celiac disease-specific antibodies is more common in patients without villous atrophy who only have duodenal lymphocytosis (marsh 1 lesions) and who respond to a gluten-free diet with histological and symptomatic improvement. duodenal biopsies according to the diagnostic criteria established by the consensus conferences (2011 and 2013), it is necessary to perform duodenal biopsies to exclude celiac disease in symptomatic people with negative specific celiac disease antibodies. because of the patchiness of the celiac disease lesions, four or more biopsies are taken from the second and third parts of the duodenum, and at least one from the duodenal bulb. even in the same biopsy fragments, different degrees of pathology may exist. duodenal biopsies in people with ncgs are always almost normal – an essential parameter for diagnosis of ncgs, although is generally accepted that a subgroup of people with ngcs may have an increased number of duodenal intraepithelial lymphocytes (iels) ( ≥25/100 enterocytes), which represent marsh i lesions. nevertheless, marsh i is considered compatible with celiac disease and the most frequent cause of these findings, especially in people positive for hla dq2 and/or dq8 haplotypes, is celiac disease, with a prevalence of 16-43%. in people with duodenal lymphocytosis – following guidelines from the european society of pediatric gastroenterology, hepatology and nutrition (espghan) – a high count of celiac disease cells (or cd/cd3 ratio) in immunohistochemical assessment of biopsies, or the presence of iga anti-tg2 and/or anti-endomysial intestinal deposits, might be specific markers for celiac disease. catassi and fasano proposed in 2010 that in patients without celiac disease antibodies, either lymphocytic infiltration associated with iga subepithelial deposits or a histological response to a gluten-free diet, could support a diagnosis of celiac disease. wheat allergy the clinical presentation may be sufficient in most cases to distinguish a wheat allergy from other entities. it is excluded when there are normal levels of serum ige antibodies to gluten proteins and wheat fractions, and no skin reaction to prick tests for wheat allergy. nevertheless, these tests are not always completely reliable. if an allergic reaction can not be clearly identified, the diagnosis should be confirmed by food provocation tests, ideally performed in a double-blinded and placebo-controlled manner. delayed allergic reactions may occur with these type of tests, which have to be negative over time, but there are no international consensus statements on diagnosing delayed wheat/food-related symptoms. usually, reactions that appear between two hours and five days after the oral challenge are considered delayed. mucosal challenge followed by confocal endomicroscopy is a complementary diagnostic technique, but this technology is not yet generally available and remains experimental. other tests evaluating the presence of antigliadin antibodies (aga) can be a useful complementary diagnostic test. up to 50% ncgs patients may have elevated aga igg antibodies, but rarely aga iga antibodies (only 7% of the cases). in these patients, unlike in those with celiac disease, the igg aga became undetectable within six months of following a gluten-free diet. people already on a gluten-free diet many people remove gluten from their diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them to be suffering from irritable bowel syndrome, and some may eliminate gluten before seeking medical attention. this fact can diminish the cd serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies. in these cases, patients should be tested for the presence of hla-dq2/dq8 genetic markers because a negative hla-dq2 and hla-dq8 result has a high negative predictive value for celiac disease. if these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies. however, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients. gluten challenge is also discouraged before the age of five and during pubertal growth. it remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. some protocols recommend eating a maximum of 10 g of gluten per day for six weeks. nevertheless, recent studies have shown that a two-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease. this new proposed protocol has shown higher tolerability and compliance. it has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected ncgs, while the remaining 93% would be confirmed as ncgs; this is not yet universally adopted. for people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies, but this test is only available at selected specialized tertiary-care centers. treatment main article: gluten-free diet after exclusion of celiac disease and wheat allergy, the subsequent step for diagnosis and treatment of ncgs is to start a strict gluten-free diet (gfd) to assess if symptoms improve or resolve completely. this may occur within days to weeks of starting a gfd, but improvement may also be due to a non-specific, placebo response. the recovery of the nervous system is slow and sometimes incomplete. recommendations may resemble those for celiac disease, for the diet to be strict and maintained, with no transgression. the degree of gluten cross contamination tolerated by people with ncgs 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. a part of people with gluten-related neuropathy or ataxia appears not to be able to tolerate even the traces of gluten allowed in most foods labeled as "gluten-free". whereas celiac disease requires adherence to a strict lifelong gluten-free diet, it is not yet known whether ncgs is a permanent or a transient condition. the results of a 2017 study suggest that ncgs may be a chronic disorder, as is the case with celiac disease. a trial of gluten reintroduction to observe any reaction after one to two years of strict gluten-free diet might be performed. a strict gluten-free diet is effective in most of the neurological disorders associated with ncgs, ameliorating or even resolving the symptoms. it should be started as soon as possible to improve the prognosis. the death of neurons in the cerebellum in ataxia is the result of gluten exposure and is irreversible. early treatment with a strict gluten-free diet can improve ataxia symptoms and prevent its progression. when dementia has progressed to an advanced degree, the diet has no beneficial effect. cortical myoclonus appears to be treatment-resistant on both gluten-free diet and immunosuppression. persistent symptoms approximately one third of presumed ncgs patients continue to have symptoms, despite gluten withdrawal. apart from a possible diagnostic error, there are multiple possible explanations. one reason is poor compliance with gluten withdrawal, whether voluntary and/or involuntary. there may be ingestion of gluten, in the form of cross contamination or food containing hidden sources. in some cases, the amelioration of gastrointestinal symptoms with a gluten-free diet is only partial, and these patients could significantly improve with the addition of a low-fodmap diet. a subgroup may not improve when eating commercially available gluten-free products, as these can be rich in preservatives and additives such as sulfites, glutamates, nitrates and benzoates, which can also have a role in triggering functional gastrointestinal symptoms. furthermore, people with ncgs may often present with ige-mediated allergies to one or more foods. it has been estimated that around 35% suffer other food intolerances, mainly lactose intolerance. history the subject of "food intolerance", including gluten sensitivity and elimination diets, was discussed in 1976. patients with symptoms including abdominal pain and diarrhea, which improved on gluten withdrawal, and who did not have celiac disease were initially described in 1976 and 1978 with the first series in 1980. debate regarding the existence of a specific condition has continued since then, but the three consensus conferences held since 2010 produced consistent definitions of ncgs and its diagnostic criteria. society and culture