The "mystery" of cutaneous sarcoidosis: facts and controversies.

The reason why the cutaneous form of sarcoidosis is well known in the literature is because of its spectrum of manifestations granting it the fame of a Great Imitator. The mystery shrouding the pathogenesis of this rare cutaneous disease is still there (in spite of the fundamental progress of the various diagnostic methods in current day medicine). The production of the morphological substrate - the epithelioid cell granuloma - which is considered to be characteristic of skin sarcoidosis, could, however, also be the end result of a reaction to i) various specific infectious agents such as Leishmaniasis cutis, coccidioidomycosis, etc., ii) certain residual bacterial or other mycobacterial antigens which, at the moment of setting the diagnosis are - by definition - non-infectious but still immunogenic, as well as iii) different tumor antigens in lesional tissue or other location. Often, differentiating between sarcodiosis and a sarcoid-like reaction, based on the updated criteria for cutaneous sarcoidosis, is problematic to downright impossible. A future characterization of the genetic signature of the two conditions, as well as the implementation of additional mandatory panels for i) the identification of certain infectious or ii) non-infectious but immunogenic and iii) tumor antigens in the epithelioid cell granuloma (or in another location in the organism), could be a considerable contribution to the process of differentiating between the two above-mentioned conditions. This will create conditions for greater accuracy when setting the subsequent therapeutic approaches.