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Varicella-Zoster Virus Infections

Part 5: Infectious Diseases | Part 5 – Infectious Diseases: Viral (incl. HIV) · Part 5 – Infectious Diseases: Viral (incl. HIV) · Chapter 198

Key Clinical Points

  1. VZV causes two distinct clinical syndromes: varicella (chickenpox) and herpes zoster (shingles).
  2. Chickenpox has an attack rate of ≥90% among susceptible individuals with a 10–21 day incubation period.
  3. Herpes zoster incidence peaks in the sixth decade of life, with reactivation from dorsal root ganglia.
  4. Shingrix vaccine has 97.2% efficacy for preventing herpes zoster.
  5. Acyclovir does not reduce HIV acquisition but lowers viral load in MSM by 1.3 log vs. 0.9 log.
  6. Aspirin use in chickenpox is contraindicated due to Reye syndrome risk.
  7. Zoster ophthalmicus with Hutchinson sign (nose tip lesion) carries high eye involvement risk.
  8. Immunocompromised patients have 30–50% visceral complication rates and 15% mortality without antivirals.
  9. VZIG should be administered within 72 h of exposure for optimal efficacy.
  10. Postherpetic neuralgia occurs in ≥50% of patients over age 50.

1. DEFINITION & OVERVIEW

Varicella-zoster virus (VZV) causes two distinct clinical syndromes: varicella (chickenpox) and herpes zoster (shingles). Humans are the only known reservoir for VZV.

Definition (Harrison's 22e): Varicella-zoster virus (VZV) causes two distinct clinical syndromes: varicella (chickenpox) and herpes zoster (shingles).

  • Chickenpox is a benign childhood illness with exanthematous vesicular rash.
  • Herpes zoster presents as unilateral dermatomal vesicles with severe pain, typically in the sixth decade of life.
  • VZV structure: lipid envelope, icosahedral nucleocapsid (180–200 nm), and ~125,000 bp double-stranded DNA.

1.1 Virus Structure & Classification

• Family: Herpesviridae • Structural Features: ◦ Lipid envelope surrounding nucleocapsid ◦ Icosahedral symmetry ◦ ~180–200 nm diameter ◦ Central double-stranded DNA (~125,000 bp)

2. EPIDEMIOLOGY

• Chickenpox: ◦ Attack rate: ≥90% in susceptible individuals ◦ Seasonality: Peaks in late winter/early spring ◦ Pre-vaccine era: 50% of cases in 5–9 year olds ◦ Post-vaccine: Significant incidence reduction in children • Herpes Zoster: ◦ Incidence: 5–10 cases/1000 persons in those ≥60 years ◦ Annual US cases: ~1.2 million • Risk Factors: ◦ Modifiable: Lack of vaccination, immunosuppression ◦ Non-modifiable: Age >50, prior infection, genetic susceptibility

3. ETIOLOGY & PATHOPHYSIOLOGY

• Transmission: Respiratory route → nasopharyngeal replication → lymphatic seeding → viremia. • Latency: Occurs in dorsal root ganglia after primary infection. • Reactivation: Mechanism unknown.

3.1 Pathogenesis Cascade

  1. Respiratory transmission
  2. Nasopharyngeal replication
  3. Lymphatic seeding
  4. Viremia
  5. Skin lesions
  6. Ganglial latency
  7. Reactivation
  8. Dermatomal rash

3.2 Histopathology

• Skin Lesions: ◦ Vesicles in dermis/corium ◦ Ballooning degeneration ◦ Multinucleated giant cells ◦ Eosinophilic intranuclear inclusions (See Figure 198-1) • CNS Involvement: Perivascular cuffing, focal hemorrhagic necrosis (rare) • Pulmonary: Interstitial pneumonitis, multinucleated giant cells

4. CLINICAL FEATURES

• Chickenpox: ◦ Incubation: 10–21 days (usually 14–17) ◦ Symptoms: Fever (37.8°C–39.4°C), malaise, rash progression from maculopapules to vesicles ◦ Lesions: Trunk/facial onset, 5–10 mm diameter, erythematous base (See Figure 198-1) • Herpes Zoster: ◦ Prodrome: Pain precedes rash by 48–72 h ◦ Distribution: Unilateral dermatomal eruption (T3–L3 most common) ◦ Complications: Postherpetic neuralgia, zoster ophthalmicus (Hutchinson sign), Ramsay Hunt syndrome

4.1 Chickenpox Clinical Presentation

• Incubation: 10–21 days • Rash Evolution: Maculopapules → vesicles over hours/days; Successive crops over 2–4 days • Mucosal Involvement: Pharynx/vagina • Lesion Count: Varies from few to 2000

4.2 Herpes Zoster Clinical Presentation

• Prodromal Pain: Precedes rash by 48–72 h • Distribution: Unilateral dermatomal (T3–L3) • Zoster sine herpetica: Pain without rash • Ramsay Hunt syndrome: Facial palsy + taste loss + ear vesicles

4.3 Complications

• Secondary Infection: S. aureus/S. pyogenes • CNS Complications: ◦ Acute cerebellar ataxia ◦ Meningitis (lymphocytes + elevated protein) • Varicella Pneumonia: Tachypnea, dyspnea, interstitial pneumonitis • Immunocompromised Risks: ◦ Visceral complications: 30–50% of cases ◦ Disseminated zoster: 40% in lymphoma patients (See Figure 198-2 and 198-3)

5. DIFFERENTIAL DIAGNOSIS

• Chickenpox Mimics: ◦ HSV infection in atopic dermatitis ◦ Coxsackievirus/echovirus vesiculopapular rashes ◦ Atypical measles (morbilliform with hemorrhagic component) • Herpes Zoster Mimics: ◦ HSV/coxsackievirus dermatomal lesions ◦ Rickettsialpox: Herald spot at mite bite site ◦ Mpox: Endemic area travel history ◦ Smallpox: Larger uniform lesions

6. INVESTIGATIONS & DIAGNOSIS

  1. Initial Screening: Tzanck smear (sensitivity ~60%)
  2. Preferred Method: PCR (vesicular fluid, blood, saliva)
  3. Serology: FAMA test/ELISA (most sensitive)
  4. CSF Analysis (for CNS involvement): ◦ Findings: Lymphocytes + elevated protein ◦ Clinical presentation: Headache, fever, photophobia

7. MANAGEMENT & TREATMENT

  1. Chickenpox Management: • Hygiene: Daily bathing, nail trimming • Antipruritics: Topical dressings, tepid baths • Contraindication: Aspirin (Reye syndrome risk)
  2. Herpes Zoster Pharmacologic Therapy: • Acyclovir: 800 mg PO q5h x 7–10d • Valacyclovir: 1 g PO q8h x 5–7d • Famciclovir: 500 mg PO q8h x 7d (not licensed for varicella)
  3. Immunocompromised Patients: • IV acyclovir: 10 mg/kg q8h x 7d • Corticosteroids: Only with antiviral therapy
  4. Corticosteroid Regimen (Elderly with moderate/severe pain): • Prednisone: 60 mg/d d1–7, 30 mg/d d8–14, 15 mg/d d15–21 • Contraindications: Osteoporosis, diabetes, hypertension
  5. Ophthalmology Management: • Referral: Immediate ophthalmologist referral for zoster ophthalmicus • Therapy: Analgesics + atropine + antivirals (acyclovir/valacyclovir/famciclovir)

7.1 Pharmacologic Therapy

• Acyclovir: ◦ Adults (chickenpox ≤24h): 800 mg PO q5h x 5–7d ◦ Herpes zoster: 800 mg PO q5h x 7–10d • Valacyclovir: Herpes zoster 1 g PO q8h x 5–7d (licensed for children) • Famciclovir: Herpes zoster 500 mg q8h x 7d (not licensed for varicella)

7.2 Corticosteroid Use

• Indications: Elderly with moderate/severe pain • Regimen: Prednisone 60 mg/d d1–7, 30 mg/d d8–14, 15 mg/d d15–21 • Contraindications: Osteoporosis, diabetes, hypertension

7.3 Ophthalmology Management

• Zoster ophthalmicus: Immediate ophthalmologist referral → Therapy: analgesics + atropine + antivirals (acyclovir/valacyclovir/famciclovir)

8. PROGNOSIS & COMPLICATIONS

• Chickenpox Duration: 7–10 days; skin normalization in 2–4 weeks • Postherpetic Neuralgia (PHN): ≥50% of patients >50 years • CNS Complications: ◦ Meningitis (benign in immunocompetent children) ◦ Rare: Granulomatous angiitis with hemiplegia • Perinatal Varicella: 30% mortality if maternal disease within 5 days of delivery

9. SPECIAL CONSIDERATIONS

• Vaccination: ◦ Varicella vaccine (children) + booster ◦ Shingrix: For patients ≥50 years, 97.2% efficacy • Post-exposure Prophylaxis: ◦ VZIG: Administered within 72 h of exposure for optimal efficacy ◦ Acyclovir: For immunocompromised contacts

10. KEY PEARLS & CLINICAL TRAPS

• Hutchinson sign: Indicates high risk of zoster ophthalmicus. • Shingrix efficacy: 97.2% (95% CI 93.7–99.0%). • Acyclovir & HIV: Does not reduce HIV acquisition in MSM; lowers viral load by 1.3 log vs. 0.9 log. • Postherpetic neuralgia: Prevalence in patients >50 years is ≥50%.