Serum Sickness

Serum Sickness is a topic covered in the 5-Minute Emergency Consult.

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  • Type III hypersensitivity reaction
  • When a foreign protein or drug (the antigen) is injected, the body's immune system responds by forming antibodies to the foreign material and subsequently forms complexes composed of the antigen, antibody, and complement.
  • These complexes then deposit in tissue, inciting an inflammatory response:
    • C3a and C5a act as anaphylatoxins.
    • C5a is strongly chemotactic for neutrophils.
    • The neutrophils then infiltrate the vessel wall at the site of the immune complex deposition and release enzymes, such as collagenase and elastase, which damage vessel walls.
  • Typically, symptoms arise 6–21 days after the primary exposure to the antigen.
  • Symptoms can start 1–4 days after exposure if there has been an initial immunizing exposure.
  • Symptoms typically last 1–2 wk before spontaneously resolving.


  • Serum sickness:
    • Vaccines containing foreign protein or serum such as pneumococcal vaccine or rabies.
    • Antivenom and tetanus inoculations made with horse or sheep protein
    • Monoclonal antibodies
  • Serum sickness–like reaction:
    • Caused by nonprotein drugs, mostly antibiotics:
      • Penicillins, amoxicillin
      • Cephalosporins (i.e., Cefaclor)
      • Sulfonamides (i.e., Bactrim)
      • Thiazides
      • Gold
      • Thiouracils
      • Hydantoins
      • Phenylbutazone
      • Aspirin
      • Streptomycin

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