Abdominal Ultrasound Does Not Reveal Significant Alterations in Patients With Nonceliac Wheat Sensitivity.

GOALS: The goal of this study was (A) to evaluate abdominal ultrasound signs in nonceliac wheat sensitivity (NCWS) patients for features useful in diagnosis and (B) to compare these aspects with those of celiac patients to assess whether ultrasound can be useful in the differential diagnosis between NCWS and celiac disease (CD). BACKGROUND: NCWS diagnosis is difficult as no biomarkers of this condition have as yet been identified. In CD ultrasound aspects have been identified that have a good diagnostic accuracy. STUDY: We prospectively recruited 45 NCWS patients (11 males, 34 females; mean age 35.7 y). Three control groups were included: (A) 99 age-matched CD patients; (B) 18 patients with seronegative CD; (C) 50 patients with irritable bowel syndrome (IBS) who did not improve on a wheat-free diet. NCWS diagnosis was confirmed on the basis of an elimination diet and double-blind placebo-controlled (DBPC) challenge. Ultrasound sign investigation included: dilatation of the small bowel loops, thickening of the small bowel wall, hyperperistalsis, enlarged mesenteric lymph nodes, ascites, hyposplenism, altered diameter of the portal vein. RESULTS: NCWS patients showed a low frequency of pathologic ultrasound findings. Dilated or thickened loops appeared more often in CD patients than in NCWS patients (88.8% vs. 20%; P<0.0001). These US signs were significantly more frequent in seronegative CD than in NCWS patients (both P<0.0001), whereas no difference was found between NCWS patients and IBS controls. CONCLUSIONS: In NCWS patients' ultrasound does not show a characteristic pattern which could be helpful for diagnosis. However, US can be useful to differentiate between NCWS and CD patients and especially those with seronegative CD. (ClinicalTrials.gov NCT03017274).

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up.

We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat-free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebo-controlled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522.

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies.

BACKGROUND & AIMS: There is much interest in wheat sensitivity among people without celiac disease (CD), but little is known about any risks associated with the condition. We evaluated the prevalence of autoimmune diseases (ADs) among patients with nonceliac wheat sensitivity (NCWS), and investigated whether they carry antinuclear antibodies (ANA). METHODS: We performed a retrospective study of 131 patients diagnosed with NCWS (121 female; mean age, 29.1 years) at 2 hospitals in Italy from January 2001 through June 2011. Data were also collected from 151 patients with CD or irritable bowel syndrome (IBS) (controls). Patient medical records were reviewed to identify those with ADs. We also performed a prospective study of 42 patients (38 female; mean age, 34 years) diagnosed with NCWS from July 2011 through March 2014 at 3 hospitals in Italy. One hundred age- and sex-matched subjects with CD or IBS served as controls. Serum samples were collected from all subjects and ANA levels were measured by immunofluorescence analysis. Participants completed a questionnaire and their medical records were reviewed to identify those with ADs. RESULTS: In the retrospective analysis, similar portions of subjects with NCWS (29%) and CD (29%) developed ADs (mainly Hashimoto's thyroiditis, 29 cases), compared with a smaller proportion of subjects with IBS (4%) (P < .001). In the prospective study, 24% of subjects with NCWS, 20% of subjects with CD, and 2% of subjects with IBS developed ADs (P < .001). In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS (median titer, 1:80), 24% of subjects with CD (P < .001), and 2% of subjects IBS (P < .001); in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with CD (P = .02), and 6% of subjects with IBS (P = .005 vs patients with NCWS). ANA positivity was associated with the presence of the HLA DQ2/DQ8 haplotypes (P < .001). CONCLUSIONS: Higher proportions of patients with NCWS or CD develop autoimmune disorders, are ANA positive, and showed DQ2/DQ8 haplotypes compared with patients with IBS.

Lactobacillus reuteri in children with functional abdominal pain (FAP).

AIM: Functional abdominal pain (FAP) is a frequent condition affecting 10-20% of children and can be considered within the classification of functional gastrointestinal disorders (FGID). The objective of this study was to determine the effect of daily supplementation with the probiotic Lactobacillus reuteri DSM 17938 in children with FAP. METHODS: The children (aged 6-16 years) were screened for FAP as defined in the Rome III criteria and 60 patients were recruited in this double-blind, randomised, placebo-controlled trial. The children were randomly allocated to receive either L. reuteri (2×10(8) CFU/day) or identical placebo for 4 weeks followed by a 4-week follow-up period without supplementation. Frequency and intensity of pain was self-recorded by the subjects. RESULTS: The L. reuteri-supplemented children had significantly lower pain intensity compared with the placebo controls. CONCLUSIONS: Supplementation with L. reuteri reduced perceived abdominal pain intensity, which may encourage clinicians to use this probiotic in children with FAP.

Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.

OBJECTIVES: Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers. METHODS: We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001-2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls. RESULTS: Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in "in vitro" assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients. CONCLUSIONS: Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

Contact Dermatitis Due to Nickel Allergy in Patients Suffering from Non-Celiac Wheat Sensitivity.

BACKGROUND:  Non-celiac wheat sensitivity (NCWS) is a new clinical entity in the world of  gluten-related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat  and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS).  Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients  diagnosed by a double-blind placebo-controlled(DBPC)challenge,and to identify  the  characteristics  of  NCWS  patients  with  nickel  allergy.  Methods: We performed  a prospective study  of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from  December  2014 to November 2016; 80 age- and sex-matched subjects with functional gastrointestina l symptoms served as controls. Patients reporting contact dermatitis related to nickel-containing objects  underwent  nickel  patch  test  (Clinicaltrials.gov  registration number: NCT02750735). RESULTS:   Six  out  of  sixty  patients  (10%)  with  NCWS  suffered  from contact dermatitis and  nickel allergy  and  this  frequency  was  statistically  higher (p = 0.04)than observed in the control group(5%. The main clinical characteristic of  NCWS  patients with nickel allergy was a  higher frequency  of  cutaneous  symptoms  after  wheat ingestion compared to NCWS patients who did not suffer  from  nickel  allergy  (p < 0.0001. CONCLUSIONS:  Contact dermatitis and nickel allergy  are more  frequent  in  NCWS  patients than  in  subjects  with  functional gastrointestinal disorders;furthermore, these patients had a very high frequency of cutaneous manifestations after wheat  ingestion.  Nickel  allergy  should  be  evaluated  in  NCWS  patients  who  have  cutaneous  manifestations after wheat ingestion.

Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis.

BACKGROUND: Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. AIM: To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. PATIENTS AND METHODS: The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. RESULTS: EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. CONCLUSION: EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in 'seronegative' patients.

Chronic constipation and food intolerance: a model of proctitis causing constipation.

OBJECTIVE: Chronic constipation in children can be linked to cow's milk intolerance (CMI) but the existence of a food intolerance-dependent proctitis is still debated. The aim of this study was to evaluate the histologic data in patients with food intolerance-related constipation. MATERIAL AND METHODS: Fifty-two consecutive patients (22 M, median age 4 years) with chronic constipation unresponsive to common treatment were enrolled. All patients were put on a cow's milk-free diet for 4 weeks and those uncured on this diet underwent a subsequent 4-week period of oligoantigenic diet. In the patients cured on elimination diet, a subsequent double-blind food challenge was performed to confirm the diagnosis of food intolerance. At entry to the study, routine hemato-chemical and immunologic assays, rectoscopy, and histologic study of the rectal mucosa were performed. In the patients cured on elimination diet, rectal histology was repeated when they were cured. RESULTS: Twenty-four patients were found to be suffering from CMI and 6 from multiple food intolerance. These patients had a normal stool frequency on elimination diet, while constipation reappeared on food challenge. The condition of the remaining 22 patients did not improve on elimination diet. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, number of intraepithelial lymphocytes and eosinophils, and number of eosinophils in the lamina propria. Study of the rectal mucus gel layer showed that the food-intolerant patients had a significantly lower thickness than the other subjects studied. In the food intolerant patients, histologic abnormalities disappeared on elimination diet, when the patients were well. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis with eosinophil infiltrate of the rectal mucosa. A reduced mucus gel layer can be considered a contributory factor in the pathogenesis of the constipation.

Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children.

BACKGROUND: Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying "organic" causes of chronic diarrhea in consecutive adults and children. METHODS: We consecutively enrolled 70 adult patients (30 males, 40 females; median age, 35 years) and 50 children (20 males, 30 females; median age, 3.5 years) with chronic diarrhea of unknown origin. All patients underwent a complete work-up to identify the causes of chronic diarrhea. FC was measured by ELISA. RESULTS: In adult patients, FC showed 64% sensitivity and 80% specificity with 70% positive and 74% negative predictive values for organic causes. False-positive results (8 of 40 cases) were associated with the use of aspirin (3 cases) or nonsteroidal antiinflammatory drugs (1 case) and with the presence of concomitant liver cirrhosis (3 cases). False-negative results mainly included patients suffering from celiac disease (5 cases). Patients with IBD (9 cases) were identified with 100% sensitivity and 95% specificity. In pediatric patients, sensitivity was 70%, specificity was 93%, and positive and negative predictive values were 96% and 56%. False-negative results (11 of 35 cases) were associated mainly with celiac disease (6 cases) or intestinal giardiasis (2 cases). CONCLUSIONS: FC assay is an accurate marker of IBD in both children and adult patients. In adults, false negatives occur (e.g., in celiac disease) and false-positive results are seen in cirrhosis or users of nonsteroidal antiinflammatory drugs. Diagnostic accuracy is higher in children.