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Because of the protean manifestations of sarcoidosis, many different diseases must be considered in the differential diagnosis. Neoplasms (lymphoma, metastases), infections (tuberculosis, fungal), noninfectious inflammation (idiopathic pulmonary fibrosis, hypersensitivity pneumonitis), pneumoconioses (berylliosis, silicosis, asbestosis), and autoimmune diseases (systemic lupus erythematosus, scleroderma, rheumatoid arthritis, ankylosing spondylitis) must be considered and ruled out before the diagnosis of sarcoidosis is accepted.
Laboratory findings of leukopenia and hypercalcemia are nonspecific. The diagnostic value of detecting elevated levels of angiotensin-converting enzyme is limited by a 40% false-negative rate and a 10% false-positive rate. It is most useful for monitoring response to treatment or the clinical course of the disease. The Kveim test is an intracutaneous injection of previously validated saline suspension of human sarcoid spleen or lymph nodes. Although the test is specific, it is limited by unavailability of the antigen, a 4-6-week reaction time, and variability in the interpretation of results (3,5).
Bronchoalveolar lavage allows evaluation of the alveolar cell population. In normal nonsmokers, more than 90% of alveolar cells found at lavage are macrophages, 9% are lymphocytes, and less than 1% are polymorphonuclear leukocytes (3). In a patient with sarcoidosis, the percentage of lymphocytes increases to 40% and the percentage of macrophages decreases to 60%. In addition to the increased number of T lymphocytes, there is an increase in the ratio of T-helper cells to T-suppressor cells. These findings are also nonspecific because they occur in drug-induced lung toxicity, pneumoconioses, and amyloidosis (3).
Biopsy specimens can be obtained from the lungs or extrapulmonary sites. Transbronchial biopsy has a diagnostic yield of 85% when four samples are obtained. Occasionally, mediastinoscopy, thoracoscopy, or thoracotomy for node or lung biopsy may be required (Figure 27) (3).
Criteria for diagnosis must therefore include a compatible clinical or radiologic picture, histologic evidence of noncaseating granulomas, and negative results of special stains and cultures for other entities (5).
Differential Diagnosis