Arthus reaction

Process

The Arthus reaction involves the in situ formation of antigen/antibody complexes after the intradermal injection of an antigen. If the individual has circulating antibody either from passive immunity or because of prior encounter with the antigen, an Arthus reaction may occur. Typical of most mechanisms of the type III hypersensitivity, Arthus manifests as local vasculitis due to deposition of IgG-based immune complexes in dermal blood vessels. The pathogenesis of the Arthus reaction is often erroneously described to be the result of complement activation, which subsequently results in neutrophil infiltration along with the other hallmarks of inflammation. However, complement in and of itself likely has a minor role in the actual process of the Arthus reaction and other type III hypersensitivities. Specifically, mice lacking the common gamma chain subunit of the Fc receptors that is required for signaling by CD64 (FcγRI) and CD16A (FcγRIIIA) as well as FcεRI have a drastic reduction in their Arthus reaction severity. Furthermore, mice with intact Fc signaling whose complement is depleted through the use of cobra venom have only a minor reduction in their Arthus reaction scores. The reaction as a whole is driven by mast cell degranulation. Subsequent investigation demonstrated that complement, specifically the anaphylatoxin C5a, can drive the Arthus reaction indirectly because the resultant signaling alters the ratio of activating to inhibitory Fc receptors on effector cells. Further aggregation of immune complex-related processes induce a local fibrinoid necrosis with ischemia-aggravating thrombosis in the tissue vessel walls. The end result is a localized area of redness and induration that typically lasts a day or so.

Arthus reactions have been infrequently reported after vaccinations containing diphtheria and tetanus toxoid. The CDC's description:

Arthus reactions (type III hypersensitivity reactions) are rarely reported after vaccination and can occur after tetanus toxoid–containing or diphtheria toxoid–containing vaccines. An Arthus reaction is a local vasculitis associated with deposition of immune complexes and activation of complement. Immune complexes form in the setting of high local concentration of vaccine antigens and high circulating antibody concentration. Arthus reactions are characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally by necrosis. These symptoms and signs usually occur 4–12 hours after vaccination. ACIP has recommended that persons who experienced an Arthus reaction after a dose of tetanus toxoid–containing vaccine should not receive Td more frequently than every 10 years, even for tetanus prophylaxis as part of wound management.