What is the recommended treatment for an older adult patient suspected of having shingles (herpes zoster) presenting with skin pain but without a rash?

Treatment of Suspected Shingles Without Rash (Zoster Sine Herpete)

Start oral antiviral therapy immediately with valacyclovir 1 gram three times daily for 7-10 days, even in the absence of visible rash, as early treatment reduces acute pain and prevents postherpetic neuralgia. 1, 2

Clinical Recognition and Diagnosis

Herpes zoster can present with prodromal pain that precedes skin findings by 24-72 hours, and in some cases, the rash may be atypical, localized, faint, or evanescent. 3 This presentation, known as zoster sine herpete, requires a high index of suspicion based on:

• Dermatomal distribution of pain (unilateral, following a specific nerve distribution) 3
• Characteristic neuropathic quality of the pain (burning, stabbing, or electric-like sensations) 4
• Patient age and risk factors (older adults, immunocompromised status, recent stress) 3

Confirmatory testing should be obtained if the presentation is atypical or the patient is immunocompromised, including Tzanck preparation, immunofluorescent viral antigen studies, culture, or PCR. 3 However, do not delay treatment while awaiting test results if clinical suspicion is high. 2

First-Line Antiviral Treatment

Standard Dosing Regimen

Valacyclovir 1 gram orally three times daily for 7-10 days is the preferred first-line treatment due to superior bioavailability and less frequent dosing compared to acyclovir. 2, 5, 6 This regimen:

• Delivers therapeutic acyclovir concentrations with better patient compliance 5
• Has been proven significantly more effective than acyclovir in reducing duration of zoster-associated pain 6
• Reduces the duration of postherpetic neuralgia and decreases the proportion of patients with pain persisting for 6 months (19.3% vs 25.7% with acyclovir) 6

Alternative Oral Options

If valacyclovir is unavailable:

• Acyclovir 800 mg orally five times daily for 7-10 days 1, 2
• Famciclovir 500 mg orally three times daily for 7-10 days 1, 4

The critical treatment endpoint is complete scabbing of all lesions, not an arbitrary 7-day duration—continue treatment if lesions are still forming or have not completely scabbed. 1, 2

Treatment Timing and Efficacy

Optimal efficacy requires initiation within 72 hours of symptom onset (whether pain or rash), as this timing reduces acute pain, accelerates healing, and prevents postherpetic neuralgia. 2, 4, 6 However, treatment should still be initiated beyond 72 hours in older adults or immunocompromised patients, as they remain at high risk for complications. 1

When to Escalate to Intravenous Therapy

Switch to intravenous acyclovir 5-10 mg/kg every 8 hours if any of the following develop: 1, 2

• Multi-dermatomal involvement or disseminated disease
• Visceral involvement or CNS complications
• Severe immunocompromise (active chemotherapy, HIV with low CD4 count, solid organ transplant)
• Complicated ophthalmic zoster with suspected ocular involvement
• Failure to respond to oral therapy within 7-10 days

Continue IV therapy for a minimum of 7-10 days and until clinical resolution is attained, then switch to oral therapy to complete the treatment course. 2

Pain Management

While antivirals address the underlying viral replication, structured pain therapy should be initiated concurrently based on pain intensity: 4

• Mild pain: Acetaminophen or NSAIDs
• Moderate pain: Gabapentin or pregabalin
• Severe pain: Combination therapy with gabapentinoids plus opioids if needed

Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain. 1

Critical Pitfalls to Avoid

• Do not use topical antivirals—they are substantially less effective than systemic therapy and are not recommended. 1, 2
• Do not routinely add corticosteroids—while prednisone may be used as adjunctive therapy in select cases of severe, widespread disease, it carries significant risks (infections, hypertension, myopathy, glaucoma, osteopenia) that do not outweigh benefits in most patients, especially elderly individuals. 1
• Do not discontinue treatment 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
• Do not delay treatment waiting for rash to appear—prodromal pain in a dermatomal distribution warrants empiric treatment. 3

Special Population Considerations

Immunocompromised Patients

All immunocompromised patients with suspected herpes zoster require antiviral treatment regardless of timing from symptom onset. 2 Consider:

• Starting with IV acyclovir 10 mg/kg every 8 hours for severely immunocompromised hosts 1
• Temporary reduction in immunosuppressive medications if disseminated or invasive disease develops 1
• Extended treatment duration beyond 7-10 days, as lesions develop over longer periods (7-14 days) and heal more slowly 1

Renal Impairment

Dose adjustments are mandatory to prevent acute renal failure. 1 For valacyclovir in herpes zoster:

• CrCl ≥50 mL/min: 1 gram three times daily
• CrCl 30-49 mL/min: 1 gram twice daily
• CrCl 10-29 mL/min: 1 gram once daily
• CrCl <10 mL/min: 500 mg once daily

Monitor renal function at initiation and once or twice weekly during treatment. 1

Prevention of Future Episodes

After recovery from the current episode, strongly recommend the recombinant zoster vaccine (Shingrix) for all adults aged ≥50 years, regardless of prior herpes zoster episodes. 1, 2 This vaccine:

• Provides >90% efficacy in preventing future recurrences 1
• Is given in 2 doses, 2-6 months apart 2
• Is not contraindicated by prior herpes zoster infection 2

Monitoring and Follow-Up

• Assess for complete healing of lesions at follow-up visits 1
• Monitor for development of postherpetic neuralgia (pain persisting >90 days after rash onset) 6
• Screen for underlying immunocompromise if presentation is atypical or severe (HIV, diabetes, malignancy, immunosuppressive medications) 3
• If lesions fail to begin resolving within 7-10 days, suspect acyclovir resistance and obtain viral culture with susceptibility testing 1