Solans-Laqué Roser, Fraile Guadalupe, Rodriguez-Carballeira Monica, Caminal Luis, Castillo Maria J, Martínez-Valle Ferran, Sáez Luis, Rios Juan J, Solanich Xavier, Oristrell Joaquim, Pasquau Francisco, Fonseca Eva, Zamora Monica, Callejas Jose L, Frutos Begoña, Abdilla Monica, Fanlo Patricia, García-Sánchez Isabel, López-Dupla Miguel, Sopeña Bernardo, Pérez-Iglesias Almudena, Bosch Josep A
Hospital Valle Hebrón, Barcelona Hospital Ramón y Cajal, Madrid Mútua Terrassa, Barcelona Hospital Central de Asturias Hospital Virgen del Rocío, Sevilla Hospital Miguel Servet, Zaragoza Hospital La Paz, Madrid Hospital Bellvitge Hospital Parc Tauli Sabadell, Barcelona Hospital Marina Baixa, Villajoyosa, Alicante Hospital Cabueñes, Asturias Hospital Virgen de las Nieves Hospital Clínico San Cecilio, Granada Hospital Fuenlabrada, Madrid Hospital La Ribera, Alzira, Valencia Clínica de Navarra Hospital Infanta Leonor, Madrid Hospital Joan XXIII, Tarragona Centro Hospitalário Vigo Hospital Ourense, Galicia, Spain.
Medicine (Baltimore). 2017 Feb;96(8):e6083. doi: 10.1097/MD.0000000000006083.
The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ± 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ± 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.
本研究旨在描述西班牙众多患者中初诊时抗中性粒细胞胞浆抗体相关性血管炎（AAV）的临床特征，并分析血管炎类型、抗中性粒细胞胞浆抗体（ANCA）特异性、预后因素及诊断时所采用的治疗方法对预后的影响。纳入了1990年1月至2014年1月间西班牙20家医院诊断的450例患者。其中，40.9%患有肉芽肿性多血管炎（GPA），37.1%患有显微镜下多血管炎（MPA），22%患有嗜酸性肉芽肿性多血管炎（EGPA）。诊断时的平均年龄为55.6±17.3岁，MPA患者年龄显著更大（P<0.001）。发热、关节痛、体重减轻、呼吸道及耳鼻喉（ENT）症状是疾病发作时最常见的症状。86.4%的病例ANCA检测呈阳性：36.2%为C-ANCA-PR3，50.2%为P-ANCA-MPO。P-ANCA-MPO与肾病风险增加（比值比2.6，P<0.001）及肺泡出血风险增加（比值比2，P=0.010）显著相关，而C-ANCA-PR3与ENT病变风险增加（比值比3.4，P<0.001）及眼部受累风险增加（比值比2.3，P=0.002）显著相关。所有患者均接受了糖皮质激素（CS）治疗，74.9%接受了环磷酰胺（CYC）治疗。中位随访时间为82个月（四分位间距100.4）。在此期间，39.9%的患者发生了细菌感染，14.6%发生了机会性感染，二者在累积使用高剂量CYC和CS的患者中最为常见（P<0.001）。36.4%的病例出现复发，平均复发率为2.5±2.3，C-ANCA-PR3患者复发更频繁（P=0.012）。初始疾病严重程度与死亡率显著相关，但与复发的发生无关。129例（28.7%）患者（74例MPA、41例GPA、14例EGPA）死亡。平均生存期为58个月（四分位间距105），MPA患者的生存期显著更低（P<0.001）。与死亡独立相关的因素包括疾病发作时的肾脏受累（P=0.010）、心力衰竭（P=0.029）、年龄超过65岁（P<0.001）以及细菌感染（P<0.001）。2000年后诊断的患者预后有所改善，死亡率和治疗相关发病率显著降低，这与采用适应疾病活动度和分期的毒性较小的治疗方案以及大幅减少CYC和CS的累积剂量有关。
