Serum sickness is a type 3 immune complex disease resulting from exposure to therapeutic heterologous (classically nonhuman) serum or chimeric therapeutic proteins. The reaction is also rarely observed after blood transfusions. Serum sickness typically occurs 7-21 days after exposure to exogenous proteins or chemicals. Inciting agents include microbial and venom antitoxins, immunomodulators, vaccines, insect stings, therapeutic fibrinolytic proteins, and allergy immunotherapy.

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.

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; however, it is high on the differential for a teenager with arthritis.

The disease is usually self-limited and lasts less than one week. Patients may also complain of gastrointestinal tract symptoms including nausea, vomiting, diarrhea, and melena. Renal (glomerulonephritis), cardiac (carditis), and neurologic (Guillain-Barré syndrome, peripheral neuritis) sequelae occur rarely. 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