IgG tTGA antibodies should be checked in selective IgA deficiency, which can be associated with celiac disease and occurs in as many as one in 40 celiac patients.Nevertheless, the absence of serological markers does not certainly exclude celiac disease. In those with celiac disease before diagnosis (on a gluten-containing diet), celiac disease serological markers are not always present. As the age of diagnosis increases, these antibody titers decrease, and may be low or even negative in older children and adults. The absence of 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.
When symptoms are limited to gastrointestinal effects, there may be an overlap with wheat allergy, irritable bowel syndrome (IBS), and (less likely) intolerance to FODMAPs.Proposed criteria for a diagnosis of NCGS suggest an improvement of gastrointestinal symptoms and extra-intestinal manifestations higher than 30% with a gluten-free diet (GFD), assessed through a rating scale, is needed to make a clinical diagnosis of NCGS. To exclude a placebo effect, a double-blind placebo-controlled gluten challenge is a useful tool, although it is expensive and complicated for routine clinical use, and so is usually performed in research studies.These suggestions were incorporated in the Salerno expert consensus on diagnostic criteria for NCGS. These recommend assessment of the response to a 6-week trial of a gluten-free diet using a defined rating scale (Step 1), followed by a double-blind, placebo-controlled challenge of gluten (or placebo) for a week of each (Step 2). A variation of greater than 30% in the main symptoms when challenged by gluten or placebo is needed for a positive result. Further research on possible biomarkers was also identified. Differential diagnosis
Examinations evaluating celiac disease and wheat allergy should be performed before patients remove gluten from their diet. It is critical to make a clear distinction between celiac disease and NCGS. Celiac disease
The main goal in diagnosing NCGS is to exclude celiac disease.