Rheumatoid Arthritis and the Lung

Pulmonary involvement is one of the most frequent extra-articular manifestation of rheumatoid arthritis. 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, hemoptysis, 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 sulphasalazine treatment. Presents with rapid-onset dyspnea 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.

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-associated lung disease in rheumatoid arthritis

• 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, dyspnea 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.

Epidemiology

• 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.

• Approximately 30% to 40% of patients with rheumatoid arthritis demonstrate either radiological or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease.

• 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.

Differential diagnosis

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

Investigations

• 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

Management

• The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results.

• Some patients appear to respond to immunosuppressive or cytotoxic medications but responses are often disappointing.

• Tumor necrosis factor blockade with infliximab has shown promising results but has also been implicated in causing serious lung toxicity.

Prognosis

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

Document References

Turesson C, O'Fallon WM, Crowson CS, et al; Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003 Aug;62(8):722-7. [abstract]

Tomioka R, King TE Jr; Gold-induced pulmonary disease: clinical features, outcome, and differentiation from rheumatoid lung disease. Am J Respir Crit Care Med. 1997 Mar;155(3):1011-20. [abstract]

Anaya JM, Diethelm L, Ortiz LA, et al; Pulmonary involvement in rheumatoid arthritis. Semin Arthritis Rheum. 1995 Feb;24(4):242-54. [abstract]

Roschmann RA, Rothenberg RJ; Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy. Semin Arthritis Rheum. 1987 Feb;16(3):174-85. [abstract]

Saag KG, Kolluri S, Koehnke RK, et al; Rheumatoid arthritis lung disease. Determinants of radiographic and physiologic abnormalities. Arthritis Rheum. 1996 Oct;39(10):1711-9. [abstract]

Vassallo R, Matteson E, Thomas CF Jr; Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-alpha inhibition. Chest. 2002 Sep;122(3):1093-6. [abstract]

Ostor AJ, Crisp AJ, Somerville MF, et al; Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab. BMJ. 2004 Nov 27;329(7477):1266.