Search

Non-celiac gluten sensitivity and celiac disease are known to be two distinct clinical entities, however, non-celiac gluten sensitivity has been detected in a proportion of first-degree relatives of celiac patients. Herein for the first time we describe the occurrence of asymptomatic celiac disease in two siblings, a girl and a boy, whose mother suffered from a proven non-celiac gluten sensitivity. Both the 12-year old girl and 9-year old boy were positive for anti-endomysial and anti-tissue transglutaminase antibodies of IgA class at a very high and low titer, respectively. Duodenal biopsy confirmed the diagnosis of active celiac disease (severe villous flattening) in the girl, whereas her brother had Marsh 1 lesion consistent with a potential celiac disease. This case report indicates that antibody screening for celiac disease can be recommended in any symptomatic or asymptomatic first-degree relatives of patients with non-celiac gluten sensitivity.

Background and Aims: Coeliac disease (CD) is a chronic enteropathy characterized by an increased mortality mainly due to its complications, i.e. refractory CD, abdominal lymphomas, and small bowel carcinoma. Recently, it was shown that overall annual incidence of these complications in CD patients is 0.2%. However, some evidence suggests that risk of developing complications varies in different type of coeliac patients, type of clinical presentation and age at diagnosis of CD being the most important discriminant factors. To calculate the risk of developing compilations according to type of clinical presentation and age at diagnosis of CD. Methods: The data obtained from our previous study were reanalysed to calculate the incidence of complicated CD among coeliac patients according to type of clinical presentation and age at diagnosis of CD. Results: Between Jan 1999 and Oct 2011, 14 (11 F, mean age at diagnosis of complication 61+12 yrs) out of 1840 coeliac patients (1379 F, mean age at diagnosis of CD 35+11 yrs) developed complications (5 refractory CD type I, 2 refractory CD type Il, 2 ulcerative jejunal-ileitis, 3 small bowel adenocarcinomas, 1 B-lymphoma, 1 enteropathy-associated T-cell lymphoma). Relative risk of complications was found to be directly related to age at diagnosis of CD: it was 4,8 for patients diagnosed at age of 30 years, 13.5 at 50 years. and 38.1 at 70 years. 622 out of 1840 coeliac patients were affected by a classical/major form of CD and 13 of them developed complications. Relative risk for these patients was much higher and again it was directly related to age at diagnosis of CD: it was 21.7 for patients diagnosed at age of 30 years, 168.7 at 50 years, and 1311.5 at 70 years. Conclusions: Risk of developing complications in coeliac patients is strongly linked to age at diagnosis and type of clinical presentation of CD. So, follow-up modalities of coeliac patients will have to be tailored according to these individual parameters.

none 6 no Background: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. none Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity Volta U;Bardella MT;Calabrò A;Troncone R;Corazza GR;Study Group for Non-Celiac Gluten Sensitivity

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (beta-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage-and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear beta-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat beta-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis.

Foods are known to be symptom trigger in a large number of patients. Although the underlying mechanisms are still far from being elucidated, the increasing number of patients presenting with a clinical picture suggestive of food intolerance has recently caught physicians’ attention. This review is intended to focus on clinical, diagnostic and therapeutic aspects of food intolerance such as those elicited by wheat/ gluten (non celiac wheat/gluten sensitivity, NCW/GS) and fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs). NCWGS is a syndrome characterized by gastrointestinal (e.g., bloating, abdominal pain and bowel habit changes) and extraintestinal (e.g., headache, skin rashes and fibromyalgia-like) symptoms related to the ingestion of gluten-containing foods in subjects testing negative for celiac disease and/or wheat allergy. Symptoms improve/disappear after gluten-free diet and recur with gluten challenge. Functional bowel symptoms overlapping those of NCW/GS are also evoked by FODMAPs and wheat proteins (e.g., amylase trypsin inhibitors). So far, there are no biomarkers for NCW/GS, although 50% of patients display IgG anti-gliadin antibodies. A double-blind, placebo-controlled food challenge is currently the only way to confirm the diagnosis of NCW/GS. There are no controlled trials to prove actual efficacy of low-FODMAPs diet vs placebo. Studies are eagerly awaited to shed light on dietary changes as measure to be used in patients with food sensitivity and related gut symptoms.

Celiac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. This condition can also affect many extraintestinal tissues, including the liver. We report a patient presenting with a marked increase of transaminases at diagnosis of CD. The immune markers for autoimmune hepatitis (AIH) were negative. Following a few months of a strict gluten-free diet (GFD), aminotransferase levels decreased significantly (< 2.5x U/L). The response to GFD suggested that the liver damage was due to a gluten-dependent celiac hepatitis, the most common liver abnormality in CD. Despite the fact that the patient never stopped the GFD, yet, in a few months, the aminotransferase levels raise again to high values (> 50x U/L). At this time, the liver autoantibodies turned to be positive thus confirming the development of a type 1 AIH. The hepatic damage progressed to a late onset liver failure requiring liver transplantation.

OBJECTIVES: Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Coeliac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. In recent years, the Internet and the non-medical press have reported a correlation between gluten-related disorders and fibromyalgia-like symptoms. The aim of our study was to verify a possible association between FM and CD, by assessing the prevalence of CD in a cohort of FM patients and vice versa. METHODS: 90 consecutive subjects from our Rheumatologic outpatient clinic who had been diagnosed with FM were serologically tested for CD and positive patients underwent esophagogastroduodenoscopy to obtain duodenal biopsies. A second group of 114 consecutive subjects from our Coeliac Disease outpatient clinic were investigated for the presence of FM-like symptoms through a questionnaire. Patients reporting chronic widespread pain were addressed to a rheumatologist for further evaluation. RESULTS: The overall prevalence of CD in our FM patients was identical to that expected in general population (around 1%). In our CD group 17 patients (14.9%) reported chronic widespread pain at the questionnaire and 13 (11.4%) satisfied ACR 1990 criteria for FM. Their symptoms had not been modified by GFD. CONCLUSIONS: A serological screening for CD is not recommended in FM patients but rather a case-finding strategy should be performed. At the same time, proposals of GFD in FM patients, in absence of a well-established diagnosis of CD, should be rigorously avoided.

Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively.