The Diagnosis of Sarcoidosis
Section snippets
Definition
Sarcoidosis has been defined as a multisystem disorder of unknown cause [1]. Clinicoradiologic findings alone are inadequate to make a diagnosis of sarcoidosis, although in special situations a presumptive diagnosis may be made (vide infra). Likewise, the presence of granulomas on tissue biopsy alone is also inadequate for the diagnosis of sarcoidosis. Even finding the histologic evidence in a patient with clinical and radiographic features of sarcoidosis is not definitive. The diagnosis is
Diagnostic approach
Fig. 1 outlines the diagnostic approach to sarcoidosis. This is a multistep process that usually involves collecting clinical information, histologic examination of tissue for the presence of granulomatous inflammation, exclusion of other known causes of granuloma formation, and documentation that the granulomatous inflammation is present in at least two organs. Establishing a diagnosis of sarcoidosis without following this algorithm is suspect and should be done with caution. In subsequent
Clinical findings
As with most diseases, establishing the diagnosis of sarcoidosis begins with collecting clinical data. Certain clinical findings suggest the diagnosis of sarcoidosis, although none of them is pathopneumonic. The process involves judging the clinical data that support the diagnosis of sarcoidosis and weighing it against data that refute it. If sufficient clinical evidence accumulates to suggest the diagnosis of sarcoidosis, a tissue biopsy is normally indicated. Table 1 outlines clinical data
Making a diagnosis of sarcoidosis based on clinical findings alone
On rare occasions, the constellation of presenting clinical findings is so typical of sarcoidosis that the diagnosis can be assumed without a tissue biopsy (see Fig. 1). Even in these situations, the clinician often must exclude alternative diagnoses before assuming that the patent has sarcoidosis (eg, Lofgren's syndrome, which is bilateral hilar adenopathy on chest radiograph and erythema nodosum skin lesions, requires the exclusion of coccidiodomycosis). Box 1 lists clinical presentations
Selection of the biopsy site
With the exception of the rare instance where the clinical findings are very specific for sarcoidosis, the diagnosis will require a tissue biopsy (see Fig. 1). Even when the patient has evidence of pulmonary or other visceral organs involved with sarcoidosis, it is in the patient's interest to select a biopsy site associated with least morbidity. For example, a skin biopsy is at lower risk of complications than a biopsy of other organs. Therefore, a careful skin examination should be performed
Pathology
Although in almost all cases granulomas are necessary to establish a diagnosis of sarcoidosis, it is important to recognize that granulomas are nonspecific inflammatory reactions, and they are not diagnostic of sarcoidosis or any other granulomatous disease [23]. Every biopsy should be searched for causes of granulomatous inflammation, such as mycobacteria, fungi, parasites, and foreign bodies (eg, talc) [24].
Although there are no specific diagnostic features of sarcoid granulomas, there may be
Exclusion of alternative causes of granulomatous inflammation
Box 2 lists the differential diagnosis for granulomata based on the organ system involved. The diagnosis of sarcoidosis requires that all of these diseases be excluded to a reasonable degree.
The exclusion of alternative causes of granulomatous inflammation requires a multifaceted approach. The histologic specimen must be examined for infectious agents and foreign bodies capable of inducing a granulomatous reaction. This requires staining the specimen for mycobacteria and fungi at a minimum.
Verifying multiple organ involvement
The presence of noncaseating granulomata in a single organ does not conclusively establish the diagnosis of sarcoidosis because sarcoidosis, by definition, is a systemic disease that should involve multiple organs. There are idiopathic granulomatous diseases of individual organs that are distinguished from sarcoidosis. For example, idiopathic granulomatous hepatitis, where noncaseating granulomas of unknown cause are found solely in the liver, is rarely found to be sarcoidosis (extrahepatic
The Kveim test
An old diagnostic test for sarcoidosis is the Kveim test, where a splenic suspension from a spleen involved with sarcoidosis is innoculated intradermally [30]. If after 4 to 6 weeks a skin nodule appears at the inoculation site, is biopsied, and reveals noncaseating granulomas, this is highly specific for the diagnosis of sarcoidosis. Unfortunately, the test is not extremely sensitive: both the sensitivity and specificity vary depending upon the spleen that is used, and the suspension is not
Examples of diagnostic dilemmas
This section describes some examples of applying the diagnostic sarcoidosis algorithm to specific cases.
Other idiopathic systemic granulomatous diseases
To confuse matters further, there are other multiorgan idiopathic granulomatous syndromes that are clinically disparate from sarcoidosis, such that they are thought to be separate entities (see Fig. 1). Blau's Syndrome consists of granulomatous arthritis, iritis, and skin rash. It is autosomal dominant with variable penetrance, and the age of onset is usually before age 12 years. It is considered a separate entity from childhood sarcoidosis on the basis of a lack of visceral (including
The future
Obviously sarcoidosis has causes. A half century ago, chronic beryllium disease was diagnosed as sarcoidosis as the metal was not known to cause a granulomatous reaction. In the future, it is likely that other “sarcoidoses” of known cause will be identified that can be pared off from what is now diagnosed as sarcoidosis.
In addition, the future diagnosis of sarcoidosis will probably couple genetics with exposure. It is thought that sarcoidosis results from the exposure of genetically susceptible
Summary
The diagnosis of sarcoidosis is never definitive. The process of diagnosis begins with the collection of clinical data. If enough data accumulate so that sarcoidosis is a reasonable possibility, a search is made for a possible organ to biopsy, selecting the least invasive biopsy location (eg, the skin). The biopsy should reveal granulomatous inflammation. Histologic examination should exclude other known causes of granulomatous inflammation, such as infectious agents and foreign bodies. Medical
Acknowledgments
The author would like to thank Dr. Beth Baker for supplying the chronic beryllium disease case.
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