Annular centrifugal erythema (ACE) belongs to the group of figured erythema and is considered as reactive erythema, developing under the influence of numerous triggers, the most significant of which are infectious agents that can cause alteration of the immune response and the formation of skin hypersensitivity reactions. Modern data on the etiology, pathogenesis, immunogenesis, and clinical features of the Darier ACE are summarized. 2 clinical cases of ACE with localization of foci in the face area are presented. An in-depth clinical and laboratory study revealed associations between the development of annular erythema and a high degree of bacterial colonization of the pharynx (S.haemolyticus, Str.Pyogenes, Klebsiella pn.) in one case and with reactivation of the infection caused by the Epstein—Barr virus in another. In addition, a reduced content of T-lymphocytes-helpers (CD3+/CD4+) interleukin-2 (IL-2) in the blood serum, activation molecules and IL-2 receptor marker CD25+. One patient also showed a deficiency in the interferon system. Patients were treated with combination therapy, including antiviral/antibacterial drugs on the background of recombinant interferon α2-β medications, inducers of interferon / bacterial immunomodulator of multicomponent vaccine (from antigens of potentially pathogenic microorganisms Staphylococcus aureus, Klebsiella pneumoniais, Proteus vulgaris and Escherichia coli). Antiviral therapy in the case of ACE associated with persistent EBV infection and recurrent herpes has reduced viral replication and contributed to the regression of ACE foci. In the second case, the administration of a multicomponent vaccine containing ligands to innate immunity receptors promoted the activation of innate and adaptive immunity effectors and had an antibacterial and immunomodulating effect, which also led to a decrease in antigenic stimulation and resolution of ACE foci.