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 antitransglutaminase 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.

Evaluation of stool antigen test, PCR on ORAL samples and serology for the noninvasive detection of Helicobacter pylori infection in children.

BACKGROUND: Endoscopy represents the gold standard for the diagnosis of Helicobacter pylori infection. We evaluated three noninvasive tests in a group of children: the immunoassay for detection of H. pylori stool antigen, the polimerase chain reaction for identification of bacterial DNA on the oral cavity and the serum specific antibodies. MATERIALS AND METHODS: One hundred and ninety children underwent endoscopy for various gastrointestinal symptoms. H. pylori stool antigen and anti-H. pylori antibodies were assayed by commercial kits. The bacterial DNA on saliva and oral plaque was detected by a seminested PCR. RESULTS: Based on the positivity of culture or urease rapid test and histology, infection was detected in 47 patients. The statistical analysis showed that, for the detection of the infection, stool antigen assay is more effective in sensitivity and negative predictive value (91.5% and 96.5%), whereas specificity and positive predictive values appear slightly better in serology (89.6% and 76.0%). Correlations between serum IgG both with patients' age (r = 0.21, p < .05) and H. pylori stool antigen (r = 0.47, p < .01) were found. The search for bacterial DNA on oral samples proved to be very specific (99.1% on saliva and 98.2% on plaque), but insensitive (22.2% and 25.7%). CONCLUSIONS. In children H. pylori stool antigen represents a sensitive test, suitable for detecting H. pylori infection. Serum IgG proved to be more specific; the PCR on the oral cavity resulted as being a very specific, but insensitive test.

Patchy villous atrophy of the duodenum in childhood celiac disease.

OBJECTIVES: Patchy villous atrophy of the duodenal mucosa has been described in adults with untreated celiac disease (CD) but not in children. The authors evaluated the presence and the distribution of villous atrophy in children with celiac disease to see whether this histologic pattern exists in children. METHODS: We studied 95 children at diagnosis (Group 1) and seven during gluten challenge (Group 2). We measured anti-endomysium antibodies (EMA) by immunofluorescence on monkey esophagus, antihuman-tissue transglutaminase autoantibodies (anti-tTG Abs) by radioimmunoprecipitation, and HLA-DQ2/DQ8 heterodimers by polymerase chain reaction using specific primers. During upper intestinal endoscopy, at least five duodenal biopsy samples were obtained, one from the duodenal bulb and four from the distal duodenum. RESULTS: Thirteen of 95 (13.7%) patients in Group 1 and in 3 of 7 (42.9%) in Group 2 had patchy villous atrophy of the duodenum. In all 16 patients, villous atrophy of the bulb was present. In four children from Group 1, villous atrophy was observed only in the bulb samples. EMA, anti-tTG Abs, and HLA-DQ2/DQ8 heterodimers were present in all patients. Fourteen of 16 had symptomatic CD, and two were silent, detected during screening in subjects at risk for CD. CONCLUSIONS: This is the first study demonstrating that children with CD may have patchy villous atrophy of the duodenum. The bulb mucosa may be the only duodenal area involved, both at diagnosis and after gluten challenge. Therefore, multiple endoscopic biopsies should always be performed, not only in the distal duodenum, but also in the bulb.