Serum Sickness

Description

• 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.

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.

Risk Factors

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.

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 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

Etiology

• 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