Collagen vascular diseases that may involve the lungs include rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, Sjögren syndrome, and polymyositis/dermatomyositis. Lung disease may occasionally precede the diagnosis of systemic disease, especially in patients with rheumatoid arthritis or polymyositis, but in most cases the patient has already been diagnosed with collagen vascular disease before lung involvement becomes manifest. Serologic changes diagnostic of collagen vascular disease may sometimes be absent in those patients whose initial presentation is lung involvement.

Pulmonary manifestations of collagen vascular disease include diffuse abnormalities— usual interstitial pneumonia, lymphoid interstitial pneumonia, and nonspecific interstitial pneumonia—and patchy or focal lesions—organizing pneumonia and rheumatoid nodules. Pulmonary hypertension, vasculitis, including capillaritis, and intra-alveolar hemorrhage may also be found, as well as pleural disease including fibrous and fibrinous pleuritis, pleural effusions, and rheumatoid nodules. Bronchial and bronchiolar lesions such as follicular bronchitis or bronchiolitis, bronchiectasis, and constrictive bronchitis may occur. Immunosuppressive and cytotoxic treatment may also cause lung disease in these patients, including drug reactions (diffuse alveolar damage, hypersensitivity pneumonitis, etc.) as well as histopathology related to opportunistic infections (interstitial pneumonia, organizing pneumonia, diffuse alveolar damage, etc.).

The various pulmonary findings in collagen vascular disease just listed overlap considerably with the findings in many other lung diseases. There are many different causes of interstitial pneumonia, for example, besides collagen vascular disease. Only the sampling of a rheumatoid nodule can be considered specific for a collagen vascular disease diagnosis. Therefore, the findings on a transbronchial biopsy may include direct manifestation of a collagen vascular disease in the differential diagnosis, but, by themselves, these histopathologic findings are not definitively diagnostic of collagen vascular disease. Clinical correlation and perhaps additional studies are needed to determine whether or not a finding is most likely a direct manifestation of a collagen vascular disease. In particular, these patients are subject to opportunistic infections and drug reactions because of their therapy. Because the histologic findings of an infection or drug reaction are similar to many of the direct manifestations of collagen vascular disease in the lung, the pathologist should also typically consider them in the differential diagnosis. Although the transbronchial biopsy may not permit a definitive diagnosis of collagen vascular disease, note that the information conveyed to the clinician about the pulmonary histopathology is of considerable value in diagnosing and managing the patient in conjunction with the clinical, imaging, and ancillary study findings.