Uncommon autoimmune syndrome characterized by autoantibodies against aminoacyl-tRNA synthetases, leading to a classic triad of myositis (inflammatory muscle disease), interstitial lung disease (ILD), and non-erosive arthritis; often accompanied by mechanic's hands, Raynaud phenomenon, and fever.
Rare (~1–3 per 100,000) but potentially severe: most patients develop ILD (the major cause of morbidity), with more severe lung involvement and higher mortality than other myositis syndromes. Early recognition can prevent progressive pulmonary fibrosis. Frequently tested on boards as a prototypical multi-system autoimmune condition associated with anti-Jo-1 antibodies.
Typically affects adults in mid-life (female > male, ~2:1).
Mechanic's hands (hyperkeratotic, cracked skin on fingertips and lateral fingers), Raynaud episodes (finger color changes in cold), and low-grade fevers often accompany the triad.
On lung exam, Velcro-like crackles may be heard (from ILD). Labs: elevated CK and other muscle enzymes (reflecting muscle damage). Many patients are ANA-positive and have a myositis-specific autoantibody (anti-Jo-1 is most common).
Confirm muscle involvement: check CK and other muscle enzymes (often very high). Obtain EMG or MRI to document myositis and guide a biopsy site if needed.
Serologic testing: order ANA and a myositis antibody panel. A positive anti-Jo-1 (anti-histidyl-tRNA synthetase) or other antisynthetase antibody strongly supports the diagnosis.
Pulmonary evaluation: perform PFTs (expect a restrictive pattern) and high-resolution CT (HRCT) of the chest to assess ILD (often shows an NSIP pattern with ground-glass opacities).
Consider tissue diagnosis: muscle biopsy (or lung biopsy in atypical cases) can confirm inflammatory myopathy or ILD and exclude other causes.
Condition
Distinguishing Feature
Polymyositis
idiopathic inflammatory myopathy causing proximal weakness but without specific antisynthetase antibodies; ILD can occur but is less common/severe
Dermatomyositis
myositis with characteristic skin findings (heliotrope rash, Gottron papules) instead of mechanic's hands; distinct autoantibodies and higher malignancy risk
Idiopathic pulmonary fibrosis
progressive fibrosing ILD (usual interstitial pneumonia pattern) in older adults, with no associated muscle weakness or autoantibodies
High-dose corticosteroids (e.g. prednisone ~1 mg/kg/day) to rapidly suppress muscle and lung inflammation. Severe cases may receive IV methylprednisolone pulses.
Steroid-sparing immunosuppressants are introduced early: e.g. methotrexate or azathioprine for muscle/joint disease, and mycophenolate mofetil or tacrolimus for ILD involvement (to improve lung function and allow steroid taper).
Refractory or severe cases: cyclophosphamide (for rapidly progressive ILD) or rituximab (B-cell therapy often used for resistant myositis/ILD). IVIG is an option for difficult-to-treat myositis.
Joe the Mechanic mnemonic: anti-Jo-1 → think of a mechanic named Joe who has cracked, greasy hands (mechanic's hands), inhaled fumes causing lung damage (ILD), and strained muscles from heavy work (myositis).
Signs of rapidly progressive ILD (worsening hypoxia, new extensive fibrosis on HRCT) – high risk of respiratory failure; requires aggressive immunosuppression (e.g. cyclophosphamide).
Pulmonary hypertension or cor pulmonale developing in ASyS – indicates advanced pulmonary involvement; consider early lung transplant evaluation.
Unexplained myositis + ILD + arthritis (any two) → suspect antisynthetase syndrome (especially if mechanic's hands or Raynaud present).
Check muscle enzymes (CK, aldolase) and obtain a myositis autoantibody panel (look for anti-Jo-1 or other anti-tRNA synthetase antibodies).
If positive (or high suspicion): confirm organ involvement – get HRCT chest for ILD and EMG/MRI for muscle inflammation; perform a muscle biopsy if diagnosis is uncertain.
Start high-dose corticosteroids promptly to treat muscle and lung inflammation. Add a second agent (e.g. methotrexate for myositis or mycophenolate for ILD) early for a steroid-sparing effect.
Monitor PFTs and clinical status frequently. If lung function declines or muscle weakness progresses despite therapy, escalate treatment (add rituximab or cyclophosphamide; consider expert referral).
Middle-aged woman with gradually worsening shoulder and hip weakness, a chronic dry cough, and rough, cracked skin on her fingers (image) – labs show ↑CK and positive anti-Jo-1 → Antisynthetase syndrome.
Patient with unexplained ILD (progressive dyspnea, basal crackles) and inflammatory arthritis, plus "mechanic's hands" on exam → suspect antisynthetase syndrome (myositis may be mild or delayed in onset).
Case 1
A 50‑year‑old woman presents with 3 months of progressive muscle weakness and dry cough.
Case 2
A 55‑year‑old man with a 6-month history of cough and dyspnea is found to have interstitial lung disease on imaging.
High-resolution CT of the lungs showing an NSIP pattern (patchy ground-glass opacities) in antisynthetase syndrome.
