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.
A 2018 review concluded that although fructan intolerance may play a role in NCGS, it only explains some gastrointestinal symptoms, but not the extradigestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis. FODMAPs cause digestive symptoms when the person is hypersensitive to luminal distension. A 2019 review concluded that wheat fructans can cause certain IBS-like symptoms, such as bloating, but are unlikely to cause immune activation or extra-digestive symptoms. Many people with NCGS report resolution of their symptoms after removing gluten-containing cereals while continue to eat fruits and vegetables with high FODMAPs content. Diagnosis
Absence of reliable biomarkers and the fact that some people do not have digestive symptoms make the recognition and diagnosis of non-celiac gluten sensitivity (NCGS) difficult.Diagnosis is generally performed only by exclusion criteria. NCGS diagnostic recommendations have been established by several consensus conferences. Exclusion of celiac disease and wheat allergy is important because these two conditions also appear in people who experience symptoms similar to those of NCGS, which improve with a gluten withdrawal and worsen after gluten consumption.The onset of NCGS symptoms may be delayed hours to a few days after gluten ingestion, whereas in celiac disease it can take days to weeks. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can lead to anaphylaxis.The presence of related extraintestinal manifestations has been suggested to be a feature of NCGS.