What is the recommended treatment for varicella, especially in high-risk individuals?

Varicella Lesion Progression and Treatment

Lesion Evolution Pattern

Varicella lesions progress through characteristic stages: macules → papules → vesicles → pustules → crusts, with all stages present simultaneously ("crops") over 3-5 days. 1

• The hallmark of varicella is the polymorphous rash with lesions at different stages of development appearing in successive waves 2
• New lesion formation typically continues for 3-5 days in immunocompetent individuals 3
• Lesions begin as small red macules that rapidly progress to papules within hours, then develop into clear fluid-filled vesicles ("dewdrop on a rose petal" appearance) 2
• Vesicles become cloudy and pustular before crusting over, with complete crusting typically occurring by day 5-7 after rash onset 1
• Patients remain contagious until all lesions are completely crusted, which serves as the endpoint for isolation precautions 1

Risk-Stratified Treatment Approach

Immunocompetent Children (<13 years)

Supportive care alone is recommended for otherwise healthy children with varicella. 1

• No antiviral therapy is indicated for routine cases in healthy children 1
• Oral acyclovir (20 mg/kg four times daily for 5 days, maximum 800 mg per dose) should be considered for children with chronic cutaneous disorders (e.g., eczema) or chronic pulmonary disease, but only if initiated within 24 hours of rash onset 1, 4
• Children receiving long-term salicylate therapy should also be considered for oral acyclovir due to increased risk of Reye syndrome 1

Adolescents and Adults (≥13 years)

Oral acyclovir 800 mg four times daily for 5 days is recommended for all persons aged ≥13 years if treatment can be initiated within 24 hours of rash onset. 1, 4

• Adults face significantly higher complication rates than children, with case-fatality rates 21.3 per 100,000 cases in adults versus 0.8 per 100,000 in children aged 1-4 years 3
• Treatment beyond 24 hours after rash onset loses efficacy and is not recommended 1, 5
• Valacyclovir 1000 mg three times daily for 5-7 days is an alternative with better bioavailability 6

Immunocompromised Patients

Intravenous acyclovir 10 mg/kg every 8 hours for 7-10 days must be initiated immediately upon diagnosis, ideally within 24 hours of rash onset. 1

• This population faces life-threatening risk of visceral dissemination affecting liver, lungs, and brain 2, 7
• Oral therapy is inadequate for immunocompromised patients due to risk of severe complications and mortality 7
• High-risk groups include: HIV-infected patients, transplant recipients, cancer patients on chemotherapy, and those receiving high-dose corticosteroids (≥2 mg/kg/day prednisone or equivalent for ≥14 days) 3, 1

Pregnant Women

Pregnant women with uncomplicated varicella do not require routine acyclovir, but those with serious complications (especially pneumonia) require intravenous acyclovir. 1, 5

• Acyclovir is FDA Category B in pregnancy with reassuring safety data from 596 first-trimester exposures showing no increased birth defect rates 5
• Oral acyclovir may be considered for pregnant women at increased risk of moderate-to-severe disease if started within 24 hours 1, 5
• Varicella pneumonia in pregnancy carries significant maternal mortality risk and mandates IV acyclovir 1

Post-Exposure Prophylaxis

Vaccination (Primary Method)

Varicella vaccine administered within 3 days (up to 5 days) of exposure is >90% effective at preventing disease in susceptible immunocompetent individuals. 3, 1, 8

• This is the preferred method for healthy individuals without evidence of immunity 8
• Even if exposure results in infection, post-exposure vaccination does not increase adverse event risk 3

VariZIG (High-Risk Individuals)

VariZIG should be administered within 96 hours (extended to 10 days per 2013 CDC guidelines) for high-risk individuals who cannot receive vaccine. 3, 8

High-risk groups requiring VariZIG include: 3

• Immunocompromised patients without evidence of immunity
• Pregnant women without evidence of immunity
• Newborns whose mothers developed varicella from 5 days before to 2 days after delivery
• Hospitalized premature infants ≥28 weeks gestation whose mothers lack immunity
• Hospitalized premature infants <28 weeks gestation or ≤1,000 g birth weight, regardless of maternal immunity

VariZIG dosing: 125 IU/10 kg body weight intramuscularly, maximum 625 IU (five vials); minimum dose 62.5 IU for infants ≤2.0 kg 3

• VariZIG may prolong the incubation period by ≥1 week, requiring monitoring for 28 days (rather than 21 days) after exposure 3
• If varicella develops despite VariZIG, antiviral therapy should be instituted immediately 3
• A recent expanded-access study (n=507) showed varicella incidence of 4.5% in immunocompromised patients, 7.3% in pregnant women, and 11.5% in infants receiving VariZIG, with similar efficacy whether given ≤96 hours or >96 hours up to 10 days post-exposure 9

Critical Pitfalls to Avoid

• Never delay acyclovir beyond 24 hours of rash onset in populations where treatment is indicated—efficacy is lost 1, 5
• Do not use oral acyclovir for immunocompromised patients—only IV formulation provides adequate drug levels 1, 7
• Do not miss the 96-hour window for VariZIG in exposed pregnant women without immunity—this is the critical timeframe for preventing severe maternal complications 5, 8
• Do not use acyclovir prophylactically in healthy individuals after exposure—vaccination is the method of choice 1, 8
• Do not discharge newborns without VariZIG if the mother developed varicella from 5 days before to 2 days after delivery—these infants face highest mortality risk 3, 5
• Airborne and contact precautions are mandatory in healthcare settings until all lesions are crusted 1