No abstract

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1–6), prognosis (CQ 7), monitoring and treatment goals (CQs 8–11), medical management and general statement (CQs 12–13), medical treatment (CQs 14–22), and surgical treatment (CQs 23–25) of BD and some specific situations (CQs 26–28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.

Background: In 2018, Japanese guidelines for autonomy support of patients with inflammatory bowel disease (IBD) in the transitional period were published. These guidelines, however, were prepared mainly by pediatric gastroenterologists. In order to improve such supportive guidelines, it is necessary for pediatric gastroenterologists to be aware of the attitudes and expectations of adult gastroenterologists. Accordingly, the first Japanese national survey designed to explore the views of adult gastroenterologists regarding successful transitional care was conducted. Methods: The survey involved institutions at which adult gastroenterologists in the Ministry of Health, Labor and Welfare of Japan's Inflammatory Bowel Diseases Study Group, were working. Physicians were contacted by conventional mail, and their answers were not anonymized. A total of 100 eligible adult institutions were identified. Further specific subgroup analysis was conducted. Results: A response rate of 34% was achieved. Seventy-six percent of the respondents had experienced some degree of difficulty when accepting patients with childhood-onset IBD referred from pediatric gastroenterologists. With regard to the ideal form of medical care for adolescent patients with IBD, transfer to adult care was supported by 94% of the respondents. Only 27% of respondents, however, stated they would have no hesitation in accepting patients referred from pediatric care centers. Two crucial areas requiring improvement were identified: inadequate clinical summaries and lack of patient independence from their parents/caregivers. Conclusions: The present survey results reinforce the importance of a transitional program of education for childhood-onset IBD patients and the need to improve communication between adult and pediatric gastroenterologists.

NICCD is an autosomal recessive genetic disorder, characterized by cholestasis, coagulopathy, hypoglycemia, fatty liver and multiple amino acidemia. NICCD develops in the neonatal/infantile period and has been reported as a "naturally curable" disease within one yr of life. Recently, we experienced an infantile NICCD who developed progressive liver failure, and required subsequent LT using a heterozygote living donor at eight months of age. Diagnosis of NICCD was established before transplantation, and donor evaluation included mutation in the SLC25A13 gene for exclusion of individuals with citrin deficiency citrullinemia. LDLT, from blood type identical mother using a left lateral segment graft, was performed without serious complication. Plasma amino acid concentration was normalized rapidly, and the patient was discharged 30 days after transplant. During one yr follow up, the recipient has been doing well without additional medication for NICCD. NICCD should be considered in the differential diagnosis as a cause of neonatal/infantile cholestatic disease. LT using a heterozygote living donor is an effective alternative in countries where a deceased donor is not available.

Objective. To assess anxiety among pediatric patients and their parents related to initial gastrointestinal endoscopy. Methods. Patients aged <19 years undergoing initial gastrointestinal (GI) endoscopy and their parents were invited to complete a self-administered questionnaire related to endoscopy in 13 institutions in Japan. Results. The subjects were 128 children, aged 1 month to 17 years. Forty-eight patients (37.5%) underwent esophagogastroduodenoscopy (EGD), 32 (25%) underwent colonoscopy (CS), 39 (30.5%) underwent both EGD and CS, 3 (2.3%) underwent balloon enteroscopy (BE), 3 (2.3%) underwent capsule endoscopy (CE), and 3 (2.3%) underwent CE and other endoscopic procedures. In the preendoscopy questionnaire, the most common concerns of the patients and parents before undergoing the procedure were “Pain” (45% of the patients underwent EGD or BE via the oral approach, and 52% of the patients underwent CS or BE via the anal approach) and “Procedural accidents related to the endoscopy” (63% of parents). In the postendoscopy questionnaire, the most common difficulty that patients and parents actually experienced before and after undergoing the procedure was “Hunger.” Conclusion. A preparatory intervention including an explanation regarding specific concerns before initial GI endoscopy, which this study revealed, could reduce anxiety experienced by both pediatric patients and parents.

Many clinical trials have been conducted for inflammatory bowel disease (IBD), so various clinical indices (CIs) and endoscopic indices (EIs) have also been evaluated. However, recently, with the progress of IBD management, review of established indices from previous studies, and establishment of new indices, the landscape of the use of indices in clinical trials have changed. We investigated the number and frequency of the indices adapted in recent clinical trials for ulcerative colitis (CI and EI) and Crohn’s disease (CI, EI, index related to magnetic resonance imaging, index for evaluating patient-reported outcomes, and health-related quality of life). Based on the results, we selected representative indices and further reviewed their content and characteristics. Moreover, various definitions, including clinical and endoscopic response or remission, have been described by means of representative indices in clinical trials.

Background Haploinsufficiency of A20 (HA20) is caused by loss-of-function TNFAIP3 variants. Phenotypic and genetic features of HA20 remain uncertain; therefore, the clinical distinction between HA20 and Behçet’s disease (BD) requires clarification. Methods We have collected 12 Japanese BD-like families. Probands of these families were analyzed by whole exome sequencing (WES) and subsequent Sanger sequencing. Clinical features were compared between 54 HA20 patients (including previously reported and new cases) and 520 Japanese BD patients. Results We identified c.1434C>A:p.(Cys478*) in one family and a 236 kb deletion at 6q23.3 containing TNFAIP3 in another family. Four HA20 patients in the two families presented with childhood-onset recurrent oral and genital ulcers and were initially diagnosed and treated as BD. Consistent with the clinical features of HA20, recurrent, refractory fever attacks (three of four patients), and digestive ulcers (two of the four patients) were observed. A comparison of clinical features between HA20 patients and cohorts of BD patients revealed several critical features specific to HA20. These were early-onset, familial occurrence, recurrent fever attacks, gastrointestinal involvement, and infrequent ocular involvement. Conclusions We identified a novel nonsense variant and deletion of the entire TNFAIP3 gene in two unrelated Japanese HA20 families. Genetic screening of TNFAIP3 should be considered for familial BD-like patients with early-onset recurrent fevers. Electronic supplementary material The online version of this article (10.1186/s13075-019-1928-5) contains supplementary material, which is available to authorized users.

Background To evaluate the role of colonoscopy in infants and young children and clarify the distribution of colonoscopy-requiring diseases in this age group. Methods Cohorts of colonoscopies performed at three children’s hospitals in Japan between April 2011 and March 2016 including infants and children younger than six years of age were retrospectively reviewed. Results In total, 453 colonoscopies were performed in 276 infants and young children. Of these 275 (60.8%) were for diagnostic purposes, 177 (39.2%) were performed as follow-up, and one case was performed for treatment. The median patient age at the time of diagnostic colonoscopy was 2.49 years, and there was a male-to-female ratio of 1.72:1. Abnormal macroscopic and/or histopathological findings were noted in 212 (77.1%) cases. Of these, definite diagnoses were established for the presence of eosinophilic gastrointestinal disorders (EGIDs), inflammatory bowel disease (IBD), and polyp/polyposis in 23, 18.5, and 14% of patients, respectively. Among 51 IBD cases, ulcerative colitis, Crohn’s disease, and IBD-unclassified were identified in 47.1, 33.3, and 7.8%, retrospectively via endoscopic examination. Of these, 11 (22%) were eventually diagnosed with monogenic diseases via genetic testing. Of those with rectal bleeding, EGIDs, polyps/polyposis, and IBD were found in 27, 19, and 18%, retrospectively. There were significantly more cases of EGIDs and fewer ones of IBD and polyps/polyposis in patients with rectal bleeding younger than two years of age. Furthermore, 68% of all follow-up colonoscopies were performed in children with IBD. There were no serious complications in our study cohort. Conclusion We determined the role of colonoscopy in infants and young children. Diseases diagnosed using colonoscopy in this age group included IBD, EGIDs, and polyps/polyposis. The increasing trend of patients with IBD and EGIDs worldwide means that the role of colonoscopy in infants and younger children will be more important in the future.