Skin involvement in classic monogenic autoinflammatory diseases. Part 1

Autoinflammatory diseases (AIDs) represent a heterogeneous group of conditions pathogenetically associated with dysregulation of innate immunity and clinically characterized by recurrent episodes of sterile inflammation in affected organs in the absence of infection, allergy, and high titers of circulating autoantibodies or autoreactive T cells. The overwhelming majority of monogenic AIDs (mAIDs) are accompanied by skin rashes, the type of which is determined by the specific disease and, to some extent, by differing pathogenetic mechanisms.

The first part of the article presents the cutaneous characteristics of the most common mAIDs: Familial Mediterranean fever (FMF), cryopyrinassociated periodic syndromes (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), periodic syndrome with hyperimmunoglobulinemia D / mevalonate kinase deficiency (HIDS/MKD). Skin involvement in these diseases reflects systemic inflammation associated with hyperproduction of the key pro-inflammatory cytokine interleukin (IL)-1β. In other AIDs, symptoms mainly depend on increased levels of cytokines such as IL-18, IL-36, etc. (NLRC4-associated autoinflammatory disease; deficiency of the IL-36 receptor antagonist – DITRA), as well as activation of interferon signaling pathways (interferonopathies). Different pathogenetic mechanisms determine the diversity of clinical phenotypes, including cutaneous manifestations. Knowledge of these features helps establishing a correct diagnosis, obtaining genetic confirmation (without which accurate identification of these rare conditions is impossible today) and selecting appropriate therapy. Pathological examination plays a special auxiliary role and should be used in diagnostically challenging situations.

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