What is the difference between herpes simplex and herpes zoster from a clinical perspective and treatment?

Clinical and Treatment Differences Between Herpes Simplex and Herpes Zoster

Herpes simplex virus (HSV) and varicella zoster virus (VZV/herpes zoster) are distinct viral infections requiring different clinical recognition and treatment approaches, with HSV typically presenting as recurrent mucocutaneous vesicles and treated with shorter antiviral courses, while herpes zoster presents as dermatomal pain with vesicular eruption requiring longer, higher-dose antiviral therapy to prevent postherpetic neuralgia.

Clinical Presentation Differences

Herpes Simplex Virus

• HSV causes recurrent grouped vesicles on an erythematous base at mucocutaneous sites, most commonly genital (HSV-2) or orolabial (HSV-1), with lesions that are typically self-limiting in immunocompetent hosts 1, 2
• Primary HSV infections are often accompanied by systemic symptoms, while reactivations are usually localized and less severe 2
• Most HSV transmission occurs from asymptomatic viral shedding - only 9% of HSV-2 seropositive persons report knowing they have genital herpes 3
• HSV lesions evolve from thin-walled vesicles to pustules before becoming small ulcers, with chronic poorly healing ulcers characteristic in immunocompromised hosts 3

Herpes Zoster (Shingles)

• Herpes zoster presents as unilateral vesicular eruption in a dermatomal distribution, often preceded by dermatomal pain 24-72 hours before skin findings appear 3, 4
• VZV reactivation (zoster) occurs in 25-45% of immunosuppressed patients during the first year after transplantation or intensive treatment, with 10-20% risk of dissemination without prompt antiviral therapy 3
• Early lesions are erythematous macules that rapidly evolve to papules then vesicles, frequently coalescing 3
• The key complication is postherpetic neuralgia, which is more common and prolonged in elderly patients 3, 5

Treatment Differences

Herpes Simplex Treatment

For first clinical episodes:

• Acyclovir 200 mg orally 5 times daily for 7-10 days 6
• Alternative: Acyclovir 400 mg orally 3 times daily for 7-10 days 6

For recurrent episodes:

• Acyclovir 200 mg orally 5 times daily for 5 days 6
• Acyclovir 400 mg orally 3 times daily for 5 days 6
• Acyclovir 800 mg orally twice daily for 5 days 6
• Valacyclovir 500 mg twice daily for 3 days (FDA-approved 3-day regimen) 7, 5, 8

For suppressive therapy:

• Acyclovir 400 mg orally twice daily 3
• Valacyclovir 500 mg once daily (only once-daily FDA-approved option) 7, 8

Key HSV treatment principles:

• Effective antiviral regimens include acyclovir, valacyclovir, and famciclovir 3
• Topical acyclovir is substantially less effective than oral therapy and should not be used 6
• Antivirals partially control symptoms but neither eradicate latent virus nor affect recurrence frequency after discontinuation 3

Herpes Zoster Treatment

For immunocompetent patients:

• Acyclovir 800 mg orally 5 times daily for 7-10 days 4, 9
• Valacyclovir 1000 mg orally 3 times daily for 7 days 4, 7
• Famciclovir 500 mg orally 3 times daily for 7 days 4
• Treatment should continue until all lesions have scabbed, not just for an arbitrary 7-day period 4, 9

For immunocompromised or disseminated disease:

• High-dose IV acyclovir 10 mg/kg every 8 hours is the treatment of choice for severely compromised hosts 3, 9
• Treatment should continue for minimum 7-10 days and until clinical resolution 9
• Consider temporary reduction in immunosuppressive medications 4, 9

Critical timing considerations:

• Treatment is most effective when initiated within 48-72 hours of rash onset to reduce pain duration and prevent postherpetic neuralgia 4, 5
• Earlier treatment initiation (within 4 days) significantly reduces mortality in herpes simplex encephalitis from 28% to 8% 3

Special Populations

HIV-Infected Patients

• HSV in HIV-infected persons requires longer treatment courses than immunocompetent individuals, with slower clinical improvement 3
• Higher oral acyclovir doses (up to 800 mg 5-6 times daily) may be needed for herpes zoster 9
• Consider long-term acyclovir prophylaxis (400 mg 2-3 times daily) for recurrent disease 9

Immunocompromised Hosts

• Acyclovir-resistant HSV should be suspected if lesions persist despite appropriate therapy 3, 10
• For acyclovir-resistant HSV, foscarnet 40 mg/kg IV three times daily or 60 mg/kg twice daily is the alternative 10
• Immunocompromised patients with herpes zoster should be considered for IV therapy even with localized disease 4

Diagnostic Confirmation

HSV Diagnosis

• Diagnosis should be confirmed by viral culture or HSV type-specific serologic tests due to high proportion of unrecognized infection 3
• Type-specific assays rely on detection of antibodies to HSV-specific glycoprotein G1 and G2 3

VZV Diagnosis

• Clinical diagnosis is usually sufficient in immunocompetent patients 2
• Laboratory confirmation is needed for immunocompromised patients with atypical presentations 9

Common Pitfalls to Avoid

• Never use topical antivirals as monotherapy - they are substantially less effective than systemic therapy 6, 4, 9
• Do not stop herpes zoster treatment at 7 days if lesions remain active - continue until all lesions have scabbed 4, 9
• Do not delay treatment waiting for laboratory confirmation in suspected herpes simplex encephalitis - start IV acyclovir immediately 3
• Avoid topical corticosteroids for HSV unless used in conjunction with antiviral therapy, as they potentiate infection 6
• Monitor renal function closely during IV acyclovir therapy with dose adjustments for renal impairment 9, 11

Prevention Strategies

• Recombinant zoster vaccine (Shingrix) is recommended for adults ≥50 years regardless of prior herpes zoster episodes 4, 9
• Vaccination should ideally occur before initiating immunosuppressive therapies 9
• Antiviral prophylaxis against HSV/VZV should be considered in patients with recurrent reactivations or additional risk factors such as high-dose steroids or rituximab 3