EPIDEMIOLOGY OF LEG ULCERS IN SICKLE CELL DISEASE: MULTICENTER REAL-WORLD DATA STUDY IN BRAZIL

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by abnormal red blood cell shapes that lead to vaso-occlusion, chronic inflammation, and tissue ischemia. Among its chronic complications, leg ulcers (LU) represent one of the most prevalent cutaneous manifestations, especially in individuals with a homozygous genotype. These lesions are difficult to heal, have a high recurrence rate, and are associated with pain, functional limitation, and a negative impact on quality of life. The pathophysiology involves multiple factors, such as endothelial dysfunction, hypercoagulability, chronic venous insufficiency, and exacerbated local inflammation, all contributing to the persistence and refractoriness of the lesions. Despite therapeutic advances in sickle cell anemia, leg ulcers remain a significant clinical challenge, with substantial physical, psychological, and economic implications. To assess the prevalence, incidence, and recurrence of leg ulcers in patients with SCD according to sex, age group, center, and genotype. A cohort study including 2,793 SCD patients enrolled in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) project, conducted in six Brazilian blood centers: Belo Horizonte, Montes Claros, Juiz de Fora, São Paulo, Rio de Janeiro, and Recife. Prevalence, incidence, and recurrence rates of LU were presented as percentages with corresponding 95% confidence intervals (95% CI). In the sex-based analysis, no significant differences were found between women and men in prevalence (4.53% vs. 3.81%), incidence (0.54% vs. 1.07%), or recurrence (3.65% vs. 4.49%). By age group, all indicators were higher among adults compared to children (prevalence 8.77% vs. 0.33%; incidence 1.33% vs. 0.33%; recurrence 8.46% vs. 0.33%). Regarding centers, the highest prevalence rates were observed in Belo Horizonte (5.37%) and Recife (4.91%); the highest incidence in Recife (2.36%); and the highest recurrence rates in Juiz de Fora (6.57%) and Recife (5.45%). By genotype, LUs were more prevalent in SS (5.29%) and SB⁰ (4.60%) patients, while the highest incidence was observed in SB⁺ (2.38%). The highest recurrence rates occurred in SS (5.34%) and in other less frequent genotypes (5.45%). Leg ulcers represent a relevant and recurrent complication in individuals with sickle cell disease, with a greater impact among adults, particularly those with SS and SB⁰ genotypes. The variation among centers suggests possible regional differences in clinical management, access to specialized care, or sociodemographic characteristics. These findings highlight the need for targeted prevention and management strategies focusing on high-risk groups to reduce the clinical burden and improve the quality of life of patients with SCD.