What is the recommended treatment for herpes zoster in adults, including antiviral regimen, duration, pain management, and indications for intravenous therapy or corticosteroids?

Herpes Zoster Treatment

First-Line Antiviral Therapy

For uncomplicated herpes zoster in adults, initiate oral valacyclovir 1000 mg three times daily or famciclovir 500 mg three times daily within 72 hours of rash onset, continuing until all lesions have completely scabbed. 1

Standard Oral Regimens

• Valacyclovir 1000 mg orally three times daily for 7-10 days is the preferred first-line agent due to superior bioavailability and convenient dosing 1, 2
• Famciclovir 500 mg orally three times daily for 7-10 days offers equivalent efficacy with less frequent dosing than acyclovir 1, 2
• Acyclovir 800 mg orally five times daily for 7-10 days remains effective but requires more frequent administration, which may reduce adherence 3, 1, 4

The critical endpoint is complete scabbing of all lesions, not an arbitrary 7-day duration—treatment must continue until this clinical milestone is reached. 1

Timing of Initiation

Treatment is most effective when started within 72 hours of rash onset, though the greatest benefit occurs within the first 48 hours. 1, 5 Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication. 1 Even when initiated beyond 72 hours, antiviral therapy may still provide benefit for pain reduction and lesion healing, particularly in high-risk patients. 2

Indications for Intravenous Acyclovir

Switch to intravenous acyclovir 10 mg/kg every 8 hours for disseminated herpes zoster (≥3 dermatomes or visceral involvement), severe immunosuppression, CNS complications, or complicated ocular/facial disease. 1

Specific IV Indications

• Disseminated disease with multi-dermatomal involvement, visceral organ involvement (hepatitis, pneumonia, encephalitis), or hemorrhagic lesions 1
• Severely immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant recipients) 1
• CNS complications including encephalitis, meningitis, or Guillain-Barré syndrome 1
• Complicated ocular or facial zoster with suspected cranial nerve involvement 1
• Failure to improve after 7-10 days of appropriate oral therapy, suggesting possible acyclovir resistance 1

In immunocompromised patients with disseminated or invasive herpes zoster, temporarily reduce or discontinue immunosuppressive medications when clinically feasible. 1 Re-introduction should occur only after all lesions have crusted, fever has resolved, and clinical improvement is documented. 1

Pain Management

Acute Neuropathic Pain

Gabapentin is the first-line oral agent for acute herpes zoster 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, requiring careful counseling. 1

• Pregabalin may be added for patients with inadequate pain control on gabapentin alone 1
• Over-the-counter analgesics (acetaminophen, ibuprofen) provide relief for mild to moderate acute pain 1
• Topical ice or cold packs reduce pain and swelling during the acute phase 1

Topical Therapies

• A single application of 8% capsaicin patch (or 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic neuropathic pain 1
• Apply 4% lidocaine for 60 minutes before capsaicin to mitigate burning and erythema 1
• Topical antivirals are substantially less effective than systemic therapy and should not be used 1

Role of Corticosteroids

Prednisone may be used as adjunctive therapy to antivirals in select cases of severe, widespread shingles, but carries significant risks in elderly patients and should be avoided in immunocompromised individuals. 1

The addition of oral corticosteroids provides only modest benefits in reducing acute pain and does not prevent postherpetic neuralgia. 6 Serious risks include increased infection susceptibility, hypertension, myopathy, glaucoma, aseptic necrosis, cataracts, Cushing syndrome, weight gain, and osteopenia—benefits do not outweigh these risks in most patients. 1

Contraindications to corticosteroids include:

• Immunocompromised status (HIV, active chemotherapy, chronic immunosuppression) 1
• Poorly controlled diabetes 1
• History of steroid-induced psychosis 1
• Severe osteoporosis or prior severe steroid toxicity 1

Special Populations

Immunocompromised Patients

Immunocompromised patients with uncomplicated herpes zoster should receive oral acyclovir 800 mg five times daily or valacyclovir 1000 mg three times daily, but maintain a low threshold for switching to IV therapy. 1

• For patients on B-cell depleting therapies (ocrelizumab, rituximab, ofatumumab), consider IV acyclovir even for apparently uncomplicated disease due to high risk of severe complications 1
• Immunocompromised patients may require extended treatment duration beyond 7-10 days, as lesions develop over longer periods (7-14 days) and heal more slowly 1
• Without adequate antiviral therapy, some immunocompromised patients develop chronic ulcerations with persistent viral replication 1

Renal Impairment

Assess baseline renal function before initiating any antiviral agent and adjust dosing based on creatinine clearance. 1

• For IV acyclovir, monitor renal function once or twice weekly during treatment 1
• Famciclovir dosing: 500 mg every 8 hours for CrCl ≥60 mL/min, down to 250 mg every 24 hours for CrCl <20 mL/min 1
• Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephrotoxicity 1

Pregnant Women

Administer varicella-zoster immune globulin (VZIG) within 96 hours of exposure to VZV-susceptible pregnant women. 1 For serious viral-mediated complications such as pneumonia, intravenous acyclovir should be considered. 3

Management of Treatment Failure and Resistance

If lesions have not begun to resolve within 7-10 days of appropriate antiviral therapy, suspect acyclovir resistance and obtain viral culture with susceptibility testing. 1

Acyclovir-Resistant VZV

• Acyclovir resistance is extremely rare in immunocompetent patients (<0.5%) but occurs in up to 7% of immunocompromised patients 1
• For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 1
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1

Monitoring During IV Therapy

• Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 1
• Monitor for signs of visceral dissemination: respiratory symptoms (pneumonia), elevated hepatic enzymes (hepatitis), or neurological changes (CNS involvement) 1

Infection Control

Patients with herpes zoster remain contagious until all lesions have completely crusted and should avoid contact with susceptible individuals during this period. 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 (>3 dermatomes), implement both airborne and contact precautions 1
• Maintain physical separation of at least 6 feet from other patients in healthcare settings 1

Post-Exposure Prophylaxis

Administer VZIG (or IVIG) within 96 hours of exposure to varicella-susceptible patients at high risk, including immunocompromised individuals, pregnant women, and premature newborns. 1

• If immunoglobulin is unavailable or >96 hours have passed, initiate a 7-day course of oral acyclovir beginning 7-10 days after varicella exposure 1
• Varicella vaccine may be administered within 3-5 days of exposure to modify disease if infection has not yet occurred 1

Vaccination for Prevention

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 episodes. 1

• Administer the two-dose series ideally before initiating immunosuppressive therapies 1
• For patients on B-cell depleting therapy, give 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 herpes zoster episode 1

Common Pitfalls to Avoid

• Do not discontinue antiviral therapy at exactly 7 days if lesions have not completely scabbed—the clinical endpoint, not calendar days, determines treatment duration 1
• Do not rely on topical antivirals as primary therapy—they are substantially less effective than systemic treatment 1
• Do not delay treatment waiting for laboratory confirmation in typical presentations—diagnosis is clinical and time is critical 5
• Do not use short-course regimens (1-3 days) designed for genital herpes—these are inadequate for VZV infection 1
• Do not apply corticosteroid cream to active shingles lesions—this can increase risk of severe disease and dissemination, particularly in immunocompromised patients 1