Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis.

OBJECTIVES: Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. METHODS: This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. RESULTS: Thirty-three patients, (23 females, [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. CONCLUSIONS: AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

Pediatric Collagenous Gastritis: Clinical and Histologic Outcomes in a Large Pediatric Cohort.

OBJECTIVE: The aim of the study was to present the clinical characteristics, treatment, and outcomes of pediatric collagenous gastritis (CG). METHOD: This is a retrospective cohort study. Patients were identified via query of the institutional pathology database. Clinical data was obtained by review of medical records. RESULTS: Forty patients (57.5% female) were identified, mean age 11.3 ±â€Š3.7 years (2-16years). Isolated CG was present in 66.7%, coexisting collagenous duodenitis (CD) in 17.5%, collagenous colitis (CC) in 7.5%, and collagenous ileitis in 2.5%. Atopic comorbidities were found in 25%, autoimmune comorbidities in 12.5%. PRESENTING SYMPTOMS: Abdominal pain (77.5%), vomiting (65%), anemia (57.5%), nausea (55.5%), diarrhea (32.5%), anorexia (25.0%), weight loss (25%), gastrointestinal bleed (22.5%), poor growth (20%), poor weight gain (12.5%). ENDOSCOPIC FINDINGS: All had abnormal endoscopic findings on esophago-gastro-duodenoscopy (EGD), most commonly gastric nodularity (77.5%), visible blood (20%), erosions/superficial ulcerations (10%), ulcers (7.5%). Histologically, all patients had increased subepithelial collagen deposition. TREATMENT: A variety of medications aimed towards inflammation and symptomatic treatment were used. Patients with anemia received iron supplementation and responded. Otherwise, there was no significant association of clinical or histologic improvement with specific treatments. CLINICAL AND HISTOLOGIC OUTCOMES: 87.5% reported improvement or resolution of symptoms at the last follow-up (34.8 ±â€Š27.0 months). Persistent sub-epithelial collagen was noted in 73.1% on the last EGD. CONCLUSIONS: Despite persistent findings of increased sub-epithelial collagen deposition during the follow-up period, most patients with CG show remission or resolution of clinical symptoms. Anemia responds to iron supplementation in all patients.

Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls.

OBJECTIVES: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. METHODS: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. RESULTS: Mean age was 14.7 ±â€Š2.5 years (42.3% female) in IBS-D and 12.6 ±â€Š2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002). CONCLUSIONS: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.

Perceptions of Pain Treatment in Pediatric Patients With Functional Gastrointestinal Disorders.

OBJECTIVES: Individual understanding of and expectations for chronic pain treatment can influence treatment adherence and thus success, but little is known about these critical factors in parents and children presenting with pain-predominant functional gastrointestinal disorders. The aim of this study was to identify parent and patient understanding of pain-predominant functional gastrointestinal disorders, expectations for treatment, and interventions utilized before presenting to a multidisciplinary clinic. MATERIALS AND METHODS: This was a prospective study of patients evaluated in a Multidisciplinary Functional Abdominal Pain Program. Before the clinic visit, parents and patients completed questionnaires regarding their understanding of chronic pain, perceptions of abdominal pain contributors, expectations regarding treatment, and identification of previous interventions utilized. RESULTS: Participants were knowledgeable regarding the biology of chronic pain. Perceptions of contributors to abdominal pain included a sensitive stomach, general stress, and nerves/worry. Most had attempted to treat their pain with medication, exercise or physical therapy, or a psychological treatment. Participants reported that receiving a definite diagnosis would be the most helpful intervention, followed by psychological treatment. DISCUSSION: Participants were knowledgeable regarding chronic pain, but still indicated that receiving a definite diagnosis would be the most helpful intervention. Most had tried multiple interventions and did not believe that further medication, testing, or surgery would solve their pain. Instead, parents presenting at this Functional Abdominal Pain Program appeared most hopeful about the benefits of multidisciplinary treatment approaches including psychological interventions, a focus on activity and functioning, and complementary and alternative medicine interventions.

Pediatric Collagenous Gastroenterocolitis Successfully Treated with Methotrexate.

A two-and-one-half-year-old previously healthy female presented with a ten-week history of watery diarrhea, nonbilious and nonbloody emesis, and low-grade fevers. She was found to have severe hypoalbuminemia and hypogammaglobulinemia. Her symptoms persisted, and she became dependent on parenteral nutrition. Biopsies obtained during subsequent endoscopic and colonoscopic studies revealed findings consistent with collagenous gastroenterocolitis. She responded to an empiric course of prednisone, but her symptoms recurred shortly after transitioning to oral budesonide. After successful reinduction with intravenous prednisone, intramuscular methotrexate was initiated. She remained asymptomatic during a 15-month course of therapy, and she continued to do well clinically until approximately nine months after weaning off methotrexate. At that point, she experienced a recurrence of diarrhea, and repeat endoscopic evaluation confirmed collagenous colitis. This responded nicely to a short course of oral budesonide, and she has since remained asymptomatic and off any therapy.

Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses.

OBJECTIVE: To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA). STUDY DESIGN: A systematic literature review using Medline, Embase, Cochrane library, and the clinical trial registry was performed up to July 2017. Random effects meta-analyses were used to compare rates of serious infections in children with JIA given biologic agents compared with controls, and the pooled relative risk calculated. Subanalyses were performed for different biologic agent classes. RESULTS: In total, 19 trials accounting for 21 individual studies were included (11 for tumor necrosis factor-alpha inhibitors [n = 814 patients], 3 for interleukin-6 inhibitors [n = 318], 6 for interleukin-1 inhibitors [n = 353], and 1 for selective T-lymphocyte costimulation modulators [n = 122]). Patients (68% female) had a mean age of 10.8 years. Seventeen serious infections were reported among 810 children receiving biologic agents and 15 among 797 controls. The most frequent infections were bronchopulmonary and varicella. No statistically significant difference in risk of serious infections was found between children receiving biologic agents compared with control groups (pooled relative risk = 1.13; 95% CI [0.63, 2.03]) during the trial study periods. The risk remained nonsignificant when evaluating the different classes of biologic agents separately. However, the analyses were underpowered to detect differences in the risk of serious infections overall or differences between classes of biologic agents. CONCLUSIONS: In this systematic review and meta-analyses, serious infections were uncommon and not significantly increased among patients with JIA receiving biologic agents compared with controls. However, the analyses were underpowered and study periods were relatively short. Ongoing careful monitoring for serious infections remains necessary for all patients with JIA, and particularly those receiving biologic agents.

A 10-Month-Old With Intermittent Hypotonia and Paralysis.

A 10-month-old boy presented with a 1-day history of flaccid quadriplegia and dysconjugate gaze. His history was remarkable for stereotyped episodes of flaccid quadriplegia or hemiplegia, oculomotor abnormalities, and limb or neck posturing, beginning in the first days of life and becoming more frequent and more prolonged over time. The patient was healthy and developmentally normal between episodes. Results of extensive laboratory evaluations, including EEG and brain imaging studies, were negative. The patient's history, diagnostic evaluation, and final diagnosis are reviewed. This case illustrates the importance of a fundamental understanding of neurologic localization in pediatric care and a focused diagnostic approach to an infant with paroxysmal neurologic signs.

MondoA is highly overexpressed in acute lymphoblastic leukemia cells and modulates their metabolism, differentiation and survival.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted therapy, we performed a comprehensive transcriptome analysis identifying MondoA (MLXIP) - a transcription factor regulating glycolysis - to be overexpressed in ALL compared to normal tissues. Using microarray-profiling, gene-set enrichment analysis, RNA interference and functional assays we show that MondoA overexpression increases glucose catabolism and maintains a more immature phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data point to an important contribution of MondoA to leukemia aggressiveness and make MondoA a potential candidate for targeted treatment of ALL.