自身免疫性疾病患者中利妥昔单抗相关肺炎的临床特点及预后分析

Clinical features and prognosis of pneumocystis pneumonia in patients treated with rituximab for autoimmune diseases

目的:分析自身免疫性疾病患者中利妥昔单抗相关肺孢子菌肺炎(PCP)的临床特点及预后。方法:回顾性分析2009年1月至2019年4月北京大学第一医院基础疾病为自身免疫性疾病的PCP患者,其中男67例,女35例,年龄17~79岁。根据是否使用利妥昔单抗治疗基础疾病分为利妥昔单抗组和非利妥昔单抗组,分析两组患者的人口学资料、临床特征、治疗转归等。结果:102例患者中,利妥昔单抗组7例(PCP起病前使用利妥昔单抗),非利妥昔单抗组95例;利妥昔单抗组年龄显著低于非利妥昔单抗组[(32.0±18.7)比(52.4±14.9)岁,P=0.010],外周血CD3^+、CD4^+、CD8^+细胞计数均显著高于非利妥昔单抗组[(1306±596)比(546±439)个/μl、(674±401)比(243±232)个/μl、(616±249)比(282±256)个/μl,均P<0.01],而B细胞计数、血浆IgG、血浆IgM均显著低于非利妥昔单抗组[0(0,0.2)比72.0(50.0,124.4)个/μl、4.0(2.6,5.8)比9.4(5.3,12.0)g/L、0.3(0.2,1.0)比1.1(0.6,1.8)g/L,均P<0.05],巨细胞病毒(CMV)肺炎发生率显著低于非利妥昔单抗组(0/7比57/95,P=0.007),而两组患者其余基线资料、重症PCP、机械通气、气管插管、合并气胸或纵隔气肿、辅助使用糖皮质激素比例以及住院期间病死率、住院时间等差异均无统计学意义。结论:外周血CD3^+、CD4^+、CD8^+细胞降低可能并非自身免疫性疾病患者发生利妥昔单抗相关PCP的危险因素,B细胞降低伴低免疫球蛋白血症等体液免疫下降可能起了更重要的作用。上述特点也决定了此类免疫缺陷患者不容易合并CMV肺炎。

Objective To determine the clinical features and outcomes of pneumocystic pneumonia(PCP)in patients treated with rituximab for autoimmune diseases.Methods PCP patients with autoimmune diseases as underlying diseases from January 2009 to April 2019 in Peking University First Hospital(male 67 cases,female 35 cases,age 17-79)were retrospectively reviewed.Patients were grouped as rituximab group and non-rituximab group based on the fact if they were treated with rituximab before the onset of PCP.Demographic data,clinical features,and outcomes of the two groups were analyzed.Results There were 102 cases altogether,and 7 patients were treated with rituximab before the onset of PCP.Patients in rituximab group were relatively younger than that in non-rituximab group[(32.0±18.7)vs(52.4±14.9)years,P=0.010].Patients in rituximab group had more CD3^+,CD4^+,CD8^+ T lymphocytes in peripheral blood samples than that in non-rituximab group[(1306±596)vs(546±439)/μl,(674±401)vs(243±232)/μl,(616±249)vs(282±256)/μl,respectively,all P<0.01].However,the B lymphocyte count and plasma level of IgG and IgM were significantly lower in rituximab group than that in non-rituximab group[0(0,0.2)vs 72(50.0,124.4)/μl,4.0(2.6,5.8)vs 9.4(5.3,12.0)g/L,0.3(0.2,1.0)vs 1.1(0.6,1.8)g/L,respectively,all P<0.05].The incidence of Cytomegalovirus(CMV)pneumonia was significantly lower in rituximab group(0/7 and 57/95,P=0.007).Other demographic data,the use of corticosteroids,the incidence of severe PCP,mechanical ventilation,intubation,pneumothorax and mediastinal emphysema complications,as well as hospital mortality and length of stay in hospital in the two groups were comparable.Conclusions In patients treated with rituximab for autoimmune diseases,the number of B lymphocytes in peripheral blood and the plasma level of immunoglobulins but not CD3^+,CD4^+,and CD8^+ T lymphocyte counts may play an important role in the pathogenesis of PCP.These patients are not vulnerable to be complicated with CMV pneumonia.