Das Anti-Jo-1-Syndrom – eine Sonderform der Myositis mit interstitieller Lungenerkrankung

Zusammenfassung

Erkrankungen des Lungenparenchyms treten häufig im Rahmen von entzündlichen Systemerkrankungen auf. Anti-Synthetase-Antikörper, einschließlich der Anti-Jo-1-Antikörper (Antihistidyl-tRNA-Synthetase), werden bei 25 – 35 % aller Patienten mit einer Myositis nachgewiesen, wobei das Auftreten von Anti-Jo-1-Antikörpern mit 80 % am häufigsten vertreten ist und einen prädiktiven Faktor für die Entwicklung einer interstitiellen Lungenerkrankung (ILE) darstellt. Umgekehrt sind Anti-Jo-1-Antikörper jedoch sehr selten bei ILE. Beim Auftreten von Myositis, Dyspnoe, Fieber, Arthralgien, Mechanikerhänden und/oder einer Raynaud-Symptomatik muss daher differenzialdiagnostisch auch an das Anti-Jo-1-Syndrom gedacht werden. Weitere diagnostische Hinweise ergeben sich aus dem radiomorphologischen Befund im HRCT, dem histopathologischen Muster der Lungenbiopsie (VATS) und evtl. auch dem Nachweis IFN-γ-induzierbarer Chemokine. Die Therapie besteht aus einer Immunsuppression, die nach Fallkontrollstudien häufig zum Erfolg führt. Kontrollierte Studien sind allerdings rar. In dieser Arbeit wird das Anti-Jo-1-Syndrom in einer Übersicht vorgestellt und eine Kasuistik als Beispiel angeführt sowie die verfügbaren Therapieoptionen diskutiert.

Abstract

Interstitial lung disease (ILD) may be associated with systemic inflammatory disorders and autoantibody production. The development of ILD has been described in detail in patients with polymyositis and dermatomyositis. Anti-synthetase antibodies, including anti-Jo-1 antibodies (antihistidyl-tRNA syntase), are found in up to 35 % of patients with myositis, 80 % of which constitute anti-Jo-1 antibodies. The anti-Jo-1 syndrome characteristically presents with myositis, shortness of breath, fever, polyarthritis/arthralgia, mechanic’s hands, dermatomyositis-like skin lesions, signs of a connective tissue disease and/or Raynaud’s phenomenon. ILD is an early diagnostic sign and shows focal infiltrates and an acinar pattern in CT scan. Non-specific interstitial pneumonitis with T-lymphocytic infiltrates in lung histology (VATS) or elevated IFN-γ-inducible chemokines are further indicators for anti-Jo-1 syndrome. Corticosteroids eventually combined with an immunosuppressant drug are often required with reported beneficial effects, although not many therapeutic studies have been performed. Here we present a review of the current literature and a case report on anti-Jo-1 syndrome.

Literatur

• 1 Mills E S, Mathews W H. Interstitial pneumonitis in dermatomyositis.  JAMA. 1956;  160 1467-1470
• 2 Broich P, Jerusalem F. Polymyositis, Dermatomyositis und andere entzündliche Muskelerkrankungen. In: Miehle W, Fehr K, Schattenkirchner M, Tillmann K, Hrsg. Rheumatologie in Praxis und Klinik. 2. Aufl. Stuttgart; Thieme 2000
• 3 Váncsa A, Csípö I, Németh J. et al . Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients.  Rheumatol Int. 2009;  29 989-994
• 4 Nishikai M, Reichlin M. Heterogeneity of precipitating antibodies in polymyositis and dermatomyositis. Characterization of the Jo-1 antibody system.  Arthitis Rheum. 1980;  23 881-888
• 5 Yoshida S, Akizuki M, Mimori T. et al . The precipitating antibody to an acidic nuclear protein antigen, the Jo-1, in connective tissue diseases: a marker for a subset of polymyositis with interstitial pulmonary fibrosis.  Arthritis Rheum. 1983;  26 604-611
• 6 Marguerie C, Bunn C C, Beynon H L. et al . Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes.  Q J Med. 1990;  77 1019-1038
• 7 Dickey B F, Myers A R. Pulmonary disease in polymyositis/dermatomyositis.  Semin Arthritis Rheum. 1984;  14 60-76
• 8 Benbassat J, Gefel D, Larholt K. et al . Prognostic factors in polymyositis/dermatomyositis: a computer-assisted analysis of ninety-two cases.  Arthritis Rheum. 1985;  28 249-255
• 9 Marie I, Hachulla E, Cherin P. et al . Interstitial lung disease in polymyositis and dermatomyositis.  Arthritis Rheum. 2002;  47 614-622
• 10 Marie I, Hachulla E, Cherin P. et al . Opportunistic infections in polymyositis and dermatomyositis.  Arthritis Rheum. 2005;  53 155-165
• 11 Dankó K, Ponyi A, Constantin T. et al . Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features: a longitudinal study of 162 cases.  Medicine. 2004;  83 35-42
• 12 Hengstman G J, van Venrooij W J, Vencovsky J. et al . The relative prevalence of dermatomyositis and polymyositis in Europe exhibits a latitudinal gradient.  Ann Rheum Dis. 2000;  59 141-142
• 13 Weitoft T. Occurrence of polymyositis in the county of Gavleborg, Sweden.  Scand J Rheumatol. 1997;  26 104-106
• 14 Fathi M, Lundberg I E. Interstitial lung disease in polymyositis and dermatomyositis.  Current Opinion in Rheumatology. 2005;  17 701-706
• 15 Rutjes S A, Vree Egberts W T, Jongen P. et al . Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy.  Clin Exp Immunol. 1997;  109 32-40
• 16 Fox S A, Ward B K, Robbins P D. et al . Inclusion body myositis: investigation of the mumps virus hypothesis by polymerase chain reaction.  Muscle Nerve. 1996;  19 23-28
• 17 Leff R L, Love L A, Miller F W. et al . Viruses in idiopathic inflammatory myopathies: absence of candidate viral genomes in muscle.  Lancet. 1992;  339 1192-1195
• 18 Friedman J M, Pachman L M, Maryjowski M L. et al . Immunogenetic studies of juvenile dermatomyositis: HLADR antigen frequencies.  Arthritis Rheum. 1983;  26 214-216
• 19 O‘Hanlon T P, Carrick D M, Arnett F C. et al . Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -DRB1 allelic profiles and motifs define clinicopathologic groups in Caucasians.  Medicine. 2005;  84 338-349
• 20 Chinoy H, Salway F, Fertig N. et al . The UK Adult Onset Myositis Immunogenetic Collaboration (AOMIC). In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype.  Arthritis Res Ther. 2006;  8 R13
• 21 Love L A, Leff R L, Fraser D D. et al . A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.  Medicine Baltimore. 1991;  70 360-374
• 22 Love L A, Miller F W. Noninfectious environmental agents associated with myopathies.  Curr Opin Rheum. 1993;  5 712-718
• 23 Bohan A, Peter J B. Polymyositis and dermatomyositis.  N Engl J Med. 1975;  292 344-347
• 24 Targoff I N. Immune manifestation of inflammatory muscle disease.  Dis Clin North Am. 1994;  20 857-880
• 25 Selva-O’Callaghan A, Labrador-Horrillo M, Solans-Laque R. et al . Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy.  Arthritis Rheum. 2006;  55 791-798
• 26 Fathi M, Dastmalchi M, Rasmussen E. et al . Interstitial lung disease, a common manifestation of newly diagnosed polymyositis and dermatomyositis.  Ann Rheum Dis. 2004;  63 297-301
• 27 La Corte R, Lo Mo Naco A, Locaputo A. et al . In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease.  Autoimmunity. 2006;  39 249-253
• 28 Takada K, Nagasaka K, Miyasaka N. Polymyositis/dermatomyositis and interstitial lung disease: a new therapeutic approach with T-cell-specific immunosuppressants.  Autoimmunity. 2005;  38 383-392
• 29 Dalakas M C. Polymyositis and dermatomyositis.  Lancet. 2003;  362 971-982
• 30 Chen I-J, Wu Y-J, Lin C-W. et al . Interstitial lung disease in polymyositis and dermatomyositis.  Clin Rheumatol. 2009;  28 639-646
• 31 Rider L G, Miller F W. Laboratory evaluation of the inflammatory myopathies.  Clin Diagn Lab Immunol. 1995;  2 1-9
• 32 Kalluri M, Sahn S A, Oddis C V. et al . Clinical Profile of Anti-PL-12 Autoantibody.  Chest. 2009;  135 1550-1556
• 33 Arahata K, Engel A G. Monoclonal antibody analysis of mononuclear cells in myopathies: I. Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells.  Ann Neurol. 1984;  16 193-208
• 34 Engel A G, Arahata K. Monoclonal antibody analysis of mononuclear cells in myopathies, II: Phenotypes of autoinvasive cells in polymyositis and inclusion body myositis.  Ann Neurol. 1984;  16 209-215
• 35 Mimori T, Imura Y, Nakashima R. et al . Autoantibodies in idiopathic inflammatory myopathy: an update on clinical and pathophysiological significance.  Curr Opin Rheumatol. 2007;  19 523-529
• 36 Bernstein R M, Morgan S H, Chapman J. et al . Anti-Jo-1 antibody: a marker for myositis with interstitial lung disease.  BMJ Clin Res Ed. 1984;  289 151-152
• 37 Schmidt W A, Wetzel W, Friedlander R. et al . Clinical and serological aspects of patients with anti-Jo-1 antibodies: an evolving spectrum of disease manifestations.  Clin Rheumatol. 2000;  19 371-377
• 38 Hengstman G J, van Engelen B G, van Venrooij W J. Myositis-specific autoantibodies: changing insights in pathophysiology and clinical associations.  Curr Opin Rheumatol. 2004;  16 692-699
• 39 Miller F W. Myositis-specific autoantibodies: touchstones for understanding the inflammatory myopathies.  JAMA. 1993;  270 1846-1849
• 40 Schwarz M I. The lung in polymyositis.  Clin Chest Med. 1998;  19 701-712
• 41 Schnabel A, Reuter M, Biederer J. et al . Interstitial lung disease in polymyositis and dermatomyositis: clinical course and response to treatment.  Semin Arthritis Rheum. 2003;  32 273-284
• 42 Frazier A R, Miller R D. Interstitial pneumonitis in association with polymyositis and dermatomyositis.  Chest. 1974;  65 403-407
• 43 Kang E H, Lee E B, Shin K C. et al . Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.  Rheumatology Oxford. 2005;  44 1282-1286
• 44 Oddis C V, Medsger T A, Cooperstein L A. A subluxing arthropathy associated with the Anti-Jo-1 antibody in polymyositis/dermatomyositis.  Arthritis Rheum. 1990;  33 1640-1645
• 45 Schumacher H R, Schimmer B, Gordon G V. et al . Articular manifestations of polymyositis and dermatomyositis.  Amer J Med. 1979;  67 287-292
• 46 Taylor A J, Wortham D C, Burge J R, Rogan K M. The heart in polymyositis: a prospective evaluation of 26 patients.  Clin Cardiol. 1993;  16 802-808
• 47 Bohan A, Peter J B. Polymyositis and dermatomyositis.  N Engl J Med. 1975;  292 403-407
• 48 Tanimoto K, Nakano K, Kano S. et al . Classification criteria for polymyositis and dermatomyositis.  J Rheumatol. 1995;  22 668-674
• 49 Fathi M, Lundberg I E, Tornling G. Pulmonary Complications of Polymyositis and Dermatomyositis.  Semin Respir Crit Care Med. 2007;  28 451-458
• 50 Epler G R, McLoud T C, Gaensler E A. et al . Normal chest roentgenograms in chronic diffuse infiltrative lung disease.  N Engl J Med. 1978;  298 934-939
• 51 Muller N L, Staples C A, Miller R R. et al . Disease activity in idiopathic pulmonary fibrosis: CT and pathologic correlation.  Radiology. 1987;  165 731-734
• 52 Muller N L, Miller R R, Webb W R. et al . Fibrosing alveolitis: CT-pathologic correlation.  Radiology. 1986;  160 585-588
• 53 Nishimura K, Kitaichi M, Izumi T. et al . Usual interstitial pneumonia: histologic correlation with high-resolution CT.  Radiology. 1992;  182 337-342
• 54 Bonnefoy O, Ferretti G, Calaque O. et al . Serial chest CT findings in interstitial lung disease associated with polymyositis-dermatomyositis.  Eur J Radiol. 2004;  49 235-244
• 55 Lee C S, Chen T L, Tzen C Y. et al . Idiopathic inflammatory myopathy with diffuse alveolar damage.  Clin Rheumatol. 2002;  21 391-396
• 56 Arakawa H, Yamada H, Kurihara Y. et al . Nonspecific interstitial pneumonia associated with polymyositis and dermatomyositis: serial high-resolution CT findings and functional correlation.  Chest. 2003;  123 1096-1103
• 57 Remy-Jardin M, Giraud F, Remy J. et al . Importance of ground-glass attenuation in chronic diffuse infiltrative lung disease: pathologic-CT correlation.  Radiology. 1993;  189 693-698
• 58 Yang Y, Fujita J, Tokuda M. et al . Chronological evaluation of the onset of histologically confirmed interstitial pneumonia associated with polymyositis/dermatomyositis.  Intern Med. 2002;  41 1135-1141
• 59 Wallaert B, Hatron P Y, Grosbois J M. et al . Subclinical pulmonary involvement in collagenvascular diseases assessed by bronchoalveolar lavage: relationship between alveolitis and subsequent changes in lung function.  Am Rev Respir Dis. 1986;  133 574-580
• 60 Tazelaar H D, Viggiano R W, Pickersgill J. et al . Interstitial lung disease in polymyositis and dermatomyositis: clinical features and prognosis as correlated with histologic findings.  Am Rev Respir Dis. 1990;  141 727-733
• 61 Bjoraker J A, Ryu J H, Edwin M K. et al . Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 1998;  157 199-203
• 62 Douglas W W, Tazelaar H D, Hartman T E. et al . Polymyositis-Dermatomyositis associated interstitial lung disease.  Am J Respir Crit Care Med. 2001;  164 1182-1185
• 63 Tansey D, Wells A U, Colby T V. et al . Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis.  histopathology. 2004;  44 585-596
• 64 Bohlmeyer T J, Wu A HB, Perryman M B. Evaluation of laboratory tests as a guide to diagnosis and therapy of myositis.  Rheum Dis Clin N Amer. 1994;  20 240-250
• 65 Bernstein R M. Autoantibodies in myositis.  Baillières clin Neurol. 1993;  2 599-615
• 66 Tillie-Leblond I, Wislez M, Valeyre D. et al . Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset.  Thorax. 2008;  63 53-59
• 67 Zampieri S, Ghirardello A, Iaccarino L. et al . Anti-jo-1 antibodies.  Autoimmunity. 2005;  38 73-78
• 68 Kubo M, Ihn H, Yamane K. et al . Serum KL-6 in adult patients with polymyositis and dermatomyositis.  Rheumatology. 2000;  39 632-636
• 69 Bandoh S, Fujita J, Ohtsuki Y. et al . Sequential changes of KL-6 in sera of patients with interstitial pneumonia associated with polymyositis/dermatomyositis.  Ann Rheum Dis. 2000;  59 257-262
• 70 Ihn H, Asano Y, Kubo M. et al . Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease.  Rheumatology. 2002;  41 1268-1272
• 71 Fujita J, Dobashi N, Tokuda M. et al . Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.  J Rheumatol. 1999;  26 2377-2382
• 72 Gillissen A, Wiechmann V, Jürgens U R. Biomarker in pulmonary disease.  Pneumologie. 2009;  63 439-450
• 73 Oddis C V. Current approach to the treatment of polymyositis and dermatomyositis.  Curr Opin Rheumatol. 2000;  12 492-497
• 74 Nawata Y, Kurasawa K, Takabayashi K. et al . Corticosteroid resistant interstitial pneumonitis in polymyositis/dermatomyositis: prediction and treatment with cyclosporine.  J Rheumatol. 1999;  26 1527-1533
• 75 Yoshida T, Koga H, Saitoh F. et al . Pulse intravenous cyclophosphamide treatment for steroid-resistant interstitial pneumonitis associated with polymyositis.  Intern Med. 1999;  38 733-738
• 76 Sakamoto N, Mukae H, Fujii T. et al . Nonspecific interstitial pneumonia with poor prognosis associated with amyopathic dermatomyositis.  Intern Med. 2004;  43 838-842
• 77 Kashiwabara K, Ota K. Rapidly progressive interstitial lung disease in a dermatomyositis patient with high levels of creatine phosphokinase, severe muscle symptoms and positive anti-Jo-1 antibody.  Intern Med. 2002;  41 584-588
• 78 Tomsic M, Sifrer F. Acute respiratory distress syndrome in a polymyositis patient with the anti-Jo-1 antibody.  Wien Klin Wochenschr. 2000;  112 728-731
• 79 Bunch T W. Prednisone and azathioprine for polymyositis.  Arthritis Rheum. 1981;  24 45-48
• 80 Schnabel A, Reuter M, Gross W L. Intravenous pulse cyclophosphamide in the treatment of interstitial lung disease due to collagen vascular diseases.  Arthritis Rheum. 1998;  41 1215-1220
• 81 Yamasaki Y, Yamada H, Yamasaki M. et al . Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis.  Rheumatology. 2007;  46 124-130
• 82 Shinohara T, Hidaka T, Matsuki Y. et al . Rapidly progressive interstitial lung disease associated with dermatomyositis responding to intravenous cyclophosphamide pulse therapy.  Intern Med. 1997;  36 519-523
• 83 Dalakas M C. Polymyositis, dermatomyositis and inclusion body myositis.  N Engl J Med. 1991;  325 1487-1498
• 84 Sauty A, Rochat T, Schoch O D. et al . Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies.  Eur Respir J. 1997;  10 2907-2912
• 85 Sauty A, Rochat T, Schoch O D. et al . A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis.  N Engl J Med. 1993;  329 1993-2000
• 86 Selva-O’Callaghan A, Labrador-Horrillo M, Munoz-Gall X. et al . Polymyositis/dermatomyositis–associated lung disease: analysis of a series of 81 patients.  Lupus. 2005;  14 534-542
• 87 Wilkes M R, Sereika S M, Fertig N. et al . Treatment of antisynthetase-associated interstitial lung disease with tacrolimus.  Arthritis Rheum. 2005;  52 2439-2446
• 88 Oddis C V, Sciurba F C, Elmagd K A, Starzl T E. Tacrolimus in refractory polymyositis with interstitial lung disease.  Lancet. 1999;  353 1762-1763
• 89 Dawson J K, Abernethy V E, Lynch M P. Effective treatment of anti Jo-1 antibodypositive polymyositis with cyclosporin.  Br J Rheumatol. 1997;  36 144-145
• 90 Majmudar S, Hall H A, Zimmermann B. Treatment of adult inflammatory myositis with rituximab: an emerging therapy for refractory patients.  Clin Rheumatol. 2009;  15 338-340
• 91 Mino M, Noma S, Taguchi Y. et al . Pulmonary involvement in polymyositis and dermatomyositis: sequential evaluation with CT.  AJR Am J Roentgenol. 1997;  169 83-87
• 92 Plotz P H, Rider L G, Targoff I N. et al . NIH conference. Myositis: immunologic contributions to understanding cause, pathogenesis, and therapy.  Ann intern Med. 1995;  122 715-724
• 93 Miller F W. Classification and prognosis of inflammatory muscle disease.  Rheum Dis Clin N Amer. 1994;  20 811-826
• 94 Fujisawa T, Suda T, Nakamura Y. et al . Differences in clinical features and prognosis of interstitial lung diseases between polymyositis and dermatomyositis.  J Rheumatol. 2005;  32 58-64
• 95 Haslam P L, Turton C W, Lukoszek A. et al . Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.  Thorax. 1980;  35 328-339
• 96 Zantos D, Zhang Y, Felson D. The overall and temporal association of cancer with polymyositis and dermatomyositis.  J Rheumatol. 1994;  21 1855-1859
• 97 Callen J P. Myositis and malignancy.  Curr Opin Rheumatol. 1994;  6 590-594
• 98 Vencovský J, Jarosová K, Machácek S. et al . Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis.  Scand J Rheumatol. 2000;  29 95-102
• 99 Sem M, Molberg O, Lund M B, Gran J T. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series.  Rheumatology. 2009;  48 968-971
• 100 Hayashi S, Tanaka M, Kobayashi H. et al . High-resolution computed tomography characterization of interstitial lung diseases in polymyositis/dermatomyositis.  J Rheumatol. 2008;  35 260-269
• 101 Atzeni F, Doria A, Carrabba M. et al . Potential target of infliximab in autoimmune and inflammatory diseases.  Autoimmun Rev. 2007;  6 529-536
• 102 Suzuki Y, Hayakawa H, Miwa S. et al . Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis.  Lung. 2009;  187 201-206