Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6–16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts’ histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group ( P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR ( P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER ( P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.

Background: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC.Methods: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared.Results: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group.Conclusions: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.

Satoyoshi syndrome is a rare multisystem disorder characterized by progressive painful muscle spasms, alopecia, and diarrhea. It causes short stature and severe joint deformities when it occurs in childhood. A 16-year-old boy complained of painful muscle spasms of the limbs and trunk since the age of nine years. He visited us at the age of 13 years because of rickets-like radiological findings and lower limb deformity. He was diagnosed with Satoyoshi syndrome based on the characteristic clinical and radiological findings, including deteriorated muscle spasms, impaired growth, frequent diarrhea, and joint deformities with metaphyseal sclerosis and growth plate widening. Corrective surgeries were performed with guided growth of genu varum and ankle valgus deformities. The correction rate was extremely slow and limited improvement was observed at skeletal maturity. Since Satoyoshi syndrome significantly disturbs longitudinal bone growth during childhood, guided growth surgery should be performed as early as possible.

Background and AimSerum 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. MethodsSubjects 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. ResultsWe enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200 mu g/mL) were significantly greater than in remission (81 mu g/mL; P < 0.001) or NC (69 mu g/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 mu g/mL) were significantly greater than in remission (65 mu g/mL; P < 0.01) but not significantly greater than in NC (69 mu g/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. ConclusionsIn pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD.

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren’s syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population.

We thank Dray and Koulaouzidis for their interest and letter regarding our article “ Safety and ef fi cacy of the endoscopic delivery of capsule endoscopes in adult and pediatric patients: Multicenter Japanese study (AdvanCE-J study). ” 1 Although they did not indicate how many patients could ingest orally or truly needed endoscopic delivery in the surgically altered gastric anatomy (SAGA) study, 2 we demonstrated that endoscopic delivery was rarely indicated in patients with SAGA. Therefore, capsule endoscopes (CE) can be orally ingested in patients with SAGA, but only in case of impossible ingestion or prolonged lodgment in the upper gastrointestinal tract by monitoring with a real-time viewer, endoscopic delivery would be chosen. These procedures were proven to be generally safe by the AdvanCE-J study, but rarely cause perforation, 3 presumably due to adhesion, in fl ammation, cancer invasion, or dissemination. Therefore, cautious deployment is needed. We should keep in mind that CE cannot enter the blind loops such as a Roux-en-Y limb and blind loops of Child, Whipple, and Billroth II reconstruction. Dray et al. described that only blood was seen at 2.8% in the SAGA study. 2 It is essential to determine where blood was seen. When CE depicts the bloody fl uid at anastomoses in patients with obscure gastrointestinal bleeding (OGIB), enteroscopy using device- assisted enteroscopes or pediatric colonoscope (only for Billroth II reconstruction) is to be chosen because bleeding origins may be localized in blind loops, hepatic portenterostomy, or pancreaticoje-junostomy. 4,5 Herein, we demonstrate the usefulness of CE and double-balloon enteroscopy for the diagnosis of metastasis from gastric cancer in the Roux-en-Y limb as the bleeding origin in a 72-year-old woman who presented with occult OGIB (hemoglobin,

We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes.

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. We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. 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. 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). 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.

An 8-year-old girl was presented to our clinic with fever, arthritis in her left knee, a necrotic right fifth toe, and multiple large deep-seated ulcerations. She was diagnosed with pyoderma gangrenosum. Treatment with corticosteroids alone was ineffective for her skin lesions, and therefore combination immunosuppressant therapy was administered. Her skin lesions rapidly improved, enabling discontinuation of the corticosteroid therapy and avoiding systemic infection through the ulcers. Combination immunosuppressant therapy may be a treatment option for patients with severe, rapidly progressive pyoderma gangrenosum.

BACKGROUND:Vaccination to prevent hepatitis B (HB) virus infection is important for children undergoing immunosuppressive treatment. Information on the efficacy of HB vaccination in children with rheumatic diseases undergoing immunosuppressive therapy is scarce.METHODS:Children with rheumatic diseases administered HB vaccine during immunosuppressive treatment between May 2013 and September 2016 were enrolled. Patients were vaccinated three times (primary series). Those who remained seronegative after the primary series received a secondary series of vaccinations. Patient baseline characteristics and treatment details from the medical records were retrospectively investigated. The proportion of patients that was seropositive for HB virus antibody after primary-and secondary series of vaccinations was calculated. Associations between immunosuppressants and serostatus were evaluated.RESULTS:Fifteen of 26 patients (58%) produced anti-hepatitis B surface antibody (anti-HBs) after the primary vaccinations. Eight of 10 patients (80%) taking methotrexate and 3 of 11 (27%) taking mycophenolate mofetil (MMF) were seropositive. Multivariate analysis adjusted for dosage of prednisolone per body weight. Multivariate analysis showed MMF was a factor impeding seroconversion (odds ratio 0.093, 95% confidence interval 0.014-0.615). In six of seven patients (86%) who received a secondary series of vaccinations, anti-HBs were produced.CONCLUSIONS:MMF may impede seroconversion after a primary series of HB vaccinations, thus requiring secondary series of vaccinations in pediatric patients with a rheumatic disease undergoing immunosuppressive therapy.

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.

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.

OBJECTIVESThis multicenter, cross-sectional study aimed to elucidate the efficacy and safety of the AdvanCE capsule endoscope delivery device for children in Japan.METHODSThe present study analyzed 183 cases of small bowel capsule endoscope (SBCE) insertion performed using the AdvanCE in 154 patients aged less than 18 years at participating institutions between 2013 and 2017. Statistical analyses were conducted to identify factors contributing to the completion rate for the entire small intestine examination, small intestine transit time, adverse events and technical issues.RESULTSThe commonest reason for using the AdvanCE was the patient's inability to swallow the SBCE, which was attributed to young age. SBCE was successfully delivered into the stomach or duodenum in 180 cases and was placed in the duodenum in 90% patients. In 89% patients, the entire small intestine was completely examined, and in 63% patients, findings leading to a new diagnosis or involving changing or maintaining the treatment strategy were obtained. No severe adverse events were observed; however, mild adverse events were observed in 35% patients. No factors considerably contributed to the completion rate for the entire small intestine examination or small intestine transit time and onset of technical issues. The factors that contributed to mild adverse events included intravenous anesthesia, technical issue, and absence of prior insertion of a patency capsule using the AdvanCE.CONCLUSIONThe AdvanCE is well tolerated and effective for children.

Objectives: This study aimed to determine the association between the dosage and pharmacokinetics of mycophenolate mofetil (MMF) in juvenile patients with autoimmune diseases. Methods: Totally, 29 patients were administered oral MMF. The blood concentrations of mycophenolate acid (MPA) at seven points, the area under the time-concentration curve (MPA-AUC(0-12h)), the peak concentration (C-max), and the time to peak concentration (T-max) were measured. To obtain a dose-normalized MPA-AUC(0-12h) value, the actual measured MPA-AUC(0-12h) value was divided by the dose value of the morning administration corrected for body weight (BW) or body surface area (BSA). The patients were classified into three age groups (group 1, <= 10 years; group 2, >10-<= 15 years; and group 3, >15 years), and pharmacokinetic parameters were compared among the groups. Results: In total, we obtained 37 measurements. The actual measured MPA-AUC(0-12h) values and the MPA-AUC(0-12h) values corrected for dose per BW and T-max were lower in young patients. The MPA-AUC(0-12h) values corrected for dose per BSA and C-max were comparable among all the groups. Conclusion: In patients with juvenile autoimmune diseases, determining MMF administration dosage according to BSA may facilitate MPA-AUC(0-12h) value prediction.

Objectives: This study investigated the association between myositis-specific autoantibodies (MSAs) and clinical subsets of juvenile dermatomyositis (JDM) in Japanese patients. Methods: Twenty-one patients at a single center who developed initial or relapsed JDM from 2011 to 2016 were analyzed. Serum concentrations of MSAs against TIF1-γ, MDA5, NXP2, Mi-2, ARS, and SAE were measured by enzyme-linked immunosorbent assays. Clinical symptoms and laboratory data were obtained from clinical records. Clinical characteristics were compared in patients with autoantibodies against TIF1-γ, MDA5, and NXP2. Results: Of the 21 patients, 20 (95.2%) were positive for one or more MSAs, including nine (42.9%), five (23.8%), six (28.6%), and one (4.8%) positive for anti-TIF1-γ, anti-MDA5, anti-NXP2, and anti-Mi-2 autoantibodies. No patient was positive for anti-ARS or anti-SAE autoantibodies. The frequency of diffuse cutaneous lesions was higher in patients with anti-TIF1-γ autoantibodies. Anti-MDA5 autoantibody-positive patients had features of interstitial lung disease on chest computed tomography. Severe muscle damage at disease onset was significantly associated with positivity for anti-NXP2 autoantibodies. Conclusion: Similar to findings in Western countries, the clinical characteristics of JDM in Japanese may differ for each type of MSAs.

Objectives: The objective of this study is to identify risk factors for hypersensitivity reaction (HSR) to tocilizumab (TCZ) in systemic juvenile idiopathic arthritis (sJIA). Methods: Clinical records of 40 patients with sJIA administered TCZ at one center were retrospectively reviewed. Patients were divided into HSR or non-HSR groups depending on the presence of HSR between the first and third TCZ administrations; clinical and laboratory assessments, including serum cytokine profile, were compared. Results: Five patients displayed HSR following the third TCZ administration. They were significantly younger, shorter, and lighter, with a higher peak body temperature than non-HSR patients following the third administration. Their serum C-reactive protein (CRP) level was undetectable following the first administration but detectable by the third administration. Before the third administration, the white blood cell counts and serum levels of CRP and sTNFRII were significantly higher in the HSR group than in the non-HSR group. The serum levels of interleukin-18 and -6 before the third TCZ administration were higher and lower than those before the first administration in the HSR and non-HSR groups, respectively. Conclusion: Patients with sJIA having a younger age, shorter stature, and lighter weight and those showing increased disease activity in the early period of TCZ administration may be at higher risk of TCZ-induced HSR.

Ingested foreign bodies are common clinical problem in children. The indication and timing of intervention depend on patient age, patient size, type of the ingested objects, location, clinical symptoms, time since ingestion, and other factors. Here, we report our experiences of management of ingested foreign bodies in children comparing to ASGE guideline.

Background and Aims: Fibroscan (Echosens,France) is a new non invasive tool for measuring liver stiffness and steatosis. It has mainly developed to evaluate chronic liver disease in adult, but usefulness and appropriate inspection method in children has not been established. We report our experience of Fibroscan to evaluate liver stiffness and steatosis in children. Methods: Pediatric patients diagnosed or suspected to have liver disease were evaluated for controlled attenuation parameter (CAP) and elasticity value (E value) using Fibroscan from August 2013 to November 2014. Results: In total, 20 procedures were performed for 19 patients (14 male, average age 11.5 year). CAP was 100 to 348 dB/m, and E value was 3.2 to 21.3 kPa. E values were higher than 10 kPa in three patients, one after receiving liver transplantation, one post Fontan procedure and one Alstrom syndrome. Liver biopsy was performed in four of them (2 Non-alcoholic steatohepatitis:NASH), 1 congenital liver fibrosis, 1 Wilson's disease) at almost the same time and E value was correlated with histological fibrosis stage (F 1-2) in them. CAP and the degree of steatosis in the liver tissue were correlated in NASH patients. After treatment not only the blood data such as transaminase and HOMA-IR but also CAP and E value of the patient of NASH were improved (CAP 323 to 299 dB/m, E value 7.7 to 4.5 kPa). Conclusion: Fibroscan might be useful for evaluating and following up liver stiffness and steatosis of children with liver disease as well as adult.