Eosinophilic gastroenteritis as a cause of non-Helicobacter pylori, non-gastrotoxic drug ulcers in children.

BACKGROUND: While Helicobacter pylori (H. pylori) ulcers has declined recently, H. pylori-negative and/or gastrotoxic drug-negative peptic ulcers (HNGN-PU) has increased. This study aimed to analyze the etiology of peptic ulcers in children and the differences in clinical, laboratory, endoscopic, and histopathologic findings of peptic ulcers according to etiology, including eosinophilic gastroenteritis (EoGE). METHODS: In total, 255 children (157 boys and 98 girls) with peptic ulcers were recruited. The subjects were categorized into 5 groups according to the etiology of the ulcer: 1) H. pylori infection (n = 51); 2) gastrotoxic drugs (n = 18); 3) idiopathic (n = 144); 4) systemic disease (n = 23); 5) EoGE (n = 19). Clinical data were reviewed and analyzed retrospectively. RESULTS: Age at diagnosis, ulcer recurrence, atopic dermatitis history, white blood cell count, blood eosinophil count, platelet count, serum albumin level, iron level, erythrocyte sedimentation rate, and C-reactive protein level differed significantly among the 5 groups (all p < 0.05). Regarding endoscopic findings, multiple ulcers and gastric mucosal nodularity differed among the 5 groups (all p < 0.05). When comparing the EoGE ulcer group with the others, EoGE group revealed older ages (p = 0.022), higher rates of ulcer recurrence (p = 0.018), atopic dermatitis history (p = 0.001), and both blood and tissue eosinophilia (both p = 0.001). CONCLUSIONS: EoGE ulcers constituted 10.2% of HNGN-PU in pediatric patients. In children with HNGN-PU, peripheral eosinophilia, ulcer recurrence, and atopic dermatitis history might imply EoGE, necessitating thorough investigation of tissue eosinophils during endoscopic biopsy. TRIAL REGISTRATION: A total of 255 children was retrospectively registered between between July 2003 and April 2017.

A Nomogram for Predicting Non-Alcoholic Fatty Liver Disease in Obese Children.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) ranges in severity from simple steatosis to steatohepatitis. Early detection of NAFLD is important for preventing the disease from progressing to become an irreversible end-stage liver disease. We developed a nomogram that allows for non-invasive screening for NAFLD in obese children. METHODS: Anthropometric and laboratory data of 180 patients from our pediatric obesity clinic were collected. Diagnoses of NAFLD were based on abdominal ultrasonographic findings. The nomogram was constructed using predictors from a multivariate analysis of NAFLD risk factors. RESULTS: The subjects were divided into non-NAFLD (n=67) and NAFLD groups (n=113). Factors, including sex, body mass index, abdominal circumference, blood pressure, insulin resistance, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γGT), uric acid, triglycerides, and insulin, were significantly different between the two groups (all p<0.05) as determined using homeostatis model assessment of insulin resistance (HOMA-IR). In our multivariate logistic regression analysis, elevated serum ALT, γGT, and triglyceride levels were significantly related to NAFLD development. The nomogram was established using γGT, uric acid, triglycerides, HOMA-IR, and ALT as predictors of NAFLD probability. CONCLUSION: The newly developed nomogram may help predict NAFLD risk in obese children. The nomogram may also allow for early NAFLD diagnosis without the need for invasive liver biopsy or expensive liver imaging, and may also allow clinicians to intervene early to prevent the progression of NAFLD to become a more advanced liver disease.

Fecal Calprotectin as a Useful Non-Invasive Screening Marker for Eosinophilic Gastrointestinal Disorder in Korean Children.

BACKGROUND: Eosinophilic gastrointestinal disorder (EoGID) is an emerging disease condition in Korean children, but its diagnosis requires invasive endoscopic biopsies. Fecal calprotectin (FCal) is a noninvasive biomarker for intestinal inflammation to differentiate organic gastrointestinal diseases from functional abdominal pain disorder. This study aimed to evaluate the diagnostic accuracy of FCal and to determine the optimal cutoff to differentiate EoGID from functional abdominal pain disorder. METHODS: A total of 253 children (122 boys, 131 girls; mean age 12.2 ± 3.6, range 2.9-17.8 years) who underwent endoscopy with biopsies for chronic gastrointestinal symptoms were recruited, except for 38 children diagnosed with inflammatory bowel disease, and divided into EoGID (n = 67) and functional abdominal pain disorder (n = 186). FCal, white blood cell (WBC) counts, eosinophil counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured in all subjects at initial diagnosis. RESULTS: FCal levels weakly correlated with WBC (r = 0.127, P = 0.044) and CRP (r = 0.126, P = 0.040) but not with ESR and eosinophil count. FCal levels were significantly higher in the EoGID group than in the functional abdominal pain disorder group (mean 179.5 ± 242.9 mg/kg vs. 44.3 ± 68.1 mg/kg; P < 0.001), while WBC, ESR, CRP, and eosinophil count did not differ between the two groups (all P > 0.05). An optimal cutoff of FCal 73.2 mg/kg distinguished EoGID from functional abdominal pain disorder with a sensitivity of 50.7% and a specificity of 84.6%. CONCLUSION: FCal is a useful and reliable noninvasive marker for differentiating EoGID from functional abdominal pain disorder in Korean children with chronic gastrointestinal symptoms when optimal cutoffs are applied.

Effects of oral zinc supplementation on zinc status and catch-up growth during the first 2 years of life in children with non-organic failure to thrive born preterm and at term.

BACKGROUND: We aimed to analyze the effect of oral zinc supplementation on serum insulin-like growth factor-1 (IGF-1) levels and catch-up growth in infants with non-organic failure to thrive (NOFTT) who were born preterm as compared to those born at term. METHODS: Totally, 105 NOFTT infants aged 2 years or less were enrolled and divided into two groups according to gestational age at birth. Oral zinc sulfate was administered for 6 months to 49/66 children born at term, and 21/39 children born preterm. Serum zinc, IGF-1, weight, and height were measured at baseline and at 6 months. RESULTS: There were no differences in baseline serum zinc levels between the two groups. In preterm NOFTT infants, zinc supplementation significantly increased serum zinc levels compared to those in the non-supplementation group (Δ zinc 0-6 month 10.3 ± 26.4 µg/dL vs. -8.8 ± 23.7 µg/dL, p = 0.018), but it did not significantly change serum IGF-1 levels or weight- and height for age Z-scores. In NOFTT infants born at term who received zinc supplementation, serum zinc levels, IGF-1, weight for age Z-score, and height for age Z-score increased at 6 months (p = 0.001, p = 0.014, p = 0.049, and p = 0.029, respectively), but this increase was not significantly greater than in the non-supplementation group. Only the increase in serum zinc levels was significant after 6 months (Δ zinc 0-6 month 16.8 ± 32.0 µg/dL vs. -10.0 ± 22.6 µg/dL, p = 0.002). CONCLUSION: Zinc supplementation in NOFTT infants improves serum zinc status, regardless of gestational age at birth. Zinc supplementation in NOFTT infants born at term may improve serum IGF-1 levels and growth, but it does not in NOFTT infants born preterm. Overall nutritional support rather than supplementation of a single nutrient may be more effective for catch-up growth in NOFTT infants born preterm.

EBV VCA IgM and cytomegalovirus IgM dual positivity is a false positive finding related to age and hepatic involvement of primary Epstein-Barr virus infection in children.

Primary Epstein-Barr virus (EBV) infection is common in childhood, and dual positivity of serum EBV IgM and cytomegalovirus (CMV) IgM antibodies occur in some cases. This study aimed to evaluate the cause of EBV and CMV IgM dual positivity to determine whether it represents a false-positive finding or a true coinfection.A total of 494 children diagnosed with primary EBV infection, manifesting as infectious mononucleosis, were recruited. The diagnosis was based on positive EBV viral capsid antigen (VCA) IgM antibodies, and serum CMV IgM antibodies and liver enzymes were also evaluated in 149 subjects.Of 149 children with primary EBV infection, 40 (26.8%) had serum EBV VCA IgM and CMV IgM dual positivity. However, true CMV infection was confirmed only in 1 child of 40 (2.5%) who was positive for both serum CMV Ag and urine CMV polymerase chain reaction (PCR) and negative for serum CMV IgG antibody. Among the children with primary EBV infection, the rate of dual positivity was higher in infants and lower in adolescents (P = .013). Liver enzymes were more significantly elevated in children with dual positivity than in those with negative results for CMV IgM antibodies (P = .026), which correlated with the serum EBV and CMV IgM titers.Serum EBV and CMV IgM dual positivity are more prevalent in children with primary EBV infection than what was previously reported. Our results indicate that serum EBV and CMV IgM dual positivity represents a false-positive finding, as opposed to an actual CMV coinfection, possibly due to antigenic cross-reactivity.

Clostridium difficile Infection at Diagnosis and during the Disease Course of Pediatric Inflammatory Bowel Disease.

PURPOSE: Clostridium difficile colonization and infection are commonly associated with poor outcomes in patients with pediatric inflammatory bowel disease (PIBD). We aimed to investigate the prevalence of C. difficile colonization and infection at the time of diagnosis and to evaluate risk factors associated with the development of C. difficile infection during the course of PIBD treatment. METHODS: We retrospectively enrolled a total of 59 children who were newly diagnosed with PIBD at the tertiary medical center. All patients underwent C. difficile toxin assays and cultures initially and at every follow-up during the disease course. Kaplan-Meier survival analysis and Cox regression test were used for statistical analysis. RESULTS: Initial cultures for C. difficile were positive in 13 (22.0%) of 59 PIBD patients, whereas initial toxin assays were positive in 3 patients (5.1%). During treatment, C. difficile cultures converted to positive in 28 (47.5%) in addition to 13 patients who were initially culture-positive, and C. difficile toxins converted to positive in 13 (22.0%) in addition to 3 originally toxin-positive patients. Antibiotic usage alone was significantly associated with the development of C. difficile colonization (p=0.011), and the length of hospitalization was associated with the development of C. difficile infection (p=0.032). CONCLUSION: C. difficile colonization and infection occur frequently during the disease course of PIBD. Antibiotic usage and longer hospital stay were significant risks factors for the conversion of C. difficile status in PIBD patients undergoing treatment.

Hair Mineral and Trace Element Contents as Reliable Markers of Nutritional Status Compared to Serum Levels of These Elements in Children Newly Diagnosed with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at high risk for nutritional deficiencies because of long-term inflammation in the gut mucosa and decreased oral intake. Because inflammation responses affect serum micronutrient concentrations, serum levels are limited in reflecting body nutrient status in acute and chronic illness. We investigated the usefulness of measuring trace elements in hair as reliable markers of nutritional status compared to serum levels in children with IBD. We retrospectively analyzed pediatric patients newly diagnosed with Crohn's disease (n = 49) and ulcerative colitis (n = 16) and controls (n = 29) from 2012 to 2016. Serum micronutrient levels, inflammatory markers, and hair trace element content were evaluated and compared at the time of diagnosis and before initiating treatment. Serum calcium (p < 0.001), iron (p < 0.001), zinc (p = 0.013), selenium (p = 0.008), albumin (p < 0.001), prealbumin (p < 0.001), hemoglobin and hematocrit (p < 0.001), and WBC (p = 0.001) and lymphocytes (p < 0.001) differed significantly between the groups. After adjustment for the erythrocyte sedimentation rate, serum zinc and selenium levels were no longer significantly different between the groups (p < 0.062 and p < 0.057, respectively). Following hair analysis for mineral and trace elements, iron (p = 0.033), selenium (p = 0.017), and manganese (p = 0.009) differed significantly between the groups. Serum micronutrient levels need cautious interpretation in conjunction with inflammatory markers. Hair mineral and trace element measurement may support understanding micronutrient status in children with IBD.

Two Cases of Colonoscopic Retrieval of a Foreign Body in Children: A Button Battery and an Open Safety Pin.

Ingestion of foreign body in children is a relatively common problem among paediatric population. The foreign bodies mostly pass spontaneously through the gastrointestinal tract. However, complications can occur according to its anatomical location, the characteristics of the foreign body, and delays in management. Although the cases of ingested button batteries or sharp objects impacted at the gastrointestinal tract can be very serious, there have been very only a few cases have reported colonoscopic removal of these dangerous foreign bodies in adults, and there have been no case reports in children. We report one case of a button battery and one case of an open safety pin, both impacted in the terminal ileum that had moved from the stomach within a few hours of ingestion and were eventually managed by colonoscopy without any complications.

Early adverse events and long-term outcomes of endoscopic sphincterotomy in a pediatric population: a single-center experience.

Background and aims: The use of endoscopic sphincterotomy (EST) in the management of pancreaticobiliary disease in children is increasing. However, studies of long-term outcomes are limited in pediatric patients. Therefore, this study evaluated the early adverse events and long-term outcomes following EST in pediatric patients. Patients and methods: We retrospectively analyzed data from 198 pediatric patients who underwent ESTs at Asan Medical Center Children's Hospital between 1994 and 2013. The median age was 8.7 years (range 18 months to17 years). We evaluated the indications, success rates, early adverse events, and long-term outcomes. Results: Long-term information was available in 198 patients with a median follow-up duration of 42 months (range, 1.8 - 232.1 months). Early adverse events (< 30 days) following 294 ESTs among 198 patients included pancreatitis in 17 (5.7 %), hemorrhages in 6 (2.0 %), sepsis in 3 (1.0 %), and perforations in 2 (0.7 %). Long-term complications ( > 30 days) developed in 12 patients (6.1 %), including cholangitis with or without bile duct stone (n = 7), and minor papilla restenosis (n = 5). The cumulative incidence rates of long-term complications were 3.1 %, 6.1 %, 9.3 %, and 9.3 %, at 1, 5, 10, and 15 years. There were no procedure-related pancreaticobiliary malignancies or deaths. All adverse events and long-term complications improved with appropriate management. Conclusions: In pediatric patients with pancreaticobiliary disease, EST has a high level of technical success. In addition, pediatric EST showed low rates of early adverse events and long-term complications, which could be managed safely. Our results suggest that EST is a safe method for treating pancreaticobiliary disease, even in the pediatric population.

Therapeutic Efficacy of Oral Enteral Nutrition in Pediatric Crohn's Disease: A Single Center Non-Comparative Retrospective Study.

PURPOSE: Exclusive enteral nutrition (EEN) therapy effectively induces clinical remission in Crohn's disease (CD). It remains unclear, however, whether partial enteral nutrition (PEN) can maintain remission. This study was performed to determine the abilities of oral EEN and oral PEN to induce and maintain clinical remission in pediatric patients with CD, respectively. MATERIALS AND METHODS: Pediatric patients with CD who received oral EEN at a single center in 2000-2014 were identified retrospectively. Remission rates of the EEN and PEN during the 2 years study period were determined. Risk factors for EEN and PEN failure were identified. RESULTS: Of the 66 patients who started EEN, 61 (92%) completed the course. Clinical remission was achieved in 88% (58/66) of the patients. All 58 patients with remission continued with PEN: 43 (74%) were treatment adherent. The cumulative remission rates at 1 and 2 years were 67% and 52%, respectively. Differing from EEN, limited therapeutic efficacy of PEN was shown in severe CD patients. Female gender associated significantly with non-adherence. CONCLUSION: Oral EEN and PEN effectively induced and maintained remission in a pediatric population. Non-adherence was a limiting factor in the success of therapy.

Diagnostic Value of Ceruloplasmin in the Diagnosis of Pediatric Wilson's Disease.

PURPOSE: Measurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis. METHODS: We retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for patients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated. RESULTS: Measurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of <20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accuracy of 94.7%. CONCLUSION: The measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level.

Cholangiographic characteristics of common bile duct dilatation in children.

AIM: To investigate whether children with congenital common bile duct dilatation (CBDD) differ from children with obstructive CBDD in cholangiographic characteristics. METHODS: In this retrospective cohort study, the baseline data and the results of imaging analyses were reviewed among children who had endoscopic retrograde cholangiopancreatography (ERCP) due to CBDD. ERCP was performed on all pediatric patients by experienced pediatric endoscopists. The maximal transverse diameter of the common bile duct (CBD) was measured on ERCP. To assess whether age-adjusted CBDD could be used for differential diagnosis, a CBDD severity index (SI) was calculated by dividing the measured CBD diameter by the age-corrected maximal diameter of a normal CBD. RESULTS: A retrospective medical chart review revealed that 85 consecutive children under 16 years of age with hepatobiliary disease and CBDD were referred to Seoul Asan Medical Center. Fifty-five (64.7%) children had congenital CBDD and 30 (35.3%) had obstructive CBDD. The two groups did not differ significantly in terms of clinical characteristics except for sex. The congenital and obstructive CBDD groups did not differ significantly in terms of mean CBD diameter (19.3 ± 9.6 mm vs 12.2 ± 4.1 mm, P > 0.05). However, congenital CBDD cases had a significantly higher mean SI than obstructive CBDD cases (3.62 ± 1.64 vs 1.98 ± 0.71, P = 0.01). In multivariate analysis, an SI value ≥ 2.32 and comorbidity with anomalous union of pancreaticobiliary duct (APBDU) in ERCP independently predicted congenital CBDD. CONCLUSION: Measuring the CBD may aid the differential diagnosis of both CBDD and APBDU in children.

Liver transplantation for metabolic liver disease: experience at a living donor dominant liver transplantation center.

PURPOSE: Metabolic liver disease (MLD) often progresses to life-threatening conditions. This study intends to describe the outcomes of liver transplantation (LTx) for MLD at a living donor-dominant transplantation center where potentially heterozygous carrier grafts are employed. METHODS: We retrospectively evaluated the medical records of 54 patients with MLD who underwent LTx between November 1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative graft and patient survival rates were analyzed according to patient age, and living or deceased donor LTx. Recurrence of the original disease was also investigated. RESULTS: The post-transplant cumulative patient survival rates at one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the patient survival rates according to the recipient age, human leukocyte antigen matching, and living or deceased donor LTx. There were also no differences in the patient survival rates between the MLD and the non-MLD groups for children. Recurrence of the original metabolic disease was not observed in any patient during the follow-up period. CONCLUSION: Our results suggest that the living donor-dominant transplantation program is well-tolerated in MLD without recurrence of the original MLD using all types of transplantation.

Clinical features, outcomes, and genetic analysis in Korean children with Alagille syndrome.

BACKGROUND: Alagille syndrome (AGS) is a multisystem autosomal dominant disorder that affects the liver, heart, eyes, face, bone, and other organs. AGS is caused by mutations in one of two genes, JAG1 or NOTCH2. We evaluated clinical features, outcomes, and the presence of JAG1 and NOTCH2 mutations in Korean children with AGS. METHODS: Between January 1997 and December 2013, 19 children were diagnosed with AGS at Asan Medical Center, Seoul, Korea. Their clinical features, outcomes, and JAG1 and NOTCH2 mutation status were retrospectively analyzed. RESULTS: The prevalence of clinical features in the 19 patients was as follows: dysmorphic facial features, 100% (n = 19); liver symptoms, 89% (n = 17); cardiac symptoms, 95% (n = 18); ophthalmologic symptoms, 67% (n = 10); skeletal deformities, 47% (n = 9); and renal symptoms, 21% (n = 4). JAG1 mutations were identified in 14 patients. The 13 different JAG1 mutations, seven of which were novel, included four deletions, three insertions, two missense mutations, three nonsense mutations, and one indel mutation. No NOTCH2 mutations were found. Two patients who received liver transplantation due to liver failure were still alive. Two patients died of comorbidities related to AGS: one of cardiac failure and one of hepatic failure. CONCLUSION: This study describes the clinical characteristics of 19 Korean AGS patients with seven novel JAG1 mutations. Neonatal cholestatic jaundice was the most common initial presenting symptom; thus the presence of neonatal cholestasis warrants screening for syndromic features of AGS. Complex heart anomalies and progressive liver dysfunction resulted in significant morbidity and mortality in AGS.

Chronic intermittent form of isovaleric aciduria in a 2-year-old boy.

Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as an acute episode of fulminant metabolic acidosis, which may lead to coma or death, or later as a "chronic intermittent form" that is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, such as infections. Here, we report the case of a 2-year old boy with IVA who presented with the chronic intermittent form. He was admitted to Asan Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis, hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and markedly increased urine isovalerylglycine concentration were noted. Sequence analysis of the IVD gene in the patient revealed the novel compound mutations-a missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del (p.Ile361fs*11). Following stabilization during the acute phase, the patient has remained in a stable condition on a low-leucine diet.