it is a T-cell mediated disease appearing in genetically susceptible individuals persuades by the ingestion of several proteins found in wheat, barley and rye. Its common symptoms are diarrhoea, abdominal pain, distension and weight loss.

Journal of  Autoimmune Disorders, Innate Immunity & Immunological Disorders, Immunobiology, Immunological Techniques in Infectious Diseases, Immunooncology

Coeliac disease or celiac disease is a long-term autoimmune disorder that primarily affects the small intestine. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite and among children failure to grow normally. This often begins between six months and two years of age. Non-classic symptoms are more common, especially in people older than two years. There may be mild or absent gastrointestinal symptoms, a wide number of symptoms involving any part of the body or no obvious symptoms Coeliac disease was first described in childhood;  however, it may develop at any age. It is associated with other autoimmune diseases, such as diabetes mellitus type 1 and thyroiditis, among others.

Coeliac disease is caused by a reaction to gluten, a group of various proteins found in wheat and in other grains such as barley and rye. Moderate quantities of oats, free of contamination with other gluten-containing grains, are usually tolerated. The occurrence of problems may depend on the variety of oat. It occurs in people who are genetically predisposed. Upon exposure to gluten, an abnormal immune response may lead to the production of several different autoantibodies that can affect a number of different organs. In the small bowel, this causes an inflammatory reaction and may produce shortening of the villi lining the small intestine (villous atrophy). This affects the absorption of nutrients, frequently leading to anaemia.

Diagnosis is typically made by a combination of blood antibody tests and intestinal biopsies, helped by specific genetic testing. Making the diagnosis is not always straightforward. Frequently, the autoantibodies in the blood are negative, and many people have only minor intestinal changes with normal villi. People may have severe symptoms and be investigated for years before a diagnosis is achieved. Increasingly, the diagnosis is being made in people without symptoms, as a result of screening. Evidence regarding the effects of screening, however, is not sufficient to determine its usefulness. While the disease is caused by a permanent intolerance to gluten proteins, it is distinct from wheat allergy, which is much rarer.

The only known effective treatment is a strict lifelong gluten-free diet, which leads to recovery of the intestinal mucosa, improves symptoms and reduces risk of developing complications in most people. If untreated, it may result in cancers such as intestinal lymphoma and a slightly increased risk of early death. Rates vary between different regions of the world, from as few as 1 in 300 to as many as 1 in 40, with an average of between 1 in 100 and 1 in 170 people. It is estimated that 80% of cases remain undiagnosed, usually because of minimal or absent gastrointestinal complaints and lack of knowledge of symptoms and diagnostic criteria. Coeliac disease is slightly more common in women than in men.

Cause

Coeliac disease is caused by a reaction to gliadins and glutenins (gluten proteins) found in wheat, and similar proteins found in the crops of the tribe Triticeae (which includes other common grains such as barley and rye  and the tribe Aveneae (oats). Wheat subspecies (such as spelt, durum and Kamut) and wheat hybrids (such as triticale) also induce symptoms of coeliac disease.

A small number of people with coeliac react to oats. Oats toxicity in coeliac people depends on the oat cultivar consumed because of prolamin genes, protein amino acid sequences, and the immunoreactivities of toxic prolamins, which are different among oat varieties. Also, oats are frequently cross-contaminated with other grains containing gluten. "Pure oat" refers to oats uncontaminated with other gluten-containing cereals. The long-term effects of pure oats consumption are still unclear and further studies identifying the cultivars used are needed before making final recommendations on their inclusion in the gluten-free diet.  Coeliac people who choose to consume oats need a more rigorous lifelong follow-up, possibly including periodic performance of intestinal biopsies.

Signs and symptoms

The classic symptoms of untreated coeliac disease include pale, loose, and greasy stool (steatorrhoea), and weight loss or failure to gain weight. Other common symptoms may be subtle or primarily occur in organs other than the bowel itself. It is also possible to have coeliac disease without any of the classic symptoms at all. This has been shown to comprise at least 43% of presentations in children. Further, many adults with subtle disease may only present with fatigue or anaemia. Many undiagnosed individuals who consider themselves asymptomatic are in fact not, but rather have become accustomed to living in a state of chronically compromised health. Indeed, after starting a gluten-free diet and subsequent improvement becomes evident, such individuals are often able to retrospectively recall and recognise prior symptoms of their untreated disease which they had mistakenly ignored.

Gastrointestinal

Diarrhoea that is characteristic of coeliac disease is chronic, pale, of large volume, and abnormally bad smelling. Abdominal pain, cramping, bloating with abdominal distension (thought to be due to fermentative production of bowel gas), and mouth ulcers may be present. As the bowel becomes more damaged, a degree of lactose intolerance may develop.Frequently, the symptoms are ascribed to irritable bowel syndrome (IBS), only later to be recognised as coeliac disease. In populations of people with symptoms of IBS, a diagnosis of coeliac disease can be made in about 3.3% of cases, or 4x more likely than in general. Screening them for coeliac disease is recommended by the National Institute for Health and Clinical Excellence (NICE), the British Society of Gastroenterology and the American College of Gastroenterology, but is of unclear benefit in North America.

Coeliac disease leads to an increased risk of both adenocarcinoma and lymphoma of the small bowel (enteropathy-associated T-cell lymphoma (EATL) or other non-Hodgkin's lymphomas). This risk is also higher in first-degree relatives such as siblings, parents and children. Whether or not a gluten-free diet brings this risk back to baseline is not clear. Long-standing and untreated disease may lead to other complications, such as ulcerative jejunitis (ulcer formation of the small bowel) and stricturing (narrowing as a result of scarring with obstruction of the bowel).

Malabsorption-related

The changes in the bowel 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 cause weight loss (or failure to thrive/stunted growth in children) and fatigue or lack 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.

Calcium and vitamin D malabsorption (and compensatory secondary hyperparathyroidism) may cause osteopenia (decreased mineral content of the bone) or osteoporosis (bone weakening and risk of fragility fractures).

Selenium malabsorption in coeliac disease, combined with low selenium content in many gluten-free foods, confers a risk of selenium deficiency,

Copper and zinc deficiencies have also been associated with coeliac disease.

A small proportion have abnormal coagulation due to vitamin K deficiency and are slightly at risk for abnormal bleeding.

Miscellaneous

Coeliac disease has been linked with a number of conditions. In many cases, it is unclear whether the gluten-induced bowel disease is a causative factor or whether these conditions share a common predisposition.

IgA deficiency is present in 2.3% of people with coeliac disease, and is itself associated with a tenfold increased risk of coeliac disease. Other features of this condition are an increased risk of infections and autoimmune disease.

Dermatitis herpetiformis, an itchy cutaneous condition, 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 no gastrointestinal symptoms are present.

Growth failure and/or pubertal delay in later childhood can occur even without obvious bowel symptoms or severe malnutrition. Evaluation of growth failure often includes coeliac screening.

Pregnancy complications can occur in case of coeliac disease as an intercurrent disease in pregnancy, with significant complications including miscarriage, intrauterine growth restriction, low birthweight and preterm birth.

Hyposplenism (a small and underactive spleen) occurs in about a third of cases and may predispose to infection given the role of the spleen in protecting against bacteria.

Abnormal liver function tests (randomly detected on blood tests) may be seen.

Coeliac disease is associated with a number of other medical conditions, many of which are autoimmune disorders: diabetes mellitus type 1, hypothyroidism, primary biliary cholangitis, microscopic colitis, gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and more.

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Journal of Autoimmune Disorders
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