Purpose:Crohn's disease (CD) is a chronic, idiopathic bowel disorder that can progress to partial or complete bowel obstruction. At present, there are no reliable diagnostic tests that can readily distinguish between acute inflammatory, purely fibrotic and mixed inflammatory and fibrotic. Our aim is to study the utility of contrast enhanced ultrasound (CEUS) in combination with shear wave elastography (SWE) to differentiate fibrotic from inflammatory strictures in children with obstructive CD of the terminal ileum. Methods:Twenty-five (19 male) children between 2016-2021 with CD of the terminal ileum were recruited into the study. Among these patients, 22 had CEUS kinetic measurements of tissue perfusion, including wash-in slope (dB/sec), peak intensity (dB), time to peak intensity (sec), area under the curve (AUC) (dB sec), and SWE. In total, 11 patients required surgery due to bowel obstruction. Histopathologic analysis was performed by a pathologist who was blinded to the CEUS and SWE test results. Results:Patients that underwent surgical resection had significantly higher mean area under the curve on CEUS compared to patients responsive to medical therapy (p=0.03). The AUC also correlated with the degree of hypertrophy and the percent fibrosis of the muscularis propria, as determined by histopathologic grading (p<0.01). There was no difference in the mean elastography measurements between these two patient groups. Conclusion:CEUS is a useful radiological technique that can help identify pediatric patients with medically refractory obstructive fibrotic strictures of the terminal ileum that should be considered for early surgical resection.

Antitumor necrosis factor (anti-TNF) therapy has proven efficacy in the induction and maintenance of remission in children with Crohn’s disease (CD). With the increased use of these medications, several adverse events have been associated, including the emergence of neurologic side effects. While demyelinating conditions and neuropathy associated with anti-TNF therapy have been reported in adults, seizures have been anecdotally described in case reports. We describe a case of an adolescent boy who experienced an infliximab-associated seizure during an infusion and the potential role that medication antibody levels may have played in this adverse event.

Polyposis and colorectal cancer in children can have various nonspecific presentations such as abdominal pain, unexplained anemia, and weight loss. Polyps in children in the absence of an underlying genetic polyposis syndrome are most often benign solitary hamartomas; however, adenomas can occur and could signal increased risk for malignancy or an underlying genetic cancer syndrome. Familial adenomatous polyposis (FAP) occurs with mutations in the adenomatous polyposis coli (APC) tumor suppressor gene; whereas Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) mutations, often involve DNA mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, or PMS2.

BACKGROUND:Bowel preparation in children can be challenging.AIM:To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid (SPMC) bowel preparation in children.METHODS:Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ½ dose × 2, SPMC 1 dose × 2, or polyethylene glycol (PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders (rating of 'excellent' or 'good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations.RESULTS:78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ½ dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was 'very easy' or 'easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG.CONCLUSION:SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.

Characterizing inflammation and fibrosis in Crohn's disease (CD) is necessary to guide clinical management, but distinguishing the two remains challenging. Novel ultrasound (US) techniques: contrast-enhanced US (CEUS) and shear wave elastography (SWE) offer great potential in evaluating disease activity in pediatric patients. Three patients ages 16 to 20 with known CD underwent CEUS and SWE to characterize bowel wall inflammation and fibrosis. Magnetic resonance enterography, endoscopy, or surgical pathology findings are also described when available. The patients' disease activity included acute inflammation, chronic inflammation with stricture formation, and a fibrotic surgical anastomosis without inflammation. CEUS was useful in determining the degree of inflammation, and SWE identified bowel wall fibrosis. Used together these techniques allow for better characterization of the degree of fibrosis and inflammation in bowel strictures. With further validation CEUS and SWE may allow for improved characterization of bowel strictures and disease flares in pediatric patients suffering from CD.

Contrast-enhanced ultrasound (CEUS) is a versatile imaging modality that improves the diagnostic potential of conventional ultrasound. It allows for portable imaging at the bedside. In this paper, we illustrate how CEUS can be used in evaluating several focal lesions in the pediatric population, including liver hemangioma, telangiectasias, splenic hamartomas, and bladder lesions. We describe the ultrasound findings and contrast enhancement patterns associated with these lesions. Findings are correlated with MRI, CT, and/or pathology when available. This paper demonstrates the value of CEUS in improving characterization of many focal lesions in the pediatric population.CONCLUSION:CEUS is a valuable bedside technique for use in the pediatric population to evaluate focal lesions in various organs, and will allow for safe, more efficient diagnostic imaging. What is Known: • CEUS offers many advantages over CT and MRI and is underutilized in the United States. • It is only FDA approved for vesicoureteral reflux and liver in the pediatric population. However, off label uses are well described. What is New: • This pictorial essay describes ultrasound findings and contrast enhancement patterns associated with liver hemangioma, liver telangiectasia, splenic hamartoma, hemorrhagic ovarian cyst, urachal remnant, spinning top urethras, and kaposiform hemangioendothelioma. • We demonstrate the utility of CEUS in expanding the diagnostic potential of conventional ultrasound.

Androgen therapy has proven efficacy in treating patients with bone marrow failure who are not candidates for bone marrow transplantation. Herein, we report on a case of colonic angioectasia secondary to oxymetholone use in an adolescent patient with Hoyeraal-Hreidarsson syndrome (HHS). A 13-year-old Caucasian male with HHS characterized by cerebellar hypoplasia, developmental delay, microcephaly, esophageal strictures and myelodysplasia presented with severe hematochezia from colonic angioectasia secondary to long-term oxymetholone therapy. These vascular lesions resolved spontaneously once this anabolic steroid was discontinued. While androgen therapy is often recommended for certain anemias and myelodysplastic syndromes, clinicians should be aware of the potential complication in developing these perceived uncommon colonic angioectasias. Moreover, pediatric gastroenterologists should familiarize themselves in identifying these vascular lesions by colonoscopy, especially among the high risk groups on long-term anabolic steroid therapy.

The purpose of this study is to develop patient-reported (PRO) and observer-reported (ObsRO) outcome measures of ulcerative colitis (UC) signs/symptoms in children aged 5–17 with mild/moderate UC. The daily ulcerative colitis signs and symptoms scale (DUCS) was developed in two phases. Phase I involved concept elicitation interviews with patients and healthcare providers, review of website posts and item generation. Phase II involved cognitive debriefing and assessment of usability and feasibility of the eDiaries. Participants were recruited from five US clinical sites, a research recruitment agency, and internet advertising. Thematic and content analysis was performed to identify concepts from Phase I. The Phase II cognitive debriefing interviews were analyzed iteratively to identify problems with clarity and relevance of eDiary content. The US Food and Drug Administration (FDA) also reviewed and provided feedback on the eDiaries.

Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC).Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified.Conclusion: Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.

OBJECTIVE:Acute pancreatitis is one of the leading causes of rising pediatric hospitalizations in North America. The aim of this study was to assess the role of nutritional status and racial influences on the severity of acute pancreatitis in children.METHODS:The institutional review board approved this retrospective chart review of children with the diagnosis of acute pancreatitis between the ages of 0 and 18 years hospitalized at the Johns Hopkins Hospital between 1998 and 2008. Parameters studied included biochemical markers associated with pancreatitis, review of severity of illness reflected through the length of stay, and pediatric intensive care unit admission.RESULTS:The length of in-patient hospitalization was longer for children with imaging findings of pseudocyst or pancreatic necrosis (23.1 ± 26.4 days vs 4.4 ± 10.6 days; P = 0.0074) and malnourished children versus normal weight and obese children (16.5 days for malnourished vs 10.6 days for normal weight vs 10.7 days for obese; P = 0.04). There was also a significant difference in the need for pediatric intensive care unit admission across ethnic groups (18% African American vs 7% white) (P = 0.04).CONCLUSIONS:Ethnicity and nutritional status may influence the severity and duration of hospitalization among children with pancreatitis.

Acute pancreatitis is one of the leading causes of rising pediatric hospitalizations in North America. The aim of this study was to assess the role of nutritional status and racial influences on the severity of acute pancreatitis in children.The institutional review board approved this retrospective chart review of children with the diagnosis of acute pancreatitis between the ages of 0 and 18 years hospitalized at the Johns Hopkins Hospital between 1998 and 2008. Parameters studied included biochemical markers associated with pancreatitis, review of severity of illness reflected through the length of stay, and pediatric intensive care unit admission.The length of in-patient hospitalization was longer for children with imaging findings of pseudocyst or pancreatic necrosis (23.1 ± 26.4 days vs 4.4 ± 10.6 days; P = 0.0074) and malnourished children versus normal weight and obese children (16.5 days for malnourished vs 10.6 days for normal weight vs 10.7 days for obese; P = 0.04). There was also a significant difference in the need for pediatric intensive care unit admission across ethnic groups (18% African American vs 7% white) (P = 0.04).Ethnicity and nutritional status may influence the severity and duration of hospitalization among children with pancreatitis.

Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (<3 years old) who failed available therapeutics for RCDI, but responded remarkably well to FMT. Besides resolution of clinical features of C difficile infection (CDI), FMT administration led to marked improvement in their growth, along with increased microbiota diversity, especially proportion of Bacteroides. Our 2 cases illustrate the efficacy of FMT in children with RCDI and its positive effect on their growth and gut microbiota.

Esophageal polyps are uncommon findings in pediatric patients, and reports have been limited to case reports. Esophageal polyps have been previously ascribed to esophagitis secondary to gastroesophageal reflux, medications, infections and recurrent vomiting. They have been associated with underlying conditions such as hiatal hernia, Barrett's esophagus, eosinophilic esophagitis and Crohn's disease. Presenting complaints of children with esophageal polyps have included vomiting, dysphagia, hematemesis and abdominal pain. The aim of this paper is to characterize the incidence, clinical presentation and progression, histologic subtypes and associated mucosal abnormalities in children with esophageal polyps. A retrospective multicenter study was performed at four institutions identifying diagnosis of esophageal polyps in pediatric patients (<21 years). Information was obtained from patient charts, endoscopy reports and histopathology reports. Specimens and slides were examined by experienced pediatric pathologists for all included cases. Esophageal polyps were identified in 13 patients (9 M) from 9438 esophagogastroduodenoscopies (0.14%). Mean age of subjects was 9.2 years. Vomiting was the most common indication for endoscopy. Polyp location was at the gastroesophageal junction in 7 of the 13 cases. Most polyps were inflammatory (n = 7). Esophagitis was noted in 69% of those with esophageal polyps. Repeat endoscopies in six patients at a mean interval of 8 months noted persistence of polyps in all six patients. This paper is the first to characterize esophageal polyps in pediatrics. These polyps are rare in children and often are associated with esophagitis. Presenting complaints seem to vary by age. Polyps did not consistently change with either time or acid suppression. The optimal management strategy has yet to be defined and likely depends on the underlying pathophysiologic process.

Ritu Walia, MD1, Assistant Professor Pediatrics, Department of Pediatric Gastroenterology Nicholas Mulhearn, DO1, Pediatric Resident. Raheel Khan, MD, Associate Professor Pediatrics, Chairman, Department of Pediatrics. Carmen Cuffari MD 2, Associate Professor Pediatrics, Department of Pediatric Gastroenterology 1University of West Virginia School of Medicine, 2 The Johns Hopkins School of Medicine by Ritu Walia, Nicholas Mulhearn, Raheel Khan, Carmen Cuffari

Background Mesalamine or 5-aminosalicylic acid (5-ASA) has proven efficacy in treating patients with ulcerative colitis (UC). Although mesalamine is considered safe, it has been associated with acute interstitial nephritis and renal failure. Methods Herein we present a case of a child with UC who developed acute renal failure on mesalamine therapy. Results A 15-year-old African-American girl with well-controlled UC presented to the Johns Hopkins Hospital with a four-day history of high fever, malaise, generalized body aches, and productive non-bloody cough. Over the next three days, she developed acute renal failure with fluid retention, and elevated serum creatinine and blood urea nitrogen. A kidney biopsy showed drug induced acute interstitial nephritis and focal segmental glomerulosclerosis with viral inclusion bodies likely secondary to cytomegalovirus. Conclusion When treating UC patients with a history of underlying renal disease, it is advised to carefully monitor renal function while on mesalamine therapy.