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Antisynthetase syndrome

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Rapidly progressive antisynthetase lung disease

Increasing oxygen need, tachypnoea or new ground-glass and organising change over days to weeks can progress to respiratory failure even when CK and limb strength are modest.

Action: Admit, support oxygenation, send bacterial, viral and opportunistic microbiology, assess embolic and cardiac causes, and coordinate urgent respiratory-rheumatology high-dose glucocorticoid plus steroid-sparing combination treatment.

Synopsis

Recognise antisynthetase syndrome when interstitial lung disease, myositis, arthritis and characteristic skin or vascular clues cluster, interpret antibody testing carefully, and treat lung-threatening disease with coordinated early combination immunosuppression.

  • Suspect antisynthetase syndrome when ILD clusters with inflammatory myopathy, non-erosive arthritis, Raynaud phenomenon, fever or hyperkeratotic fissured mechanic hands.
  • A patient need not show the full classic triad at presentation; lung disease may precede weakness and CK may remain normal, especially with non-Jo-1 antibodies.
  • Request an experienced myositis antibody panel when phenotype supports it and confirm surprising line-blot results because low-level isolated reactivity can be false.

Key red flags

Rapidly worsening dyspnoea, resting hypoxia, falling FVC or diffuse new HRCT change requires same-day assessment for ILD progression and infection.

Rapidly progressive ILD

Increasing oxygen need and bilateral ground-glass or organising change over days to weeks is an emergency despite modest CK or muscle findings.

Investigation priorities

01
Myositis antibody panelFirst step

Identify an antisynthetase specificity and associated risk phenotype within compatible clinical disease.

Management branches

Diagnostic sequenceConnect lung, muscle, joint and skin

Unexplained ILD or myositis accompanies mechanic hands, arthritis, Raynaud or fever.

  1. Document onset and tempo, occupational and medicine exposures, full skin and joint examination, objective strength, swallowing, cough and respiratory physiology.
  2. Request HRCT, PFT or DLCO, muscle enzymes and phenotype-led myositis antibodies, confirming discordant serology with the laboratory.
Stable active diseaseUse a steroid-sparing lung plan

Clinically meaningful ILD, myositis or arthritis is active without immediate respiratory failure.

Key medicines

PrednisoloneFor active muscle or lung disease, specialists commonly start 0.5–1 mg/kg orally once daily, with lower exposure for milder disease and a documented taper once the steroid-sparing regimen takes effect.
Mycophenolate mofetilStart 500 mg orally twice daily and increase every one to two weeks as tolerated toward 1–1.5 g twice daily under the specialist ILD protocol.
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Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom