Serum sickness is a classic example of a type III hypersensitivity reaction, which usually develops as a complication of antitoxin or antivenom administration.

Epidemiology

Etiology

• Antivenom or antitoxin containing animal proteins or serum (→ “serum” sickness), such as:
  • Equine anti-snake venom
  • Equine anti-spider venom
  • Equine or bovine anti-rabies antitoxin
  • Equine botulinum antitoxin
• Medications: most frequently antibiotics (e.g., penicillin, amoxicillin, cefaclor, trimethoprim-sulfamethoxazole)
• Infections: Hepatitis B virus

Pathophysiology

Exposure to an antigen (e.g., antivenom, drug) → formation of antibodies → deposition of antibody-antigen complexes in tissue → activation of the complement cascade → tissue damage and systemic inflammation

Clinical features

• Fever
• Rash (urticarial or purpuric)
• Arthralgias, myalgia
• Lymphadenopathy

Diagnostics

• Histologic examination of affected tissues typically shows small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration.
• Deposition of IgG and/or IgM complement-fixing antibodies results in localized complement consumption and hypocomplementemia (decreased serum C3 levels).

Differential Diagnostics

Serum sickness-like reaction

• Epidemiology: much more common than actual serum sickness
• Etiology: similar to that of serum sickness
  • Infections (e.g., hepatitis B, rabies)
  • Medications that can act as haptens (e.g., allopurinol, cephalosporins, penicillin)
• Pathogenesis: unclear (likely not the result of a type III hypersensitivity reaction)
• Clinical features
  • Similar to classic serum sickness

Treatment