Antisynthetase Syndrome

Antisynthetase syndrome (ASyS) is an autoimmune disease with antibodies against aminoacyl tRNA synthetases (anti-Jo-1 most common, also PL-7, PL-12, EJ, OJ, KS, Zo, Ha) and the triad of interstitial lung disease, myositis and arthritis.

• Also features Raynaud phenomenon, mechanic's hands, fever.

• Interstitial lung disease is the major determinant of prognosis (present in 70 to 90%), with NSIP and organising pneumonia patterns.

• Anti-Jo-1 associates with myositis and arthritis; anti-PL-7/PL-12 with more severe lung disease and less myositis.

• Dyspnoea, dry cough, bibasal crackles; subacute or acute respiratory failure possible.

• Proximal muscle weakness, myalgia, dysphagia.

• Symmetric non-erosive arthritis, mechanic's hands (fissured, hyperkeratotic skin of fingers), Raynaud, fever, weight loss.

• Dermatomyositis skin signs in a minority.

• Antisynthetase antibodies by immunoblot (confirm; some are missed by ANA); ANA cytoplasmic pattern, anti-Ro52 often co-present (associates with severe ILD).

• CK, aldolase, AST/ALT, LDH, ESR/CRP.

• HRCT chest, full pulmonary function with DLCO, six minute walk test.

• Muscle MRI, EMG, and muscle biopsy (perifascicular necrosis, perimysial inflammation) when myositis.

• Exclude malignancy screen (low risk but appropriate), infection, drug-induced lung disease.

• Induction: prednisolone 0.5 to 1 mg/kg/day (or methylprednisolone 500 to 1000 mg IV for 3 days in severe ILD) with a steroid-sparing agent from the start: mycophenolate mofetil 1 to 1.5 g twice daily, azathioprine 2 to 2.5 mg/kg, or tacrolimus 0.075 mg/kg/day (trough 5 to 10 ng/mL; useful in ILD).

• Severe or refractory ILD: rituximab 1 g on days 1 and 15, cyclophosphamide 0.5 to 1 g/m2 monthly for 6 months, IVIG 2 g/kg monthly, tocilizumab, JAK inhibitor.

• Progressive fibrosing ILD: nintedanib 150 mg twice daily.

• Myositis: methotrexate 15 to 25 mg weekly, IVIG; physiotherapy.

• Pneumocystis prophylaxis (co trimoxazole 960 mg three times weekly), bone protection, vaccination.

• Oxygen, pulmonary rehabilitation; lung transplant referral in end stage.

• Monitor CK, spirometry, DLCO every 3 months.