Humoral aspects of polymyositis/dermatomyositis

Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma–PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder.     

Humoral aspects of polymyositis/dermatomyositis

Abstract

Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma–PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder.     

多发性肌炎/皮肌炎合并急性呼吸衰竭临床特点分析及治疗

目的 探讨多发性肌炎/皮肌炎合并急性呼吸衰竭患者的临床特点及治疗方法.方法 回顾性分析11例多发性肌炎/皮肌炎合并急性呼吸衰竭患者的临床资料、治疗方法及预后的差异.结果 患者起病时和出现呼吸衰竭时肌酸激酶（CK）、补体C4、免疫球蛋白M（IgM）水平及血氧饱和度（SaO2）、氧分压（PO2）比较,差异有统计学意义（P＜0.05）;丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、白蛋白（ALB）、球蛋白（GLO）、红细胞沉降率（ESR）、C反应蛋白（CRP）、降钙素原（PCT）、补体C3、IgG、IgA比较差异无统计学意义（P＞0.05）.11例患者均合并急性亚急性肺间质病变及肺部感染,均予激素、免疫抑制剂、丙种球蛋白大剂量冲击治疗、血浆置换、抗感染等综合性治疗,5例患者在疾病不同时期死亡,7例予血浆置换治疗患者中6例好转,长期随诊病情缓解.结论 多发性肌炎/皮肌炎合并急性呼吸衰竭患者死亡率高,CK下降对于是否出现急性呼吸衰竭无指导意义,血浆置换对此类患者治疗有效,可明显改善患者预后.     

Dermatomyositis/polymyositis associated with malignancy: our experience with ten patients and review of relevant literature

Objective: To analyse the clinical and laboratory data of patients diagnosed with malignancy associated dermatomyositis/polymyositis (DM/PM) seen between January 2002 and February 2007. Methods: The demographic, clinical, treatment and follow‐up data from the case records of all 10 patients diagnosed with malignancy‐associated inflammatory muscle diseases (IMD) namely, DM/PM, were entered in a proforma and analysed. Results: In patient nos. 1–8, malignancy was diagnosed prior to the diagnosis of myositis; in patient no. 9, it was detected during screening and patient no. 10 developed breast cancer 5 years after PM diagnosis. All the patients had typical clinical and laboratory features of IMD, except two patients, who had amyopathic dermatomyositis with predominantly cutaneous features, creatine kinase levels less than two times the upper limit of normal and minimal muscle weakness. Breast cancer (6/10) and ovarian cancer (3/10) were the most commonly associated malignancies. All but one (patient no. 8) responded to treatment. Malignancy relapsed in four patients with concurrent relapse of myositis in three. These three patients died of the malignancy. One patient was lost to follow‐up. The mean duration of follow‐up in others was 21 months (range 12–60 months). Conclusion: DM is more commonly associated with malignancy. Carcinoma of the breast was the most commonly associated malignancy. Myositis responded in most patients. Death was due to the underlying malignancy. In most cases, the two conditions occur within 1 year.     

Current diagnosis and treatment of polymyositis and dermatomyositis

Abstract

Idiopathic inflammatory myopathies (IIMs) are heterogeneous disorders that affect the skeletal muscles. Polymyositis, dermatomyositis, and inclusion body myositis are major IIM subsets. Immune-mediated necrotizing myopathy became recognized as a potentially new IIM subset. Since the new classification criteria published by the International Myositis Classification Criteria Project have higher sensitivity and specificity for IIM classification and subclassification than the previous criteria, they should help precise diagnosis. It should be noted that several tests available in current clinical practice, such as electromyography, magnetic resonance imaging, and other myositis-specific autoantibodies than anti-Jo-1 antibodies, were not included in the new criteria. As for treatment, glucocorticoids are used empirically as the first-line treatment despite their various adverse effects. Concomitant treatment with steroid-sparing immunosuppressive agents, including methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, and cyclophosphamide, reduces successfully initial glucocorticoid doses for the remission induction, the relapse risk during glucocorticoid tapering, and adverse effects of glucocorticoids. Treatment with biologics, including rituximab and abatacept, seems promising in some IIM patients. Multi-target treatment with glucocorticoids and several steroid-sparing immunosuppressive agents is effective in refractory IIM patients. Considering proven steroid-sparing efficacy and tolerability of multi-target treatment in patients with other autoimmune diseases, it should be a good therapeutic option for IIMs.     

Prevalence and incidence of polymyositis and dermatomyositis in Japan

Abstract

Objectives. To estimate the number of patients with polymyositis/dermatomyositis (PM/DM) in Japan and the prevalence rate and incidence rate of the disease.

Methods. The electronic database in the nationwide registration system on intractable diseases from 2003 to 2010 was utilized to identify the number of prevalent and incident cases of PM/DM. The electronic data entry rate was used to establish the total number of registered cases.

Results. The estimated total number of patients with PM/DM and the prevalence rate in Japan in 2010 were 17,000 and 13.2 per 100,000 population, respectively. The prevalence of PM/DM ranged from 10 to 13 per 100,000 population with a trend toward increasing over time. The incidence of PM/DM was estimated within the range 10–13 per 1,000,000 person-years, except for 2003.

Conclusions. We report the prevalence and incidence of PM/DM recently in Japan for the first time at the nationwide population level. Because the prevalence seems to be increasing recently, continued monitoring of these epidemiologic features is required.     

12例间质性肺疾病合并肺癌临床分析

目的 了解间质性肺疾病合并肺癌的临床特点和治疗.方法 回顾性分析12例北京协和医院住院患者中诊断间质性肺疾病合并肺癌患者的临床症状、影像学、病理、治疗及预后.结果 12例患者,平均年龄(61±8)岁,男女比例11:1,平均吸烟指数(26±5)包·年,8例为特发性肺纤维化.临床表现包括干咳(10/12)、活动后气短(9/...     

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。     

Epidemiologic analysis of the clinical features of Japanese patients with polymyositis and dermatomyositis

Objectives: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system.

Methods: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM.

Results: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness.

Conclusions: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.     

皮肌炎/多发性肌炎与恶性肿瘤

目的　了解皮肌炎 (dermatomyositis ,DM)及多发性肌炎 (polymyositis,PM )患者的恶性肿瘤发生情况。方法　收集 1989— 1998年北京协和医院收治的资料完整的DM/PM患者 143例 ,全部符合 1975年Bohan和Peter提出的DM /PM诊断标准 ,对其中 18例合并肿瘤的患者与非肿瘤患者进行临床分析 ,肿瘤诊断及分型标准根据我国卫生部制定的肿瘤诊断分级标准而定。两组资料采用t及 χ2 检验。结果　 143例患者男性 46 ,女性 97例。发病年龄 4～ 76岁 ,平均年龄 (42± 38)岁 ,其中PM5 0例 ,男 14例 ,女 36例 ,DM93例 ,男 2 4例 ,女 6 9例。PM的肿瘤发生率为 8% ,DM的肿瘤发生率为 15 6 %。肿瘤分型 :卵巢癌 3例 ,鼻咽癌 3例 ,恶组 2例 ,乳癌 2例 ,宫颈癌、子宫内膜卵巢样癌、肺癌、胃癌、前列腺癌、直肠癌、多发性骨髓瘤、淋巴瘤各 1例。肿瘤先行发生者 3例 (16 6 % ) ,后续发生者 5例 (2 7 8% ) ,同时发生者 10例 (5 5 6 % )。本组病例中 10例死亡 ,从PM /DM诊断到死亡的时间为 1～ 84个月 [中位数为 (18± 2 7)个月 ],死亡原因包括肿瘤扩散 ,肿瘤相关的多脏器功能衰竭及感染。发病年龄、肺部和心脏受累 ,吞咽困难等指标在两组间显示有统计学意义。其中 1例在肿瘤切除 1年后 ,PM症状消失 ,另 1例在肿瘤切除后 1 5年     

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.     

Transbronchial biopsy is clinically useful in classifying patients with interstitial pneumonia associated with polymyositis and dermatomyositis

Background and objective: The histological type of intraluminal fibrosis is an important prognostic factor for interstitial pneumonia. We therefore examined whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the clinical course and prognosis of patients with interstitial pneumonia associated with polymyositis and dermatomyositis (PM/DM), with particular attention to the different types of intraluminal fibrosis. Methods: Twenty‐five cases of interstitial pneumonia associated with PM/DM were classified according to the pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and response to treatment were compared. Interstitial fibrosis was evaluated by sequential thin‐section CT scans. Results: In 19 of 25 (76%) cases, there was sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis was classified as bud (polyp) type or mural incorporation type (either alone or mixed with bud type). The bud type was seen in five cases and these improved following treatment with corticosteroids only. The mural incorporation type was seen in 14 cases. In 11 of these 14 cases, progressive long‐term fibrosis developed and four cases were fatal, in spite of corticosteroid and immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P < 0.05) were significantly greater in patients with bud‐type than mural incorporation‐type intraluminal fibrosis. Conclusions: Classification of the pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the response to treatment, clinical course and prognosis of interstitial pneumonia associated with PM/DM.     

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。     

Advanced gallbladder cancer accompanied with cancer-associated dermatomyositis: A case report and literature review

Rationale:Muscle weakness due to cancer-associated dermatomyositis (CADM) can be misdiagnosed as cancer cachexia and disuse atrophy.Patient concerns:A 75-year-old female was admitted to our institute with muscle weakness, dysphagia, and suspected gallbladder cancer. Computed tomography and cytopathological examinations of the liver biopsy and fine-needle aspiration from swollen lymph nodes using endoscopic ultrasonography revealed cancer in the gallbladder body and metastasis to the lymph nodes around the abdominal aorta. We avoided the administration of anticancer drugs due to her poor general condition.Diagnosis:Subsequently, we diagnosed her with muscle weakness and dysphagia as a result of CADM using species from muscle and skin biopsy.Interventions and Outcomes:Prednisolone therapy and anticancer agents partially improved the patient symptoms.Lessons:CADM is reported to be associated with a high incidence of dysphagia, which may aid in the diagnosis of this disease.     

Clinical features of polymyositis/dermatomyositis associated with silicosis and a review of the literature

There are few reports which describe the association of polymyositis/dermatomyositis (PM/DM) and silicosis. The purpose of this study is to describe the clinical features of PM/DM associated with silicosis. We first describe clinical features of two cases and provide a review of the literature. Finally, seven patients with PM/DM associated with silicosis are retrospectively evaluated. There were one female and six males. Histological specimens were obtained by open lung biopsy in five cases and not examined in two. The mechanism of the association between silicosis and PM/DM is discussed.     

Anti-SS-A/Ro antibody positivity as a risk factor for relapse in patients with polymyositis/dermatomyositis

Objective: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM).

Methods: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004–2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared.

Results: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p?=?.03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p?=?.007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p?=?.03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500?IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4–25.1).

Conclusions: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.     

A case of polymyositis with a significantly high level of KL-6 associated with pancreatic cancer

A 53-year-old man was diagnosed with polymyositis (PM) in 1997 and treated with prednisolone. The subjective symptoms of pneumonitis were poor. However, the KL-6 values were elevated to 2230 IU/l in March 2001. Abdominal computer tomography findings revealed a pancreatic-tail tumor and multiple liver nodules, diagnosed as primary pancreatic adenocarcinoma with multiple liver metastasis. The stage of the pancreatic cancer was IV, and curative surgery of the tumor was not indicated. Chemotherapy and radiotherapy were administered for the liver metastasis. However, these therapies were ineffective against the tumors. The patient died on 12 September 2001. If a high level of KL-6 is found without the increasing activity of lung disease containing interstitial pneumonia in PM patients, examination for the internal malignancies including pancreatic cancer should be performed, although cases of PM with a significantly high level of KL-6 associated with pancreatic cancer are rare.     

A case of polymyositis with a significantly high level of KL-6 associated with pancreatic cancer

Abstract

A 53-year-old man was diagnosed with polymyositis (PM) in 1997 and treated with prednisolone. The subjective symptoms of pneumonitis were poor. However, the KL-6 values were elevated to 2230?IU/l in March 2001. Abdominal computer tomography findings revealed a pancreatic-tail tumor and multiple liver nodules, diagnosed as primary pancreatic adenocarcinoma with multiple liver metastasis. The stage of the pancreatic cancer was IV, and curative surgery of the tumor was not indicated. Chemotherapy and radiotherapy were administered for the liver metastasis. However, these therapies were ineffective against the tumors. The patient died on 12 September 2001. If a high level of KL-6 is found without the increasing activity of lung disease containing interstitial pneumonia in PM patients, examination for the internal malignancies including pancreatic cancer should be performed, although cases of PM with a significantly high level of KL-6 associated with pancreatic cancer are rare.     

Soluble CD4, CD8 in patients with polymyositis/dermatomyositis

Summary The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/DM). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8⁺ cells are related to muscular involvement.