The impact of endoscopic and histological mucosal healing on outcomes in adult settings is impressive. Despite many clinical parallels, pediatric ulcerative colitis (UC) is set apart from adult disease in several respects. Many frequently used indices are not fully validated, especially in pediatric settings, and consensus on precise definitions in clinical settings are lacking. Endoscopic mucosal healing is an acceptable long-term treatment goal in pediatrics, but not histologic normalization. Early prediction of disease course in UC may allow treatment stratification of patients according to risks of relapse, acute severe colitis, and colectomy. Putative endoscopic and histologic predictors of poor clinical outcomes in adults have not held true in pediatric settings, including baseline endoscopic extent, endoscopic severity, and specific histologic characteristics which are less prevalent in pediatrics at diagnosis. In this mini-review we appraise predictive endoscopic and histologic factors in pediatric UC with reference to relapse, severe colitis, and colectomy risks. We recommend that clinicians routinely use endoscopic and histologic sores to improve the quality of clinical and research practice. The review summarizes differences between adult and pediatric prediction data, advises special consideration of those with primary sclerosing cholangitis, and suggests areas for future study in this field.

Background: Outcomes in pediatric ulcerative colitis (UC) are heterogeneous and predictors of disease course eagerly sought. Mucosal atrophy (MA) is characterized by histological abnormalities of colonic intestinal glands. Objective: To determine the prevalence of MA in a national inception cohort of pediatric UC and its impact on outcomes. Methods: Irish children < 16 years old with UC are diagnosed at a single referral center. At diagnosis, patients underwent phenotyping by Paris classification and activity assessment by Pediatric Ulcerative Colitis Activity Index. Biopsies from all colonic segments were evaluated for MA. Patients were followed prospectively. The primary outcome was corticosteroid-free remission at 1 year. Secondary outcomes included relapse, treatment escalation, and colectomy by 2 years. Results: Of 251 pediatric patients with UC (mean age 11.8 years, 55% male), 38 (15%) had MA on diagnostic biopsy. Baseline characteristics were similar between groups with/without MA and there was no difference in steroid-free remission or rates of moderate-severe UC at 1 year. Patients with MA had higher use of steroids (29% vs 15%, P = 0.04) and immunomodulators (40% vs 21%, P = 0.04) at 6 months, higher biologic use at 1 year (34% vs 16%, P = 0.03), earlier first relapse (mean ± SD 29.4 ± 26.1 vs 46.7 ± 43.4 weeks after diagnosis, P = 0.02), and higher colectomy rates by 2 years (21% vs 8%, P = 0.01). Conclusions: Children with MA at diagnosis had higher colectomy rates despite earlier treatment escalation and similar baseline severity scores. We identify MA as a promising new prognostic marker in children with newly diagnosed UC.

Background Anti Tumour Necrosis Factor-α agents have revolutionised the management of inflammatory bowel disease. Cutaneous adverse events complicate therapy in up to 20% of cases. Most reactions are mild and do not warrant a change of therapy. Henoch–Schönlein purpura (HSP) has rarely been associated with anti-TNFα therapy. It is an acute vasculitis of small vessels that presents with cutaneous purpura of the lower limb, arthritis, nephritis and gastrointestinal involvement. Aims To describe the clinical course of a 16-year-old male presenting with recurrent HSP secondary to adalimumab for treatment of inflammatory bowel disease Methods A retrospective chart review of the patient’s electronic medical record. A literature review of the relevant medical literature. Results History 16 year old boy with Crohn’s disease, initial induction with exclusive enteral nutrition and maintained on adalimumab monotherapy since May 2017. Adalimumab initially 40 mg every 2 weeks, increased to every 10 days in September 2019 due to loose stool and mild inflammation throughout the colon on reassessment colonoscopy. Four separate incidences of purpuric rashes occurring 2–3 days after receiving adalimumab between November 2019 and July 2020. Purpura and petechiae of the lower limb with associated swelling of the feet and heel pain consistent with HSP. Purpura resolved within 1 to 3 weeks, treated with oral steroids on 1 occasion. First episode occurred following increase in dose frequency to every 10 days. Adalimumab frequency was further increased to every 7 days in March 2020. Following this he had 3 further HSP episodes. There was no history of preceding illness or other clear inciting event for HSP. Physical Exam Scattered petechiae on the lower limb bilaterally with large palpable purpura to his feet. Mild swelling to the right foot with tenderness to heel on palpation. Nil other joint swelling. No petechiae elsewhere. Investigations Urinalysis showed trace blood, no proteinuria. Mildly elevated CRP and ESR. Fecal calprotectin elevated &gt;1800. Clinical Progress Rheumatology and Dermatology were consulted. Due to recurrent HSP and active luminal Crohn’s disease on repeat colonoscopy, adalimumab was discontinued and he started Ustekinumab September 2020. There has been no recurrence of relapsing rash and joint pains. Conclusions Four previous cases of HSP associated with Adalimumab have been described, three with Crohn’s disease and 1 with Ulcerative Colitis. Cutaneous manifestations occurred within 18 months of treatment in all previously reported cases. Our patient was treated with Adalimumab for 30 months prior to his first episode of HSP. This association with HSP is not unique to adalimumab, extending to other members of the anti TNFα class including infliximab and etanercept. Hypothesized mechanisms include antibody production, eosinophil activation, shifts in T cell responses and direct drug toxicity to vessel walls. Funding Agencies None

Aims To assess the efficacy of rituximab at inducing and maintaining remission in nephrotic syndrome. Methods A retrospective chart review of 13 patients with nephrotic syndrome who received rituximab in our hospital between September 2006 and October 2013. Results We present 13 children with nephrotic syndrome who failed to maintain remission with other immunosupressive regimes. Mean age at diagnosis was 6.84 years (range 14 years – 2 years). Mean time period of nephrosis prior to rituximab was 5.84 years. Previous treatments: Tacrolimus (11/13) Mycophenolate (11/13) Cyclosporine A (11/13) Cyclophosphamide (6/13). 38% received all 4 immunosupressors. Of those that underwent biopsy: 2 MCD, 3 FSGS, 3 IgM nephropathy and 1 MPGN. Indications for Rituximab: steroid resistance (2/13), steroid dependent frequent relapse (8/13) and steroid dependent excessive steroid side effects (3/13). Rituximab dose was 375 mg/m2. 2 doses were administered while the 2 cases of MPGN received4 doses. Average number of relapses the year prior to Rituximab was 2.87, decreasing to 0.38 the year post. One steroid resistant patient did not achieve full remission. The mean dosage of steroids at time of first Rituximab was 0.27 mg/kg/d, decreasing to 0.06 mg/kg/d two months post. The mean length of time to stopping steroids was 4.63 months. B cell depletion was monitored in 11 patients (84.6%): 8 (72.7%) achieved complete B cell depletion. Six patients (46.1%) received a second cycle of Rituximab at a mean interval of 18.5 months (range 1224). All patients had B cell recovery prior to relapse. At most recent follow up 12 out of 13 patients remain on an immunosuppressor. Conclusion Rituximab markedly decreased both the frequency of relapse and steroid dependency. Only one patient did not achieve remission post Rituximab; this patient was steroid resistant and did not have complete B cell depletion (B cells 2% at lowest count). 46% of patients required subsequent doses within 2 years, while 92% of patients remain on an immunosupressor. Optimal initial dosing of Rituximab to achieve B cell depletion and the need for ongoing immunosuppression post an adequate cycle needs to be reviewed.

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