Coxsackievirus infection and the development of polymyositis/dermatomyositis

Recently, it has been suggested that coxsackievirus plays an etiologic role in juvenile dermatomyositis (DM). Neutralizing antibodies to 12 coxsackievirus antigens were measured in the sera of four clinical subsets of patients with adult polymyositis (PM)/DM. Elevated antibody titers to coxsackievirus A7, B3, and B4 were detected in patients with adult PM, adult DM, and adult PM/DM with malignancy, respectively. The development of these three subsets of idiopathic inflammatory myopathies may be related to infection with specific coxsackievirus serotypes.     

以肾脏损害为主要表现的多发性肌炎与皮肌炎四例临床分析

目的 探讨以肾脏损害为主要表现的多发性肌炎(PM)与皮肌炎(DM)的诊断和临床特点.方法 回顾性分析4例肾脏损害合并PM与DM患者的临床资料,并结合文献复习其临床特点和诊治进展.结果 4例患者均为女性,中位年龄数为55岁,肾脏表现分别为局灶节段硬化性肾小球肾炎、肾小球轻微病变、Ⅰ型肾小管酸中毒和慢性肾衰竭.其中1例合并膀胱肿瘤,同时出现肾衰竭.另3例肾脏病变轻微,临床表现为微量白蛋白尿或少量蛋白尿,肾功能正常.上述肾脏损害在PM/DM中均不常见.结论 PM和DM的诊断应结合临床资料、肌酶水平和肌电图检查,有条件者应行肌肉活检以确诊,同时应排除可能的恶性疾病.该病肾脏损害少见,常见的病理类型为系膜增生性肾小球肾炎,治疗可用糖皮质激素、免疫抑制剂等,也可试用免疫球蛋白或甲泼尼龙冲击治疗.     

Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features

Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders predominantly affecting skeletal muscles, resulting in muscle inflammation and weakness. The 3 most common inflammatory myopathies are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This review details the clinical findings noted in PM, DM, and the emerging entity of autoimmune necrotizing myopathy.     

Mortality of Chinese patients with polymyositis and dermatomyositis

Clinical Rheumatology - To investigate the mortality and the causes of death in Chinese patients with polymyositis (PM) and dermatomyositis (DM). The clinical data of all consecutive adult PM/DM...     

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.     

Treatment of early and refractory dermatomyositis with infliximab: a report of two cases

The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.     

Interstitial lung disease in polymyositis and dermatomyositis: clinical course and response to treatment

OBJECTIVES: To assess the prevalence, clinical characteristics, and treatment options of patients with interstitial lung disease (ILD) in polymyositis and dermatomyositis (PM/DM). Patients and Methods: Sixty-three consecutive patients with PM/DM underwent standardized screening. Patients with ILD were monitored prospectively, and graded immunosuppression was administered according to the rate of clinical progression. RESULTS: ILD was diagnosed in 20 of 63 patients (32%). Generally, the clinical and serologic findings of the anti-Jo1 syndrome were present. Follow-up evaluation disclosed either a progressive or a nonprogressive course. The 10 patients with progressive ILD were distinguished from the nonprogressive group by extensive ground-glass opacities on high-resolution computed tomography (HRCT) and by bronchoalveolar lavage (BAL) neutrophilia. Intravenous pulse cyclophosphamide prevented further progression in all 10 patients and led to some functional improvement. In the 10 patients without rapidly progressive lung disease, immunosuppression of moderate intensity stabilized pulmonary findings during a median 35 months of follow-up. CONCLUSIONS: The prevalence of ILD in our patients with PM/DM was 32%; this emphasizes the need for pulmonary screening in all PM/DM patients. Progressive disease, featuring ground-glass opacities on HRCT and an inflammatory BAL cell profile, is amenable to intensive immunosuppression. Conversely, patients who do not have these HRCT and BAL features appear to have a low risk of pulmonary deterioration. RELEVANCE: Because the treatment for ILD seems to depend on the rate of clinical progression, future therapeutic trials of lung disease in PM/DM should stratify patients accordingly.     

Chronological evaluation of the onset of histologically confirmed interstitial pneumonia associated with polymyositis/dermatomyositis

OBJECTIVE: The present study was designed to determine the chronological sequence of interstitial pneumonia, skin involvement, and muscle involvement associated with polymyositis/dermatomyositis (PM/DM). METHODS: We examined our own cases of histologically confirmed interstitial pneumonia associated with PM/DM. In addition, a review of the literature was done to evaluate other cases of histologically confirmed interstitial pneumonia associated with PM/DM. Lung involvement was the first clinical symptom for all of our 8 patients. RESULTS: Including the literature review and our 8 cases, there were 94 patients with PM/DM in whom interstitial pneumonia was histologically confirmed (36 PM, 50 DM, and 8 amyopathic DM). Chronological evaluation between the diagnosis of PM/DM and lung involvement demonstrated that most lung involvement occurred just before or just after the diagnosis of PM/DM. Interstitial pneumonia was preceded in 35 of 87 evaluable patients [21 cases with PM (61.8%), 14 cases with DM and amyopathic DM (40.2%)]. In 60 of 87 evaluable patients (69.0%), lung involvement occurred as a clinical manifestation at the diagnosis of PM/DM. CONCLUSION: The present data demonstrate that interstitial pneumonia was frequently the initial onset in patients with PM/DM.     

Use of muscular MRI in inflammatory myopathies

PURPOSE: Inflammatory myopathies include polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) which differ in terms of clinical, immuno-histological presentations, evolution and treatment. Diagnosis is based on the muscular biopsy but histological distinction between PM and IBM can be difficult; biopsies can be insufficient as well as during follow-up to detect active areas within the muscle. CURRENT KNOWLEDGE AND KEY POINTS: Muscular MRI is an important tool both in the diagnosis and the follow-up of IMM in the following circumstances: Distinction between PM and IBM: fatty infiltration and involvement of the anterior group of the thighs are characteristic of IBM whereas isolated inflammation and involvement of the three thighs or posterior muscle groups are characteristic of PM. Biopsy guidance on the inflammatory lesions depicted on the STIR sequence either initially or after a non-conclusive biopsy. To differentiate, active disease from steroid myopathy. FUTURE PROSPECTS AND PROJECTS: Several multicentric trials are in development both in spectro and morphologic MRI to study hypoxic phenomenon in early course of IMM and muscular volume evaluation both in normal subjects, congenital or acquired myopathies.     

Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review

The objectives of this study are to review and summarize published information on the use, effectiveness, and adverse effects of intravenous immunoglobulin (IVIG) in patients with polymyositis (PM) or dermatomyositis (DM) and to search MEDLINE and CNKI (Chinese) databases from 1985 to 2011 to retrieve clinical research articles concerning IVIG in adult patients with PM/DM. Of the 14 articles selected, two were randomized controlled trials, nine prospective open studies, and three retrospective studies with a total of 308 adult patients. IVIG has been used successfully in the treatment of PM/DM. The standard dose is 2 g/kg, given in two to five individual daily doses. The course of IVIG treatment is usually 3~6 months. IVIG therapy seemed rarely employed as first-line therapy in PM/DM. In a double-blind study conducted in patients with refractory DM, IVIG combined with corticosteroid significantly improved muscle strength and decreased serum creatine kinase level, compared with placebo. The beneficial effect of IVIG in refractory, flare-up, rapidly progressive, or severe PM/DM has been documented in many open-label trials. IVIG was shown to be effective in most of PM/DM patients with lung involvement and esophageal involvement. In some patients, IVIG can lower the corticosteroid dose required for maintenance, demonstrating the most effective steroid-sparing effect. Adverse effects were generally tolerable. IVIG is effective in the treatment of adult patients with PM/DM and appears to be relatively well tolerated and safe. IVIG may be a good choice especially in patients with refractory, flare-up, rapidly progressive, or severe PM/DM, and can be tried in patients with a contraindication for corticosteroid.     

An uncommon association: celiac disease and dermatomyositis in adults

We describe the case of a patient with a two-year history of adult dermatomyositis (DM) who developed malabsorption revealing celiac disease. Our observation raises the question of an association between DM and celiac disease as part of a continuum, suggesting that celiac disease may be included within the spectrum of the gastrointestinal manifestations of DM and polymyositis (PM). From a practical point of view, our data indicate that the diagnosis of celiac disease should be suspected in PM/DM patients exhibiting malabsorption syndrome. Based on our findings, we further emphasize that an evaluation for celiac disease, including anti-gliadin antibodies, anti-endomysium antibody and tissue trans-glutaminase antibodies should be considered in PM/DM patients presenting with unusual and unexplained gastrointestinal features. This could lead to the early management of such patients, resulting in decreased morbidity (i.e., malnutrition and malignancy) related to misdiagnosed celiac disease.     

Influence of age on characteristics of polymyositis and dermatomyositis in adults.

In a retrospective study of 79 consecutive patients, we evaluated characteristics of polymyositis (PM) and dermatomyositis (DM) and compared clinical presentation, biochemical findings, histologic changes, evolution, complications, and mortality rate of elderly patients (aged > or = 65 yr) and younger patients (aged < or = 64 yr) at the onset of PM/DM. We found a high prevalence of PM/DM in elderly patients: 23 patients (29%) were aged 65 years or over. We also found that esophageal involvement (34.8% versus 16.1%, respectively) and bacterial pneumonia related to both ventilatory insufficiency and esophageal impairment (21.7% versus 5.4%, respectively) were more common in elderly patients compared with younger patients, resulting in increased morbidity and mortality rates. Moreover, malignancy frequency was higher in elderly patients compared with younger patients (47.8% versus 9.1%, respectively, p = 0.0001), particularly patients with DM (10/11). Fifty percent of malignancies were colon malignancies in elderly patients. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and ferritin levels were also higher in the elderly patient group compared with the younger group, and the presence of serum hypoprotidemia, hypoalbuminemia, and anemia was more frequent. Finally, PM/DM complete remission was less frequent (13.6% versus 41.1%) and the mortality rate (47.8% versus 7.3%) was higher in elderly patients than in younger patients. The main causes of death in elderly patients were bacterial pneumonia, due to ventilatory insufficiency and esophageal impairment, and malignancies. Our findings therefore indicate that PM/DM-related esophageal and lung involvement should be systematically searched for in elderly patients. Esophageal manometry and pulmonary function tests should become an integral part of initial evaluation in elderly patients for early detection of impairment. Moreover, as we observed a marked overrepresentation of colon cancer in elderly patients with DM, we suggest that the search for malignancies in elderly patients with DM should include lower gastrointestinal tract investigations.     

Antibody to signal recognition particle in polymyositis

Using immunoprecipitation, we identified 13 patients with antibodies to the signal recognition particle (SRP) from a collection of sera representing 265 polymyositis/dermatomyositis (PM/DM) patients. Antibody reactivity with SRP was confirmed by enzyme-linked immunosorbent assay and immunoprecipitation with isolated dog pancreas SRP. The antibody was present in the serum of 4% of PM/DM patients, and 18% of PM/DM patients with anticytoplasmic antibodies other than anti-Jo-1, but not in patients with other conditions who had anticytoplasmic antibodies. Anti-SRP was associated with classic adult PM, and some of these cases were unusually severe and/or of rapid onset; it was not found in patients with overlap syndromes or with DM involvement. Unlike patients with antibodies to aminoacyl-transfer RNA synthetases, patients with anti-SRP had a low frequency of pulmonary fibrosis, as well as of arthritis and Raynaud's phenomenon. Anti-SRP antibodies may serve as a marker for a second, distinct subgroup of adult PM.     

Histopathologic aspects of polymyositis and dermatomyositis. Correlation with the clinical course. Study of 57 cases

Muscle biopsies from 57 patients with dermatomyositis or polymyositis were histologically evaluated and compared with the disease's clinical course. Perifascicular atrophy, perivascular infiltrates and tubular inclusions in endothelial cells were significantly more frequent in young patients with dermatomyositis. On the other hand, in adult polymyositis, which evolves more slowly, necrosis with slight muscular atrophy and perinecrotic infiltrates was observed. This division into two groups was clear when the clinical evolution and histological patterns were compared. The mean age of each group was different, but there was a large overlap. Two different pathogenetic mechanisms can be envisaged: primary involvement of muscle capillaries with muscle ischemia in young patients with dermatomyositis and primary involvement of muscle fibers in adults afflicted with polymyositis.     

Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.

OBJECTIVE: Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury. METHODS: 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM. RESULTS: CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes. CONCLUSION: These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.     

多发性肌炎或皮肌炎心脏损害的临床分析

目的分析多发性肌炎或皮肌炎（polymyositis/dermatomyositis,PM/DM）心脏损害的特征,探讨心脏损害发生的危险因素.方法收集423例PM/DM的临床资料,分析心脏损害的发生率、心脏损害的类型以及可能诱发心脏损害的危险因素.结果心脏损害的发生率为42.6%（180/423）,表现为心肌缺血、心律失常、心包炎、心肌损害、肺动脉高压、瓣膜病变、传导阻滞、肢导低电压和其他心脏损害;多因素分析发现血沉是心脏损害发生的危险因素.结论心脏损害是PM/DM的常见并发症,表现复杂多样.血沉增快提示心脏损害的危险性增加,而与年龄、性别及病程长短等因素无关.     

Pulse intravenous cyclophosphamide treatment for steroid-resistant interstitial pneumonitis associated with polymyositis.

Interstitial pneumonitis (IP) is a serious complication in polymyositis/dermatomyositis (PM/DM), leading to significant morbidity or mortality. Here, we report the successful treatment by pulse intravenous administration of cyclophosphamide in the early course of lung involvement in PM, and with subsequent low-dosage oral administration of azathioprine in a patient with steroid-resistant IP associated with PM/DM. Although the precise pharmacological mechanism induced by cyclophosphamide in this disease remains unclear, such a cytotoxic drug raises the possibility of control of steroid-resistant PM/DM-associated IP when used in the early course of IP.     

皮肌炎/多发性肌炎并发肺孢子虫肺炎的临床诊治

目的总结皮肌炎/多发性肌炎（DM/PM）患者并发肺孢子虫肺炎（PCP）的诊治经过,提高对该病的认识。方法对8例DM/PM患者（其中DM6例、PM2例）进行回顾性分析其并发PCP的危险因素、临床表现、影像学改变、治疗和转归。结果 8例患者中6例合并肺间质病变,均联合应用大剂量糖皮质激素和免疫抑制剂治疗。多数（6/8）诊断为DM/PM的患者在6个月内发生PCP,临床表现为发热、咳嗽和进行性呼吸困难;平均动脉血氧分压为44（40.7～66）mmHg（1mmHg=0.133kPa）;胸部影像学示双肺间质磨玻璃或多发弥漫斑片影。平均外周血淋巴细胞计数为0.46（0.16～0.76）×109/L,平均CD4＋T细胞计数为0.14（0.05～0.25）×109/L。3例患者痰中、4例患者支气管肺泡灌洗液中找到肺孢子虫,3例患者痰中肺孢子虫聚合酶链反应（PCR）阳性;4例患者合并其他病原体感染。8例患者均应用复方磺胺异噁唑和糖皮质激素治疗,死亡6例。结论 PCP为DM/PM患者少见,但其致命性、机会性感染在临床诊治时需提高警惕。     

Interstitial lung disease in polymyositis and dermatomyositis

OBJECTIVES: To assess prevalence, characteristics, and long-term outcome of interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To determine predictive variables of ILD course in PM/DM, and to define both clinical and biochemical features associated with ILD onset in PM/DM. METHODS: The medical records of 156 consecutive PM/DM patients in 3 medical centers were reviewed. RESULTS: Thirty-six PM/DM patients (23.1%) developed ILD. We observed that 19.4% of patients with ILD had resolution of pulmonary disorders, whereas 25% experienced ILD deterioration. Morbidity and mortality rates were as high as 13.9% and 36.4%, respectively, in PM/DM patients with ILD. Parameters of PM/DM that related to ILD poor outcome were identified as follows: Hamman-Rich-like pattern, initial diffusing capacity of carbon monoxide <45%, neutrophil alveolitis, and histologic usual interstitial pneumonia. Additionally, for the group with ILD, polyarthritis, higher values of erythrocyte sedimentation rate and C-reactive protein, presence of anti-Jo-1 antibody, and characteristic microangiopathy were significantly more frequent. CONCLUSION: Our series underlines the high frequency of ILD in PM/DM patients, resulting in increased morbidity and mortality rates. It also indicates that PM/DM patients should routinely be screened for ILD, even those patients without anti-Jo-1 antibody, because 69% of our ILD patients were seronegative for the anti-Jo-1 antibody. Our findings further suggest that PM/DM patients presenting with factors predictive of ILD poor outcome may require more aggressive therapy.     

成人多发性肌炎或皮肌炎并发慢性假性肠梗阻的临床特点

目的探讨成人多发性肌炎皮肌炎(polymyositisdermatomyositis,PMDM)合并慢性假性肠梗阻(chronic intestinal pseudo-obstruction,CIPO)患者的临床特点及预后,以提高对此类疾病的认识。方法收集北京协和医院2003年11月至2013年10月临床成人PMDM合并CIPO患者的临床资料,回顾性分析及总结临床表现、实验室检查、诊治及转归。结果合并CIPO的成人PM患者2例,DM患者4例,分别占同期住院成人PMDM患者的0.45%(2441)及0.54%(4747)。6例患者男女比例为1∶2,平均年龄(41±15)岁。CIPO均非临床首发症状,发病时间为PMDM诊断后1~10年,部位均位于小肠。83%(56)患者病程中合并出现急性上消化道出血,2例患者经胃镜明确出血部位分别为胃小弯及十二指肠降部,镜下均表现为多发黏膜溃疡出血。6例患者中33%(26)在出现肠梗阻时并无明确肌肉受累表现,67%(46)肌酸激酶、红细胞沉降率及超敏C反应蛋白均处于正常范围。1例患者发病时肌肉活检示小血管炎性病理改变。6例患者中5例接受足量激素(1 mgkg)治疗,2例接受大剂量激素冲击(甲泼尼龙1 gd)联合静脉用人免疫球蛋白治疗,50%(36)患者最终完全缓解。结论成人PMDM患者合并CIPO发病机制尚不清楚,不除外与继发血管炎有关,由于病程中通常合并急性消化道出血,临床处理非常困难,总体死亡率高。早期识别并及时给予大剂量糖皮质激素和免疫抑制剂可能有助于改善预后。