Pulmonary involvement in systemic disease requires clinicopathological correlation. While the majority of patients will already have a diagnosis of a connective tissue disease before the onset of pulmonary symptoms, a few may not, in which case the features described can be suggestive of an association with a connective tissue disease, prompting the clinician to further work up this possibility. Although there are specific features associated with some of the individual diseases, there are many overlaps; therefore, the exact systemic disease cannot be diagnosed based on lung involvement alone. Common features include a pattern of nonspecific interstitial pneumonia (NSIP) alone or in combination with usual interstitial pneumonia (UIP) and heavy chronic inflammatory infiltrate, often with germinal centers.
Definition
• A chronic autoimmune disease with systemic manifestations, including pulmonary involvement by a variety of pathologies
Clinical features
Epidemiology
• In patients with RA, up to half will have lung disease, about a quarter of which will be clinically significant
• Although RA is more common in women, RA-associated lung disease is more common in men
• Lung disease is more common in RA patients who are also smokers
Presentation
• Lung disease is usually diagnosed in patients with known RA; however, rarely, lung disease can precede other RA manifestations
• Positive serologic test for rheumatoid factor or anti-citrullinated protein antibody
• Shortness of breath and coughing
• Imaging may show ground-glass opacities or reticulonodular pattern on CT
• Lung hyperinflation with dyspnea is suggestive of bronchiolitis obliterans
Prognosis and treatment
• RA patients with lung disease have a worse prognosis than RA patients without lung disease
• RA patients with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) patterns have a better prognosis than those patients with idiopathic UIP or NSIP
• Bronchiolitis obliterans has a worse outcome
• Immunosuppressive therapies for RA, including corticosteroids, methotrexate, and azathioprine
Pathology
Histology
• Pleural involvement is common and can include lymphoid aggregates with germinal centers, fibrosis, fibrin deposition associated with effusion, mesothelial hyperplasia, multinucleated giant cells, and rheumatoid nodules
• Parenchymal lymphoid aggregates with germinal centers, especially around airways and along interlobular septa (follicular bronchiolitis)
• Chronic lung injury patterns (interstitial fibrosis, lymphoplasmacytic interstitial inflammation [i.e., UIP or NSIP patterns]) with superimposed subacute patterns (organizing diffuse alveolar damage, organizing pneumonia, reactive type II pneumocytes)
• Parenchymal rheumatoid nodules (fibrinoid material with palisading histiocytes) and reactive intrapulmonary lymph nodes may be present
• Other findings may include nonnecrotizing vasculitis, capillaritis, secondary pulmonary hypertensive change, secondary amyloidosis, pulmonary hemorrhage, bronchiolitis obliterans, bronchiectasis, eosinophilic infiltrate, and granulomas
• Look for evidence of superimposed drug reaction or infection
Immunopathology/special stains
• IgM and IgG may be demonstrated in the alveolar septa and capillaries by immunofluorescence, although this is not routinely done
Main differential diagnoses
• Idiopathic interstitial pneumonias (UIP, NSIP, organizing pneumonia): should not have prominent lymphoid aggregates with germinal centers and pleural involvement
• Lung disease associated with other connective tissue diseases
• Hypersensitivity pneumonitis
• Other causes of follicular bronchiolitis
• Wegener granulomatosis: c-ANCA positive in 90%; correlates with clinical presentation
Fig 1 Rheumatoid arthritis. Areas of fibrosis with lymphoid aggregates, bronchial metaplasia, and mucostasis, consistent with UIP are present in this patient with RA.
Fig 2 Rheumatoid arthritis. Hyaline membranes indicative of diffuse alveolar damage are present in other sections from the same patient.
Fig 3 Rheumatoid arthritis. This pulmonary rheumatoid nodule has central neutrophils and fibrin surrounded by palisading histiocytes. Wegener granulomatosis would be in the differential diagnosis.
Fig 4 Rheumatoid arthritis. Pleural involvement in this case of RA consists of lymphoid aggregates, fibrosis, mesothelial hyperplasia, and fibrin deposition.
Fig 5 Rheumatoid arthritis. Follicular bronchiolitis is prominent in this 14-year-old with juvenile RA and pulmonary fibrosis.