Bitzan Martin, Anselmo Mark, Carpineta Lucy
Department of Pediatrics, Division of Nephrology, Montreal Children's Hospital and McGill University, Montreal, Quebec, Canada.
Pediatr Pulmonol. 2009 Sep;44(9):922-34. doi: 10.1002/ppul.20864.
Pulmonary toxicity of delayed onset is a rare complication of B-lymphocyte depleting antibody therapy and has been almost exclusively reported in older patients with B-cell malignancies.
To describe a pediatric patient with rituximab-associated lung injury (RALI), to systematically analyze previous reports of pulmonary complications, and to summarize common clinico-pathological features, treatment, and outcome.
A teenage boy with focal segmental glomerulosclerosis (FSGS) presented with progressive dyspnea, fever, hypoxemia and fatigue 18 days after the completion of a second course of rituximab infusions for calcineurin inhibitor-dependent nephrotic syndrome. Respiratory symptoms started while he received high-dose prednisone for persistent proteinuria. Bilateral, diffuse ground-glass infiltrates corresponded to the presence of inflammatory cells in the bronchioalveolar lavage fluid. Empiric antibiotic treatment including clarithromycin was given, but the microbiological work-up remained negative. Serum IgE, C3, and C4 concentrations were normal. He recovered within 3 weeks after onset.We systematically reviewed 23 reports describing 30 additional cases of rituximab-associated lung disease. Twenty eight patients had received rituximab for B-cell malignancies, one for graft-versus-host disease and one for immune thrombocytopenia. Median age was 64 years (interquartile range [IQR] 58-69 years). Seventy one percent received concomitant chemotherapy. Time to onset from the last rituximab dose was 14 days (IQR 11-22 days). Eleven of 31 patients required mechanical ventilation, and 9 died (29%). Ventilation was a significant predictor of fatal outcome (odds ratio 46.7; confidence interval 9.5-229.9). High dose glucocorticoid therapy did not improve survival or prevent severe lung disease or death.
With the expanding use of rituximab for novel indications, additional cases of RALI affecting younger age groups are expected to emerge. Mechanical ventilation predicts poor outcome. Glucocorticoids may not be protective.
迟发性肺毒性是B淋巴细胞清除抗体治疗的一种罕见并发症，几乎仅在患有B细胞恶性肿瘤的老年患者中报道过。
描述一名患有利妥昔单抗相关肺损伤（RALI）的儿科患者，系统分析既往关于肺部并发症的报道，并总结常见的临床病理特征、治疗方法及预后情况。
一名患有局灶节段性肾小球硬化（FSGS）的青少年男性，在完成第二疗程利妥昔单抗输注以治疗钙调神经磷酸酶抑制剂依赖型肾病综合征18天后，出现进行性呼吸困难、发热、低氧血症和疲劳。呼吸症状在他因持续性蛋白尿接受大剂量泼尼松治疗时开始出现。双侧弥漫性磨玻璃样浸润与支气管肺泡灌洗液中存在炎性细胞相符。给予了包括克拉霉素在内的经验性抗生素治疗，但微生物学检查结果仍为阴性。血清IgE、C3和C4浓度正常。他在发病后3周内康复。我们系统回顾了23篇描述另外30例利妥昔单抗相关肺部疾病的报道。28例患者接受利妥昔单抗治疗是用于B细胞恶性肿瘤，1例用于移植物抗宿主病，1例用于免疫性血小板减少症。中位年龄为64岁（四分位间距[IQR]58 - 69岁）。71%的患者同时接受了化疗。自最后一剂利妥昔单抗给药至发病的时间为14天（IQR 11 - 22天）。31例患者中有11例需要机械通气，9例死亡（29%）。机械通气是死亡结局的一个重要预测因素（比值比46.7；置信区间9.5 - 229.9）。大剂量糖皮质激素治疗并未改善生存率，也未能预防严重肺部疾病或死亡。
随着利妥昔单抗在新适应症中的使用不断增加，预计会出现更多影响较年轻年龄组的RALI病例。机械通气预示预后不良。糖皮质激素可能没有保护作用。
