Serum sickness is a type 3 immune-complex-mediated hypersensitivity reaction that classically presents with urticaria, fever, myalgias, polyarthralgias, polyarthritis, and lymphadenopathy. It arises 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 lead to complement activation and release vasoactive amines and cytokines, which give rise to the clinical features mentioned above.

Risk factors for the development of serum sickness include a higher dose of the medication, certain preparations, repeated exposure, older age, cryoglobulinemia or hypergammaglobulinemia, and an intermittent dosing schedule. Children are less likely to get serum sickness reaction than adults.

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