Rheumatoid Arthritis and the Lung

Pulmonary involvement is one of the most frequent extra-articular manifestation of rheumatoid arthritis.¹ Most common lung diseases associated with rheumatoid arthritis are interstitial lung diseases (ILD) and pleural effusions. The range of pulmonary problems includes:

• Rheumatoid nodules:
  • The only pulmonary manifestation specific to rheumatoid arthritis
  • Typically benign but can lead to pleural effusion, pneumothorax, haemoptysis, secondary infection, and bronchopulmonary fistula
• Caplan's syndrome:
  • The combination of rheumatoid arthritis with pneumoconiosis related to mining dust
  • Look for rapid development of multiple basal peripheral nodules in the rheumatoid arthritis patient who has a history of exposure to mining dusts.
  • This can progress to severe pulmonary fibrosis
• Interstitial lung disease:
  • Radiographic findings of ILD occur in 2-5% of patients, while diffusion capacity abnormalities occur in 40%.
  • High resolution CT scan and histology have shown even higher rates, but clinically significant disease probably occurs in 5-10% of rheumatoid patients.
• Bronchiolitis:
  • Bronchiolitis obliterans with organising pneumonia: bilateral parenchymal opacities, often with preserved lung volumes. Typically presents as a relapsing, non-resolving pneumonia that does not respond to antibiotics. Steroids can be curative.
  • Obliterative bronchiolitis: rare, usually fatal condition. Associated with penicillamine, gold, and sulfasalazine treatment. Presents with rapid-onset dyspnoea and dry cough. Fever is uncommon.
• Bronchiectasis:
  • 10% of patients may show radiographic signs of bronchiectasis; it may occur in the absence of ILD.
  • Rheumatoid arthritis patients that get this are more likely to be heterozygous for the CTFR mutation seen in cystic fibrosis.
• Arteritis:
  • Arteritis of the pulmonary artery and lung is rare; signs of systemic vasculitis are usually present.
• Infection:
  • Respiratory infections account for 15 to 20% of deaths in rheumatoid patients.
• Drug toxicity:
  • Acute interstitial pneumonitis may occur in 1-5% of patients treated with methotrexate (see below).
  • Penicillamine and gold may also cause pulmonary complications.²
• Pleural effusions:
  • Common in RA; they are exudative and have a low glucose
  • Occasionally an empyema may develop
• Lung cancer is more common in rheumatoid arthritis patients than in normal control subjects.
• Other diseases:
  • RA patients can get apical fibro-bullous disease (apical fibrotic cavity lesions similar to ankylosing spondylitis).
  • Thoracic cage immobility causing restrictive lung disease
  • Primary pulmonary hypertension (rare); secondary pulmonary hypertension (due to ILD) is more common.

• Methotrexate pneumonitis is an unpredictable and life-threatening side effect of methotrexate therapy.
• Presentation is often subacute with symptoms often present for several weeks or months before diagnosis.
• Presents most often with cough, dyspnoea and fever. May progress rapidly to respiratory failure.
• Early diagnosis, cessation of methotrexate, and treatment with corticosteroids and/or cyclophosphamide are important in management.
• There is a high rate of recurrence of lung injury after re-challenge with methotrexate.

• Although rheumatoid arthritis is more common in women, rheumatoid lung disease occurs more frequently in men who have long-standing rheumatoid disease, positive rheumatoid factor and subcutaneous nodules.³
• Approximately 30% to 40% of patients with rheumatoid arthritis demonstrate either radiological or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease.⁴
• Although rheumatoid arthritis disease activity is important, smoking has been shown to be the most consistent independent predictor of radiological and physiological abnormalities suggestive of ILD in rheumatoid arthritis.⁵

The association of rheumatoid arthritis with lung disease may be due to:

• Rheumatoid-associated lung disease
• Drug-related lung disease secondary to drugs used to treat rheumatoid arthritis
• Infection secondary to immunosuppression
• Coexistent medical conditions

• Blood tests for evaluation of rheumatoid arthritis, including serology
• Respiratory function tests
• Chest x-ray
• Aspiration of pleural fluid
• CT or MRI scan
• Lung biopsy

There have been new guidelines and NICE guidance published recently.^6,7,8,9 These are important guidelines for improvement of the management of RA. They do not include details of the management of lung disease in RA.

• The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results.⁴
• Some patients appear to respond to immunosuppressive or cytotoxic medications but responses are often disappointing.⁴, ¹⁰
• Tumour necrosis factor blockade with infliximab has shown promising results but has also been implicated in causing serious lung toxicity.¹¹

Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis.³