• Clinical science

Shingles (Herpes zoster)

Abstract

Shingles (herpes zoster) is a dermatomal rash with painful blistering that is caused by the reactivation of the varicella-zoster virus (VZV). The initial infection with VZV usually occurs early in life, presenting as chickenpox (varicella), after which the virus remains dormant in the dorsal root ganglia. Immunocompromised individuals (e.g., from stress or as a result of naturally declining immune function with age) are at increased risk of VZV reactivation. Shingles is generally a clinical diagnosis, although further testing (e.g., PCR) may be indicated in unclear cases. Treatment with antiviral drugs, such as acyclovir, is usually effective. Potential complications include encephalitis and, particularly in the elderly population, painful postherpetic neuralgia.

VZV may also affect the cranial nerves. Involvement of the trigeminal nerve may cause visual impairment up to blindness (herpes zoster opthalmicus), while involvement of the facial and vestibulocochlear nerves can cause facial paralysis and hearing loss (herpes zoster oticus). These presentations, in particular, require urgent medical attention to prevent serious complications.

Epidemiology

  • Incidence: 215/100,000 per year
  • Sex: =
  • Peak incidence: Approx. ⅔ of patients are older than 50 years; incidence increases with age

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Immunocompromised individuals are at particular risk of VZV reactivation and may be caused by:

References:[3][4][5][2]

Pathophysiology

  • Primary infection (chickenpox): respiratory transmission → VZV inoculates the lymphoid tissue of the nasopharynx and, subsequently, regional lymphoid tissue → viremia + chickenpox → recovery from chickenpox, but virus remains dormant in dorsal root ganglia (unless reactivated → recurrent infection)
  • Recurrent infection (shingles): VZV reactivated (e.g., due to immunocompromise) → virus replicates in the dorsal root ganglia → travels through peripheral sensory nerves to the skin → shingles (less contagious than primary infection)

References:[4][5][6]

Clinical features

  • Fever, headaches, fatigue
  • Dermatomal distribution typically of 1–3 dermatomes on one side of the body, most commonly between T3 and L3 → torso, hips, waist, groin, and ventral region of the upper legs)
    • Severe pain
      • Usually described as “burning”, “throbbing”, or “stabbing”
      • Allodynia may occur
    • Rash
      • Erythematous maculopapular rash that quickly evolves into vesicular lesions
        • Vesicles are initially clear → pustulation and rupture typically occur after 3 or 4 days
        • Crusting and involution typically occurs between day 7 and 10
      • Lesions may become necrotic (herpes zoster gangrenosum), generalized (herpes zoster generalisatus ) or may not present at all (zoster sine herpete) .
    • Paresthesia
    • Itching
    • Motor deficits (rare)
  • Disseminated disease (rash involves more than the primary 1–3 dermatomes) may occur in immunocompromised individuals
  • Herpes zoster in children: usually milder course and lower risk of complications
  • In newborns congenital varicella syndrome

References:[7][2][5][6][4]

Subtypes and variants

Herpes zoster ophthalmicus

  • Definition: reactivation of VZV in the ophthalmic division of the trigeminal nerve
  • Clinical features
    • Fever and skin symptoms as in shingles (see “Symptoms/clinical findings” above)
    • Herpes zoster keratitis
    • Involvement of the ophthalmic nerve: reduced corneal sensitivity with severe pain in the innervated regions (forehead, bridge and tip of the nose)
    • Involvement of the nasociliary nerve:

Herpes zoster oticus

  • Definition: : reactivation of VZV in the geniculate ganglion, affecting the seventh (facial) and eighth (vestibulocochlear) cranial nerves (also known as Ramsay Hunt syndrome)
  • Clinical features
    • Fever and skin symptoms as in shingles in the auditory canal and pinna (see “Symptoms/clinical findings” above)
    • Eighth nerve → vertigo and sensorineural hearing loss (SNHL)
    • Seventh nerve → facial paralysis
  • Diagnosis: tone audiometry

Herpes zoster ophthalmicus can lead to blindness! Herpes zoster oticus can result in hearing loss and permanent facial paralysis on the affected side!

Herpes zoster, herpes zoster oticus, and herpes zoster ophthalmicus present with identical rashes!

References:[5][2][7][4][8]

Diagnostics

  • Clinical presentation is usually sufficient for diagnosis.
  • If the clinical picture is not conclusive, diagnosis is confirmed by laboratory tests (e.g., PCR, DFA test), especially if encephalitis is suspected )
    • PCR
    • Direct flourescent antibody (DFA) test
    • Viral culture
  • Tzanck test of lesions shows multinucleated giant cells with eosinophilic, intranuclear Cowdry A inclusions

Potential malignancies should be ruled out in a recurrent herpes zoster infection of unknown cause! References:[2][5]

Treatment

Antiviral therapy should be initiated as early as possible since the effectiveness of antiviral treatment decreases as the disease progresses!References:[2][9]

Complications

  • Post-herpetic neuralgia
    • Epidemiology
      • Occurs in ∼ 10–15% of overall herpes zoster cases
      • Strong association with age
    • Clinical features: attacks of acute, intense pain, persisting for at least 3 months in the area previously affected by the rash
    • Treatment
    • Prognosis: Chronic pain develops in approximately 25–50% of affected individuals if remission does not occur within 12 months
  • Herpes zoster encephalitis
    • Risk factors: impaired immunity, more than one prior episode of herpes zoster infection, cranial/cervical affliction or disseminated zoster
    • Usually manifests as delirium within days after vesicular eruption
    • Often results in stroke

References:[10][11][7]

We list the most important complications. The selection is not exhaustive.

Prevention

References:[5][12][13][14][15]