Serum Sickness
Basics
Description
- 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 and synovial joint fluid 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
- Activation of complement proteins differentiates serum sickness from serum sickness–like reaction, as the latter may not involve complement activation and multisystem dysfunction
- Typically, symptoms arise 6–14 d after the primary exposure to the antigen during the body’s process of clearing immune complexes and subsequent inflammatory response
- Symptoms can start 1–7 d after exposure if there has been an initial immunizing exposure, often with a more severe onset
- Symptoms typically last 1–2 wk before spontaneously resolving
- Serum sickness resolves with cessation of the offending agent
Etiology
- 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 (eg, rituximab, infliximab)
- Serum sickness–like reaction:
- Caused by nonprotein drugs, mostly antibiotics:
- Penicillins, amoxicillin
- Cephalosporins (eg, cefaclor)
- Sulfonamides (eg, trimethoprim-sulfamethoxazole)
- Thiazides
- Fluoxetine
- Bupropion
- Gold
- Thiouracils
- Hydantoins
- Phenylbutazone
- Aspirin
- Streptomycin
- Caused by nonprotein drugs, mostly antibiotics:
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Citation
Schaider, Jeffrey J., et al., editors. "Serum Sickness." 5-Minute Emergency Consult, 7th ed., Wolters Kluwer, 2027. Emergency Central, emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307429/5.0/Serum_Sickness_.
Serum Sickness. In: Schaider JJJ, Barkin RMR, Hayden SRS, et al, eds. 5-Minute Emergency Consult. Wolters Kluwer; 2027. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307429/5.0/Serum_Sickness_. Accessed July 13, 2026.
Serum Sickness. (2027). In Schaider, J. J., Barkin, R. M., Hayden, S. R., Wolfe, R. E., Barkin, A. Z., Shayne, P., & Rosen, P. (Eds.), 5-Minute Emergency Consult (7th ed.). Wolters Kluwer. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307429/5.0/Serum_Sickness_
Serum Sickness [Internet]. In: Schaider JJJ, Barkin RMR, Hayden SRS, et al, eds. 5-Minute Emergency Consult. Wolters Kluwer; 2027. [cited 2026 July 13]. Available from: https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307429/5.0/Serum_Sickness_.
* Article titles in AMA citation format should be in sentence-case
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5-Minute Emergency Consult

