The Spectrum of Duodenal Histologic Findings in Patients With Trisomy 21: A Multicenter Study.

OBJECTIVES: Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies. METHODS: Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD). RESULTS: We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA-CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%). CONCLUSIONS: Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD.

Intussusception as Rare Presenting Sign of Pediatric Celiac Disease: A Case Series.

Intussusception is the most common cause of gastrointestinal obstruction in children and typically presents with acute abdominal pain. Intussusception usually occurs in children under the age of 3 in the ileocecal region. Over the past 5 years, multiple patients at the Children's Hospital of Philadelphia have been diagnosed with both intussusception and biopsy-confirmed celiac disease (CD). Intussusception may be a presenting sign of pediatric CD and should raise clinical suspicion for celiac screening, especially if it is a small bowel-small bowel intussusception that occurs after the age of 3 in a malnourished patient.

Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders.

The aim of the study was to determine the correlation between duodenal mucosal biopsies and tissue transglutaminase immunoglobulin A (tTG-IgA) levels in pediatric patients with biopsy-confirmed celiac disease (CD) and eosinophilic gastrointestinal disorders (EGID) who have had repeat duodenal biopsies after initiating a gluten-free diet. Methods: A retrospective chart review was performed of children with CD and EGID seen at the Children's Hospital of Philadelphia between 2003 and 2018. Data collected included duodenal biopsy pathology, celiac serology including tTG-IgA, and symptom reports. Duodenal healing was defined as normal villous architecture and no intraepithelial lymphocytes. These data were compared with tTG-IgA level. Data were analyzed with Fisher exact test and t test methods. Results: Thirty-nine patients had normal IgA and diagnoses of both CD and EGID. At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values. Sixty percent (9/15) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels, and 57% (8/14) of patients with normal tTG-IgA levels had evidence of active disease on biopsy. Conclusions: The data show that an abnormal tTG-IgA drawn after initiation of a gluten-free diet is not correlated with duodenal mucosal injury in pediatric patients with CD and EGID. This suggests that serologic surveillance with tTG-IgA is not sufficient to monitor CD intestinal healing in this patient cohort. Persistent elevations of tTG-IgA in CD patients with normal duodenal biopsies should prompt investigation into other potential causes.

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis.

OBJECTIVES: TSLP has been shown to be associated with eosinophilic esophagitis (EoE). Specifically, children with EoE often have the nucleotides AA or AG instead of GG at the single nucleotide polymorphism position RS3806932. Presently, the phenotypic characteristics in EoE children with the TSLP EoE risk allele are unknown. METHODS: A retrospective analysis was performed of all children with EoE who had TSLP genotyping at The Children's Hospital of Philadelphia from 2008-2014. EoE food allergen triggers, presence of atopic features, IgE mediated food allergy and skin prick testing results were reviewed. The number and type of EoE food allergen triggers were compared with genotype using chi-square analysis. Primary cell cultures from EoE patients with or without the risk allele were stimulated with ovalbumin and TSLP secretion was measured by ELISA. RESULTS: Fifty three of 309 patients were found to have no copies of the TSLP risk allele, whereas 256 patients were found to have one or more copies of the risk allele. There was an increase in the number of patients with three or more EoE food allergens among those who were either homozygous or heterozygous for the risk allele compared to those without the risk allele (P < 0.0001). This was independent of their atopic background. Primary cultures from patients homozygous for the risk allele had greater TSLP secretion than those isolated from heterozygous patients. CONCLUSIONS: The TSLP risk allele is associated with having multiple EoE food allergen triggers. This novel EoE genotypic-phenotypic correlation may guide future treatment for those with the TSLP risk allele.

Eosinophilic Gastrointestinal Disorders.

Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an isolated infiltration of eosinophils into the epithelium of the esophagus and is triggered by specific allergens. Patients should undergo an upper endoscopy with biopsy after 6 to 8 weeks of treatment with a proton pump inhibitor in order to make the diagnosis of EoE. Eosinophilic gastroenteritis is a pathologic eosinophilic infiltration of any portion of the gastrointestinal tract, and eosinophilic proctocolitis is an eosinophilic infiltration in the colon alone.

Influence of perinatal factors in short- and long-term outcomes of infants born at 23 weeks of gestation.

OBJECTIVE: Investigate the influence of perinatal factors on short- and long-term outcomes for infants born at 23 weeks of gestation. STUDY DESIGN: This is a retrospective study over a 25-year period (1987-2011) of 87 successfully resuscitated infants at 23 weeks of gestation. We investigated the effects of poor prenatal care, race, gender, chorioamnionitis, antenatal corticosteroids, delivery route/location, low 5-minute Apgar score, birth weight, and multiple births on short- and long-term outcomes. RESULTS: The mortality rate was 43% (37/87). A total of 88% (44/50) of the survivors were followed at 2 years corrected age with 66% (29/44) diagnosed with a moderate-to-severe neurological impairment. Outborn and multiple birth infants had significantly higher mortality (p-value 0.042 and 0.006, respectively). Lack of exposure to antenatal steroids and lower birth weight significantly increased the disability score (p-value 0.042 and 0.003, respectively). CONCLUSION: Multiple perinatal factors significantly influence outcomes at the threshold of viability.