Varicella-Zoster Virus Infections¶
Chapter 198 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Varicella-zoster virus (VZV) causes two distinct syndromes: varicella (chickenpox) and herpes zoster (shingles).
- VZV is a neurotropic herpesvirus with a lipid envelope and double-stranded DNA genome.
- Antiviral therapy (acyclovir, valacyclovir, famciclovir) is critical for immunocompromised patients to prevent visceral complications.
- Vaccination (varicella vaccine for children, Shingrix for adults ≥ 50) significantly reduces incidence of both varicella and shingles.
- Postherpetic neuralgia is the most common complication of herpes zoster, particularly in older adults.
1. DEFINITION & OVERVIEW¶
Varicella-zoster virus (VZV) causes two distinct clinical syndromes: varicella (chickenpox) and herpes zoster (shingles). Chickenpox is a highly contagious, exanthematous vesicular rash of childhood, while herpes zoster presents as a dermatomal vesicular rash with severe pain. VZV is a member of the Herpesviridae family, with a lipid envelope, icosahedral nucleocapsid, and ~125,000 bp double-stranded DNA.
1.1 Clinical Syndromes¶
Varicella (chickenpox): Benign childhood infection with exanthematous vesicular rash. Herpes zoster (shingles): Reactivation of latent VZV in dorsal root ganglia, presenting as dermatomal vesicular rash with severe pain.
1.2 Viral Structure¶
Lipid envelope surrounds a nucleocapsid with icosahedral symmetry. Total diameter ~180–200 nm. Central double-stranded DNA ~125,000 bp in length.
2. EPIDEMIOLOGY¶
Chickenpox is highly contagious with attack rate ≥ 90% in seronegative individuals. Incidence peaks in temperate zones during late winter/early spring. Varicella pneumonia occurs more frequently in adults (up to 20% of cases) and is severe in pregnant women. Shingles incidence peaks in sixth decade of life (5–10 cases/1000 persons).
2.1 Chickenpox¶
Endemic in populations; epidemics occur in susceptible individuals. 50% of cases occur in children 5–9 years old. Annualized incidence decreased by ~90% after chickenpox vaccination. Neonatal HSV cases could be prevented by reducing maternal HSV acquisition in third trimester.
2.2 Shingles¶
Annual incidence ~1.2 million in U.S. Vaccination likely reduced incidence. Recurrent shingles is rare except in immunocompromised hosts (e.g., HIV/AIDS).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Primary infection occurs via respiratory route, leading to viremia and cutaneous lesions. Reactivation from dorsal root ganglia causes herpes zoster. VZV can cause CNS involvement (encephalitis, meningitis) and visceral complications (pneumonia, hepatitis) in immunocompromised hosts.
3.1 Primary Infection¶
Respiratory transmission leads to nasopharyngeal replication, lymphatic dissemination, and viremia. Skin lesions develop with multinucleated giant cells and eosinophilic inclusions.
3.2 Reactivation¶
Latent VZV in dorsal root ganglia reactivates, causing dermatomal rash. Mechanism of reactivation unclear. CNS involvement may occur with perivascular cuffing and focal necrosis.
4. CLINICAL FEATURES¶
Chickenpox presents with low-grade fever, malaise, and exanthematous vesicular rash. Shingles presents with unilateral dermatomal rash, often with severe pain. Complications include bacterial superinfection, encephalitis, pneumonia, and postherpetic neuralgia.
4.1 Chickenpox¶
Rash evolves from maculopapules to vesicles (5–10 mm), crusting over 2–4 weeks. Complications: bacterial superinfection (Staphylococcus, Streptococcus), CNS involvement (acute cerebellar ataxia), varicella pneumonia, and Reye syndrome (aspirin-associated).
4.2 Shingles¶
Unilateral dermatomal vesicular rash with severe pain. Commonly involves T3–L3 dermatomes. Zoster ophthalmicus may cause blindness. Ramsay Hunt syndrome involves facial palsy and auricular vesicles.
5. DIFFERENTIAL DIAGNOSIS¶
Chickenpox: Disseminated HSV, coxsackievirus, echovirus, atypical measles. Shingles: HSV, coxsackievirus, bacterial infections. Mpox and smallpox (bioterrorism concern) have larger, uniform lesions. Rickettsialpox mimics chickenpox with herald spot and headache.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis confirmed by PCR detection of VZV DNA in vesicular fluid, blood, or saliva. Serology (FAMA, ELISA) detects IgM/IgG. Tzanck smear shows multinucleated giant cells (60% sensitivity). VZIG used for high-risk exposures within 96 h.
Table 198-1: Indications for Varicella-Zoster Immune Globulin (VZIG)¶
| Indication | Population | Timing |
|---|---|---|
| Neonatal varicella | Infants born to mothers with chickenpox within 5 days before delivery or within 48 h postpartum | Within 96 h (preferably 72 h) of exposure |
| Immunocompromised patients | Patients with HIV, cancer, or transplant recipients | Within 96 h of exposure |
| High-risk contacts | Healthcare workers, pregnant women, immunocompromised individuals | Within 96 h of exposure |
6.1 Diagnostic Methods¶
PCR (gold standard for VZV DNA), serology (IgM/IgG), Tzanck smear, and viral culture. CSF analysis for CNS involvement (pleocytosis, elevated protein).
7. MANAGEMENT & TREATMENT¶
Antiviral therapy (acyclovir, valacyclovir, famciclovir) reduces severity and complications. Supportive care includes analgesia, antipruritics, and wound care. Corticosteroids may be used for severe cases but require concurrent antiviral therapy.
7.1 Antiviral Therapy¶
Acyclovir (800 mg TID for 7–10 days), valacyclovir (1 g TID for 5–7 days), famciclovir (500 mg TID for 7 days). Preferred for immunocompromised patients. IV acyclovir (10 mg/kg every 8 h) for severe cases.
7.2 Supportive Care¶
Hygiene, antipruritics (calamine, antihistamines), analgesia (NSAIDs, opioids), and wound care. Avoid aspirin to prevent Reye syndrome.
8. PROGNOSIS & COMPLICATIONS¶
Chickenpox is generally benign but can be severe in adults and immunocompromised. Shingles has a 5–10% mortality rate in immunocompromised patients. Postherpetic neuralgia affects 50% of patients >50 years. VZV reactivation can cause visceral complications (pneumonia, hepatitis).
8.1 Complications¶
Chickenpox: Bacterial superinfection, CNS involvement, pneumonia, Reye syndrome. Shingles: Postherpetic neuralgia, bacterial superinfection, visceral dissemination (10% mortality).
9. SPECIAL CONSIDERATIONS¶
Vaccination: Live attenuated varicella vaccine for children (2 doses), Shingrix for adults ≥ 50. Pregnancy: Avoid varicella vaccine; acyclovir safe in pregnancy. HIV: Tenofovir reduces HSV-2 acquisition but not established infection. Neonatal HSV: Prevent by reducing maternal HSV acquisition in third trimester.
9.1 Vaccination¶
Varicella vaccine (Oka strain) for children >1 year, 2 doses. Shingrix (HZ/su) for adults ≥ 50 (97.2% efficacy). Inactivated vaccine reduces shingles in transplant recipients.
9.2 Pregnancy¶
Avoid varicella vaccine; acyclovir safe. Neonatal varicella mortality ~30% without maternal antibodies. Varicella pneumonia severe in pregnant women.
10. KEY POINTS & CLINICAL PEARLS¶
VZV causes varicella and shingles; vaccines prevent both. Antiviral therapy reduces complications in immunocompromised. Postherpetic neuralgia is common in older adults. VZIG used for high-risk exposures within 96 h. Avoid aspirin in chickenpox to prevent Reye syndrome.