Coeliac disease

{{Short description|Autoimmune disorder}} {{Featured article}} {{CS1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=August 2025}} {{Use British English|date=April 2012}} {{Infobox medical condition (new) | name = Coeliac disease | image = Coeliac disease endoscopy.jpg | caption = [[Endoscopy]] of the [[duodenum]] showing fissured folds with a scalloped appearance | alt = An endoscopy of the intestines | field = [[Gastroenterology]], [[internal medicine]] | pronounce = {{IPAc-en|ˈ|s|iː|l|i|æ|k|audio=LL-Q1860 (eng)-Flame, not lame-Coeliac disease.wav}} {{respell|SEE|lee|ak}} | synonyms = Coeliac sprue, nontropical sprue, endemic sprue, gluten enteropathy | symptoms = None or [[Non-specific symptoms|non-specific]], [[diarrhea|diarrhoea]], [[malabsorption]], and weight loss. | complications = [[Iron-deficiency anemia|Iron-deficiency anaemia]], [[osteoporosis]], [[infertility]], [[cancer]]s, and nutritional deficiencies. | onset = Any age | duration = Lifelong | causes = [[Gluten]] | risks = [[Genetic predisposition]] and environmental factors | diagnosis = Blood tests and intestinal [[biopsy|biopsies]] | differential = [[Inflammatory bowel disease]], [[intestinal parasites]], and [[irritable bowel syndrome]] | prevention = | treatment = [[Gluten-free diet]] | medication = | prognosis = | frequency = Between 1 in 50 and 1 in 200 | deaths = }} '''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]], [[Diarrhea|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]], [[anemia|anaemia]], and other consequences of [[Malnutrition|nutritional deficiencies]]. In people with a [[genetic predisposition]] to the condition, eating gluten causes [[inflammation]] in the small intestine, damaging its [[Intestinal epithelium|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 test]]s, 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 [[Diagnostic delay|delay in diagnosis]]. Current research indicates that there is not enough evidence to advocate for [[Screening (medicine)|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 [[American and British English spelling differences#ae and oe|Commonwealth English]], whereas "celiac disease" is typically used in [[North American English]].<ref>{{Cite web |url=https://dictionary.cambridge.org/dictionary/english/coeliac-disease |title=COELIAC DISEASE {{!}} meaning in the Cambridge English Dictionary|website=dictionary.cambridge.org |access-date=15 December 2018}}</ref><ref>{{Cite web |url=http://www.glutenfreedublin.com/coeliac-vs-celiac |title=Coeliac vs. Celiac |website=www.glutenfreedublin.com |access-date=15 December 2018 |archive-date=17 December 2018 |archive-url=https://web.archive.org/web/20181217110644/http://www.glutenfreedublin.com/coeliac-vs-celiac }}</ref> 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.<ref name="v667">{{cite journal | last1=Ludvigsson | first1=Jonas F | last2=Leffler | first2=Daniel A | last3=Bai | first3=Julio C | last4=Biagi | first4=Federico | last5=Fasano | first5=Alessio | last6=Green | first6=Peter H R | last7=Hadjivassiliou | first7=Marios | last8=Kaukinen | first8=Katri | last9=Kelly | first9=Ciaran P | last10=Leonard | first10=Jonathan N | last11=Lundin | first11=Knut Erik Aslaksen | last12=Murray | first12=Joseph A | last13=Sanders | first13=David S | last14=Walker | first14=Marjorie M | last15=Zingone | first15=Fabiana | last16=Ciacci | first16=Carolina | title=The Oslo definitions for coeliac disease and related terms | journal=Gut | volume=62 | issue=1 | date=2013 | issn=0017-5749 | pmid=22345659 | pmc=3440559 | doi=10.1136/gutjnl-2011-301346 | pages=43–52 }}</ref> [[Gluten-related disorders]] are conditions related to gluten such as coeliac disease, [[gluten ataxia]], [[wheat allergy]], [[dermatitis herpetiformis]], and [[Non-celiac gluten sensitivity|non-coeliac gluten sensitivity]].<ref name="d664">{{cite book | last1=Asri | first1=Nastaran | last2=Rostami-Nejad | first2=Mohammad | title=Gluten-Related Disorders | chapter=Gluten-related disorders definition | publisher=Elsevier | date=2022 | isbn=978-0-12-821846-4 | doi=10.1016/b978-0-12-821846-4.00003-6 | url=https://linkinghub.elsevier.com/retrieve/pii/B9780128218464000036 | access-date=2025-12-06 | pages=49–57}}</ref>

Many individuals with coeliac disease are asymptomatic,<ref name="o723"/> 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.<ref name="v667"/> Coeliac disease can be symptomatic (previously called ''overt coeliac disease'') or subclinical.<ref name="v667"/><ref name="o723"/> 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 ([[anemia|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.<ref name="v667"/> Symptomatic coeliac disease (characterised by symptoms related to gluten) can be further categorised into classical and non-classical.<ref name="o723"/> Classical coeliac disease, which in the past has also been called typical coeliac disease, is coeliac disease presenting with [[malnutrition]], [[malabsorption]], and [[Diarrhea|diarrhoea]]. Non-classical coeliac disease, historically referred to as atypical coeliac disease, is when individuals primarily present with symptoms unrelated to malabsorption.<ref name="v667"/>

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.<ref name="v667"/>

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.<ref name="b177">{{cite journal | last1=Al-Toma | first1=Abdulbaqi | last2=Volta | first2=Umberto | last3=Auricchio | first3=Renata | last4=Castillejo | first4=Gemma | last5=Sanders | first5=David S | last6=Cellier | first6=Christophe | last7=Mulder | first7=Chris J | last8=Lundin | first8=Knut E A | title=European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders | journal=United European Gastroenterology Journal | volume=7 | issue=5 | date=2019 | issn=2050-6406 | pmid=31210940 | pmc=6545713 | doi=10.1177/2050640619844125 | pages=583–613 }}</ref><ref name="f561"/> 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.<ref name="f561"/>

==Signs and symptoms== Coeliac disease causes a wide range of symptoms and complications that can involve several different organs.<ref name="o723">{{cite book |vauthors=Varma S, Krishnareddy S |title=Refractory Celiac Disease | chapter=Uncomplicated Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-90141-7 | doi=10.1007/978-3-030-90142-4_2 | chapter-url=https://link.springer.com/10.1007/978-3-030-90142-4_2 | access-date=17 August 2025 | pages=5–19}}</ref> The presentation of coeliac disease can be classified as classic, non-classic, and subclinical.<ref name="s519"/> 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]].<ref name="o723"/><ref name="d428">{{cite journal | last1=Tarar | first1=Zahid Ijaz | last2=Zafar | first2=Muhammad Usman | last3=Farooq | first3=Umer | last4=Basar | first4=Omer | last5=Tahan | first5=Veysel | last6=Daglilar | first6=Ebubekir | title=The Progression of Celiac Disease, Diagnostic Modalities, and Treatment Options | journal=Journal of Investigative Medicine High Impact Case Reports | volume=9 | date=2021 | issn=2324-7096 | pmid=34693776 | pmc=8767653 | doi=10.1177/23247096211053702 | doi-access=free | article-number=23247096211053702 }}</ref> Non-classic coeliac disease is seen more often in adults, and symptoms primarily manifest outside the [[intestine]] (extraintestinal).<ref name="d428"/> 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.<ref name="o776">{{cite journal | last1=Lebwohl | first1=Benjamin | last2=Rubio-Tapia | first2=Alberto | title=Epidemiology, Presentation, and Diagnosis of Celiac Disease | journal=Gastroenterology | volume=160 | issue=1 | date=2021 | doi=10.1053/j.gastro.2020.06.098 | doi-access=free | pages=63–75 | pmid=32950520 | url=http://www.gastrojournal.org/article/S0016508520351659/pdf | access-date=2025-08-20}}</ref><ref name="h248">{{cite journal | last1=Kvamme | first1=Jan-Magnus | last2=Sørbye | first2=Sveinung | last3=Florholmen | first3=Jon | last4=Halstensen | first4=Trond S. | title=Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet | journal=Scientific Reports | volume=12 | issue=1 | date=2022-07-25 | issn=2045-2322 | pmid=35879335 | pmc=9314380 | doi=10.1038/s41598-022-16705-2 | doi-access=free | url=https://www.nature.com/articles/s41598-022-16705-2.pdf | access-date=2025-08-20 | article-number=12647 | bibcode=2022NatSR..1212647K }}</ref><ref name=LionettiGatti2015>{{cite journal |vauthors=Lionetti E, Gatti S, Pulvirenti A, Catassi C |title=Celiac disease from a global perspective |journal=Best Practice & Research. Clinical Gastroenterology |volume=29 |issue=3 |pages=365–379 |date=June 2015 |pmid=26060103 |doi=10.1016/j.bpg.2015.05.004 |type=Review}}</ref>

===Gastrointestinal=== [[diarrhea|Diarrhoea]] that is characteristic of coeliac disease is chronic, sometimes pale, of large volume, and abnormally [[Steatorrhea|foul in odour]]. Other symptoms of coeliac disease include [[abdominal pain]], cramping, [[bloating]] with [[abdominal distension]], and [[mouth ulcer]]s.<ref name="c042">{{cite book | last=de Villasante | first=Gemma Castillejo | title=Advances in Celiac Disease | chapter=Classical and Non-classical Forms of CD in Paediatrics | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_3 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_3 | access-date=17 August 2025 | pages=23–33}}</ref><ref name="a113">{{cite journal | last1=Ludvigsson | first1=Jonas F. | last2=Yao | first2=Jialu | last3=Lebwohl | first3=Benjamin | last4=Green | first4=Peter H. R. | last5=Yuan | first5=Shuai | last6=Leffler | first6=Daniel A. | title=Coeliac disease: complications and comorbidities | journal=Nature Reviews Gastroenterology & Hepatology | date=2025-01-28 | volume=22 | issue=4 | pages=252–264 | issn=1759-5045 | doi=10.1038/s41575-024-01032-w | url=https://www.nature.com/articles/s41575-024-01032-w | access-date=2025-12-13 | pmid=39875649 | url-access=subscription }}</ref> As the bowels become more damaged, [[lactose intolerance]] can develop.<ref name="h881">{{cite journal | last1=Lenti | first1=Marco Vincenzo | last2=Hammer | first2=Heinz Florian | last3=Tacheci | first3=Ilja | last4=Burgos | first4=Rosa | last5=Schneider | first5=Stephane | last6=Foteini | first6=Anastasiou | last7=Derovs | first7=Aleksejs | last8=Keller | first8=Jutta | last9=Broekaert | first9=Ilse | last10=Arvanitakis | first10=Marianna | last11=Dumitrascu | first11=Dan Lucian | last12=Segarra-Cantón | first12=Oscar | last13=Krznarić | first13=Željko | last14=Pokrotnieks | first14=Juris | last15=Nunes | first15=Gonçalo | last16=Hammer | first16=Johann | last17=Pironi | first17=Loris | last18=Sonyi | first18=Marc | last19=Sabo | first19=Cristina Maria | last20=Mendive | first20=Juan | last21=Nicolau | first21=Adrien | last22=Dolinsek | first22=Jernej | last23=Kyselova | first23=Denisa | last24=Laterza | first24=Lucrezia | last25=Gasbarrini | first25=Antonio | last26=Surdea-Blaga | first26=Teodora | last27=Fonseca | first27=Jorge | last28=Lionis | first28=Christos | last29=Corazza | first29=Gino Roberto | last30=Di Sabatino | first30=Antonio | title=European Consensus on Malabsorption—UEG & SIGE, LGA, SPG, SRGH, CGS, ESPCG, EAGEN, ESPEN, and ESPGHAN: Part 2: Screening, Special Populations, Nutritional Goals, Supportive Care, Primary Care Perspective | journal=United European Gastroenterology Journal | volume=13 | issue=5 | date=2025 | issn=2050-6406 | pmid=40088199 | pmc=12188380 | doi=10.1002/ueg2.70011 | doi-access=free | pages=773–797}}</ref>

===Extraintestinal manifestations=== [[File:Bone metabolism celiac disease.jpg|thumb|upright=1.2|Dysfunctional [[Bone remodeling|bone metabolism]] in coeliac disease|alt=A visual explaining the mechanisms for bone manifestations of coeliac disease]] 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.<ref name="consequences">{{Cite journal |last1=Laurikka |first1=Pilvi |last2=Kivelä |first2=Laura |last3=Kurppa |first3=Kalle |last4=Kaukinen |first4=Katri |date=July 2022 |title=Review article: Systemic consequences of coeliac disease |journal=Alimentary Pharmacology & Therapeutics |volume=56 |issue=S1 |pages=S64–S72 |doi=10.1111/apt.16912 |issn=0269-2813 |pmc=9543231 |pmid=35815828}}</ref> These manifestations may be related to malabsorption or systemic inflammation.<ref name="i778">{{cite journal | last1=Lazzano | first1=Pilar | last2=Fracas | first2=Elia | last3=Nandi | first3=Nicoletta | last4=Scaramella | first4=Lucia | last5=Elli | first5=Luca | title=Extraintestinal complications of celiac disease: treatment considerations | journal=Expert Review of Gastroenterology & Hepatology | volume=18 | issue=12 | date=2024 | issn=1747-4124 | doi=10.1080/17474124.2024.2443053 | pages=761–777 | pmid=39673511 | url=https://www.tandfonline.com/doi/full/10.1080/17474124.2024.2443053 | access-date=2025-12-13| url-access=subscription }}</ref> Common extraintestinal manifestations of coeliac disease include [[headache]]s, [[fatigue]], [[brain fog]], [[muscle pain]], and [[Arthralgia|joint pain]].<ref name="i778"/><ref name="r109">{{cite journal | last1=Therrien | first1=Amelie | last2=Kelly | first2=Ciaran P. | last3=Silvester | first3=Jocelyn A. | title=Celiac Disease: Extraintestinal Manifestations and Associated Conditions | journal=Journal of Clinical Gastroenterology | volume=54 | issue=1 | date=2020 | issn=0192-0790 | doi=10.1097/MCG.0000000000001267 | pages=8–21 | pmid=31513026 | pmc=6895422 }}</ref>

Nutritional status in coeliac disease may be compromised due to lower intake, maldigestion, and malabsorption, leading to [[Malnutrition|nutritional deficiencies]]. Common deficiencies in coeliac disease include [[Iron deficiency|iron]], [[Folate deficiency|folate]], [[Zinc deficiency|zinc]], [[Vitamin D deficiency|vitamin D]], and [[Vitamin B12 deficiency|vitamin B12]].<ref name="a113"/><ref name="r109"/> Vitamin D deficiency can cause [[secondary hyperparathyroidism]]. [[Hyperoxaluria]] and [[Kidney stone disease|kidney stones]] can be caused by malabsorption of fats, and [[peptide]]s.<ref name="r109"/> Iron deficiency may lead to [[anemia|anaemia]], which is one of the most common extraintestinal presentations of coeliac disease.<ref name="i778"/> Coeliac disease also often affects the bones, causing low [[Bone density|bone mass density]] ([[osteopenia]]) and [[osteoporosis]]. Causes of bone changes in coeliac disease are believed to be caused by malabsorption, inflammation, and [[autoimmunity]].<ref name="consequences"/>

If left untreated, coeliac disease can affect [[hormone]]s, causing [[Delayed menstruation|delayed periods]] or [[Delayed puberty|puberty]] and [[Reproductive system disease|reproductive disorders]].<ref name="a113"/><ref name="consequences"/> Coeliac disease is associated with [[infertility]] and complications during pregnancy such as [[Intrauterine growth restriction|intra-uterine growth restriction]] and [[spontaneous abortion]]. Reproductive disorders are thought to be caused by nutritional deficiencies, particularly zinc, iron, folate, and [[Selenium deficiency|selenium]] deficiencies in coeliac disease.<ref name="r109"/>

Coeliac disease often affects the liver, causing [[Elevated transaminases|increased transaminase levels]].<ref name="a113"/> This elevation of [[transaminase]]s 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 disease|autoimmune]] or viruses that could cause [[Liver disease|liver abnormalities]], characterise coeliac hepatitis.<ref name="i778"/><ref name="r109"/>

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.<ref name="i778"/> Some of these more uncommon manifestations include [[peripheral neuropathy]], [[epilepsy]], [[psoriasis]], [[recurrent aphthous stomatitis]], [[pericardial effusion]], and Lane-Hamilton syndrome.<ref name="r109"/>

==Causes== [[File:Pathogenesis of celiac disease.jpg|thumb|upright=1.3|Factors involved in the pathogenesis of coeliac disease|alt=A visual describing the factors involved in developing coeliac disease]]

Coeliac disease is caused by an [[Inflammation|inflammatory]] reaction to [[gliadin]]s and [[glutenin]]s (gluten proteins)<ref name="j116">{{cite journal | last1=Ahmadzadeh | first1=Alireza | last2=Rezaei-Tavirani | first2=Mostafa | title=Pathogenesis and genetics of celiac disease; a systematic review | journal=Egyptian Journal of Medical Human Genetics | volume=26 | issue=1 | date=2025-05-06 | issn=2090-2441 | doi=10.1186/s43042-025-00713-8 | doi-access=free | article-number=85 }}</ref> 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]] ([[oat]]s).<ref name="n430">{{cite journal | last1=Calado | first1=João | last2=Verdelho Machado | first2=Mariana | title=Celiac Disease Revisited | journal=GE - Portuguese Journal of Gastroenterology | volume=29 | issue=2 | date=2022 | issn=2341-4545 | pmid=35497669 | pmc=8995660 | doi=10.1159/000514716 | doi-access=free | pages=111–124 | url=https://www.karger.com/Article/Pdf/514716 | access-date=2025-08-20}}</ref> Wheat subspecies (such as [[spelt]], [[durum]], and [[khorasan wheat]]) and wheat hybrids (such as [[triticale]]) also cause symptoms of coeliac disease.<ref name="b300">{{cite book | last=Crespo-Escobar | first=Paula | title=Advances in Celiac Disease | chapter=Gluten Free Diet | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_9 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_9 | access-date=2025-12-07 | pages=121–136}}</ref>

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 [[cultivar]]s or dietary intolerance to oats.<ref name="o804">{{cite journal | last1=McDermid | first1=Joann M. | last2=Almond | first2=M. Angie | last3=Roberts | first3=Kristen M. | last4=Germer | first4=Emily M. | last5=Geller | first5=Marilyn G. | last6=Taylor | first6=Theresa A. | last7=Sinley | first7=Rachel C. | last8=Handu | first8=Deepa | title=Celiac Disease: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline | journal=Journal of the Academy of Nutrition and Dietetics | volume=123 | issue=12 | date=2023 | doi=10.1016/j.jand.2023.07.018 | pages=1793–1807.e4 | pmid=37499866 | url=https://linkinghub.elsevier.com/retrieve/pii/S2212267223012868 | access-date=2025-08-20| url-access=subscription }}</ref><ref name="m090">{{cite journal | last1=Kosová | first1=Klára | last2=Leišová-Svobodová | first2=Leona | last3=Dvořáček | first3=Václav | title=Oats as a Safe Alternative to Triticeae Cereals for People Suffering from Celiac Disease? A Review | journal=Plant Foods for Human Nutrition | volume=75 | issue=2 | date=2020 | issn=0921-9668 | doi=10.1007/s11130-020-00800-8 | pages=131–141 | pmid=32133597 | bibcode=2020PFHN...75..131K | url=http://link.springer.com/10.1007/s11130-020-00800-8 | access-date=2025-08-20| url-access=subscription }}</ref> Most people with coeliac disease do not have adverse reactions to uncontaminated or 'pure' oats, however [[Medical guideline|clinical guidelines]] differ on whether those with coeliac disease should consume oats.<ref name="n132">{{cite journal | last1=Lee | first1=Anne R. | last2=Dennis | first2=Melinda | last3=Lebovits | first3=Jessica | last4=Welstead | first4=Lori | last5=Verma | first5=Ritu | last6=Therrien | first6=Amelie | last7=Lebwohl | first7=Benjamin | title=Dietary assessments in individuals living with coeliac disease: key considerations | journal=Journal of Human Nutrition and Dietetics | volume=38 | issue=1 | date=2025 | issn=0952-3871 | pmid=39501424 | pmc=11589401 | doi=10.1111/jhn.13380 | doi-access=free | article-number=e13380 }}</ref><ref name="u195">{{cite journal | last1=Raiteri | first1=Alberto | last2=Granito | first2=Alessandro | last3=Giamperoli | first3=Alice | last4=Catenaro | first4=Teresa | last5=Negrini | first5=Giulia | last6=Tovoli | first6=Francesco | title=Current guidelines for the management of celiac disease: A systematic review with comparative analysis | journal=World Journal of Gastroenterology | volume=28 | issue=1 | date=2022-01-07 | issn=1007-9327 | pmid=35125825 | pmc=8793016 | doi=10.3748/wjg.v28.i1.154 | doi-access=free | pages=154–176}}</ref>

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.<ref name="e027">{{cite journal | last1=Demirkesen | first1=Ilkem | last2=Ozkaya | first2=Berrin | title=Recent strategies for tackling the problems in gluten-free diet and products | journal=Critical Reviews in Food Science and Nutrition | volume=62 | issue=3 | date=2022-01-25 | issn=1040-8398 | doi=10.1080/10408398.2020.1823814 | pages=571–597 | pmid=32981341 | url=https://www.tandfonline.com/doi/full/10.1080/10408398.2020.1823814 | access-date=2025-08-21| url-access=subscription }}</ref><ref name="l303">{{cite journal | last1=Luque | first1=Veronica | last2=Crespo-Escobar | first2=Paula | last3=Hård af Segerstad | first3=Elin M. | last4=Koltai | first4=Tunde | last5=Norsa | first5=Lorenzo | last6=Roman | first6=Enriqueta | last7=Vreugdenhil | first7=Anita | last8=Fueyo-Díaz | first8=Ricardo | last9=Ribes-Koninckx | first9=Carmen | title=Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease | journal=Journal of Pediatric Gastroenterology and Nutrition | volume=78 | issue=4 | date=2024 | issn=0277-2116 | doi=10.1002/jpn3.12079 | doi-access=free | pages=973–995 | pmid=38291739 }}</ref>

===Risk modifiers=== Environmental factors such as infections, geographic [[latitude]], birth weight, [[antibiotic]] use, [[gut microbiota|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.<ref name="f561">{{cite book | last1=Leffler | first1=Daniel A. | last2=Dennis | first2=Melinda | last3=Lebwohl | first3=Benjamin | title=Yamada's Textbook of Gastroenterology | chapter=Celiac disease | publisher=Wiley | date=2022-04-15 | isbn=978-1-119-60016-9 | doi=10.1002/9781119600206.ch56 | url=https://onlinelibrary.wiley.com/doi/10.1002/9781119600206.ch56 | access-date=2025-08-21 | pages=1122–1136}}</ref><ref name="j116"/><ref name="d428"/> 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.<ref name="z823">{{cite journal | last1=Szajewska | first1=Hania | last2=Shamir | first2=Raanan | last3=Stróżyk | first3=Agata | last4=Chmielewska | first4=Anna | last5=Zalewski | first5=Bartłomiej M. | last6=Auricchio | first6=Renata | last7=Koletzko | first7=Sibylle | last8=Korponay-Szabo | first8=Ilma R. | last9=Mearin | first9=M. Luisa | last10=Meijer | first10=Caroline | last11=Ribes-Koninckx | first11=Carmen | last12=Troncone | first12=Riccardo | author13=the PreventCD project group | title=Systematic review: early feeding practices and the risk of coeliac disease. A 2022 update and revision | journal=Alimentary Pharmacology & Therapeutics | volume=57 | issue=1 | date=2023 | issn=0269-2813 | doi=10.1111/apt.17290 | pages=8–22 | pmid=36411726 | hdl=1887/3576015 | url=https://onlinelibrary.wiley.com/doi/10.1111/apt.17290 | access-date=2025-08-21| hdl-access=free }}</ref><ref name="w859">{{cite book | last=Mearin | first=M. Luisa | title=Advances in Celiac Disease | chapter=Celiac Disease Prevention | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_11 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_11 | access-date=2025-08-21 | pages=153–159}}</ref>

==Mechanism== Coeliac disease appears to be multifactorial, both in that more than one genetic factor can cause the disease, and in that more than one factor is necessary for the disease to manifest in a person.<ref name="a020">{{cite journal | last1=Gnodi | first1=Elisa | last2=Meneveri | first2=Raffaella | last3=Barisani | first3=Donatella | title=Celiac disease: From genetics to epigenetics | journal=World Journal of Gastroenterology | volume=28 | issue=4 | date=2022-01-28 | issn=1007-9327 | pmid=35125829 | pmc=8790554 | doi=10.3748/wjg.v28.i4.449 | doi-access=free | pages=449–463}}</ref>

Almost all people with coeliac disease have either the [[HLA-DQ2]] variant ([[allele]]) or, less commonly, the [[HLA-DQ8]] allele.<ref name="s519">{{cite journal | last1=Catassi | first1=Carlo | last2=Verdu | first2=Elena F |last3=Bai | first3=Julio Cesar | last4=Lionetti | first4=Elena | title=Coeliac disease |journal=The Lancet | volume=399 | issue=10344 | date=2022 | doi=10.1016/S0140-6736(22)00794-2 |pages=2413–2426 | pmid=35691302 | url=https://linkinghub.elsevier.com/retrieve/pii/S0140673622007942 |access-date=2025-08-22| url-access=subscription }}</ref> However, about 40% of people without coeliac disease have also inherited either of these alleles.<ref name="h601">{{cite journal | last1=Galipeau | first1=Heather J. |last2=Hinterleitner | first2=Reinhard | last3=Leonard | first3=Maureen M. | last4=Caminero |first4=Alberto | title=Non-Host Factors Influencing Onset and Severity of Celiac Disease |journal=Gastroenterology | volume=167 | issue=1 | date=2024 | pmid=38286392 | pmc=11653303 | doi=10.1053/j.gastro.2024.01.030 | pages=34–50 }}</ref> This suggests that additional factors are needed for coeliac disease to develop; that is, the predisposing HLA risk allele is necessary but not sufficient to develop coeliac disease. Furthermore, a small percentage of those who do develop coeliac disease do not have typical HLA-DQ2 or HLA-DQ8 alleles.<ref name="s519"/><ref name="u789"/> [[File:HLA-DQ2 and HLA-DQ8 graphic.jpg|thumb|upright=1.3|[[Antigen-presenting cell]]s bind peptides and "present" them to [[T cell]]s, which detect HLA–peptide complexes through [[T-cell receptor]]s. In coeliac disease, T cells respond to gluten peptides bound to HLA-DQ2 or HLA-DQ8. Gluten-derived peptides (red diamond) bind only with low affinity to HLA-DQ2 and HLA-DQ8, but TG2 can modify such peptides, turning them into high-affinity binders. Consequently, the HLA–gluten peptide complexes are more stable, which facilitates and enhances T-cell responses.|alt=A visual graphic showing how peptides bind in coeliac disease and healthy individuals]]

===Genetics=== The vast majority of people with coeliac disease have one of two types (out of seven) of the [[HLA-DQ]] protein.<ref name="s519"/> HLA-DQ is part of the [[Major histocompatibility complex|MHC class II antigen-presenting receptor]]<ref name="y647">{{cite journal | last1=Choung | first1=Rok Seon | last2=Mills | first2=John R. | last3=Snyder | first3=Melissa R. | last4=Murray | first4=Joseph A. | last5=Gandhi | first5=Manish J. | title=Celiac disease risk stratification based on HLA-DQ heterodimer (HLA-DQA1 ~ DQB1) typing in a large cohort of adults with suspected celiac disease | journal=Human Immunology | volume=81 | issue=2–3 | date=2020 | doi=10.1016/j.humimm.2020.01.006 | pages=59–64 | pmid=32005535 | url=https://linkinghub.elsevier.com/retrieve/pii/S0198885919312996 | access-date=2025-08-22| url-access=subscription }}</ref> (also called the [[human leukocyte antigen]]) system and is used by the [[immune system]] to distinguish between the body's own cells and others.<ref name="t711">{{cite journal | last1=Apcher | first1=Sebastien | last2=Vojtesek | first2=Borek | last3=Fahraeus | first3=Robin | title=In search of the cell biology for self- versus non-self- recognition | journal=Current Opinion in Immunology | volume=83 | date=2023 | doi=10.1016/j.coi.2023.102334 | doi-access=free | article-number=102334 | pmid=37210933 }}</ref><ref name="f602">{{cite book | last1=Jin | first1=Hui | last2=Arase | first2=Hisashi | title=Basic Immunology and Its Clinical Application | chapter=Neoself Antigens Presented on MHC Class II Molecules in Autoimmune Diseases | series=Advances in Experimental Medicine and Biology | publisher=Springer Nature Singapore | publication-place=Singapore | volume=1444 | date=2024 | isbn=978-981-99-9780-0 | doi=10.1007/978-981-99-9781-7_4 | chapter-url=https://link.springer.com/10.1007/978-981-99-9781-7_4 | access-date=2025-09-07 | pages=51–65 | pmid=38467972 }}</ref> The two subunits of the HLA-DQ protein are encoded by the HLA-DQA1 and HLA-DQB1 genes, located on the short arm of [[chromosome 6]].<ref name="i415">{{cite book | last1=Núñez | first1=Concepción | last2=Rubio | first2=Mercedes | title=Advances in Celiac Disease | chapter=Value and Use of Genetic Test of Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_8 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_8 | access-date=2025-08-22 | pages=99–119}}</ref>

There are seven [[HLA-DQ]] variants (DQ2 and DQ4–DQ9). Over 95% of people with coeliac disease have the [[Protein isoform|isoform]] of DQ2 or DQ8, which is inherited in families. The reason these genes increase the 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. Therefore, these forms of the receptor are more likely to activate [[T cell|T lymphocytes]] and initiate the autoimmune process.<ref name="i415"/>

Most people with coeliac bear a two-gene HLA-DQ2 [[haplotype]] called [[HLA-DQ2#DQ2.5|DQ2.5]]. This haplotype is composed of two adjacent gene alleles, DQA1*0501 and [[HLA-DQ2#DQB1*0201|DQB1*0201]], which encode the two subunits, DQ α5 and DQ β2.<ref name="c506">{{cite journal | last1=Siddiqui | first1=Komal | last2=Uqaili | first2=Arsalan Ahmed | last3=Rafiq | first3=Muhammad | last4=Bhutto | first4=Muhammad Aqeel | title=Human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes in celiac, celiac with type 1 diabetic, and celiac suspected pediatric cases | journal=Medicine | volume=100 | issue=11 | date=2021-03-19 | issn=0025-7974 | doi=10.1097/MD.0000000000024954 | doi-access=free | article-number=e24954 | pmid=33725967 | pmc=7982179 }}</ref><ref name="f457">{{cite journal | last1=Tolone | first1=Carlo | last2=Piccirillo | first2=Marisa | last3=Dolce | first3=Pasquale | last4=Alfiero | first4=Salvatore | last5=Arenella | first5=Mattia | last6=Sarnataro | first6=Marina | last7=Iardino | first7=Patrizia | last8=Pucciarelli | first8=Alessia | last9=Strisciuglio | first9=Caterina | title=Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study | journal=Italian Journal of Pediatrics | volume=47 | issue=1 | date=2021 | issn=1824-7288 | pmid=33952340 | pmc=8097774 | doi=10.1186/s13052-021-01052-1 | doi-access=free | article-number=107 }}</ref> In most individuals, this DQ2.5 isoform is encoded by one of two chromosomes 6 inherited from parents (DQ2.5cis). Most coeliacs inherit only one copy of this DQ2.5 haplotype, while some inherit it from ''both'' parents; the latter are especially at risk of coeliac disease as well as being more susceptible to severe complications.<ref name="s600">{{cite journal | last1=Pritchard | first1=Deborah | last2=Anand | first2=Arthi | last3=De'Ath | first3=Amy | last4=Lee | first4=Helena | last5=Rees | first5=Margaret Tracey | title=UK NEQAS and BSHI guideline: Laboratory testing and clinical interpretation of HLA genotyping results supporting the diagnosis of coeliac disease | journal=International Journal of Immunogenetics | volume=51 | issue=S1 | date=2024 | issn=1744-3121 | doi=10.1111/iji.12649 | pages=3–20 | pmid=38153308 | doi-access=free }}</ref> The frequency of coeliac disease haplotypes can vary by geography.<ref name="a020"/><ref name="h824"/>

Some individuals inherit DQ2.5 from one parent and an additional portion of the haplotype (either DQB1*02 or DQA1*05) from the other parent, increasing risk. Less commonly, some individuals inherit the DQA1*05 allele from one parent and the DQB1*02 from the other parent (DQ2.5trans), and these individuals are at similar risk of coeliac disease as those with a single DQ2.5-bearing chromosome 6.<ref name="s600"/><ref name="i415"/> Among those with coeliac disease who do not have DQ2.5 (cis or trans) or DQ8 (encoded by the haplotype DQA1*03:DQB1*0302), 2-5% have the [[HLA-DQ2#DQ2.2 and gluten|DQ2.2]] isoform, and the remaining 2% lack DQ2 or DQ8.<ref name="s600"/>

Other genetic factors have been reported in coeliac disease, but involvement in the disease has variable geographic recognition. Only the HLA-DQ loci show a consistent involvement across the global population. Many of the detected loci are associated with other autoimmune diseases.<ref name="u789">{{cite journal | last1=Gaba | first1=Kajal | last2=Malhotra | first2=Parveen | last3=Kumar | first3=Anil | last4=Suneja | first4=Pooja | last5=Dang | first5=Amita Suneja | title=Understanding the Genetic Basis of Celiac Disease: A Comprehensive Review | journal=Cell Biochemistry and Biophysics | volume=82 | issue=3 | date=2024 | issn=1085-9195 | doi=10.1007/s12013-024-01371-0 | pages=1797–1808 | pmid=38907939 | url=https://link.springer.com/10.1007/s12013-024-01371-0 | access-date=2025-08-23| url-access=subscription }}</ref> The prevalence of the HLA-DQ2 genotype and gluten consumption has increased over time. Since untreated coeliac disease can cause serious health problems and affect fertility, it would be expected that HLA-DQ2 and HLA-DQ8 would become [[Negative selection (natural selection)|less common]]. The opposite is true—they are most common in areas where gluten-rich foods have been eaten for thousands of years.<ref name="j218">{{cite journal | last1=Makharia | first1=Govind K. | last2=Singh | first2=Prashant | last3=Catassi | first3=Carlo | last4=Sanders | first4=David S. | last5=Leffler | first5=Daniel | last6=Ali | first6=Raja Affendi Raja | last7=Bai | first7=Julio C. | title=The global burden of coeliac disease: opportunities and challenges | journal=Nature Reviews Gastroenterology & Hepatology | volume=19 | issue=5 | date=2022 | issn=1759-5045 | doi=10.1038/s41575-021-00552-z | pages=313–327 | pmid=34980921 | url=https://www.nature.com/articles/s41575-021-00552-z | access-date=2025-09-12| url-access=subscription }}</ref> The HLA-DQ2 gene may have been [[Positive Selection|genetically favoured]] in the past because it helps protect against [[tooth decay]].<ref name="h824">{{cite journal | last1=Del Pozzo | first1=Giovanna | last2=Farina | first2=Federica | last3=Picascia | first3=Stefania | last4=Laezza | first4=Mariavittoria | last5=Vitale | first5=Serena | last6=Gianfrani | first6=Carmen | title=HLA class II genes in precision-based care of childhood diseases: what we can learn from celiac disease | journal=Pediatric Research | volume=89 | issue=2 | date=2021 | issn=0031-3998 | doi=10.1038/s41390-020-01217-4 | doi-access=free | pages=307–312 | pmid=33122841 | url=https://www.nature.com/articles/s41390-020-01217-4.pdf | access-date=2025-09-12}}</ref><ref name="t139">{{cite book | last1=Espino | first1=Laura | last2=Núñez | first2=Concepción | title=International Review of Cell and Molecular Biology | chapter=The HLA complex and coeliac disease | publisher=Elsevier | volume=358 | date=2021 | isbn=978-0-323-85311-8 | doi=10.1016/bs.ircmb.2020.09.009 | url=https://linkinghub.elsevier.com/retrieve/pii/S1937644820301015 | access-date=2025-09-12 | pages=47–83 | pmid=33707057 }}</ref>

===Prolamins=== [[File:Transglutaminase 2.jpg|thumb|upright=1.4|Small-bowel mucosal TG2 (red)-specific IgA deposits (green). A) Positive staining (arrow) in the mucosal villous of a short-term treated coeliac disease patient (gluten-free diet for three years). B) Negative IgA deposits (arrow) in the small-bowel mucosa of a long-term treated coeliac disease patient (gluten-free diet for eight years). Co-localisation of IgA deposits with TG2 is shown in yellow.|alt=Biopsy of the intestines of someone with coeliac disease showing antibody deposits]] Most of the proteins in food responsible for the immune reaction in coeliac disease are [[prolamin]]s. These are storage proteins rich in [[proline]] (''prol-'') and [[glutamine]] (''-amin'') that dissolve in [[Alcohol (chemistry)|alcohols]] and are resistant to [[protease]]s and [[peptidase]]s of the gut.<ref name="v575">{{cite book | last1=Arranz | first1=Eduardo | last2=Garrote | first2=José A. | title=Advances in Celiac Disease | chapter=Immunopathogenesis of Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_4 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_4 | access-date=2025-08-23 | pages=35–49}}</ref> Prolamins are found in cereal grains with different grains having different but related prolamins: wheat (gliadin), barley ([[hordein]]), rye ([[secalin]]) and oats ([[avenin]]).<ref name="n430"/><ref name="s519"/>

===Tissue transglutaminase=== Tissue transglutaminase modifies gluten [[peptide]]s into a form that may stimulate the immune system more effectively.<ref name="v575"/> These peptides are modified by tTG in two ways, [[deamidation]] or [[transamidation]].<ref name="h206">{{cite journal | last1=Yao | first1=Zhouzhou | last2=Fan | first2=Yuhua | last3=Lin | first3=Lizhen | last4=Kellems | first4=Rodney E. | last5=Xia | first5=Yang | title=Tissue transglutaminase: a multifunctional and multisite regulator in health and disease | journal=Physiological Reviews | volume=104 | issue=1 | date=2024-01-01 | issn=0031-9333 | doi=10.1152/physrev.00003.2023 | pages=281–325 | pmid=37712623 | url=https://journals.physiology.org/doi/10.1152/physrev.00003.2023 | access-date=2025-08-24| url-access=subscription }}</ref> [[File:Mucosal celiac disease pathogenesis.jpg|thumb|upright=1.4|Schematic representation of intestinal mucosal events involved in coeliac disease pathogenesis|alt=Visual graphic describing the mechanisms of coeliac disease within the intestines]] Deamidation is the reaction by which a glutamate residue is formed by cleavage of the epsilon-amino group of a glutamine side chain.<ref name="r274">{{cite journal | last1=Amundsen | first1=Sunniva F. | last2=Stamnaes | first2=Jorunn | last3=du Pré | first3=Marie Fleur | last4=Sollid | first4=Ludvig M. | title=Transglutaminase 2 affinity and enzyme-substrate intermediate stability as determining factors for T-cell responses to gluten peptides in celiac disease | journal=European Journal of Immunology | volume=52 | issue=9 | date=2022 | issn=0014-2980 | pmid=35715890 | pmc=9545004 | doi=10.1002/eji.202249862 | doi-access=free | pages=1474–1481 | url=https://www.duo.uio.no/bitstream/10852/98229/1/Postnr%2b2058660_Amundsen%2bet%2bal_Eur%2bJ%2bImmunol%2b-%2b2022_Transglutaminase%2b2%2baffinity%2band%2benzyme%25E2%2580%2590substrate%2bintermediate%2bstability%2bas%2bdetermining.pdf | access-date=2025-08-24}}</ref> Transamidation is the [[cross-link]]ing of a glutamine residue from the gliadin peptide to a [[lysine]] residue of tTg in a reaction that is catalysed by the transglutaminase.<ref name="h206"/> Cross-linking may occur either within or outside the active site of the enzyme. The latter case yields a permanently [[Covalent bond|covalently]] linked complex between the gliadin and the tTg. This results in the formation of new epitopes believed to trigger the primary immune response of the autoantibodies against tTg.<ref name="s887">{{cite journal | last1=Lexhaller | first1=Barbara | last2=Ludwig | first2=Christina | last3=Scherf | first3=Katharina Anne | title=Identification of Isopeptides Between Human Tissue Transglutaminase and Wheat, Rye, and Barley Gluten Peptides | journal=Scientific Reports | volume=10 | issue=1 | date=2020-05-04 | issn=2045-2322 | pmid=32367038 | pmc=7198585 | doi=10.1038/s41598-020-64143-9 | doi-access=free | url=https://www.nature.com/articles/s41598-020-64143-9.pdf | access-date=2025-08-24 | article-number=7426 | bibcode=2020NatSR..10.7426L }}</ref>

Stored biopsies from people with suspected coeliac disease have revealed that [[autoantibody]] deposits in the [[wikt:subclinical|subclinical]] coeliacs are detected before clinical disease.<ref name="v575"/>

===Villous atrophy and malabsorption=== The inflammatory process, mediated by [[T cell]]s, 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 [[nutrient]]s from food.<ref name="u789"/><ref name="h601"/>

Alternative causes of this tissue damage have been proposed. They involve the release of [[interleukin 15]] and activation of the [[innate immune system]] by a shorter gluten peptide (p31–43/49).<ref name="v575"/>

==Diagnosis== The variety in symptoms, overlap with other disorders, and lack of awareness in medical professionals often complicate the [[diagnosis]] of coeliac disease by leading to a [[Diagnostic delay|delay in the diagnosis]].<ref name="v697">{{cite journal | last1=Shiha | first1=Mohamed G | last2=Sanders | first2=David S | title=What is new in the management of coeliac disease? | journal=European Journal of Internal Medicine | volume=134 | date=2025 | doi=10.1016/j.ejim.2025.01.028 | pages=1–8 | pmid=39894725 | url=https://linkinghub.elsevier.com/retrieve/pii/S095362052500038X | access-date=2025-08-29| url-access=subscription }}</ref><ref name="o776"/> A diagnosis may take more than a decade after symptoms develop, and most people with coeliac disease remain undiagnosed.<ref name="h248"/><ref name="d488">{{cite journal | last1=Dhar | first1=Jahnvi | last2=Samanta | first2=Jayanta | last3=Sharma | first3=Megha | last4=Kumar | first4=Sanjay | last5=Sinha | first5=Saroj Kant | last6=Kochhar | first6=Rakesh | title=Impact of delay in diagnosis in patients with celiac disease: A study of 570 patients at a tertiary care center | journal=Indian Journal of Gastroenterology | volume=41 | issue=1 | date=2022 | issn=0254-8860 | doi=10.1007/s12664-021-01214-3 | pages=30–36 | pmid=35064913 | url=https://link.springer.com/10.1007/s12664-021-01214-3 | access-date=2025-08-29| url-access=subscription }}</ref> Delays in diagnosis can reduce [[quality of life]], use more medical resources and increase risk of complications associated with the disease.<ref name="v697"/><ref name="q422">{{cite journal | last1=Kårhus | first1=Line Lund | last2=Hansen | first2=Susanne | last3=Rumessen | first3=Jüri J. | last4=Linneberg | first4=Allan | title=Diagnostic Delay in Coeliac Disease: A Survey among Danish Patients | journal=Canadian Journal of Gastroenterology and Hepatology | volume=2022 | date=2022-12-28 | issn=2291-2797 | pmid=36618766 | pmc=9812619 | doi=10.1155/2022/5997624 | doi-access=free | pages=1–7}}</ref><ref name="q309">{{cite journal | last=Tye-Din | first=Jason A | title=Evolution in coeliac disease diagnosis and management | journal=JGH Open | volume=8 | issue=7 | date=2024 | article-number=e13107 | issn=2397-9070 | pmid=38957478 | pmc=11217771 | doi=10.1002/jgh3.13107 | doi-access=free}}</ref>

Coeliac disease is diagnosed based on symptoms, blood tests, and [[biopsies]] of the small intestine.<ref name="v697"/> To make an accurate diagnosis, an individual must be consuming gluten, as the reliability of biopsies and blood tests reduces if a person is on a [[gluten-free diet]]. In those who have already reduced their gluten intake, reintroducing gluten ([[Gluten challenge test|gluten challenge]]) may be required to reach an accurate diagnosis.<ref name="r906">{{cite journal | last1=Shiha | first1=Mohamed G | last2=Hadjisavvas | first2=Nikolaos | last3=Sanders | first3=David S | last4=Penny | first4=Hugo A | title=Optimising the Diagnosis of Adult Coeliac Disease: Current Evidence and Future Directions | journal=British Journal of Hospital Medicine | date=2024-09-30 | volume=85 | issue=9 | issn=1750-8460 | doi=10.12968/hmed.2024.0362 | pages=1–21 | pmid=39347683 | doi-access=free }}</ref> Within months of eliminating gluten from one's diet, [[antibodies]] associated with coeliac disease decrease, meaning that gluten has to be reintroduced several weeks before diagnostic testing.<ref name="r906"/><ref name="m760">{{cite journal | last1=Elli | first1=Luca | last2=Leffler | first2=Daniel | last3=Cellier | first3=Christophe | last4=Lebwohl | first4=Benjamin | last5=Ciacci | first5=Carolina | last6=Schumann | first6=Michael | last7=Lundin | first7=Knut E. A. | last8=Chetcuti Zammit | first8=Stefania | last9=Sidhu | first9=Reena | last10=Roncoroni | first10=Leda | last11=Bai | first11=Julio C. | last12=Lee | first12=Anne R. | last13=Dennis | first13=Melinda | last14=Robert | first14=Marie E. | last15=Rostami | first15=Kamran | last16=Khater | first16=Sherine | last17=Comino | first17=Isabel | last18=Cebolla | first18=Angel | last19=Branchi | first19=Federica | last20=Verdu | first20=Elena F. | last21=Stefanolo | first21=Juan Pablo | last22=Wolf | first22=Randi | last23=Bergman-Golden | first23=Sheba | last24=Trott | first24=Nick | last25=Scudeller | first25=Luigia | last26=Zingone | first26=Fabiana | last27=Scaramella | first27=Lucia | last28=Sanders | first28=David S. | title=Guidelines for best practices in monitoring established coeliac disease in adult patients | journal=Nature Reviews Gastroenterology & Hepatology | volume=21 | issue=3 | date=2024 | issn=1759-5045 | doi=10.1038/s41575-023-00872-2 | doi-access=free | pages=198–215 | pmid=38110546 | url=https://www.nature.com/articles/s41575-023-00872-2.pdf | access-date=2025-08-29}}</ref>

===Blood tests=== [[File:ENDOMYSIAL ANTIBODIES.jpg|thumb|[[Immunofluorescence]] staining pattern of endomysial antibodies on a monkey oesophagus tissue sample|alt=Immunofluorescence stain of antibodies]] Current [[medical guideline]]s recommend testing tissue transglutaminase 2 [[immunoglobulin A]] (TTG IgA) in those with suspected coeliac disease.<ref name="t879">{{cite journal | last1=Husby | first1=Steffen | last2=Koletzko | first2=Sibylle | last3=Korponay-Szabó | first3=Ilma | last4=Kurppa | first4=Kalle | last5=Mearin | first5=Maria Luisa | last6=Ribes-Koninckx | first6=Carmen | last7=Shamir | first7=Raanan | last8=Troncone | first8=Riccardo | last9=Auricchio | first9=Renata | last10=Castillejo | first10=Gemma | last11=Christensen | first11=Robin | last12=Dolinsek | first12=Jernej | last13=Gillett | first13=Peter | last14=Hróbjartsson | first14=Asbjørn | last15=Koltai | first15=Tunde | last16=Maki | first16=Markku | last17=Nielsen | first17=Sabrina Mai | last18=Popp | first18=Alina | last19=Størdal | first19=Ketil | last20=Werkstetter | first20=Katharina | last21=Wessels | first21=Margreet | title=European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020 | journal=Journal of Pediatric Gastroenterology and Nutrition | volume=70 | issue=1 | date=2020 | issn=0277-2116 | doi=10.1097/MPG.0000000000002497 | doi-access=free | pages=141–156 | pmid=31568151 | hdl=1887/3184859 | hdl-access=free }}</ref><ref name="j161">{{cite journal | last1=Rubio-Tapia | first1=Alberto | last2=Hill | first2=Ivor D. | last3=Semrad | first3=Carol | last4=Kelly | first4=Ciarán P. | last5=Greer | first5=Katarina B. | last6=Limketkai | first6=Berkeley N. | last7=Lebwohl | first7=Benjamin | title=American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease | journal=American Journal of Gastroenterology | volume=118 | issue=1 | date=2023 | issn=0002-9270 | doi=10.14309/ajg.0000000000002075 | doi-access=free | pages=59–76 | pmid=36602836 }}</ref> Because [[Selective immunoglobulin A deficiency|IgA deficiency]] is more common in those with coeliac disease,<ref name="n382">{{cite book | last1=Ribes-Koninckx | first1=C. | last2=Roca | first2=M. | last3=Donat | first3=E. | title=Advances in Celiac Disease | chapter=Value and Use of Serologic Markers of Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_6 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_6 | access-date=2025-08-30 | pages=63–78}}</ref> guidelines recommend testing for IgA deficiency as a part of the diagnostic workup for coeliac disease. If an individual with IgA deficiency is getting tested for coeliac disease, [[immunoglobulin G]] (IgG) based tests such as deamidated gliadin peptide IgG (DGP IgG) or [[Anti-transglutaminase antibodies|endomysial antibody]] (EMA) can be used instead of IgA-based tests.<ref name="t879"/><ref name="j161"/> [[Anti-gliadin antibodies|Antigliadin antibodies]] (AGA) and antireticulin antibodies (ARA) were historically used to test for coeliac disease; however, due to the development of more accurate tests, they are no longer recommended.<ref name="f561"/><ref name="n382"/> Due to the risk of [[False positives and false negatives|false positive or negative]] serological tests and the consequences of leaving coeliac disease untreated or introducing unnecessary dietary restrictions. In the case of a false positive, biopsies are used to confirm the diagnosis regardless of blood test results.<ref name="f561"/><ref name="j161"/>

TG2 IgA has a high [[Sensitivity and specificity|sensitivity]] (92.8%) and specificity (97.9%), and is cost-efficient and widely available, making it the first choice for serological tests in the diagnosis of coeliac disease.<ref name="h960">{{cite journal | last=Anderson | first=Robert P. | title=Review article: Diagnosis of coeliac disease: a perspective on current and future approaches | journal=Alimentary Pharmacology & Therapeutics | volume=56 | issue=S1 | date=2022 | pages=S18–S37 | issn=0269-2813 | doi=10.1111/apt.16840 | url=https://onlinelibrary.wiley.com/doi/10.1111/apt.16840 | access-date=2025-08-30 | pmid=35815826 | url-access=subscription }}</ref><ref name="r906"/> Performance of the TG2 IgA test differs between labs and no formal standardisation between assays exists.<ref name="o776"/> The severity of small intestine damage generally correlates with the levels of TG2 IgA found in the blood, meaning that the sensitivity is lower in people who have less damage to their intestines.<ref name="h960"/><ref name="n382"/> EMA has a lower sensitivity, but its specificity is near 100%;<ref name="h960"/> it can be used to confirm coeliac disease in those who have borderline TG2 IgA levels.<ref name="r906"/> EMA testing is costly, hard to interpret, and vulnerable to [[Inter-observer reliability|inter-observer]] and inter-site variability.<ref name="o776"/><ref name="i273">{{cite journal | last1=Shiha | first1=Mohamed G. | last2=Chetcuti Zammit | first2=Stefania | last3=Elli | first3=Luca | last4=Sanders | first4=David S. | last5=Sidhu | first5=Reena | title=Updates in the diagnosis and management of coeliac disease | journal=Best Practice & Research Clinical Gastroenterology | volume=64-65 | date=2023 | doi=10.1016/j.bpg.2023.101843 | article-number=101843 | pmid=37652646 | url=https://linkinghub.elsevier.com/retrieve/pii/S1521691823000239 | access-date=2025-08-31| url-access=subscription }}</ref> DGP IgG is used to evaluate coeliac disease in those with IgA deficiency. Coeliac disease is more common in those with IgA deficiency, so medical guidelines recommend that people being tested for coeliac disease are also tested for IgA deficiency. Because IgA-based tests are unreliable in those with IgA deficiency, IgG-based tests are used instead. These include EMA IgG, DGP IgG, and TTG IgA, which are less accurate than IgA testing.<ref name="n382"/><ref name="g555">{{cite journal | last1=Di Tola | first1=Marco | last2=Bizzaro | first2=Nicola | last3=Gaudio | first3=Mariarosa | last4=Maida | first4=Carlotta | last5=Villalta | first5=Danilo | last6=Alessio | first6=Maria Grazia | last7=Previtali | first7=Giulia | last8=Fabris | first8=Martina | last9=Deleonardi | first9=Gaia | last10=Tampoia | first10=Marilina | last11=Brusca | first11=Ignazio | last12=Pesce | first12=Giampaola | last13=Porcelli | first13=Brunetta | last14=Manfredi | first14=Mariangela | last15=Infantino | first15=Maria | author16=On behalf of the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine | title=Diagnosing and Monitoring Celiac Patients with Selective IgA Deficiency: Still an Open Issue | journal=Digestive Diseases and Sciences | volume=66 | issue=10 | date=2021 | issn=0163-2116 | doi=10.1007/s10620-021-07204-x | pages=3234–3241 | pmid=34383199 | url=https://link.springer.com/10.1007/s10620-021-07204-x | access-date=2025-08-31| url-access=subscription }}</ref> Multiparametric serological assays allowing simultaneous detection of TG2 IgA and total IgA have been proposed to improve screening efficiency for coeliac disease. A study evaluating the Polycheck ® Celiac IgA + total IgA test reported high sensitivity and specificity for TG2 IgA and total IgA measurements in coeliac disease diagnostics. <ref>{{Cite journal |last1=Majsiak |first1=Emilia |last2=Cukrowska |first2=Bożena |last3=Choina |first3=Magdalena |last4=Bielawski |first4=Kornel |last5=Cielecka-Kuszyk |first5=Joanna |last6=Konopka |first6=Ewa |last7=Wysokiński |first7=Mariusz |last8=Bierła |first8=Joanna Beata |date=2022-12-31 |title=Evaluation of the Usefulness of a Serological Test for Diagnosis of Celiac Disease Simultaneously Detecting Specific Antibodies and Total IgA |journal=Nutrients |language=en |volume=15 |issue=1 |pages=202 |doi=10.3390/nu15010202 |doi-access=free |issn=2072-6643 |pmc=9823504 |pmid=36615859}}</ref>

A 2020 guideline by the [[European Society for Paediatric Gastroenterology, Hepatology & Nutrition|European Society of Paediatric Gastroenterology]], Hepatology, and Nutrition (ESPGHAN) suggests biopsy can be avoided in children who have symptoms of coeliac disease, TTG IgA levels ten times higher than normal, and a positive EMA antibody. There is insufficient evidence to suggest that a nonbiopsy approach can be used in adults.<ref name="j161"/> Genetic testing is not needed to diagnose coeliac disease, but is sometimes used to clarify discrepancies between blood tests and histology. In those who have already started a gluten-free diet, HLA testing can help to determine whether a gluten challenge should be performed.<ref name="j161"/>

===Endoscopy=== [[File:Celiac endo.JPG|thumb|[[Endoscopy|Endoscopic]] still of [[duodenum]] of a person with coeliac disease showing scalloping of folds and "cracked-mud" appearance to mucosa|alt=Endoscopic image of the intestines of an individual with coeliac disease]] An [[esophagogastroduodenoscopy|upper endoscopy]] with [[biopsy]] of the [[duodenum]] (beyond the [[duodenal bulb]]) or [[jejunum]] is performed to obtain multiple samples from the duodenum.<ref name="j161"/> Not all areas may be equally affected; if biopsies are taken from healthy bowel tissue, the result would be a false negative. Even in the same bioptic fragment, different degrees of damage may be present.<ref name="r906"/>

Most people with coeliac disease have a small intestine that appears to be normal on endoscopy before the biopsies are examined.<ref name="c132">{{cite book | last=Yoon | first=Soon Man | title=Small Intestine Disease | chapter=Celiac Disease | publisher=Springer Singapore | publication-place=Singapore | date=2022 | isbn=978-981-16-7238-5 | doi=10.1007/978-981-16-7239-2_51 | chapter-url=https://link.springer.com/10.1007/978-981-16-7239-2_51 | access-date=2025-11-15 | pages=265–267}}</ref> Endoscopic features of coeliac disease include scalloping of the small bowel folds (''pictured''), fissures, a [[mosaic]] pattern to the [[mucous membrane|mucosa]], prominence of the [[submucosa]] blood vessels, and a nodular pattern to the mucosa.<ref name="n430"/>

[[Capsule endoscopy]] (CE) allows identification of typical mucosal changes observed in coeliac disease and may be used as an alternative to endoscopy in those who cannot or do not want one.<ref name="f561"/>

===Pathology=== [[File:Villous atrophy duodenum.jpg|thumb|Histology of biopsy from the second part of the duodenum, showing villous atrophy|alt=Image showing histology results from a biopsy taken from a person with coeliac disease]] The Marsh-Oberhuber classification is commonly used to assess the [[Pathology|pathological]] changes seen in coeliac disease.<ref name="d428"/> [[Michael Newton Marsh|Marsh]] originally described three different stages of coeliac disease lesions in 1992. These three stages were updated in 1999 by Oberhuber to classify stage three further.<ref name="o371"/><ref name="u896">{{cite journal | last1=Butterworth | first1=Jeffrey | last2=Los | first2=Louis | title=Coeliac disease | journal=Medicine | volume=52 | issue=3 | date=2024 | doi=10.1016/j.mpmed.2023.12.003 | pages=174–180 | url=https://linkinghub.elsevier.com/retrieve/pii/S1357303923002888 | access-date=2025-09-14| url-access=subscription }}</ref> The Marsh classification is based on three [[Histology|histological]] features: [[intraepithelial lymphocyte]]s count above 25/100 enterocytes (intraepithelial lymphocytosis), elongated [[crypts of Lieberkuhn]] (crypt hyperplasia), and shortening or absence of villi (villous atrophy). As these features can be seen in other disorders, they are not diagnostic for coeliac disease without serological or clinical indications.<ref name="o371"/> Current guidelines do not recommend a repeat biopsy unless there is no improvement in the symptoms on a gluten-free diet <ref name="m760"/>

{| class="wikitable" |+ Marsh classification<ref name="o371">{{cite book |last1=Vincenzo |first1=Villanacci |chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_7 |title=Advances in Celiac Disease |last2=Gloria |first2=Simoncelli |last3=Melissa |first3=Monica |last4=Alessandro |first4=Caputo |last5=Rachele |first5=Del Sordo |date=2022 |publisher=Springer International Publishing |isbn=978-3-030-82400-6 |publication-place=Cham |pages=79–97 |chapter=Histopathological Assessment of Celiac Disease |doi=10.1007/978-3-030-82401-3_7 |access-date=2025-09-14}}</ref><ref name="d428"/> |- ! Type !! Increased intraepithelial lymphocytes !! Crypt hyperplasia !! Villi |- |0 (normal) |<40 lymphocytes/100 enterocytes | rowspan="2" |Normal | rowspan="3" |Normal |- | 1 (infiltrative) || rowspan="5" | >40 lymphocytes/100 enterocytes |- | 2 (hyperplastic) || rowspan="4" | Increased |- | 3a (destructive) || Mild atrophy |- | 3b (destructive) || Moderate atrophy |- | 3c (destructive) || Complete atrophy |}

===Gluten challenge=== A gluten challenge is no longer required to confirm the diagnosis in patients with intestinal lesions compatible with coeliac disease and a positive response to a gluten-free diet. A gluten challenge involves consuming over 10 grams of gluten a day for three months or until an individual tests positive for TG2 IgA.<ref name="h960"/> Nevertheless, in some cases, a gluten challenge with a subsequent biopsy may be useful to support the diagnosis, for example, in people with positive HLA genetic testing who have negative blood antibodies and are already on a gluten-free diet.<ref name="f561"/> Gluten challenge is discouraged before the age of 6 years and during [[puberty|pubertal]] growth.<ref name="h960"/>

===Differential diagnosis=== The histopathological features associated with coeliac disease can arise from other conditions as well.<ref name="i273"/> Differential diagnosis of negative coeliac blood tests and villous atrophy or increased inter-epithelial lymphocytes includes [[tropical sprue]], [[eosinophilic gastroenteritis]], lactose intolerance, lymphoma, [[Crohn's disease]], [[Helicobacter pylori]], drug-induced enteropathy ([[azathioprine]], [[methotrexate]], [[mycophenolate]], [[olmesartan]], [[colchicine]]non, [[Nonsteroidal anti-inflammatory drug|non-steroidal anti-inflammatory drugs]], and [[Proton-pump inhibitor|proton pump inhibitors]]), [[Whipple's disease]], [[giardiasis]], [[Radiation enteropathy|radiation enteritis]], [[tuberculosis]], [[Zollinger–Ellison syndrome]], [[Collagenous spherulosis|collagenous sprue]], [[common variable immunodeficiency]], [[autoimmune enteropathy]], [[HIV]] enteropathy, [[small intestinal bacterial overgrowth]], and [[gastrinoma]] with acid hypersecretion.<ref name="c132"/><ref name="n430"/><ref name="u896"/><ref name="i273"/> If the histological changes improve with a gluten-free diet despite negative coeliac disease blood tests, a diagnosis of seronegative coeliac disease may be made.<ref name="n430"/>

Positive blood tests for coeliac disease with a lack of changes in the bowels can be caused by errors in collecting blood for the test, recent infections, [[congestive heart failure]], [[chronic liver disease]], and [[hypergammaglobulinemia]]. Potential coeliac disease, formerly known as "latent coeliac disease", is diagnosed when there are positive coeliac blood tests, positive HLA genetic testing, and a lack of villous atrophy.<ref name="i273"/><ref name="f561"/>

[[Non-celiac gluten sensitivity]] (NCGS) is a [[functional disorder]] that causes intestinal and extraintestinal symptoms in response to gluten. The symptoms of NCGS are often similar to those seen in coeliac disease; they tend to have a more rapid onset and offset when compared to coeliac disease. The diagnosis of NCGS is made by excluding coeliac disease and wheat allergy, and a resolution of symptoms after adhering to a gluten-free diet.<ref name="u896"/><ref name="n430"/>

==Screening== There is debate as to the benefits of widespread [[Screening (medicine)|screening]] measures for coeliac disease.<ref name="q309"/> In 2017, the [[United States Preventive Services Task Force]] published a report which found insufficient evidence to make a recommendation regarding screening for coeliac disease in those without symptoms.<ref name=USPSTF2017>{{cite journal |vauthors=Bibbins-Domingo K, Grossman DC, Curry SJ, Barry MJ, Davidson KW, Doubeni CA, Ebell M, Epling JW, Herzstein J, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW |title=Screening for Celiac Disease: US Preventive Services Task Force Recommendation Statement |journal=JAMA |volume=317 |issue=12 |pages=1252–1257 |date=March 2017 |pmid=28350936 |doi=10.1001/jama.2017.1462 |url=https://escholarship.org/uc/item/8zp7n5t2 }}</ref> Due to the lack of evidence that screening for coeliac disease in those without symptoms, clinical guidelines advise testing people based on symptoms and selective screening for certain populations at a higher risk of developing coeliac disease.<ref name="r906"/><ref name="f561"/>

{| class="wikitable" |+ [[National Institute for Health and Clinical Excellence]] (NICE) indications of testing for coeliac disease<ref name="v697" /><ref name="r906" /> |- ! Testing recommended !! Testing considered |- | * Persistent unexplained gastrointestinal symptoms * Faltering growth * Chronic fatigue * Severe or persistent [[mouth ulcer]]s * Unexplained iron, vitamin B12, or folate deficiency * At the diagnosis of type 1 diabetes * At the diagnosis of an autoimmune thyroid disease * Irritable bowel syndrome in adults * First-degree relative of those with coeliac disease || * [[Metabolic bone disease]] (reduced [[bone mineral density]] or [[osteomalacia]]) * Unexplained neurological symptoms (such as [[peripheral neuropathy]] and [[ataxia]]) * Fertility problems or recurrent [[miscarriage]] * Persistently raised [[liver enzymes]] with unknown cause * [[Tooth enamel|Dental enamel]] defects * [[Down syndrome]] * [[Turner syndrome]] |}

==Management== Currently, the only treatment for coeliac disease is a lifelong [[gluten-free diet]] (GFD). Current guidelines recommend regular follow-up doctor's appointments, monitoring the disease activity, [[preventative care]], and consultation with a [[dietitian]].<ref name="v697"/>

===Diet=== {{Main|Gluten-free diet}} A GFD involves removing all food and drink that contains wheat, rye, barley, and gluten derivatives.<ref name="s787"/> Coeliac disease symptoms can improve within days of adopting a GFD, and the diet improves [[quality of life]], prevents further complications, and can normalise some effects of the disease such as stunted growth.<ref name="j161"/>

The GFD can be difficult, requiring significant education and motivation. Additionally, the GFD diet may lead to nutritional deficiencies due to difficulties accessing nutritionally balanced gluten-free food.<ref name="f561"/> As such, a referral to a dietitian is recommended by treatment guidelines.<ref name="j161"/> A dietitian can help those with coeliac disease identify gluten-containing food and maintain a nutritionally balanced diet.<ref name="f561"/>

The exact amount of gluten that may be tolerable for those with coeliac disease varies, with some people able to consume around 35 mg per day without damage to the intestines, while others can not tolerate more than 10 mg a day. Currently, international regulatory agencies require a product to contain less than 20 ppm (about 6 mg per day) of gluten to be labelled as gluten-free.<ref name="s787"/><ref name="n430"/>

===Monitoring=== Long-term monitoring of those with coeliac disease is an important aspect of managing the disease. Usually, someone newly diagnosed with coeliac disease is advised to visit their doctor multiple times a year, with follow-ups becoming less frequent (once or twice a year) after initial diagnosis. After the diagnosis, follow-up doctor's appointments focus on controlling symptoms, improving compliance with the GFD, preventative care, monitoring for [[comorbidity|comorbid]] diseases, and detection of complications.<ref name="j161"/> The exact testing done depends on an individual's needs but may include a [[complete blood count]], [[Iron tests|iron panel]], [[Thyroid function tests|thyroid testing]], [[Liver function tests|liver enzymes]], and [[Calcifediol|vitamin D levels]]. Due to [[osteoporosis]] being a common complication of coeliac disease, bone mineral density may be tested with a [[Dual-energy X-ray absorptiometry|DEXA scan]].<ref name="f561"/>

Although negative anti-TG2 IgA tests do not always correlate with adherence to a GFD, guidelines recommend routine testing for anti-TG2 IgA, as positive values may indicate gluten intake.<ref name="m760"/> The role of repeat biopsies is controversial, with studies finding little evidence that it is beneficial outside of investigating persistent symptoms<ref name="m760"/><ref name="f561"/><ref name="j161"/>

Alongside [[Vaccination schedule|routine vaccinations]], current guidelines recommend [[Pneumococcal vaccine|pneumococcal vaccination]] due to increased risk of [[pneumonia]] in coeliac disease.<ref name="v697"/><ref name="s787">{{cite journal | last1=Blom | first1=Jedid-Jah | last2=Gidrewicz | first2=Dominica | last3=Turner | first3=Justine | last4=Duerksen | first4=Donald R. | last5=Pinto-Sánchez | first5=M. Ines | title=Diagnosis and management of celiac disease | journal=Canadian Medical Association Journal | volume=197 | issue=38 | date=2025-11-11 | issn=0820-3946 | pmid=41218835 | pmc=12594544 | doi=10.1503/cmaj.230091 | pages=E1258–E1265 }}</ref>

==Non-responsive coeliac disease== [[File:Non-responsive coeliac disease.jpg|thumb|upright=1.4|Approach to investigating non-responsive coeliac disease|alt=Visual graphic showing the steps taken to diagnose non-responsive coeliac disease]] Around 20–40% of those with coeliac disease experience non-responsive coeliac disease (NRCD), which is the continuation of symptoms despite elimination of gluten from their diets for at least 6 to 12 months.<ref name="s787"/><ref name="f561"/>

The most common cause of NRCD is unintentional gluten ingestion; however other conditions such as [[small intestinal bacterial overgrowth]], [[giardiasis]], [[disaccharide]] or [[FODMAP]] intolerance, Crohn's disease, [[Fructose malabsorption|fructose intolerance]], [[microscopic colitis]], [[Exocrine pancreatic insufficiency|pancreatic insufficiency]], irritable bowel syndrome, and [[lactose intolerance]] can cause persistent symptoms or villous atrophy despite adhering to the GFD.<ref name="s787"/><ref name="f561"/>

===Refractory coeliac disease=== About 1.5% of those with coeliac disease develop refractory coeliac disease (RCD), which is the persistence of symptoms of malabsorption and villous atrophy despite at least one year of the GFD.<ref name="d428"/><ref name="n430"/> RCD has a high [[Mortality rate|mortality]] and morbidity rate, is associated with more severe symptoms and is more common in older individuals (50<).<ref name="i273"/> Those with RCD are often referred to specialists and the diagnostic process usually includes monitoring compliance with the GFD, confirming the initial diagnoses of coeliac disease, and excluding alternative explanations for small intestine damage such as Crohn's disease, peptic [[duodenitis]], small intestinal bacterial overgrowth, [[hypogammaglobulinemia]], common variable immunodeficiency, autoimmune enteropathy, tropical sprue, collagenous sprue, and eosinophilic [[enteritis]].<ref name="i273"/><ref name="f561"/>

There are two subtypes of RCD, type 1 and type 2. Biopsies of the duodenum and [[Immunochemistry|analysis]] of the intraepithelial lymphocytes in the duodenum are required to distinguish between the two types.<ref name="i273"/><ref name="d428"/> Type 2 RCD is characterised by abnormal T cells in the small intestine; these findings are absent in type 1 RCD.<ref name="f561"/> In type 2 RCD, healthy [[lymphocyte]]s are replaced by abnormal lymphocytes, increasing the risk of complications such as [[enteropathy-associated T-cell lymphoma]] (EATL), severe malabsorption, and ulcerative jejunoileitis, and results in poorer outcomes.<ref name="i273"/><ref name="f561"/>

Type 1 RCD is treated with [[steroid]]s, [[azathioprine]], and [[budesonide]]. The treatment of type 2 RCD is more complicated as it often does not improve with steroids, and azathioprine may increase the risk of EATL. Proposed treatment of type 2 RCD includes [[cladribine]], [[cyclosporine]], and [[stem cell transplant]]s.<ref name="n430"/><ref name="d428"/>

==Outlook== Individuals with coeliac disease have a higher risk of developing [[cancer]] in certain parts of the gastrointestinal tract ([[Oropharyngeal cancer|oropharynx]], [[Esophageal cancer|oesophagus]], and [[Small intestine cancer|small intestine]]) compared to those without the disease. Small intestinal [[lymphoma]] is the most common cancer caused by complications of coeliac disease; however, it is still considered a rare complication.<ref name="f561"/><ref name="s787"/> The prognosis for [[Enteropathy-associated T-cell lymphoma|enteropathy‐associated T‐cell lymphoma]] (EATL) is poor with low survival rates.<ref name="n430"/><ref name="f561"/> Risk factors for developing cancer among those with coeliac disease include older age and refractory coeliac disease.<ref name="s787"/> Coeliac disease also increases [[Mortality rate|mortality]] risk; however, the extent of the increase is inconsistent across research.<ref name="f561"/><ref name="n430"/>

==Epidemiology== In most countries, between 1 in 50 and 1 in 200 people have coeliac disease.<ref name=Catassi2022>{{cite journal|title=Coeliac disease |vauthors=Catassi C, Verdu EF, Boi C, Lionetti E |journal=Lancet |date=2022 |volume=399 |issue=10344 |pages=2413–2426 |doi=10.1016/S0140-6736(22)00794-2 |pmid=35691302}}</ref> [[Prevalence|Rates]] vary in different regions of the world; coeliac disease is less common in places where gluten-containing crops are rarely eaten, and in parts of east Asia and sub-Saharan Africa where populations rarely carry the HLA-DQ genes that predispose to the disease.<ref name=Catassi2022/> The risk of developing coeliac disease is higher in those who have a first-degree relative with the disease; a less dramatic increase in risk is also seen in second-degree relatives.<ref name="u068">{{cite book | last1=Rajput | first1=Mahendra Singh | last2=Chauhan | first2=Ashish | last3=Makharia | first3=Govind K. | title=Advances in Celiac Disease | chapter=Epidemiology of Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_2 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_2 | access-date=2025-11-03 | page=7–22}}</ref>

Diagnoses of coeliac disease have increased dramatically in recent decades due to increased awareness of the disease and the availability of blood testing. However, the disease is still thought to be underdiagnosed, with an estimated 70% of people with coeliac disease undiagnosed and untreated. Undiagnosed cases are more common in poorer areas and in countries that do not regularly test at-risk people.<ref name=Catassi2022/>

While coeliac disease can arise at any age, most people develop the disease before age 10.<ref name=Lebwohl2021>{{cite journal |vauthors=Lebwohl B, Rubio-Tapia A |title=Epidemiology, Presentation, and Diagnosis of Celiac Disease |journal=Gastroenterology |volume=160 |issue=1 |pages=63–75 |date=January 2021 |pmid=32950520 |doi=10.1053/j.gastro.2020.06.098 |url=}}</ref> Roughly 20 percent of individuals with coeliac disease are diagnosed after 60 years of age.<ref name="j472">{{cite journal | last1=Ching | first1=Charlotte K. | last2=Lebwohl | first2=Benjamin | title=Celiac Disease in the Elderly | journal=Current Treatment Options in Gastroenterology | volume=20 | issue=3 | date=2022-08-05 | issn=1534-309X | pmid=36818495 | pmc=9937540 | doi=10.1007/s11938-022-00397-8 | doi-access=free | pages=238–249 }}</ref> Coeliac disease is slightly more common in women than in men, though some of that may be due to differences in diagnostic practice, as men with gastrointestinal symptoms are less likely to receive a biopsy than women.<ref name=Lebwohl2021/> Other populations at increased risk for coeliac disease, include individuals with [[Down syndrome|Down]] and [[Turner syndrome]]s, [[type 1 diabetes]], and autoimmune thyroid disease, including both [[hyperthyroidism]] (overactive [[thyroid]]) and [[hypothyroidism]] (underactive thyroid).<ref name="u896"/>

==History== ===Etymology and early history=== The term ''coeliac'' comes from Greek {{lang|el|κοιλιακός}} ({{Transliteration|engvar=gb|el|koiliakós}}) '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]].<ref name="Aretaeus">{{Cite book |author=Aretaeus, the Cappadocian |author-link=Aretaeus of Cappadocia |translator=Francis Adams |translator-link=Francis Adams (translator) |title=The extant works of Aretaeus, The Cappadocian |url=https://books.google.com/books?id=v4gIAAAAIAAJ&pg=PT1 |chapter=On The Cœliac Affection |pages=350–351|chapter-url=https://books.google.com/books?id=v4gIAAAAIAAJ&pg=PA350 |access-date=12 December 2009 |year=1856 |publisher=Sydenham Society |location=London}}</ref><ref name="Losowsky">{{cite journal |vauthors=Losowsky MS |title=A history of coeliac disease |journal=Digestive Diseases |volume=26 |issue=2 |pages=112–120 |year=2008 |pmid=18431060 |doi=10.1159/000116768}}</ref>

Humans first cultivated grains in the [[Neolithic]] period (beginning about 9500 BCE) in the [[Fertile Crescent]] in Western Asia; coeliac disease likely did not occur before this time.<ref name="n993">{{cite journal | last=Freeman | first=Hugh J. | title=Celiac Disease: A Disorder Emerging from Antiquity, Its Evolving Classification and Risk, and Potential New Treatment Paradigms | journal=Gut and Liver | volume=9 | issue=1 | date=2015-01-15 | issn=1976-2283 | pmid=25547088 | pmc=4282854 | doi=10.5009/gnl14288 | doi-access=free | pages=28–37}}</ref> Aretaeus of Cappadocia, living in the 2nd century in the same area, recorded a malabsorptive syndrome with chronic diarrhoea, causing a debilitation of the whole body.<ref name="Aretaeus"/> A 15th-century medical prescription from [[Mamluk Sultanate|Mamluk]] Cairo, attributed to Shams al-Din ibn al-'Afif, the personal physician to Sultan [[Barsbay]] and director of the [[Qalawun complex]] hospital, describes a treatment for symptoms consistent with coeliac disease. The remedy combines herbs and plant waters for patients intolerant to wheat.<ref>{{Cite web |last=Sayour |first=Salah |title=Medical prescription in Discover Islamic Art, Museum With No Frontiers, 2025. |url=https://islamicart.museumwnf.org/database_item.php?id=object;ISL;eg;Mus01;16;en |access-date=21 April 2025 |website=islamicart.museumwnf.org}}</ref>

===Post-1800s=== Aretaeus of Cappadocia's "Cœliac Affection" gained the attention of Western medicine when [[Francis Adams (translator)|Francis Adams]] presented a translation of Aretaeus's work at the [[Sydenham Society]] in 1856. The patient described in Aretaeus's work had stomach pain and was atrophied, pale, feeble, and incapable of work. The diarrhoea manifested as loose stools that were white, malodorous, and flatulent, and the disease was intractable and liable to periodic return. Aretaeus believed a lack of heat in the stomach, necessary for digestion, and a reduced ability to distribute the digestive products throughout the body, caused this incomplete digestion, resulting in 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."<ref name="Aretaeus" /><ref name="Losowsky" />

The paediatrician [[Samuel Gee]] gave the first modern-day description of the condition in children in a lecture at the [[Great Ormond Street Hospital|Hospital for Sick Children, Great Ormond Street]], London, in 1887. Gee acknowledged earlier descriptions and terms for the disease and adopted the same term as Aretaeus (coeliac disease). 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 [[starch]]ed 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 fed "a quart of the best Dutch [[mussel]]s daily"; the child could not bear this diet for more than one season.<ref name=Losowsky/><ref>{{Cite journal | vauthors = Gee SJ |year=1888 |title=On the coeliac affection |journal=St Bartholomew's Hospital Report |volume=24 |pages=17–20 |url=http://web2.bium.univ-paris5.fr/livanc/?cote=epo0466&p=1&do=page |archive-url=https://web.archive.org/web/20070926231536/http://web2.bium.univ-paris5.fr/livanc/?cote=epo0466&p=1&do=page |archive-date=26 September 2007 |access-date=20 March 2007}}</ref>

[[Christian Archibald Herter (physician)|Christian Archibald Herter]], an American physician, wrote a book in 1908 on children with coeliac disease, which he called "intestinal [[infantilism (disorder)|infantilism]]". 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.<ref name=Herter1908>{{Cite book | vauthors = Herter CA |year=1908 |title=On infantilism from chronic intestinal infection; characterized by the overgrowth and persistence of flora in the nursing period |url=https://archive.org/details/oninfantilismfr01hertgoog |publisher=Macmillan & Co |location=New York}} as cited by WhoNamedIt</ref><ref name=whoNamedItHerter>{{cite web |url=http://www.whonamedit.com/doctor.cfm/1490.html |title=Christian Archibald Herter |access-date=20 March 2007 |vauthors=Enersen OD |publisher=Who Named It? |url-status=live |archive-url=https://web.archive.org/web/20061231203644/http://www.whonamedit.com/doctor.cfm/1490.html |archive-date=31 December 2006 }}</ref> [[Sidney V. Haas]], an American paediatrician, reported positive effects of [[Specific Carbohydrate Diet|a diet of bananas]] in 1924.<ref>{{Cite journal |vauthors=Haas SV |year=1924 |title=The value of the banana in the treatment of coeliac disease |doi=10.1001/archpedi.1924.04120220017004 |journal=Am J Dis Child |volume=24 |pages=421–437 |issue=4}}</ref> This diet remained in vogue until the actual cause of coeliac disease was determined.<ref name=Losowsky/>

While a role for carbohydrates had been suspected, the link with wheat was not made until the 1940s by the Dutch paediatrician [[Willem Karel Dicke]].<ref>{{cite journal |vauthors=van Berge-Henegouwen GP, Mulder CJ |title=Pioneer in the gluten free diet: Willem-Karel Dicke 1905–1962, over 50 years of gluten free diet |journal=Gut |volume=34 |issue=11 |pages=1473–1475 |year=1993 |pmid=8244125 |pmc=1374403 |doi=10.1136/gut.34.11.1473}}</ref> Clinical improvement of his patients during the [[Dutch famine of 1944–1945]] (during which flour was scarce) likely contributed to his discovery.<ref>{{Cite book |vauthors=Dicke WK |title=Coeliakie: een onderzoek naar de nadelige invloed van sommige graansoorten op de lijder aan coeliakie, PhD thesis |language=nl |location=Utrecht, the Netherlands |publisher=University of Utrecht |year=1950}}</ref> Dicke noticed that the shortage of bread led to a significant drop in the death rate among children affected by coeliac disease from greater than 35% to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels.<ref>{{Cite journal |vauthors=Fasano A |title=Celiac Disease Insights: Clues to Solving Autoimmunity |journal=Scientific American |issue=August |year=2009 |pages=49–57 |url=https://www.scientificamerican.com/article/celiac-disease-insights/ }}</ref> The link with the gluten component of wheat was made in 1952 by a team from [[Birmingham]], England.<ref>{{cite journal |vauthors=Anderson CM, French JM, Sammons HG, Frazer AC, Gerrard JW, Smellie JM |title=Coeliac disease; gastrointestinal studies and the effect of dietary wheat flour |journal=Lancet |volume=1 |issue=17 |pages=836–842 |year=1952 |pmid=14918439 |doi=10.1016/S0140-6736(52)90795-2}}</ref> Villous atrophy was described by British physician John W. Paulley in 1954 on samples taken at surgery.<ref>{{cite journal |vauthors=Paulley JW |title=Observation on the aetiology of idiopathic steatorrhoea; jejunal and lymph-node biopsies |journal=Br Med J |volume=2 |issue=4900 |pages=1318–1321 |year=1954 |pmid=13209109 |pmc=2080246 |doi=10.1136/bmj.2.4900.1318}}</ref> This encouraged biopsy samples taken by endoscopy.<ref name=Losowsky/> Throughout the 1960s, other features of coeliac disease were elucidated. Its hereditary character was recognised in 1965.<ref>{{cite journal |vauthors=Macdonald WC, Dobbins WO, Rubin CE |title=Studies of the familial nature of celiac sprue using biopsy of the small intestine |journal=N Engl J Med |volume=272 |issue=9 |pages=448–456 |year=1965 |pmid=14242522 |doi=10.1056/NEJM196503042720903}}</ref> In 1966, dermatitis herpetiformis was linked to [[gluten sensitivity]].<ref name=Losowsky/><ref name=Marks>{{cite journal |vauthors=Marks J, Shuster S, Watson AJ |title=Small-bowel changes in dermatitis herpetiformis |journal=Lancet |volume=2 |issue=7476 |pages=1280–1282 |year=1966 |pmid=4163419 |doi=10.1016/S0140-6736(66)91692-8}}</ref>

==Society and culture== {{See also|List of people diagnosed with coeliac disease}} May has been designated as "Coeliac Awareness Month" by several coeliac organisations.<ref>{{Cite news |date=11 May 2010 |title=Buy Me Some Gluten-Free Peanuts, Cracker Jacks |periodical=QSR Magazine |publisher=Journalistic |url=http://www.qsrmagazine.com/news/buy-me-some-gluten-free-peanuts-cracker-jacks |access-date=30 December 2010 |url-status=live |archive-url=https://web.archive.org/web/20111204091018/http://www.qsrmagazine.com/news/buy-me-some-gluten-free-peanuts-cracker-jacks |archive-date=4 December 2011 }}</ref><ref>{{Cite news | vauthors = Hillson B |date=9 January 2008 |title=May as Celiac Awareness Month |periodical=Celiac Disease Foundation |url=http://www.celiac.org/index.php?option=com_content&view=article&id=86&Itemid=119 |archive-url=https://web.archive.org/web/20100224094719/http://www.celiac.org/index.php?option=com_content&view=article&id=86&Itemid=119 |archive-date=24 February 2010 |access-date=1 July 2011}}</ref>

===Dietary challenges=== Adhering to the GFD can negatively impact those with coeliac disease, requiring major changes for an individual and their family. The restrictive nature of the GFD can lead to no longer enjoying food and pressure to be constantly vigilant about diet.<ref name="i208">{{cite journal | last1=Kowalczuk | first1=Anna | last2=Moor | first2=Fiona | title=A Meta-Synthesis Exploring Daily Experiences of Adults With Coeliac Disease in Adhering to a Gluten-Free Diet | journal=Journal of Human Nutrition and Dietetics | volume=38 | issue=2 | date=2025 | issn=0952-3871 | pmid=40197759 | pmc=11977448 | doi=10.1111/jhn.70043 | article-number=e70043 }}</ref> The social life of those with coeliac disease is also negatively affected by the GFD.<ref name="i208"/> [[Contamination|Cross-contamination]]—gluten-free food coming into contact with gluten—is a common worry for those eating away from home.<ref name="b300"/> Eating out may cause anxiety as it requires disclosing dietary restrictions and risking potential cross-contamination.<ref name="f561"/><ref name="r307">{{cite journal | last1=Wall | first1=Elizabeth | last2=Semrad | first2=Carol E. | title=Celiac Disease, Gluten Sensitivity, and Diet Management | journal=Current Gastroenterology Reports | volume=26 | issue=8 | date=2024 | issn=1522-8037 | doi=10.1007/s11894-024-00931-x | pages=191–199 | pmid=38865028 | url=https://link.springer.com/10.1007/s11894-024-00931-x | access-date=2025-12-16| url-access=subscription }}</ref> Receiving a diagnosis of coeliac disease and the dietary changes required to manage the disorder can affect a person's relationship with food and lead to [[disordered eating]] as well as [[Anxiety disorder|anxiety]] and [[Depression (mood)|depression]].<ref name="p489">{{cite journal | last1=Rose | first1=Catharine | last2=Law | first2=Gary U. | last3=Howard | first3=Ruth A. | title=The psychosocial experiences of adults diagnosed with coeliac disease: a qualitative evidence synthesis | journal=Quality of Life Research | volume=33 | issue=1 | date=2024 | issn=0962-9343 | pmid=37516676 | pmc=10784387 | doi=10.1007/s11136-023-03483-1 | pages=1–16 }}</ref><ref name="r307"/> A diagnosis of coeliac disease can carry [[Social stigma|stigma]], which may affect individuals' ability to seek help or disclose their condition when needed.<ref name="p489"/>

Accessing gluten-free food can be a burden due to limited availability and variety, as well as higher costs compared to gluten-containing foods.<ref name="i208"/><ref name="f561"/> Over the past ten years, the costs of gluten-free food have decreased; however, it remains significantly more expensive than gluten-containing food.<ref name="b300"/><ref name="r307"/> There has been an increase in the popularity of the GFD among those without coeliac disease, which has improved the availability of gluten-free foods. However, the increase in those without coeliac disease eating gluten-free may lead to decreased vigilance of food manufacturers and misunderstandings around the importance of avoiding cross-contamination.<ref name="i208"/>

Many gluten-free substitutions are lower in nutritional quality and may lack vitamins and nutrients that their gluten-containing counterparts have. Ingredients commonly used in gluten-free substitutes, such as rice, potato, corn, and [[tapioca]] starches, have lower levels of [[Fiber|fibre]], [[carbohydrate]]s, and vitamins but are higher in sugars and fats than gluten-containing diets.<ref name="b300"/><ref name="s787"/><ref name="r307"/>

Currently, there are no [[Code of Federal Regulations|federal regulations]] for gluten in non-food products such as medications, [[cosmetics]], and hygiene products. Although the amount of gluten in non-food products is usually minimal, mislabelling of gluten products can confuse people and potentially adversely impact health.<ref name="r307"/><ref name="f561"/>

===Christian churches and the Eucharist=== Speaking generally, the various denominations of Christians celebrate a [[Eucharist]] in which a wafer or small piece of [[sacramental bread]] from wheat bread is blessed and then eaten.<ref>{{cite web | url = http://www.eden.co.uk/shop/peoples-alter-breads-single-cross-sealed-edge-white-125972.html | title = One on-line site sells 1200 wafers weighing a total of 523 g | archive-url = https://web.archive.org/web/20110916215312/http://www.eden.co.uk/shop/peoples-alter-breads-single-cross-sealed-edge-white-125972.html |date=16 September 2011 | work = Eden.co.uk | archive-date = 16 September 2011 | access-date = 3 September 2013 }}</ref> Small communion wafers typically contain 2–5 mg of gliadin if they are not a gluten-free variety,<ref>{{Cite journal |date=3 August 1989 |title=Holy Communion Wafers and Celiac Disease |url=http://www.nejm.org/doi/abs/10.1056/NEJM198908033210518 |journal=New England Journal of Medicine |volume=321 |issue=5 |page=332 |doi=10.1056/NEJM198908033210518 |pmid=2747779 |issn=0028-4793 | vauthors = Moriarty KJ, Loft D, Marsh MN, Brooks ST, Gordon D, Garner GV |url-access=subscription }}</ref> and many people with coeliac disease report altering their religious practices because of coeliac symptoms caused by these wafers.<ref>{{Cite journal |last=Bentley |first=Annette C. |date=January 1988 |title=A Survey of Celiac-Sprue Patients: Effect of Dietary Restrictions on Religious Practices |url=http://www.tandfonline.com/doi/abs/10.1080/00221309.1988.9711083 |journal=The Journal of General Psychology |volume=115 |issue=1 |pages=7–14 |doi=10.1080/00221309.1988.9711083 |pmid=3351491 |issn=0022-1309|url-access=subscription }}</ref>

Some Christian churches such as the [[United Methodist Church|United Methodist]], [[Christian Reformed Church in North America|Christian Reformed]], [[Episcopal Church (United States)|Episcopal]], [[Anglicanism|Anglican]] and [[Lutheranism|Lutheran]] churches offer their communicants gluten-free alternatives, usually in the form of a rice-based cracker or gluten-free bread. [[Catholic Church|Catholics]] may receive from the [[chalice]] alone, or ask for gluten-reduced hosts; gluten-free ones however are not considered still to be wheat bread, and hence are invalid matter.<ref>{{cite web | url = http://www.catholicceliacs.org/Bishops.html | title = Statement by the National Conference of Catholic bishops on the use of low gluten hosts at Mass | archive-url = https://web.archive.org/web/20130716100106/http://www.catholicceliacs.org/Bishops.html |archive-date=16 July 2013 | work = BCL Newsletter | date = November 2003 }}</ref>

[[Catholic theology|Roman Catholic doctrine]] states that for a valid Eucharist, the bread to be used at [[Mass in the Catholic Church|Mass]] must be made from wheat. Low-gluten [[Host (Holy Communion)|hosts]] meet all of the Catholic Church's requirements, but they are not entirely gluten-free.<ref>{{Cite news |agency=Associated Press |url=http://www.nbcnews.com/id/5762478 |archive-url=https://web.archive.org/web/20131113165203/http://www.nbcnews.com/id/5762478/ |archive-date=13 November 2013 |title=Girl with digestive disease denied Communion |work=NBC News |publisher=Microsoft |date=8 December 2004 |access-date=30 May 2006 }}</ref> As of 2017, the [[Vatican City|Vatican]] still disapproves of the use of gluten-free bread for Holy Communion.<ref>{{Cite news |url=https://www.telegraph.co.uk/news/2017/07/08/vatican-outlaws-use-gluten-free-bread-holy-communion/ |title=Vatican outlaws use of gluten free bread for Holy Communion |access-date=3 August 2017 |url-status=live |archive-url=https://web.archive.org/web/20170804012531/http://www.telegraph.co.uk/news/2017/07/08/vatican-outlaws-use-gluten-free-bread-holy-communion/ |archive-date=4 August 2017 |newspaper=The Telegraph |date=8 July 2017 | vauthors = Millward D }}</ref>

===Passover=== The Jewish festival of [[Passover|Pesach]] (Passover) may present problems with its obligation to eat [[matzah]], which is unleavened bread made in a strictly controlled manner from wheat, barley, spelt, oats, or rye. In addition, many other grains that are normally used as substitutes for people with gluten sensitivity, including rice, are avoided altogether on Passover by [[Ashkenazi Jews]]. Many [[kosher]]-for-Passover products avoid grains altogether and are therefore gluten-free. [[Potato starch]] is the primary starch used to replace grains.<ref>{{Cite news |last=Friedman |first=Gabe |date=2017-04-03 |title=Here's the spiel on gluten-free matzah |url=http://www.timesofisrael.com/gluten-free-matzah-heres-what-you-should-know/ |access-date=2025-10-25 |work=The Times of Israel |issn=0040-7909}}</ref>

==Research directions== Research into diagnosis has aimed to develop new blood tests, including tests that could be used for those who are not currently eating gluten. These tests measure certain immune cells that react to gluten, such as [[CD4+ T cells]] and HLA-DQ-gluten [[tetramer]]s.<ref name="h960"/><ref name="o845">{{cite book | last1=Guz-Mark | first1=Anat | last2=Shamir | first2=Raanan | title=Advances in Celiac Disease | chapter=New Fields of Research in Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_15 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_15 | access-date=2025-12-12 | pages=215–224}}</ref><ref name="t774">{{cite journal | last1=Pinto-Sanchez | first1=M. Ines | last2=Silvester | first2=Jocelyn A. | last3=Lebwohl | first3=Benjamin | last4=Leffler | first4=Daniel A. | last5=Anderson | first5=Robert P. | last6=Therrien | first6=Amelie | last7=Kelly | first7=Ciaran P. | last8=Verdu | first8=Elena F. | title=Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease | journal=Nature Reviews Gastroenterology & Hepatology | volume=18 | issue=12 | date=2021 | issn=1759-5045 | pmid=34526700 | pmc=8441249 | doi=10.1038/s41575-021-00511-8 | pages=875–884 }}</ref>

New technologies have been developed to help people follow a GFD in recent years. Food sensors, such as the Nima sensor, could help people measure the amount of gluten in food to prevent accidental gluten consumption. Testing kits that measure gluten levels in urine and waste may help measure adherence the GFD.<ref name="x940">{{cite journal | last=Lee | first=Anne R. | title=Review article: Dietary management of coeliac disease | journal=Alimentary Pharmacology & Therapeutics | volume=56 | issue=S1 | date=2022 | pages=S38–S48 | issn=0269-2813 | doi=10.1111/apt.16974 | url=https://onlinelibrary.wiley.com/doi/10.1111/apt.16974 | access-date=2025-12-12 | pmid=35815831 | url-access=subscription }}</ref>

Many strategies have been proposed to develop new treatments for coeliac disease. Altering wheat to be safer for those with coeliac disease has been explored using methods such as genetic wheat manipulation and using a chemical process ([[transamidation]]) that changes gluten proteins so they no longer trigger an immune reaction.<ref name="o845"/><ref name="y859">{{cite book | last1=Gianfrani | first1=Carmen | last2=Vitale | first2=Serena | last3=Troncone | first3=Riccardo | title=Advances in Celiac Disease | chapter=New Therapeutic Strategies in Celiac Disease | publisher=Springer International Publishing | publication-place=Cham | date=2022 | isbn=978-3-030-82400-6 | doi=10.1007/978-3-030-82401-3_13 | chapter-url=https://link.springer.com/10.1007/978-3-030-82401-3_13 | access-date=2025-12-12 | pages=171–191}}</ref> Medications and techniques such as [[chitosan]] and AGY gluten sequestering aim to prevent gluten from interacting with the immune system.<ref name="o845"/> Glutenases are enzymes taken with food designed to help break down and neutralise gluten in the intestines. Glutenases being studied {{As of|2022|lc=y}} include latiglutenase–ALV003, [[Aspergillus niger]] prolyl [[Endopeptidase|endoprotease]], Kuma030–TAK-062, and endoproptease-40.<ref name="y859"/><ref name="f561"/>

[[Larazotide|Larazotide acetate]] is a peptide that helps tighten the junctions between intestinal cells, reducing [[intestinal permeability]]. It helps decrease reactions to gluten by preventing gluten fragments from passing through the gut lining and triggering the immune system.<ref name="f561"/> Treatments focused on [[immunomodulation]] aim to target the T cells that react to gluten and reduce intolerance to gluten.<ref name="y859" />

==References== {{Reflist}}

==External links== {{Sister project links||d=Q11088|c=Category:Coeliac disease|n=no|q=no|b=no|v=no|voy=no|m=no|mw=no|s=no|wikt=Coeliac disease|species=no}}

{{Medical condition classification and resources |DiseasesDB=2922 |ICD11={{ICD11|DA95}} |ICD10={{ICD10|K|90|0|k|90}} |ICD9={{ICD9|579.0}} |ICDO= |OMIM=212750 |MedlinePlus=000233 |eMedicineSubj=med |eMedicineTopic=308 |eMedicine_mult={{eMedicine2|ped|2146}} {{eMedicine2|radio|652}} |MeshID=D002446 |GeneReviewsNBK=NBK1727 |GeneReviewsName=Celiac Disease }} {{Gastroenterology}} {{Hypersensitivity and autoimmune diseases}} {{Gluten sensitivity}} {{Portal bar|Biology|Medicine}} {{Authority control}}

[[Category:Autoimmune diseases]] [[Category:Gastrointestinal tract disorders]] [[Category:Genetic diseases and disorders]] [[Category:Gluten sensitivity]] [[Category:Malnutrition]] [[Category:Pediatrics]] [[Category:Steatorrhea-related diseases]] [[Category:Wikipedia medicine articles ready to translate]]