The lung in autoimmune disease
- Topic
Connective tissue diseases can scar the interstitium, inflame the pleura, form nodules or narrow the pulmonary arteries.
What it is
Systemic autoimmune (connective tissue) diseases often involve the lung, sometimes before the joints or skin. The pleura, airways, interstitium and vessels can all be hit, and several patterns may coexist. NSIP is the most frequent interstitial pattern, with UIP and organizing pneumonia less often. Lung involvement is a leading cause of death in systemic sclerosis.
Structure
- Rheumatoid nodule: central fibrinoid necrosis surrounded by palisading histiocytes and an outer rim of lymphocytes and plasma cells.
- Interstitial disease: NSIP or UIP pattern with lymphoid aggregates and germinal centres, more than in idiopathic forms.
- Pleura: fibrinous pleuritis with effusion, later fibrous thickening.
- Pulmonary hypertension: medial hypertrophy and intimal fibrosis of small arteries.
Step by step
- Autoantibodies and autoreactive T cells target endothelium, epithelium and matrix.
- Immune complexes and complement inflame the pleura and small vessels.
- Chronic interstitial inflammation activates fibroblasts and TGF-β, giving fibrosis.
- In systemic sclerosis endothelial injury and intimal proliferation narrow small pulmonary arteries.
- Drug toxicity (methotrexate) and opportunistic infection add to the picture in treated patients.
Lung patterns by autoimmune disease
| Disease | Main lung lesions | Classic clue |
|---|---|---|
| Systemic sclerosis | NSIP-type fibrosis, pulmonary arterial hypertension | Anti-topoisomerase I (Scl-70) with fibrosis |
| Rheumatoid arthritis | Pleuritis, UIP or NSIP, necrobiotic nodules | Caplan syndrome with dust exposure |
| Systemic lupus erythematosus | Pleuritis and effusion, lupus pneumonitis, alveolar hemorrhage | Painful pleurisy |
| Inflammatory myopathy | NSIP, organizing pneumonia | Anti-synthetase (anti-Jo-1) antibodies |
| Sjögren disease | Lymphocytic interstitial pneumonia, follicular bronchiolitis | Risk of MALT lymphoma |
Clinical notes
- Screen patients with scleroderma for interstitial disease (CT, DLCO) and for pulmonary hypertension (echocardiography).
- A new interstitial lung disease warrants a search for antinuclear, rheumatoid factor, anti-CCP and myositis antibodies.
- In treated patients, consider drug pneumonitis and infection before progression of disease.
Test yourself
Think of the answer, then tap the question to see it.
What is Caplan syndrome?
Rheumatoid arthritis combined with pneumoconiosis, producing multiple, rapidly developing lung nodules.
What are the two main pulmonary causes of death in systemic sclerosis?
Interstitial lung fibrosis, mostly of NSIP pattern, and pulmonary arterial hypertension.
What is the most common thoracic manifestation of lupus?
Pleuritis with or without pleural effusion.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Interstitial Lung Disease (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.