R.P.L. Luparia

Duodenal bulb biopsies in celiac disease: a multicenter study

Objectives: Celiac disease (CD)–related lesions have been reported in duodenal bulb biopsies, sometimes the bulb mucosa being the only one affected. The aim was to verify in a significant series whether histological lesions are always present in the bulb of celiac patients, what is the prevalence of lesions when isolated to the bulb, and if similar lesions are present in nonceliac subjects. Methods: We studied 665 children with CD (241 males, range 9 months–15 years, 8 months), at diagnosis on a gluten-containing diet, and 348 age- and sex-matched gastroenterological controls submitted to upper endoscopy for gastroenterological complaints. During endoscopy, multiple biopsies (1 bulb and 4 distal duodenum samples) were taken. Anti-endomysium antibodies were evaluated by immunofluorescence method, anti–human tissue–transglutaminase antibodies by an enzyme-linked immunosorbent assay or radioimmunoassay. Human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes were typed by polymerase chain reaction sequence–specific primers repeat method. Results: In all of the patients with CD, histological lesions were present in the bulb sample; in 16 of them, the lesions were present only in the bulb. Patchy villous atrophy was found in 20 children. All of the patients with CD were anti-endomysium and/or anti-transglutaminase positive. The controls showed neither autoantibody positivity nor mucosal changes compatible with CD. Conclusions: This study demonstrated that CD-related histological lesions are always present in the bulb; sometimes this specific site is the only one affected. Therefore, we suggest taking 2 biopsies from the bulb and 2 from the distal duodenum for CD diagnosis.

Serologic and genetic markers of celiac disease: A sequential study in the screening of first degree relatives

Objectives: The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy. Methods: We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy. Results: TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up. Conclusions: On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.

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.

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.

PA36 PSYCHOLOGICAL IMPACT OF COELIAC DIAGNOSIS AND GLUTEN-FREE DIET IN SILENT SALIVARY SCREENING-DETECTED SCHOOL CHILDREN

Objectives: Lymphocytic gastritis (LG) has been described in coeliac disease (CD) patients and in patients with Helicobacter pylori (Hp) infection but the pathogenetic mechanism remains unknown. Aims: The aim of our study was to evaluate the characteristics of the gastric mucosa and the prevalence of lymphocytic gastritis in a large series of CD children and adolescents. Methods: 167 CD children at the diagnosis (F 108; range 11 months–18 years), consecutive performing the upper-intestinal endoscopy at our Department over the period Jan 2008-Dec 2009, were enrolled. Duodenal (2 bulb and 4 distal duodenum samples) together with gastric antral biopsies, were performed. CD diagnosis was performed according to the NASPGHAN criteria. Hp infection was diagnosed by histology and the rapid urease test. Gastric lesions and duodenal biopsies were classified according to the modified Updated Sydney System and to the modified Marsh classification, respectively. Anthropometric and clinical data of each patient were registered at the diagnosis. Moreover, gastric parietal cells antibodies (APCA) were determined with an ELISA. Results: Gastric alterations was found in 38/167 CD children (23%). Particularly, lymphocytic gastritis was found in 13 CD patients (7.8%); superficial chronic gastritis (SCG) was detected in 24 celiacs (14.4%); and one child (0.6%) showed severe interstitial chronic gastritis (ICG). 3/38 children (one with LG, one with SCG and one with ICG) presented Hp infection. Ten patients with LG were symptomatic (7 typical and 3 atypical) while four were silent. Among patients with SCG, 16 children were typical, 5 atypical and 3 silent, and the prevalent symptoms were diarrhoea, abdominal pain and low weight growth. In the table are shown histological grading of the gastric mucosa in LG and SCG patients. The most frequent duodenal lesion, total villous atrophy (Marsh 3C), was detected in 100% and 92% of LG and SCG CD patients. Among CD children, no APCA were found in patients without gastritis, while 3/22 with gastric lesions were positive for APCA (one with mild LG and the other two with mild SCG).

PA37 RETROSPECTIVE ANALYSIS OF COAGULATION DISORDERS IN CHILDREN AND ADOLESCENTS WITH COELIAC DISEASE AT DIAGNOSIS

Objectives: Lymphocytic gastritis (LG) has been described in coeliac disease (CD) patients and in patients with Helicobacter pylori (Hp) infection but the pathogenetic mechanism remains unknown. Aims: The aim of our study was to evaluate the characteristics of the gastric mucosa and the prevalence of lymphocytic gastritis in a large series of CD children and adolescents. Methods: 167 CD children at the diagnosis (F 108; range 11 months–18 years), consecutive performing the upper-intestinal endoscopy at our Department over the period Jan 2008-Dec 2009, were enrolled. Duodenal (2 bulb and 4 distal duodenum samples) together with gastric antral biopsies, were performed. CD diagnosis was performed according to the NASPGHAN criteria. Hp infection was diagnosed by histology and the rapid urease test. Gastric lesions and duodenal biopsies were classified according to the modified Updated Sydney System and to the modified Marsh classification, respectively. Anthropometric and clinical data of each patient were registered at the diagnosis. Moreover, gastric parietal cells antibodies (APCA) were determined with an ELISA. Results: Gastric alterations was found in 38/167 CD children (23%). Particularly, lymphocytic gastritis was found in 13 CD patients (7.8%); superficial chronic gastritis (SCG) was detected in 24 celiacs (14.4%); and one child (0.6%) showed severe interstitial chronic gastritis (ICG). 3/38 children (one with LG, one with SCG and one with ICG) presented Hp infection. Ten patients with LG were symptomatic (7 typical and 3 atypical) while four were silent. Among patients with SCG, 16 children were typical, 5 atypical and 3 silent, and the prevalent symptoms were diarrhoea, abdominal pain and low weight growth. In the table are shown histological grading of the gastric mucosa in LG and SCG patients. The most frequent duodenal lesion, total villous atrophy (Marsh 3C), was detected in 100% and 92% of LG and SCG CD patients. Among CD children, no APCA were found in patients without gastritis, while 3/22 with gastric lesions were positive for APCA (one with mild LG and the other two with mild SCG).