Activation of blood coagulation in autoimmune skin disorders

The immune system and blood coagulation are simultaneously activated in several inflammatory systemic disorders, such as lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Proinflammatory cytokines, such as IL-6 and TNF-alpha, induce the expression of tissue factor, the main initiator of blood coagulation. Activated proteases of coagulation in turn act on protease-activated receptors, inducing the expression of various proinflammatory cytokines. This cross-talk between inflammation and coagulation amplifies and maintains the activation of both systems. This review focuses on three skin disorders: chronic urticaria (CU), which is considered autoimmune in approximately 50% of cases, bullous pemphigoid (BP), which is the prototype of autoimmune blistering disease, and psoriasis, which is an immune-mediated dermatitis. In CU, the activation of coagulation, which is due to the involvement of eosinophils and tissue factor pathways with the generation of thrombin, has local implications by increasing dermal vascular permeability. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. In BP, the activation of coagulation seems to have both local and systemic implications. Locally, eosinophils and thrombin participate in bulla formation and tissue damage; systemically, the activation of coagulation may explain the increased thrombotic risk observed in these patients. In psoriasis, the activation of coagulation seems to be mainly systemic, potentially contributing to the increased cardiovascular risk associated with this disease.