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
Tip
Symptoms appear 1–3 weeks following initial exposure (because antibodies take several days to form) and typically resolve within a few weeks after discontinuation of the offending agent.
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