coeliac disease react. Many wheat subspecies, such as spelt, semolina and durum wheat, and related species such as barley, rye, triticale and Kamut also induce symptoms of coeliac disease. It should be noted that a small percentage of coeliac sufferers also react to oats. Though it is likely that oats only produce a reaction due to cross contamination with other grains in the fields or in the distribution channels.

Other cereals such as maize (corn), millet, sorghum, teff, rice, and wild rice are safe for patients to consume, as well as non cereals such as amaranth, quinoa or buckwheat. Other carbohydrate staples, potatoes, banans and plantains, sweet potatoes, cassava and yams do not contain gluten and do not trigger symptoms.

As mentioned earlier, coeliac disease is an autoimmune disorder. In fact, it is associated with a cell surface antigen labelled HLA-DQ. This is a protein generated by a gene known as CELIAC1 which is present on chromosome 6 of the human genome.

This gene is part of the MHC class II antigen-presenting receptor (also called the human leukocyte antigen) system and distinguishes cells between self and non-self for the purposes of the immune system. Thus the gene is critical in helping to distinguish between cells that are part of the body and those which are not.

Seven variants (mutations) of HLA-DQ have been characterised and these are known as DQ2 and DQ4 to 9, inclusive. Over 95% of coeliac patients have the variants DQ2 or DQ8 and both these variants are heritable (ie inherited in families).

Studies have shown that the receptors formed by these variant genes bind to gliadin peptides more tightly than other forms of the antigen-presenting receptor. Therefore, these forms of the receptor are more likely to activate T lymphocytes which are responsible for initiating the autoimmune process.

Most ceoliac disease patients have a particular combination of adjacent genes known as the DQ2.5 haplotype. This is because the receptor in this haplotype is formed from the β2 (also known as DQ2) and α5 subunits (hence DQ2.5). The other common haplotype in coeliac disease being DQ8, where the receptor is formed from the β3 and α3 subunits.

DQ2.5 is most prevalent in Northern and Western Europe (particularly in the Basque Country, Ireland and West Wales), whereas DQ* has a much wider global distribution, though it is particularly common in South and Central America.

In those susceptible to coeliac disease, the natural process of the degradation of gluten molecules by the enzyme tissue transglutaminase leads to tight binding with the cell surface receptors that then leads an immune response. This immune response becomes mis-directed towards both the cells of the small intestine and towards the tissue transglutaminase enzyme. This inflammatory process, mediated by T cells, leads to disruption of the structure and function of the small bowel's mucosal lining and causes malabsorption as it impairs the body's ability to absorb nutrients, minerals and fat-soluble vitamins A, D, E and K from food. Lactose intolerance may be present due to the decreased bowel surface and reduced production of lactase but typically resolves once the condition is treated.

However, the possession of of susceptibility genes is not the only story as there are other factors involved. Current theories about these destabilizing factors include infection by rotaviruses and human intestinal adenoviruses. It also appears that the timing of the exposure of gluten in early childhood in a very important risk modifier. People exposed to wheat, barley, or rye before the gut barrier has fully developed (within the first three months after birth) had five times the risk of developing coeliac disease relative to those exposed at four to six months after birth. Those exposed even later than six months after birth were found to have only a slightly increased risk relative to those exposed at four to six months after birth.

If you believe that you may have coeliac disease, then you should consult your doctor. However, do not eliminate gluten from your diet, as this will reduce the effectiveness of any diagnostic tests. Indeed, if you have already removed gluten from the diet it may be necessary to re-challenge the body with gluten-containing food in one meal a day over 2–6 weeks before any clinical investigations can begin.

The first diagnostic test is invariably a blood test. The first test is usually to measure the presence of anti-tissue transglutaminase antibodies as this is an easy test to perform. If the result is unequivocal, then a diagnosis can be made. However, if anti-tissue transglutaminase are inconclusive, then a further test is made to determine the levels of antibodies to endomysium in the blood. Historically, two other antibodies have also been measured: anti-reticulin (ARA), anti-gliadin (AGA). Serology may be unreliable in young children, with anti-gliadin performing somewhat better than other tests in children under five.

Guidelines recommend that a total serum IgA level is checked in parallel, as coeliac patients with IgA deficiency may be unable to produce the antibodies on which these tests depend ("false negative"). In those patients, IgG antibodies against transglutaminase (IgG-tTG) may be diagnostic. As a result, professional guidelines recommend that a positive blood test is still followed by an endoscopy/gastroscopy and biopsy. As a result, tissue biopsy is still considered the gold standard in the diagnosis of coeliac disease.

This is still considered the 'gold standard' method for diagnosing coeliac disease. Typically, an upper endoscopy with biopsy of the duodenum (beyond the duodenal bulb) or jejunum is performed. It is important for the physician to obtain multiple samples (four to eight) from the duodenum as not all areas may be equally affected. Most patients with coeliac disease have a small bowel that appears normal on endoscopy; however, five concurrent endoscopic findings have been associated with a high specificity for coeliac disease: scalloping of the small bowel folds (pictured), paucity in the folds, a mosaic pattern to the mucosa (described as a "cracked-mud" appearance), prominence of the submucosa blood vessels, and a nodular pattern to the mucosa.

As coeliac disease is multi-factoral, further investigations may also be performed to help identify complications. Typically these are iron deficiency (by full blood count and iron studies), folic acid and vitamin B12 deficiency and hypocalcaemia (low calcium levels, often due to decreased vitamin D levels). Thyroid function tests may be requested during blood tests to identify hypothyroidism, which is more common in people with coeliac disease.

The only truly effective treatment for coeliac disease is to change the diet so that it is gluten-free. Indeed, no medication exists that will prevent damage or prevent the body from attacking the gut when gluten is present. This then means that the only possible treatment is to completely remove gluten from the diet.

Indeed, strict adherence to a gluten-free diet allows the intestines to heal, leading, in the vast majority of cases, to a resolution or reversal of all symptoms. If the dietary regimen is initiated soon enough then this can also eliminate the heightened risk of osteoporosis and intestinal cancer and in some cases sterility.

For this to be effective, the patient needs to be aware precisely which foods contain gluten so that they can be avoided or replaced by gluten-free equivalents. The problem is that wheat products are an integral part of the Western diet, so maintaining a gluten-free regimen can be cumbersome. However, failure to maintain the diet will, almost certainly, lead to a relapse.

It should also be noted that the term gluten free actually means an effectively harmless level of gluten rather than the complete absence of gluten. Though it should also be noted that the exact level at which gluten is harmless remains a point of controversy. Current best knowledge is that consumption of less than 10 mg of gluten per day is unlikely to cause histological abnormalities (though few truly reliable studies have been performed).

For those who want gluten-free recipes or substitutes for wheat flour, then this site has a growing number of gluten-free recipes.

It used to be believed that coeliac disease was extremely rare, with incidences estimated as 1 in 5000. However, these days it is believed that the incidence is higher, with numbers ranging from 1 in 1750 (as defined by the incidence of clinical cases) to 1 in 105 (as defined by the presence of anti-tissue transglutaminase antibodies in the blood of blood donors. The actual figure may be around 1 in 500 which indicates that the vast majority of coeliac disease sufferers remain undiagnosed.

Human beings have not evolved to consume grains. Our primordial diet consisted of fruit, nuts, berries and tubers supplemented by meat.

It was only some 11 000 years ago (about 9500 BCE) that Neolithic peoples began to cultivate grains in the region of the Fertile Crescent in Western Asia. Before this time, with the absence of grains in the human diet, coeliac disease, almost certainly, did not exist.

It was Aretaeus of Cappadocia (circa 200 CE) who first described the disease. In his writings he records a malabsorptive syndrome with chronic diarrhoea which he calls 'cœliac affection' (coeliac from Greek κοιλιακός koiliakos, "abdominal").

However, it was not until until 1856 that the disorder gained the attention of Western medicine, as it was in this year that Francis Addams presented a translation of Aretaeus's work at the Sydenham Society. The patient described in Aretaeus' work had stomach pain and was atrophied, pale, feeble and incapable of work. The diarrhoea manifested as loose stools that were white, malodorous and flatulent, and the disease was intractable and liable to periodic return.He regarded this as an affliction of the old and more commonly affecting women, explicitly excluding children.

In 1887, Samuel Gee gave the first modern-day description of the condition in children in a lecture at Hospital for Sick Children, Great Ormond Street, London. Gee adopted the same naming convention as Aretaeus (coeliac disease) but noted 'If the patient can be cured at all, it must be by means of diet'.

Through successive decades, a link with carbohydrates was suspected. However, the link with wheat was not made until the 1940s by the Dutch paediatrician Dr. Willem Karel Dicke when the association was made with the absence of wheat from the diet during the Dutch famine of 1944.

The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England. Villous atrophy was described by British physician John W. Paulley in 1954 on samples taken at surgery.