Most often, urticaria, erythema multiforme, erythema nodosum, and lcukocytoclastic vasculitis develop as a result of immunologic reactions to antigens. For example, when erythema multiforme occurs as a result of herpes simplex infection, the eruption is due to the antigenic rather than infective properties of the virus. Thus, the herpes simplex virus can cause vesicles of the lip as a result of direct infection and can also cause a bullous erythema multifonne through immunologic mechanisms.
Urticaria. The prototypic explanation for the development of urticaria involves a type 1, IgE-mediated, hypersensitivity response. During the process of sensitization, IgE antibody is synthesized and attached to the cytoplasmic membrane of mast cells. The next exposure to the sensitizing agent results in the binding of that antigen to two adjacent IgE antibody molecules on the mast cell.
This “bridging” attachment then results in mast cell degranulation and increase in number of inflammatory mediators. It should be noted, however, that IgE-mediated urticarias are uncommon, most urticarial reactions occur through other, unknown mechanisms.
Urticaria and angioedema can also be caused through complement-mediated events (cryoglobulin-induced urticaria, hereditary angioedema) and through non immunologic mechanisms such as direct pharmacologic stimulation of mast cells and induction of the lipoxygenase pathway of arachidonic acid metabolism.
Erythema Multifanne. The specific immunologic mechanism responsible for the development of erythema multiforme is unknown. Circulating immune complexes are frequently present and, at least in those instances resulting from herpes simplex infection, may be deposited at the site of the lesions. This immune complex disease differs from that which occurs in leukocytoclastic vasculitis, however, in that immunoglobulins are usually not deposited in lesional sites and only rarely does there appear to be deposition of complement. The marked histologic presence of lymphocytes in the lesions has caused some investigators to suggest that cell-mediated (type IV) mechanisms are important. Mediator release as a result of mast cell degranulation probably occurs, but the mechanism through which this occurs is unknown.
Erythema Nodosum. Essentially nothing is known about the pathway through which the lesions of erythema nodosum arise. Histologically, the process is a mixed lymphocyte-histiocyte-mediated panniculitis; some minor degree of lymphocytic vasculitis also is often present. The presence of lymphocytes suggests the possibility of a cell-mediated (type IV) reaction. No immunoreactants are deposited within the lesions, suggesting that a standard type III immune complex mechanism is not an important component of the reaction.
Leukocytoclastic Vasculitis. Results of studies suggest that all or nearly all examples of leukocytoclastic vasculitis develop as a result of immune complex (type III) formation and deposition. In this process, circulating immune complexes are deposited on the basement membrane of venules. This deposition requires some disturbance of the endothelial cells (possibly occurring as a result of mediator release from mast cells) in order for the complexes to gain direct exposure to the underlying basement membrane. Once complexes are deposited, complement is activated. As part of the complement cascade, chemoattractant molecules are released that draw neutrophils into the area. These neutrophils attempt to phagocytize the deposited immune complexes and in so doing release destructive proteolytic lysosomal enzymes. The vascular wall damage done by these enzymes allows for fibrin deposition in the vessels, fragmentation of neutrophil nuclei, and extravasation of erythrocytes. This whole process requires only 24 to 72 hours, at which time the neutrophils are slowly replaced by mononuclear cells as part of the reparative phase of the reaction.
Tags:cryoglobulin, erythema multiforme, herpes simplex infection, herpes simplex virus, Human Anatomy and Physiology, leukocytoclastic vasculitis, mast cell degranulation urticaria
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