Loyola University Medical Education Network Diagnosis

Sarcoidosis can be difficult to differentiate from other diseases, especially chronic infections such as fungal diseases and tuberculosis and some types of lymphoma.

The diagnosis of sarcoidosis is based on combined clinical, radiologic and histologic findings. Laboratory tests are seldom important in the diagnosis.


Most patients are asymptomatic or have mild nonspecific symptoms. Some, however, have suggestive findings of the skin, eye, or other organ systems on physical examination.

Reaction to antigen introduced into the skin is an expression of delayed-type hypersensitivity. Loss of this reactivity, cutaneous anergy, is common in sarcoidosis. This decreased immunologic response in the skin is probably the result of depletion of circulating immunoreactive cells which are taken out of the circulation by active granulomatous inflammation.


In the U.S. more than 90% of patients have characteristic ,but not specific, thoracic lymphadenopathy which is visible on chest radiographs, and almost 50% have parenchymal lung disease.

The most common pattern of thoracic lymphadenopathy in sarcoidosis is bilateral symmetric hilar and mediastinal lymph node enlargement. This pattern, however, can be identical to lymphadenopathy due to other causes, especially neoplastic diseases such as lymphoma and chronic infectious diseases due to fungi.  It is noteworthy, however, that patients with sarcoidosis can have very large thoracic lymph nodes and parenchymal lung disease and yet be asymptomatic and have no abnormalities on physical examination. This disparity in radiographic and clinical findings is highly suggestive of sarcoidosis but is still not diagnostic.

The first indication that a patient has sarcoidosis is often an abnormal chest radiograph. Many patients have abnormality of the lung parenchyma in addition to lymphadenopathy. The parenchymal disease has a wide variety of appearances which can closely resemble other interstitial lung diseases, pneumonia, lung metastases, and even miliary tuberculosis. The radiographic patterns must be considered in conjunction with clinical findings and the histology of biopsied tissue in order to arrive at the correct diagnosis.


A definitive diagnosis requires the histologic identification of noncaseating granulomas. Histology by itself, however, is not sufficient to make the diagnosis of sarcoidosis because a variety of infections and other diseases including malignancies are also associated with noncaseating granulomas. The histologic diagnosis of sarcoidosis is one of exclusion. The biopsy must be considered in conjuction with clinical, radiograph, and laboratory data in order to arrive at a correct diagnosis.

The most frequent site biopsied is the lung. Transbronchial biopsies are positive in 65-95% of patients, even if no lung parenchymal abnormalities are imaged. Tissue from mediastinoscopy is positive in as many as 95% of patients, but this is a more invasive procedure. Scalene node biopsy is positive in about 80% of patients. Positive tissue can, of course, be obtained from any involved site.


Serum angiotensin converting enzyme (ACE) is thought to arise in vascular endothelial cells. Serum ACE is commonly elevated in sarcoidosis, but this elevation is both nonspecific and insensitive.

Up to 10% of patients have hypercalcemia. Hypercalcuria is more frequent than this. Despite this hypercalcemia, development of kidney stones is unusual and deposition of calcium in the kidney parenchyma, nephrocalcinosis, is rare.

Lymphocytopenia, eosinophilia, elevation of the sedimentation rate, and hyperglobulinemia are common but nonspecific. Other serum abnormalities may be detected when the liver, kidney, and other organs are involved by sarcoid granulomas.

Pulmonary function studies can be normal initially. If the disease is more advanced, abnormalities associated with interstitial lung disease are found. Most patients have restrictive lung disease, but endobronchial granulomas can result in an element of airway obstruction also.



Terrence Demos, M.D.
Last Updated: March 14, 1996
Created: March 1, 1996