What is antisynthetase syndrome, also known as (Anti-Synthetase Syndrome)?

From the Guidelines

Antisynthetase syndrome should be treated with immunosuppressive therapy, prioritizing corticosteroids like prednisone as first-line treatment, to improve morbidity, mortality, and quality of life outcomes. This rare autoimmune disorder is characterized by the presence of antibodies against aminoacyl-tRNA synthetases, which are enzymes involved in protein synthesis 1. The condition typically presents with a triad of symptoms: inflammatory myopathy (muscle inflammation), interstitial lung disease, and inflammatory arthritis. Patients may also experience Raynaud's phenomenon, mechanic's hands (cracked, rough skin on the hands), and fever.

Key Characteristics

• The most common antibody associated with this syndrome is anti-Jo-1, though others include anti-PL-7, anti-PL-12, and anti-EJ 1.
• Treatment generally involves immunosuppressive therapy, with corticosteroids like prednisone (starting at 0.5-1 mg/kg/day) as first-line treatment.
• Additional immunosuppressants such as methotrexate (15-25 mg weekly), azathioprine (2-3 mg/kg/day), or mycophenolate mofetil (1-3 g/day) are often added as steroid-sparing agents.
• For severe or refractory cases, rituximab (1000 mg IV on days 1 and 15, repeated every 6 months) or cyclophosphamide may be necessary.

Management Considerations

• Pulmonary involvement requires aggressive treatment as it significantly impacts prognosis.
• Physical therapy is important to maintain muscle strength and function.
• Regular monitoring of muscle enzymes, pulmonary function tests, and imaging is essential to assess disease activity and treatment response.
• Early diagnosis and treatment are crucial to prevent irreversible organ damage and improve long-term outcomes, as highlighted in the study published in the Mayo Clinic Proceedings 1.

From the Research

Clinical Manifestations of Antisynthetase Syndrome

• Antisynthetase syndrome (ASyS) is an autoimmune disease characterized by interstitial lung disease, myositis, and arthritis 2
• Other common clinical manifestations include Raynaud's syndrome, fever, and rashes 2
• The syndrome is associated with the presence of antibodies against various aminoacyl transfer RNA synthetases, including Jo-1 and others 2, 3

Diagnosis and Treatment of Antisynthetase Syndrome

• Diagnosis can be challenging due to variable presentations, and recognition of the syndrome is crucial for appropriate and timely therapy 3
• Treatment strategies should target the most severe and life- or organ-threatening disease manifestations 2
• Common treatments include high-dose prednisone, cyclophosphamide, azathioprine, and tacrolimus 3, 4, 5
• Rituximab has also been shown to be effective in treating AS-related interstitial lung disease, with superior pulmonary progression-free survival at 2 years compared to cyclophosphamide 4

Prognosis and Long-Term Treatment

• Patients with antisynthetase syndrome have a worse prognosis than those with pure inflammatory myopathies, mainly due to interstitial lung disease 6
• Long-term treatment with azathioprine and mycophenolate mofetil can improve lung function and reduce prednisone dose in myositis-related interstitial lung disease 5
• Further research is needed to investigate the pathogenesis of antisynthetase syndrome and identify new therapeutic targets 6