What is the treatment for serum sickness?

Treatment of Serum Sickness

Discontinue the offending agent immediately and initiate corticosteroids for moderate to severe cases, with antihistamines and NSAIDs providing symptomatic relief for milder presentations. 1, 2, 3

Immediate Management

First-Line Actions

• Stop the causative drug or antiserum immediately upon clinical suspicion, as serum sickness is self-limited once the antigen is removed 2, 3
• Identify the triggering agent through careful medication history, as common culprits include penicillins, cephalosporins, trimethoprim-sulfamethoxazole, tetracyclines, doxycycline, minocycline, and heterologous antisera 4, 2, 5

Pharmacologic Treatment Algorithm

Mild Cases (Rash, Low-Grade Fever, Mild Arthralgias)

• NSAIDs (aspirin 66 mg/kg/day in children) for symptomatic relief of fever and joint pain 2
• Antihistamines (diphenhydramine HCl 4 mg/kg/day) for pruritus and urticaria 2, 3
• Monitor for progression over 24-48 hours 2

Moderate to Severe Cases (Debilitating Joint Symptoms, Significant Edema, Nephritis, or Life-Threatening Angioedema)

• Prednisone 40-60 mg daily for adults (or 1 mg/kg/day), with symptom resolution typically occurring within 24 hours of initiation 3
• Hydrocortisone 20 mg/kg/day IV can be used in pediatric patients or those unable to take oral medications 2
• Taper corticosteroids over 1-2 weeks after clinical improvement to prevent rebound symptoms 3
• Epinephrine 0.01 mL/kg IM should be administered immediately if angioedema or anaphylactoid features are present 2

Combination Therapy for Severe Cases

The most effective regimen based on documented rapid response combines:

• Corticosteroids (as above) 2, 3
• Antihistamines for symptomatic relief 2
• NSAIDs for arthralgias 2
• Single dose of epinephrine if airway compromise or severe angioedema 2

Monitoring Parameters

Clinical Assessment

• Monitor for resolution of fever, rash, and arthralgias, which typically improve dramatically by day 3 after discontinuing the offending agent 2
• Track urinalysis in patients with hematuria or proteinuria, as renal involvement can occur 2

Laboratory Findings (Supportive but Not Diagnostic)

• Eosinophilia (may be present but not universal) 2
• Decreased C4 and total complement levels (supportive finding) 5
• Elevated ESR (nonspecific) 5
• No specific laboratory finding is universally present or definitively diagnostic—the diagnosis remains clinical 3

Expected Clinical Course

• Serum sickness is self-limited with complete resolution expected once the antigen is removed 2
• Symptoms typically begin 7-14 days after initial exposure (or 1-5 days with re-exposure) 2, 6
• With appropriate treatment, dramatic improvement occurs within 24-72 hours 2, 3
• Urinalysis abnormalities resolve completely with treatment 2

Critical Pitfalls to Avoid

• Do not delay corticosteroid therapy in severe cases while waiting for laboratory confirmation, as diagnosis is clinical and delays can prolong morbidity 3
• Do not use short courses of corticosteroids (less than 7-10 days) in severe cases, as premature discontinuation may lead to symptom recurrence 3
• Do not confuse serum sickness with ongoing infection, particularly when fever and rash develop during antibiotic treatment—the timing (typically 4-10 days after drug initiation) and constellation of symptoms (fever, rash, arthralgias, lymphadenopathy) distinguish serum sickness 2
• Recognize that serum sickness can occur with commonly prescribed drugs beyond just heterologous sera, including clarithromycin, tetanus toxoid, and thymoglobulin 5, 7, 6