The “Mystery” of Cutaneous Sarcoidosis: Facts and Controversies

Abstract

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.

Challenges in the diagnosis and treatment of neurosarcoidosis

“…aluminium), or those derived from occupational exposure (e.g. agricultural employment or insecticides used at work) (14)(15)(16)(17).…”

Sarcoid-like reactions (SLRs) or autonomous sarcoidosis (AS)? Differentiation probably important?

“…This explains why at later stages in the described patients, different tumor types are often registered and the patients' condition is usually described as sarcoidosis-associated with a type of tumor [3]. In practice, these cases are concerned with the paraneoplastic form of sarcoid-type reaction, occurred on the basis of molecular mimicry due to a cross mediated immunoreactivity [3].…”

“…The lack of uniform (inclusion or exclusion) criteria for the definition of the disease such as sarcoidosis or sarcoid type of reaction in the study presented [1], would not only result (in the case of the proposed by authors regimens) to the progression of the sarcoid-type reaction (within the immunological response to certain infectious or non-infectious but still immunogenic antigens), but also to the progression of a certain type of tumors within the frame of the so-called paraneoplastic type of sarcoid reaction [2]. The introduction of immunosuppressive therapy with azathioprine, methotrexate, or corticosteroids often appears to play an important role as a costimulatory factor for carcinogenesis due to the fact that such therapy limits the ability of the immune system to eliminate tumor cells and thus indirectly support the tumor-escape mechanisms [2,3]. This explains why at later stages in the described patients, different tumor types are often registered and the patients' condition is usually described as sarcoidosis-associated with a type of tumor [3].…”

“…The introduction of immunosuppressive therapy with azathioprine, methotrexate, or corticosteroids often appears to play an important role as a costimulatory factor for carcinogenesis due to the fact that such therapy limits the ability of the immune system to eliminate tumor cells and thus indirectly support the tumor-escape mechanisms [2,3]. This explains why at later stages in the described patients, different tumor types are often registered and the patients' condition is usually described as sarcoidosis-associated with a type of tumor [3]. In practice, these cases are concerned with the paraneoplastic form of sarcoid-type reaction, occurred on the basis of molecular mimicry due to a cross mediated immunoreactivity [3].…”

“…Sarcoid-like granulomatosis, described in the literature in the frame of course with etanercept [5], is also another clear and typical example of progredient type sarcoid-like reaction after wrongly introduced initial therapy, as the final result is incorrectly identified or classified as the autonomous disease sarcoidosis [2,3].…”