varicella-zoster%20virus%20infection
VARICELLA-ZOSTER VIRUS INFECTION
Varicella, also known as chickenpox, is a self-limited benign disease caused by primary varicella-zoster virus (VZV) infection characterized by fever, malaise, and generalized pruritic vesicular rash.
The average incubation period is 14-16 days. It is transmitted via direct contact with vesicular fluid or inhalation of aerosolized respiratory secretions or via droplet route during face-to-face contact.
Hallmark sign is pruritic rash that begins in the scalp and face which eventually spreads to the trunks and extremities.

History

Varicella

  • Determine if the patient had a previous exposure to patient with chickenpox
  • Identify immunocompromised patients [human immunodeficiency virus (HIV)-seropositive, leukemia and organ transplant patients]
    • Have higher risk of developing varicella-associated morbidity and mortality
    • Systemic corticosteroid use can also increase morbidity

Herpes Zoster

  • Determine if the patient already had varicella
  • Identify immunocompromised patients (HIV-seropositive, leukemia and organ transplant patients)
    • Have higher risk of developing varicella-associated morbidity and mortality
    • Systemic corticosteroid use can also increase morbidity

Laboratory Tests

Varicella

  • Lab confirmation of the diagnosis is not necessary for most cases of varicella but may be necessary in subsequent episodes of varicella, atypical clinical presentation or in cases of drug resistance
  • Skin specimen, obtained by unroofing a fresh, fluid-filled vesicle and rubbing the base of the lesion with a polyester swab, is used for confirmation of varicella while blood specimen is used to test for immunity to Varicella
  • Confirmatory tests either demonstrate viral DNA/protein through polymerase chain reaction (PCR) and direct fluorescent antibody (DFA) or isolate the virus through viral culture
  • Culture
    • Gold standard for virologic confirmation, providing results within 2-3 days in newer techniques, but not highly sensitive due to high lability of varicella-zoster virus (VZV)
  • Tzanck smear
    • Convenient to perform but will not differentiate VZV from herpes simplex virus (HSV)
  • Viral DNA
    •  Hybridization and PCR are sensitive and specific for the detection of Varicella zoster virus in clinical specimens
    •  PCR: Preferred method for rapid clinical diagnosis providing results within hours
  • Serology
    • May be used as confirmatory test based on presence of immunoglobulin M (IgM) or fourfold rise in acute- & convalescent-phase immunoglobulin G (IgG) antibodies to VZV; however, test lacks sensitivity and specificity
    • Complement fixation test requires paired sera & cross-react with HSV
  • Direct & Indirect Immunofluorescence
    • Fluorescence microscopy: Rapid and sensitive in determining presence of VZV proteins in cells scraped from lesions
    • May be an alternative to PCR but is less sensitive and requires skills in obtaining and handling specimen

Herpes Zoster

  • Clinical diagnosis is sufficient in the typical case of herpes zoster, but lab diagnostic testing is useful for differentiating herpes zoster from herpes simplex, for suspected organ involvement and for atypical presentations
  • Swabs from fresh lesions or tissue biopsies can be submitted for viral culture, direct fluorescent antigen testing, or PCR should be done for uncertain diagnosis and atypical lesions
  • Scabs are very good specimen for PCR testing
  • Lesion PCR is the most sensitive and specific method for diagnosis of VZV infections
  • Culture, serology, direct and indirect immunofluorescence studies are the same with varicella

Complications

Varicella

Multiple complications can result from varicella infection:

  • Immunocompromised patients, neonates and adults (especially pregnant women) are most at risk for complications
  • Most common complication among healthy children is bacterial superinfection caused by Staphylococcus aureus or Streptococcus pyogenes that manifests as impetigo, furuncles, cellulitis, erysipelas or bullous skin lesions
    • Life-threatening disease known as necrotizing fasciitis has been reported as a complication in children
  • Extracutaneous complications are neurologic which includes acute cerebellar ataxia & meningoencephalitis as major manifestations
    • Reye’s syndrome, transverse myelitis, polyradiculitis, Guillain-Barré syndrome may also occur but are rare
  • Varicella pneumonia is the leading cause of varicella-associated morbidity among adults, pregnant and immunocompromised individuals
  • Less frequent complications are arthritis, myocarditis, glomerulonephritis
  • Transient hepatitis occurs in most children and is usually asymptomatic but fulminant liver failure may occur
  • Immune-mediated thrombocytopenia is associated with bleeding into skin lesions, petechiae, purpura, epistaxis, hematuria & gastrointestinal (GI) hemorrhage

Herpes Zoster

  • Postherpetic neuralgia (PHN)
    • PHN is pain that persists in the affected area after resolution of rash or for 3 months or more after onset of rash
    • Common complication of herpes zoster which is debilitating
    • Incidence of PHN is age-related & affects approximately 50% of patients >60 years
    • Patient may experience constant pain described as burning, aching or throbbing; intermittent pain described as stabbing or shooting; and stimulus-evoked pain (eg allodynia - pain triggered by a non-painful stimulus such as wind or piece of clothing)
  • Ophthalmic zoster (herpes zoster ophthalmicus)
    • Begins with fever, headache, decreased vision, droopy eyelid and generalized feeling of being unwell accompanied by pain or extreme sensitivity of the eye, forehead and top of the head
    • One of the frequent complications of herpes zoster involving the nasociliary branch of trigeminal nerve and has the potential to produce corneal ulceration accompanied by ocular palsy, lid ptosis, conjunctivitis, panophthalmitis, retinal vasculitis, retinal artery occlusion, optic neuritis, choroidal detachment, glaucoma and visual impairment which may lead to loss of vision
  • Acute Retinal Necrosis (ARN)
    • Seen in patients with herpes encephalitis history and some immunocompetent patients
    • Rapid progression is characteristic in advanced AIDS with 82% chance of bilateral eye involvement and 70% sustains retinal detachment
    • Patients complains of blurring of vision and pain on the affected eye
    • Clinical features: Acute iridocyclitis, vitritis, necrotizing retinitis, occlusive retinal vasculitis with rapid vision loss and retinal detachment
    • Causes high rate of visual loss
  • Progressive Outer Retinal Necrosis (PORN)
    • Occurs in AIDS patients with CD4 count of <100 cells/μL
    • Ocular findings: minimal inflammation in the aqueous and vitrous humor, absence of retinal vasculitis, multiple discrete peripheral lesion in the outer retinal layer
    • Lesions rapidly coalesce causing full thickness retinal necrosis and subsequent retinal detachment
    • Causes high rates of vision loss
  • Ramsay Hunt Syndrome
    • Also known as herpes zoster oticus 
    • Polycranial neuropathy with frequent involvement of the cranial nerves V, IX, and X
    • Reported in association with herpes simplex type 2
    • Less common complication involving the geniculate ganglion of facial nerve which presents as peripheral facial nerve palsy, tinnitus, vertigo, deafness, otalgia, loss of taste, vesicles on the ear, hard palate or tongue, nausea and vomiting
  • Disseminated Herpes Zoster
    • Can be serious to life-threatening
    • Spreads to other organs but mostly affects the lungs
    • Immunocompromised patients are more prone to danger
    • Occurs in patients with CD4 counts of <200 cells/μL
    • In patients with HIV co-infections, CNS is the primary target
    • Symptoms include CNS vasculitis, multifocal leukoencephalitis, ventriculitis, myelitis and myeloradiculitis, optic neuritis, cranial nerve palsies and focal brainstem lesions and aseptic meningitis
  • Zoster-Associated Encephalitis
    • Delirium may occur a few days after vesicular eruption, before onset of rash, or ≥6 months after a zoster episode
    • Most cases occur in immunosuppressed patients (eg HIV-infected individuals)
    • Major risk factors: Cranial or cervical dermatomal involvement, 2 or more prior episodes of zoster, disseminated herpes zoster, and impaired cell-mediated immunity
  • Stroke Syndromes
    • Occurs as secondary to infection of cerebral arteries which may be due to direct VZV invasion of the arterial surface via spread along the intracranial branches of the trigeminal nerve
    • Granulomatous angiitis or ischemic stroke syndrome involving inflammation of internal carotid artery or its branches from extension of infection in the trigeminal ganglion
    • Presents as abrupt onset of severe headache and rapid evolution to contralateral motor weakness
  • Other complications are dermatologic superinfections (impetigo, cellulitis, necrotizing fasciitis, herpes gangrenosum); neurologic (meningoencephalitis, myelitis, zoster encephalitis, zoster paresis depending on affected dermatome eg diaphragmatic paralysis, altered mentation, granulomatous angiitis or ischemic stroke syndrome involving inflammation of internal carotid artery or its branches from extension of infection in the trigeminal ganglion)
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