What is the recommended treatment for a widespread herpes simplex virus (HSV) outbreak with crusted lesions in an adult?

Treatment of Widespread HSV Outbreak with Crusted Lesions

For a widespread HSV outbreak with crusting in an adult, initiate oral valacyclovir 1000 mg twice daily or famciclovir 500 mg twice daily for 7-10 days, continuing until all lesions are completely crusted and healed. 1, 2

Initial Assessment and Route Selection

The presence of widespread lesions with crusting indicates an active HSV outbreak that has progressed beyond the early vesicular stage. The key decision point is whether the patient requires oral versus intravenous therapy:

• Oral therapy is appropriate for immunocompetent patients with extensive but uncomplicated mucocutaneous disease 1, 2
• Intravenous acyclovir 5-10 mg/kg every 8 hours is mandatory for severe disease requiring hospitalization, disseminated infection (encephalitis, pneumonitis, hepatitis), or immunocompromised patients with extensive involvement 1, 3

First-Line Oral Antiviral Regimens

For widespread HSV in immunocompetent adults:

• Valacyclovir 1000 mg orally twice daily for 7-10 days offers superior bioavailability and convenient twice-daily dosing 2, 4
• Famciclovir 500 mg orally twice daily for 7-10 days provides equivalent efficacy with less frequent dosing than acyclovir 2, 5
• Acyclovir 400 mg orally 5 times daily for 7-10 days remains effective but requires more frequent administration 1, 4

The critical endpoint is continuing treatment until all lesions have completely crusted, not stopping at an arbitrary 7-day mark 1, 3, 2

Special Populations Requiring Modified Approach

Immunocompromised Patients

• Higher oral doses are required: acyclovir 400 mg orally 3-5 times daily until clinical resolution 1, 6
• Consider intravenous therapy (acyclovir 5-10 mg/kg IV every 8 hours) for extensive disease, as immunocompromised patients have prolonged episodes with extensive disease and higher risk of dissemination 1, 3, 6
• Acyclovir resistance occurs in up to 7% of immunocompromised patients versus <0.5% in immunocompetent hosts 2, 6

HIV-Infected Patients

• Famciclovir 500 mg twice daily for 7 days is specifically indicated for recurrent orolabial or genital herpes in HIV-infected adults 5
• Episodes may be more severe and prolonged, potentially requiring extended treatment duration 1, 2

Management of Treatment Failure and Resistance

If lesions fail to improve after 5-7 days of standard therapy:

1. Increase oral acyclovir to 800 mg five times daily and reassess after 5-7 days 6
2. Obtain viral culture with susceptibility testing if available 6
3. For confirmed acyclovir-resistant HSV, switch to foscarnet 40 mg/kg IV every 8 hours until complete resolution 1, 2, 6
4. Topical trifluridine (TFT) ophthalmic solution applied 3-4 times daily may be used for accessible mucocutaneous lesions resistant to systemic therapy 6

All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 2

Critical Treatment Principles

• Topical antivirals are substantially less effective than systemic therapy and should not be used as primary treatment 1, 3, 2
• Treatment must continue until all lesions are fully crusted, which is the standard clinical endpoint indicating substantial reduction in viral shedding and transmission risk 1, 3, 2
• Adequate hydration is essential during systemic acyclovir or valacyclovir therapy to minimize risk of crystalluria and nephrotoxicity 3
• Renal function must be assessed before initiating therapy, with dose adjustments required for creatinine clearance <60 mL/min 3, 5

Infection Control Measures

• Patients remain contagious until all lesions are fully crusted 1, 3, 2
• Avoid direct contact with lesions and do not share towels, utensils, or other objects that may contact affected areas 2
• Cover lesions with clothing or dressings to minimize transmission risk 3

Common Pitfalls to Avoid

• Do not discontinue therapy at exactly 7 days if lesions are still forming or have not completely scabbed 3
• Do not rely on topical therapy alone for widespread disease 1, 3, 2
• Do not use short-course regimens (1-3 days) designed for genital herpes, as these are inadequate for extensive HSV infection 3
• Do not delay escalation to IV therapy in immunocompromised patients or those with severe disease 1, 3