Jonathan presented a case of a 39yo M with no significant medical history, presenting with 1 month of non-improving dry cough, dyspnea on exertion, subjective fevers, and leg weakness. His CK was significantly elevated on admission to 27k, and CXR revealed peri-hilar lung base opacities which could represent pneumonia. His exam was significant for debilitating proximal muscle weakness (distal strength was intact!) with hyporreflexia. Ultimately Anti-Jo1 antibodies returned positive, and CT Cx revealed predominantly lower lobe GGO without evidence of honeycombing or traction atelectasis. This constellation of findings (myopathy, lung pathology, anti-synthetase antibody positivity) is consistent with Anti-synthetase syndrome!

Anti-synthetase syndrome

Epidemiology

• Up to 30% of patients with DM or PM will have this constellation of clinical findings, terms Anti-Synthetase syndrome.
• More acute onset of the following:

Presentation: Often acute

• Constitutional symptoms i.e. fever
• Myositis
• Raynaud’s phenomenon
• Mechanic hands
• Non-erosive arthritis
• ILD: Often severe and rapidly progressive, frequently predominates other symptoms
• Cardiac arrhythmias or ventricular dysfunction

Diagnosis

• Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
• Antibodies:
  • Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
  • Anti-PM-Scl
  • Anti-U1 RNP
  • Anti PL-7 & PL12 (seen in pts with predominantly ILD sx, often very severe)
  • If antiRo or ANA present, suspect more of an myositis associated ILD
• CT:
  • Most common findings are traction bronchiectasis, GGO
• Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.

Management

• Often requires multiple immunosuppressives for symptomatic control.
• First line: Corticosteroids, monotherapy associated with more frequent lung disease recurrence
• Other agents often added i.e. azathioprine, mycophenolate, tacrolimus, rituximab, cyclophosphamide.

Monitoring

• Chronic steroids: osteoporosis, PJP prophylaxis if > 20mg > 1 month
• Hep B reactivation
• Azathioprine: Check TPMT levels!

Prognosis

• Not associated with inc risk of malignancy
• Anti PL7 and PL12 are associated with more aggressive ILD, and worse prognosis.
• Presence of Anti-Jo1 and arthritis/myositis are actually good prognostic indicators.
  • Single center study: 10 year survival for Anti-Jo1 was 70%, vs 49% for non-Jo1