to one or more foods and it is estimated that around 35% of people with some food intolerances, mainly lactose intolerance. wheat allergy main article: wheat allergy people can also experience adverse effects of wheat as result of a wheat allergy. gastrointestinal symptoms of wheat allergy are similar to those of coeliac disease and non-celiac gluten sensitivity, but there is a different interval between exposure to wheat and onset of symptoms. wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and could be anaphylaxis. the treatment of wheat allergy consists of complete withdrawal of any food containing wheat and other gluten-containing cereals. nevertheless, some people can tolerate barley, rye or oats. other conditions or risk factors antibodies to α-gliadin have been significantly increased in non-celiacs individuals with oral ulceration. anti-α-gliadin antibodies are frequently found in celiac disease (cd), to a lesser degree subclinical cd, but are also found in a subset who do not have the disease. of people with pseudo-exfoliation syndrome, 25% showed increased levels of anti-gliadin iga. other people that are also at risk are those taking gluten despite having the disorder, or whose family members have cd. in addition people with autoimmune conditions are also at risk for cd. it has just been found that there is a risk of death in cd. therefore, gluten intake should be limited before or even after the diagnosis. one-fourth of people with sjögren's syndrome had responses to gluten; of five that had positive response to gluten, only one could be confirmed as cd and another was potentially gse, the remaining three appeared to be gluten-sensitive. all were hla-dq2 and/or dq8-positive. symptoms more than 250 symptoms of gluten sensitivity have been reported, including bloating, abdominal discomfort or pain, constipation and diarrhea. sensitivity may also present with extraintestinal symptoms, including headache, "brain fog", tingling and/or numbness in hands and feet, fatigue, as well as muscular disturbances and bone or joint pain; also neuropsychiatric manifestations ("gluten-sensitive idiopathic neuropathies") have been reported on. complications studies using anti-gliadin antibodies (aga) reveal that diagnosed or untreated individuals with aga have an increasing risk for lymphoid cancers and decreased risk for other conditions associated with affluence. causes when enteropathy develops in early childhood, symptomatic disease is more rapidly evident. a survey of geriatrics with celiac disease in finland revealed that the incidence of disease was much higher than the general population. allergic disease may rise or fall with age; certain evidence points to the increased or daily use of non-steroidal anti-inflammatory factors (aspirin, ibuprofen) as an increased risk factor for urticaria or anaphylaxis, and the sensitizing dose may include low-dose aspirin therapy used in the treatment of heart disease. ncgs may be a late-onset condition: in a prospective study performed among adults of 18 to 80 years, the median age of disease onset was found to be 55 years, with a six times higher prevalence in females than in males. the pathogenesis of ncgs is not yet well understood. there is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named atis which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. atis are potent activators of the innate immune system. fodmaps, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in persons with ncgs. as of 2019, reviews have concluded that although fodmaps may play a role in ncgs, they only explain certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with ncgs may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis. immunochemistry of glutens main article: gluten immunochemistry triticeae glutens are important factors in several inflammatory diseases. the immunochemistry can be subdivided into innate responses (direct stimulation of immune system), class ii mediated presentation (hla-dq), class i mediated stimulation of killer cells, and antibody recognition. the responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. the response is also dependent on the genetic makeup of the human leukocyte antigen genes. in enteropathy, there are at least 3 types of recognition, innate immunity (a form of cellular immunity priming), hla-dq and antibody recognition of gliadin and transglutaminase. in ncgs, there is high aga igg in more than half of the cases. in wheat allergy, there appears to be an innate component and the response pathways are mediated through ige against gliadin and other wheat proteins. pathophysiology compared to the pathophysiology of celiac disease, the pathophysiology of ncgs is far less understood. a literature review of 2014 found that people with ncgs "are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis and clinical history, and, probably, clinical course". genetics celiac disease (cd) and ncgs are closely linked with human leukocyte antigen (hla) class ii genes, hla-dq2 and hla-dq8, located on chromosome 6p21. nearly all cd people are hla-dq2/hla-dq8 positive, with 95% hla-dq2 and the rest usually hla-dq8 (which is carried by 30% of caucasians). however, the specificity of hla-dq2 and/or hla-dq8 for cd is low, with estimates ranging from 36% to 53%. in persons with ncgs, the hla-dq2 and/or hla-dq8 alleles are present in only about 50%, which is still a greater proportion than in the general population. diagnosis a literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (cd) and wheat allergy. persons suspected of having celiac disease may undergo serological testing for iga anti-tissue transglutaminase antibodies (abbreviated anti-ttg antibodies or anti-tg2 antibodies) and anti-endomysial antibodies (abbreviated ema) provided the iga-level is high, and if iga is low, testing for certain igg antibodies; in case of positive serological indication, a duodenal biopsy may confirm active celiac disease. eliminating the possibility of cd can generally also be done by adding hla-dq typing. the absence of hla-dq2 and hla-dq8 has a very high negative predictive value for cd, and the predictive value can be further enhanced by including hla-dq7.5 (hla-dq2 and hla-dq8 are found in coeliac disease 98% of the time in caucasians, hla-dq7.5 present in the remaining 1.6% and only 0.4% of caucasians are missed with the combination of these three). without serological or hla-dq2/8 positivity, celiac disease is likely not present. hla-dq typing has a practical advantage in that it is the only diagnostic test that allows to exclude cd when a person is already on a gluten-free diet; however, as not only celiacs are hla-dq2/hla-dq8 positive, this method has a higher false positive rate than anti-tg2 and ema antibody testing. a four-of-five rule was proposed 2010 for confirming celiac disease, with the disease confirmed if at least four of the following five criteria are satisfied: typical symptoms of celiac disease; positivity of serum celiac disease immunoglobulin, a class autoantibodies at high titer; human leukocyte antigen (hla)-dq2 or dq8 genotypes; celiac enteropathy at the small bowel biopsy; and response to the gluten-free diet. for diagnosis of wheat allergy, allergy tests are available. treatment main article: gluten-free diet for people with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date; for people diagnosed with non-celiac gluten sensitivity, there are still open questions concerning for example the duration of such a diet. the results of a 2017 study suggest that non-celiac gluten sensitivity may be a chronic disorder, as is the case with celiac disease. for people with wheat allergy, the individual average is six years of gluten-free diet, excepting persons with anaphylaxis, for whom the diet is to be wheat-free for life. preferably, newly diagnosed celiacs seek the help of a dietician to receive support for identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. knowledge of hidden sources of gluten is important for people with celiac disease as they need to be very strict regarding eating only gluten-free food. the degree of gluten cross contamination tolerated by people with non-celiac gluten sensitivity is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts. sporadic accidental contaminations with gluten can reactivate movement disorders associated with non-celiac gluten sensitivity. a part of people with gluten-related neuropathy or gluten ataxia appears not to be able to tolerate even the traces of gluten allowed in most foods labeled as "gluten-free". the inclusion of oats in gluten-free diets remains controversial. avenin present in oats may also be toxic for individuals with celiacs. its toxicity depends on the cultivar consumed. furthermore, oats are frequently cross-contaminated with gluten-containing cereals. risks of non-medical and self-diagnosed adoption of a gluten-free diet withdrawing gluten from the diet without previously carrying out a complete medical examination can hamper the diagnosis of celiac disease. diagnostic tests (antibodies and duodenum biopsies) lose their usefulness if the person is already eating a gluten-free diet. potential nutritional deficiencies gluten proteins have low nutritional value and replacing grains that contain gluten is easy from the nutritional point of view. however, an unbalanced selection of food and an incorrect choice of gluten-free replacement products may lead to nutritional deficiencies. replacing flour from wheat or other gluten-containing cereals with gluten-free flours in commercial products may lead to a lower intake of important nutrients, such as iron and b vitamins. some gluten-free commercial replacement products are not enriched or fortified as their gluten-containing counterparts, and often have greater lipid/carbohydrate content. children especially often over-consume these products, such as snacks and biscuits. pseudocereals (quinoa, amaranth, and buckwheat) and some minor cereals are healthier alternatives to these prepared products and have higher nutritional value. furthermore, they contain protein of higher nutritional quality than those of wheat, and in greater quantities. nutritional complications can be prevented by a correct dietary education. epidemiology in the united states, fewer cases of cd have been found compared to other countries. the incidence of celiac disease and of wheat allergy is estimated each to lie at around 1% of the population. there has been a 6.4 increase in the case reports of celiac disease between 1990 and 2009. the incidence of ncgs is unknown; some estimates range from 0.6% to 6%, and a systematic review of 2015 reported on studies with ncgs prevalence rates between 0.5% and 13%. in europe, the average consumption of gluten is 10g to 20g per day, with parts of the population reaching 50g or more per day. histology changes in inflammatory cells affect the body, which reduces the intake of "nutrients, fat-soluble vitamins and minerals" in the body. regulations crossed-grain symbol, similar to that of the association of european coeliac societies (aoecs) in various countries, regulations and labelling requirements for gluten-free food products have been implemented. for europe, the commission regulation (ec) no. 41/2009 of 20 january 2009 concerning the composition and labelling of foodstuffs suitable for people intolerant to gluten has laid down harmonised rules on the content and labelling of these foodstuffs, setting out the conditions under which foods may be labelled as "gluten-free" or "very low gluten". having entered into force on 10 february 2009 and taken effect on 1 january 2012, these rules have been repealed with effect as of 20 july 2016. the background is that, in line with the regulation (eu) no 609/2013 on food for specific groups, gluten-free foods shall, in future, be legislated for under the eu food information for consumers regulation (regulation (eu) no. 1169/2011). furthermore, the commission implementing regulation (eu) no 828/2014 of 30 july 2014 on the requirements for the provision of information to consumers on the absence or reduced presence of gluten in food extends the rules of regulation (ec) 41/2009 on "gluten-free" and "very low gluten" statements also to non pre-packed foods such as those served in restaurants. the implementing regulation also clarifies how consumers are to be informed of the difference between foods that are naturally free of gluten and products that are specially formulated for gluten-intolerant persons. recognition of gluten-free packaged foods is facilitated by the crossed-grain symbol, representing a crossed ear of wheat. the symbol is used as a logo that facilitates food shopping for people with cd and other gluten-related disorders. the symbol, which is protected as a trademark in europe and