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The Antisynthetase Syndrome

2011; Elsevier BV; Volume: 124; Issue: 9 Linguagem: Inglês

10.1016/j.amjmed.2011.02.010

1555-7162

Harsh C. Patel, Naudia N. Lauder,

Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

The idiopathic inflammatory myopathies are a heterogeneous group of rare chronic autoimmune diseases that include polymyositis and dermatomyositis. Antisynthetase syndrome is recognized as a subset of the idiopathic inflammatory myopathies with a relatively homogenous clinical profile.Case ReportA 43-year-old man presented with diffuse body aches, arthralgias, worsening dyspnea, productive cough, and intermittent fever lasting several months. His medical history was significant for cryptogenic organizing pneumonia that was diagnosed 2 years previously when he presented with flu-like symptoms, cough, and subacute respiratory failure. Since then, he had been maintained on chronic prednisone and continuous home oxygen therapy. On admission, physical examination revealed fine crackles at the lung bases and fissuring/hyperkeratosis of the skin overlying the digital pulps (Figure 1). Initial laboratory results showed a creatinine kinase level greater than 6000 IU/L. Inpatient workup revealed interstitial pulmonary fibrosis and patchy ground-glass opacities on chest computed tomography. An electromyogram of the left biceps muscle was consistent with an irritative myopathy. A muscle biopsy revealed perifascicular atrophy and degeneration. Serologic workup was ultimately positive for the presence of anti-Jo-1 antibodies. Thus, the patient was diagnosed with antisynthetase syndrome. He was treated with a higher dose of prednisone, and azathioprine was initiated. At short-term follow-up, he reported significant improvement in his myalgias and dyspnea.DiscussionAntisynthetase syndrome is characterized by myositis, interstitial lung disease, arthralgias/arthritis, mechanic's hands, fever, and Raynaud's phenomenon. It is associated with autoantibodies against aminoacyl-tRNA synthetases, with anti-Jo-1 being the most commonly found antibody. In the majority of cases, the occurrence of myositis precedes or is concurrent with the development of lung disease. We report a rare manifestation of antisynthetase syndrome in which the pulmonary symptoms predated the onset of dermatomyositis by 2 years. In this case, the diagnosis was missed at the initial presentation because of early absence of antisynthetase antibodies. Sauty et al1Sauty A. Rochart T. Schoch O. et al.Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies.Eur Respir J. 1997; 10: 2907-2912Crossref PubMed Scopus (92) Google Scholar reported similar cases of antisynthetase syndrome-associated interstitial lung disease in which anti-Jo-1 antibodies were not found until 2.5 to 19 months after onset of symptoms. Although fibrosing alveolitis is the most common pulmonary pathology found in antisynthetase syndrome, organizing pneumonia and acute respiratory distress syndrome also have been reported.2Chan W. Ip M. Lau C. et al.Anti-Jo-1 syndrome presenting as cryptogenic organizing pneumonia.Respir Med. 1995; 89: 639-641Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 3Clawson K. Oddis C. Adult respiratory distress syndrome in polymyositis patients with the anti-Jo-1 antibody.Arthritis Rheum. 1995; 38: 1519-1523Crossref PubMed Scopus (52) Google Scholar Our patient initially presented with clinical and radiologic findings suggestive of organizing pneumonia but ultimately developed evidence of fibrosing alveolitis. To our knowledge, this is the first reported case of antisynthetase syndrome with 2 different interstitial lung disease patterns.ConclusionsThis case illustrates the importance of having a high index of suspicion for antisynthetase syndrome in patients with interstitial lung disease. The diagnosis is important because of its prognostic and therapeutic implications. Anti-Jo-1 myositis carries a worse prognosis in comparison with the other inflammatory myopathies. Anti-Jo-1 myositis is less responsive to treatment with corticosteroids, and 60% of patients experience resurgence of disease during steroid tapering.4Love L. Leff R. Fraser 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: 360-374Crossref PubMed Scopus (830) Google Scholar Thus, although corticosteroids are considered the mainstay of treatment, additional immunosuppression is often required to achieve disease control. Commonly used agents include azathioprine, mycophenolate, cyclophosphamide, and calcineurin inhibitors. Comparative efficacy data for the various agents are lacking, and specific indications for their use are mostly based on evidence from case series. Azathioprine seems to be the most frequently used second agent.5Douglas W. Tazelaar H. Hartman T. et al.Polymyositis-dermatomyositis-associated interstitial lung disease.Am J Respir Crit Care Med. 2001; 164: 1182-1185Crossref PubMed Scopus (460) Google Scholar The idiopathic inflammatory myopathies are a heterogeneous group of rare chronic autoimmune diseases that include polymyositis and dermatomyositis. Antisynthetase syndrome is recognized as a subset of the idiopathic inflammatory myopathies with a relatively homogenous clinical profile. Case ReportA 43-year-old man presented with diffuse body aches, arthralgias, worsening dyspnea, productive cough, and intermittent fever lasting several months. His medical history was significant for cryptogenic organizing pneumonia that was diagnosed 2 years previously when he presented with flu-like symptoms, cough, and subacute respiratory failure. Since then, he had been maintained on chronic prednisone and continuous home oxygen therapy. On admission, physical examination revealed fine crackles at the lung bases and fissuring/hyperkeratosis of the skin overlying the digital pulps (Figure 1). Initial laboratory results showed a creatinine kinase level greater than 6000 IU/L. Inpatient workup revealed interstitial pulmonary fibrosis and patchy ground-glass opacities on chest computed tomography. An electromyogram of the left biceps muscle was consistent with an irritative myopathy. A muscle biopsy revealed perifascicular atrophy and degeneration. Serologic workup was ultimately positive for the presence of anti-Jo-1 antibodies. Thus, the patient was diagnosed with antisynthetase syndrome. He was treated with a higher dose of prednisone, and azathioprine was initiated. At short-term follow-up, he reported significant improvement in his myalgias and dyspnea. A 43-year-old man presented with diffuse body aches, arthralgias, worsening dyspnea, productive cough, and intermittent fever lasting several months. His medical history was significant for cryptogenic organizing pneumonia that was diagnosed 2 years previously when he presented with flu-like symptoms, cough, and subacute respiratory failure. Since then, he had been maintained on chronic prednisone and continuous home oxygen therapy. On admission, physical examination revealed fine crackles at the lung bases and fissuring/hyperkeratosis of the skin overlying the digital pulps (Figure 1). Initial laboratory results showed a creatinine kinase level greater than 6000 IU/L. Inpatient workup revealed interstitial pulmonary fibrosis and patchy ground-glass opacities on chest computed tomography. An electromyogram of the left biceps muscle was consistent with an irritative myopathy. A muscle biopsy revealed perifascicular atrophy and degeneration. Serologic workup was ultimately positive for the presence of anti-Jo-1 antibodies. Thus, the patient was diagnosed with antisynthetase syndrome. He was treated with a higher dose of prednisone, and azathioprine was initiated. At short-term follow-up, he reported significant improvement in his myalgias and dyspnea. DiscussionAntisynthetase syndrome is characterized by myositis, interstitial lung disease, arthralgias/arthritis, mechanic's hands, fever, and Raynaud's phenomenon. It is associated with autoantibodies against aminoacyl-tRNA synthetases, with anti-Jo-1 being the most commonly found antibody. In the majority of cases, the occurrence of myositis precedes or is concurrent with the development of lung disease. We report a rare manifestation of antisynthetase syndrome in which the pulmonary symptoms predated the onset of dermatomyositis by 2 years. In this case, the diagnosis was missed at the initial presentation because of early absence of antisynthetase antibodies. Sauty et al1Sauty A. Rochart T. Schoch O. et al.Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies.Eur Respir J. 1997; 10: 2907-2912Crossref PubMed Scopus (92) Google Scholar reported similar cases of antisynthetase syndrome-associated interstitial lung disease in which anti-Jo-1 antibodies were not found until 2.5 to 19 months after onset of symptoms. Although fibrosing alveolitis is the most common pulmonary pathology found in antisynthetase syndrome, organizing pneumonia and acute respiratory distress syndrome also have been reported.2Chan W. Ip M. Lau C. et al.Anti-Jo-1 syndrome presenting as cryptogenic organizing pneumonia.Respir Med. 1995; 89: 639-641Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 3Clawson K. Oddis C. Adult respiratory distress syndrome in polymyositis patients with the anti-Jo-1 antibody.Arthritis Rheum. 1995; 38: 1519-1523Crossref PubMed Scopus (52) Google Scholar Our patient initially presented with clinical and radiologic findings suggestive of organizing pneumonia but ultimately developed evidence of fibrosing alveolitis. To our knowledge, this is the first reported case of antisynthetase syndrome with 2 different interstitial lung disease patterns. Antisynthetase syndrome is characterized by myositis, interstitial lung disease, arthralgias/arthritis, mechanic's hands, fever, and Raynaud's phenomenon. It is associated with autoantibodies against aminoacyl-tRNA synthetases, with anti-Jo-1 being the most commonly found antibody. In the majority of cases, the occurrence of myositis precedes or is concurrent with the development of lung disease. We report a rare manifestation of antisynthetase syndrome in which the pulmonary symptoms predated the onset of dermatomyositis by 2 years. In this case, the diagnosis was missed at the initial presentation because of early absence of antisynthetase antibodies. Sauty et al1Sauty A. Rochart T. Schoch O. et al.Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies.Eur Respir J. 1997; 10: 2907-2912Crossref PubMed Scopus (92) Google Scholar reported similar cases of antisynthetase syndrome-associated interstitial lung disease in which anti-Jo-1 antibodies were not found until 2.5 to 19 months after onset of symptoms. Although fibrosing alveolitis is the most common pulmonary pathology found in antisynthetase syndrome, organizing pneumonia and acute respiratory distress syndrome also have been reported.2Chan W. Ip M. Lau C. et al.Anti-Jo-1 syndrome presenting as cryptogenic organizing pneumonia.Respir Med. 1995; 89: 639-641Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 3Clawson K. Oddis C. Adult respiratory distress syndrome in polymyositis patients with the anti-Jo-1 antibody.Arthritis Rheum. 1995; 38: 1519-1523Crossref PubMed Scopus (52) Google Scholar Our patient initially presented with clinical and radiologic findings suggestive of organizing pneumonia but ultimately developed evidence of fibrosing alveolitis. To our knowledge, this is the first reported case of antisynthetase syndrome with 2 different interstitial lung disease patterns. ConclusionsThis case illustrates the importance of having a high index of suspicion for antisynthetase syndrome in patients with interstitial lung disease. The diagnosis is important because of its prognostic and therapeutic implications. Anti-Jo-1 myositis carries a worse prognosis in comparison with the other inflammatory myopathies. Anti-Jo-1 myositis is less responsive to treatment with corticosteroids, and 60% of patients experience resurgence of disease during steroid tapering.4Love L. Leff R. Fraser 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: 360-374Crossref PubMed Scopus (830) Google Scholar Thus, although corticosteroids are considered the mainstay of treatment, additional immunosuppression is often required to achieve disease control. Commonly used agents include azathioprine, mycophenolate, cyclophosphamide, and calcineurin inhibitors. Comparative efficacy data for the various agents are lacking, and specific indications for their use are mostly based on evidence from case series. Azathioprine seems to be the most frequently used second agent.5Douglas W. Tazelaar H. Hartman T. et al.Polymyositis-dermatomyositis-associated interstitial lung disease.Am J Respir Crit Care Med. 2001; 164: 1182-1185Crossref PubMed Scopus (460) Google Scholar This case illustrates the importance of having a high index of suspicion for antisynthetase syndrome in patients with interstitial lung disease. The diagnosis is important because of its prognostic and therapeutic implications. Anti-Jo-1 myositis carries a worse prognosis in comparison with the other inflammatory myopathies. Anti-Jo-1 myositis is less responsive to treatment with corticosteroids, and 60% of patients experience resurgence of disease during steroid tapering.4Love L. Leff R. Fraser 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: 360-374Crossref PubMed Scopus (830) Google Scholar Thus, although corticosteroids are considered the mainstay of treatment, additional immunosuppression is often required to achieve disease control. Commonly used agents include azathioprine, mycophenolate, cyclophosphamide, and calcineurin inhibitors. Comparative efficacy data for the various agents are lacking, and specific indications for their use are mostly based on evidence from case series. Azathioprine seems to be the most frequently used second agent.5Douglas W. Tazelaar H. Hartman T. et al.Polymyositis-dermatomyositis-associated interstitial lung disease.Am J Respir Crit Care Med. 2001; 164: 1182-1185Crossref PubMed Scopus (460) Google Scholar