BACKGROUND

Nowadays, the growing number of people following a gluten-free diet far exceeds the number of patients affected by Celiac Disease (CD) [1] and they all complain both gastrointestinal symptoms (diarrhea, abdominal pain, bloating), as well as extraintestinal manifestations (headache, lethargy, attention-deficit/hyperactivity disorder, ataxia, recurrent oral ulceration, psoriasis).

Non-Celiac Gluten Sensitivity (NCGS) has recently been identified as a possible answer to this trend: it is a new clinical entity, different from CD but included in the spectrum of gluten-related disorders whose main treatment is the strict, life-long gluten-free diet and its prevalence is estimated even about  6% [2].

CD and NCGS are two distinct gluten-related conditions. CD diagnosis is based on the presence of duodenal mucosa villous atrophy together with serum anti-endomisium (EMA) and anti-transglutaminase (anti t-TG) positive results.

NCGS is characterized by symptoms receding on gluten free diet but it is still lacking of diagnostic markers: in only 56,4% of cases the serological pattern of NCGS is characterized by IgG AGA positive results, while EMA, t-TGA and DGP-AGA show serological negative results [3].

Among gluten-related disorders nowadays known, wheat allergy plays a role too (prevalence about 0.1 %) and it must be considered for a differential diagnosis.

Recent studies have introduced a new concept called “Allergic Contact Mucositis” (ACM) as possible explanation to nickel-containing food adverse effects [4]. Translating this concept, we hypothesized that also NCGS may be caused by a contact mucositis.

OBJECTIVE

Our aim was to find a method capable of showing macroscopic mucosa lesions provoked by direct contact with gluten in patients affected by NCGS.

On the basis of a suggestive analogy between oral and small intestinal mucosa already shown in literature [5], we tried to find out if a positive gluten oral mucosa patch test (GOMPT) could be sign of NCGS.

MATERIALS AND METHODS

POPULATION

The population studied consisted of 4 different groups of patients:

Group A (NCGS): consisted of 38 patients presenting gastrointestinal and extra-gastrointestinal symptoms occurring after the ingestion of gluten, disappearing after gluten is withdrawn from the diet, and re-presenting after a re-challenge.

In order to make differential diagnosis with CD and allergic disease, we investigated: HLA DQ2 DQ8 typing; serological EMA IgA and IgG, anti t-TG IgA and IgG, AGA IgA and IgG, AGA DGP IgA and IgG; esophagogastroduodenoscopy (EGDS) with histological examination of duodenal biopsies; organ culture of duodenal biopsies; RAST test for wheat, barley, oats, rye, gluten and cow's milk proteins.

Group B (CD at diagnosis): consisted of 10 patients presenting current serological, endoscopic and histological positive results for CD. RAST test for wheat, barley, oats, rye, gluten and cow's milk proteins presented negative results.

Group C (CD in remission): consisted of 10 CD patients in remission presenting clinical, serological, endoscopic and histological negative results. RAST test for wheat, barley, oats, rye, gluten and cow's milk proteins presented negative results.

Group D (healthy controls): consisted of 10 healthy volunteers, presenting clinical and serological negative results for CD and allergic disease.

GLUTEN ORAL MUCOSA PATCH TEST (GOMPT)

The oral mucosa patch test was performed on the upper lip mucosa of all patients studied. A 5-mm filter paper disk saturated with a 10% solution of gluten in vaseline was applied on the test site and held in place by an adhesive transparent film (FIRMA). Gluten quantity applied was 1,2 mg. The patch was removed after 2 hours. Erythema, edema and/or vesicles presence on the application site were considered as positive result.

DISCUSSION

This study documents the presence of local macroscopic inflammatory lesions triggered by gluten specifically on oral mucosa of NCGS patients. We hypothesize that the same gluten-related lesions induced and observed on oral mucosa could also involve intestinal mucosa, suggesting gluten as real responsible for NCGS symptomatology complained by patients.

Therefore, oral mucosa patch test could be considered as a useful tool to test NCGS.

References

1. Aziz I, Hadjivassiliou M, Sanders DS Does gluten sensitivity in the absence of coeliac disease exist? BMJ. 2012 Nov 30; 345:e7907.

2. Sapone A, Bai JC et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012 Feb 7;10:13.

3. Volta U, Tovoli F et al. Serological tests in gluten sensitivity (nonceliac gluten intolerance). J Clin Gastroenterol. 2012 Sep;46(8):680-5.

4. Picarelli A, Di Tola M et al. Oral mucosa patch test: a new tool to recognize and study the adverse effects of dietary nickel exposure. Biol Trace Elem Res. 2011 Feb;139(2):151-9.

5. Vetrano S, Zampaletta U et al. Detection of anti-endomysial and anti-tissue transglutaminase autoantibodies in media following culture of oral biopsies from patients with untreated coeliac disease. Dig Liver Dis. 2007 Oct;39(10):911-6.