Background and Aims: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. Methods: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical, and laboratory data, as well as adverse events (AEs), were recorded at Week 8 post-induction. Results: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3–17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. Adverse events were recorded in 37 children, including 1 serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n = 13), acne (n = 12), and infections (n = 10, 5 of whom with herpes viruses). Conclusions: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.

Juvenile Primary Fibromyalgia Syndrome (JPFS) is a complex, multifactorial condition characterized by widespread musculoskeletal pain, often accompanied by sleep disturbances, headaches, cognitive and mood disorders, and fatigue, resulting in a significant impact on the quality of life for affected children, adolescents, and their families. Although recent advances have improved the understanding of the underlying pathophysiological mechanisms and therapeutic approaches, its etiology and optimal treatments remain largely unknown. In this review, we summarize recent advances in the etiopathogenesis, clinical assessment, and treatment of JPFS. Our aim is to support clinicians in the diagnosis and management of JPFS patients, while also highlighting key areas that require further research to improve diagnostic accuracy and therapeutic outcomes.

Purpose: Adalimumab biosimilars are increasingly used in paediatric Inflammatory Bowel Disease (PIBD), but data remain limited. This study assessed their durability, efficacy, safety and cost implications in PIBD. Patients and Methods: Consecutive PIBD patients who started adalimumab biosimilars between October 2018 and December 2023 at two centres in Scotland and Italy, with at least 6 months follow-up, were included. Demographic, disease, treatment, and adverse event data were collected. Disease activity was assessed at baseline, 6, 12, 24, 36 months, and at last follow-up. Durability was evaluated using Kaplan-Meier analysis. Results: In total 130 patients (81 males; median age 12.3 years) were included (115 Crohn’s Disease, 7 Ulcerative Colitis, 8 IBD unclassified). The biosimilars were ABP 501 (85%), GP2017 (14%), SB5 (1%); 41 (32%) patients switched from originator. After a median follow-up of 26 months, 87/130 (67%) patients remained on biosimilars, while 43 discontinued at a median of 14 months. Durability probabilities were 93%, 86%, 75%, 62%, and 57% at 6, 12, 24, 36, and 54 months, respectively. Patients previously exposed to ADA originator had a lower risk of biosimilar failure (hazard ratio, adjusted for age at diagnosis: 0.51 [95% confidence interval: 0.26– 0.99], p=0.047). Trough levels ≥ 11.6 μg/mL at 6 months were associated with greater durability (AUC=0.68, p=0.007). Adverse events occurred in 46/130 patients, mainly psoriasis and injection site reactions (13% each), with one lymphoma. Estimated cost savings were 5,030€ per patient/year. Conclusion: This real-life study demonstrated high durability and remission rates for adalimumab biosimilars in PIBD, confirming their clinical, cost-effectiveness and safety profile in children.