This disease, of as yet unknown etiology, is manifested by noncaseating granulomatous lesions in many organ systems, most commonly in the lungs and thoracic lymph nodes. The disease is much more common in African Americans. Laboratory results are variable and nonspecific. Anemia is not frequent but appears in about 5% of cases. Splenomegaly is present in 10%-30% of cases. Leukopenia is found in approximately 30%. Eosinophilia is reported in 10%-60%, averaging 25% of cases. Thrombocytopenia is very uncommon, reported in less than 2% of patients in several large series. Serum protein abnormalities are common, with polyclonal hyperglobulinemia in nearly 50% of patients and with albumin levels frequently decreased. Hypercalcemia is reported in about 10%-20% of cases, with a range in the literature of 2%-63%. Uncommonly, primary hyperparathyroidism and sarcoidosis coexist. Alkaline phosphatase (ALP) levels are elevated in nearly 35% of cases, which probably reflects either liver or bone involvement.

The major diagnostic tests that have been used include the Kveim skin test, biopsy (usually of lymph nodes), and assay of angiotensin-converting enzyme (ACE).

The Kveim test consists of intradermal inoculation of an antigen composed of human sarcoidal tissue. A positive reaction is indicated by development of a papule in 4-6 weeks, which, on biopsy, yields the typical noncaseating granulomas of sarcoidosis. The test is highly reliable, yielding less than 3% false positives. The main difficulty is inadequate supplies of sufficiently potent antigen. For this reason, few laboratories are equipped to do the Kveim test. Between 40% and 80% of cases give positive results, depending on the particular lot of antigen and the duration of disease. In chronic sarcoidosis (duration more than 6 months after onset of illness), the patient is less likely to have a positive result on the Kveim test. Steroid treatment depresses the Kveim reaction and may produce a negative test result. The value of the Kveim test is especially great when no enlarged lymph nodes are available for biopsy, when granulomas obtained from biopsy are nonspecific, or when diagnosis on an outpatient basis is necessary. One report has challenged the specificity of the Kveim test, suggesting that a positive test is related more to chronic lymphadenopathy than to any specific disease.

Biopsy is the most widely used diagnostic procedure at present. Peripheral lymph nodes are involved in 60%-95% of cases, although often they are small. The liver is said to show involvement in 75% of cases, although it is palpable in 20% or less. Difficulties with biopsy come primarily from the fact that the granuloma of sarcoidosis, although characteristic, is nonspecific. Other diseases that sometimes or often produce a similar histologic pattern are early miliary tuberculosis, histoplasmosis, some fungal diseases, some pneumoconioses, and the so-called pseudosarcoid reaction sometimes found in lymph nodes draining areas of carcinoma.

Angiotensin-converting enzyme (ACE) is found in lung epithelial cells and converts angiotensin I (derived from inactive plasma angiotensinogen in a reaction catalyzed by renin) to the vasoconstrictor angiotensin II. It has been found that serum ACE values are elevated in approximately 75%-80% of patients with active sarcoidosis (literature range, 45%-86%). Sensitivity is much less in patients with inactive sarcoidosis (11% in one report) or in patients undergoing therapy. Unfortunately, 5%-10% of ACE elevations are not due to sarcoidosis (literature range, 1%-33%). The highest incidence of ACE abnormality in diseases other than sarcoidosis is seen in Gaucher’s disease, leprosy, active histoplasmosis, and alcoholic cirrhosis. Other conditions reported include tuberculosis, non-Hodgkin’s lymphoma, Hodgkin’s disease, scleroderma, hyperthyroidism, myeloma, pulmonary embolization, nonalcoholic cirrhosis, and idiopathic pulmonary fibrosis. Usually patients with these diseases (and normal persons) have a less than 5% incidence of elevated ACE values. However, either normal or increased ACE levels must be interpreted with caution. ACE levels are useful to follow a patient’s response to therapy. Certain conditions such as adult respiratory distress syndrome, diabetes, hypothyroidism, and any severe illness may decrease ACE levels.