Advances in the mechanisms of initiation and progression of pretibial myxedema

In autoimmune thyroid diseases, circulating autoantibodies bind to autoantigens on dermal fibroblasts. IL-16 and RANTES (regulated on activation, normal T cell expressed and secreted) produced by the autoantibody-binding fibroblasts chemoattract CD4 + T lymphocytes to infiltrate nnto the dermis. The infiltrated CD4+ T cells interact with and activate the fibroblasts to produce interleukin (IL)-6, IL-8 and macrophage chemotactic protein (MCP)-1, which recruit more inflammatory leukocytes and result in perivasculitis. In these processes, large amounts of cytokines, autoantibodies, together with the interactions between T lymphocytes and fibroblasts lead to the accumulation of hyalumnan in dermis, which results in pretibial myxedema. Local trauma or infection may initiate the above immunological processes. Large amounts of cytokines and hyaluronan persistently stimulate the fibroblasts to propagate and differentiate into myofibroblasts, as well as to overproduce extracellular matrices, which together causes dermal fibrosis and cutaneous sclerosis. Key words: Myxedema; Immunity;  Fibroblasts