What could be the cause of pedal edema, mild rise in local temperature, and mild redness without pain in a patient who received Rabies Immunoglobulin (RIG) and Anti-Rabies Vaccine (ARV) after a cat scratch?

Pedal Edema After RIG Infiltration: Most Likely Local Reaction to Rabies Immunoglobulin

The pedal edema with mild warmth and redness without pain is most likely a local inflammatory reaction to the RIG infiltration itself, which is a common and expected adverse event that does not require discontinuation of rabies prophylaxis.

Primary Differential Diagnosis

Local Reaction to RIG (Most Likely)

• Local reactions following RIG administration are extremely common, with pain, erythema, and swelling reported in up to 100% of recipients in clinical trials 1
• The Advisory Committee on Immunization Practices documents that local pain and low-grade fever (mild temperature rise) routinely follow RIG administration 1
• In a prospective study of 123 patients receiving HRIG, local adverse events including erythema and swelling occurred in 11.4% of cases, all of which were mild and self-limited 2
• The absence of pain is reassuring and suggests this is not an infectious process or severe hypersensitivity reaction 2

Type III Hypersensitivity (Serum Sickness-Like Reaction) - Less Likely

• Type III hypersensitivity reactions typically occur 2-21 days after administration, not immediately, and are more common with booster doses (93% of cases) rather than primary vaccination 1
• These reactions present with generalized urticaria, arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise—not isolated pedal edema 1
• A recent case report documented serum sickness-like illness after equine RIG presenting on day 8 with widespread urticarial rash, fever, and arthralgias 3
• The timing (early in course), localized nature, and absence of systemic symptoms make this diagnosis unlikely 1, 3

Secondary Wound Infection - Must Exclude

• While the cat scratch itself could become infected, proper wound toilet should have been performed as part of standard PEP 2
• The absence of pain is atypical for bacterial cellulitis, which usually presents with significant tenderness 2
• Monitor for progression of warmth, expanding erythema, purulent drainage, or development of pain, which would indicate infection requiring antibiotics

Recommended Management Algorithm

Immediate Actions

• Continue the rabies vaccine series without interruption on days 14 and 28, as rabies prophylaxis must never be discontinued for local or mild systemic reactions 1, 4
• Manage symptoms with anti-inflammatory agents (ibuprofen or acetaminophen) and antihistamines if needed 1, 4
• Elevate the affected foot to reduce edema
• Apply cool compresses to the injection site for comfort

Monitoring Parameters

• Observe for progression of local symptoms over 24-48 hours 2
• Watch for development of systemic symptoms (fever >38.5°C, generalized rash, joint pain, malaise) that would suggest Type III hypersensitivity 1, 3
• Assess for signs of infection (increasing pain, purulent drainage, lymphangitic streaking, regional lymphadenopathy)

When to Escalate Care

• If symptoms worsen or systemic features develop, seek consultation with state health department or CDC for management guidance 1
• Report any serious adverse events to VAERS, though this mild local reaction does not meet that threshold 1

Critical Clinical Pitfalls to Avoid

• Never discontinue rabies prophylaxis for local reactions, as rabies is uniformly fatal once clinical symptoms develop 1, 4
• Do not confuse common local reactions (expected in up to 100% of RIG recipients) with serious adverse events requiring intervention 1, 2
• Avoid premature diagnosis of serum sickness without the characteristic timing (2-21 days post-dose) and systemic manifestations 1, 3
• The patient's risk of rabies must always outweigh concerns about mild adverse reactions when making treatment decisions 1

Expected Clinical Course

• Local reactions following RIG are typically mild and self-limited, resolving within a few days without complications 2
• All 123 subjects in a recent prospective study who experienced local adverse events from HRIG remained healthy and alive at 6-month follow-up, demonstrating excellent clinical outcomes with continued prophylaxis 2
• Reassure the patient and family that this is an expected reaction that does not compromise vaccine effectiveness or indicate treatment failure 4, 2