SELF-REPORTED NON-CELIAC GLUTEN SENSITIVITY IN ITALIAN YOUNG ADULTS: A CROSS-SECTIONAL STUDY. A DIETARY FAD?

OBJECTIVES: In different countries, the exact prevalence of people that refer symptoms after gluten ingestion is increasing and the unavailability of reliable laboratory tests to diagnose the condition known as non-celiac gluten sensitivity (NCGS) has opened the door to the spread of survey-based studies to hypothesize a prevalence of this condition with highly discordant results. We aim to describe the attitude toward gluten consumption in a large population of young adults in Italy. METHODS: A questionnaire-based cross-sectional study was conducted in thirteen Italian cities to investigate the dietary attitudes of more than 9400 people distributed throughout the country about gluten consumption. Only those referring to gluten-related symptoms with a frequency equal to "always" or "most of the time" were considered self-reported NCGS (SR-NCGS) patients. RESULTS: Five thousand two hundred and thirty-four of 9432 eligible participants (55.5%) fully completed the questionnaire. Excluding those with previous gastrointestinal diagnoses of celiac disease and wheat allergy, we have finally analyzed 4987 questionnaires. Four hundred and eighty-seven participants indicated gluten-related symptoms "always" or "most of the time" (SR-NCGS subjects), while 121 already had a medical diagnosis of NCGS. The minimum prevalence figure of SR-NCGS is 6.4% (95%CI: 6.0-6.9), with a higher prevalence in females (79.9%). The most frequent gluten-related symptoms were bloating, abdominal pain and tiredness. CONCLUSIONS: The high prevalence of people reporting symptoms after gluten ingestion requires that the diagnosis of NCGS should be ascertained with a double-blind controlled study to limit the number of people who improperly approach a gluten-free diet.

Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet.

BACKGROUND & AIMS: We studied the prevalence of functional abdominal pain disorders (FAPDs) and functional constipation (FC) in a large prospective cohort of children with celiac disease on a strict gluten-free diet (GFD). METHODS: We performed a prospective cohort study, from 2016 through 2018, in a tertiary care center in Italy, of 417 patients (37% male; mean age, 13.7 y) with a diagnosis of celiac disease (European Society for Paediatric Gastroenterology Hepatology, and Nutrition criteria) who had been on a strict GFD for more than 1 year and had negative results from serologic tests after being on the GFD. Parents and children (>10 y) were asked to fill in a questionnaire on pediatric gastrointestinal symptoms, according to Rome IV criteria. Patients' closest siblings (or cousins) who had negative results from serologic test for celiac disease were used as controls (n = 373; 39% male; mean age, 13.5 y). RESULTS: We found a higher prevalence of FAPDs among patients with celiac disease (11.5%) than controls (6.7%) (P < .05); the relative risk (RR) was 1.8 (95% CI, 1.1-3.0). Irritable bowel syndrome (IBS) and FC defined by the Rome IV criteria were more prevalent in patients with celiac disease (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively); the RR for IBS was 2.3 (95% CI, 1.1-4.6) and the RR for functional constipation was 2.1 (95% CI, 1.4-3.2). We found no differences in the prevalence of other subtypes of FAPDs. A logistic regression showed that younger age (P < .05) and a higher level of anti-transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration. CONCLUSIONS: Celiac disease is associated with an increased risk of IBS and FC. Strategies are needed to manage IBS and FC in patients with celiac disease.

Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.

GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.

Introduction of gluten, HLA status, and the risk of celiac disease in children.

BACKGROUND: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Mode of Delivery and Risk of Celiac Disease: Risk of Celiac Disease and Age at Gluten Introduction Cohort Study.

OBJECTIVE: To determine whether the mode of delivery is associated with the risk of celiac disease (CD) in a cohort of children genetically predisposed to CD prospectively followed from birth. STUDY DESIGN: By telephone interview, we recorded information on the mode of delivery of children participating in the Risk of Celiac Disease and Age at Gluten Introduction study, a multicenter, prospective intervention trial that compared early and delayed introduction of gluten in infants with at least 1 first-degree relative affected with CD. The human leukocyte antigen genotype was determined at 15 months of age, and serologic screening for CD was performed at 15, 24, and 36 months of age and at 5, 8, and 10 years of age. Patients with positive serologic findings underwent intestinal biopsy. The primary outcome of the current study was the prevalence of CD autoimmunity and overt CD at 5 years of age, according to the mode of delivery. RESULTS: The study-group included 553 children at CD risk because of positivity for human leukocyte antigen-DQ2, -DQ8, or both. We obtained data on the mode of delivery from 431 of 553 children; 233 of 431 children were born by vaginal delivery (54%). At 5 years of age, the prevalence of CD autoimmunity or overt CD was not different between children born by cesarean or vaginal delivery (24% and 19%, P = .2; 19% and 14%, P = .2 respectively, by the log-rank test). CONCLUSIONS: In this cohort of children genetically predisposed to CD, the mode of delivery did not influence the risk of developing CD.

Impact of the birth's season on the development of celiac disease in Italy.

Celiac disease (CD) is an immune-mediated systemic disorder induced by a trigger factor in genetically susceptible individuals. There is emerging evidence about the impact of the month of birth on the development of several autoimmune diseases. Our aim was to investigate whether, in Italian CD children, the season of birth is associated with development of CD later in life. We report a survey conducted at two Italian referral centers for CD in Rome and Bari. The CD database was created to enable retrospective examination of the data of all the consecutive patients, born between 2003 and 2010, who had received a diagnosis of CD. This CD patient group comprising 596 children was compared with a reference group that included all subjects born in the same period and in the same cities (439,990 controls). Overall, there was a summer birth preponderance in CD patients compared to controls (28.2 % of CD patients vs 23.0 % of the control population; OR 1.315; 95 % CI 1.100 to 1.572). Stratifying the caseload by gender and age, the summer birth preponderance was maintained for females (28.6 % CD females vs 22.6 % control females; OR 1.368; 95 % CI 1.069 to 1.750). CONCLUSIONS: our survey confirms that in Italy, children born in summer are at higher risk to develop CD than subjects born in other seasons. The identification of a responsible seasonal factor or factors, such as timing of the first introduction of gluten and/or acute viral gastrointestinal infections, would be very important for disease prevention strategies. WHAT IS KNOWN: • Environmental factors could be involved in the pathogenesis of CD. • Data about the impact of season of birth on CD development is so far derived from North American, Northern European and Israeli surveys. WHAT IS NEW: • This is the first study in Southern Europe to find a relationship between season of birth (summer) and development of CD. • Summer-born infants are introduced to complementary feeding (gluten) in winter, when the rotavirus infection is at its highest peak; this may be the link between season of birth and development of CD.

Clinical, serologic, and histologic features of gluten sensitivity in children.

OBJECTIVE: To describe the clinical, serologic, and histologic characteristics of children with gluten sensitivity (GS). STUDY DESIGN: We studied 15 children (10 males and 5 females; mean age, 9.6 ± 3.9 years) with GS who were diagnosed based on a clear-cut relationship between wheat consumption and development of symptoms, after excluding celiac disease (CD) and wheat allergy, along with 15 children with active CD (5 males and 10 females; mean age, 9.1 ± 3.1 years) and 15 controls with a functional gastrointestinal disorder (6 males and 9 females; mean age, 8.6 ± 2.7 years). All children underwent CD panel testing (native antigliadin antibodies IgG and IgA, anti-tissue transglutaminase antibody IgA and IgG, and anti-endomysial antibody IgA), hematologic assessment (hemoglobin, iron, ferritin, aspartate aminotransferase, erythrocyte sedimentation rate), HLA typing, and small intestinal biopsy (on a voluntary basis in the children with GS). RESULTS: Abdominal pain was the most prevalent symptom in the children with GS (80%), followed by chronic diarrhea in (73%), tiredness (33%), bloating (26%), limb pain, vomiting, constipation, headache (20%), and failure to thrive (13%). Native antigliadin antibodies IgG was positive in 66% of the children with GS. No differences in nutritional, biochemical, or inflammatory markers were found between the children with GS and controls. HLA-DQ2 was found in 7 children with GS. Histology revealed normal to mildly inflamed mucosa (Marsh stage 0-1) in the children with GS. CONCLUSION: Our findings support the existence of GS in children across all ages with clinical, serologic, genetic, and histologic features similar to those of adults.

Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multifactorial etiology, characterized by impairment in two main functional areas: (1) communication and social interactions, and (2) skills, interests and activities. ASD patients often suffer from gastrointestinal symptoms associated with dysbiotic states and a "leaky gut." A key role in the pathogenesis of ASD has been attributed to the gut microbiota, as it influences central nervous system development and neuropsychological and gastrointestinal homeostasis through the microbiota-gut-brain axis. A state of dysbiosis with a reduction in the Bacteroidetes/Firmicutes ratio and Bacteroidetes level and other imbalances is common in ASD. In recent decades, many authors have tried to study and identify the microbial signature of ASD through in vivo and ex vivo studies. In this regard, the advent of metabolomics has also been of great help. Based on these data, several therapeutic strategies, primarily the use of probiotics, are investigated to improve the symptoms of ASD through the modulation of the microbiota. However, although the results are promising, the heterogeneity of the studies precludes concrete evidence. The aim of this review is to explore the role of intestinal barrier dysfunction, the gut-brain axis and microbiota alterations in ASD and the possible role of probiotic supplementation in these patients.

Prevalence and natural history of potential celiac disease in at-family-risk infants prospectively investigated from birth.

OBJECTIVE: To evaluate the frequency and the natural history of potential (serology positive/Marsh 0-1 histology) celiac disease (CD) in children with a family risk of CD and factors associated with potential instead of overt (serology positive/Marsh 2-3 histology) CD expression. STUDY DESIGN: Two-year follow-up study of 96 children (57 females; mean age: 29 ± 12 months) prospectively investigated from birth with: (1) a CD-affected first-degree relative; (2) positivity of serum IgA anti-tissue transglutaminase (tTG) or IgG antigliadin and IgA deficiency; and (3) the results of small intestinal biopsy. Children with potential CD were advised to remain on a gluten containing diet, repeat the celiac antibodies every 6 months, and to have an intestinal biopsy performed in case of persistently high anti-tTG level. Factors discriminating between potential and overt CD were analyzed by decision tree analysis based on the C4.5 algorithm. RESULTS: Twenty-four children had potential and 72 overt CD. The stronger predictors of potential CD were lack of symptoms, anti-tTG level lower than 11-fold the upper normal limit, age lower than 24 months, and breastfeeding longer than 8 months. Eighteen out of 21 (86%) patients with potential CD continuing a gluten-containing diet became antibody negative, 1/21 (5%) developed overt CD, and 2/21 (9%) had fluctuating antibodies levels after 2 years. CONCLUSIONS: The prevalence of potential CD and the percentage of short-term loss of CD-related-antibodies are high in infants at-family-risk for CD. In symptomless children with a positive celiac serology, the decision of performing an intestinal biopsy should be preceded by a period of repeated serological testing.

Case report: Late-onset hypertrophic pyloric stenosis in a 3-year-old boy: It is never too late.

Hypertrophic Pyloric Stenosis (HPS) represents a relatively rare occurrence beyond infancy. Here, we present the case of a barely 3-year-old boy diagnosed with late-onset HPS and successfully treated with extra-mucosal pyloromyotomy. We review the literature, challenging the principle that more aggressive surgical approaches should be preferred over less invasive ones.

Probiotics and gastrointestinal diseases.

During the past decades, scientists have discovered the intimate role of the gut microbiome in human health, and since then, several papers have been published to investigate if the use of biotics (probiotics, prebiotics, synbiotics, and postbiotics) may have a beneficial impact on human health both in treatment and prevention. We now ask ourselves whether we have reached the finish line or just a new starting point, as the evidence supporting the use of biotics in several conditions still needs a lot of work. Many questions remain unanswered today because the evidence differs depending on the indication, used strain, and amount and duration of administration. Herein we will summarize the evidence on probiotics in some gastrointestinal diseases such as infantile colic, functional abdominal pain disorders, celiac disease, acute gastroenteritis, inflammatory bowel disease, and Helicobacter pylori infection.

Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study.

The association between eosinophilic esophagitis and celiac disease is still controversial and its prevalence is highly variable. We aimed to investigate the prevalence of esophageal eosinophilia and eosinophilic esophagitis in a large group of children with celiac disease, prospectively followed over 11 years. METHODS: Prospective observational study performed between 2008 and 2019. Celiac disease diagnosis was based on ESPGHAN criteria. At least four esophageal biopsies were sampled in patients who underwent endoscopy. The presence of at least 15 eosinophils/HPF on esophageal biopsies was considered suggestive of esophageal eosinophilia; at the same time, eosinophilic esophagitis was diagnosed according to the International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. RESULTS: A total of 465 children (M 42% mean age 7.1 years (range: 1-16)) were diagnosed with celiac disease. Three hundred and seventy patients underwent endoscopy, and esophageal biopsies were available in 313. The prevalence of esophageal eosinophilia in children with celiac disease was 1.6% (95% CI: 0.54-2.9%). Only one child was diagnosed as eosinophilic esophagitis; we calculated a prevalence of 0.3% (95% CI: 0.2-0.5%). The odds ratio for an association between eosinophilic esophagitis and celiac disease was at least 6.5 times higher (95% CI: 0.89-47.7%; p = 0.06) than in the general population. CONCLUSION: The finding of an increased number of eosinophils (>15/HPF) in celiac patients does not have a clinical implication or warrant intervention, and therefore we do not recommend routine esophageal biopsies unless clinically indicated.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

OBJECTIVE: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance. STUDY DESIGN: Post hoc retrospective cohort study in a tertiary referral center for pediatric gastroenterology in southern Italy. All 168 children who were positive for Helicobacter pylori were enrolled. Patients had received clarithromycin-based 7-day triple therapy (73 children) or 10-day sequential therapy regimen (95 children). Real-time polymerase chain reaction for assessing clarithromycin resistance was performed on sections of paraffin-embedded gastric biopsy samples. RESULTS: H pylori eradication was achieved in 16 of 32 (50%) children with the A2143G mutation, in 8 of 10 patients with either A2142G or A2142C strains (80%), and in 112 of 116 children with susceptible strains (88.9%). The presence of A2143G mutation was associated with a lower cure rate compared with the rate in the absence of this mutation (50% vs. 89%; P = .001). The sequential regimen achieved a higher cure rate than triple therapy in patients with A2143G mutant strains (80% vs nil; P < .001). CONCLUSIONS: The A2143G mutation confers higher risk of treatment failure. Sequential regimen has higher efficacy than standard therapy, even in children with A2143G mutatant strains.

Celiac disease seropositivity in Saharawi children: a follow-up and family study.

BACKGROUND: Celiac disease (CD) is a common disease in the Saharawi population of Arab-Berber origin. Saharawi patients with CD and their families were invited to participate in a follow-up study aimed at checking the CD serology status in patients being treated with the gluten-free diet (GFD) and investigating the prevalence of CD in first-degree relatives. PATIENTS AND METHODS: We investigated 975 subjects (62.8% females and 37.2% males, age range 0.7 to 75.4 years, median age 13.4 years) belonging to 212 families, by determining the serum immunoglobulin A anti-transglutaminase and anti-endomysial antibody levels. Thirty-two first-degree relatives were already receiving GFD when tested. RESULTS: Overall, 42.2% of the 244 treated subjects with CD showed a borderline/positive anti-transglutaminase determination, and 36.6% were also anti-endomysial positive. The serologic family screening detected 33 previously undiagnosed CD cases. The 65 affected first-degree relatives were sibling (42), mother (12), son/daughter (7), and father (4). The overall prevalence of CD among first-degree relatives was 65 of 763 (8.5%, 95% confidence interval 6.5-10.5). Based on our previous estimate of CD prevalence in the pediatric Saharawi population (5.6%), the sibling relative risk was 1.5. CONCLUSIONS: The risk of CD in the Saharawis is only modestly increased in first-degree relatives compared with the general population, probably because of the higher frequency of CD predisposing genes in the general population. Saharawi patients with CD receiving GFD showed poor adherence to the treatment, which could contribute to residual CD-related morbidity and mortality.

Comparison of esophageal pH and multichannel intraluminal impedance testing in pediatric patients with suspected gastroesophageal reflux.

BACKGROUND: Multichannel intraluminal impedance (MII) is a pH-independent method of assessing gastroesophageal reflux. AIM: To evaluate the diagnostic accuracy of MII-pH as compared with conventional pH monitoring in detecting reflux events (REs) and symptom association in different age groups. METHODS: : A prospective direct comparison of 2 diagnostic techniques on 291 consecutive patients referred for suspected gastroesophageal reflux disease. Sensitivity and diagnostic accuracy of MII-pH versus pH monitoring and symptom association were measured. RESULTS: MII-pH detected 13631 REs, 6260 (46%) of which were nonacid. The prevalence of weakly acid refluxes in the 24 hours and postprandial period as well as the proximal extension of refluxate were significantly greater in infants as compared with children (P < 0.001, P < 0.001, and P < 0.01, respectively). The diagnostic accuracy of combined MII-pH in revealing all RE and acid RE were significantly higher in infants as compared with children (92% vs 82%, P < 0.01 and 83% vs 76%, P < 0.04, respectively). The addition of MII to conventional pH monitoring significantly increases the diagnostic yield of symptom association analysis in revealing an association between atypical symptoms and refluxes irrespective of age, whereas in studying typical symptoms it was true only for infants. CONCLUSIONS: Addition of MII to conventional pH monitoring significantly increases the diagnostic yield in detecting REs, prevalently in infants, and in revealing an association between refluxes and symptoms, prevalently respiratory ones and in infants group.

Long-Term Outcome of Potential Celiac Disease in Genetically at-Risk Children: The Prospective CELIPREV Cohort Study.

BACKGROUND: The long-term outcome of potential celiac disease (CD) is still a debated issue. We aimed to evaluate the progression of potential CD versus overt CD after 10-years of follow-up in a cohort of children genetically predisposed to CD. METHODS: The CELIPREV study is prospectively following from birth 553 children with CD-predisposing HLA genes. Children with a diagnosis of potential CD continued to receive a normal diet and repeated the serological screening for CD every year. An intestinal biopsy was taken in presence of persistent positive serology. RESULTS: Overall, 26 (4.7%) children received a diagnosis of potential CD (50% females, median age 24 months). All children were symptom-free. Twenty-three children continued a gluten-containing diet; at 10 years from the first biopsy, three children developed overt CD (13%), 19 (83%) became antibodies negative at 1 year from the first biopsy and remained negative up to 10 years of follow-up and one subject (4%) had fluctuating antibody course with transiently negative values and persistently negative biopsy. CONCLUSIONS: In children genetically predisposed to CD with a diagnosis of potential CD the risk of progression to overt CD while on a gluten-containing diet is very low in the long-term.

Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study.

BACKGROUND: Several studies report an inhibitory effect of probiotics on Helicobacter pylori. AIM: To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment. MATERIALS AND METHODS: In a double-blind placebo-controlled study, 40 H. pylori-positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, (13)C-urea breath test, and H. pylori stool antigen determination at entry and (13)C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all. RESULTS: In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both (13)C-urea breath test delta-value and H. pylori stool antigen quantification after 4 weeks of treatment (p < .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value (p < .05) that was not present in those receiving placebo (p = not significant). No difference in eradication rates was observed. CONCLUSIONS: L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.

High rate of spontaneous normalization of celiac serology in a cohort of 446 children with type 1 diabetes: a prospective study.

OBJECTIVE: In children with type 1 diabetes mellitus (T1DM), elevated levels of antitissue transglutaminase (anti-tTG) antibody may spontaneously normalize, despite continued consumption of gluten. We aimed to investigate the prevalence of spontaneous normalization of anti-tTG levels and the existence of factors predictive for this outcome. RESEARCH DESIGN AND METHODS: All children referred from 2002 to 2012 were screened for celiac disease (CD) at diabetes onset and at specific intervals. In the presence of a high anti-tTG titer or clinical symptoms, children were offered endoscopy, and asymptomatic patients with a low anti-tTG titer were invited to a second serological test after 6 months of eating a gluten-containing diet. RESULTS: The study included 446 children. Of these, 65 (14.5%) became positive for celiac serology: 38 (58%) had a persistently elevated anti-tTG titer and 27 (41%) fluctuating anti-tTG titer; 18 (28%) became negative. The prevalence of positive CD autoimmunity and overt CD was 14.3% (95% CI 11-17) and 8.5% (95% CI 5-10), 15- and 8-times higher than the general pediatric population, respectively. Asymptomatic children older than 9.1 years at T1DM onset had the lowest risk to develop CD. CONCLUSIONS: Serum anti-tTG levels decreased spontaneously in 40% of children with T1DM and became negative in 20%, despite gluten consumption. This finding supports the hypothesis of a state of temporary positivity of celiac serology in children with diabetes. In absence of clinical symptoms or signs of CD, histological confirmation of the disease and the gluten-free diet should be postponed to avoid unnecessary procedures and reduce an additional psychological burden.