Maurizio Mennini

First salivary screening of celiac disease by detection of anti-transglutaminase autoantibody radioimmunoassay in 5000 Italian primary schoolchildren.

Objective: The high prevalence of celiac disease (CD) prompted us to evaluate a new, noninvasive disease screening strategy. The aim was to identify CD in 6- to 8-year-old children for a timely diagnosis, start gluten-free diet (GFD) in compliant subjects, achieve the growth target, and prevent CD complications. Methods: Five thousand subjects were invited to participate in the study. Four thousand forty-eight saliva samples were tested for anti-tissue transglutaminase (tTG) immunoglobulin (Ig)A using a fluid-phase radioimmunoprecipitation method. Positive children were tested for serum radioimmunoassay tTG IgA, enzyme-linked immunosorbent assay tTG IgA, and anti-endomysium IgA. Children confirmed as positive by serum assays underwent endoscopy with duodenal biopsies and, at the diagnosis of CD, were suggested to start GFD. Results: Consent was obtained from 4242 parents (84.8%) for the screening to be performed, and adequate saliva samples were collected from 4048 children (95.4%). Thirty-two children were found to be salivary tTG IgA positive and 9 with borderline autoantibody levels. Thirty-one of the 32 and 3 of the 9 subjects were also serum positive. Twenty-eight children showed villous atrophy when undergoing intestinal biopsy, whereas 1 had Marsh 1 lesions; 3 children were suggested to start GFD without performing endoscopy. CD prevalence in the population investigated (including 19 CD known cases) was 1.16%. The ratio between screening-detected patients and those diagnosed before the screening was 3:2. The ratio between symptomatic and asymptomatic patients was 1:1.6. Conclusions: We demonstrated that it is possible to perform a powerful, simple, well-accepted, and sensitive CD screening using saliva. Until now, the compliance with GFD in children with CD has been optimal.

The Celiac Iceberg: Characterization of the Disease in Primary Schoolchildren

Objective: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy. Identifying CD in schoolchildren to characterize CD iceberg and evaluate the effect of diagnosis in screening-detected children. Methods: A total of 7377 5- to 8-year-old children were invited to participate. A total of 5733 salivary samples were collected and tested for anti-transglutaminase antibodies (tTGAb), using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy and then started gluten-free diet (GFD) and periodical follow-up. Results: Forty-six subjects were found salivary tTGAb–positive and 16 border-line. Forty-five of 46 and 5 of 15 of them were also serum antibody–positive. Forty-two children showed duodenal villous atrophy and 1 had only type 1 lesions. Three children started GFD without performing endoscopy. CD prevalence (including 23 previously diagnosed children with CD) was 1.2%. Considering all 65 celiacs in our sample, a silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%. All patients showed strict adherence to GFD, weight and stature increase, and well-being improvement. Eighty-five percent and all but 2 screening-detected children with CD had Italian parents. Conclusions: Our sample size, representative of primary schoolchildren of our region, demonstrated that CD prevalence is growing in Italy, with a modified clinical spectrum and iceberg deepness.

Detection of respiratory viruses in the 2009 winter season in Rome: 2009 Influenza A (H1N1) complications in children and concomitant type 1 diabetes onset

We investigated clinical characteristics and complications, particularly type 1 diabetes onset, in children hospitalized for 2009 pandemic influenza A (H1N1) virus and compared number of consultations, rate of hospitalization and virus identification in children hospitalized for acute respiratory symptoms (ARS) during the winter season 2009–2010 and 2004–2005. Patients were tested for 2009 H1N1 virus and 14 respiratory viruses on pharyngeal brush/nasal aspirates, using a RT-PCR or nested PCR assays. Consultations and hospitalizations were extracted from operative system GIPSE. The total number of consultations increased by 12%, consultation rate for ARS by 13% and number of hospitalizations by 56% from 2004–2005 to 2009–2010. In 2004–2005, Influenza A virus was identified in only 7% of hospitalized children, while in 2009–2010 the 2009 H1N1 virus was identified in 21%. Three children attending the hospital for ARS and 2009 H1N1 infection had ketoacidosis as the onset manifestation of type 1 diabetes. By comparing the number of new diabetes diagnoses among the two winter seasons, we found a higher number of new diagnoses in October 2009 January 2010 than in the same period in 2004–2005 (19 vs 10). Six children (13%), all presenting with pre-existing diseases, were admitted to the pediatric intensive care unit. No children died. The outbreak of this novel virus has increased pediatric consultation rates and hospitalizations compared with previous winters without causing deaths. The children at highest risk for severe infection are those with comorbidities. The 2009 H1N1 virus seems in some way involved in the pathogenesis of type 1 diabetes.

Duodenal bulb in celiac adults: The "whether biopsying" dilemma

Background: Celiac disease (CD)-related lesions were described in duodenal bulb of celiac patients. Goal: Our aim was to evaluate the morphology of bulb mucosa in adult celiac patients and in controls to evaluate its usefulness for CD diagnosis. Study: We studied 43 celiac patients (10 male, median age: 35.2 y) at diagnosis and 43 gastroenterological controls (10 male, median age: 37.8 y), submitted to upper endoscopy for gastroenterological complaints. Histologic lesions were assayed by an experienced pathologist according to the Marsh modified classification. Antiendomysium antibodies and antitransglutaminase antibodies-tTGAb (ELISA and/or RIA) have been tested. In selected patients, DNA was typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer polymerase chain reaction. Results: In all celiac patients lesions were present in the bulb mucosa. One female with thyroiditis, who had a CD daughter, showed lesions only in the duodenal bulb. Patchy villous atrophy was found in another patient. All celiacs were antiendomysium and/or tTGAb positive. DQ2 heterodimer was present in 5 CD patients. The gastroenterological controls showed normal mucosa in the duodenum. Conclusions: This study demonstrates that CD-related histologic lesions are present in duodenal bulb of adult patients. Moreover, the normal aspect of this mucosa in gastroenterological controls implies the high negative predictive value of this finding. Therefore, we suggest taking at least 1 biopsy on the bulb area and 1 from the distal duodenum for CD diagnosis, in all the patients submitted to upper endoscopy, to avoid missed or delayed diagnosis.

Immediate effect on fertility of a gluten-free diet in women with untreated coeliac disease

In a recent paper in Gut , describing a Swedish population-based cohort, Zugna et al found that women with coeliac disease had normal fertility, but their fertility had decreased in the 2 years preceding the diagnosis of coeliac disease.1 This study provides important answers to fertility problems in patients with coeliac disease by analysing a nationwide database. The results, however, must be interpreted with caution. This paper may be considered confusing because the role of coeliac disease as one of the causes of infertility has been underestimated taking into account population studies in general. Infertility, spontaneous abortion and delayed puberty represent subclinical coeliac disease presentations …

Endoscopic and Histological Gastric Lesions in Children With Celiac Disease: Mucosal Involvement Is Not Only Confined to the Duodenum

Objectives: Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC). Methods: In a retrospective study on 226 patients with CD (82 M; median age: 5.7years) at diagnosis and 154 GC (66 M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti-gastric parietal cell antibodies (GPCA) were assayed by enzyme-linked immunosorbent assay. Results: A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) children with GC (91.7% had CSG). Among patients with CSG, Hp infection was more frequent in controls than in celiac children (P < 0.0001). Ten of 90 patients with CD and 1 of 29 controls were positive for GPCA. Conclusions: Gastritis is a common finding in children with CD and adolescents. In celiac subjects, CSG is the most frequently detected. Our data suggest the hypothesis that LG may be related to a longer exposure to gluten. The presence of GPCA may suggest the presence of an underlying autoimmune process.

Fecal HMGB1 Reveals Microscopic Inflammation in Adult and Pediatric Patients with Inflammatory Bowel Disease in Clinical and Endoscopic Remission.

Background:Fecal high mobility group box 1 (HMGB1) has been suggested to be a novel noninvasive biomarker of gut inflammation. We aimed to assess the reliability of fecal HMGB1, compared with fecal calprotectin (FC), in detecting intestinal inflammation in pediatric and adult patients with inflammatory bowel disease (IBD) and to evaluate the accuracy of HMGB1 in identifying patients with IBD in clinical and endoscopic remission who still have histologic features of inflammation. Methods:Stool samples from 85 children with IBD (49 Crohns disease [CD] and 36 ulcerative colitis [UC] and 119 adults [57 Crohns disease and 62 ulcerative colitis]) were analyzed for the study. Age-matched healthy subjects were used as controls. Fecal HMGB1 and fecal calprotectin were detected through western blot and ELISA, respectively. Results:Fecal HMGB1 expression was significantly increased in pediatric and adult patients with Crohns disease and ulcerative colitis and strongly correlated with the disease severity. Fecal calprotectin and HMGB1 significantly correlated in pediatric (r: 0.60, P < 0.001) and adult (r: 0.72, P < 0.001) IBD patients. Moreover, in patients with clinical and endoscopic remission only fecal HMGB1 showed a strong match with the degree of histological scores of inflammation (CGHAS/IGHAS for Crohns disease and Geboes Score for ulcerative colitis). Conclusions:Fecal HMGB1 is confirmed to be a reliable biomarker of intestinal inflammation; indeed, it significantly correlates with fecal calprotectin in pediatric and adult IBD patients. Moreover, only fecal HMGB1 identifies histologic inflammation in subjects with IBD in clinical and endoscopic remission.

Coeliac disease screening among a large cohort of overweight/obese children.

ABSTRACT Coeliac disease (CD) is a chronic, gluten-dependent enteropathy with a prevalence of approximately 1% in Western countries. Up to now, CD has been described only in sporadic cases of obesity. Our study aimed to evaluate retrospectively CD prevalence in a large series of overweight/obese children and adolescents. Among the 1527 overweight/obese children and adolescents consecutively evaluated, 17 (7 boys, 1.11%) were positive for serology and showed villous atrophy. In all of the patients with CD a well-balanced gluten-free diet was started, and a loss of weight rapidly obtained. Our study demonstrates that CD prevalence in overweight/obese children is similar to the general paediatric population in Italy.

Anti-transglutaminase immunoreactivity and histological lesions of the duodenum in coeliac patients

Coeliac disease (CD) is characterized by several markers, including anti-transglutaminase auto-antibodies (tTGAb) directed against multiple epitopes of the gliadin protein. We aimed to investigate the correlation among CD duodenal lesions, tTGAb titres and the immunoreactivity against tTG constructs. A total of 345 CD patients (209 females, 136 males, overall median age: 7.3 years) were tested for full-length (fl) tTGAb with a fluid-phase radioimmunoassay. Out of the total, 231 patients were also tested for immunoreactivity against tTG fragments (F1: a.a. 227-687 and F2: a.a. 473-687). Patients were classified according to diffuse (D), patchy (P) or bulb (B) histological lesions. All sera were found fltTGAb positive. Patients with D, P and B lesions had a mean Ab index of 0.84±0.39, 0.57±0.39 and 0.45±0.24, respectively. Mean tTGAb titre varied between D and localized (P+B) patients (0.84±0.39 versus 0.52±0.34, P < 0.0001). Overall, 86.1% of patients were F1 auto-antibody (F1Ab) positive (D: 89%, P: 75%, B: 40%; D versus P+B: P = 0.004) and 49% of patients were F2 auto-antibody (F2Ab) positive (D: 53%, P: 19%, B: 10%; D versus P+B: P = 0.0006). Of the D patients 50.7% showed combined F1Ab-F2Ab (D versus P+B: P = 0.001), whereas 60% of B patients were negative for both F1Ab and F2Ab (B versus D: P < 0.0001). Coeliac-specific tTGAb immunoreactivity correlates with the grading and extension of histological duodenal lesions in CD patients at diagnosis. The immunoreactivity against single and combined tTG fragments is significantly higher in patients with D lesions. This is the first evidence of a distinct coeliac-specific immunoreactivity in patients with different duodenal involvement.

Duodenal bulb for diagnosing adult celiac disease: much more than an optimal biopsy site

monopolar snare polypectomy in both establishing a histologic diagnosis and offering treatment.5 The application of a detachable snare for the induction of polyp ischemia and necrosis may be an attractive option in selected cases with large polyps and high risk for polypectomy. In this case, pathologic analysis is mandatory, and regular follow-up and endoscopic examination are suggested after the procedure.6