Clinical and Genetic Characteristics of Pediatric Patients with Inflammatory Bowel Disease Transitioning to Adult Medicine: A Single-Center Ten-Year Experience

<b>Background/Objectives</b>: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. <b>Methods</b>: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. <b>Results</b>: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2-17). After a median disease duration of 5 years (IQR: 1-16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1-84)] and CD patients [4.5 months (IQR: 1-48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; <i>p</i> < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (<i>p</i> = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (<i>p</i> < 0.009492), along with a stenosing phenotype (<i>p</i> < 0.024) and increased surgical risk (<i>p</i> < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. <b>Conclusions</b>: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients.