全身型幼年特发性关节炎合并肺间质病变临床分析

Clinical analysis of systemic onset juvenile idiopathic arthritis complicated with interstitial lung disease

目的研究全身型幼年特发性关节炎(SoJIA)合并肺间质病变(ILD)的临床特征及预后。方法收集2010年10月至2019年12月期间温州医科大学附属第二医院儿童风湿科住院确诊SoJIA患儿75例,分析SoJIA合并ILD的临床表现、影像学特征及预后。结果75例SoJIA中合并ILD 12例(占16%),其中男性6例,女性6例,平均发病年龄(7.9±2.6)岁。12例均有发热,伴关节炎10例,以大关节多见,按发生率高到低依次为膝、髋、肩关节;起病初无关节受累2例,随访过程中一直无关节症状出现。同时具备发热、皮疹、关节炎三联征9例(75%)。ILD相关的临床表现大多数为非特异性表现,其中咳嗽8例(75%),呼吸急促7例(58%),胸痛3例(25%),肺部查体闻及爆裂音4例(33%),肺动脉高压1例(8%)。实验室检查炎性指标均明显升高,其中CRP为(235±112)mg/L,ESR为(39±25)mm/1 h,血清铁蛋白(SF)为(1312±384)ng/ml,血清淀粉样蛋白A(SAA)为(212±101)mg/L。胸部高分辨率CT(HRCT)表现为网状/线状影12例,实变影7例,小叶间隔增厚5例,磨玻璃影4例,蜂窝状1例。ILD发生在SoJIA早期(病程≤6个月)的4例(占33%),出现在病程中晚期(>6个月)的8例(占67%),但均出现在SoJIA的活动期。12例全部应用糖皮质激素治疗,大剂量激素(>1 mg·kg^(-1)·d^(-1))为11例,其中行甲泼尼龙针冲击治疗2例。均同时应用慢作用抗风湿药或免疫抑制剂治疗,同时需使用两联以上的5例(42%)。肺损害发生前曾使用过生物制剂的1例,其余11例之前未使用过生物制剂,在诊断SoJIA合并ILD后有4例应用托珠单抗。12例患儿中合并巨噬细胞活化综合征(MAS)7例,发生2次及以上MAS占25%。完全缓解或部分缓解10例,死亡2例,死因均为呼吸衰竭。结论SoJIA合并ILD起病隐匿,与原发疾病活动状态有关,HRCT对早期诊断非常重要。治疗中病情容易反复,容易合并MAS,死亡率高,需引起广大临床医师的高度重视。

Objective To investigate the clinical characters and prognosis of patients with systemic-onset juvenile idiopathic arthritis associated interstitial lung disease(SoJIA-ILD).Methods Clinical manifestations,imaging features and prognosis were analyzed in 75 patients with SoJIA between October 2010 and December 2019 in the Second Affiliated Hospital of Wenzhou Medical University.Results Seventy-five patients with SoJIA were enrolled.Among 12 children with SoJIA-ILD,6 were male and 6 were female.The mean age of onset was(7.9±2.6)years.All of the 12 patients had fever.Ten patients had arthritis which mainly occurred in large joints.The incidence of arthritis was knee,hip and shoulder from high to low.Two patients had no joint involvement at the onset of the disease and had no joint symptoms during the follow-up.Nine patients(75%)had fever,rash and arthritis at the same time.The clinical features of ILD were mostly nonspecific,including cough in 8 cases(75%),shortness of breath in 7 cases(58%),chest pain in 3 cases(25%),velcro sound in 4 cases(33%)and pulmonary hypertension in 1 case(8%).Inflammatory indicators were all signifi-cantly elevated,among which was CRP(235±112)mg/L,ESR(39±25)mm/1 h,serum ferritin(SF)(1312±384)ng/ml and serum amyloid A(SAA)(212±101)mg/L.High resolution computed tomography(HRCT)of the chest presented as reticular or line shadows in 12 patients,consolidation in 7 patients,ground interlobular septal thickening in 5 patients,glass opacity in 4 patients and honeycomb lung in 1 patient.ILD occurred in 4 cases(33%)in the early stage of SoJIA(disease course≤6 months),and 8 cases(67%)in the medium and late stages of the disease course(>6 months),but all appeared in the active status of SoJIA.All of 12 patients received glucocorticoids therapy,11 patients received high dose of glucocorticoid(>1 mg·kg^(-1)·d^(-1))and 2 pa-tients received intravenous methylprednisolone pulse therapy.All of 12 patients were treated with glucocorti-coids combined with immunosuppressant or disease modifying antirheumatic drugs and 5 patients needed dual therapy or triple therapy.One case had been treated with biological agents before the occurrence of lung injury and the other 11 cases had not used biological agents before.After the diagnosis of SoJIA complicated with ILD,4 cases were treated with tocilizumab.Macrophage activation syndrome(MAS)was found in 7 cases and 25%had MAS for two times or more.Ten patients had partial remission or complete remission and 2 patients died of respiratory failure.Conclusion SoJIA-ILD maybe asymptomatic at the early stage of the disease.It is associated with disease activity of SoJIA.HRCT examination is very important for early diagnosis.Patients with SoJIA-ILD have higher rate of recurrence,death and MAS.It needs to arouse the clinicians'attention.