What is the cause of itchy, red, and hardened skin at the injection site after receiving an anti-rabies (rabies) vaccination?

Injection Site Reactions After Rabies Vaccination

The itchy, red, and hardened skin at your injection site is a common local inflammatory reaction that occurs in 60-90% of rabies vaccine recipients and represents a normal immune response to the vaccine components, not a serious adverse event. 1

What Causes These Symptoms

Primary Mechanism: Local Inflammatory Response

• Pain, redness (erythema), swelling, and induration (hardening) are the most frequently reported local reactions, occurring in 60.0%-89.5% of people receiving HDCV (human diploid cell vaccine) and 11%-57% receiving PCECV (purified chick embryo cell vaccine). 1
• These reactions result from nonspecific inflammation and irritation at the injection site rather than true allergic reactions in most cases. 2
• The symptoms are mild and resolve spontaneously within a few days without requiring treatment. 1

Timing and Pattern

• Local reactions typically appear within hours to days after vaccination. 1
• If you received rabies immune globulin (RIG) in addition to the vaccine, local reactions occur in up to 100% of recipients, with pain, erythema, and swelling being extremely common. 3

When to Worry vs. When to Reassure

Expected Normal Reactions (No Action Needed)

• Itching, redness, swelling, and hardness at the injection site 1
• Local pain (reported in 21%-77% of vaccine recipients) 1
• Symptoms lasting a few days 1

Warning Signs Requiring Evaluation

• Progression of symptoms beyond 24-48 hours that worsen rather than improve 3
• Signs of infection: increasing pain, purulent drainage, red streaking (lymphangitis), or swollen lymph nodes 3
• Systemic symptoms developing 6-14 days after vaccination: generalized hives (urticaria), joint pain, swelling of face/lips (angioedema), nausea, vomiting, or fever—these suggest Type III hypersensitivity reaction, which occurs in approximately 6% of people receiving booster doses 1

Management Approach

For Typical Local Reactions

• Continue the rabies vaccination series without interruption—this is critical because rabies is uniformly fatal once symptoms develop, and prophylaxis must never be discontinued for local or mild reactions. 1, 3
• Manage symptoms with anti-inflammatory agents (such as ibuprofen or aspirin) and antihistamines if itching is bothersome. 1, 3
• Monitor for 24-48 hours to ensure symptoms are improving rather than progressing. 3

Important Clinical Pitfall

• Do not confuse common local reactions with serious adverse events—the vast majority of injection site reactions are benign and self-limited. 3
• Never discontinue rabies prophylaxis based on local reactions alone, as the risk of rabies death far outweighs the discomfort of injection site reactions. 1, 3

Underlying Immunologic Mechanisms

For HDCV Vaccine Specifically

• Some reactions, particularly with booster doses, may involve Type III hypersensitivity related to betapropiolactone-altered human albumin in the vaccine, leading to IgE antibody development. 1
• This immune complex-like reaction occurs in approximately 6% of booster recipients, typically 2-21 days after administration. 1

Adjuvant-Related Reactions

• Allergic contact dermatitis can occasionally develop due to vaccine adjuvants like aluminum, though this is less common with rabies vaccines. 2, 4

Reassurance About Safety

• No serious adverse events were observed in multiple studies of rabies postexposure prophylaxis with both vaccine and immune globulin. 1
• No deaths have been reported from local or systemic allergic reactions to modern rabies vaccines. 1
• Local reactions do not correlate with vaccine efficacy or development of problematic antibodies. 5