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!
- 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
- Raynaud’s phenomenon
- Mechanic hands
- Non-erosive arthritis
- ILD: Often severe and rapidly progressive, frequently predominates other symptoms
- Cardiac arrhythmias or ventricular dysfunction
- Poorly defined as a condition, but in general, diagnostic criteria based on expert consensus is positive antisynthetase antibodies plus at least 1 feature
- Antibodies to aminoacyl-rRNA synthetases (antisynthetase antibodies), i.e. Anti-Jo1 (most common)
- 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
- Most common findings are traction bronchiectasis, GGO
- Diagnosis usually is made by combination of CT findings, serology, PFT, and clinical findings.
- 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.
- Chronic steroids: osteoporosis, PJP prophylaxis if > 20mg > 1 month
- Hep B reactivation
- Azathioprine: Check TPMT levels!
- 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