Cyclophosphamide treatment of interstitial pulmonary fibrosis in polymyositis/dermatomyositis

Interstitial pulmonary fibrosis is a serious complication of inflammatory muscle disease associated with significant morbidity and mortality. We describe 3 consecutive cases complicating dermatomyositis (1 case, anti-Jo-1 antibody negative) and polymyositis (2 cases, anti-Jo-1 antibody positive) in which cyclophosphamide was added to prednisone therapy with favorable outcomes.     

Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis

OBJECTIVE: To assess the difference in clinical features and prognosis of patients with interstitial lung disease (ILD) comparing polymyositis (PM) and dermatomyositis (DM). METHODS: Medical records of 28 ILD patients with PM/DM (16 PM-ILD, 12 DM-ILD) were reviewed retrospectively. RESULTS: Serum CPK concentrations were significantly higher in PM-ILD than in DM-ILD. Bronchoalveolar lavage analysis showed that the percentages of lymphocytes and eosinophils were significantly higher in DM-ILD than in PM-ILD. Ten patients (5 PM-ILD, 5 DM-ILD) underwent surgical lung biopsy, and 3 (3 DM-ILD) had an autopsy. Nonspecific interstitial pneumonia (NSIP) was found in 7 (4 PM-ILD, 3 DM-ILD) and usual interstitial pneumonia (UIP) in 3 (1 PM-ILD, 2 DM-ILD). Interestingly, diffuse alveolar damage (DAD) was found in 3 patients with DM-ILD, who all died of deterioration of ILD; but no one with PM-ILD had DAD. Corticosteroid treatment alone achieved a favorable response in 6 patients (37.5%) with PM-ILD, but in only one (8.3%) with DM-ILD. Administration of cyclosporine in the early phase of onset benefited 4 corticosteroid-resistant patients with DM-ILD. Conclusively, survival in DM-ILD was significantly worse than that in PM-ILD. CONCLUSION: DM-ILD is more refractory to corticosteroid therapy, resulting in poorer prognosis compared with PM-ILD. These data indicate that intensive therapy, including cyclosporine, should be considered for DM-ILD.     

Antibody to Jo-1 in polymyositis/dermatomyositis: association with interstitial pulmonary disease

Forty-four patients with polymyositis/dermatomyositis (PM/DM) were studied for precipitating antibody to Jo-1. Ten (23%) had anti-Jo-1 antibodies including 8 (47%) of 17 PM patients and 2 (15%) of 13 PM-overlap patients. None of the 11 DM nor 3 PM/DM-cancer patients had anti-Jo-1 antibody. Interstitial pulmonary disease was present in 5 (50%) of the 10 anti-Jo-1 positive compared to 5 (13%) of the 34 anti-Jo-1 negative patients (odds ratio = 5.8, p = 0.05). No differences in other demographic or clinical features or survivorship were noted between these groups. These data confirm the association of anti-Jo-1 antibody with an increased frequency of interstitial pulmonary disease in PM/DM patients.     

Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis

Objective

Spontaneous pneumomediastinum is a rare complication of dermatomyositis (DM) and polymyositis (PM). The aim of this study was to characterize this complication and determine its prognostic factors.

Methods

We retrospectively collected a multicenter series of PM/DM cases complicated by pneumomediastinum. We analyzed all published cases and combined those that were exploitable with ours for an investigation of the factors associated with poor survival.

Results

We collected 11 PM/DM cases complicated by interstitial lung disease and pneumomediastinum. Five of the 9 DM patients had clinically amyopathic DM without muscle weakness and high serum creatine kinase levels. The outcome was favorable in 7 of these patients and 6 had no sequelae. In total, ～25% of our patients of the 21 analyzable cases studied died within 1 month. With a median followup of 240 days, the cumulative estimated Kaplan‐Meier survival rate was 64% at 1 year and 55% at 2 years. Poor survival was associated with absence of muscle weakness (P = 0.02), initial low vital capacity (P = 0.006), and initial low carbon monoxide diffusion capacity (P = 0.04).

Conclusion

In this first large series of patients with connective tissue disease complicated by pneumomediastinum to be reported, most patients had DM and half amyopathic DM, as in previous reports. Pneumomediastinum may occur before DM diagnosis and may thus reveal DM with minimal or no muscle involvement. Death was associated with an absence of muscle weakness and severe pulmonary involvement before the onset of pneumomediastinum. Corticosteroids and immunosuppressive therapy can result in complete recovery, as in half our cases.     

多发性肌炎和皮肌炎合并肺间质病变特点比较分析

目的：了解 PM 和 DM 合并肺间质病变（ILD）的临床特点。方法收集并整理114例 PM/DM合并 ILD 患者的临床资料,将其分为 PM-ILD 和 DM-ILD 2组,分析2组患者的一般资料、临床表现、实验室检查、高分辨率 CT（HRCT）、肺功能、血气分析、治疗及转归有无差异,率之间采用四格表χ2检验和 Fisher 确切概率法进行比较。结果 PM/DM-ILD 发病率为35.8%（114/318）,DM 较 PM 更易合并 ILD （χ2=5.019,P=0.025）。 PM-ILD 组和 DM-ILD 组在性别构成比上差异有统计学意义（χ2=4.929,P=0.026）;DM-ILD 组患者更易出现关节痛/关节炎（χ2=7.756,P=0.005）;PM 患者 ILD 更易出现于肌炎之前（χ2=15.555,P<0.01）,而 DM 患者 ILD 更易出现于肌炎或皮肤表现之后（χ2=7.002,P=0.008）, PM-ILD 组患者更易出现抗 Jo-1抗体阳性（χ2=11.395,P=0.001）。 HRCT 表现上, PM-ILD 组更易出现磨玻璃影（χ2=7.940, P=0.005）和心包积液（χ2=6.322,P=0.012）,DM-ILD 组更易出现斑片影（χ2=5.105,P=0.024）;2组患者在肺功能及血气分析上差异无统计学意义;在治疗差异无统计学意义情况下,DM-ILD 组患者的转归明显差于PM-ILD 组（χ2=7.595,P=0.006）。结论 PM-ILD 和 DM-ILD 患者在性别构成、临床表现、实验室检查、影像学表现和转归上差异有统计学意义,因此推测 PM 和 DM 不同的免疫病理机制导致 PM-ILD 和 DM-ILD 具有不同的临床特点。     

皮肌炎多发性肌炎患者间质性肺病病理资料推断性分析

目的 分析皮肌炎(DM)、多发件肌炎(PM)合并间质性肺病(ILD)患者的胸部X线、胸部高分辨CT(HRCT)及肺功能等肺部表现临床特点及其预后.方法 回顾性分析上海长海医院风湿免疫科1999年1月至2007年1月期间收住院的33例DM/PM合并ILD除外感染患者的临床资料.结果 33例ILD患者经胸部X线及HRCT证实.根据临床-影像学特点并结合血气分析、肺功能测定,参照美国胸科学会和欧洲呼吸协会问质性肺炎的分类诊断标准,推断分析病理类型主要为非特异性间质性肺炎(NSIP)(57%)和寻常性间质性肺炎(UIP)(25%). UIP类型预后差、病死率高(70%).结论 结合患者的影像学资料、肺功能、血气分析推断病理类型主要为NSIP和UIP,其中UIP病死率高、预后差.     

High-resolution computed tomography characterization of interstitial lung diseases in polymyositis/dermatomyositis

OBJECTIVE: Interstitial lung disease (ILD) associated with polymyositis (PM) and dermatomyositis (DM) sometimes progresses rapidly and is resistant to therapy. Clinical features that forecast the prognosis of the disease remain to be elucidated. Our aim was to assess if selected clinical features and high-resolution computed tomography (HRCT) findings can assist in predicting the clinical course of ILD in PM/DM. METHODS: We examined HRCT findings retrospectively for ILD identified in 17 patients with PM and 16 with DM. Radiological patterns and clinical features are analyzed in comparison with clinical course. RESULTS: Mortality rates were 12% and 44% for ILD associated with PM and DM, respectively. Most patients with DM died of rapidly progressive lung deterioration. No patient in the PM group died of respiratory failure. In the DM group, all patients with fatal ILD had ground-glass attenuation and reticular opacity as the principal radiological findings. Consolidation was recognized frequently as the principal pattern in nonfatal cases. Radiological patterns were categorized into 3 groups; A: consolidation dominant, B: ground-glass attenuation/reticular opacity dominant without chronic fibrosing process, and C: ground-glass attenuation/reticular opacity dominant with chronic fibrosing process. Occurrences of fatal disease were 0%, 83%, and 20%, in groups A, B, and C. CONCLUSION: The prognosis of ILD associated with DM differs from that with PM. The former can be classified into 3 subgroups on the basis of radiological findings, which are closely associated with clinical course.     

多发性肌炎/皮肌炎合并间质性肺疾病预测因素的Meta分析

目的 系统分析和评价多发性肌炎/皮肌炎合并间质性肺疾病的预测因素,为临床早期诊治提供循证依据。方法 利用Meta分析方法分析国内外23篇关于多发性肌炎(PM)/皮肌炎合并间质性肺疾病( ILD)预测因素的文献,应用Rev-Man 4.2分析软件进行异质性和敏感性分析,并根据异质性检验结果,采用固定效应或随机效应模型计算合并比值比（OR值）和95％可信区间(95％CI)。应用Stata 10.0软件进行发表偏倚识别。结果 对关节炎/关节痛、发热、抗Jo-1抗体阳性、抗核抗体阳性、Gottron征、吞咽困难、雷诺现象共7个因素进行Meta分析,结果显示与PM/皮肌炎合并ILD存在关联性的因素及其OR值和95％CI分别是：抗Jo-1抗体阳性6.94(4.74～10.16)、发热4.90( 3.82～6.29)、关节炎/关节痛3.93(3.21～4.80)、Gottron征2.52(1.24～5.14)和抗核抗体阳性1.59( 1.02～2.47)。而与PM/皮肌炎合并ILD无关联性的因素及其OR值和95％CI分别为雷诺现象1.40(0.97～2.01)和吞咽困难1.21 (0.94～1.56)。结论 抗Jo-1抗体阳性、发热、关节炎/痛、Gottron征和抗核抗体阳性可作为PM/皮肌炎合并ILD的主要预测因素。     

Cyclosporine treatment of steroid resistant interstitial pneumonitis associated with dermatomyositis/polymyositis

We report the successful treatment with cyclosporine of a patient with steroid resistant interstitial pneumonitis associated with polymyositis and review the literature regarding the use of cyclosporine in the treatment of interstitial lung disease.     

Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis

OBJECTIVES: To study the efficacy and safety of monthly intravenous pulse cyclophosphamide (IVCYC) therapy for progressive interstitial pneumonia in polymyositis/dermatomyositis (PM/DM). METHODS: Seventeen patients with PM/DM/amyopathic DM (mean age 51.4 +/- 10.4, mean follow-up 32 months) who received IVCYC for progressive interstitial pneumonia between August 1993 and October 2002 were studied. Nine patients had failed to respond to previous treatment with high-dose steroid and/or immunosuppressant. Cyclophosphamide (300-800 mg/m2) was given at least six times every 4 weeks. Oral prednisolone (0.5-1 mg/kg/day) was administered for the first 2 weeks and was gradually tapered. Response to treatment was evaluated based on the degree of exertional dyspnea, pulmonary function test and high-resolution computed tomography (HRCT). RESULTS: Eleven of 17 patients showed improvement in their dyspnea; six out of seven patients who had required oxygen treatment before IVCYC no longer did so after IVCYC. Eight of 17 patients had >or=10% improvement of vital capacity (VC)% and 9/17 had >or=10 point reduction in their HRCT score. Twelve patients had exhibited at least one result. Two patients with anti-Jo-1 antibodies showed a flare-up of interstitial pneumonia or myositis. After the IVCYC therapy, mean VC% improved by 15% (from 68 to 83%, P = 0.0034). The extent of abnormal lesions in HRCT was reduced from 24 to 13% (P = 0.0055). There was neither death nor severe toxicities observed. CONCLUSIONS: In this open-label study, IVCYC improved symptoms, pulmonary function tests and HRCT findings in patients with PM/DM. Longitudinal controlled studies are required to further confirm the efficacy of IVCYC.