血浆置换治疗抗MDA5阳性皮肌炎伴肺间质纤维化临床疗效及安全性分析

来源期刊：广州医药 | 1166-1171 发布时间：2024-11-05 收稿时间：2025/11/13 18:44:21 阅读量：55

作者：: 郑朝恩,

郑迪,

刘正海,

罗娇,

田应波,

刘丽,

关键词：: 抗MDA5抗体阳性皮肌炎环磷酰胺血浆置换肺间质纤维化; anti-melanoma differentiation-associated gene 5（MDA5）dermatomyositis cytoxan plasmapheresis interstitial lung disease

DOI：: 10.20223/j.cnki.1000-8535.2024.10.011

收稿时间：: 2023-11-22
修订日期：
接收日期：
引用总数：: 0

目的探讨血浆置换联合泼尼松（PDN）联合环磷酰胺（CTX）治疗抗黑色素瘤分化相关基因5（MDA5）抗体阳性皮肌炎（DM）伴肺间质纤维化（ILD）患者疗效及安全性。方法回顾性分析2014年6月—2023年6月普洱市人民医院诊断的MDA5阳性DM伴ILD患者40例,其中治疗组20例,采用血浆置换联合PDN 1 mg/kg每日1次口服,4周后减量,每周减总量10%,CTX 1 g每月1次静脉滴注,共6次治疗;另20例设为对照组,采用PDN 1 mg/kg每日1次口服,4周后减量,每周减总量10%,CTX 1 g每月1次静脉滴注,共6次治疗,分别于治疗后3月、6月检测一氧化碳弥散量（DLCO）、第1秒用力呼气量（FEV₁）,血清铁蛋白（SF）、C-反应蛋白（CRP）、涎液化糖链抗原（KL-6）、MDA5转阴率行疗效评估。结果在治疗3个月和6个月时,两组患者的DLCO、FEV1、SF、CRP、KL-6、MDA5转阴率等指标的完全缓解率不一致。其中,3个月时,治疗组上述指标的完全缓解率依次为95%、85%、90%、90%、90%、85%,对照组依次为15%、20%、20%、15%、0%、0%。两组患者在治疗3个月的DLCO、FEV1、SF、CRP、KL-6水平和MDA5转阴数均有所不同。其中治疗组的DLCO、KL-6、CRP水平均较对照组降低（P<0.01）,治疗组FEV₁水平较对照组升高（P<0.01）,治疗组SF水平较对照组降低（P<0.05）,两组治疗6个月时,治疗组上述指标缓解率依次为95%、85%、90%、90%、90%、85%,对照组依次为20%、25%、20%、20%、20%、5%。两组患者在DLCO、FEV₁、SF、CRP、KL-6水平以及MDA5转阴数和死亡例数方面比较差异均有统计学意义,其中治疗组的DLCO、KL-6和CRP水平均较对照组降低（P<0.01）,治疗组FEV₁水平较对照组升高（P<0.01）,SF水平治疗组较对照组降低（P<0.05）。结论在MDA5抗体阳性DM伴ILD患者治疗中,给予血浆置换联合PDN、CTX治疗,可以提高疗效,降低病死率。

Objective To explore the effect of plasmapheresis combined with prednisone（PDN）plus cytoxan（CTX）on patients with anti-melanoma differentiation-associated gene 5（MDA 5）antibody-positive dermatomyositis（DM）with interstitial lung disease（ILD）. Methods The data of 40 patients with MDA 5 positive DM and ILD diagnosed in the People's Hospital of Pu'er City from June 2014 to June 2023 were retrospectively was analyzed．Twenty patients of the treatment group were treated with plasmapheresis combined with PDN 1mg / kg once daily,which was reduced by 10% per week after 4 weeks．The other 20 patients of the control group were treated with PDN 1mg / kg once daily,which was reduced after 4 weeks by 10% per week,and CTX 1g once per month．diffusing capacity of the lungs for carbon monoxide（DLCO）,forced expiratory volume in the first second（FEV₁）,serum ferritin（SF）,C-reactive protein（CRP）,Krebs Von den Lungen-6（KL-6）and MDA5 negative conversion rate were measured at 3 and 6 months after treatment,respectively. Results At 3 and 6 months of treatment,complete remission rates of DLCO,FEV₁,SF,CRP,KL-6,MDA 5 conversion and other indicators were inconsistent．Among them,at 3 months,the complete response rate of the above indicators in the treatment group was successively：95%,85%,90%,90%,90% and 85%．The control group was 15%,20%,20%,15%,and 0%,0%．Statistical analysis showed that the levels of DLCO,FEV₁,SF,CRP,KL-6 and MDA 5 significantly varied at 3 months of treatment．Pairwise comparison of LSD found that the DLCO,KL-6 and CRP levels in the treatment group were significantly lower than the control group（P<0.01）,the FEV₁ level in the treatment group was significantly higher（P<0.01）,and the SF level in the treatment group was significantly lower（P<0.05）．After 6 month of treatment,the complete response rate of the above indicators in the treatment group were 95%,85%,90%,90%,90% and 85%,and the complete response rate of the above indicators in the control group was 20%,25%,20%,20%,20% and 5%．Statistical analysis showed the levels of DLCO,FEV₁,SF,CRP,KL-6 for the amount of MDA 5 and the number of deaths between two groups were significantly different．Further pairwise comparison of LSD showed that the DLCO,KL-6 and CRP levels in the treatment group were significantly lower compared with the control group（P<0.01）,the FEV₁ level was significantly increased compared with the control group（P<0.01）,and the SF treatment group was significantly decreased compared with the control group（P<0.05）. Conclusions In the treatment of patients with MDA 5 antibody positive DM with ILD,the treatment of plasmapheresis combined with PDN and CTX can significantly improve the efficacy and reduce the mortality rate．

1、 HALL J C,CASCIOLA-ROSEN L,SAMEDY L A,et al.Anti-melanoma differentiation-associated protein 5-associated dermatomyositis:Expanding the clinical spectrum[J].Arthritis Care Res,2013,65(8):1307-1315.

2、 CAO H,PAN M,KANG Y,et al.Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti-melanoma differentiation-associated gene 5 antibody[J].Arthritis Care Res,2012,64(10):1602-1610.

3、 KAMPERMAN R G,van der KOOI A J,de VISSER M,et al.Pathophysiological mechanisms and treatment of dermatomyositis and immune mediated necrotizing myopathies:A focused review[J].Int J Mol Sci,2022,23(8):4301.

4、 ITO M,KAISE S,SUZUKI S,et al.Clinicolaboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease[J].Clin Rheumatol,1999,18(6):462467.

5、 HUC,WUC,YANG E,et al.Serum KL-6 is associated with the severity of interst itial lung disease in Chinese patients with polymyositis and dermatomyositis[J].Clin Rheumatol,2019,38(8):2181-2187.

6、 YE Y,FU Q,WANG R,et al.Serum KL6 level is a prognostic marker in patients with antiMDA5 antibodypositive dermatomyositis associated with interstitial lung disease[J].J Clin Lab Anal,2019,33(8):e22978.

7、 HU Y,WANG L S,JIN Y P,et al.Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients[J].Clin Respir J,2017,11(3):337-345.

8、 MARIE I.Morbidity and mortality in adult polymyositis and dermatomyositis[J].Curr Rheumatol Rep,2012,14(3):275-285.

9、熊倩,江涛.多发性肌炎、皮肌炎合并肺间质性肺炎的诊治[J].医学信息,2020,33(6)43-46.

10、赵江峰,叶霜.抗mda5抗体相关皮肌炎的诊疗进展[J].中华检验医学杂志,2021,44(11)1070-1075.

11、 BOHAN A,PETER J B.Polymyositis and dermatomyositis(second of two parts)[J].N Engl J Med,1975,292(8):403-407.

12、 TSUJI H,NAKASHIMA R,HOSONO Y,et al.Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with highdose glucocorticoid,tacrolimus,and cyclophosphamide in interstitial lung diseases accompanied by antimelanoma differentiationassociated gene 5positive dermatomyositis[J].Arthritis Rheumatol,2020,72(3):488498.

13、 YE S,CHEN XX,LU XY,et al.Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease:A retrospective cohort study[J].Clin Rheumatol,2007,26(10):16471654.

14、 GONO T,SATO S,KAWAGUCHI Y,et al.AntiMDA5 antibody,ferritin and IL18 are useful for the evaluation of response to treatment in interstitial lung disease with antiMDA5 antibodypositive dermatomyositis[J].Rheumatology,2012,51(9):15631570.

15、 KOGA T,FUJIKAWA K,HORAI Y,et al.The diagnostic utility of antimelanoma differentiationassociated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM[J].Rheumatology,2012,51(7):12781284.

16、 FUJIKI Y,KOTANI T,ISODA K,et al.Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients[J].Mod Rheumatol,2018,28(1):133-140.

17、 KISHABA T,MCGILL R,NEI Y,et al.Clinical characteristics of dermatomyosits/polymyositis associated interstitial lung disease according to the autoantibody[J].J Med Invest,2018,65(3.4):251-257.

18、 BETTERIDGE Z,MCHUGH N.Myositis-specific autoantibodies:An important tool to support diagnosis of myositis[J].J Intern Med,2016,280(1):8-23.

19、赵稳,王延生,周霞,等.肺纤维化急性加重患者短期内死亡危险因素分析[J].广州医药,2020,51(5):1-4,20.