Management of Herpes Zoster
First-Line Antiviral Therapy
For immunocompetent adults with uncomplicated herpes zoster, initiate oral valacyclovir 1 gram three times daily or acyclovir 800 mg five times daily within 72 hours of rash onset, continuing treatment until all lesions have completely scabbed (minimum 7-10 days). 1, 2, 3, 4
Oral Antiviral Options for Uncomplicated Disease
Valacyclovir 1 gram orally three times daily is the preferred first-line agent due to superior bioavailability and less frequent dosing compared to acyclovir, improving adherence 1, 2, 4
Acyclovir 800 mg orally five times daily remains an effective alternative when valacyclovir is unavailable, though requires more frequent dosing 1, 2, 3
Famciclovir 500 mg orally three times daily offers comparable efficacy with better bioavailability than acyclovir 1, 2
Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 1, 5, 6
Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint 1, 2
Treatment Duration Considerations
Standard treatment duration is 7-10 days minimum, but must be extended if new lesions continue to form or healing is incomplete 1, 2, 3
Immunocompromised patients may develop new lesions for 7-14 days and heal more slowly, requiring treatment extension well beyond 7-10 days 1
Do not discontinue antiviral therapy at exactly 7 days if lesions are still forming or have not completely scabbed—short-course therapy designed for genital herpes is inadequate for VZV infection 1
Intravenous Therapy for Severe or Complicated Disease
For disseminated herpes zoster, immunocompromised patients, ophthalmic involvement, CNS complications, or visceral disease, immediately initiate intravenous acyclovir 10 mg/kg every 8 hours. 1, 2, 7
Indications for IV Acyclovir
Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1, 2
Severely immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant, high-dose immunosuppression >40 mg prednisone daily) 1, 7
Ophthalmic herpes zoster with vision-threatening complications (corneal involvement, anterior uveitis, elevated intraocular pressure) 1, 7
CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
Visceral organ involvement (hepatitis, pneumonia) 1
IV Acyclovir Dosing and Monitoring
Dose: 10 mg/kg IV every 8 hours for severely immunocompromised hosts 1, 7
Alternative dosing of 5-10 mg/kg IV every 8 hours may be used based on severity 2
Continue IV therapy for minimum 7-10 days and until clinical resolution (all lesions completely scabbed) 1, 2
Switch to oral therapy once clinical improvement occurs to complete the treatment course 2
Monitor renal function at initiation and once or twice weekly during IV acyclovir therapy, with mandatory dose adjustments for renal impairment 1, 3
Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 1
Ensure adequate hydration during systemic acyclovir therapy to reduce risk of crystalluria and acyclovir-induced nephropathy 1
Management in Immunocompromised Patients
All immunocompromised patients with herpes zoster require antiviral treatment regardless of timing, and severely immunocompromised patients should receive IV acyclovir even for apparently uncomplicated disease. 1, 2, 7
Risk Stratification
High-risk immunocompromised status includes active chemotherapy, HIV infection, chronic immunosuppressive agents (thiopurines, biologics, B-cell depleting therapies), organ transplantation, or high-dose corticosteroids >40 mg prednisone daily 1
B-cell depleting disease-modifying therapies (ocrelizumab, rituximab, ofatumumab) carry the highest risk of severe herpes zoster and may require extended antiviral courses or IV therapy even when infection appears uncomplicated 1
Treatment Modifications
Consider temporary reduction or discontinuation of immunosuppressive medications in cases of disseminated or invasive herpes zoster if clinically feasible 1, 2
Re-introduce immunosuppressive agents only after all vesicular lesions have crusted, fever has resolved, and patient shows clinical improvement on antiviral therapy 1
Kidney transplant recipients with uncomplicated herpes zoster should receive oral acyclovir or valacyclovir, but escalate to IV therapy for disseminated or invasive disease 1
Prophylaxis Considerations
- Long-term acyclovir prophylaxis (400-800 mg twice daily) should be considered for patients receiving proteasome inhibitor-based therapies (bortezomib) or purine analog-based/alemtuzumab combination therapy 1, 7
Ophthalmic Herpes Zoster
Herpes zoster ophthalmicus requires urgent ophthalmology evaluation and immediate IV acyclovir 10 mg/kg every 8 hours in immunocompromised patients—oral antivirals represent inadequate treatment and risk permanent vision loss. 7
Critical Management Steps
Urgent ophthalmology consultation is mandatory for any patient with ophthalmic involvement, including eyelid erythema, crusting, discharge, blurred vision, or suspected corneal/uveal involvement 7
Immunocompromised patients with ophthalmic involvement require IV acyclovir without waiting for confirmatory testing 7
Immunocompetent patients with ophthalmic involvement may be treated with oral valacyclovir 1 gram three times daily or famciclovir 500 mg three times daily, but maintain low threshold for IV therapy 1
Do not apply topical corticosteroids before establishing adequate antiviral therapy, as this can cause devastating progression of infection 7
Topical corticosteroids may be considered later for stromal inflammation, but only after adequate antiviral coverage 7
Facial and Cranial Nerve Involvement
Facial herpes zoster requires particular urgency due to risk of ophthalmic and cranial nerve complications—initiate oral valacyclovir 1 gram three times daily or famciclovir 500 mg three times daily within 72 hours, with low threshold for IV therapy. 1
Special Considerations
Treatment is most effective when initiated within 48 hours of rash onset, though the 72-hour window is the maximum timeframe for optimal efficacy 1
Continue treatment until all lesions have scabbed, not just for an arbitrary 7-day period 1
Elevation of the affected area to promote drainage of edema and inflammatory substances is recommended 1
Keep skin well hydrated with emollients to avoid dryness and cracking 1
Escalate to IV acyclovir for complicated facial zoster with suspected CNS involvement or severe ophthalmic disease 1
Renal Dose Adjustments
Acyclovir and valacyclovir require mandatory dose adjustments for renal impairment to prevent acute renal failure. 1, 3
Acyclovir Oral Dosing Adjustments (for 800 mg every 4 hours regimen)
- CrCl >25 mL/min: 800 mg every 4 hours, 5 times daily 3
- CrCl 10-25 mL/min: 800 mg every 8 hours 3
- CrCl 0-10 mL/min: 800 mg every 12 hours 3
- Hemodialysis: Administer additional dose after each dialysis 3
Famciclovir Dosing Adjustments (for herpes zoster)
- CrCl ≥60 mL/min: 500 mg every 8 hours 1
- CrCl 20-39 mL/min: 500 mg every 24 hours 2
- CrCl <20 mL/min: 250 mg every 24 hours 1
Acyclovir-Resistant Herpes Zoster
For confirmed or suspected acyclovir-resistant VZV (lesions failing to resolve within 7-10 days despite adequate therapy), switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 1, 2
Recognition and Management
Suspect acyclovir resistance when cutaneous lesions have not begun to resolve within 7-10 days after starting therapy 1
Obtain viral culture with susceptibility testing to confirm resistance 1
Acyclovir resistance is rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients, particularly those receiving prolonged suppressive therapy 1
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1
Foscarnet 40 mg/kg IV every 8 hours is the treatment of choice for proven or suspected acyclovir-resistant herpes zoster 1, 2
Foscarnet requires close monitoring of renal function and electrolytes (hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia) 2
Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative option 1
Post-Herpetic Neuralgia Prevention and Management
Early initiation of antiviral therapy within 72 hours of rash onset is the only proven intervention to reduce the risk of post-herpetic neuralgia. 5, 6, 8
Acute Pain Management
Over-the-counter analgesics (acetaminophen, ibuprofen) are recommended for acute pain relief in otherwise healthy adults 1
Topical ice or cold packs can reduce pain and swelling during the acute phase 1
Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain 1
Post-Herpetic Neuralgia Treatment
First-line systemic agents (in decreasing order of recommendation): gabapentin, pregabalin, tricyclic antidepressants (amitriptyline, nortriptyline, desipramine), opioid analgesics (tramadol, morphine, oxycodone, methadone) 6, 8
Topical lidocaine patches and capsaicin cream offer moderate pain relief to some patients 5, 6, 8
For patients at high risk of developing PHN, consider early initiation of gabapentin or amitriptyline after onset of herpes zoster 6
Corticosteroid Controversy
Prednisone may be used as adjunctive therapy in select cases of severe, widespread shingles, but benefits in pain reduction do not outweigh risks in most patients 1, 9
Prednisone carries significant risks (infections, hypertension, myopathy, glaucoma, aseptic necrosis, cataracts, Cushing syndrome, weight gain, osteopenia), particularly in elderly patients 1
Prednisone should be avoided in immunocompromised patients due to increased risk of disseminated infection 1
Contraindications to prednisone include poorly controlled diabetes, history of steroid-induced psychosis, severe osteoporosis, or prior severe steroid toxicity 1
Topical corticosteroids are contraindicated during active shingles in immunocompromised patients, as they can increase risk of severe disease and dissemination 1
Prevention and Vaccination
The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes, providing >90% efficacy in preventing future recurrences. 1, 2, 7
Vaccination Recommendations
Shingrix (recombinant zoster vaccine) is preferred over live-attenuated vaccine (Zostavax) for prevention of herpes zoster and related complications 2
Two-dose series provides superior protection compared to live attenuated vaccine 1
Vaccination should ideally occur before initiating immunosuppressive therapies (JAK inhibitors, B-cell depleting agents), but can also be given after recovery from acute episode 1
For patients on B-cell depleting therapy, administer Shingrix at least 4 weeks prior to the next scheduled dose to maximize immunogenicity 1
Live-attenuated vaccines (Zostavax) are contraindicated in immunocompromised patients due to risk of uncontrolled viral replication 1
Shingrix is under investigation for immunocompromised patients, as it is not live 1
Post-Exposure Prophylaxis
For varicella-susceptible patients exposed to active varicella zoster infection, administer varicella-zoster immune globulin (VZIG) within 96 hours of exposure. 1, 2
High-Risk Populations Requiring VZIG
- Pregnant women who are VZV-susceptible 1, 2
- Immunocompromised patients (HIV-infected, cancer, chronic immunosuppression) 1
- Premature newborns <28 weeks gestation or <1,000 g 1
Alternative Prophylaxis
If VZIG is unavailable or >96 hours have passed, initiate a 7-day course of oral acyclovir beginning 7-10 days after varicella exposure 1, 2
Varicella vaccine within 3-5 days of exposure may modify disease if infection has not yet occurred 1
Infection Control Measures
Patients with herpes zoster must avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to individuals who have not had chickenpox or vaccination. 1
Isolation Precautions
Cover lesions with clothing or dressings to minimize transmission risk 1
Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust 1
For disseminated zoster (≥3 dermatomes), implement both airborne and contact precautions in addition to standard precautions 1
For immunocompromised patients with herpes zoster, implement airborne and contact precautions due to higher risk of dissemination 1
Physical separation of at least 6 feet from other patients is recommended in healthcare settings 1
Common Pitfalls to Avoid
Never use topical antivirals for shingles—they are substantially less effective than systemic therapy 1, 2
Do not apply any products to active vesicular lesions—emollients may be used only after lesions have crusted 1
Do not rely on clinical diagnosis alone in immunocompromised patients or atypical presentations—laboratory confirmation is needed 1
Do not use oral antivirals as initial therapy in severely immunocompromised patients with ophthalmic involvement—this represents inadequate treatment and risks permanent vision loss 7
Avoid unnecessary prolonged suppressive therapy in immunocompromised patients to prevent development of resistance 1
Do not initiate or continue immunomodulatory therapy during active chickenpox or herpes zoster infection 1