Serum Sickness
BASICS
DESCRIPTION
- Classic serum sickness
- Type III hypersensitivity reaction that occurs 7 to 21 days after administration of foreign protein or serum (e.g., biologic drug or streptokinase)
- Clinical syndrome consists of skin rash, itching, fever, malaise, proteinuria, edema, joint pain lymphadenopathy, and vasculitis.
- Serum sickness–like reactions
- Similar reaction to classic serum sickness, most commonly associated with medications
- Etiology is not well understood.
- Immune complexes, vasculitis, and hypocomplementemia are absent.
- Characterized by fever, rash, lymphadenopathy, and arthralgia
- Occur 1 to 3 weeks after drug exposure, can be sooner if previously sensitized to the drug
- Significantly more common than classic serum sickness
- Clinically, these entities present and are treated in a similar manner.
EPIDEMIOLOGY
- 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.
ETIOLOGY
- Common causative agents for classic serum sickness:
- Horse or rabbit antithymocyte globulins (ATGs)
- Biologics (especially infliximab and rituximab)
- Human diploid-cell rabies vaccine
- Streptokinase
- Insect stings (Hymenoptera venom)
- Antivenom (snake, spider)
- Antitoxins (diphtheria, rabies, botulinum)
- Common causative agents for serum sickness–like reactions
- Penicillins
- Cephalosporins (especially cefaclor)
- Sulfonamides
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Carbamazepine
- Bupropion
- Minocycline
- Metronidazole
- Fluoxetine
GENERAL PREVENTION
- No known way to prevent first occurrence
- Obtain careful history of previous allergic reactions.
PATHOPHYSIOLOGY
- 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 deposit in the skin, joints, kidneys, and other organs.
- 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
- Drugs and/or their metabolites may act as haptens to bind plasma proteins and may elicit an abnormal immune response.
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Citation
Cabana, Michael D., editor. "Serum Sickness." 5-Minute Pediatric Consult, 9th ed., Wolters Kluwer, 2025. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness.
Serum Sickness. In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness. Accessed June 10, 2026.
Serum Sickness. (2025). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult (9th ed.). Wolters Kluwer. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617395/all/Serum_Sickness
Serum Sickness [Internet]. In: Cabana MDM, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. [cited 2026 June 10]. 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
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DB - Pediatrics Central
DP - Unbound Medicine
ER -

5-Minute Pediatric Consult

