Primary Mediastinal Large B-Cell Lymphoma Presenting as Acute Pancreatitis.

Pancreatitis is an inflammatory pancreatic disease; common etiologies include infection, anatomic abnormalities, biliary, inborn errors of metabolism, trauma, and rarely malignancy. Primary mediastinal large B-cell lymphoma commonly presents in younger women with principally mediastinal involvement. We report the first documented case of a pediatric patient presenting with acute pancreatitis secondary to metastatic primary mediastinal large B-cell lymphoma. Since diagnosis, the patient underwent a combination of chemotherapy and immunotherapy treatments, and the tumor burden had decreased significantly. Malignancy is a rare documented presentation of acute pancreatitis in the pediatric population, and it should be included in a broad differential diagnosis.

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification. AIM: To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE. METHODS: Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC). RESULTS: The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined. CONCLUSION: Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

Congenital sodium diarrhoea caused by rare de novo activating guanylate cyclase mutation.

A male infant with prenatal history significant for polyhydramnios requiring multiple amnioreductions with suspicion of small bowel atresia was born at 31 weeks 5 days' gestation with abdominal distension. He underwent three exploratory laparotomies and ileostomy for small bowel obstruction and was found to have fluid-filled intestinal dilatation. Serum and stool chemistries suggested sodium secretory diarrhoea. A rapid whole-exome sequencing confirmed de novo guanylate cyclase mutation variant as a cause for his congenital sodium secretory diarrhoea. He required large volume of fluid and electrolyte replacement along with total parenteral nutrition. Several medications to restore normal sodium homeostasis by targeting molecular mechanisms and pathogenesis described in previous literature failed to decrease stool output and electrolyte loss. He was discharged home at 11 months of age on total parenteral nutrition and weekly iron therapy.

Eosinophilic Esophagitis for the General Pediatrician.

This article reviews pediatric eosinophilic esophagitis (EoE), a clinicopathologic disorder with symptoms related to esophageal dysfunction and characterized by eosinophil-predominant inflammation present on esophageal biopsy. As part of this review, we outline the pathophysiology, clinical features, diagnostic criteria, approved treatment options, and emerging therapies of EoE. Although previously considered a rare condition, EoE has emerged primarily in Western countries, with an estimated incidence of 4 per 100,000 persons. Understanding disease manifestation, diagnosis, and treatment options are critical for primary care physicians and specialists alike as EoE presentation varies by patient age. Several treatment options are approved for first-line management and can be used interchangeably based on symptoms and patient preference. Additionally, the collaboration of gastroenterologists, allergist-immunologists, and nutritionists is recommended for a multidisciplinary approach to long-term EoE management. [Pediatr Ann. 2021;50(8):e325-e329.].

Constipation in Pediatrics: A Clinical Review.

Constipation is a common problem encountered in the pediatric setting. For many children, constipation is functional in nature-potentially stemming from a pattern of stool output that is infrequent or not fully productive (ie, incomplete stool evacuation)-and includes behavioral concerns like stool withholding. In many cases of functional constipation (FC), the pattern may have started in the toddler years during or before toilet training and may now be well established. Additional factors often include inadequate fluids and fiber, or excess dietary dairy or carbohydrates. In a small percentage of cases, constipation is a symptom of an underlying organic disease process. Laboratory tests and imaging may be helpful in determining most organic concerns. In the absence of an organic process, FC can be treated by properly educating families about the nature of FC as well as careful attention to dietary fiber and fluid intake, use of stool softeners, laxatives, and behavioral modifications. [Pediatr Ann. 2021;50(8):e320-e324.].

Urinary Cannabis Metabolite Concentrations in Cannabis Hyperemesis Syndrome.

OBJECTIVE: Cannabis Hyperemesis Syndrome (CHS) is characterized by recurrent episodes of intractable emesis associated with heavy use of cannabis. Recognition of CHS can be problematic due to the lack of specific biomarkers, which can point the clinician to the diagnosis. We present, retrospectively, a series of adolescent/young adult patients who presented to a pediatric gastroenterology (GI) service with acute on chronic nausea and vomiting, subsequently found to have CHS with associated elevated urinary cannabis metabolite concentrations. METHODS: We describe 15 patients referred to our pediatric GI division for intractable emesis with spot urinary cannabis metabolite carboxy-THC (THC-COOH) concentrations from January 1, 2018 through April 20, 2019. Urinary testing was performed using gas chromatography mass-spectrometry (GC-MS) in a manner consistent with Clinical Laboratory Improvement Amendments (CLIA) requirements at Mayo Clinic laboratory (Rochester, MN). The laboratory cutoffs were 3.0 ng/mL. Data was extracted via chart review and analyzed via online statistical application. RESULTS: Fifteen patients (seven females, eight males) were studied with an average age of 17.7 years. All patients reported frequent cannabis use for at least 1 month and exhibited intractable, non-bilious emesis for at least 2 weeks. Twelve patients also reported weight loss. Two patients had underlying gastrointestinal disease (one with Crohn disease and one with irritable bowel syndrome). All patients had essentially normal GI workup including laboratory tests, imaging studies and endoscopies.Fourteen of 15 patients had urinary THC-COOH concentrations >100 ng/mL, with seven individuals exhibiting levels >500 ng/mL. One patient had a urinary TCH-COOH concentration level under 100 ng/mL had not used cannabis for 2 weeks. Most other patients had used cannabis within 2 days of providing a urine sample. The Binomial test for CHS patients with urinary THC-COOH levels over 100 ng/mL was significant with a P-value of <0.0005 (one tail test). CONCLUSION: CHS is associated with an elevated urinary THC-COOH level usually exceeding 100 ng/mL, which is indicative of significant chronic cannabis exposure. In patients with a history consistent with CHS, urine THC-COOH testing may help guide the diagnostic evaluation of these patients and decrease the need for further workup.

Paneth cell defects in Crohn's disease patients promote dysbiosis.

BACKGROUND: Paneth cell dysfunction has been implicated in a subset of Crohn's disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients. METHODS: Pediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome. RESULTS: The prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome. CONCLUSION: Paneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop. FUNDING: The research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohn's and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).

Clinical Review of Failure to Thrive in Pediatric Patients.

Failure to thrive (FTT) is a common problem that occurs when caloric intake is insufficient to maintain growth. For the majority of children it can be reversed with behavioral modifications and increased caloric provisions. In a minority of cases, FTT is the symptom of underlying organic disease. Routine evaluation with laboratory tests, imagining studies, and endoscopy results in an etiology of FTT in <1.4% of cases, and when investigations are positive the organic etiology is most often suspected based on history and/or physical examination. Therefore, these evaluations should be limited to those children with clear symptoms of organic disease and those who fail to grow with behavioral and nutritional interventions.

Nonalcoholic Fatty Liver Disease in Pediatrics.

A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease.

Respiratory syncytial virus and pediatric liver transplant: one center's experience.

Respiratory syncytial virus (RSV) is a ubiquitous virus responsible for acute infections of the respiratory tract in patients of all ages. RSV presents significant health risks to immunocompromised patients. Two patients, 1 before a liver transplant and 1 after a liver transplant, died of a severe RSV infection. Because of the high risk of death, we recommend expanding the criteria for palivizumab prophylaxis to 2 types of patients: (1) patients with chronic liver disease or who have received a liver transplant and are 24 months old or less and (2) transplant recipients with underlying pulmonary conditions who are less than 36 months old. Further research is indicated in pediatric solid-organ transplant centers to evaluate the effective management of RSV infection to prevent morbidity.

Identifying youth nonadherence in clinical settings: data-based recommendations for children and adolescents with inflammatory bowel disease.

BACKGROUND: To examine the validity of patient self-report of thiopurine adherence in pediatric inflammatory bowel disease (IBD) against an objective electronic monitoring adherence measure, and to investigate the role of youth and maternal involvement in remembering to take daily medications as predictors of medication adherence. METHODS: Fifty-one youths with IBD, ages 11-18 years, participated. Youths completed questionnaire assessments of their own and their maternal caregiver's involvement in remembering to take daily medications at baseline, completed monthly interviews assessing thiopurine adherence over the past week for a period of 6 months, and utilized a Medication Events Monitoring System (MEMS) electronic monitor for their thiopurine medication for 6 months. Participants were grouped into adherent (at least 80% of doses taken based on objective MEMS caps) or nonadherent for analyses. RESULTS: Youths who were nonadherent based on electronic monitoring overestimated their adherence by 23%, whereas adherent youths overestimated their adherence by only 2%, and as such patient self-report offered little utility in identifying youths who were nonadherent. Youths who reported high levels of involvement in remembering to take their medications were nearly eight times less likely to be nonadherent. CONCLUSIONS: The current findings provide evidence that clinicians who work with children and adolescents with IBD may benefit from modifying their approach to nonadherence screening. Asking about youth involvement in remembering daily medications may be more informative than asking them to recall their medication-taking behavior over the last week in identifying those at highest risk for nonadherence.

HIDA, percutaneous transhepatic cholecysto-cholangiography and liver biopsy in infants with persistent jaundice: can a combination of PTCC and liver biopsy reduce unnecessary laparotomy?

BACKGROUND: Historically, HIDA is the initial diagnostic test in the evaluation of biliary atresia (BA). Non-excreting HIDA scans can yield false-positive results leading to negative laparotomy. OBJECTIVE: Cholestatic infants must be evaluated promptly to exclude biliary atresia (BA) and other treatable hepatic conditions. Intraoperative cholangiogram (IOC) is the gold standard for diagnosing BA, but requires surgical intervention. Percutaneous transhepatic cholecysto-cholangiography (PTCC) and liver biopsy are less invasive and have been described in small case series. We hypothesized that PTCC and liver biopsy effectively exclude BA, thus avoiding unnecessary IOC. MATERIALS AND METHODS: Retrospective review of cholestatic infants who underwent PTCC, biopsy or cholescintigraphy at a tertiary children's hospital from August 1998 to January 2009. Group differences were evaluated and the receiver operator curve and safety of PTCC determined. RESULTS: One-hundred twenty-eight cholestatic infants were reviewed. Forty-six (36%) underwent PTCC. Forty-one out of 46 (89%) had simultaneous PTCC and liver biopsy. PTCC was completed successfully in 19/23 (83%) children despite a small or absent GB on initial US. Negative laparotomy rate was 1/6 (17%) for simultaneous PTCC/liver biopsy. Complications occurred in 4/46 including bleeding (n=2), fever with elevated transaminases (n=1) and oxygen desaturations (n=1). CONCLUSION: PTCC, particularly when performed in combination with simultaneous liver biopsy, effectively excludes BA in cholestatic infants with acceptable morbidity. PTCC can frequently be performed when a contracted gallbladder is seen on initial US exam. Negative laparotomy rate is lowest when PTCC is coupled with simultaneous liver biopsy.

Predictors of nonalcoholic steatohepatitis in obese children.

As the prevalence of childhood obesity increases, the incidence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) also escalates. This study's purpose was to identify the clinical criteria to aid in determining when a liver biopsy is indicated for this growing population because currently no guidelines exist. We performed a retrospective chart review on all patients who were seen in the Nutrition Exercise and Weight Loss Kids™ Program at the Children's Hospital of Wisconsin from July 2003 through December 2004. We analyzed only individuals who underwent liver biopsy with the following criteria: (1) no evidence of other liver disease and (2) aspartate transaminase or alanine aminotransferase greater than 200 IU/L or any elevation of or for more than 6 months. Of the 284 patients reviewed, only eight patients (3%) met the criteria for analysis. Biopsy results demonstrated that 100% had histological evidence of NASH with steatosis, and seven of the eight (87.5%) had NASH with fibrosis, cirrhosis, or both. Obese children with an aspartate transaminase or alanine aminotransferase greater than 200 IU/L or any elevation of aspartate transaminase or alanine aminotransferase for more than 6 months, have a strong likelihood of having NASH with or without fibrosis, cirrhosis, or both.

Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis.

OBJECTIVE: To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH. STUDY DESIGN: We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD. RESULTS: Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohn's disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001). CONCLUSIONS: Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Role of nutrition in pediatric chronic liver disease.

The liver plays a central role in energy and nutrient metabolism. Malnutrition is highly prevalent among patients with chronic liver disease and leads to increased morbidity and mortality rates. This review addresses the causes of malnutrition, methods used to assess nutrition status, and appropriate treatment strategies in pediatric patients with chronic liver disease.

Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility.

BACKGROUND: Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon. METHODS: We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location. RESULTS: We found an age-related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first-decade onset patients (P = 4.57 x 10(-5), odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72-4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset. CONCLUSIONS: In early-onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early-onset disease.