1 - Gastrenterology And Hepatology Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal,
2 - Primary Immunodeficiencies Unit, Central Lisbon Universitary Hospital, Lisboa, Portugal,
3 - Gastrenterology And Heptology Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal,
4 - European Reference Network on Hepatological Diseases (ERN RARE-LIVER); Pediatric Gastroenterology/Hepatology Center, Lisbon, Portugal,
5 - Paediatric Gastroenterology And Hepatology Unit, Hospital Dona Estefânia, CHULC, Lisboa, Portugal,
6 - Primary Immunodeficiencies Unit, Paediatric Department, Hospital Dona Estefânia, CHULC, Lisboa, Portugal
- Poster, 56th Annual Meeting of the European Society for Pediatric Gastroenterology, Hepatology and Nutricion (ESPGHAN), Milão, 15-18 de maio 2024
RESUMO:
Objectives and Study: To characterize cases of inborn immune defects associated with inflammatory bowel disease (IBD-IMP).
Methods: Descriptive retrospective study by reviewing clinical records of patients with IBD-IMP at a level III hospital who underwent genetic sequencing (Next Generation Sequencing panel). Demographic variables, disease characteristics, and treatments carried out were assessed. Patients were categorized into three groups: G1 (Genetic Diagnosis Established), G2 (Negative Study), and G3 (Heterozygous Variants of "Uncertain" Significance)
Results: Included 26 patients, 17 (65%) of whom with clinical presentation before the age of 2 years-old with a predominance female (62%). Median age at diagnosis 19 months (1-60). Current median age 7 years (2-17). Bloody diarrhea was the most frequent gastrointestinal symptom (77%) and eight patients (31%) had extra-intestinal manifestations. All patients had colon disease, eight (31%) perianal disease and five (19%) small bowel disease, classified as: Crohn's disease (31%), ulcerative colitis (35%), undetermined IBD (35%). During follow-up, the disease phenotype changed in four (15%). In G1 (n=10; 38%; mutations identified PLCG2; CYBB; G6PC3; 2x IL10RB; STXBP3; IL10RA; TTC7A; LRBA, ADCY7.): 70% presented < 2Y; the majority benefited from targeted therapy. Most exhibited symptoms beyond the digestive system. Four patients underwent haematopoietic cell transplantation. In G2: (n=9; 34%): absence of involvement of other systems, with a predominant occurrence of colon disease. In G3: (n=7; 27%): predominantly indeterminate IBD, lower requirement for biologics, higher prevalence of autoimmunity, and none presented with small bowel disease. Current treatment: biologics n=7, azathioprine n=9, mesalazine n=7, JAK inhibitor n=1, subcutaneous immunoglobulin n=1, calcineurin inhibitor n=1, abatacept n=1. Three patients were refractory to more than 2 biologics. Two patients were submited to total colectomy and two died.
Conclusions: IBD-IMP patients typically do not respond to conventional therapy. Ideally, targeted treatment is beneficial and it was possible in 6 cases (23%). Diagnosis relies on NGS sequencing, with clinical picture often suggestion the genetic diagnosis.