Anti-Synthetase Syndrome 1/8/2019

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.

Antibodies.png

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.

meds

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

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s