Carolina Tomba

Evidence for the presence of non-celiac gluten sensitivity in patients with functional gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten challenge

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

Cereal crops and cereal consumption have had a vital role in Mankinds history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patients clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

microRNA profiles in coeliac patients distinguish different clinical phenotypes and are modulated by gliadin peptides in primary duodenal fibroblasts

CD (coeliac disease) is a frequent autoimmune disorder of the small bowel, which is characterized by an immunological reaction against gluten and transglutaminase in genetically predisposed subjects. However, the molecular determinants underpinning CD pathogenesis are yet to be fully elucidated and little data are available about the involvement of miRNAs (microRNAs) in CD. In the present study, the duodenal mucosa miRNA expression was profiled in adult untreated CD presenting with a classic phenotype or iron-deficiency anaemia, treated patients with or without duodenal normalization, and non-CD subjects as controls. Deregulation of seven miRNAs (miR-31-5p, miR-192-3p, miR-194-5p, miR-551a, miR-551b-5p, miR-638 and miR-1290) was determined in a larger series of CD patients with different clinical phenotypes compared with non-CD subjects. These seven microRNAs were then analysed in duodenal fibroblasts obtained from CD patients and incubated with gliadin peptides (13- and 33-mer). The miRNA cluster miR-192/194, involved in matrix remodelling, was deregulated in CD according to the different clinical presentations, and miR-192-3p levels were modulated by gliadin peptides in vitro. In conclusion, the analysis of miRNAs deserves further consideration for its potential use in the treatment and management of CD.

Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen

Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism.

Enteroscopy for the early detection of small bowel tumours in at-risk celiac patients

BACKGROUND A subset of celiac patients shows a high risk for small bowel malignancies. AIMS To select celiac patients considered at risk and evaluate the diagnostic yield of enteroscopy in this context. METHODS Celiac patients were enrolled from a tertiary referral centre during the period June 2011-June 2013, based on the following criteria: (i) patients diagnosed when aged 50+ and with poor response to gluten-free dieting; (ii) low dietary compliance; (iii) alarm symptoms. The patients underwent small bowel capsule endoscopy and/or double-balloon enteroscopy. Control populations were represented by the 165 non-celiac patients undergoing capsule endoscopy for obscure gastrointestinal bleeding, and the 815,362-strong population of the Italian province of Varese as a registered cohort. RESULTS Fifty-three patients (19% males, mean age 43.6±17.4 years) were evaluated. Two jejunal adenocarcinomas and one ileal neuro-endocrine tumour were diagnosed by enteroscopy (the diagnostic yield for malignancies in the selected population being 5.7%). In the non-celiac controls the detection rate of small bowel tumours by capsule endoscopy was 0.6% (P=0.04). When compared to the registered population, the relative risk for intestinal malignancy was 1282 (95% CI, 407-4033; P<0.0001). CONCLUSIONS Capsule endoscopy and double-balloon enteroscopy can be considered for early disease management of a subset of celiac patients.

Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands

Background/Aim: Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. Methods: During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Results: Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). Conclusion: The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs.

Does TMPRSS6 RS855791 Polymorphism Contribute to Iron Deficiency in Treated Celiac Disease

Does TMPRSS6 RS855791 Polymorphism Contribute to Iron Deficiency in Treated Celiac Disease?

Evaluation of a Modified Italian European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire for Individuals with Celiac Disease

BACKGROUND To date, it is unclear whether individuals with celiac disease following a gluten-free (GF) diet for several years have adequate intake of all recommended nutrients. Lack of a food frequency questionnaire (FFQ) for individuals with celiac disease could be partly responsible for this still-debated issue. OBJECTIVE The aim of the study is to evaluate the performance of a modified European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ in estimating nutrient and food intake in a celiac population. DESIGN In a cross-sectional study, the dietary habits of individuals with celiac disease were reported using a modified Italian EPIC FFQ and were compared to a 7-day weighed food record as a reference method. PARTICIPANTS/SETTING A total of 200 individuals with histologically confirmed celiac disease were enrolled in the study between October 2012 and August 2014 at the Center for Prevention and Diagnosis of Celiac Disease (Milan, Italy). MAIN OUTCOME MEASURES Nutrient and food category intake were calculated by 7-day weighed food record using an Italian food database integrated with the nutrient composition of 60 GF foods and the modified EPIC FFQ, in which 24 foods were substituted with GF foods comparable for energy and carbohydrate content. STATISTICAL ANALYSES PERFORMED An evaluation of the modified FFQ compared to 7-day weighed food record in assessing the reported intake of nutrient and food groups was conducted using Spearmans correlation coefficients and weighted κ. RESULTS One hundred individuals completed the study. The Spearmans correlation coefficients of FFQ and 7-day weighed food record ranged from .13 to .73 for nutrients and from .23 to .75 for food groups. A moderate agreement, which was defined as a weighted κ value of .40 to .60, was obtained for 30% of the analyzed nutrients, and 40% of the nutrients showed values between .30 and .40. The weighted κ exceeded .40 for 60% of the 15 analyzed food groups. CONCLUSIONS The modified EPIC FFQ demonstrated moderate congruence with a weighed food record in ranking individuals by dietary intakes, particularly food groups.

Gluten-free diet or alternative therapy: a survey on what parents of celiac children want

Abstract Objectives: Celiac disease (CD) is treated by life-long gluten-free diet (GFD). Novel therapies are under development. Willingness of CD children’s parents to alternative therapies and GFD impact were evaluated. Methods: Parents of celiac children on GFD were investigated on need and preference for novel CD therapies, children’s enrolment in trials, compliance to and personal judgment on GFD, health status (HS) and quality of life (QoL). Results: About 59.5% surveyed parents expressed the need for alternative therapies with a preference for vaccine-based strategy (39.9%). About 37.7% would accept enrollment in an ad hoc trial, 20.3% would agree to endoscopy during the trial. GFD compliance was 97.4% and well accepted by 93.8%. HS and QoL significantly improved during GFD (p < 0.001). Conclusions: The introduction of novel therapies for CD is desirable for over half of parents, with preference for vaccines. Parents frown upon enrolment in new clinical trials and the subsequent need for additional endoscopy.

Sucrosomial Iron Supplementation in Anemic Patients with Celiac Disease Not Tolerating Oral Ferrous Sulfate: A Prospective Study

Patients with celiac disease (CD) frequently suffer from iron deficiency anemia (IDA) and may benefit from iron supplementation. However, intolerance to iron sulfate and duodenal atrophy could reduce the efficacy of this supplementation. This study evaluated the efficacy of a new sucrosomial iron formulation in patients with CD. Consecutive patients with CD and IDA were divided into two groups: patients with a known intolerance to iron sulfate were treated with sucrosomial iron (30 mg of iron/day), while those receiving iron supplementation for the first time were assigned to iron sulfate (105 mg of iron/day). Forty-three patients were enrolled (38 females, mean age 49 ± 9 years). After a follow-up of 90 days both groups showed an increase in Hb levels compared to baseline (+10.1% and +16.2% for sucrosomial and sulfate groups, respectively), and a significant improvement in all iron parameters, with no statistical difference between the two groups. Patients treated with sucrosomial iron reported a lower severity of abdominal symptoms, such as abdominal and epigastric pain, abdominal bloating, and constipation, and a higher increase in general well-being (+33% vs. +21%) compared to the iron sulfate group. Sucrosomial iron can be effective in providing iron supplementation in difficult-to-treat populations, such as patients with CD, IDA, and known intolerance to iron sulfate.