[10] Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally.

[30][31] The only known effective treatment is a strict lifelong gluten-free diet, which leads to recovery of the intestinal lining (mucous membrane), improves symptoms, and reduces the risk of developing complications in most people.

Indeed, after starting a gluten-free diet and subsequent improvement becomes evident, such individuals are often able to retrospectively recall and recognise prior symptoms of their untreated disease that they had mistakenly ignored.

[20] The long-term effects of pure oat consumption are still unclear,[55] and further studies identifying the cultivars used are needed before making final recommendations on their inclusion in a gluten-free diet.

Prolonging breastfeeding until the introduction of gluten-containing grains into the diet appears to be associated with a 50% reduced risk of developing coeliac disease in infancy; whether this persists into adulthood is not clear.

One locus, the LPP or lipoma-preferred partner gene, is involved in the adhesion of extracellular matrix to the cell surface, and a minor variant (SNP=rs1464510) increases the risk of disease by approximately 30%.

[77] Gliadin in wheat is the best-understood member of this family, but other prolamins exist, and hordein (from barley), secalin (from rye), and avenin (from oats) may contribute to coeliac disease.

[89] The inflammatory process, mediated by T cells, leads to disruption of the structure and function of the small bowel's mucosal lining and causes malabsorption as it impairs the body's ability to absorb nutrients, minerals, and fat-soluble vitamins A, D, E, and K from food.

[citation needed] Alternative causes of this tissue damage have been proposed and involve the release of interleukin 15 and activation of the innate immune system by a shorter gluten peptide (p31–43/49).

While positive serology and typical biopsy are highly suggestive of coeliac disease, lack of response to the diet may require these alternative diagnoses to be considered.

[41] Diagnosis is often difficult and as of 2019, there continues to be a lack of awareness among physicians about the variability of presentations of coeliac disease and the diagnostic criteria, such that most cases are diagnosed with great delay.

[98] European guidelines suggest that in children and adolescents with symptoms compatible with coeliac disease, the diagnosis can be made without the need for intestinal biopsy if anti-tTG antibodies titres are very high (10 times the upper limit of normal).

Currently, 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.

[13] A careful interpretation of the symptomatic response is needed, as a lack of response in a person with coeliac disease may be due to continued ingestion of small amounts of gluten, either voluntary or inadvertent,[11] or be due to other commonly associated conditions such as small intestinal bacterial overgrowth (SIBO), lactose intolerance, fructose,[110] sucrose,[111] and sorbitol[112] malabsorption, exocrine pancreatic insufficiency,[113][114] and microscopic colitis,[114] among others.

[111][112][115][116][117] They normally revert or improve several months after starting a gluten-free diet, but may need temporary interventions such as supplementation with pancreatic enzymes,[116][117] dietary restrictions of lactose, fructose, sucrose or sorbitol containing foods,[111][115] or treatment with oral antibiotics in the case of associated bacterial overgrowth.

[120] The NICE also recommend offering serological testing for coeliac disease in people with metabolic bone disease (reduced bone mineral density or osteomalacia), unexplained neurological disorders (such as peripheral neuropathy and ataxia), fertility problems or recurrent miscarriage, persistently raised liver enzymes with unknown cause, dental enamel defects and with diagnose of Down syndrome or Turner syndrome.

[21] Some evidence has found that early detection may decrease the risk of developing health complications, such as osteoporosis, anaemia, and certain types of cancer, neurological disorders, cardiovascular diseases, and reproductive problems.

[122] Serology has been proposed as a screening measure, because the presence of antibodies would detect some previously undiagnosed cases of coeliac disease and prevent its complications in those people.

A recent systematic review tentatively concluded that consumption of less than 10 mg of gluten per day is unlikely to cause histological abnormalities, although it noted that few reliable studies had been done.

[134] However, Mårild et al. suggested considering additional vaccination against influenza because of an observed increased risk of hospital admission for this infection in celiac patients.

[41] Refractory coeliac disease should not be confused with the persistence of symptoms despite gluten withdrawal[114] caused by transient conditions derived from the intestinal damage,[111][112][115] which generally revert or improve several months after starting a gluten-free diet,[116][117] such as small intestinal bacterial overgrowth, lactose intolerance, fructose,[110] sucrose,[111] and sorbitol[112] malabsorption, exocrine pancreatic insufficiency,[113][114] and microscopic colitis[114] among others.

Refractory celiac disease type I more frequently exhibits diarrhea, anemia, hypoalbuminemia, parenteral nutrition need, ulcerative jejuno-ileitis, and extended small intestinal atrophy.

[33] A large multicentre study in the U.S. found a prevalence of 0.75% in not-at-risk groups, rising to 1.8% in symptomatic people, 2.6% in second-degree relatives (like grandparents, aunt or uncle, grandchildren, etc.)

[149][150] Humans first started to cultivate grains in the Neolithic period (beginning about 9500 BCE) in the Fertile Crescent in Western Asia, and, likely, coeliac disease did not occur before this time.

[156] 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.

On 24 July 2003, the Congregation for the Doctrine of the Faith stated, "Given the centrality of the celebration of the Eucharist in the life of a priest, one must proceed with great caution before admitting to Holy Orders those candidates unable to ingest gluten or alcohol without serious harm.

[168] [citation needed] The Jewish festival of 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.

[169][170] The search for environmental factors that could be responsible for genetically susceptible people becoming intolerant to gluten has resulted in increasing research activity looking at gastrointestinal infections.

[178][needs update] Other modifiers of other well-understood steps in the pathogenesis of coeliac disease, such as the action of HLA-DQ2 or tissue transglutaminase and the MICA/NKG2D interaction that may be involved in the killing of enterocytes.