Abstract Background Leishmaniasis is an emerging opportunistic infection in patients with Inflammatory Bowel Disease (IBD) living in Mediterranean endemic areas. Valencian Community (Spain) reported the highest incidence rate1. Clinical disease primarily affects hosts with impaired cellular immunity, been IBD patients a potential risk group scarcely explored to date. Clinical spectrum includes cutaneous, visceral and mucocutaneous involvement, although its atypical presentation and challenging diagnosis is well known 2-3. The true magnitude and treatment-related factors are still unknown, and no controlled study has quantified its risk4. We aimed to estimate incidence of symptomatic Leishmania infection and identify factors associated with it. Methods We conducted an observational multicenter study in the Valencian Community between 2015 and 2022. 16 hospitals participated, comprising a population-based retrospective cohort to estimate incidence of Leishmania in IBD patients, a multicenter case series of confirmed IBD–Leishmaniasis cases to characterize this opportunistic infection, and a matched 1:2 case–control study including 82 cases and 164 controls in order to identify factors associated. Cases were adults with Crohn’s disease or Ulcerative Colitis and symptomatic Leishmania infection confirmed by PCR, histology or culture. Controls were matched by sex, IBD type and birth year. Immunosuppressive exposure at the index date was recorded. Conditional logistic regression was used to identify independent predictors. Results Eighty-two cases were identified (80.5% cutaneous, 14.6% visceral). Mean annual incidence was 0.464 per 1000 IBD patients, 16-fold higher than in the general population (0.029 per 1000; p 0.001) (Figure 1). Comorbidities were more frequent among cases, especially obesity (13.6% vs 2.4% p-valor 0,001). Diagnosis often required PCR, with ≥2 biopsies needed in 26.2% of cases. At infection, 90.1% of cases vs 44.5% of controls were receiving biologics (p 0.001). Anti-TNF exposure, combination therapy and intensified regimens were more frequent in Leishmania patients (p 0.001). 90.7% achieve cure after 1st line treatment. First line treatment and withdrawal or maintenance of immunosuppressive drugs did not show significant differences in achieving cure. In multivariable conditional analysis, biologic therapy (adjusted OR 16.1; 95% CI 4.56–57.1) and comorbidity (6.47; 1.66–25.2) independently increased the odds of infection (Table 1). Conclusion IBD patients in the endemic Mediterranean region have a markedly increased risk of symptomatic leishmaniasis. Biologic therapy is the principal driver of infection risk, underscoring the need for heightened clinical vigilance and updated opportunistic infection guidance for endemic areas. References: 1. Fernández Martínez, B. (2023). Situación de leishmaniasis en España. Años 2019, 2020 y 2021. Boletín Epidemiológico Semanal, 31(2), 83–92. https://doi.org/10.4321/s2173-92772023000200002. 2. Gimeno-Pitarch, L., Almela, P., & Nos, P. (2024). Leishmania infection in patients with inflammatory bowel disease: Case series and literature review. Gastroenterología y Hepatología (English Edition), 47(1), 82–92. https://doi.org/10.1016/j.gastre.2023.04.002 3. Madero-Velázquez, L., Mínguez, A., Mayorga, L., Ramírez, J. J., Moreno, N., Amorós, C., Nieto, M. A., Mena, R., Benítez, J. M., Gimeno-Pitarch, L., Maroto, N., Suria, C., Rodríguez-Moranta, F., Ordás, I., Ruiz, L., García-Brenes, M. A., Martín-Cardona, A., de Célix, C. R., Cárdenas, K., …, Gutiérrez, A. (2025). Leishmaniasis in Patients With Inflammatory Bowel Disease: A National Multicenter Study of GETECCU. United European Gastroenterology Journal, 13(5), 674–684. https://doi.org/10.1002/ueg2.12740 4. Kucharzik, T., Ellul, P., Greuter, T., Rahier, J. F., Verstockt, B., Abreu, C., Albuquerque, A., Allocca, M., Esteve, M., Farraye, F. A., Gordon, H., Karmiris, K., Kopylov, U., Kirchgesner, J., Macmahon, E., Magro, F., Maaser, C., de Ridder, L., Taxonera, C., … Vavricka, S. (2021). ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. In Journal of Crohn’s and Colitis (Vol. 15, Issue 6, pp. 879–913). Oxford University Press. https://doi.org/10.1093/ecco-jcc/jjab052 Conflict of interest: Dr. Gimeno-Pitarch, Leticia: No conflict of interest Iborra, Marisa: No conflict of interest Crespo, Ana: No conflicts Sanchis, Laura: No conflict of interest Antón, Maria Rosario: No conflict of interest Pastor, Miguel Angel: No conflict of interest Marti Romero, Lidia: No conflict of interest Herreros Martinez, Belén: No conflict of interest Peña Duran, Carmen Cristina: No conflict of interest Ruiz Sánchez, Lucía: No conflict of interest Pérez, Amparo Almudena: No conflict of interest Diaz Jaime, Francia Carolina: No conflict of interest Maroto Arce, Nuria: No conflict of interest Laveda, Raquel: No conflict of interest Madero Velázquez, Lucía: None Buendía Sánchez, Lidia: No conflict of interest Nos Mateu, Pilar: No conflict of interest
Gimeno-Pitarch et al. (Thu,) studied this question.