Serum sickness is a type 3 immune-complex disease resulting from exposure to therapeutic heterologous (nonhuman) protein antigens or chimeric therapeutic proteins. Common offending agents include intravenous immunoglobulin, serum albumin, antithymocyte globulin, rituximab, and infliximab. The reaction is also rarely observed after blood transfusions, immunizations, microbial and venom antitoxins, and insect bites.

Serum sickness typically occurs 7-21 days after exposure to exogenous proteins or chemicals. Antigens induce antibody production resulting in circulating antigen-antibody complexes that deposit within postcapillary venules. Subsequent complement activation releases vasoactive amines and cytokines, leading to symptoms and signs that include urticaria (often first noticed at the site of injection), fever, myalgias, arthralgias, arthritis, and lymphadenopathy. The disease is usually self-limited and lasts less than one week. Renal, hepatic, pulmonary, gastrointestinal tract, and central nervous system involvement may rarely occur. Previously sensitized hosts can see an accelerated onset of symptoms occurring 1-3 days after exposure to the antigen.

Related topic: Serum sickness-like reaction