What is the recommended post-exposure prophylaxis (PEP) for a patient exposed to chickenpox (varicella), considering factors such as immunocompromised status, pregnancy, and age?

Post-Exposure Chickenpox Prophylaxis

Administer VariZIG (varicella-zoster immune globulin) as soon as possible within 10 days of exposure for high-risk patients without evidence of immunity, or provide post-exposure varicella vaccination within 3-5 days for eligible individuals without contraindications. 1

Determining Who Needs Prophylaxis

The decision to provide post-exposure prophylaxis depends on three critical factors 1:

• Evidence of immunity: Positive varicella IgG, documented history of chickenpox or shingles, or receipt of 2 doses of varicella vaccine constitutes immunity (except bone marrow transplant recipients who should always be considered non-immune) 2, 1
• Significant exposure: Face-to-face indoor contact for >5 minutes to 1 hour (not transient contact) with someone who has active varicella or disseminated/uncovered herpes zoster 1
• High-risk status: Immunocompromised patients, pregnant women, or specific neonatal populations 1

High-Risk Groups Requiring VariZIG

Administer VariZIG to the following populations without evidence of immunity 1:

• Immunocompromised patients: Including those with oncologic conditions, primary immunodeficiency, solid organ transplant, hematopoietic cell transplant, or receiving immunosuppressive therapy (>2 mg/kg/day prednisone or equivalent) 1, 3
• Pregnant women: All pregnant women without evidence of immunity 1
• Neonates:
  • Infants whose mothers developed varicella 5 days before to 2 days after delivery 1, 4
  • Premature infants ≥28 weeks gestation whose mothers lack immunity 1, 4
  • Premature infants <28 weeks gestation or ≤1,000 g birth weight, regardless of maternal immunity 1, 4

VariZIG Dosing and Administration

Dose: 125 IU per 10 kg body weight intramuscularly, up to maximum 625 IU (5 vials) 1, 4:

• Patients ≤2.0 kg: 62.5 IU (0.5 vial minimum)
• Patients 2.1-10.0 kg: 125 IU (1 vial minimum)
• Patients >10 kg: 125 IU/10 kg (maximum 625 IU)

Timing: Administer as soon as possible, ideally within 96 hours but up to 10 days post-exposure remains effective 1, 5. A 2019 study of 507 high-risk patients showed similar varicella incidence whether VariZIG was given ≤96 hours (6.2%) versus >96 hours up to 10 days (9.4%) post-exposure 5.

Repeat dosing: For patients with additional exposures ≥3 weeks after initial VariZIG, administer another full dose 1, 4

Post-Exposure Vaccination for Eligible Patients

For immunocompetent individuals without evidence of immunity 1:

• Unvaccinated: Administer varicella vaccine within 3-5 days of exposure to prevent or attenuate disease 1
• Previously received 1 dose: Give second dose within 3-5 days post-exposure (if ≥4 weeks since first dose) 1
• Vaccination >5 days post-exposure: Still indicated to provide protection against future exposures even if current exposure results in infection 1

Alternative Prophylaxis: Antiviral Therapy

For patients where VariZIG window has expired or is unavailable, consider oral acyclovir or valacyclovir 6, 7:

• Acyclovir: 800 mg orally 4 times daily for 7-10 days, starting 7-10 days post-exposure 8, 6
• Evidence is limited but suggests effectiveness in preventing or attenuating disease, particularly in immunocompromised children 7
• A 2022 study showed only 2.2% of immunocompromised children developed varicella when given acyclovir/valacyclovir prophylaxis versus 20% without prophylaxis 7

Post-Prophylaxis Monitoring

After VariZIG administration 1, 4:

• Monitor closely for 28 days (extended from typical 21-day incubation due to potential prolongation by immune globulin) 1
• Institute antiviral therapy immediately if any signs or symptoms of varicella develop 1, 4
• Delay varicella vaccination for ≥5 months after VariZIG to avoid interference with vaccine response 1, 4

After post-exposure vaccination 1:

• Monitor for 8-21 days post-exposure for fever, rash, or systemic symptoms
• Healthcare personnel should be excluded from work during this period if unvaccinated prior to exposure 1

Special Considerations and Pitfalls

Patients receiving regular IGIV: Those receiving monthly high-dose IGIV (>400 mg/kg) within 3 weeks of exposure likely have adequate protection and may not require VariZIG 1, 4

Bone marrow transplant recipients: Always consider non-immune regardless of prior history or positive antibody status 2, 1

Patients who received 2 vaccine doses before immunosuppression: Generally considered protected and do not require VariZIG; monitor closely and treat with antivirals if breakthrough disease occurs 1

HIV-infected children: Asymptomatic, non-immunosuppressed HIV-infected children (immunologic category 1) can receive live varicella vaccine, but other HIV-infected children should not due to dissemination risk 1

Safety Profile

VariZIG is well-tolerated with minimal adverse effects 4, 5:

• Most common: Injection site pain (2%) and headache (2%)
• Serious adverse events are rare (serum sickness reported in <1%) 5, 3
• Contraindications: History of anaphylaxis to human immune globulins; IgA deficiency with anti-IgA antibodies 1, 4