Granuloma annulare – A genetic disorder that sustain an incomplete foreign-body granuloma reaction

Abstract

Granuloma annulare (GA) is a common dermatosis characterized by an annular arrangement of erythematous papules, plaques, rarely nodules or patches. It is a type of non-infectious granuloma with unknown etiology. Hypothesis. The immune reaction always begins with the foreign-body granuloma formation. However, if during the process the antigen is recognized as too small the immune reaction stops the granuloma development. In the case of GA the dysfunctional control mechanism continues to sustain the granulomatous formation. Because the target does not exist anymore, the initiated process starts the "search" for a new target (circular spreading). Different histological and clinical presentations depends on which gene of the control mechanism is dysfunctional, while the distribution depends on the type of antigen and its distribution at the start of the immune reaction. The disappearance of GA after biopsy, that occurs in some cases, could be attributable to the specific defective gene involved (the biopsy can disrupt only some type of GA). So, new therapies for solitary GA formations could be directed to the disruption and creation of a new and healthy immune response from the point of disruption. A comparative analysis of the gene expression of GA and the foreign-body granuloma in the same patient, and GA among different patients could clarify which genes are involved in granulomatous formations. The cells affected by those genetic defects are probably histiocytes and lymphocytes (both always present in GA). Because of some similarity, necrobiosis lipoidica could also be a specific type of GA.