Eating disorder or oesophageal achalasia during adolescence: diagnostic difficulties

International audienceMarine was a fourteen and a half-year-old adolescent female hospitalized for an eating disorder (ED) of the anorexic type with purging behaviors. She has had a complicated life course, made up of disruptions and discontinuities, both family and school. Since the age of five, Marine had been intermittently treated in psychiatry for a diagnosis of oppositional defiant disorder. The current illness started with spontaneous and induced vomiting associated with major weight loss (body mass index, 15.27 kg m−2). The diagnosis of anorexia nervosa was established after several opinions from professionals in five Parisian university pediatric departments, where additional investigations were carried out without any somatic cause being identified. In this context, Marine was transferred to a child psychiatry unit. There, she had acute dyspnea during the insertion of a nasogastric tube. As a result, a new specialized opinion was sought from a pediatric gastroenterologist and further explorations were performed (oeso-gastroduodenal transit and manometry), leading to the conclusion to an oesophageal achalasia requiring surgical treatment. This case report highlights that the exclusion of any organic disorder should be a priority in the diagnostic assessment of an ED. Oesophageal achalasia is a rare differential diagnosis and should be considered in case of swallowing difficulties or dysphagia. Health care professionals should take care to provide appropriate somatic follow-up for patients with psychiatric disorders

Mucosal healing and bacterial composition in response to enteral nutrition versus steroid based induction therapy - a randomized prospective clinical trial in children with Crohn's disease

International audienceExclusive Enteral Nutrition (EEN) is as efficacious as corticosteroids (CS) to induce remission in Crohn's disease (CD), without their adverse effects. EEN seems to be more efficient than steroids to induce mucosal healing, but the underlying molecular mechanisms are only sparsely understood. We aimed in the present work to study the anti-inflammatory effects of EEN with Modulen IBD® versus CS in active pediatric CD and to assess its modulatory effects on the intestinal microbiota as compared to steroids. MATERIAL AND METHODS: Nineteen patients with new-onset active CD (Harvey Bradshaw index HBI> 5), aged from 6 to 17 years, were included in this prospective randomized induction trial with CS (n=6) or EEN (n=13). Patients were assessed at Week 0 and 8 using clinical parameters HBI, endoscopic findings (CDEIS score) and analysis of fecal microbiota composition. RESULTS: At 8 weeks, clinical remission (HBI<5) was achieved in 13/13 patients on EEN and 5/6 patients on steroids, while the mucosal healing rate was significantly higher in the EEN (89%) compared to steroid group (17%). There were no significant differences between groups regarding biological markers, while the intestinal microbiota profiles shifted upon EEN-induced remission to a higher proportion of Ruminococcus bacteria compared to steroid induced remission (p=0.049), with higher proportions of bacteria belonging to Clostridium in EEN-treated patients. CONCLUSION: Both steroids and EEN induced clinical remission, however, patients with EEN-induced remission showed a higher rate of mucosal healing and this was associated with a different gut microbiota compositional shift in these children. This clinical trial was registered under the number ClinicalTrials.gov Identifier: NCT00265772

Adalimumab therapy in pediatric Crohn’s Disease: a two-year follow-up comparing ‘top-down’ and ‘step-up’ strategies.

International audienceObjective: European Crohn’s Colitis Organization (ECCO) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the early use of anti-TNF biologicals in pediatric Crohn disease (CD) patients with positive predictors for poor outcome.The objective of the present study was to compare early "Top-Down" use of Adalimumab (ADA) immunomodulator/biologics-naïve patients to conventional "Step-Up" management.Methods: One hundred and twenty consecutive patients with a confirmed diagnosis of CD and treated with Adalimumab (ADA) between 2008 and 2019 were included and allocated to the ADA-Top Down (n=59) or ADA-Step Up group (n=61). The primary endpoint was prolonged steroid-/enteral nutrition-free clinical remission at 24 months, defined by a wPCDAI < 12.5. Clinical and biological data were collected at 12 and 24 months.Results: At start of ADA, disease activity was comparable between the ADA-Top Down group and the ADA-Step Up group (wPCDAI=31 ± 16 versus 31.3 ± 15.2 respectively, p=0.84). At 24 months, the remission rate was significantly higher in the ADA-Top Down group (73% versus 51%, p<0.01). After propensity score, the Top-Down strategy is still more effective than the Step-Up strategy in maintaining remission at 24 months (HR=0.36, 95%CI[0.15-0.87], p=0.02). Patients in the ADA-Top Down group were mainly on monotherapy compared to patients in the ADA-Step Up group (53/55 versus 28/55 respectively, p<0.001). Serum levels of Adalimumab were higher in the ADA-Top Down group than in the ADA-Step Up group (12.8µg/ml±4.3 versus 10.4µg/ml±3.9 respectively, p<0.01).There were no serious adverse events.Conclusion: Early use of ADA appears to be more effective in maintaining relapse-free remission at 2 years, while using it as monotherapy. These findings further favor the recommendation of early anti-TNF use in high-risk CD patients

Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center

Parenteral nutrition (PN) is the main treatment for intestinal failure

Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds.

International audienceMutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling

Intestinal dysbiosis in Inflammatory Bowel Disease associated with primary immunodeficiency.

International audienceThe gut microbiota plays a key role 63 in host physiology and is an actor in inflammatory bowel disease pathogenesis. Patients with primary immunodeficiency causing intestinal inflammation have disease-specific dysbiosis

Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5‐Year French National Survey

International audienceDetailed comparative assessment of procedure‐related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. Aims We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure‐related factors associated with FMT success in CDI. Methods We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Results Six hundred fifty‐eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty‐seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20–3.88]), non‐severe refractory CDI (OR: 15.35, [1.94–318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11–5.67]), insufficient bowel cleansing (OR: 5.47, [1.57–20.03]) and partial FMT retention (OR: 9.97, [2.62–48.49]) were associated with CDI recurrence within 8 weeks. Conclusions Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real‐life practice, whereas it had lower efficacy in severe CDI and non‐severe refractory CDI

Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients

A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-κB activity, F. prausnitzii had no effect on IL-1β-induced NF-κB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-γ production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment