Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli.

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.

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.

[3] 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.

[4][5] Further aggregation of immune complex-related processes induce a local fibrinoid necrosis with ischemia-aggravating thrombosis in the tissue vessel walls.