Single measurement of bowel wall thickness using intestinal ultrasonography in children with ulcerative colitis.

BACKGROUND: Endoscopic monitoring of disease activity in patients with ulcerative colitis (UC) is important. However, frequent colonoscopic examinations are difficult to perform because of their invasiveness, especially in children. Bowel wall thickness (BWT) measurement using intestinal ultrasonography and fecal calprotectin (FC) measurement are useful noninvasive evaluation methods. METHODS: We retrospectively analyzed BWT and FC levels and evaluated the Mayo endoscopic subscore (MES) using colonoscopy in pediatric patients with UC during the same period. The BWT was evaluated using the maximum BWT (mBWT), which was the maximum value of each colonic BWT; the sum of BWT (sBWT), which was the sum of each colonic BWT; and the sum of the adjusted BWT (saBWT), which was corrected using sBWT. RESULTS: In 54 procedures from 40 patients, FC, mBWT, sBWT, and saBWT were significantly different between MES 0-1 and MES 2. The agreement between BWT and MES 2 was 193 out of 216 segments (89.4%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FC were 68.8%, 84.2%, 64.7%, 86.5%, and 79.6% respectively, while those of saBWT were 81.2%, 89.5%, 76.5%, 91.9%, 87.0%, respectively. CONCLUSIONS: BWT in each colonic segment, particularly saBWT, was more useful than FC for detecting moderate colonic inflammation (MES 2) in pediatric patients with UC. Therefore, intestinal ultrasonography may be helpful in the less invasive management of pediatric patients with UC.

Serum leucine-rich alpha-2 glycoprotein and calprotectin in children with inflammatory bowel disease: A multicenter study in Japan.

BACKGROUND AND AIM: Serum leucine-rich alpha-2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. METHODS: Subjects under 17 years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200 µg/mL) were significantly greater than in remission (81 µg/mL; P < 0.001) or NC (69 µg/mL; P < 0.001). Serum calprotectin concentrations in active CD (2941 ng/mL) also were significantly greater than in remission (962 ng/mL; P < 0.05) or NC (872 ng/mL; P < 0.05). Serum LRG concentrations in active UC (134 µg/mL) were significantly greater than in remission (65 µg/mL; P < 0.01) but not significantly greater than in NC (69 µg/mL); serum calprotectin concentrations in active UC (1058 ng/mL) were not significantly different from those in remission (671 ng/mL) or NC (872 ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C-reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C-reactive protein, or erythrocyte sedimentation rate. CONCLUSIONS: In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD.

Serum Zinc and Selenium in Children with Inflammatory Bowel Disease: A Multicenter Study in Japan.

BACKGROUND: Reports of zinc and selenium deficiencies accompanying inflammatory bowel disease (IBD) mostly have originated from Western countries and concerned adult patients. Whether Japanese children with IBD have similar deficiencies remained unclear. AIM: We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. METHODS: Children under 17 years old undergoing care at 12 Japanese pediatric centers were retrospectively enrolled between November 2016 and February 2018 to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illnesses. Serum zinc and selenium were measured by atomic absorption spectrophotometry. Zinc and selenium deficiencies were defined by serum concentrations < 70 µg/dL and < 9.5 µg/dL, respectively. RESULTS: Subjects included 98 patients with CD (median age, 13 years), 118 with UC (11 years), and 43 NC (11 years). Serum zinc and selenium were significantly lower in CD (median, 64 and 12.6 µg/dL respectively) than in UC (69 and 14.6; P < 0.05 and P < 0.001) or NC (77 and 15.7; P < 0.01 and P < 0.001). Zinc deficiency was significantly more prevalent in CD (60.2%) than in NC (37.2%; P < 0.05), but not than in UC (51.7%; P = 0.22). Selenium deficiency was significantly more prevalent in CD (15.3%) than in UC (5.9%; P < 0.05) or NC (0%; P < 0.01). CONCLUSIONS: In Japanese children under 17 years old, serum zinc and selenium were significantly lower in CD than in UC or NC. Zinc and selenium should be monitored, and supplemented when deficient, in children with IBD, especially CD.

Usefulness of ultrasonography for small intestinal evaluations in pediatric Crohn's disease.

BACKGROUND: Small bowel capsule endoscopy (SBCE) for Crohn's disease is useful; however, its use has some limitations, such as invasiveness when endoscopic assistance is required in patients who cannot swallow the capsule, and the burden of interpretation on a physician. In contrast, intestinal ultrasonography (IUS) is a non-invasive modality for children. The purpose of this study is to evaluate the accuracy of IUS for pediatric patients with established Crohn's disease. METHODS: Small bowel capsule endoscopy and IUS findings from the same period in pediatric patients with established Crohn's disease were analyzed retrospectively. First, we compared the Lewis score (LS), small bowel endoscopic activity, and IUS findings by small bowel wall thickness (SBWT) and mesenteric lymph node size (MLNS). Second, we compared the performance of IUS findings with those of some biomarkers. RESULTS: In 22 procedures, SBWT and MLNS were correlated with LS (r = 0.52, P < 0.05, and r = 0.45, P < 0.05, respectively). Small bowel wall thickness, erythrocyte sedimentation rate, and fecal calprotectin levels had the highest accuracy (81.8%, 81.8%, and 81.8%, respectively). The combination of SBWT and MLNS had the highest positive predictive value and negative predictive value (100% and 83.3%, respectively). CONCLUSIONS: Intestinal ultrasonography findings, including SBWT and MLNS, are useful for monitoring small bowel lesions in pediatric patients with established Crohn's disease. We suggest first evaluating small bowel inflammation by IUS in pediatric patients with Crohn's disease before SBCE because IUS is less invasive than SBCE.

Diagnostic accuracy of serum proteinase 3 antineutrophil cytoplasmic antibodies in children with ulcerative colitis.

BACKGROUND AND AIM: Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS: Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS: Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3-ANCA was 0.79, significantly greater than for MPO-ANCA (0.58; P < 0.001). Using a cut-off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3-ANCA showed significantly greater sensitivity (64.9%) than MPO-ANCA (cut-off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). CONCLUSIONS: In Japanese children and adolescents, PR3-ANCA performed better as a serologic marker for diagnosis of UC than MPO-ANCA. To our knowledge, this is the first report of such a comparison.

Helicobacter pylori test-and-treat strategy for second-year junior high school students aimed at the prevention of gastric cancer in Takatsuki City.

BACKGROUND: More than 90% of gastric cancer cases are caused by Helicobacter pylori infections. To prevent gastric cancer, an H pylori test-and-treat strategy targeting young people has been implemented in various places in Japan. In this study, we evaluated the effectiveness of an H pylori test-and-treat strategy for second-year junior high school students in Takatsuki City. MATERIALS AND METHODS: In 2014-2017, a urine-based H pylori test was used for initial screening. The final infection status was determined by a 13 C-urea breath test (13 C-UBT). Successful H pylori eradication was confirmed by 13 C-UBT 3 months after treatment. First-line eradication therapy was changed from 10 mg of rabeprazole, 750 mg of amoxicillin, and 200 mg of clarithromycin twice daily for 7 days in 2014 to 20 mg of vonoprazan, 750 mg of amoxicillin, and 200 mg of clarithromycin twice daily for 7 days in 2015-2017. Second-line eradication therapy included 10 mg of rabeprazole, 750 mg of amoxicillin, and 250 mg of metronidazole twice daily for 7 days. RESULTS: In total, 8067 of 13 055 students participated this project and 206 students were diagnosed with H pylori infection. The success rate of first-line therapy was 45.9% in 2014 and 83.8% after the revised first-line therapy was administered. The final eradication rate was 98.5%. There were no severe side effects. CONCLUSION: Our results support the use of the H pylori test-and-treat strategy for junior high school students as a safe approach for the prevention of gastric cancer. H pylori eradication therapy with vonoprazan could be a standard therapy in children.

Correlation of the endoscopic findings for small and large bowels in pediatric patients with established Crohn's disease.

Small bowel capsule endoscopy can detect subtle mucosal lesions in pediatric patients with Crohn's disease, and our aim was to evaluate its application in established ileocolonic Crohn's disease. Colonic inflammation was evaluated with the colonic Simple Endoscopic Score for Crohn's Disease (SES-CD) (excluding the score of the terminal ileum). Small bowel inflammation was evaluated with the Lewis score and/or Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). A Lewis score <135 was defined as small bowel inactive. A colonic SES-CD of 0 (colonic inactive group) was observed in 22/42 procedures (52.4%), and active small bowel lesions were observed in 11/22 procedures (50.0%). The Lewis score was lower in the colonic inactive group compared to the colonic active group. Correlations between the colonic SES-CD, the Lewis score and CECDAI were weak. The Lewis score and CECDAI in the colonic inactive group had significant correlation with fecal calprotectin levels. We suggest that Crohn's disease patients without both colonic active lesions and elevation of fecal calprotectin levels may not need to receive small bowel capsule endoscopy due to low incidence of lesions in small bowel.

Treatment with infliximab for pediatric Crohn's disease: Nationwide survey of Japan.

BACKGROUND AND AIM: Childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression. Infliximab (IFX), cyclosporin (CYA), and tacrolimus (FK506) are increasingly used to treat pediatric IBD; however, their long-term effects and adverse events have not been properly investigated in pediatric patients. The aim of this study was to characterize the effects of these biologics and immunomodulators on pediatric IBD patients in Japan. Additionally, we assessed IFX use in pediatric patients with Crohn's disease (CD). METHODS: A national survey of IFX, adalimumab, CYA, and FK506 use in pediatric IBD patients (< 17 years of age) was sent to 683 facilities in Japan from December 2012 to March 2013. Secondary questionnaires were sent to pediatric and adult practitioners with the aim of assessing the effectiveness and safety of IFX for pediatric CD patients. RESULTS: The response rate for the primary survey was 61.2% (N  =  418). Among 871 pediatric CD patients, 284 (31.5%), 24, 4, and 15 received IFX (31.5%), adalimumab, CYA, and FK506, respectively, from 2000 to 2012. According to the secondary survey, extensive colitis (L3, Paris classification) was diagnosed in 69.4% of pediatric CD patients who received IFX. Regarding the effectiveness of IFX in this population, 54.7% (99/181) of patients were in remission, and 42.0% (76/181) were on maintenance therapy. However, 32.0% (58/181) of patients experienced adverse events, and one patient died of septic shock. CONCLUSIONS: Infliximab is reasonably safe and effective in pediatric CD patients and should therefore be administered in refractory cases.

Supplementation with carnitine reduces the severity of constipation: a retrospective study of patients with severe motor and intellectual disabilities.

Carnitine is an essential nutrient for the mitochondrial transport of fatty acids. Carnitine deficiency causes a variety of symptoms in multiple organs. Patients with severe motor and intellectual disabilities often have carnitine deficiency. This study aimed to determine the correlation between constipation and carnitine deficiency in them. Patients with severe motor and intellectual disabilities at our hospital were retrospectively reviewed. The correlation between level of free carnitine and severity of constipation was examined. Constipation and non-constipation groups were compared for age; sex; body mass index; bed rest period; use of anti-epileptic drugs, valproate sodium, or enteral nutrition; and serum levels of albumin, pre-albumin, totalcholesterol, free carnitine, folic acid, and trace elements. Moreover, severity of constipation before and after carnitine supplementation was assessed. Twenty-seven patients were enrolled. Of these, 14 were assigned to the constipation group and 13 to the non-constipation group. The free carnitine level was significantly correlated with severity of constipation (R = 0.7604, p<0.01). Free carnitine was significantly lower in the constipation compared with the non-constipation group (p<0.01). No other significant differences between the groups were found. The severity of constipation was significantly relieved after carnitine supplementation (p<0.001). In conclusion, carnitine supplementation could reduce the severity of constipation.

Fasting and bed rest, even for a relatively short period, are risk factors for ceftriaxone-associated pseudolitiasis.

BACKGROUND: Cholelithiasis is one of the side-effects of ceftriaxone (CTRX). Reportedly, the cholelithiasis resolves relatively soon after cessation of CTRX, hence, it is called pseudolithiasis. Previous reports have suggested that biliary pseudolithiasis can cause not only gallstone attacks, but also severe adverse events, such as cholecystitis and pancreatitis. The purpose of this study was to prospectively elucidate the risk factors and clinical features of CTRX-associated pseudolithiasis in pediatric patients. METHODS: We prospectively examined the incidence and clinical outcome of CTRX-associated biliary pseudolithiasis. Subjects included infants and children who were admitted to hospital with acute disease. Ultrasonography was used to confirm the absence of stones and sludge in the gallbladder before CTRX therapy, and in assessment of pseudolithiasis on days 3, 5, 7 and 10 after initiation of CTRX in all subjects. The pseudolithiasis group was then compared with the non-pseudolithiasis group in terms of age, sex, CTRX dose, CTRX duration, duration of fever, fasting period, period of bed rest, and blood test results. RESULTS: Sixty patients were enrolled in the study. Eleven of them had biliary pseudolithiasis on ultrasonography (18.3%). Formation of biliary pseudolithiasis was prevalent in the fasting and bed rest groups, appearing relatively early in these groups. CONCLUSIONS: Special attention should be paid to the degree of oral intake and patient activity when CTRX is prescribed. We recommend regular ultrasonographic follow up of patients receiving CTRX, to evaluate the formation of biliary pseudolithiasis.

Usefulness of a novel and rapid assay system for fecal calprotectin in pediatric patients with inflammatory bowel diseases.

BACKGROUND AND AIM: Fecal calprotectin (FC) has become a reliable biomarker for intestinal inflammation in inflammatory bowel diseases (IBDs). However, a simple and rapid assay to replace conventional ELISA is necessary for wider use in clinical practice. In this study, we investigated the usefulness of a novel method for measuring FC using a colloidal gold aggregation (CGA) assay for assessing mucosal inflammation in pediatric IBDs. METHODS: FC levels were determined by ELISA and CGA assay in 309 fecal samples (ulcerative colitis [UC]: 131; Crohn's disease [CD]: 121; healthy controls: 57). For endoscopic evaluation, the modified Matts' grading system for UC and the simple endoscopic score for CD were used. RESULTS: A strong correlation was found between the FC values determined by the two methods (r = 0.98, P < 0.01). FC levels, determined by CGA assay, strongly correlated with the endoscopic score for UC (r = 0.70, P < 0.01) and CD (r = 0.58, P < 0.01). In the UC patients with endoscopic remission, the FC levels determined by CGA assay (median: 31.5 µg/g, n = 14) were as low as in healthy controls. For patients in clinical remission but showing an active status endoscopically, FC was more likely to be abnormal than commonly used laboratory markers. CONCLUSIONS: Our simple and rapid assay system has excellent performance for assessing mucosal inflammation of IBDs and can be replaced for ELISA. Practical application of this assay system enables us to use FC measurement more widely in clinical practice.

[Three cases of childhood-onset autoimmune pancreatitis].

Here we present 3 cases of childhood-onset autoimmune pancreatitis: 2 cases in boys aged 4 and 16 years, diagnosed with ulcerative colitis; 1 case in a previously healthy 10-year-old boy. All 3 boys presented with abdominal pain associated with elevated pancreatic enzyme levels. Immunoglobulin G4 levels were elevated only in the 16-year-old boy. However, pancreatic enlargement together with narrowing of the main pancreatic duct was evident on computed tomography in all 3 cases. Autoimmune pancreatitis is an uncommon disease in childhood, and only 3 cases affecting patients under 17 years of age have previously been reported in Japan. Autoimmune pancreatitis may be latent in children with pancreatitis who have chronic or intermittent abdominal symptoms. In addition, it is necessary to recognize autoimmune pancreatitis as a complication of pediatric inflammatory bowel disease. The clinical features of pediatric autoimmune pancreatitis remain unclear, and an accumulation of cases is necessary.

Neutralization of complement component C5 ameliorates the development of dextran sulfate sodium (DSS)-colitis in mice.

The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease, we evaluated the effects of anti-C5 antibodies on the development of dextran sulfate sodium-induced colitis in mice. Dextran sulfate sodium-colitis was induced in BALB/c mice with intraperitoneal administrations of anti-C5 antibodies (1 mg/body [DOSAGE ERROR CORRECTED]) every 48 h. Tissue samples were evaluated by standard histological procedures. The mucosal mRNA expression of the inflammatory cytokines was analyzed by real-time PCR. Body weight loss in the mice was completely blocked by the administration of anti-C5 antibody. The disease activity index was significantly lower in the anti-C5 antibody-treated mice than the dextran sulfate sodium mice. The colonic weight/length ratio, histological colitis score and mucosal myeloperoxidase activity were significantly lower in the anti-C5 antibody-treated mice than the dextran sodium sulfate mice. The administration of the anti-C5 antibody significantly reduced the mucosal expression of mRNAs for tumor necrosis factor-α, interleukin-1ß and interleukin-6. In conclusion, the complement system plays a role in the development of dextran sodium sulfate-induced experimental colitis.

Terminal restriction fragment length polymorphism analysis of the gut microbiota profiles of pediatric patients with inflammatory bowel disease.

BACKGROUND/AIM: We analyzed the fecal microbiota profiles of pediatric patients with inflammatory bowel disease. METHOD: Terminal restriction fragment length polymorphism analysis was performed in 10 fecal samples from Crohn's disease (CD), 14 samples from ulcerative colitis (UC) and 27 samples from healthy individuals. The bacterial diversity was evaluated by the Shannon diversity index. RESULT: In CD patients, a setting of similarity generated three major clusters. The majority of CD patients were classified into CD clusters I and II (9 out of 10), but the majority of healthy individuals (21 of 27) were classified into CD cluster III. In UC patients, a setting of similarity also generated three major UC clusters, but each cluster was not characteristic for UC patients or healthy individuals. The changes in simulated bacterial composition indicated that the class Clostridia, including the genus Faecalibacterium, was significantly decreased in CD patients as compared to UC patients and/or healthy individuals. The genus Bacteroides was also decreased as compared to healthy individuals. The bacterial diversity measured by the Shannon diversity index was significantly reduced in CD patients as compared to healthy individuals. CONCLUSION: The gut microbiota profile of pediatric CD patients was different from that of healthy children.

The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range.

BACKGROUND: We hypothesized that the severity of dextran sodium sulfate (DSS)-induced colitis could differ between DSS preparations of the same molecular weight, and that this difference may be affected by the sulfur content. To test this, we used three DSS preparations of similar molecular weights but with different sulfur contents. METHODS: Three DSS preparations with molecular weights of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab Depot (The Lab). Epithelial cell lines were used to assess the levels of poly (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week-old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed to investigate the effects of the DSS preparations in vivo. RESULTS: In vitro experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2 cells treated with DSS from USB as compared to The Lab Mice treated with The Lab DSS had significantly decreased body weight losses on day 7 as compared to mice receiving DSS from MP Bio and USB. This result was supported by their DAI score, colon weight/length ratio, and histological scores. CONCLUSION: The severity of colitis can differ between similar DSS preparations of the same molecular weight range. This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation.

Characteristics and Frequency of Pediatric Inflammatory Bowel Disease-Associated Pancreatitis: A Japanese Nationwide Survey.

Acute pancreatitis (AP) develops in approximately 2% of patients with the diagnosis of inflammatory bowel disease (IBD), but the characteristics and frequency of childhood-onset IBD-associated AP in Japan have not been studied. The present study aimed to clarify the characteristics of IBD-associated AP in Japan. Methods: A nationwide survey of pediatric patients with IBD (age, <17 years) was conducted from December 2012 to March 2013 at 683 hospitals and medical centers in Japan. A secondary survey was also sent to the centers with the target patients to evaluate their characteristics. Results: The response rate to the first part of the survey was 61.2% (n = 418). In total, 871 patients with Crohn disease and 1671 patients with ulcerative colitis were enrolled. The second part of the survey found that 11 (1.3%) patients with Crohn disease and 23 (1.4%) patients with ulcerative colitis experienced IBD-associated AP caused by medication (n = 18, 53%), a primary disease (n = 11, 32%), autoimmune pancreatitis (n = 1, 3%), or an anatomical abnormality (n = 1, 3%). All the patients had only mild AP. Conclusions: IBD-associated AP was not very frequent and was generally mild. The major cause of the pancreatitis was the medication used to treat the IBD.

Fecal calprotectin is a useful marker for disease activity in pediatric patients with inflammatory bowel disease.

BACKGROUND: Studies evaluating the correlation between endoscopic disease activity and noninvasive markers are scarce in inflammatory bowel disease (IBD). AIM: The aim of this study is to evaluate the accuracy of the fecal calprotectin (FC) assay as a marker of disease activity of IBD, as determined by an extensive endoscopic scoring system. METHODS: Thirty-five children and adolescents with IBD [17 with ulcerative colitis (UC) and 18 with Crohn's disease (CD)] and 28 healthy volunteers were enrolled. FC levels were determined by ELISA. The sum of Matts' score for UC and the simple endoscopic score for Crohn's disease (SES-CD) were used. The ileal lesions were evaluated by ultrasonography. RESULTS: In UC patients, there was a strong correlation between FC levels and the sum of Matts' score (r=0.838, p<0.01). FC levels were significantly elevated in endoscopically active patients (median 1,562.5 µg/g) as compared to patients in endoscopic remission (median 38.9 µg/g) or healthy controls (median 19.9 µg/g). In CD patients, there was a strong correlation between FC levels and the SES-CD score (r=0.760, p<0.01). The FC levels were significantly higher in endoscopically active patients (median 2,037.5 µg/g) than in endoscopically inactive patients (median 172.5 µg/g) or healthy controls (median 19.9 µg/g), respectively. The FC levels of patients with ileal wall thickening (median 2,225.0 µg/g) were significantly higher than healthy controls (median 19.9 µg/g) and patients lacking ileal wall thickening (median 17.5 µg/g), respectively. CONCLUSIONS: The FC assay is a useful marker for the detection of mucosal inflammation in pediatric IBD patients.

Fulminant hepatitis B and acute hepatitis B due to intrafamilial transmission of HBV after chemotherapy for non-Hodgkin's lymphoma in an HBV carrier.

Hepatitis B virus (HBV) reactivation after chemotherapy has been investigated, but little is known about the risk of horizontal transmission from an immunocompromised host with HBV reactivation. We treated two children with fulminant hepatitis B and acute hepatitis B, respectively, whose grandmother, an HBV carrier, had been undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R+CHOP) therapy for lymphoma. The grandmother was also suffering from fulminant hepatitis when both children became ill. The complete HBV DNA sequences of the three family members were identical. The full genome sequence analysis of HBV provided strong evidence of intrafamilial transmission of HBV. Treatments that cause immunosuppression, such as R+CHOP therapy for lymphoma, can increase the levels of serum HBV DNA and the risk of intrafamilial HBV infection when given to HBV carriers. In conclusion, specific antiviral prophylaxis is indispensable for preventing horizontal transmission as well as reactivation of HBV in chemotherapy-treated HBV carriers.

Antibodies to Crohn's disease peptide 353 as a diagnostic marker for pediatric Crohn's disease: a prospective multicenter study in Japan.

BACKGROUND: Various serologic markers such as anti-glycoprotein 2 antibodies and anti-Saccharomyces cerevisiae antibodies have been reported to be diagnostically useful in Crohn's disease. Mitsuyama et al. reported that antibodies to Crohn's disease peptide 353, a newly proposed serologic marker, were more useful in Japanese adults than anti-Saccharomyces. We addressed the same issue in Japanese children and adolescents. METHODS: Prospectively enrolled subjects under 17 years old assessed and treated at 12 pediatric centers in Japan included groups with Crohn's disease, ulcerative colitis, other intestinal diseases, or good health. The 3 serum markers were analyzed by enzyme-linked immunosorbent assays. RESULTS: Enrolled subjects, numbering 367, included 120 with Crohn's disease, 148 with ulcerative colitis, 56 with other intestinal diseases, and 43 healthy subjects. In Crohn's disease, anti-Crohn's disease peptide 353, anti-glycoprotein 2, and anti-Saccharomyces concentrations (median, 2.25, 3.0, and 8.9 U/mL) were significantly greater than in ulcerative colitis (1.1, 1.9, and 3.4; all P < 0.001), other intestinal diseases (1.1, 1.85, and 2.95; all P < 0.001), and healthy controls (1.1, 1.7, and 2.8; all P < 0.001), respectively. At 95% specificity, sensitivity of anti-Crohn's disease peptide (45.0%) was significantly higher than for anti-glycoprotein 2 (30.8%; P < 0.05) or anti-Saccharomyces (26.7%; P < 0.01). CONCLUSIONS: Anti-Crohn's disease peptide 353 proved more useful for diagnosis of Crohn's disease in Japanese children than the other 2 markers. To our knowledge, this is the first pediatric report to that effect.

Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry.

BACKGROUND/AIMS: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children. METHODS: This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data. RESULTS: A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn's disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturing/non-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01). CONCLUSIONS: Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.