Antisynthetase syndrome (ASS)

• Antisynthetase syndrome (ASS) is an idiopathic inflammatory myopathy and chronic, systemic autoimmune disease with the presence of antisynthetase antibodies such as anti-Jo-1
  • the anti-Jo-1 ASS is characterized by systemic involvement of muscle (myositis), lungs (interstitial lung disease) and articulation (chronic polyarthritis) besides fever, Raynaud's phenomenon and "mechanical hands"
  • ASS is a rare syndrome, its prevalence in the general population is unknown
    
    
  • ASS affects mainly adult individuals at a ratio of 2.3 females : 1 male
    
    
  • ASS can present antibodies against different aminoacyl-tRNA synthetases
    • these cytoplasmatic proteins belong to the enzyme family whose function is to catalyze the bonding of specific aminoacids to respective tRNA
    • the presence of these antibodies is found in approximately 20-40% of polymyositis and 5% of adult dermatomyositis
    • the most frequent is anti-Jo-1 against histidyl-tRNA synthetase
      
      
  • Clinical features
    • clinical manifestation of ASS is relatively homogeneous with one or more of the following features: myositis, interstitial pulmonary disease and articular involvement. The presence of fever, Reynaud's phenomenon and "mechanical hands" may also be observed
      • the muscle feature is found in more than 90% of cases with manifestation of myalgia, muscle weakness, atrophy and fibrosis
        • initially usually proximal muscle involvement
        • changes are evident on muscle biopsy, electromyography and muscle enzyme increases
          
          
      • pulmonary involvement is found in more than 60% of cases and is the main cause of morbidity where this involvement can occur in the absence of muscle features
        • in some cases interstitial pulmonary disease is predominant in ASS
          • can show rapid onset and lead to acute respiratory insufficiency
          • features include dyspnoea, cough, thoracic pain, intolerance to physical exercises and respiratory insufficiency
        • pulmonary radiography images can reveal an interstitial pattern
        • CT scan can reveal a variety of findings -ground-glass pulmonary lesion, linear opacities, consolidations parenchymal, micronodules
        • pulmonary function test shows a restrictive pattern
        • the presence of pulmonary hypertension is reported in the literature and is associated to interstitial pulmonary disease
        • the presence of anti-Ro antibody has been associated to pulmonary fibrosis in ASS
          
          
      • articular involvement affects 50% of cases, with arthralgia and/or arthritis, with or without bone erosions
        
        
      • Raynaud's phenomenon, "mechanical hands", photosensitivity, malar rash may also be present. Cutaneous vasculitis has been also described
        
        
      • cardiac involvement has also been observed, but its prevalence appears not to differ from that of polymyositis/dermatomyositis
        
        
      • mesangial proliferative glomerulonephritis has been described in ASS, where its manifestation is rare and has a good prognosis
        
        
  • Management
    • corticosteroid therapy is the first-line treatment for myositis and also for interstitial pneumopathy in ASS
    • with regard to immunosuppressive use, no consensus has been reached
      • most routinely used immunosuppressives are cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus
        
        
  • Mortality rate ranges from 12 to 40%

Reference:

• 1) Shinjo SK, Levy-Neto M. Anti-Jo-1 antisynthetase syndrome. Rev Bras Reumatol. 2010 Oct;50(5):492-500.