Quintana-Castanedo Lucía, Maseda Rocío, Pérez-Conde Isabel, Butta Nora, Monzón-Manzano Elena, Acuña-Butta Paula, Crespo María G, Buño-Soto Antonio, Jiménez Eva, Valencia Jaris, Arriba María C, Zuluaga Pilar, de Lucas Raúl, Del Río Marcela, Vicente Ángeles, Escámez María J, Sacedón Rosa
Department of Dermatology, Hospital La Paz, Madrid, Spain.
Department of Dermatology, Marqués de Valdecilla University Hospital, Santander, Spain.
Blood Adv. 2025 May 13;9(9):2321-2335. doi: 10.1182/bloodadvances.2024015271.
Recessive dystrophic epidermolysis bullosa (RDEB) is a genodermatosis characterized by severe cutaneous and mucosal fragility, and frequently complicated by multifactorial chronic anemia that responds poorly to conventional therapies. This cross-sectional study investigates the factors contributing to anemia in RDEB by analyzing a representative cohort, that was stratified by disease severity, anemia, and iron status, to examine their hematological parameters, cytokine profile, and the erythropoietin-erythroferrone-hepcidin (EPO-ERFE-hepcidin) axis. Anemia was present in 50% of the cohort. Hemoglobin levels showed a strong negative correlation with the percentage of body surface area affected and C-reactive protein levels (CRP), identifying these as anemia risk factors in RDEB. Moderate-severe inflammation (CRP ≥ 15 mg/L) was observed in all patients with anemia, but no specific cytokine profile was linked with anemia risk because of variability in interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor, and interferon-γ levels. The regulation of the EPO-ERFE-hepcidin axis showed discrepancies with the patterns expected based on patients' anemia severity and iron status. According to the reticulocyte production index, an inadequate bone marrow response was observed in 90% of patients with anemia, irrespective of EPO levels. Patients with functional or true iron deficiency had higher ERFE levels, although ERFE showed no consistent correlation with EPO and was elevated in both patients with anemia and those without anemia. Elevated hepcidin was primarily linked to the highest ferritin levels, mostly in patients with a history of iron infusions and/or transfusions. These findings highlight the need for personalized, targeted approaches that address the complex interplay between inflammation and iron dysregulation, to improve anemia management in RDEB and other chronic inflammatory conditions.
隐性营养不良性大疱性表皮松解症（RDEB）是一种遗传性皮肤病，其特征为皮肤和黏膜严重脆弱，常并发多因素慢性贫血，对传统治疗反应不佳。这项横断面研究通过分析一个具有代表性的队列来调查导致RDEB贫血的因素，该队列按疾病严重程度、贫血和铁状态进行分层，以检查其血液学参数、细胞因子谱以及促红细胞生成素 - 促红细胞生成素铁调节因子 - 铁调素（EPO - ERFE - 铁调素）轴。该队列中50%的患者存在贫血。血红蛋白水平与受影响的体表面积百分比和C反应蛋白水平（CRP）呈强烈负相关，表明这些是RDEB贫血的危险因素。在所有贫血患者中均观察到中度至重度炎症（CRP≥15mg/L），但由于白细胞介素 - 6（IL - 6）、IL - 1β、IL - 10、肿瘤坏死因子和干扰素 - γ水平存在差异，没有特定的细胞因子谱与贫血风险相关。EPO - ERFE - 铁调素轴的调节与基于患者贫血严重程度和铁状态预期的模式存在差异。根据网织红细胞生成指数，90%的贫血患者观察到骨髓反应不足，无论EPO水平如何。功能性或真性缺铁患者的ERFE水平较高，尽管ERFE与EPO没有一致的相关性，且在贫血患者和非贫血患者中均升高。铁调素升高主要与最高的铁蛋白水平相关，主要见于有铁输注和/或输血史的患者。这些发现凸显了需要采取个性化、针对性的方法来解决炎症和铁代谢失调之间的复杂相互作用，以改善RDEB和其他慢性炎症性疾病的贫血管理。
