Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%.

Hereditary angioedema: the clinical syndrome and its management.

Urticaria and angioedema are common disorders affecting approximately 15-20% of the population at least once during their lifetime (Swinny, 1941; Sheldon et al., 1954; McKee, 1966). Urticarial lesions result from localized dilatation and transudation of fluid from small venules, and in their simplest form are thought to represent the same sort of wheal-and-flare reaction observed when histamine is injected into the skin. Clinically, one observes the presence of pruritic, erythematous cutaneous wheals that blanch with pressure, reflecting the underlying edema and dilated blood vessels. The histopathological features of urticaria are dilatation of cutaneous blood vessels and lymphatics in the superficial dermis, widening of dermal papillae, flattening of rete pegs, and swelling of collagen fibers.

http://www.fitzpatricksdermatology.com/references/Fitzpatricks_Derm8e_Ref_Ch038.pdf

Urticaria and Angioedema

Disseminated intravascular coagulation (DIC): An approach☆

C1 inhibitor and hereditary angioneurotic edema

A fragment of activated Hageman factor (HFf) has been demonstrated to activate the classical pathway of complement in a manner that is analogous to complement activation by antigen-antibody complexes or aggregated IgG. Thus C1, C4, C2, C3, and C5 were found to be depleted on addition of HFf to serum. The reduction of serum hemolytic activity was maximal upon addition of 5 micrograms HFf and an incubation time of 60 min at 37 degrees C. Consumption of the total complement activity and of the individual components proceeded in a dose-dependent fashion. No comparable activity was observed when equimolar concentrations of either the native Hageman factor (HF) or two-chain activated form of Hageman factor (HFa) were incubated with serum. Further, the ability of HFf to convert serum C3 and C4 was similar to that of aggregated IgG as assessed by immunoelectrophoresis. This function of HFf appeared to be independent of plasminogen (or plasmin) since plasminogen-free serum was indistinguishable from normal serum. Radial double immunodiffusion experiments using antiserum to C1q, C1r, and C1s on HFf-treated serum demonstrated the dissociation of the C1 trimolecular complex, with concomitant reduction of C1r antigenicity that is indicative of C1 activation. Thus, HFf appears to lead to C1 activation upon incubation with serum or when incubated with partially purified C1. This may represent a control link between activation of the intrinsic coagulation-kinin pathway and the initiation of the classical complement cascade.

/pdf/activation-of-the-classical-pathway-of-complement-by-hageman-5ch0sndugt.pdf

Activation of the classical pathway of complement by Hageman factor fragment.

The generation of C'1 esterase activity in siliconed plasma obtained from individuals with hereditary angioneurotic edema in remission tends to occur spontaneously, but can be hastened during its incubation with preparations of activated Hageman factor. This effect of activated Hageman factor could not be shown during its incubation with normal siliconed plasma, nor could consumption of normal serum inhibition of C'1 esterase be clearly shown. Soy bean trypsin inhibitor and heparin could impair this enhanced generation of C'1 esterase but neither inhibits the esterolytic function of C'1 esterase once formed. Trasylol was less effective in blocking this effect of activated Hageman factor. While the mechanism of the effect of activated Hageman factor upon C'1 activation remains obscure, it is apparent that some intermediate steps, possibly involving a kinin-forming system of plasma, may play a role.

/pdf/mechanisms-of-activation-of-c-1-esterase-in-hereditary-x049lcw2ur.pdf

Virginia H. Donaldson

Papers

Mechanisms of activation of C'1 esterase in hereditary angioneurotic edema plasma in vitro.