Treatment of Shingles (Herpes Zoster)
For immunocompetent adults with uncomplicated shingles, initiate oral valacyclovir 1 gram three times daily for 7–10 days (continuing until all lesions have completely scabbed), starting within 72 hours of rash onset to reduce acute pain, accelerate healing, and prevent postherpetic neuralgia. 1
Antiviral Therapy: First-Line Treatment
Standard Oral Regimens for Immunocompetent Patients
Valacyclovir 1000 mg three times daily for 7–10 days is the preferred first-line agent due to superior bioavailability, convenient dosing, and proven efficacy in reducing zoster-associated pain faster than acyclovir 1, 2
Famciclovir 500 mg three times daily for 7–10 days offers equivalent efficacy to valacyclovir and is an appropriate alternative, with the advantage of less frequent dosing than acyclovir 1, 3
Acyclovir 800 mg five times daily for 7–10 days remains effective but requires more frequent dosing, which may reduce adherence 1, 4
Treatment must be initiated within 72 hours of rash onset for optimal reduction of acute pain, lesion healing, and prevention of postherpetic neuralgia, though observational data suggest benefit even when started later 1, 2
Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint 1
Critical Timing Considerations
Peak viral shedding occurs in the first 24 hours after lesion onset, making early initiation essential for blocking viral replication 1
Starting treatment after 72 hours still provides benefit for pain control and healing, but efficacy diminishes with delay 1, 2
Escalation to Intravenous Therapy
Indications for IV Acyclovir
Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) requires IV acyclovir 10 mg/kg every 8 hours 1
Immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant, chronic immunosuppression) should receive IV acyclovir 10 mg/kg every 8 hours, even for uncomplicated disease 1
Complicated facial zoster with suspected CNS involvement, severe ophthalmic disease, or Ramsay Hunt syndrome warrants IV therapy 1
Visceral organ involvement (hepatitis, pneumonia, encephalitis) mandates IV acyclovir 1
Continue IV therapy for at least 7–10 days and until all lesions have completely scabbed 1
Immunosuppression Management
In patients with disseminated or invasive herpes zoster, temporarily reduce or discontinue immunosuppressive medications when clinically feasible 1
Re-introduce immunosuppressive agents only after all vesicular lesions have crusted, fever has resolved, and clinical improvement is evident 1
Pain Management
Acute Neuropathic Pain Control
Gabapentin is the first-line oral agent for acute zoster-associated neuropathic pain, titrated in divided doses up to 2400 mg per day 1
Gabapentin improves sleep quality but causes somnolence in approximately 80% of patients—counsel accordingly 1
Pregabalin may be added for patients whose pain remains uncontrolled with gabapentin alone, particularly in postherpetic neuralgia 1
Over-the-counter analgesics (acetaminophen, ibuprofen) provide relief for acute pain in otherwise healthy adults 1
Topical ice or cold packs reduce pain and swelling during the acute phase 1
Topical Therapies for Chronic Pain
A single application of an 8% capsaicin patch (or 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic peripheral neuropathic pain 1
To mitigate capsaicin-induced erythema and burning, apply 4% lidocaine for 60 minutes, then remove before capsaicin administration 1
Topical anesthetics provide minimal benefit during the acute phase and are not recommended as primary therapy 1
Prevention of Postherpetic Neuralgia
Evidence for Antiviral Impact
Valacyclovir and famciclovir reduce the duration of postherpetic neuralgia significantly compared to placebo, with famciclovir reducing median PHN duration by 3.5 months in patients ≥50 years 2, 3
Acyclovir reduces acute zoster-associated pain but has conflicting evidence regarding postherpetic neuralgia prevention 4, 5
Early antiviral initiation (within 72 hours) is critical for maximizing reduction in postherpetic neuralgia risk 1, 2
Role of Corticosteroids
Prednisone may be used as adjunctive therapy in select cases of severe, widespread shingles, but carries significant risks in elderly patients 1
A 21-day course of prednisone (40 mg daily, tapered over 3 weeks) combined with acyclovir provides only slight benefit over acyclovir alone and does not reduce postherpetic neuralgia frequency 5
Avoid prednisone in immunocompromised patients due to increased risk of disseminated infection 1
Patients with poorly controlled diabetes, history of steroid-induced psychosis, severe osteoporosis, or prior severe steroid toxicity should avoid prednisone 1
Special Populations
Immunocompromised Patients
High-dose IV acyclovir 10 mg/kg every 8 hours is the treatment of choice for severely compromised hosts, continuing for at least 7–10 days until clinical resolution 1
Immunocompromised patients may develop new lesions for 7–14 days and heal more slowly, requiring extended treatment duration well beyond 7–10 days 1
Without adequate antiviral therapy, some immunocompromised patients develop chronic ulcerations with persistent viral replication 1
Acyclovir prophylaxis (400 mg daily) is recommended for patients receiving proteasome inhibitor-based therapies (e.g., bortezomib) to prevent herpes zoster 1
Facial and Ophthalmic Zoster
Facial zoster requires particular attention due to risk of cranial nerve complications, including ophthalmic involvement 1
Initiate oral valacyclovir 1 gram three times daily or famciclovir 500 mg three times daily within 72 hours of rash onset, continuing for 7–10 days until all lesions have scabbed 1
Elevation of the affected area promotes drainage of edema and inflammatory substances 1
Keep skin well hydrated with emollients to avoid dryness and cracking 1
Renal Impairment
Dose adjustments are mandatory to prevent acute renal failure, with specific adjustments based on creatinine clearance 1
For famciclovir in herpes zoster: 500 mg every 8 hours for CrCl ≥60 mL/min, down to 250 mg every 24 hours for CrCl <20 mL/min 1
Monitor renal function at initiation and once or twice weekly during IV acyclovir therapy 1
Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephropathy 1
Monitoring and Treatment Failure
Clinical Monitoring
Monitor for complete healing of lesions—treatment should continue until all lesions have scabbed 1
If lesions fail to begin resolving within 7–10 days, suspect acyclovir resistance and obtain viral culture with susceptibility testing 1
Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 1
Acyclovir-Resistant VZV
Acyclovir resistance is extremely rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients receiving prolonged suppressive therapy 1
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1
For confirmed acyclovir-resistant herpes zoster, foscarnet 40 mg/kg IV every 8 hours until clinical resolution is the treatment of choice 1
Infection Control and Prevention
Transmission Precautions
Patients remain contagious until all lesions have crusted—avoid contact with susceptible individuals (pregnant women, immunocompromised patients, those without prior varicella infection or vaccination) 1
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 (lesions in >3 dermatomes), implement both airborne and contact precautions 1
Post-Exposure Prophylaxis
Varicella zoster immunoglobulin (VZIG) within 96 hours of exposure is recommended for varicella-susceptible patients, including pregnant women, immunocompromised patients, and premature newborns <28 weeks gestation 1
If immunoglobulin is not available or >96 hours have passed, a 7-day course of oral acyclovir beginning 7–10 days after varicella exposure is recommended 1
Vaccination
Recombinant Zoster Vaccine (Shingrix)
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
Vaccination should ideally occur before initiating immunosuppressive therapies (e.g., JAK inhibitors, B-cell depleting agents) 1
For patients already receiving B-cell depleting therapy, administer Shingrix at least 4 weeks prior to the next scheduled dose to maximize immunogenicity 1
The vaccine can be administered after recovery from an acute episode to prevent future recurrences 1
Live-attenuated vaccines (Zostavax) are contraindicated in immunocompromised patients due to risk of uncontrolled viral replication 1
Common Pitfalls to Avoid
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
Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended 1
Do not apply corticosteroid cream to active shingles rash—this can increase risk of severe disease and dissemination, particularly in immunocompromised patients 1
Avoid relying solely on topical treatments when oral therapy is more effective 1
Do not use acyclovir 400 mg three times daily—this dose is only appropriate for genital herpes or HSV suppression, not for shingles 1