Serum sickness is a type III hypersensitivity reaction that usually develops as a complication of antitoxin or antivenom administration, but can also occur after antibiotic administration and hepatitis B infection. Symptoms typically occur 1–3 weeks after exposure to the offending agent and include fever, rash, and arthralgia. It is diagnosed clinically and treatment consists primarily of removing the offending agent.
Serum sickness is a classic example of a type III hypersensitivity reaction, which usually develops as a complication of antitoxin or antivenom administration.
- Antivenom or antitoxin containing animal proteins or serum (→ “serum” sickness), such as:
- Medications: most frequently antibiotics (e.g., penicillin, amoxicillin, cefaclor, trimethoprim-sulfamethoxazole) 
- Infections: Hepatitis B virus
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
- Rash (urticarial or purpuric)
- Arthralgias, myalgia
- Hand edema
- Headache, blurred vision
- Abdominal pain, diarrhea, nausea/vomiting
- Mucosal involvement is uncommon
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.
- Clinical diagnosis: see “Clinical features.”
- Laboratory studies: Urinalysis may show mild proteinuria.
See also “Hypersensitivity reactions.”
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)
- Similar to classic serum sickness
- May manifest with severe erythema multiforme and arthralgias
The differential diagnoses listed here are not exhaustive.
- Stop the offending agent.
- Consider pharmacotherapy, e.g.: 
- Systemic glucocorticoids
- H1 blockers
- NSAIDs as needed for arthralgias
Prognosis is excellent once the offending drug is stopped or the causative infection has resolved.