Coeliac disease Classification and external resources
Biopsy of small bowel showing coeliac disease manifested by blunting of villi, crypt hyperplasia, and lymphocyte infiltration of crypts. In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises Intestinal villi (singular villus) are tiny finger-like projections that come out from the wall of the Small intestine and have additional extensions called microvilli A lymphocyte is a type of White blood cell in the Vertebrate Immune system.
ICD-10	K90.0
ICD-9	579.0
OMIM	212750
DiseasesDB	2922
MedlinePlus	000233
eMedicine	med/308  ped/2146 radio/652
MeSH	D002446

Coeliac disease (pronounced /ˈsiːliːˌæk/), also spelled celiac disease, is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings K00-K93 - Diseases of the digestive system (K00-K14 Diseases of oral cavity salivary glands and jaws ( Disorders of Tooth development and Eruption The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises A genetic predisposition is a genetic effect which influences the Phenotype of an organism but which can be modified by the environmental conditions Symptoms include chronic diarrhoea, failure to thrive (in children), and fatigue, but these may be absent and symptoms in all other organ systems have been described. In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Failure to thrive (FTT is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in Infancy. It is estimated to affect about 1% of all Indo-European populations, but is thought to be significantly underdiagnosed. A growing portion of diagnoses are being made in asymptomatic persons as a result of increased screening. Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease ^[1]

Coeliac disease is caused by a reaction to gliadin, a gluten protein found in wheat (and similar proteins of the tribe Triticeae which includes other cultivars such as barley and rye). Gliadin is a Glycoprotein present in Wheat and several other Cereals within the grass genus Triticum. Gluten is a composite of the proteins Gliadin and Glutenin. These exist conjoined with Starch, in the Endosperms of some Wheat ( Triticum spp is a worldwide cultivated grass from the Levant area of the Middle East. In Biology, a tribe &mdashor infrafamily&mdashis a Taxonomic rank between family and Genus. Triticeae is a tribe within the Pooideae subfamily of grasses that includes genera with many domesticated species A cultivar is a cultivated Plant that has been selected and given a unique name because of its decorative or useful characteristics it is usually distinct from similar Barley ( Hordeum vulgare) is an annual Cereal Grain, which serves as a major animal Feed crop, with smaller amounts used for Rye ( Secale cereale) is a grass grown extensively as a grain and forage crop Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the bowel tissue, causing an inflammatory reaction. Tissue transglutaminase (abbreviated as TG2 or tTG) is an Enzyme ( of the Transglutaminase family An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens That leads to flattening of the lining of the small intestine (called villous atrophy). This interferes with the absorption of nutrients because the intestinal villi are responsible for absorption. Malabsorption is a state arising from abnormality in Digestion or Absorption of food nutrients across the gastrointestinal(GI tract. The only effective treatment is a lifelong gluten-free diet. A gluten-free diet is recommended amongst other things in the treatment of Coeliac disease and Wheat allergy. While the disease is caused by a reaction to wheat proteins, it is not the same as wheat allergy. Wheat Allergy, also known as wheat hypersensitivity is most commonly a Food allergy, but can also be a respiratory or contact allergy resulting

This condition has several other names, including: cœliac disease (with "œ" ligature), c(o)eliac sprue, non-tropical sprue, endemic sprue, gluten enteropathy or gluten-sensitive enteropathy, and gluten intolerance. This article is about the typographic ligature for other uses see Oe Œ The term coeliac derives from the Greek κοιλιακός (koiliakόs, abdominal), and was introduced in the 19th century in a translation of what is generally regarded as an ancient Greek description of the disease by Aretaeus of Cappadocia. Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Aretaeus ( is one of the most celebrated of the ancient Greek Physicians of whose life however few particulars are known ^[2]

Contents 1 Signs and symptoms 1.1 Gastrointestinal 1.2 Malabsorption-related 1.3 Miscellaneous 1.4 Other grains 2 Diagnosis 2.1 Blood tests 2.1.1 Antibody testing 2.1.2 HLA genetic typing 2.2 Endoscopy 2.3 Pathology 2.4 Other diagnostic tests 3 Pathophysiology 3.1 Genetics 3.2 Prolamins 3.3 Tissue transglutaminase 3.4 Villous atrophy and malabsorption 3.5 Risk modifiers 4 Treatment 4.1 Diet 4.2 Refractory disease 4.3 Experimental treatments 5 Screening and case finding 6 Epidemiology 7 Social and religious issues 7.1 Christian churches & the Eucharist 7.2 Roman Catholic position 7.3 Coeliacs and Passover 8 History 9 References 10 External links

Signs and symptoms

This article is part of the Gluten sensitivity series. Gluten sensitivity (GS encompasses a collection of medical conditions in which Gluten has an adverse effect

Coeliac disease

Wheat allergy

Gluten-sensitive idiopathic neuropathies

Triticeae glutens

Gluten-free diet

GSE associated conditions

Anti-gliadin antibodies

Anti-transglutaminase antibodies

HLA-DQ2, HLA-DQ8

Classic symptoms of coeliac disease include diarrhea, weight loss (or stunted growth in children), and fatigue, but while coeliac disease is primarily a bowel disease, bowel symptoms may also be limited or even absent. Wheat Allergy, also known as wheat hypersensitivity is most commonly a Food allergy, but can also be a respiratory or contact allergy resulting Diagnosis of gluten-sensitive Neuropathies without a clear cause is on the rise Triticeae glutens are seed storage Proteins found in mature seeds of grass tribe Triticeae. A gluten-free diet is recommended amongst other things in the treatment of Coeliac disease and Wheat allergy. Gluten-sensitive enteropathy has a wide variety of associated conditions however the key symptoms are typically restricted to the bowel and associated tissues Anti-gliadin antibodies are produced in response to Gliadin, a Prolamin found in the Wheat. Anti-transglutaminase antibodies (ATA are Antibodies found more frequently in certain Autoimmune diseases High levels ( Titers of ATA are found in HLA-DQ2 (DQ2 is a Serotype group within HLA-DQ (DQ serotyping system HLA-DQ8 (DQ8 is a Human leukocyte antigen Serotype within the HLA-DQ (DQ serotype group In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid Some patients are diagnosed with symptoms related to the decreased absorption of nutrients or with various symptoms which, although statistically linked, have no clear relationship with the malfunctioning bowel. Given this wide range of possible symptoms, the classic triad is no longer a requirement for diagnosis.

Children between 9 and 24 months tend to present with bowel symptoms and growth problems shortly after first exposure to gluten-containing products. Older children may have more malabsorption-related problems and psychosocial problems, while adults generally have malabsorptive problems. ^[3] Many adults with subtle disease only have fatigue or anaemia. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative ^[1]

Gastrointestinal

The diarrhoea characteristic of coeliac disease is pale, voluminous and malodorous. Steatorrhea is the presence of excess fat in Feces. Stools may also float due to excess gas have an oily appearance and be foul smelling Abdominal pain and cramping, bloatedness with abdominal distention (thought to be due to fermentative production of bowel gas) and mouth ulcers^[4] may be present. Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease An oral ulcer (from Latin ulcus) is the name for the appearance of an open sore inside the mouth caused by a break in the Mucous membrane or the epithelium As the bowel becomes more damaged, a degree of lactose intolerance may develop. Lactose intolerance is the inability to metabolize Lactose, a sugar found in Milk and other Dairy products because the required enzyme However, the variety of gastrointestinal symptoms that may be present in patients with coeliac disease is great, and some may have a normal bowel habit or even tend towards constipation. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that Frequently the symptoms are 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 may be justified. In Gastroenterology, irritable bowel syndrome ( IBS) is a Functional bowel disorder characterized by mild to severe Abdominal pain, discomfort ^[5]

Coeliac disease leads to an increased risk of both adenocarcinoma and lymphoma of the small bowel, which returns to baseline with diet. Adenocarcinoma is a cancer that originates in Glandular tissue Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) Longstanding disease may lead to other complications, such as ulcerative jejunitis (ulcer formation of the small bowel) and stricturing (narrowing as a result of scarring). ^[6]

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. ^[3]

• 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. Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid Failure to thrive (FTT is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in Infancy.
• 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. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative For a discussion of iron deficiency more broadly see the Wikipedia article iron deficiency. Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 Megaloblastic anemia is an Anemia (of macrocytic classification which results from inhibition of DNA synthesis in red blood cell production
• 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). Calcium (Ca2+ plays a vital role in the Anatomy, Physiology and Biochemistry of Organisms and of the cell, particularly Vitamin D is a group of fat-soluble Prohormones, the two major forms of which are vitamin D2 (or Ergocalciferol) and vitamin D3 (or Hyperparathyroidism is overactivity of the Parathyroid glands resulting in excess production of Parathyroid hormone (PTH Osteopenia is a condition where Bone mineral density is lower than normal Osteoporosis is a Disease of Bone that leads to an increased risk of fracture.
• A small proportion (10%) have abnormal coagulation due to deficiency of vitamin K, and are slightly at risk for abnormal bleeding. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that
• Coeliac disease is also associated with bacterial overgrowth of the small intestine, which can worsen malabsorption, or cause malabsorption after treatment. Small bowel bacterial overgrowth syndrome ( SBBOS) or small intestinal bacterial overgrowth ( SIBO) also termed bacterial overgrowth; is In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises ^[7]

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% of patients with coeliac disease, and in turn this condition features a tenfold increased risk of coeliac disease. Selective immunoglobulin A (IgA deficiency is a relatively mild genetic Immunodeficiency. ^[8][9] Other features of this condition are an increased risk of infections and autoimmune disease. An infection is the detrimental Colonization of a host Organism by a foreign Species. Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body
• Dermatitis herpetiformis; this itchy cutaneous condition has been linked to a transglutaminase enzyme in the skin, features small bowel changes identical to those in coeliac disease^[10] and occurs more often (in 2%) in patients with coeliac disease. Dermatitis herpetiformis, or DH, is a Skin disorder often associated with Celiac disease. ^[3]
• Neurological associations: epilepsy, ataxia (coordination problems), myelopathy, peripheral neuropathy, and schizophrenia ^[11] have all been linked with coeliac disease, but the strength of these associations and the causality are still subject to debate. Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. Ataxia (from Greek α- as a negative prefix + -τάξις, meaning "lack of order" is a neurological sign and symptom consisting Spinal cord injury causes myelopathy or damage to white matter or myelinated fiber tracts that carry sensation and motor signals to and from the brain Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn ^[12]
• Growth failure and/or pubertal delay in later childhood can occur even without obvious bowel symptoms or severe malnutrition. Growth failure is a medical term for a pattern of a child's growth which is poorer than normal for age sex stage of maturation and genetic height expectation Puberty is described as delayed when a boy or girl has passed the usual age of onset of Puberty with no physical or hormonal signs that it is beginning Malnutrition is a general term for a medical condition caused by an improper or insufficient diet. Evaluation of growth failure often includes coeliac screening.
• Miscarriage and infertility. Miscarriage or spontaneous abortion is the natural or spontaneous end of a Pregnancy at a stage where the embryo or fetus is incapable of surviving generally defined Female infertility|Male infertility Infertility primarily refers to the biological inability of a Man or a Woman to contribute to conception.
• Hyposplenism (a small and underactive spleen) - it is unclear whether this actually increases infection risk in the same way as in other people without a functioning spleen. This article is about the medical condition For the Moth Genus, see Armadini. The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red ^[13]
• Other auto-immune disorders: diabetes mellitus type 1,^[14] autoimmune thyroiditis,^[15] primary biliary cirrhosis,^[16] and microscopic colitis. Diabetes mellitus type 1 (Type 1 diabetes Type I diabetes T1D T1DM IDDM juvenile diabetes is a form of Diabetes mellitus. Thyroiditis is the inflammation of the thyroid gland The thyroid gland is located on the front of the neck below the Laryngeal prominence, and makes hormones that Primary biliary cirrhosis is an Autoimmune disease of the Liver marked by the slow progressive destruction of the small bile ducts ( Bile canaliculi) within Microscopic colitis refers to two medical conditions which cause Diarrhoea: Collagenous colitis and Lymphocytic colitis. ^[17]

Other grains

Wheat varieties or subspecies containing gluten and related species such as barley and rye also induce symptoms of coeliac disease. ^[18] A small minority of coeliac patients also react to oats. Oats redirects here It may mean either the common cereal oat discussed here or any cultivated or wild species of the Genus Avena. ^[19][20] It is most probable that oats produce symptoms due to cross contamination with other grains in the fields or in the distribution channels. ^[3] Generally, oats are therefore not recommended. ^[18] Other cereals, such as maize (corn), quinoa, millet, sorghum, and rice are safe for patients to consume. Maize (ˈmeɪz ( Zea mays L. ssp mays) known as corn in some countries is a cereal grain domesticated in Mesoamerica For the town with a similar name see Quinua Peru. "Quinoa" is also a title of a 1992 music album by Tangerine Dream. The millets are a group of small- Seeded Species of Cereal crops or grains widely grown around the world for Food and Fodder Sorghum is a genus of numerous species of grasses, some of which are raised for grain and many of which are used as Fodder plants either cultivated or as part Rice is a Cereal foodstuff which forms an important part of the diet of many people worldwide and as such it is a staple food for many Non-cereal carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms. The potato is a Starchy Tuberous crop Vegetable from the perennial Solanum tuberosum of the Solanaceae For the fruit see Banana. For other meanings see Banana (disambiguation.

Diagnosis

There are several tests that can be used to assist in diagnosis. The level of symptoms may determine the order of the tests, but all tests lose their usefulness if the patient is already taking a gluten-free diet. Intestinal damage begins to heal within weeks of gluten being removed from the diet, and antibody levels decline over months. For those who have already started on a gluten-free diet, it may be necessary to perform a re-challenge with 10 g of gluten (four slices of bread) per day over 2–6 weeks before repeating the investigations. Those who experience severe symptoms (e. g. diarrhoea) earlier can be regarded as sufficiently challenged and can be tested earlier. ^[3]

Combining findings into a prediction rule to guide use of endoscopy reported a sensitivity of 100% (it would identify all the cases) and specificity of 61% (it would be incorrectly positive in 39%). The prediction rule recommends that patients with high risk symptoms or positive serology should undergo endoscopy. The study defined high risk symptoms as weight loss, anaemia (haemoglobin less than 120 g/l in females and less than 130 g/l in males), or diarrhoea (more than three loose stools per day). ^[21]

Blood tests

Antibody testing

Serology by blood test is useful both in diagnosing coeliac disease (high sensitivity of about 98%, i. Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via e. it misses 2 in 100 cases) and in excluding it (high specificity of over 95%, i. e. a positive test is most likely confirmative of coeliac disease rather than another condition). Because of the major implications of a diagnosis of coeliac disease, professional guidelines recommend that a positive blood test is still followed by an endoscopy. A negative test may still prompt a biopsy if the suspicion remains very high; this would pick up the remaining 2% undiagnosed cases, as well as offering alternative explanations for the symptoms. As such, endoscopy with biopsy is still considered the gold standard in the diagnosis of coeliac disease. In Medicine, a gold standard test or criterion standard test is a Diagnostic test or benchmark that is regarded as definitive ^[3][6]

Blood antibody tests for coeliac disease^[22]

Test	sensitivity	specificity
AGA IgA	50%	98%
AGA IgA	25%	98%
Anti-EMA	81%	99%
ATA (Anti-TTG)	81%	99%

Four serological blood tests exist for coeliac disease. Anti-gliadin antibodies are produced in response to Gliadin, a Prolamin found in the Wheat. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity Anti-gliadin antibodies are produced in response to Gliadin, a Prolamin found in the Wheat. Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity The endomysium, literally meaning within the muscle is a layer of connective tissue that ensheaths a muscle fiber and is composed mostly from reticular fibers Anti-transglutaminase antibodies (ATA are Antibodies found more frequently in certain Autoimmune diseases High levels ( Titers of ATA are found in Tissue transglutaminase (abbreviated as TG2 or tTG) is an Enzyme ( of the Transglutaminase family The most widely used ones detect an antibody of the IgA type against particular antigens in the small bowel. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Immunoglobulin A ( IgA) is an Antibody playing a critical role in mucosal immunity An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Older tests detected antibodies against reticulin (ARA) or gliadin (AGA), but recent evidence supports the use of the more modern tests, namely those detecting IgA antibodies against endomysium (EMA) or tissue transglutaminase (TTG). Reticular fibers or reticulin is a histological term used to describe a type of Structural fiber composed of Type III collagen. Gliadin is a Glycoprotein present in Wheat and several other Cereals within the grass genus Triticum. Anti-gliadin antibodies are produced in response to Gliadin, a Prolamin found in the Wheat. The endomysium, literally meaning within the muscle is a layer of connective tissue that ensheaths a muscle fiber and is composed mostly from reticular fibers Tissue transglutaminase (abbreviated as TG2 or tTG) is an Enzyme ( of the Transglutaminase family Generally, serology may be unreliable in young children, with anti-gliadin performing somewhat better than other tests in children under five. ^[23] Serology tests are based on indirect immunofluorescence (reticulin, gliadin and endomysium) or ELISA (gliadin or tissue transglutaminase). Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology ^[24]

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 Statistics, the terms Type I error (also α error, or false positive) and type II error ( β error, or a false negative In those patients, IgG antibodies against transglutaminase (IgG-TTG) may be diagnostic. ^[25]

Blood HLA tests for coeliac disease^[22]

Test	sensitivity	specificity
HLA-DQ2	94%	73%
HLA-DQ8	12%	81%

HLA genetic typing

Antibody testing and HLA testing have similar accuracies. HLA-DQ2 (DQ2 is a Serotype group within HLA-DQ (DQ serotyping system HLA-DQ8 (DQ8 is a Human leukocyte antigen Serotype within the HLA-DQ (DQ serotype group The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans ^[22]

Endoscopy

An upper endoscopy with biopsy of the duodenum (beyond the duodenal bulb) or jejunum is performed. In Anatomy of the Digestive system, the jejunum is the central of the three divisions of the Small intestine and lies between the Duodenum and A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum The duodenal bulb is the portion of the Duodenum which is closest to the Stomach. In Anatomy of the Digestive system, the jejunum is the central of the three divisions of the Small intestine and lies between the Duodenum and It is important for the physician to obtain multiple samples (four to eight) from the duodenum. Not all areas may be equally affected; if biopsies are taken from healthy bowel tissue, the result would be a false negative. ^[6]

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 submucosal blood vessels, and a nodular pattern to the mucosa. Art History Mosaics of the 4th century BC are found in the Macedonian palace-city of Aegae, and they enriched the floors of Hellenistic The mucous membranes (or mucosae; singular mucosa) are linings of mostly endodermal origin covered in Epithelium, which are involved in ^[26]

Until the 1970s, biopsies were obtained using metal capsules attached to a suction device. The capsule was swallowed and allowed to pass into the small intestine. After X-ray verification of its position, suction was applied to collect part of the intestinal wall inside the capsule. One often-utilized capsule system is the Watson capsule. The Watson peroral small intestinal biopsy capsule was a system used through the 1960s and -70s to obtain small intestinal wall biopsies in patients with suspected Coeliac disease This method has now been largely replaced by fibre-optic endoscopy, which carries a higher sensitivity and a lower frequency of errors. ^[27]

Pathology

The classic pathology changes of coeliac disease in the small bowel are categorized by the "Marsh classification":^[28]

• Marsh stage 0: normal mucosa
• Marsh stage 1: increased number of intra-epithelial lymphocytes, usually exceeding 20 per 100 enterocytes
• Marsh stage 2: proliferation of the crypts of Lieberkuhn
• Marsh stage 3: partial or complete villous atrophy
• Marsh stage 4: hypoplasia of the small bowel architecture

The changes classically improve or reverse after gluten is removed from the diet, so many official guidelines recommend a repeat biopsy several (4–6) months after commencement of gluten exclusion. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Enterocytes, or intestinal absorptive cells, are Simple columnar Epithelial cells found in the Small intestines and Colon. The crypts of Lieberkühn (or intestinal glands) are Glands found in the Epithelial lining of the Small intestine and colon. Intestinal villi (singular villus) are tiny finger-like projections that come out from the wall of the Small intestine and have additional extensions called microvilli Atrophy is the partial or complete Wasting away of a part of the Body. Hypoplasia is underdevelopment or incomplete development of a tissue or organ In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises Gluten is a composite of the proteins Gliadin and Glutenin. These exist conjoined with Starch, in the Endosperms of some A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues ^[3]

In some cases a deliberate gluten challenge, followed by biopsy, may be conducted to confirm or refute the diagnosis. A normal biopsy and normal serology after challenge indicates the diagnosis may have been incorrect. ^[3] Patients are warned that one does not "outgrow" coeliac disease in the same way as childhood food intolerances.

Other diagnostic tests

Other tests that may assist in the diagnosis are blood tests for a full blood count, electrolytes, calcium, renal function, liver enzymes, vitamin B12 and folic acid levels. A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is An electrolyte is any substance containing free Ions that behaves as an electrically conductive medium Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. Liver function tests (LFTs or LFs which include liver enzymes, are groups of Clinical biochemistry laboratory blood assays designed to give information about the Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9 Coagulation testing (prothrombin time and partial thromboplastin time) may be useful to identify deficiency of vitamin K, which predisposes patients to hemorrhage. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby The prothrombin time ( PT) and its derived measures of prothrombin ratio ( PR) and international normalized ratio ( INR) are measures The partial thromboplastin time' (PTT or activated partial thromboplastin time ( aPTT or APTT) is a performance indicator measuring the efficacy of both the "intrinsic" Vitamin K (K from "Koagulations-Vitamin" in German Danish Swedish and Norwegian denotes a group of Lipophilic, Hydrophobic Vitamins that Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from These tests should be repeated on follow-up, as well as anti-tTG titres. Anti-transglutaminase antibodies (ATA are Antibodies found more frequently in certain Autoimmune diseases High levels ( Titers of ATA are found in ^[3]

Some professional guidelines^[3] recommend screening of all patients for osteoporosis by DXA/DEXA scanning. Osteoporosis is a Disease of Bone that leads to an increased risk of fracture. Dual energy X-ray absorptiometry ( DXA, previously DEXA is a means of measuring Bone mineral density (BMD

Pathophysiology

Coeliac disease appears to be polyfactorial, both in that more than one abnormal factor can cause the disease and also more than one factor is necessary for the disease to manifest in a patient.

Almost all coeliac patients have an abnormal HLA DQ2 allele. HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms ^[1] However, about 20–30% of people without coeliac disease have inherited an abnormal HLA-DQ2 allele. HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms ^[22] This suggests additional factors are needed for coeliac disease to develop. Furthermore, about 5% of those people who do develop coeliac disease do not have the DQ2 gene. ^[1]

The HLA-DQ2 allele shows incomplete penetrance, as the gene alleles associated with the disease appear in most patients, but are neither present in all cases nor sufficient by themselves to cause the disease. HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms Penetrance is a term used in Genetics describing the proportion of individuals carrying a particular variation of a Gene (an Allele or genotype that also An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms

Genetics

The vast majority of coeliac patients have one of two types of HLA DQ. HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type ^[22] 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. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor There are 7 HLA DQ variants (DQ2 and DQ4 through 9). Two of these variants—DQ2 and DQ8—are associated with coeliac disease. HLA-DQ2 (DQ2 is a Serotype group within HLA-DQ (DQ serotyping system HLA-DQ8 (DQ8 is a Human leukocyte antigen Serotype within the HLA-DQ (DQ serotype group The gene is located on the short arm of the sixth chromosome, and as a result of the linkage this locus has been labeled CELIAC1. Chromosome 6 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Genetic linkage occurs when particular genetic loci or Alleles for genes are inherited jointly In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Major histocompatibility complex class II DQ beta 1, also known as HLA-DQB1, is a human Gene and also denotes the genetic locus which contains this gene

Over 95% of coeliac patients have an isoform of DQ2 (encoded by DQA1*05 and DQB1*02 genes) and DQ8 (encoded by the haplotype DQA1*03:DQB1*0302), which is inherited in families. HLA-DQ8 (DQ8 is a Human leukocyte antigen Serotype within the HLA-DQ (DQ serotype group The term haplotype is a contraction of the term " haploid Genotype. The reason these genes produce an increase in risk of coeliac disease is that the receptors formed by these genes bind to gliadin peptides more tightly than other forms of the antigen-presenting receptor. Gliadin is a Glycoprotein present in Wheat and several other Cereals within the grass genus Triticum. Therefore, these forms of the receptor are more likely to activate T lymphocytes and initiate the autoimmune process. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. ^[1]

Most coeliac patients bear a two-gene HLA-DQ haplotype referred to as DQ2.5 haplotype. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type The term haplotype is a contraction of the term " haploid Genotype. HLA-DQ2 (DQ2 is a Serotype group within HLA-DQ (DQ serotyping system This haplotype is composed of 2 adjacent gene alleles, DQA1*0501 and DQB1*0201, which encode the two subunits, DQ α⁵ and DQ β². An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms HLA-DQ2 (DQ2 is a Serotype group within HLA-DQ (DQ serotyping system In most individuals, this DQ2. 5 isoform is encoded by one of two chromosomes 6 inherited from parents. Chromosome 6 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Most coeliacs inherit only one copy of this DQ2. 5 haplotype, while some inherit it from both parents; the latter are especially at risk for coeliac disease, as well as being more susceptible to severe complications. ^[30] Some individuals inherit DQ2. 5 from one parent and portions of the haplotype (DQB1*02 or DQA1*05) from the other parent, increasing risk. HLA-DQ (DQ is a cell surface receptor type Protein found on Antigen presenting cells DQ is an αβ Heterodimer of the MHC Class II type Less commonly, some individuals inherit the DQA1*05 allele from one parent and the DQB1*02 from the other parent, called a trans-haplotype association, and these individuals are at similar risk for coeliac disease as those with a single DQ2. 5 bearing chromosome 6, but in this instance disease tends not to be familial. Among the 6% of European celiacs that do not have DQ2. 5(cis or trans) or DQ8, 4% are DQ2 and 2% DQA1*05, 0. 4% cannot be linked to DQ8, DQA1*05, or DQB1*02. ^[31]

The frequency of these genes varies geographically. DQ2. 5 has high frequency in peoples of North and Western Europe (Basque Country, Ireland,^[32] with highest frequencies), portions of Africa, and is associated disease in India,^[33] but is not found along portions of the West Pacific rim. Ireland (pronounced /ˈaɾlənd/ Éire) is the third largest island in Europe, and the twentieth-largest island in the world DQ8, spread more globally than DQ2. 5, is more prevalent from South and Central America (up to 90% phenotype frequency). A phenotype is any observable characteristic of an Organism, such as its morphology, Development, biochemical or physiological properties ^[34]

In addition to the CELIAC1 locus, CELIAC2 (5q31-q33 - IBD5 locus), CELIAC3 (2q33 - CTLA4 locus), CELIAC4 (19q13. Chromosome 5 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Chromosome 2 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome Chromosome 19 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome 1 - MYOIXB locus), have been linked to coeliac disease. The CTLA4 and myosin IXB genes have been found to be linked to coeliac disease and other autoimmune diseases. CTLA4 ( C ytotoxic T - L ymphocyte A ntigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. Myosins are a large family of Motor proteins found in Eukaryotic tissues. ^[35][36] Two additional loci on chromosome 4, 4q27 (IL2 or IL21 locus) and 4q14, have been found to be linked to coeliac disease. Chromosome 4 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome ^[37][38]

Prolamins

The proteins in food responsible for the immune reaction in coeliac disease are the prolamins. Prolamins are a group of plant storage proteins having a high Proline content and found in the seeds of cereal grains Wheat ( Gliadin) Barley These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to pepsin and chymotrypsin, the two main digestive proteases in the gut. Proline (abbreviated as Pro or P) is an α- Amino acid, one of the twenty DNA -encoded amino acids Glutamine (abbreviated as Gln or Q; the abbreviation Glx or Z represents either glutamate or Glutamic acid) is one of the 20 Pepsin is a digestive Protease ( released by the chief cells in the Stomach that functions to degrade food Proteins into Chymotrypsin (bovine γ chymotrypsin,) is a digestive enzyme that can perform Proteolysis. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link Gliadin in wheat is the best-understood member of this family, but other prolamins exist and hordein (from barley), and secalin (from rye) may contribute to coeliac disease. Hordein is a Glycoprotein, present in Barley and some other Cereals together with Gliadin and other glycoproteins as Gluten. Secalin is a protein found in the grain Rye. Secalin is one of the forms of Gluten that people with Coeliac disease cannot tolerate and thus rye should ^[1] However, not all prolamins will cause this immune reaction and there is ongoing controversy on the ability of avenin (the prolamin found in oats) to induce this response in coeliac disease. Avenin is the Prolamin (protein high in Proline and Glutamine) found in Oats. Oats redirects here It may mean either the common cereal oat discussed here or any cultivated or wild species of the Genus Avena.

Tissue transglutaminase

Anti-transglutaminase antibodies to the enzyme tissue transglutaminase (tTG) are found in an overwhelming majority of cases. Anti-transglutaminase antibodies (ATA are Antibodies found more frequently in certain Autoimmune diseases High levels ( Titers of ATA are found in Tissue transglutaminase (abbreviated as TG2 or tTG) is an Enzyme ( of the Transglutaminase family ^[39] Tissue transglutaminase modifies gluten peptides into a form that may stimulate the immune system more effectively. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino ^[1]

Stored biopsies from suspected coeliac patients has revealed that autoantibody deposits in the subclinical coeliacs are detected prior to clinical disease. An autoantibody is an Antibody (a type of Protein) manufactured by the Immune system that is directed against one or more of the individual's own proteins These deposits are also found in patients who present with other autoimmune diseases, anemia or malabsorption phenomena at a much increased rate over the normal population. ^[40] Endomysial component of antibodies (EMA) to tTG are believed to be directed toward cell surface transglutaminase, and these antibodies are still used in confirming a coeliac disease diagnosis. However, a 2006 study showed that EMA-negative coeliac patients tend to be older males with more severe abdominal symptoms and a lower frequency of "atypical" symptoms including autoimmune disease. ^[41] In this study the anti-tTG antibody deposits did not correlate with the severity of villous destruction. These findings, coupled with recent work showing that gliadin has an innate response component,^[42] suggests that gliadin may be more responsible for the primary manifestations of coeliac disease whereas tTG is a bigger factor in secondary effects such as allergic responses and secondary autoimmune diseases. In a large percentage of coeliac patients the anti-tTG antibodies also recognize a rotavirus protein called VP7. Rotavirus is a Genus of Double-stranded RNA virus in the family Reoviridae. These antibodies stimulate monocytes proliferation and rotavirus infection might explain some early steps in the cascade of immune cell proliferation. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. ^[43] Indeed, earlier studies of rotavirus damage in the gut showed this causes a villous atrophy. ^[44] This suggests that viral proteins may take part in the initial flattening and stimulate self-crossreactive anti-VP7 production. Antibodies to VP7 may also slow healing until the gliadin mediated tTG presentation provides a second source of crossreactive antibodies.

Villous atrophy and malabsorption

The 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. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Malabsorption is a state arising from abnormality in Digestion or Absorption of food nutrients across the gastrointestinal(GI tract. A nutrient is food or chemicals that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment A vitamin is an Organic compound required as a Nutrient in tiny amounts by an Organism. Food is any substance usually composed primarily of Carbohydrates Fats water and/or Proteins that can be eaten or drunk by an Lactose intolerance may be present due to the decreased bowel surface and reduced production of lactase but typically resolves once the condition is treated. Lactose intolerance is the inability to metabolize Lactose, a sugar found in Milk and other Dairy products because the required enzyme Lactase (LCT a part of the β-galactosidase family of Enzymes is a Glycoside hydrolase involved in the Hydrolysis

Alternative causes of this tissue damage have been proposed and involve release of interleukin 15 and activation of the innate immune system by a shorter gluten peptide (p31–43/49). Interleukin 15 (IL-15 is a Cytokine with structural similarity to IL-2 that is secreted by mononuclear phagocytes (and some other cells following This would trigger killing of enterocytes by lymphocytes in the epithelium. Enterocytes, or intestinal absorptive cells, are Simple columnar Epithelial cells found in the Small intestines and Colon. In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body ^[1] The villous atrophy seen on biopsy may also be due to unrelated causes, such as tropical sprue, giardiasis and radiation enteritis. Tropical sprue is a Malabsorption disease commonly found in the tropical regions marked with abnormal flattening of the Villi and Inflammation of the lining Giardiasis — popularly known as beaver fever or backpacker's diarrhea — is a disease caused by the flagellate protozoan Giardia lamblia Radiation enteropathy or radiation enteritis is the syndrome that develops after the Intestine is exposed to Radiation. While positive serology and typical biopsy are highly suggestive of coeliac disease, lack of response to diet may require these alternative diagnoses to be considered. ^[6]

Risk modifiers

There are various theories as to what determines whether a genetically susceptible individual will go on to develop coeliac disease. Major theories include infection by rotavirus^[45] or human intestinal adenovirus. Rotavirus is a Genus of Double-stranded RNA virus in the family Reoviridae. Adenoviruses are medium-sized (90–100 nm) Nonenveloped (naked Icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA ^[46] Some research has suggested that smoking is protective against adult onset coeliac disease. ^[47]

A 2005 prospective and observational study found that timing of the exposure to gluten in childhood was an important risk modifier. People exposed to wheat, barley, or rye before the gut barrier has fully developed (three months after birth) had five times the risk of developing coeliac disease over those exposed at 4 to 6 months. The gut flora are the Microorganisms that normally live in the Digestive tract and can perform a number of useful functions for their hosts Those exposed later had a slightly increased risk relative to those exposed at 4 to 6 months. ^[48] However a 2006 study with similar numbers found just the reverse, that early introduction of grains was protective. ^[49] Breastfeeding may also reduce risk. A meta-analysis indicates that prolonging breastfeeding until the introduction of gluten-containing grains into the diet was associated with a 52% reduced risk of developing coeliac disease in infancy; whether this persists into adulthood is not clear. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses Breastfeeding is the feeding of an Infant or young Child with Breast milk directly from human Breasts, not from a Baby bottle or other ^[50]

Treatment

Diet

Main article: Gluten-free diet

Presently, the only effective treatment is a life-long gluten-free diet. A gluten-free diet is recommended amongst other things in the treatment of Coeliac disease and Wheat allergy. A gluten-free diet is recommended amongst other things in the treatment of Coeliac disease and Wheat allergy. ^[18] No medication exists that will prevent damage, or prevent the body from attacking the gut when gluten is present. Strict adherence to the diet allows the intestines to heal, leading to resolution of all symptoms in the vast majority of cases and, depending on how soon the diet is begun, can also eliminate the heightened risk of osteoporosis and intestinal cancer. ^[51] Dietician input is generally requested to ensure the patient is aware which foods contain gluten, which foods are safe, and how to have a balanced diet despite the limitations. A dietitian (also 'dietician' though 'dietitian' is used consistently by professionals is an expert in Food and Nutrition. In many countries gluten-free products are available on prescription and may be reimbursed by health insurance plans. A prescription (℞ is a health-care program implemented by a Physician or other medical practitioner in the form of instructions that govern the plan of care for an individual The term health insurance is generally used to describe a form of Insurance that pays for medical expenses More manufacturers are producing gluten-free products, some of which are almost indistinguishable from their gluten-containing counterparts.

The diet can be cumbersome; failure to comply with the diet may cause relapse. Many food products contain traces of gluten even if apparently wheat-free. Gluten-free products are usually more expensive and harder to find than common wheat-containing foods.

Even while on a diet, health-related quality of life (HRQOL) may be decreased in people with coeliac disease. Some have persisting digestive symptoms or dermatitis herpetiformis, mouth ulcers, osteoporosis and fractures. Dermatitis herpetiformis, or DH, is a Skin disorder often associated with Celiac disease. Symptoms suggestive of irritable bowel syndrome may be present, and there is an increased rate of anxiety, fatigue, dyspepsia and musculoskeletal pain. In Gastroenterology, irritable bowel syndrome ( IBS) is a Functional bowel disorder characterized by mild to severe Abdominal pain, discomfort Dyspepsia (from the Greek "δυς-" (Dys- and "πέψη" (Pepse known in plain English as indigestion, meaning hard ^[52]

Refractory disease

A tiny minority of patients suffer from refractory disease, 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 on diet alone, or because the patient is not adhering to the diet, or because the patient is consuming foods that are inadvertently contaminated with gluten. If alternative causes have been eliminated, steroids or immunosuppressants (such as azathioprine) may be considered in this scenario. Glucocorticoids (GC are a class of Steroid hormones characterised by an ability to bind with the glucocorticoid receptor ( GR) and trigger similar effects For a list of immunosuppressive drugs see the Transplant rejection page. Azathioprine is an immunosuppressant used in Organ transplantation Autoimmune disease such as Rheumatoid arthritis and Pemphigus or inflammatory ^[6]

Experimental treatments

Various other approaches are being studied that would reduce the need of dieting. All are still under development, and are not expected to be available to the general public for a while:^[1]

• Genetically engineered wheat species, or wheat species that have been selectively bred to be minimally immunogenic. Genetic engineering, Recombinant DNA technology, genetic modification/manipulation (GM and gene splicing are terms that apply to the direct Plant breeding is the art and science of changing the genetics of plants for the benefit of humankind This, however, could interfere with the effects that gliadin has on the quality of dough.
• A combination of enzymes (prolyl endopeptidase and a barley glutamine-specific cysteine endopeptidase (EP-B2)) that degrade the putative 33-mer peptide in the duodenum. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins '''Prolyl endopeptidase''' (PREP or prolyl oligopeptidase ( sometimes post-proline cleaving enzyme) is a large cytosolic Enzyme that belongs to a distinct class Proteases are Enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic Cysteine In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum This combination would enable coeliac disease patients to consume gluten-containing products. ^[53]
• Inhibition of zonulin, an endogenous signaling protein linked to increased permeability of the bowel wall and hence increased presentation of gliadin to the immune system. Zonulin is a Protein that participates in Tight junctions between cells of the wall of the Digestive tract. ^[54]
• Other treatments aimed at other well-understood steps in the pathogenesis of coeliac disease, such as the action of HLA-DQ2 or tissue transglutaminase and the MICA/NKG2D interaction that may be involved in the killing of enterocytes (bowel lining cells). Enterocytes, or intestinal absorptive cells, are Simple columnar Epithelial cells found in the Small intestines and Colon.

Screening and case finding

There is significant debate as to the benefits of screening. Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease Some studies suggest that early detection would decrease the risk of osteoporosis and anaemia. In contrast, a cohort studied in Cambridge suggested that people with undetected coeliac disease had a beneficial risk profile for cardiovascular disease (less overweight, lower cholesterol levels). A cohort study or panel study is a form of Longitudinal study used in Medicine and Social science. The city of Cambridge (ˈkeɪmbrɪdʒ is a university town and the administrative centre of the county of Cambridgeshire, England Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Overweight is generally defined as having more body fat (adipose tissue than is optimally Healthy Being overweight is a common condition especially where Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian ^[1]

Due to its high sensitivity, serology has been proposed as a screening measure, because the presence of antibodies would detect previously undiagnosed cases of coeliac disease and prevent its complications in those patients. Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum Serology may also be used to monitor adherence to diet: in those who still ingest gluten, antibody levels remain elevated. ^[3][6]

In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends screening for coeliac disease in patients with newly diagnosed chronic fatigue syndrome^[55] and irritable bowel syndrome. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Chronic fatigue syndrome ( CFS) is the most common name given to a poorly understood variably debilitating disorder or disorders of uncertain causation In Gastroenterology, irritable bowel syndrome ( IBS) is a Functional bowel disorder characterized by mild to severe Abdominal pain, discomfort ^[56]

Other clinical scenarios in which screening may be justified include type 1 diabetes,^[14] unexplained iron-deficiency anemia,^[57][58] Down's syndrome, Turner's syndrome, lupus, and autoimmune thyroid disease. Down syndrome, Down's syndrome, or trisomy 21 is a Chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. Turner syndrome or Ullrich-Turner syndrome encompasses several conditions of which monosomy X is the most common Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming ^[59]

Epidemiology

The prevalence of clinically diagnosed disease (symptoms prompting diagnostic testing) is 0. 05–0. 27% in various studies. However, population studies from parts of Europe, India, South America, Australasia and the USA (using serology and biopsy) indicate that the prevalence may be between 0. 33 and 1. 06% in children (5. 66% in one study of Saharawi children^[60]) and 0. The Sahara (الصحراء الكبرى aṣ-ṣaḥrā´ al-kubra, "The Great Desert" is the world's largest hot Desert and the world's second largest 18–1. 2% in adults. ^[1] People of African, Japanese and Chinese descent are rarely diagnosed; this reflects a much lower prevalence of the genetic risk factors. Population studies also indicate that a large proportion of coeliacs remain undiagnosed; this is due to many clinicians being unfamiliar with the condition. ^[61]

A large multicentre study in the U. S. found a prevalence of 0. 75% in not-at-risk groups, rising to 1. 8% in symptomatic patients, 2. 6% in second-degree relatives of a patient with coeliac disease and 4. 5% in first-degree relatives. This profile is similar to the prevalence in Europe. ^[62]

Social and religious issues

Christian churches & the Eucharist

With exception of the Roman Catholic Church, most mainline Christian churches offer their communicants gluten-free alternatives to the sacramental bread, usually in the form of a rice-based cracker or gluten-free bread. Sacramental bread, sometimes called Lamb or Host is the bread which is used in the Christian ritual of the Eucharist. These include United Methodist, Christian Reformed, Episcopal, Lutheran, The Church of Jesus Christ of Latter-day Saints, and many others. ^[63]

Roman Catholic position

Roman Catholic doctrine states that for a valid Eucharist the bread must be made from wheat. Doctrine (Latin doctrina) is a codification of beliefs or "a body of teachings quot or "instructions" taught principles or positions as the The Eucharist, also called Holy Communion or Lord's Supper and other names is a Christian Sacrament by which in a common interpretation those In 2002, the Congregation for the Doctrine of the Faith approved German-made low-gluten hosts, which meet all of the Catholic Church's requirements, for use in Italy; although not entirely gluten-free, they were also approved by the Italian Celiac Association. The Congregation for the Doctrine of the Faith (CDF ( Congregatio pro Doctrina Fidei) previously known as the Supreme Sacred Congregation of the Holy Office, Sacramental bread, sometimes called Lamb or Host is the bread which is used in the Christian ritual of the Eucharist. ^[64] Some Catholic coeliac sufferers have requested permission to use rice wafers; such petitions have always been denied. ^[65] The issue is more complex for priests. Though a Catholic (lay or ordained) receiving under either form is considered to have received Christ "whole and entire", the priest, who is acting in persona Christi, is required to receive under both species when offering Mass — not for the validity of his Communion, but for the fullness of the sacrifice of the Mass. In persona Christi - a Latin phrase meaning "in the person of Christ" - is an important theological concept of the Catholic Church and the confessional On August 22, 1994, the Congregation for the Doctrine of the Faith apparently barred coeliacs from ordination, stating, "Given the centrality of the celebration of the Eucharist in the life of the priest, candidates for the priesthood who are affected by coeliac disease or suffer from alcoholism or similar conditions may not be admitted to holy orders. Events 392 - Arbogast has Eugenius elected Western Roman Emperor. Year 1994 ( MCMXCIV) was a Common year starting on Saturday (link will display full 1994 Gregorian calendar) The Congregation for the Doctrine of the Faith (CDF ( Congregatio pro Doctrina Fidei) previously known as the Supreme Sacred Congregation of the Holy Office, " After considerable debate, the congregation softened the ruling on 24 July 2003 to "Given the centrality of the celebration of the Eucharist in the life of a priest, one must proceed with great caution before admitting to Holy Orders those candidates unable to ingest gluten or alcohol without serious harm. Events 1132 - Battle of Nocera between Ranulf II of Alife and Roger II of Sicily. Year 2003 ( MMIII) was a Common year starting on Wednesday of the Gregorian calendar. "^[66]

As of January 2004, an extremely low-gluten host became available in the United States. The Benedictine Sisters of Perpetual Adoration in Clyde, MO, after ten years of perseverance, trial, and error, have produced a low-gluten host safe for celiacs and also approved by the Catholic Church for use at Mass. Benedictine Sisters of Perpetual Adoration is a Roman Catholic religious order founded by Sister Mary Anselma in Clyde Missouri at the Benedictine Each host is made and packaged in a dedicated wheat-free / gluten-free environment. The hosts are made separately by hand, unlike the common host which is stamped out of a long thin sheet of bread by a cutter. Therefore, each host is a slightly different size and shape. Most importantly, the finished hosts have been analyzed for gluten content. The gluten content of these hosts is reported as 0. 01 %. In actuality, the gluten content is probably less than 0. 01%. Sister Lynn, OSB, said that the result of the analysis of the finished host revealed "no gluten detected". The hosts are labeled as 0. 01 % since the lowest limit of detection of this analysis was 0. 01 %. In an article from the Catholic Review (February 15, 2004) Dr. Events 590 - Khosrau II is crowned as king of Persia 1637 - Ferdinand III becomes Holy Roman Emperor "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " Alessio Fasano was quoted as declaring these hosts "perfectly safe for celiac sufferers. " ^[67]

Coeliacs and Passover

The Jewish festival of Pesach (Passover) may present problems with its obligation to eat matzo, which is unleavened bread made in a strictly controlled manner from wheat, barley, spelt, oats, or rye. Passover ( Hebrew, Yiddish: פֶּסַח Pesach, Tiberian: pɛsaħ Israeli: Pesah, Pesakh, Yiddish Matza (also Matzah, Matzoh, or Matsah) מַצָּה in Ashkenazi matzo or matzoh, and in Yiddish, matze This rules out many other grains that are normally used as substitutes for people with gluten sensitivity, especially for Ashkenazi Jews who also avoid rice. Ashkenazi Jews, also known as Ashkenazic Jews or Ashkenazim ( Hebrew: אַשְׁכֲּנָזִים, ˌaʃkəˈnazim sing Rice is a Cereal foodstuff which forms an important part of the diet of many people worldwide and as such it is a staple food for many Many kosher for Passover products avoid grains altogether and are therefore gluten-free. Potato starch is the primary starch used to replace the grains. Consuming matzo is mandatory on the first night of Pesach only. Jewish law holds that a person should not seriously endanger one's health in order to fulfill a commandment. Thus, a person with severe coeliac disease is not required, or even allowed, to eat any matzo other than gluten-free matzo. The most commonly used gluten-free matzo is made from oats. ^[68]

History

Aretaeus of Cappadocia, living in the second century, recorded a malabsorptive syndrome with chronic diarrhoea. Aretaeus ( is one of the most celebrated of the ancient Greek Physicians of whose life however few particulars are known His "Cœliac Affection" (coeliac from Greek κοιλιακός koiliakos, abdominal) gained the attention of Western medicine when Francis Adams presented a translation of Aretaeus' work at the Sydenham Society in 1856. Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Francis Adams (1796 – February 26, 1861) was a Scottish Medical doctor and Translator of Greek medical works The patient 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. The problem, Aretaeus believed, was a lack of heat in the stomach necessary to digest the food and a reduced ability to distribute the digestive products throughout the body, this incomplete digestion resulting in the diarrhoea, He regarded this as an affliction of the old and more commonly affecting women, explicitly excluding children. The cause, according to Aretaeus, was sometimes either another chronic disease or even consuming "a copious draught of cold water". ^[2]

The paediatrician, Samuel Gee, gave the first modern-day description of the condition in a lecture at Hospital for Sick Children, Great Ormond Street, London in 1887. Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents Samuel Jones Gee ( September 13, 1839 – August 3, 1911) was an English Physician and Paediatrician. The Great Ormond Street Hospital (GOSH is a medical institution specialising in the care of children Gee acknowledged earlier descriptions and terms for the disease and adopted the same term as Aretaeus (coeliac disease). Unlike Aretaeus, he included children in the scope of the affliction, particularly those between one and five years old. Gee found the cause to be obscure and failed to spot anything abnormal during post-mortem examination (the lining of the small bowel quickly deteriorates on death). ^[69] He perceptively stated "if the patient can be cured at all, it must be by means of diet. " Gee recognised that milk intolerance is a problem with coeliac children and that highly starched foods should be avoided. However, he forbade rice, sago, fruit and vegetables, which all would have been safe to eat and he recommended raw meat as well as thin slices of toasted bread. Gee highlighted particular success with a child "who was fed upon a quart of the best Dutch mussels daily". The common name mussel is used for members of several different families of Clams or Bivalve Molluscs, from both saltwater and freshwater habitats However, the child could not bear this diet for more than one season. ^[70]

Christian Archibald Herter, an American physician, wrote a book in 1908 on children with coeliac disease, which he called "intestinal infantilism". Christian Archibald Herter ( September 3, 1865 – December 5, 1910) was an American Physician and pathologist He noted their growth was retarded and that fat was better tolerated than carbohydrate. The eponym Gee-Herter disease was sometimes used to acknowledge both contributions. ^[71][72] Sydney V. Haas, an American paediatrician, reported positive effects of a diet of bananas in 1924. For the fruit see Banana. For other meanings see Banana (disambiguation. ^[73] This diet remained in vogue until the actual cause of coeliac disease was determined.

While a role for carbohydrates had been suspected, the link with wheat was not made until the 1940s by the Dutch paediatrician Dr Willem Dicke. ^[74] It is likely that clinical improvement of his patients during the Dutch famine of 1944 (during which flour was sparse) may have contributed to his discovery. The Dutch famine of 1944 (known as hongerwinter ("Hunger winter" in Dutch was a Famine that took place in the Netherlands during the winter ^[75] The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England. Birmingham ( ˈbɜːmɪŋəm Ber -ming-um ^[76] Villous atrophy was described by British physician John W. Paulley in 1954. ^[77] Paulley was able to examine biopsies taken from patients during abdominal operations. ^[69] Dr Margo Shiner, working on Prof Sheila Sherlock's team at the Postgraduate Medical School in London, described the principles of small bowel biopsy in 1956. The Royal Postgraduate Medical School (RPMS was an independent Medical school in England. ^[78]

Throughout the 1960s other features of coeliac disease were elucidated. Its hereditary character was recognized in 1965. ^[79] In 1966 dermatitis herpetiformis was linked to gluten sensitivity. Dermatitis herpetiformis, or DH, is a Skin disorder often associated with Celiac disease. ^[10]

References

External links

• Coeliac disease at the Open Directory Project
• Celiac.com - U. The Open Directory Project ( ODP) also known as dmoz (from directory S. resource
• Coeliac UK - leading UK charity
• Celiac Disease Awareness Campaign from the National Institutes of Health
• Celiac Disease Foundation - U. S.
• Celiac Disease practice guideline from the World Gastroenterology Organisation (WGO)
• Celiac Sprue Association - U. S.
• Outcomes of 2004 consensus development conference, U. S. National Institutes of Health
• National Digestive Diseases Clearinghouse - page on coeliac disease
• National Foundation for Celiac Awareness - U. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. S.
• University of Maryland Center for Celiac Research - U. S.

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