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Serum Sickness

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

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  • Serum sickness
    • Type III hypersensitivity reaction that occurs 7 to 21 days after injection of foreign protein or serum (e.g., biologics or streptokinase)
    • Immune complexes deposit in the skin, joints, kidneys, and other organs
    • Clinical syndrome consists of skin rash, itching, fever, malaise, proteinuria, edema, joint pain, lymphadenopathy, and vasculitis.
  • Serum sickness–like reactions
    • Characterized by fever, rash, lymphadenopathy, and arthralgia
    • Occur 1 to 3 weeks after drug exposure, can be sooner if previously sensitized to the drug
    • Immune complexes, vasculitis, and hypocomplementemia are absent.
    • This type of reaction, most commonly associated with medications, is commonly referred to as serum sickness as well.
    • More common than true serum sickness because equine serum antitoxins have been replaced with human antitoxin sera
  • Clinically, these entities present and are treated in the same manner.


  • Limited information is available regarding the incidence of adverse drug reactions in children; generally believed to occur less frequently in children than in adults
  • >90% of serum sickness cases are drug-induced.
  • <5% of serum sickness cases are fatal.

Risk Factors


People with a genetic predisposition to produce IgE are more susceptible.

General Prevention

  • No known way to prevent first occurrence
  • Obtain careful history of previous allergic reactions.
  • Skin testing prior to antiserum administration will prevent anaphylaxis but not serum sickness.
  • When the need for antiserum arises, consider prophylactic antihistamines.


  • Serum sickness—type III immune complex, antigen–antibody complement reaction
    • Antibodies form 6 to 10 days after the introduction of foreign material.
    • Antibodies interact with antigens, forming immune complexes that diffuse across the vascular walls.
    • They become fixated in tissue and activate the complement cascade.
    • C3a and C5a are produced, resulting in increased vascular permeability and activated inflammatory cells.
    • Polymorphonuclear cells and monocytes cause diffuse vasculitis.
  • Serum sickness–like reaction
    • Abnormal inflammatory reaction in response to defective metabolism of drug by-products


  • Common causative agents:
    • Horse antithymocyte globulins
    • Biologics (especially infliximab and rituximab)
    • Human diploid-cell rabies vaccine
    • Streptokinase
    • Insect stings (Hymenoptera venom)
    • Antivenom
    • Penicillins
    • Cephalosporins (especially cefaclor)
    • Sulfonamides
    • Hydralazine
    • Thiouracils
    • Metronidazole
    • Naproxen
    • Dextrans
  • Case-reported agents:
    • Minocycline
    • Carbamazepine
    • IVIG
    • Bupropion
    • H1N1 vaccination

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Cabana, Michael D., editor. "Serum Sickness." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness.
Serum Sickness. In: Cabana MD, ed. 5-Minute Pediatric Consult. 8th ed. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness. Accessed March 24, 2019.
Serum Sickness. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult. Available from https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness
Serum Sickness [Internet]. In: Cabana MD, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2019 March 24]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Serum Sickness ID - 617395 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -