Figure 1.

Mechanisms of eosinophil and mast cell activation in chronic spontaneous urticaria. Mast cells release histamine and other effector molecules after stimulation by autoantibodies directed against the high-affinity IgE receptor (FcεRI) and IgE, complement anaphylatoxin C5a, eosinophil-derived major basic protein (MBP), thrombin, and IgE-autoallergen complexes. The most important autoallergens are: interleukin-24 (IL-24), double stranded DNA (dsDNA), thyroperoxidase (TPO), tissue factor. Eosinophils are activated by autoantibodies directed against the low-affinity IgE receptor (FcεRII) and potentially by other factors. Upon their activation, eosinophils release MBP, and express tissue factor which in turn activates the coagulation cascade (factors VII, X, VIII, V, and prothrombin) leading to thrombin generation. Thrombin induces mast cell degranulation as well as increased vascular permeability. Thrombin generation is demonstrated by the presence of fragment F1+2 released from prothrombin after its activation. Finally, fibrin degradation is documented by elevated plasma levels of the fibrin fragment D-dimer during the active phase of the disease.