Alka Goyal

Lay summary: We describe biochemically and functionally validated primary bile acid malabsorption caused by novel biallelic SLC10A2 variants in a child initially diagnosed with Crohn’s disease. Pediatric IBD cohort reanalysis identified PBAM-compatible genotypes, supporting selective testing when clinical features are suggestive.

Objectives: Ustekinumab and vedolizumab are used off‐label for pediatric inflammatory bowel disease (PIBD). Real‐world data are needed to determine their positioning and safety. To assess the (1) 6‐month and 1‐year clinical outcome on ustekinumab and vedolizumab in PIBD based on Pediatric Ulcerative Colitis Activity Index, short Pediatric Crohn's Disease Activity Index, and calprotectin, and (2) secondary measures including safety and endoscopy. Methods: Retrospective chart review of children and young adults with inflammatory bowel disease (IBD) treated at a pediatric academic hospital and two outpatient practices. Patients 0.90). Most patients receiving vedolizumab or ustekinumab achieved calprotectin p = 0.20) and 1 year (60% vs. 63%, p = 0.90), respectively. A greater proportion of biologic‐naïve patients received vedolizumab, whereas most patients on ustekinumab were biologic‐exposed. Adverse events occurred in 6.6% and 10% of patients on vedolizumab and ustekinumab, respectively. Conclusions: Ustekinumab and vedolizumab are safe and effective in achieving clinical remission at 6 months and 1 year in PIBD. Comparative efficacy clinical trials are needed.

Background: Disseminated mycobacterium poses a significant risk for patients with NEMO deficiency. Hematopoietic stem cell transplant (HSCT) corrects the NEMO defect in hematopoietic cells thus treating the immunodeficiency.Methods: We present a patient with NEMO deficiency who successfully underwent HSCT despite a disseminated Mycobacterium szulgai infection.Results: Despite successful engraftment and resolution of the mycobacterium infection, he developed inflammatory disease leading to his death.Conclusion: HSCT does not cure all aspects of the NEMO protein defect and posttransplant inflammatory diseases involving nonhematopoietic cell types may manifest clinically.

A group of Inflammatory Bowel Disease (IBD) specialists have been utilizing a weekly live video conference “IBD Live” to discuss multidisciplinary management of challenging cases. Since 2009 the conference has featured robust interactive case discussions among 150-200 gastroenterologists and colorectal surgeons from multiple academic institutions. Although the majority of cases presented are IBD, there have been a number of cases where IBD was not the ultimate diagnosis. Hence, we sought to characterize these “IBD mimics” to provide a structure for differential diagnosis. All 106 hours of case conferences recorded and archived between May 2018 and June 2021 were reviewed. A total of 183 of the 215 cases discussed had an IBD diagnosis including 124 Crohn’s disease (CD), 54 ulcerative colitis (UC) and 5 IBD unclassified. Many of the remaining 32 (14.9%) cases (Table 1) were referred to a specialist with a prior diagnosis of IBD. There were 10 cases of colonic inflammation initially diagnosed as UC. Etiologies included drug-induced colitis secondary to checkpoint inhibitors for cancers, ocrelizumab for multiple sclerosis, and nintedanib for pulmonary fibrosis. There were cases of ischemic colitis, idiopathic myointimal hyperplasia of mesenteric veins, segmental colitis associated with diverticulosis, and diversion colitis. There were 8 cases of systemic diseases, diagnosed as Common Variable Immunodeficiency, sarcoidosis and vasculitis, including cases of Henoch–Schönlein purpura and CTLA4 haploinsufficiency with autoimmune infiltrates. There were 5 cases of ileal disorders, ultimately diagnosed as lymphoma, tuberculosis, Meckel’s diverticulum, and appendiceal carcinoid all previously thought to be CD. There were small bowel mucosal disorders including collagenous sprue and autoimmune enteropathy, and 2 polyposis cases secondary to Cronkhite-Canada and juvenile polyposis syndromes. There were also cases thought to be penetrating complications of CD, including a case of abdominal actinomyces infection. Finally, there were 3 cases where no consensus diagnosis was made, with broad differential diagnoses including cryptogenic multifocal ulcerous stenosis enteritis. IBD mimics were found in 15% of cases presented at a global IBD webinar in a 3-year period. Clinicians should have a high level of suspicion and actively pursue alternative etiologies when patients do not respond as anticipated to IBD therapy and/or when the disease characteristics are not completely consistent with IBD. These non-IBD diagnoses will lead to a significant change in medical, surgical and pharmacological treatment approaches, which will impact total cost, unplanned care and quality. Our IBD Live conference has positively impacted the care of our patients, and magnified the importance of considering a broad differential for IBD "mimics."

Statural growth impairment is more common in males with Crohn’s disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study. Crohn’s disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score. One hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was −0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was −0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (−1.0) was significantly lower than in males (−0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6–14.6) years. Our screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

Clostridium difficile infection (CDI) is associated with dysbiosis and a higher risk of complications in patients with ulcerative colitis. This study reveals a possible association between CDI, dysbiosis, suppression of methionine synthesis, and increased risk of surgery in Crohn’s disease.