Coagulation and Skin Autoimmunity

Abstract

Several lines of evidence indicate that the immune system, inflammation, and coagulation are simultaneously activated in autoimmune and immune-mediated skin diseases. Pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha induce the expression of the main initiator of coagulation, i.e., tissue factor. The proteases of coagulation in turn act on protease-activated receptors inducing the expression of various pro-inflammatory cytokines triggering inflammation. The cross-talk among immune system, inflammation, and coagulation amplifies and maintains the activation of all three pathways. This review focuses on three skin disorders as chronic spontaneous urticaria (CSU), angioedema, and bullous pemphigoid (BP), in which the relationships among the three systems have been investigated or their clinical consequences are relevant. Markers of thrombin generation, fibrinolysis, and inflammation have been reported to be increased in the plasma during flares of CSU and angioedema, as well as in the active phase of BP, with the marker levels reverting to normal during remission. The coagulation activation seems to be important only at local level in CSU and angioedema while both at local and systemic levels in BP which is the only condition associated with an increased thrombotic risk. The prothrombotic state in autoimmune skin diseases raises the question of the indication of anticoagulant treatment, particularly in the presence of other cardiovascular risk factors.

Bullous Pemphigoid: Trigger and Predisposing Factors

“…It has been consistently reported that the risk of thrombosis is increased in patients with BP [ 202 , 215 , 216 ]. Cugno and coworkers have focused on the relationships among immune response, inflammation, and blood coagulation in bullous pemphigoid [ 217 ]. As is known, the dermo-epidermal detachment is due to the interaction of autoAbs with BP180 and BP230 hemidesmosomal antigens, followed by complement activation and leukocyte infiltration.…”

“…Moreover, eosinophils strongly express tissue factor, which is the main initiator of the coagulation cascade (factors VII, X, VII, V, and prothrombin) leading to generation of thrombin [ 226 , 227 ]. This increases the permeability of blood vessels [ 228 ], thus favoring the transendothelial migration of inflammatory cells and their accumulation in the skin [ 217 ]. Neutrophils contribute to the pathogenesis of BP by releasing reactive oxygen species (ROS) and proteases.…”

The Role of Secretory Activity Molecules of Visceral Adipocytes in Abdominal Obesity in the Development of Cardiovascular Disease: A Review

“…Nonetheless, after tissue and vascular endothelium are damaged, and the physical barrier separating intravessel factor VII from TF is disrupted, the factor VII-TF complex is formed. Furthermore, during stimulation of monocytes, macrophages, and endothelial cells by endotoxins, cytokines, and lectins, the expression of TF increases in these cells in parallel with an increase in procoagulant activity [76]. In ACS, concentrations of inflammatory cytokines, such as TNF-α and interleukins, increase at the site of coronary artery occlusion to such an extent that TF is produced in vascular cells.…”

Dietary habits in Japanese patients with chronic spontaneous urticaria

“… 2 . Though the pathogenesis of CSU remains unclear, autoimmunity, inflammation, coagulation and autoallergy might be related 3‐6 …”

“…2 Though the pathogenesis of CSU remains unclear, autoimmunity, inflammation, coagulation and autoallergy might be related. [3][4][5][6] It has recently been reported that CSU patients have increased risk of obesity or metabolic syndromes, 2,7 particularly dyslipidemia. 8 Serum cholesterol or low-density lipoprotein (LDL) levels in CSU patients are increased and correlated with disease severity.…”