Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists,neurologists and dermatologists

Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.     

Current pharmacological treatment of idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies are uncommon and heterogeneous disorders. Their classification is based on distinct clinicopathologic features. Although idiopathic inflammatory myopathies share some similarities, different subtypes may have variable responses to therapy, so it is very important to distinguish the correct subtype.

There are few randomised, double blind placebo controlled studies to support the current treatment. High dose corticosteroids continue to be the first-line therapy and other immunosupressive drugs are used in refractory cases, as well as steroid-sparing agents.

Some novel therapeutic approaches have emerged as potential treatment including tacrolimus, intravenous immunoglobulin and rituximab, following good outcomes reported in case studies. However, more randomised controlled trials are needed.

This review considers the current and the potential future therapies for inflammatory myopathies.     

Autoantibodies to protein transport and messenger RNA processing pathways: endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes, and GW bodies

Over 50 years ago the lupus erythematosus (LE) cell phenomenon was described and this was quickly followed by the introduction of the LE cell test and indirect immunofluorescence (IIF) to detect antinuclear antibodies (ANA) in clinical laboratories. Recently, attention has turned to the identification of the autoantigens that bind to cytoplasmic organelles such as the Golgi complex, endosomes and other "cytoplasmic somes". Three endosome autoantigens include early endosome antigen 1 (EEA1, 160 kDa), cytoplasmic linker protein-170 (CLIP-170, 170 kDa), and lysobisphosphatidic acid (LBPA). Antibodies to EEA1 were seen in a variety of conditions but approximately 40% of the patients had a neurological disease. Despite the prominence of lysosomes in cells and tissues, reports of autoantibodies are limited to the lysosomal antigen h-LAMP-2 and the cytoplasmic antineutrophil antibodies (cANCA). Autoantigens in the Golgi complex include giantin/macrogolgin, golgin-245, golgin 160, golgin-97, golgin 95/gm130, and golgin-67. More recently, there has been an interest in autoantibodies that bind components of the "SMN complex" or the "assemblyosome". Arginine/glycine (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are antigen targets in a variety of diseases. More recently, components of a novel cytoplasmic structure named GW bodies (GWBs) have been identified as targets of human autoantibodies. Components of GWBs include GW182, a unique mRNA-binding protein, like Sm proteins (LSms), and decapping (hDcp1) and exonuclease (Xrn) enzymes. Current evidence suggests that GWBs are involved in the cytoplasmic processing of mRNAs. Autoantibodies to the "cytoplasmic somes" are relatively uncommon and serological tests to detect most of them are not widely available.     

Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis

Aims and methods: Pulmonary parenchymal disease is common in patients with connective tissue disorders (CTDs). However, most reports precede recognition of non‐specific interstitial pneumonia (NSIP). We have therefore reviewed 54 lung biopsies from 37 patients with polymyositis/dermatomyositis (PM/DM) (n = 13), Sjögren's syndrome (n = 5), rheumatoid arthritis (n = 17) and systemic lupus erythematosus (SLE) (n = 2) to assess the overall and relative frequencies of patterns of interstitial pneumonia and their impact on prognosis. Results and conclusions: NSIP was the most common pattern with an overall biopsy prevalence of 39% and patient prevalence of 41%. There was variation in prevalence between individual CTDs, with PM/DM commonly showing organizing pneumonia (n = 5), rheumatoid arthritis showing follicular bronchiolitis (n = 6) and Sjögren's syndrome showing chronic bronchiolitis (n = 4). These patterns presented either separately or in association with NSIP, occasionally with different patterns in biopsies from separate lobes. Only four patients showed a pattern of usual interstitial pneumonia (UIP): two with rheumatoid arthritis and one each with PM/DM and SLE. Overall mortality was 24%, the most frequently associated pattern being fibrotic NSIP (n = 5). In nine cases, pulmonary presentation preceded the systemic manifestation of the CTDs. When patients with CTDs present with chronic interstitial lung disease, the most common pattern is NSIP, although there is variation in pattern prevalence between individual disorders and patterns of interstitial pneumonia frequently overlap. These data suggest a different biology for intestitial pneumonias in CTDs when compared with the idiopathic interstitial pneumonias where UIP is the most common pattern. Mortality is similar to that seen in idiopathic NSIP and, coupled with pulmonary presentation occurring prior to the systemic manifestation of disease, this may have a bearing on the origin of some cases of putative idiopathic NSIP.     

Feline immunodeficiency virus associated myopathy in the adult cat

Human immunodeficiency virus (HIV-1) associated myopathy can be a debilitating disease in humans, leading to weakness, myalgia, and muscle wasting. Subclinical neuromuscular involvement is also common. A range of histologic lesions have been described in both forms that include both inflammatory and degenerative changes. The purpose of this study was to determine whether a myopathy was present in adult cats experimentally infected with feline immunodeficiency virus (FIV). Six specific pathogen-free, laboratory-housed cats were challenged intravenously with 1000 TCID₅₀ of the Maryland isolate of FIV (FIV-MD) at 8 months of age. The highest serum creatine kinase values were seen at 18 months postinfection (mean 9838, SD 4805 U/L) compared to preinfection (mean 950, SD 374 U/L). Needle EMG studies revealed abnormal spontaneous activity in 2 cats. All FIV-MD infected cats exhibited at least one abnormality in muscle pathology. Of the 24 muscle samples, 15 (63%) had histopathologic lesions. The predominant histologic abnormalities consisted of perivascular and pericapillary lymphocytic infiltration, and myofiber necrosis, phagocytosis, and regeneration. Lymphocytic infiltration was graded 2+ or higher in 12 of 24 muscle samples (0 = negligible; 4+ = extensive). Immunohistochemical phenotypic lymphocyte labeling in all cats demonstrated only CD8+ lymphocyte staining. This report demonstrates the presence of a FIV associated inflammatory myopathy in the adult cat. Several similarities are apparent in comparison to HIV-1 associated polymyositis reported in humans. Future studies in the cat may thus prove useful in elucidating the pathogenesis of retrovirus related myopathy in humans. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1680–1685, 1998     

Magnetic resonance imaging of skeletal muscles in the polymyositis

Magnetic resonance imaging of skeletal muscles was performed in 11 patients with polymyositis. Two types of muscle lesions were revealed. The first, inflammation, showed increased signal intensity on T2-weighted images and iso-intensity on T1-weighted images. The second, fatty replacement, showed increased signal intensity on both images. The coronal sections could elucidate the extension of the lesion in each affected muscle. Inflammation was relatively diffuse, while homogeneous fatty replacement tended to begin at the lower myotendinous junctions. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1463–1466, 1997     

Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis ordermatomyositis: a retrospective study

Background Interstitial lung disease （ILD） is a serious lung complication in polymyositis （PM） and dermatomyositis （DM） which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM （ADM）. Methods From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD （69 patients） and a non-lLD group （128 patients）. The clinical features, laboratory findings, and prognosis were compared. Results The multivariate analysis indicated that older age at onset （OR 1.033, 95%C/1.009-1.058, P=0.007）, fever （OR 4.109, 95%CI 1.926-8.767, P 〈0.001） and arthritis/arthralgia （OR 2.274, 95%C/1.101-4.695, P=0.026） were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever （OR 4.912, 95%CI 2.121-11.376, P 〈0.001） was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset （RR 0.122, 95%CI 0.049-0.399, P 〈0.001）, ADM/DM/PM-ILD （RR 0.140, 95%C/0.031-0.476, P=0.002）, cardiac involvement （RR 4.654, 95%CI 1.391-15.577, P=-0.013） and serum albumin level （RR 0.910, 95%CI 0.831-0.997, P=-0.042）. Conclusions Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.     

Diagnosis and classification of idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis‐specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti‐SRP and anti‐HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables.     

多发性肌炎和皮肌炎消化道受累的临床研究

目的:研究多发性肌炎(PM)和皮肌炎(DM)合并消化道受累的发生率、临床表现特点及危险因素.方法:回顾性分析中日友好医院风湿免疫科1986年3月～ 2010年6月住院的192例PM/DM患者的临床表现、辅助检查、实验室参数的特点,比较伴消化道受累与不伴消化道受累的PM/DM患者的差异.结果:192例患者中82例(42.7％)合并消化道受累:其中吞咽功能障碍71例,食道裂孔功能障碍8例,食管炎4例,食道蠕动减弱10例,胃蠕动减弱6例,胃张力减低2例,伪膜性肠炎1例,肠气囊肿1例.在PM和DM中,上述消化道受累类型的发生率无显著性差异.消化道受累组与不合并消化道受累组在诊断、性别方面无统计学差异;前者平均发病年龄小于后者,抬头困难的发生率较后者高,间质性肺疾病的发生率低于后者(均P＜0.05).其他常见临床表现,如四肢无力、Gottron征及向阳性皮疹的发生率、实验室检查中的肌酸激酶、血沉、C反应蛋白的升高程度在2组间无显著差异.结论:发病年龄较轻及有抬头困难的PM/DM患者更易合并消化道受累,而合并肺间质疾病的PM/DM患者消化道受累率相对较低.