Yuhki Yanase, Shunsuke Takahagi, Koichiro Ozawa y Michihiro Hide

Cells. 2021 Jul 12;10(7):1759. doi: 10.3390/cells10071759.

Chronic spontaneous urticaria is a skin condition characterized by skin edema and itchy flares for more than six weeks. Inflammatory mediators, such as histamine, are released from skin mast cells and/or peripheral basophils at the cell level. It is known that the extrinsic coagulation cascade triggered by tissue (TF) and complement factors is based on the pathogenesis of chronic spontaneous urticaria (CSU).

This review aimed to give a detailed role of vascular endothelial cells, leukocytes, extrinsic coagulation factors, and complement components on TF-induced activation of skin mast cells and peripheral basophils to form edema.

The extrinsic coagulation system triggered by TF and activated coagulation factors has been suggested in urticaria’s pathogenesis. Some studies have reported its improvement with heparin or warfarin treatment.

The detailed role of vascular endothelial cells in plasma leakage, especially at local areas of the skin in CSU is unclear. In vitro studies revealed that vascular endothelial cells might have a role in the early stage of CSU pathogenesis, as human umbilical vein endothelial cells and human dermal microvascular endothelial cells express a large amount of TF on their surface in response to the combination of several molecules such as histamine. TF-expressing leucocytes can generate the extrinsic coagulation cascade and produce activated coagulation factors, followed by the induction of intercellular gap formation of human umbilical vein endothelial cells. TF expression on monocytes may be utilized as a marker for pathological conditions of CSU and a therapeutic target of severe and refractory CSU. Studies have also shown that complement factors, such as C5a are increased in people with CSU.

Medications that target the activated coagulation factors and/or complement components may constitute a new and effective treatment for severe and refractory urticaria, namely low-molecular-weight antagonists of C5a and targets of the TF-triggered extrinsic coagulation pathway – complement system – mast cell and/or basophil activation axis.

This document is only available for registered healthcare professionals


La información que está a punto de visualizar está dirigida únicamente a los profesionales sanitarios aptos para prescribir o dispensar medicamentos. La correcta utilización de su contenido requiere de formación como profesional sanitario.

Debe hacer clic en Aceptar para confirmar que es usted profesional de la salud y continuar con la navegación.