今日の臨床サポート

皮膚筋炎、多発性筋炎

著者: 山下裕之 国立国際医療研究センター 膠原病科

監修: 金子礼志 国立国際医療研究センター 膠原病科

著者校正/監修レビュー済:2020/06/19
患者向け説明資料

概要・推奨   

  1. 将来、特発性炎症性筋疾患(idiopathic inflammatory myopathies)と統一された病名になる可能性がある。
 
  1. 多発性筋炎(PM)・皮膚筋炎(DM)の診断基準として、Bohan & Peterの分類、または厚生省の診断基準を用いることが推奨される(推奨度2)
  1. 多発性筋炎(PM)・皮膚筋炎(DM)の病像は多様で、その病型分類は治療法の選択、予後の推定に有用である(推奨度1)
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  1. 多発性筋炎および皮膚筋炎は悪性腫瘍合併の可能性が通常より高く、筋炎発症時および発症後において悪性腫瘍検索を行うことが推奨される。また、悪性腫瘍合併筋炎は原発性筋炎と異なる点が多く、治療方針が異なり、基本的に悪性腫瘍の治療が優先されるため、それが疑われた場合は抗TIF1-γ抗体の測定も推奨される(推奨度2)。
  1. 抗ARS抗体(抗Jo-Ⅰ抗体など)、抗SRP抗体(保険適応外)、抗TIF1-γ抗体などの筋炎特異抗体は特発性炎症性筋炎の臨床的診断、分類、予後予測因子にとって有用なマーカーであり、その測定が強く推奨される(推奨度1)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
山下裕之 : 特に申告事項無し[2021年]
監修:金子礼志 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報  
  1. 多発性筋炎(PM)は、四肢近位筋・頚部対称性筋力低下を来す原因不明の慢性炎症性疾患である。筋炎に特徴的な皮膚症状を伴う場合は皮膚筋炎(DM)と呼ばれる。
  1. 日本の年間発病率は5~10人/100万人、有病率は2~5人/10万人程度で、成人では1:2の割合で女性に多いが小児では性差はない。あらゆる年齢層に発症するが、小児期(5~14歳)と成人期(35~64歳)にピークを持つ2峰性分布を示す。
  1. PM/DMの診断は臨床症状(筋力低下、特徴的な皮膚症状)と検査成績(血清筋原性酵素、筋電図、筋生検)を組み合わせ、総合的に判断する。
  1. 一般的に診断基準として使用されているものには、Bohan & Peterによる診断基準および厚生省自己免疫疾患調査研究班の改訂診断基準(2015年)がある。
  1. 皮膚筋炎/多発性筋炎は、指定難病であり、研究班による分類基準を用い、①~④のいずれかに該当する場合などでは、申請し認定されると保険料の自己負担分の一部が公費負担として助成される。([平成27年1月施行])
  1.  難病法に基づく医療費助成制度 
 
  1. 多発性筋炎(PM)・皮膚筋炎(DM)の診断基準として、Bohan & Peterの分類、または厚生省の診断基準を用いることが推奨される(推奨度2)
  1. 多発性筋炎(PM)は、四肢近位筋・頚部対称性筋力低下を来す原因不明の慢性炎症性疾患で、筋炎に特徴的な皮膚症状を伴う場合には皮膚筋炎と呼ばれる。
  1. わが国の年間発病率は5~10人/100万人、有病率は2~5人/10万人程度で、成人では1:2の割合で女性に多いが小児では性差はない。あらゆる年齢層に発症するが、小児期(5~14歳)と成人期(35~64歳)にピークを持つ二峰性分布を示す。
  1. PM/DMの診断は臨床症状(筋力低下、特徴的な皮膚症状)および検査成績(血清筋原性酵素、筋電図、筋生検)を組み合わせ、総合的に判断する。
  1. 一般的に診断基準として汎用されているのは、Bohan & Peterによる診断基準[1]および厚生省自己免疫疾患調査研究班の改訂診断基準(2015年)[2]がある。
  1. 下に「多発性筋炎/皮膚筋炎の改訂診断基準(厚生労働省、2015年)」を示す。
  1. 診断基準項目
  1. 皮膚症状
  1. a)ヘリオトロープ疹 b)ゴットロン徴候 c)ゴットロン丘疹
  1. 上肢または下肢の近位筋の筋力低下
  1. 筋肉の自発痛または把握痛
  1. 血清中筋原酵素(CKまたはアルドラーゼ)の上昇
  1. 筋電図の筋原性変化
  1. 骨破壊を伴わない関節炎または関節痛
  1. 全身性炎症所見
  1. 抗Jo-Ⅰ抗体を含む抗ARS抗体
  1. 筋生検での筋炎の病理所見:筋線維変性および細胞浸潤
  1. 診断基準判定
  1. 皮膚筋炎:1)の皮膚症状a)~c)の1項目以上を満たし、かつ経過中に2~9の項目中4項目以上を満たす
  1. 多発性筋炎:2~9の項目中4項目以上を満たすもの
  1. 鑑別を要する疾患
    感染による筋炎、薬剤性ミオパチー、内分泌異常に基づくミオパチー、筋ジストロフィーそのほかの先天性筋疾患
  1. この診断基準を使用すると、皮膚症状の1項目を満たし、ほかの4項目を満たした場合の専門医の皮膚筋炎の診断に対する感度は94.1%、皮膚症状以外の4項目を満たせば多発性筋炎に対する感度は98.9%、両者の特異度は95.2%であった。
  1. このことより、PM/DMの診断基準としては、厚生省の診断基準(またはBohen&Peter)を用いることが推奨される。
  1. 診断基準を満たしながら、最終診断が異なった例として、皮膚筋炎に特徴的な皮疹に類似した症状を呈し、CK上昇を伴い、さらに筋電図所見および筋生検にて筋炎所見を認め、皮膚筋炎の診断基準を満たしていたが、症状一過性で対症療法で自然治癒したウイルス性筋炎と思われた症例や、当初、筋痛・近位筋有意の筋力低下、CK上昇などを認め「多発性筋炎/皮膚筋炎の改訂診断基準(厚生労働省、2015年)」上、多発性筋炎の診断基準を満たすものの、結果的に糖原病(McArdle病)であった1例などがあった。
問診・診察のポイント  
ポイント:
  1. 1)筋炎の進行速度、2)筋力低下・筋痛の訴えと罹患分布、3)皮膚筋炎の皮膚症状の特徴、4)間質性肺炎の合併、5)悪性腫瘍の合併、6)その他の症状――の6つの症状に、特に注意しながら診察する。
  1. 筋炎の進行速度:
  1. 多発性筋炎の進行速度は患者によって非常に不均一で、年余にわたって診断されずに歩行・立ち上がり困難のまま生活していたという例がある一方で、週単位で体重減少(筋量低下)、歩行不能、嚥下障害(誤嚥・窒息の危険)、換気障害に至る例もある。しかし、基本的に急性発症はしない。

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文献 

著者: A Bohan, J B Peter
雑誌名: N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706.
Abstract/Text
PMID 1090839  N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NE・・・
著者: A Bohan, J B Peter, R L Bowman, C M Pearson
雑誌名: Medicine (Baltimore). 1977 Jul;56(4):255-86.
Abstract/Text
PMID 327194  Medicine (Baltimore). 1977 Jul;56(4):255-86.
著者: C D Reimers, M Finkenstaedt
雑誌名: Curr Opin Rheumatol. 1997 Nov;9(6):475-85.
Abstract/Text Myositides are characterized by perivascular and intrafascicular inflammatory infiltrates and often by fiber de- and regeneration. In chronic disease, muscle size decreases, and replacement of muscle parenchyma by adipose and fibrous tissue (and, in childhood myositis, calcifications of the muscles and subcutaneous fat) occurs. Muscle imaging techniques such as ultrasonography and magnetic resonance (MR) imaging facilitate the assessment of the type (edema, inflammation, fat, fibrosis, and calcifications), degree, and localization of these alterations. Both methods allow evaluation of the activity, chronicity, and severity of myositis and assist in directing the biopsy site. However, MR imaging is more sensitive in the detection of muscle edema, which is common in the early stages of inflammatory myopathies. In general, MR tomographic features provide more information regarding the differential diagnosis than do creatine kinase activity and even electromyography. Muscle imaging techniques should be considered in the diagnostic evaluation and to assist in treatment of inflammatory myopathies. This paper reviews the value and limitations of muscle imaging in inflammatory myopathies.

PMID 9375276  Curr Opin Rheumatol. 1997 Nov;9(6):475-85.
著者: C Dorph, I Nennesmo, I E Lundberg
雑誌名: J Rheumatol. 2001 Jul;28(7):1591-9.
Abstract/Text OBJECTIVE: To evaluate the diagnostic yield, performance simplicity, and safety of the percutaneous conchotome muscle biopsy technique for clinical and research purposes in an outpatient rheumatology clinic.
METHODS: Biopsies taken by rheumatologists in an outpatient clinic during 1996 and 1997 were evaluated for histopathological and clinical diagnoses.
RESULTS: A total of 149 biopsies were performed on 122 patients. Physicians learned the method easily. Samples were of adequate size and quality to allow for diagnostics. In total 106 biopsies were taken due to different diagnostic suspicions: 24 polymyositis (PM) or dermatomyositis (DM); 43 PM, DM, or vasculitis in addition to another rheumatic condition; 19 systemic vasculitis; and 20 myalgias. Criteria for definite or probable PM/DM were fulfilled in 21 patients, 18 with positive biopsies. Thirteen patients received vasculitis as clinical diagnosis, 3 with positive biopsies. No patient with myalgia had a biopsy with inflammatory changes. Fifteen of 43 rebiopsies performed to assess disease activity had signs of active inflammation. In 48% there were changes in immunosuppressive therapy after biopsy results. Four complications occurred; one was a serious subfascial hematoma.
CONCLUSION: The percutaneous conchotome muscle biopsy technique gives a good size sample that allows for diagnostic evaluation and has a high yield in patients with myositis. It is a simple procedure, easy to learn and to perform, with a low complication rate and minimum discomfort for the patient. The method can preferably be used as a diagnostic tool and to perform repeated biopsies to assess the effect of a given therapy for both clinical and research purposes.

PMID 11469467  J Rheumatol. 2001 Jul;28(7):1591-9.
著者: M E Sayers, S M Chou, L H Calabrese
雑誌名: J Rheumatol. 1992 Sep;19(9):1385-9.
Abstract/Text Inclusion body myositis is characterized by an insidious onset, progressive indolent course, and is generally felt to be refractory to standard therapy for myositis. We reviewed the charts of 32 patients with muscle biopsy findings suggestive of inclusion body myositis. The average time from symptom onset to diagnosis was 37 months, but initially 40% were incorrectly diagnosed. Twenty-eight patients (88%) were classified as definite or probable inclusion body myositis and were treated with various combinations of prednisone and immunosuppressive agents. Sixty-eight percent of those treated experienced a decrement in function and muscle strength. Three patients exhibited longterm improvement while 12 patients experienced delayed progression, defined by short term improvement in strength or a stable functional class, All of these patients received therapy, 5 in the form of methotrexate and prednisone. All untreated patients deteriorated clinically. In summary, (1) inclusion body myositis is a clinically distinct entity which is frequently misdiagnosed initially. (2) While clinical improvement with therapy is rare, our observations support recent reports that therapy may be associated with a slower rate of clinical progression. (3) Optimal therapy remains uncertain, but the use of low dose methotrexate and prednisone may warrant further study.

PMID 1331441  J Rheumatol. 1992 Sep;19(9):1385-9.
著者: Hajime Yoshifuji, Takao Fujii, Shio Kobayashi, Yoshitaka Imura, Yoshimasa Fujita, Daisuke Kawabata, Takashi Usui, Masao Tanaka, Sonoko Nagai, Hisanori Umehara, Tsuneyo Mimori
雑誌名: Autoimmunity. 2006 May;39(3):233-41. doi: 10.1080/08916930600622884.
Abstract/Text In the treatment of polymyositis and dermatomyositis (PM/DM), the complication of interstitial lung disease (ILD) is an important prognostic factor. It has been reported that autoantibodies against aminoacyl-tRNA synthetases (ARS) are strongly associated with ILD. The aim of this study is to examine the correlation between anti-ARS and the clinical course of ILD. We investigated 41 cases of PM/DM with ILD. The response of ILD to corticosteroids (CS) was determined according to the change in respiratory symptoms, image findings, and pulmonary function between, before and 2 months after the treatment. Anti-ARS (anti-Jo-1, PL-7, PL-12, EJ, OJ and KS) antibodies were screened with the RNA immunoprecipitation assay. In the stratification into ILD-preceding, simultaneous and myopathy-preceding types, anti-ARS antibodies were significantly frequent in the ILD-preceding type (p < 0.05). In the stratification into anti-ARS-positive and negative groups, the response of ILD to CS was significantly better in the positive group (p < 0.05). However, recurrence of ILD was significantly more frequent in the positive group (p < 0.01), and 2 year prognoses of pulmonary function (%VC and %DLCO) were not different between the two groups. In conclusion, screening of anti-ARS may be useful to predict late-onset myopathy in ILD-preceding patients and to predict the clinical course of ILD in PM/DM patients.

PMID 16769657  Autoimmunity. 2006 May;39(3):233-41. doi: 10.1080/08916・・・
著者: Margaret R Wilkes, Susan M Sereika, Noreen Fertig, Mary R Lucas, Chester V Oddis
雑誌名: Arthritis Rheum. 2005 Aug;52(8):2439-46. doi: 10.1002/art.21240.
Abstract/Text OBJECTIVE: To assess the efficacy of tacrolimus in patients with anti-aminoacyl-transfer RNA synthetase (anti-aaRS)-associated interstitial lung disease (ILD) and idiopathic inflammatory myopathy (IIM).
METHODS: Ninety-eight patients with anti-aaRS autoantibodies were identified in our IIM cohort of 536 patients. The medical records of 15 patients with anti-aaRS-associated ILD treated with tacrolimus between 1992 and 2003 were retrospectively reviewed. Pulmonary parameters of response included forced vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. Manual muscle testing results, serum creatine kinase (CK) levels, and the daily corticosteroid dosage were used to assess improvement in myositis. Random coefficient modeling considering polynomials of time was used to assess the clinical response to tacrolimus.
RESULTS: All patients, except for 1, who had pure ILD, had definite or probable IIM. Two patients received tacrolimus for fewer than 3 months, and their data were not analyzed. For the remaining 13 patients, the mean age at onset of ILD was 46.9 years, and the mean duration of pulmonary disease was 14.7 months. Twelve patients had anti-histidyl-transfer RNA synthetase autoantibody (anti-Jo-1) and 1 had anti-alanyl-transfer RNA synthetase autoantibody (anti-PL-12). Patients received tacrolimus for an average of 51.2 months. A significant improvement was observed in all pulmonary parameters measured. The serum CK level declined significantly, and 10 patients had either an improvement in muscle strength or maintained normal muscle strength. A statistically significant reduction in the corticosteroid dosage was also observed.
CONCLUSION: Tacrolimus is a well-tolerated and effective therapy for managing refractory ILD and myositis in anti-aaRS-positive patients.

PMID 16052580  Arthritis Rheum. 2005 Aug;52(8):2439-46. doi: 10.1002/a・・・
著者: A Escalante, L Miller, T D Beardmore
雑誌名: J Rheumatol. 1993 Aug;20(8):1340-4.
Abstract/Text OBJECTIVE: To determine the effect of a resistive exercise program in the rehabilitation of patients with polymyositis/dermatomyositis (PM/DM).
METHODS: Five patients participated in a rehabilitation program that included resistive exercises. In 4 of the patients, these exercises were randomly alternated with nonresistive exercise. Each type of exercise was assigned for periods of 2 weeks, and at the end of each one, muscle strength was measured by means of manual muscle testing (MMT), an activities of daily living (ADL) score, and peak isometric torque (PIT) generated by muscle groups in the lower extremities. Creatine phosphokinase (CPK) levels were used to measure disease activity. The acute response to resistive exercise was studied in 4 of the patients by measuring serial levels of CPK following a session on an exercise bicycle.
RESULTS: Of the 4 patients who participated in both types of exercises, 3 experienced increases in strength during both resistive and nonresistive exercise periods. The patient who participated only in resistive exercises had considerable improvements in muscle strength. One patient made no improvements in strength with either type of exercise. None of the patients experienced clinically significant elevations in CPK attributable to either type of exercise. Following a session of resistive exercise, the mean CPK elevation in 4 patients was 7.7%, returning to pre-exercise levels by 8 h in all cases.
CONCLUSIONS: Patients with PM/DM may participate in a rehabilitation program which includes resistive exercises. Such programs may be accompanied by increased strength without clinically significant rises in serum levels of muscle enzymes.

PMID 8230016  J Rheumatol. 1993 Aug;20(8):1340-4.
著者: Yves Troyanov, Ira N Targoff, Jean-Luc Tremblay, Jean-Richard Goulet, Yves Raymond, Jean-Luc Senécal
雑誌名: Medicine (Baltimore). 2005 Jul;84(4):231-49.
Abstract/Text Our objective was to improve the currently imperfect classifications of idiopathic inflammatory myopathies (IIM). In clinical practice, overlap features are common in IIM. This provided a rationale for positioning overlap clinical features at the core of a new classification system. We conducted a longitudinal study of 100 consecutive adult French Canadian patients with IIM. Clinical and laboratory data were obtained by retrospective chart review. Sera were analyzed for autoantibodies (aAbs) by protein A-assisted immunoprecipitation and double immunodiffusion. Overlap aAbs encompassed aAbs to synthetases, systemic sclerosis-associated aAbs, anti-signal recognition particle (SRP) and anti-nucleoporins. Patients were classified both at IIM diagnosis, based on data at presentation, and at the end of follow-up, based on cumulative findings. Three classifications were used: 1) the Bohan and Peter original classification, 2) a new version of that classification as modified by us, and 3) a novel clinicoserologic classification. As investigators were blinded to aAb results, the modified classification is strictly a clinical classification. Its core concept is the attribution of diagnostic significance to the presence of overlap features, that is, their presence resulted in a diagnosis of overlap myositis (OM). This approach allowed direct comparison with the original Bohan and Peter classification. By integrating aAb results to the modified classification, we also defined the clinicoserologic classification, which allowed to examine the added value of aAbs to diagnostic, therapeutic and prognostic stratification. Whereas polymyositis (PM) was the most common IIM according to the original classification, accounting for 45% of the cohort at diagnosis, its frequency fell to 14% with the modified classification. Conversely, while the frequency of myositis associated with connective tissue disease was 24% according to the original classification, the frequency of OM was 60% when using the modified classification. At last follow-up, the frequency of PM fell further to only 9%, while the frequency of OM rose to 67%. Systemic sclerosis was the most common connective tissue disease associated with IIM, accounting for 42.6% of OM patients and 29% of the cohort. The frequencies of overlap aAbs in the cohort and in OM patients were 48% and 70.5% (n =48/68), respectively. The presence of overlap aAbs at IIM diagnosis identified additional OM patients unrecognized by the modified classification. The sensitivity of the modified classification for OM at diagnosis was 87%, suggesting that clinicians may rely on the modified classification for identification of most OM patients, while awaiting results of aAb assays. The new classifications predicted the response to prednisone and IIM course. Using stringent definitions, IIM was classified as responsive or refractory after an adequate initial corticosteroid therapy, and the disease course as monophasic or chronic after a single adequate trial of prednisone. PM was always chronic and was associated with the highest rate (50%) of refractoriness to initial corticosteroid treatment. Dermatomyositis was almost always chronic (92% rate); however, its responsiveness to initial corticosteroid treatment was high (87%). OM was almost always responsive to corticosteroids (89%-100% rates). When OM patients were divided according to aAb subsets, anti-synthetase, SRP, or nucleoporin aAbs were markers for chronic myositis, whereas aAbs to U1RNP, Pm-Scl, or Ku were markers for monophasic myositis. We conclude that the original Bohan and Peter classification should be abandoned as it leads to misclassification of patients. Much of IIM is composed of OM. The proposed modified and clinicoserologic classifications have diagnostic, prognostic, and therapeutic value.

PMID 16010208  Medicine (Baltimore). 2005 Jul;84(4):231-49.
著者: Jessica E Hoogendijk, Anthony A Amato, Bryan R Lecky, Ernest H Choy, Ingrid E Lundberg, Michael R Rose, Jiri Vencovsky, Marianne de Visser, Richard A Hughes
雑誌名: Neuromuscul Disord. 2004 May;14(5):337-45. doi: 10.1016/j.nmd.2004.02.006.
Abstract/Text
PMID 15099594  Neuromuscul Disord. 2004 May;14(5):337-45. doi: 10.1016・・・
著者: Andrew L Mammen
雑誌名: Ann N Y Acad Sci. 2010 Jan;1184:134-53. doi: 10.1111/j.1749-6632.2009.05119.x.
Abstract/Text Dermatomyositis (DM) and polymyositis (PM) are autoimmune myopathies characterized clinically by proximal muscle weakness, muscle inflammation, extramuscular manifestations, and frequently, the presence of autoantibodies. Although there is some overlap, DM and PM are separate diseases with different pathophysiological mechanisms. Furthermore, unique clinical phenotypes are associated with each of the myositis-specific autoantibodies (MSAs) associated with these disorders. This review will focus on the clinical features, pathology, and immunogenetics of PM and DM with an emphasis on the importance of autoantibodies in defining unique phenotypes and, perhaps, as clues to help elucidate the mechanisms of disease.

PMID 20146695  Ann N Y Acad Sci. 2010 Jan;1184:134-53. doi: 10.1111/j.・・・
著者: Hideto Kameda, Hayato Nagasawa, Hiroe Ogawa, Naoya Sekiguchi, Hirofumi Takei, Michihide Tokuhira, Koichi Amano, Tsutomu Takeuchi
雑誌名: J Rheumatol. 2005 Sep;32(9):1719-26.
Abstract/Text OBJECTIVE: Acute/subacute interstitial pneumonia (A/SIP) in patients with polymyositis/dermatomyositis (PM/DM) is frequently fatal within months despite high dose prednisolone (PSL) therapy. Our objective was to improve the survival rate of patients with A/SIP associated with PM/DM; and to characterize patients with PM/DM who are at high risk of developing A/SIP.
METHODS: We conducted a pilot trial of combined immunosuppressive therapy with high dose PSL, 10-30 mg/kg of intravenous pulse cyclophosphamide (IVCYC) every 3-4 weeks, and 2-4 mg/kg/day of cyclosporin A (CSA) for patients with A/SIP. A/SIP was diagnosed based on a history of rapidly worsening respiratory symptoms, progressive radiological findings or hypoxemia, and compatible findings in high resolution computed tomography images.
RESULTS: Before December 2000, 12 patients with DM among 83 PM/DM patients developed A/SIP, and 9 patients died despite treatment using high dose PSL with or without a choice of CSA, cyclophosphamide, or azathioprine. Thereafter, 10 patients with DM among 27 PM/DM patients developed A/SIP, and they were given combination therapy with PSL, CSA, and IVCYC. Five patients survived and are doing well for more than 2 years, although the remaining 5 patients died of respiratory failure within 3 months. DM patients with A/SIP showed the following characteristic features: mild myositis, palmar papule, fever, and negative or low titer of antinuclear antibody.
CONCLUSION: Immediate institution of intensified immunosuppressive therapy should be considered for patients with A/SIP complicating DM. However, even early recognition of A/SIP and immediate commencement of a regimen including CSA and IVCYC in addition to high dose PSL may not be sufficient for some of those patients.

PMID 16142867  J Rheumatol. 2005 Sep;32(9):1719-26.
著者: Shinji Sato, Michito Hirakata, Masataka Kuwana, Akira Suwa, Shinichi Inada, Tsuneyo Mimori, Takeji Nishikawa, Chester V Oddis, Yasuo Ikeda
雑誌名: Arthritis Rheum. 2005 May;52(5):1571-6. doi: 10.1002/art.21023.
Abstract/Text OBJECTIVE: To identify novel autoantibodies specific for dermatomyositis (DM), especially those specific for clinically amyopathic DM (C-ADM).
METHODS: Autoantibodies were analyzed by immunoprecipitation in 298 serum samples from patients with various connective tissue diseases (CTDs) or idiopathic pulmonary fibrosis (IPF). Antigen specificity of the sera was further examined by immunoblotting and indirect immunofluorescence (IF). The disease specificity and clinical features associated with the antibody of interest were determined.
RESULTS: Eight sera recognized a polypeptide of approximately 140 kd (CADM-140 autoantigen) by immunoprecipitation and immunoblotting. Immunoreactivity was detected in the cytoplasm, and indirect IF revealed a granular or reticular pattern. Anti-CADM-140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other CTDs or IPF. Interestingly, all 8 patients with anti-CADM-140 antibodies had C-ADM. Among 42 patients with DM, those with anti-CADM-140 autoantibodies had significantly more rapidly progressive interstitial lung disease (ILD) when compared with patients without anti-CADM-140 autoantibodies (50% versus 6%; P = 0.008).
CONCLUSION: These results indicate that the presence of anti-CADM-140 autoantibodies may be a novel marker for C-ADM. Further attention should be directed to the detection of rapidly progressive ILD in those patients with anti-CADM-140 autoantibodies.

PMID 15880816  Arthritis Rheum. 2005 May;52(5):1571-6. doi: 10.1002/ar・・・
著者: Ira N Targoff
雑誌名: Curr Rheumatol Rep. 2006 Jun;8(3):196-203.
Abstract/Text Recent studies have continued to examine the clinical associations of the group of autoantibodies that occurs predominantly in patients who have myositis (antibodies to aminoacyl-tRNA synthetases, to signal recognition particle [SRP], and to the nuclear helicase Mi-2). The anti-synthetase syndrome has been further studied, and the value of tacrolimus in treatment of the associated interstitial lung disease has been noted. The low frequency of myositis specific autoantibodies in non-myositis neuromuscular disorders has been more clearly demonstrated. The clinical associations of anti-Mi-2 and anti-SRP were further studied, and patients with antibodies without myositis were reported. Evidence suggested that ultraviolet light exposure may influence the expression of dermatomyositis and anti-Mi-2. A new classification for myositis using overlap clinical features and autoantibodies was proposed. A new autoantibody, anti-caDM-140, was described, associated with clinically amyopathic dermatomyositis and interstitial lung disease. The possibility was raised that increased antigen expression in regenerating muscle may help to perpetuate the disease. These antibodies continue to be the subject of active investigation.

PMID 16901077  Curr Rheumatol Rep. 2006 Jun;8(3):196-203.
著者: M M Joffe, L A Love, R L Leff, D D Fraser, I N Targoff, J E Hicks, P H Plotz, F W Miller
雑誌名: Am J Med. 1993 Apr;94(4):379-87.
Abstract/Text PURPOSE: To identify factors associated with responses to treatment with prednisone, methotrexate, or azathioprine in patients with idiopathic inflammatory myopathy, and to compare the efficacy of these drugs.
PATIENTS AND METHODS: Data were collected on 113 adult patients meeting criteria for definite idiopathic inflammatory myopathy in this retrospective cohort study. Patients were categorized as responding completely, partially, or not at all to each therapeutic trial based upon clinical and laboratory criteria.
RESULTS: Clinical group, presence of certain myositis-specific autoantibodies, and time from disease onset to diagnosis influenced rates of complete clinical response to these therapeutic agents. Patients with inclusion body myositis responded comparatively poorly to prednisone and the other drugs: 43% had no clinical response to prednisone and none responded completely to any medication. Patients with autoantibodies to aminoacyl-tRNA synthetases or to signal recognition particle proteins were likely to respond partially, but not completely, to prednisone. No patient with a long delay to diagnosis (greater than 18 months) responded completely, compared with 34% of those with a short delay (less than 3 months). A patient's response to the first course of prednisone predicted subsequent responses to prednisone and to azathioprine better than response to methotrexate. Men responded to methotrexate better than women. Among certain subgroups of patients, responses to methotrexate were better than to either azathioprine or retreatment with prednisone.
CONCLUSION: Determining the clinical group, autoantibody status, and time from disease onset to diagnosis of patients with myositis provides useful information in predicting clinical responses to therapy, and these factors should be considered in designing future therapeutic trials. Methotrexate therapy may be superior to either azathioprine or further steroid treatment alone in certain patients who do not respond completely to an initial adequate course of prednisone.

PMID 8386437  Am J Med. 1993 Apr;94(4):379-87.
著者: E D Newman, D W Scott
雑誌名: J Clin Rheumatol. 1995 Apr;1(2):99-102.
Abstract/Text The objective of this study was to evaluate the efficacy of low-dose oral methotrexate (MTX) in improving muscle strength and reducing the corticosteroid requirement of patients with polymyositis (PM) and dermatomyositis (DM). The method used was a retrospective chart review of our clinic's PM/DM cohort, Between September 1989 and May 1993, 12 of 53 patients with PM/DM received low-dose oral MTX (mean maximum dose 14.4 +/- 1.2 mg/wk, range 7.5-20 mg/wk). A significant increase in strength coupled with a fall in prednisone requirement (42.5 +/- 5.8 mg/d to 13.0 +/- 5.4 mg/d) was seen during the mean follow-up time of 24.0 +/- 4.3 months of MTX therapy. The number of flares per year fell from 1.00 +/- 0.35 before oral MTX institution to 0.07 +/- 0.05 during oral MTX therapy. Toxicity was minimal. Three patients were able to stop corticosteroids altogether. Low-dose oral MTX therapy should be considered early in the treatment course of patients with PM/DM to improve strength and lower the required dose of corticosteroids.

PMID 19077954  J Clin Rheumatol. 1995 Apr;1(2):99-102.
著者: Nicolino Ruperto, Angela Pistorio, Sheila Oliveira, Francesco Zulian, Ruben Cuttica, Angelo Ravelli, Michel Fischbach, Bo Magnusson, Gary Sterba, Tadej Avcin, Karine Brochard, Fabrizia Corona, Frank Dressler, Valeria Gerloni, Maria T Apaz, Claudia Bracaglia, Adriana Cespedes-Cruz, Rolando Cimaz, Gerard Couillault, Rik Joos, Pierre Quartier, Ricardo Russo, Marc Tardieu, Nico Wulffraat, Blanca Bica, Pavla Dolezalova, Virginia Ferriani, Berit Flato, Ana G Bernard-Medina, Troels Herlin, Maria Trachana, Antonella Meini, Emma Allain-Launay, Clarissa Pilkington, Veronika Vargova, Carine Wouters, Simona Angioloni, Alberto Martini, Paediatric Rheumatology International Trials Organisation (PRINTO)
雑誌名: Lancet. 2016 Feb 13;387(10019):671-8. doi: 10.1016/S0140-6736(15)01021-1. Epub 2015 Nov 30.
Abstract/Text BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis.
METHODS: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960.
FINDINGS: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study.
INTERPRETATION: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate.
FUNDING: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 26645190  Lancet. 2016 Feb 13;387(10019):671-8. doi: 10.1016/S014・・・
著者: T W Bunch, J W Worthington, J J Combs, D M Ilstrup, A G Engel
雑誌名: Ann Intern Med. 1980 Mar;92(3):365-9.
Abstract/Text A controlled, prospective, double-blind, therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis. Sixteen patients received 60 mg prednisone per day plus either azathioprine (2 mg/kg of body weight per day) or placebo for a period of 3 months. Creatine phosphokinase (CPK) levels fell to normal slightly sooner in the placebo group, but not significantly so. The azathioprine group did not become significantly stronger (P = 0.58) and did not manifest significantly greater improvement of histopathologic features of muscle (P = 0.80) than the placebo group. Initial CPK elevations were significantly related to the degree of muscle inflammation (P = 0.037), but this was not the case at 3 months (P greater than 0.05). Normalization of the CPK could not be equated with disease control. Type II fiber atrophy, attributed to steroid therapy, was more marked in women than in men (P less than 0.03).

PMID 6986827  Ann Intern Med. 1980 Mar;92(3):365-9.
著者: M C Dalakas, I Illa, J M Dambrosia, S A Soueidan, D P Stein, C Otero, S T Dinsmore, S McCrosky
雑誌名: N Engl J Med. 1993 Dec 30;329(27):1993-2000. doi: 10.1056/NEJM199312303292704.
Abstract/Text BACKGROUND: Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.
METHODS: We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies.
RESULTS: The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens.
CONCLUSIONS: High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis.

PMID 8247075  N Engl J Med. 1993 Dec 30;329(27):1993-2000. doi: 10.10・・・
著者: K A Qushmaq, A Chalmers, J M Esdaile
雑誌名: J Rheumatol. 2000 Dec;27(12):2855-9.
Abstract/Text OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CSA) in the treatment of refractory adult polymyositis/dermatomyositis (PM/DM).
METHODS: The province-wide British Columbia database for CSA use for persons with rheumatic diseases at Mary Pack Arthritis Centre was reviewed to identify all patients with PM/DM for the period January 1991 through June 1998. Also, a Medline search of English language literature was conducted for this topic from 1976 until January 1999, using the terms dermatomyositis, polymyositis, inflammatory myopathy, and cyclosporin A, and the reference lists of all papers were screened to include articles not identified by the Medline search.
RESULTS: In British Columbia, 172 CSA users of whom 6 had PM/DM were identified (4 PM, 2 DM). Previous therapy included high dose prednisone (N = 6), methotrexate (N = 4), azathioprine (N = 4), intravenous immunoglobulin (N = 3), and cyclophosphamide (N = 3). The mean CSA dose was 3.5 mg/kg/day. All patients improved. Creatinine kinase (CK) levels declined 52% from baseline. All 6 patients continued CSA a median of 6 months (range 3-44 mo) after initiation of therapy. Toxicity included an increase in serum creatinine > 30% of baseline in 3 patients and hypertension in one patient. The literature review identified an additional 59 cases. Forty-eight (81%) had a reduction in CK levels and improved clinically, 9/59 (15%) developed nephrotoxicity, 5/59 (8%) hypertension responsive to dose reduction, and 9/59 (15%) had hypertrichosis, gingival hyperplasia, or tremor.
CONCLUSION: Our population based experience with 6 patients and the 59 published cases suggests CSA is an effective therapy for resistant PM/DM, and toxicity is possibly more than expected in other rheumatic diseases.

PMID 11128676  J Rheumatol. 2000 Dec;27(12):2855-9.
著者: J Vencovský, K Jarosová, S Machácek, J Studýnková, J Kafková, J Bartůnková, D Nemcová, F Charvát
雑誌名: Scand J Rheumatol. 2000;29(2):95-102.
Abstract/Text OBJECTIVE: To determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active polymyositis (PM) and dermatomyositis (DM).
PATIENTS AND METHODS: Thirty-six patients (20 with DM, 16 with PM) were enrolled into the study and randomized in MTX (n = 17) and CyA (n = 19) groups. Muscle endurance and functional test (MEFT), clinical assessment (CA), global patient's assessment (GPA), muscle MRI, serum CK, myoglobin, IL-1Ra, and autoantibody status were used to assess the response to therapy after 1, 3, and 6 months.
RESULTS: Significant improvement in MEFT, CA, GPA, and muscle MRI was found in both groups. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in the MTX group decreased significantly after 1, 3, and 6 months, whereas a significant reduction in the CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in the CyA group after two weeks, whereas in the MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA, and GPA), none of them showed any correlation with CK or IL-1Ra levels.
CONCLUSIONS: Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.

PMID 10777122  Scand J Rheumatol. 2000;29(2):95-102.
著者: K Maeda, R Kimura, K Komuta, T Igarashi
雑誌名: Scand J Rheumatol. 1997;26(1):24-9.
Abstract/Text Polymyositis and dermatomyositis are inflammatory muscular diseases of unknown etiology which have interstitial pneumonitis as a serious complication. From 1987 to 1994, we used cyclosporine to treat 14 polymyositis/dermatomyositis patients (8 with and 6 without interstitial pneumonitis). In combination with prednisolone, cyclosporine was either added to or substituted for conventional cytotoxic drugs (azathioprine, cyclophosphamide and methotrexate). Cyclosporine was effective against both myositis and interstitial pneumonitis when used early in the course of the disease.

PMID 9057798  Scand J Rheumatol. 1997;26(1):24-9.
著者: C V Oddis, F C Sciurba, K A Elmagd, T E Starzl
雑誌名: Lancet. 1999 May 22;353(9166):1762-3. doi: 10.1016/S0140-6736(99)01927-3.
Abstract/Text
PMID 10347992  Lancet. 1999 May 22;353(9166):1762-3. doi: 10.1016/S014・・・
著者: Kazuki Takada, Kenji Nagasaka, Nobuyuki Miyasaka
雑誌名: Autoimmunity. 2005 Aug;38(5):383-92. doi: 10.1080/08916930500124023.
Abstract/Text Interstitial lung disease (ILD) is a common complication of polymyositis (PM) and dermatomyositis (DM), and accounts for a significant proportion of their morbidity and mortality because of the resistance to therapeutic agents including corticosteroids. Its pathogenic mechanism is not known, but several studies have provided findings implicating that T-cells, especially activated CD8+ cells, may play essential roles, and thus could be therapeutic targets in this disease. To test this hypothesis, we began clinical investigation of the efficacy of T-cell-specific immunosuppressants, cyclosporine (CsA) and FK506, in PM/DM patients with ILD. In our retrospective nationwide multi-center study compiling a total of 53 patients, a combination of CsA and corticosteroids resulted in favorable early and long-term outcome in the majority of patients except for DM patients with acute ILD. In this subset, those who received the combination as an initial therapy had better survival than those who initially received corticosteroids alone. FK506 has a similar mode of action but is up to 100-fold more potent than CsA in vitro, and has been used in more refractory ILD cases. We next reviewed 5 PM/DM patients with ILD who failed on various immunosuppressants including CsA and were subsequently treated with FK506 in our hospital, and found that 3 improved promptly, 1 gradually and steadily, and another case responded slowly after prednisolone dose was increased. None developed adverse effects. In summary, these T-cell targeted therapies have a potential to be the cornerstone of the treatment for ILD in PM/DM patients. The combination therapy with CsA and corticosteroids may be efficacious especially when used early. FK506 may be advantageous even in refractory cases to CsA. These findings indicate that further investigation is warranted. Currently, prospective investigation of FK506 is underway.

PMID 16227154  Autoimmunity. 2005 Aug;38(5):383-92. doi: 10.1080/08916・・・
著者: S Ochi, T Nanki, K Takada, F Suzuki, Y Komano, T Kubota, N Miyasaka
雑誌名: Clin Exp Rheumatol. 2005 Sep-Oct;23(5):707-10.
Abstract/Text Two cases of progressive interstitial lung disease associated with polymyositis/dermatomyositis are presented. Both patients were refractory to conventional therapy with high-dose corticosteroids, cyclosporine, and intermittent pulse cyclophosphamide, and thus a therapeutic trial of tacrolimus was instituted. Tacrolimus was markedly effective in achieving subjective, laboratory and radiographic improvement in both patients.

PMID 16173253  Clin Exp Rheumatol. 2005 Sep-Oct;23(5):707-10.

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