Inflammatory Bowel Diseases (IBD) are chronic immune-mediated disorders diagnosed in both adult and pediatric populations. In recent years, there has been a significant global increase in pediatric-onset IBD, not only in Western countries but also in newly industrialized regions. Age of onset plays a crucial role in disease behavior and prognosis, with pediatric onset often associated with a more extensive and aggressive disease. As a systemic inflammatory condition, IBD can involve multiple organ systems beyond the gastrointestinal tract, thus resulting in extraintestinal manifestations (EIMs) of variable severity. These manifestations (musculoskeletal, dermatological, oral, ocular, and hepatobiliary) may significantly impact patients' quality of life, sometimes even more than intestinal symptoms. To support this review, a PubMed search was conducted using the terms inflammatory bowel disease, Crohn's disease, ulcerative colitis, pediatric inflammatory bowel disease, extraintestinal manifestations, focusing on the most relevant papers with no time restrictions. This review aims to provide a comprehensive revision and comparison of the presentation, course, and management of EIMs in pediatric- versus adult-onset IBD. A deeper understanding of EIMs in different age groups is essential for timely diagnosis and holistic care, ultimately improving the overall quality of clinical management of patients with IBD.

Background/Objectives: Conjugation of polyethylene glycol (PEG) to L-asparaginase (ASP) reduces immunogenicity and prolongs the half-life of this biological drug used to treat acute lymphoblastic leukemia (ALL). However, some patients develop anti-drug antibodies (anti-ASP and anti-PEG), which may impair efficacy through neutralization or faster elimination and may cause hypersensitivity reactions. Their clinical impact remains debated, partly due to variability in analytical methods and cut-points often defined by statistical rather than clinical outcomes. Methods: To address this issue, we used two assays to measure anti-PEG antibodies in 27 sera from 25 children with ALL who showed reactions to PEG-ASP—either clinical allergy with reduced ASP activity (n = 18) or allergic-like reactions without major activity loss (n = 9)—and in 25 sera from 19 children with ALL but without clinically relevant reactions. Sera from 16 healthy children were used as controls. This design enabled assessment of sensitivity and specificity using clinically relevant cut-points. Results: Anti-PEG IgG (but not IgM), measured by ELISA, correlated with reduced drug activity, showing 83% sensitivity and 91% specificity. We also developed a surface plasmon resonance (SPR) assay, capable of detecting simultaneously both anti-PEG and anti-ASP antibodies and analyzing binding kinetics. ROC analysis of SPR data showed 78% sensitivity and 94% specificity. Conclusions: Overall, these findings highlight the importance of clinically defined cut-points, support a key role of anti-PEG antibodies in hypersensitivity with reduced drug activity, and suggest that measuring anti-PEG antibodies may help guide therapeutic decisions.

The case of a 13-month-old girl with recurrent cholestasis finally diagnosed with BRIC (Benign Recurrent Intrahepatic Cholestasis) is described. The clinical, therapeutic and prognostic implications of BRIC are also discussed.