Postherpetic Neuralgia & HSV Overview

Introduction

• Viruses consist of only one type of nucleic acid, either DNA or RNA.

Classification

• DNA viruses include herpes viruses, parvovirus, papovaviruses (human papovaviruses), poxviruses (molluscum contagiosum virus), and parapoxviruses (Milker's nodule virus).
• RNA viruses include paramyxovirus (measles virus), rubivirus (rubella virus), picornaviruses (Coxsackie virus A16 and enterovirus 71), and retroviruses (HIV).

Herpes Viruses

• HSV-1 causes herpes labialis.
• HSV-2 causes genital herpes.
• HHV-3 causes chickenpox (varicella) and shingles (herpes zoster).
• HHV-4 causes Epstein-Barr virus (Infectious Mononucleosis and oral hairy leukoplakia).
• HHV-5 causes cytomegalovirus (congenital deafness, blindness due to retinitis in AIDS patients).
• HHV-6 causes roseola infantum.
• HHV-7 causes roseola infantum and pityriasis rosea.
• HHV-8 causes Kaposi's sarcoma.

Herpes Simplex

• Etiology: Caused by herpes simplex virus (HSV). HSV comprises two antigenic types.
• HSV-1 is usually associated with facial infections, mainly in infants and young children.
• HSV-2 is classically found in genital infections, mainly after puberty and transmitted sexually.
• Sites infected by HSV types often overlap.
• Transmission: Via direct contact or droplets of infection (usually in children) and sexual contact (usually in adults).
• Primary infection: Incubation period (3-7 days). Characterized by fever/malaise, burning/painful lesions (vesicles) on erythematous base, grouping tendencies (with tender regional lymph nodes), crusting of lesions, and resolution within 2-6 weeks.
• Latent Infection: HSV gene expression severely restricted in sensory ganglia causing undetectability by host defenses.
• Recurrent infection: Due to reactivation of virus due to risk factors such as old age, immune dysfunction, trauma, stress, etc. Virus travels to the trigeminal ganglion (for HSV-1) or sacral ganglion (for HSV-2) causing recurrent disease.
• Sites of predilection: Outer third of lower lip and perioral areas (herpes labialis).

Clinical Varieties

• Herpes labialis (facial) near vermillion border/perioral areas
• Herpetic gingivostomatitis (high grade fever, painful oral ulcers)
• Eczema herpeticum (Kaposi's varicelliform eruption)
• Herpetic whitlow (infection of digits in dental and medical personnel who don't routinely use gloves)
• Keratoconjunctivitis
• Herpetic folliculitis (mainly beard region in males)
• Herpetic pneumonia (fatal)
• HS encephalitis (seizures, lethargy, irritability, tremors, poor feeding, temperature instability)
• Herpetic gladiatorum (wrestlers)
• Disseminated HS in compromised host

Neonatal Herpes

• 70% due to HSV-2.
• Clinical spectrum: localized infections (skin, eyes, and mouth); CNS disease (severe disseminated disease); sepsis, encephalitis, hepatitis, pneumonia; coagulopathy; fatality up to 50%.
• Incubation period up to 3/52 (weeks). Often diagnosed after hospital discharge.
• 70% of mothers are asymptomatic.
• Treatment: IV acyclovir (250mg/m2 every 8 hours for 7 days).

Genital Herpes

• Primary infection: often asymptomatic, but can manifest with painful/tender erosions on external genitalia, vagina, cervix, buttocks, and perineum (more common and prominent in women). Possible lymphadenopathy/dysuria (in women). Higher percentage of extragenital involvement in women. Can cause urinary retention and aseptic meningitis (10%).
• Recurrent infection: Mildly symptomatic with vesicles lasting about 1 week; frequency of outbreaks typically decreases over time.

Eczema Herpeticum

• Etiology: Due to widespread HSV-1 infection of damaged skin. Occurs in patients with atopic dermatitis, seborrheic dermatitis, scabies, or Darier's and Hailey-Hailey diseases. Patients often appear more toxic/ill.
• Diagnosis and Investigations are key.

Investigations (HSV-1 and HSV-2)

• Tzanck smear (giant multinucleated epithelial cells)
• Nonspecific
• Direct fluorescence antibody test (results available in hours; virus specific)
• Biopsy with immuno-peroxidase staining
• PCR
• Viral culture (results available in 48-72 hours)
• Serology (does not indicate current lesion or its partner)

Management of HSV Infections

• Mild uncomplicated eruptions: No systemic antiviral treatment needed; keep lesions clean and dry; topical antibacterial agents for secondary infections.
• Severe primary infection: Start antiviral therapy.
• Systemic antiviral agents (dosages depend on age- see slide 21).

Antiviral Therapy

• Primary herpes genitalis: Acyclovir cream/ointments (applied 4-5 times) are beneficial.
• Recurrent herpes genitalis: Topical imiquimod may have a beneficial effect in some cases. Topical acyclovir is not beneficial.
• First line drug: IV Foscarnet
• Second line or failure/intolerance: Cidofovir

Varicella (Chickenpox)

• Epidemiology: Very common in childhood, especially during cooler months.
• Infection with VZV (HHV-3). More severe with age/immune suppression.
• Lifelong immunity to natural infection. Prodromal symptoms (fever, malaise, headache) often precede rash by 2-3 days.
• Skin eruption: Dewdrop-like, rose petal; smaller vesicles surrounded by erythema. Lesions develop in different stages.
  • Lesions begin on face, spread to trunk, least on peripheral limbs (centripetal distribution).
• Transmission: Direct contact and respiratory droplet
• Contagious period: 4+ days before lesions to crusted lesions.
• Complications: Pneumonia (more common in adults), encephalitis and ataxia (common neurologic effects), osteomyelitis, septicemia, myocarditis, DIC, purpura fulminans, Reye's syndrome, Hepatitis, Acute encephalopathy
• Treatment: Acyclovir (20mg/kg-up to 800mg qid x 5/7)

Varicella (Chickenpox) - Transportation

• During varicella, VZV travels from skin centripetally along sensory fibers to sensory ganglia.
• The virus establishes a latent infection and persists for life.

Varicella (Chickenpox) - Recurrence

• Reactivation under certain conditions (older age, immune suppression, local trauma, etc.).
• Virus reactivates in ganglia.
• Virus spreads down sensory nerve endings, causing clusters of vesicles in dermatome.
• Herpes zoster develops from these clusters.

Varicella in Pregnant Women and Neonates

• Congenital Varicella Syndrome: Maternal infection during first 20 weeks of gestation (fetal).
• Risk of spontaneous abortion (3%) and preterm labor; risk of fetal anomalies (LBW; hypoplastic ribs/limb anomalies, ocular and CNS issues- developmental delays/microphthalmia/cataracts/nystagmus/chorioretinitis; hydrocephalus)
• Neonatal varicella: Maternal primary infection 7 days before to 2 days after delivery. Presents at 0-14 days with vesicles on erythematous base, generalized distribution. Severe cases require treatment with VZIG and IV Acyclovir.

Treatment (Varicella)

• Normal children: Benign self-limiting. Treat symptomatically with oral antihistamines/antipyretics and topical soothing agents (like calamine lotion). Routine acyclovir not typically required.
• Adolescents/Adults: Oral acyclovir (800mg 5 times/day for 7 days) as soon as possible (due to potential for life-threatening pneumonia).
• Immunosuppressed patients: Lesions similar to normal patients but more numerous, necrotic, and larger.

Herpes Zoster (Shingles)

• Etiology: VZV (chickenpox virus) reactivates in sensory root ganglion and remains dormant for years, causing herpes zoster during reactivation.
• Predisposing factors: Older age, underlying HIV infection, immunosuppression (lymphoreticular malignancies, e.g., Hodgkin's disease and leukemia).
• Pain: Almost always present; burning/excruciating/intolerable.
• Zoster sine herpete: Pain without skin lesions.
• Morphology: Closely grouped vesicles on an erythematous base, unlike the random distribution of varicella. Vesicles restricted to dermatome
• Course: Evolves more slowly than varicella; patients older than 50 frequently show more severe eruptions lasting longer (3-4 weeks).
• Complications: Secondary bacterial infection. Disseminated zoster (more than 20 lesions outside dermatome). Rule out underlying lymphoreticular malignancies (e.g., Hodgkin's disease, leukemia), and HIV infections. Involvement of eye. (Hutchinson's sign - vesicles on tip or side of nose innervated by nasociliary branch of trigeminal nerve).
• Swelling of eyelids, Ramsay Hunt syndrome (facial palsy, herpes zoster of external ear, ear pain, vertigo, and deafness), Postherpetic neuralgia.

Postherpetic Neuralgia (PHN)

• Persistent neuralgic pain in affected dermatome after healing of herpes zoster lesions.
• Most common, most troublesome, and intractable complication of herpes zoster.
• Less common/less severe in children. Frequency/severity increases with age.
• Risk factor for PHN is severe pain. Pain may be continuous or spasmodic in form. Allodynia: pain after the slightest touch or from clothing or wind. Can affect sleep routines and daily life.
• Treatment: Requires symptomatic treatment with topical therapy; oral analgesics, nerve blocks. Systemic antiviral treatment needed within the first 72 hrs to avoid this.

Recurrence (HIV)

• HIV-infected patients have a unique tendency for multiple recurrences or to involve multiple dermatomes simultaneously.

Diagnosis

• Diagnosis of herpes zoster (shingles) is based on the following:
  • severe burning pain
  • unilateral and dermatomal distribution
  • grouped vesicular eruptions on an erythematous base

Treatment (Herpes Zoster)

• Mild cases: Require symptomatic treatment using topical therapies (like calamine lotion) and oral analgesics. Avoid topical antiviral agents.
• Severe cases: Parenteral analgesics (e.g., combination of pentazocine and pheniramine maleate) for night-time pain relief. Patient reassurance is also important if the problem has accurately diagnosed.
• Antiviral therapy: Should be started within 72 hours of rash onset.

Indications for Antiviral Therapy

• Patients over 50
• Ophthalmic zoster
• Immunocompromised (or HIV-infected) Patients
• Severe involvement (e.g., disseminated or hemorrhagic or multi-dermatomal lesions)
• Antiviral drugs: Aciclovir, Valaciclovir, Famciclovir

Drugs (Herpes)

• All three drugs are pregnancy category B. Give 1 orally.
  • Aciclovir 800mg 5 times/day for 7-10 days
  • Valaciclovir 1gm TDS for 7 days
  • Famciclovir 250 or 500 mg TDS for 7 days.
• IV antiviral therapy may be indicated for severely compromised patients and advanced AIDS patients.

Epstein-Barr Virus (HHV-4)

• Gamma herpesvirus
• Infects mucosal epithelial cells and B lymphocytes.
• 95% of the population are latently infected by age 20
• Spread via oral secretions
• Causes Infectious Mononucleosis ("glandular fever"); characterized by: Fever, Adenopathy, Splenomegaly, Atypical Lymphocytosis.
• Oral Hairy Leukoplakia: Not a reactivation; a repeated direct infection. Does not scrape off with tongue blade. No treatment needed. This diagnosis should prompt HIV testing.

CMV/HHV-5

• Beta herpesvirus.
• 90% of exposed infants are asymptomatic.
• Other symptoms: Jaundice, Splenomegaly, cerebral calcifications, chorioretinitis, microcephaly, MR, deafness.
• AIDS patients (CD4 counts <50) may show retinitis, cholangitis, colitis, encephalitis, adrenalitis.
• Treatment: ganciclovir, foscarnet, cidofovir.

Roseola Infantum (Exanthem Subitum/6th Disease) - HHV-6

• High fever and LADs (lymphadenopathy).
• Fever lasts 4 days
• Fevers drop, Morbilliform rash appears
• Possible: diarrhea; otitis media; meningoencephalitis.
• Enanthem of soft palate (Nagayama spots).

HHV 7

• Associated with pityriasis rosea.
• Self-limiting skin condition; typically starts with a single large, round, or oval patch.

HHV-8

• Kaposi's sarcoma

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