- Design
- worldwide physician-reported multicentre registry with multivariable logistic regression and Cox proportional hazards modelling
- Population
- 1,868 patients with anti-synthetase syndrome and 2,043 autoimmune disease controls from 103 centres
- Primary outcome
- prevalence of pulmonary hypertension and its association with all-cause mortality
- Effect
- prevalence 8.9%; 5-year survival 94% overall vs 88.3% with pulmonary hypertension; adjusted HR for death 2.52 (95% CI 1.41-4.53)
Anti-synthetase syndrome is defined clinically by its interstitial lung disease, and surveillance in these patients has followed the lung parenchyma. This worldwide physician-reported registry analysed 1,868 patients with anti-synthetase syndrome against 2,043 controls with other autoimmune diseases, from 103 centres, to establish how often the pulmonary vasculature is involved as well.
Pulmonary hypertension was present in 8.9%. That is higher than in non-anti-synthetase myositis (3%, P < 0.001), rheumatoid arthritis (4%, P = 0.009) and interstitial pneumonia with autoimmune features (3%, P = 0.003), and not significantly different from systemic sclerosis (13%, P = 0.07) or lupus (11%, P = 0.57) — the two diseases in which vascular screening is already routine. In adjusted models the odds were higher than non-anti-synthetase myositis (OR 1.91) and interstitial pneumonia with autoimmune features (OR 3.72), and lower than systemic sclerosis (0.62) and lupus (0.24).
The survival difference is what makes this actionable. Five-year survival was 94% overall and 88.3% among those with pulmonary hypertension, and the association held after adjustment for age, sex and interstitial lung disease (HR 2.52, 95% CI 1.41-4.53). Crucially, that adjustment means the excess mortality is not simply a marker of worse parenchymal disease.
The change is in what the follow-up looks for. A patient with anti-synthetase syndrome whose breathlessness is worsening is usually investigated for progressive interstitial lung disease, and pulmonary hypertension is a separate and treatable explanation that will not be found unless it is sought. Echocardiography as part of the assessment of new or disproportionate breathlessness, and a low threshold for referral where the estimate is raised, follows directly from a prevalence near that of lupus.
- Include echocardiography in the assessment of new or disproportionate breathlessness in anti-synthetase syndrome
- Do not attribute worsening breathlessness to progressive interstitial lung disease without considering the pulmonary vasculature
- Note that the mortality association persisted after adjustment for interstitial lung disease — this is not a marker of worse parenchymal disease
- Treat the prevalence as comparable to lupus, where vascular assessment is already part of practice
- Refer for specialist pulmonary hypertension assessment where echocardiography raises the possibility, rather than observing
Why it matters
Breathlessness in these patients is attributed to the lung parenchyma by default, and the vascular cause is treatable.
Don't overread it
Registry data with physician-reported diagnoses cannot establish true prevalence, and ascertainment differs between the diseases compared.
The statistics, in plain English
A hazard ratio of 2.52 with an interval from 1.41 to 4.53 sits entirely above 1.0, so the association with mortality is secure in direction though imprecise in size. This is a physician-reported registry, so both the diagnosis of pulmonary hypertension and how hard it was looked for vary between the 103 centres — a disease screened for more often in systemic sclerosis will be found more often there, which could understate the gap. The comparison with lupus, P = 0.57, means no difference was detected rather than that the prevalences are equal.
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