Coeliac disease

Coeliac disease or celiac disease is a chronic autoimmune disease, mainly affecting the small intestine. It is caused by an abnormal immune system response to gluten, a protein found in wheat and other grains such as barley and rye. Coeliac disease causes a wide range of symptoms and complications that can affect multiple organs outside the gastrointestinal

Coeliac disease (Commonwealth English) or celiac disease (American English) is a chronic autoimmune disease, mainly affecting the small intestine. It is caused by an abnormal immune system response to gluten, a protein found in wheat and other grains such as barley and rye. Coeliac disease causes a wide range of symptoms and complications that can affect multiple organs outside the gastrointestinal tract.

The classic form of the disease can affect any age group, but is usually diagnosed in early childhood and causes symptoms of malabsorption such as weight loss, diarrhoea, and stunted growth. Non-classic coeliac disease is more commonly seen in adults, characterised by vague abdominal symptoms and complications in organs outside the gastrointestinal tract, such as bone disease, anaemia, and other consequences of nutritional deficiencies. In people with a genetic predisposition to the condition, eating gluten causes inflammation in the small intestine, damaging its lining and leading to malabsorption. The development of coeliac disease is believed to be influenced by other environmental factors, such as infections.

Diagnosis is based on symptoms, blood tests, and biopsies of the small intestine. For people who have already cut gluten from their diet, gluten may need to be reintroduced before testing to ensure an accurate diagnosis. A lack of awareness and the diverse symptoms, which overlap with other disorders, often complicate the diagnosis by leading to a delay in diagnosis. Current research indicates that there is not enough evidence to advocate for mass screening for coeliac disease in those without symptoms.

The only treatment for coeliac disease is a lifelong gluten-free diet (GFD). A GFD involves removing all food and drink containing wheat, rye, barley, and gluten derivatives. Symptoms can improve within days of adopting a GFD, and the diet can improve quality of life, prevent further complications, and normalise some effects of the disease such as stunted growth.

Approximately 1 in 200 to 1 in 50 people have coeliac disease. Diagnoses of coeliac disease have increased recently due to increased awareness and availability of blood testing. The disease is still thought to be underdiagnosed, with a significant number of people with the condition remaining undiagnosed and untreated. The disease usually develops before age 10; it is slightly more common in women than in men.

Terminology and classification

"Coeliac disease" is the preferred spelling in Commonwealth English, whereas "celiac disease" is typically used in North American English.[1][2] The terms sprue, coeliac sprue, gluten-sensitive enteropathy, non-tropical sprue and idiopathic steatorrhoea have been used as synonyms for coeliac disease in the past. Both gluten intolerance and gluten sensitivity have been used as synonyms of coeliac disease or to describe other symptoms triggered by gluten. The terms are nonspecific and lack a consistent definition.[3] Gluten-related disorders are conditions related to gluten such as coeliac disease, gluten ataxia, wheat allergy, dermatitis herpetiformis, and non-coeliac gluten sensitivity.[4]

Many individuals with coeliac disease are asymptomatic,[5] meaning they do not have any symptoms associated with coeliac disease. Those with asymptomatic coeliac disease are commonly diagnosed through screening programs. The term "silent coeliac disease" is equivalent to asymptomatic, but usage is discouraged.[3] Coeliac disease can be symptomatic (previously called overt coeliac disease) or subclinical.[3][5] Subclinical coeliac disease has historically had many different definitions, such as those with symptoms mainly outside the gastrointestinal tract, or those with clinical signs of the disease (anaemia, laboratory abnormalities, and endoscopic features) but no symptoms. Subclinical coeliac disease is now used when individuals who do not have symptoms that commonly warrant testing for coeliac disease have positive serology for coeliac disease.[3] Symptomatic coeliac disease (characterised by symptoms related to gluten) can be further categorised into classical and non-classical.[5] Classical coeliac disease, which in the past has also been called typical coeliac disease, is coeliac disease presenting with malnutrition, malabsorption, and diarrhoea. Non-classical coeliac disease, historically referred to as atypical coeliac disease, is when individuals primarily present with symptoms unrelated to malabsorption.[3]

Potential coeliac disease refers to those who have positive serology for coeliac disease but no changes in the small intestine. The term latent coeliac disease has been used interchangeably with potential coeliac disease, but has no consistent definition, and its use is therefore discouraged.[3]

Sometimes, those with coeliac disease will continue to experience symptoms or signs of the disease despite being on a gluten-free diet. "Slow responders" or "non responsive coeliac disease" (NRCD) is the persistence of symptoms despite exclusion of gluten for 6 to 12 months.[6][7] Refractory coeliac disease (RCD) is the persistence of malabsorption and damage to the small intestine after at least 12 months of a gluten-free diet. Most people with NRCD do not have RCD; instead, their symptoms are caused by some other factor. There are two types of RCD: type one has histopathological changes similar to those seen in untreated coeliac disease, whereas type two has abnormal histopathological changes not consistent with untreated coeliac disease.[7]

Signs and symptoms

Coeliac disease causes a wide range of symptoms and complications that can involve several different organs.[5] The presentation of coeliac disease can be classified as classic, non-classic, and subclinical.[8] Classic coeliac disease is commonly seen in young children, but can affect any age group, and is characterised by malabsorption manifesting as diarrhoea, weight loss, and failure to thrive.[5][9] Non-classic coeliac disease is seen more often in adults, and symptoms primarily manifest outside the intestine (extraintestinal).[9] 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. After starting a gluten-free diet and a subsequent improvement becomes evident, such individuals are often able to retrospectively recall and recognise prior symptoms of their untreated disease that they had mistakenly ignored.[10][11][12]

Gastrointestinal

Diarrhoea that is characteristic of coeliac disease is chronic, sometimes pale, of large volume, and abnormally foul in odour. Other symptoms of coeliac disease include abdominal pain, cramping, bloating with abdominal distension, and mouth ulcers.[13][14] As the bowels become more damaged, lactose intolerance can develop.[15]

Extraintestinal manifestations

Coeliac disease is a systemic disorder, meaning it affects the entire body. Although many common symptoms of the disease are related to the gastrointestinal tract, those with coeliac disease may also experience symptoms and complications in other organs, known as extraintestinal manifestations.[16] These manifestations may be related to malabsorption or systemic inflammation.[17] Common extraintestinal manifestations of coeliac disease include headaches, fatigue, brain fog, muscle pain, and joint pain.[17][18]

Nutritional status in coeliac disease may be compromised due to lower intake, maldigestion, and malabsorption, leading to nutritional deficiencies. Common deficiencies in coeliac disease include iron, folate, zinc, vitamin D, and vitamin B12.[14][18] Vitamin D deficiency can cause secondary hyperparathyroidism. Hyperoxaluria and kidney stones can be caused by malabsorption of fats, and peptides.[18] Iron deficiency may lead to anaemia, which is one of the most common extraintestinal presentations of coeliac disease.[17] Coeliac disease also often affects the bones, causing low bone mass density (osteopenia) and osteoporosis. Causes of bone changes in coeliac disease are believed to be caused by malabsorption, inflammation, and autoimmunity.[16]

If left untreated, coeliac disease can affect hormones, causing delayed periods or puberty and reproductive disorders.[14][16] Coeliac disease is associated with infertility and complications during pregnancy such as intra-uterine growth restriction and spontaneous abortion. Reproductive disorders are thought to be caused by nutritional deficiencies, particularly zinc, iron, folate, and selenium deficiencies in coeliac disease.[18]

Coeliac disease often affects the liver, causing increased transaminase levels.[14] This elevation of transaminases seen in coeliac disease is known as coeliac hepatitis. Mildly increased transaminases without symptoms and without other possible factors Mildly increased transaminases without symptoms and without other possible factors such as autoimmune or viruses that could cause liver abnormalities, characterise coeliac hepatitis.[17][18]

Due to the systemic nature of coeliac disease and its potential to affect any organ, there are many rarer presentations of coeliac disease, some of which have an unclear relationship to the disease.[17] Some of these more uncommon manifestations include peripheral neuropathy, epilepsy, psoriasis, recurrent aphthous stomatitis, pericardial effusion, and Lane-Hamilton syndrome.[18]

Causes

Coeliac disease is caused by an inflammatory reaction to gliadins and glutenins (gluten proteins)[19] found in wheat and to similar proteins found in the crops of the tribe Triticeae (which includes other common grains such as barley and rye) and to the tribe Aveneae (oats).[20] Wheat subspecies (such as spelt, durum, and khorasan wheat) and wheat hybrids (such as triticale) also cause symptoms of coeliac disease.[21]

A small number of people with coeliac disease react to oats. Sensitivity to oats in coeliac disease may be due to cross-contamination of oats and other foods with gluten, differences between gluten content, immunoreactivity, and genetic variability seen between oat cultivars or dietary intolerance to oats.[22][23] Most people with coeliac disease do not have adverse reactions to uncontaminated or 'pure' oats, however clinical guidelines differ on whether those with coeliac disease should consume oats.[24][25]

Other cereals such as maize, millet, sorghum, teff, rice, and wild rice are safe for people with coeliac disease to consume, as well as non-cereals such as amaranth, quinoa, and buckwheat. Noncereal carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms.[26][27]

Risk modifiers

Environmental factors such as infections, geographic latitude, birth weight, antibiotic use, intestinal microbiota, socioeconomic status, hygiene, breastfeeding, and the timing of introduction of gluten into an infant's diet are theorised to contribute to the development of coeliac disease in genetically predisposed individuals.[7][19][9] The consumption of gluten and timing of introduction, in a baby's life does not appear to increase the risk of coeliac disease, however in those who are genetically predisposed to coeliac disease, large amounts of gluten early in life may increase the risk of developing coeliac disease.[28][29]