Suchitra K. Hourigan

Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease

Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis.

Relation between vitamin D status and nonalcoholic fatty liver disease in children.

Objectives: In adults, vitamin D deficiency is common in patients with nonalcoholic fatty liver disease (NAFLD) and has been associated with the severity of histology. There are known differences between adult and pediatric NAFLD, with little data regarding the relation between vitamin D and pediatric NAFLD. The aim of the present study was to examine the relation between vitamin D levels and NAFLD in children. Methods: Clinical and histological data were used from children ages 2 to 18 years with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network studies. 25(OH) vitamin D levels were measured from serum. Data examined included demographics, anthropometrics, laboratory markers, and liver histology. Data were analyzed using 3 categories of vitamin D level: deficient (⩽20 ng/mL), insufficient (21–29 ng/mL), and sufficient (≥30 ng/mL). Results: A total of 102 children were studied. There was a high prevalence (80/102, 78%) of vitamin D deficiency or insufficiency; however, there were no significant associations between vitamin D level and the histological characteristics or severity of NAFLD. Significantly higher levels of triglycerides were found in those with vitamin D deficiency (P = 0.004), but there was no association with other features of the metabolic syndrome. Conclusions: There is a high prevalence of vitamin D deficiency and insufficiency in children with biopsy-proven NAFLD; however, no association was found between vitamin D deficiency and the severity of disease on biopsies. This differs from adult NAFLD studies in which vitamin D deficiency correlates with histological severity, suggesting differences in the risk factors for or consequences of pediatric NAFLD.

The Full Spectrum of Hepatic Steatosis in Children

Objective: We aim to identify the spectrum of etiologies of steatosis in pediatric liver biopsies. Methods: Information was collected from 155 children with steatosis on liver biopsy, including anthropometrics, laboratory, and radiologic data. Biopsies were reviewed by a liver pathologist. Results: The 4 major diagnoses associated with hepatic steatosis were nonalcoholic fatty liver disease (37%), metabolic disease (9%), oncologic disease (8%) and viral hepatitis (7%). Patients with nonalcoholic fatty liver disease were older (P = .0001) and more likely to have a body mass index z score >2 (P < .0001). Patients with a metabolic diagnosis were younger (P = .0002). Radiologic imaging of the liver yielded normal results in 44 of 108 of children (30%); 7 of these had >66% macrovesicular fatty change on biopsy, and 3 had severe fibrosis/cirrhosis. Conclusions: The range of causes of steatosis in pediatric liver biopsies is broad. Not all patients, even with advanced liver disease, had abnormalities with liver imaging, emphasizing the role for liver biopsy in certain cases.

Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease.

Abstract:Children with inflammatory bowel disease (IBD) are disproportionately susceptible to Clostridium difficile infection (CDI) and the incidence is increasing. There has also been growing recognition of asymptomatic C. difficile colonization in pediatric IBD, which can sometimes be very difficult to distinguish from symptomatic C. difficile–associated disease in this population. In this study, we discuss the current knowledge of C. difficile infection in children with IBD, reviewing epidemiology, risk factors, and outcomes that often differ from the adult IBD population, and discuss the complexities and dilemmas of diagnosing and treating CDI in pediatric IBD.

Gastrointestinal sarcoidosis in an adolescent presenting with hemorrhage from a bleeding duodenal ulcer.

Gastrointestinal (GI) sarcoidosis is uncommon, with duodenal involvement rarely occurring. Diagnosis of sarcoidosis may be difficult, especially if no other typical features are present. Here we present a case of duodenal sarcoidosis with hemorrhage, which exemplifies the rarity of the condition and the diagnostic dilemma of differentiating sarcoidosis from Crohn disease.

Genomic analysis of an infant with intractable diarrhea and dilated cardiomyopathy

We describe a case of an infant presenting with intractable diarrhea who subsequently developed dilated cardiomyopathy, for whom a diagnosis was not initially achieved despite extensive clinical testing, including panel-based genetic testing. Research-based whole-genome sequences of the proband and both parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy integrating features of variants, genes, and phenotypes, which was implemented using publicly available tools. Although the intestinal morphological abnormalities characteristic of congenital tufting enteropathy (CTE) were not observed in the initial clinical gastrointestinal tract biopsies of the proband, an intronic variant, EPCAM c.556-14A>G, previously identified as pathogenic for CTE, was found in the homozygous state. A newborn cousin of the proband also presenting with intractable diarrhea was found to carry the same homozygous EPCAM variant, and clinical testing revealed intestinal tufting and loss of EPCAM staining. This variant, however, was considered nonexplanatory for the probands dilated cardiomyopathy, which could be a sequela of the childs condition and/or related to other genetic variants, which include de novo mutations in the genes NEDD4L and GSK3A and a maternally inherited SCN5A variant. This study illustrates three ways in which genomic sequencing can aid in the diagnosis of clinically challenging patients: differential diagnosis despite atypical clinical presentation, distinguishing the possibilities of a syndromic condition versus multiple conditions, and generating hypotheses for novel contributory genes.

Comparison of Infant Gut and Skin Microbiota, Resistome and Virulome Between Neonatal Intensive Care Unit (NICU) Environments

Background: There is a growing move to provide care for premature infants in a single family, private room neonatal intensive care unit (NICU) in place of the traditional shared space, open bay NICU. The resultant effect on the developing neonatal microbiota is unknown. Study Design: Stool and groin skin swabs were collected from infants in a shared-space NICU (old NICU) and a single-family room NICU (new NICU) on the same hospital campus. Metagenomic sequencing was performed and data analyzed by CosmosID bioinformatics software package. Results: There were no significant differences between the cohorts in gestational age, length of stay, and delivery mode; infants in the old NICU received significantly more antibiotics (p = 0.03). Differentially abundant antimicrobial resistance genes and virulence associated genes were found between the cohorts in stool and skin, with more differentially abundant antimicrobial resistance genes in the new NICU. The entire bacterial microbiota analyzed to the genus level significantly differed between cohorts in skin (p = 0.0001) but not in stool samples. There was no difference in alpha diversity between the two cohorts. DNA viruses and fungi were detected but did not differ between cohorts. Conclusion: Differences were seen in the resistome and virulome between the two cohorts with more differentially abundant antimicrobial resistance genes in the new NICU. This highlights the influence that different NICU environments can have on the neonatal microbiota. Whether the differences were due to the new NICU being a single-family NICU or located in a newly constructed building warrants exploration. Long term health outcomes from the differences observed must be followed longitudinally.

Do pediatric gastroenterology doctors address pediatric obesity

Objectives: To assess how often obesity is acknowledged at pediatric gastroenterology outpatient visits. Methods: A retrospective chart review was performed to identify obese children seen at a gastroenterology subspecialty clinic over a 1-year period of time; 132 children were identified. Demographics, obesity comorbidities, reasons for referral, diagnosis of obesity, and a plan to address obesity were abstracted. Chi-square or Fisher’s exact tests were used to examine statistical associations. Results: Only 49% of children were given a diagnosis of obesity. In total, 52% of children were given a body mass index reduction plan. Those diagnosed with obesity were more likely to receive a body mass index reduction plan (p < 0.0001). Younger children and males were more likely to receive an obesity diagnosis (p = 0.002 and p = 0.02, respectively). Diagnosis of obesity was more likely in patients with obesity-related comorbidities (p = 0.0004) and those referred for obesity or related comorbidities (p = 0.01). Conclusion: Obesity is diagnosed less than 50% of the time in pediatric gastroenterology outpatient clinics. To increase opportunities for addressing childhood obesity in the pediatric gastroenterology outpatient setting, further investigation of barriers and optimal provider education is urgently required.

A Case of Henoch–Schönlein Purpura Presenting With a Gastrocutaneous Fistula

An 8-year-old boy with a history of repaired tetrology of Fallot, and failure to thrive status post gastrostomy tube (G-tube) for the first year of life, presented to the Pediatric Emergency Department complaining of bilateral hand and foot swelling. Approximately 2 weeks prior to presentation, he had noticed leakage from his prior G-tube site that had fully closed 7 years ago after removal when no longer needed. Over the past 2 weeks, the patient experienced increased leakage from the G-tube site, occurring primarily with movement and oral intake, and associated with mild crampy abdominal pain. Three days prior to presentation to the Pediatric Emergency Department, the patient began to complain of lower extremity pruritis, bilateral swelling of his ankles, pain when walking, and mild swelling of both hands; these had been gradually increasing over the past three days. Review of systems was notable only for clear rhinorrhea, sore throat, and cough. He had no fever, urinary symptoms, periorbital or scrotal swelling. The patient was afebrile with vital signs within normal limits and examination at the time revealed marked edema of the lower extremties bilaterally up to the level of his knees and mild edema of the dorsal surface of his hands and wrists. He had pain with active and passive movement of his feet and wrists and had a noticeable limp while walking. On dermatological examination, he had raised purpuric papules of 1 to 2 cm over his ankles, feet, and the lateral aspects of his lower legs, as well as flesh-colored raised papules over his medial upper legs. His perineum and buttocks were not involved. Over the course of his emergency department visit, he developed 1-cm purpuric lesions over the dorsal aspect of his hands bilaterally. There was yellow drainage from the former G-tube site with no visible opening. The surrounding skin was without erythema or induration. His abdomen was nontender, nondistended, with normal bowel sounds. Neurologic exam was within normal limits. A complete blood count was obtained that showed a white blood count of 6410/mm, hemoglobin of 12.4 g/dL, and platelets of 329 000/mm. His C-reactive protein was 1.7 mg/dL and erythrocyte sedimentation rate was 10 mm/h. His complete metabolic panel was unremarkable, including a serum creatinine of 0.6 mg/dL, total protein of 7.3 g/dL, and albumin of 4.3 g/dL. The prothrombin time and activated partial thromboplastin time were within normal limits. His urinary analysis was notable for an absence of proteinuria or hematuria. Occult blood was not found in the stool. A bacterial surface culture of the fluid from the G-tube site showed light skin flora and group B Streptococcus. A throat culture was positive for group A Streptococcus. An abdominal ultrasound of the former G-tube site demonstrated no abscess or visible fistula. A lower extremity ultrasound ruled out deep vein thromboses. The pediatric dermatology service was consulted and thought his skin findings to be most consistent with acute hemorrhagic edema of childhood, although Henoch–Schönlein purpura (HSP) could not be excluded. He was discharged home with a prescription for penicillin to treat streptococcal pharyngitis and antihistamines with topical steroid cream for the pruritis. At this time there was no explanation for his new onset of leakage from his former gastrostomy site. The patient presented to an outpatient pediatric clinic 5 days later with increasing drainage of yellow fluid from his former G-tube site and worsening rash. Examination of his skin revealed bilateral deep purple palpable purpura extending from his feet to upper thighs on the anterior, lateral, and posterior aspects, with sparing of his buttocks. He had been compliant with the