Shingles

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 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 ophthalmicus), 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. The recombinant zoster vaccine is recommended for the prevention of herpes zoster in all individuals ≥ 50 years of age and immunocompromised individuals ≥ 19 years of age.

• Incidence ^[1]
  • Overall: 2.5–4/1,000 per year in the US ^[2]
  • Among individuals ≥ 60 years old: 10/1,000 per year in the US
  • Incidence of recurrence: unknown
• Prevalence: increasing among adults in the US ^[1][3]
• Sex: ♀ > ♂ ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Causative pathogen: : varicella-zoster virus (VZV)
• Transmission: via respiratory droplets and direct contact with VZV-infected vesicular fluid, causing chickenpox in those infected
• Risk factors for VZV reactivation: Reactivation typically occurs in immunocompromised individuals.
  • Decline in immune function with advancing age
  • Malignancy
  • HIV infection
  • Immunosuppressive therapy
  • Malnutrition
  • Chronic stress

• Primary infection (chickenpox): respiratory transmission → VZV inoculates the lymphoid tissue of the nasopharynx and, subsequently, regional lymphoid tissue → viremia and chickenpox → recovery from chickenpox, but virus remains dormant in dorsal root ganglia (unless reactivated → recurrent infection)
• Reactivation (shingles): VZV reactivated, often many years after the primary infection (e.g., especially in immunocompromised individuals) → virus replicates in the dorsal root ganglia → travels through peripheral sensory nerves to the skin → shingles (less contagious than primary infection) ^[4]

• Main symptoms: dermatomal distribution, typically affecting 1–3 dermatomes on one side of the body (most commonly affects the cervical, trigeminal, thoracic, and lumbar dermatomes) ; ^[5]
  • Pain ^[5]
    • The most frequent symptom and may precede the rash
    • Usually described as “burning”, “throbbing”, or “stabbing”
    • Allodynia may occur.
  • Erythematous maculopapular rash that quickly evolves into vesicular lesions ^[5]
    • 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, generalized, or may not be present at all.
• Additional symptoms ^[5]
  • Fever, headache, and fatigue
  • Paresthesia
  • Itching
  • Motor deficits (rare)
  • Children: usually milder course and lower risk of complications
  • Newborns: See “Congenital varicella syndrome.”
• Disseminated herpes zoster
  • Herpes zoster characterized by > 20 extradermatomal lesions, involvement of ≥ 3 dermatomes, and/or visceral organ involvement ^[6][7]
    • Pneumonia ^[8]
      • Acute course with dyspnea, tachypnea, chest pain, hemoptysis
      • Imaging shows nodular interstitial infiltrates
    • Hepatitis
    • Meningoencephalitis
    • Acute retinal necrosis
  • Typically seen in immunocompromised patients
• Atypical presentation: may be seen in immunocompromised individuals
  • No rash
  • Recurrent herpes zoster
  • Disseminated zoster

Herpes zoster ophthalmicus (HZO) ^[9]

• Definition: reactivation of VZV in the ophthalmic division of the trigeminal nerve
• Epidemiology: occurs in 10–20% of herpes zoster cases ^[9]
• Clinical features ^[10]
  • Fever and skin symptoms as in shingles (see “Clinical features” above)
  • Herpes zoster conjunctivitis
  • 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:
    • Possible severe intraocular infection (uveitis, iritis, conjunctivitis, keratitis, and optic neuritis)
    • Positive Hutchinson sign of the nose: a vesicular rash on the nasal alae
• Diagnosis
  • Slit-lamp examination with fluorescein staining
  • Fundoscopy to assess for retinal involvement
• Treatment ^[10][11][12]
  • Consult an ophthalmologist urgently, as HZO is a vision-threatening condition.
  • Start antiviral therapy for herpes zoster.
  • Consider IV antiviral therapy for immunocompromised patients or those with retinal involvement.
  • Topical treatment may be added depending on the presentation. ^[10][12]
  • Consider oral analgesia and lubricating eye drops to help manage pain.
  • See also “HIV-associated ocular manifestations” for the management of HZO in patients with HIV.
• Complication
  • Can result in blindness, if not treated properly
  • Glaucoma

Herpes zoster oticus ^[13]

• Definition: reactivation of VZV in the geniculate ganglion, affecting the seventh (facial) and eighth (vestibulocochlear) cranial nerves (also known as Ramsay Hunt syndrome)
• Epidemiology: occurs in 0.3–18% of patients
• Clinical features
  • Fever and skin symptoms as in shingles in the auditory canal and pinna (see “Clinical features” above)
  • Vestibulocochlear nerve involvement → vertigo and sensorineural hearing loss (SNHL)
  • Facial nerve involvement → ipsilateral facial paralysis
• Diagnosis: tone audiometry

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

Clinical presentation is usually sufficient for a diagnosis. ^[10][14]

• PCR of VZV DNA ^[10][15]
  • Indications: confirmation of herpes zoster, recurrent herpes zoster, atypical presentations
  • May be performed on a variety of specimens
    • Skin lesions (vesicular fluid) ^[15]
    • CSF
    • Blood
• Additional tests to consider ^[10][15]
  • Serologic assay of VZV (IgM and IgG): can be used to identify active or passive immunity and diagnose primary VZV infection ^[16]
  • Direct fluorescent antibody (DFA) of skin scrapings: not routinely recommended because it has a low sensitivity
  • Tzanck test of skin vesicles
    • Not routinely recommended because it has a low sensitivity and specificity
    • Multinucleated giant cells with eosinophilic, intranuclear Cowdry A inclusions may be seen.
  • Patients with recurrent herpes zoster infection or disseminated zoster: Consider evaluation for underlying malignancies, immunosuppression, or other causes (e.g., herpes simplex).

Approach ^[10][14][16]

• Rash onset < 72 hours
  • Start oral antiviral therapy for herpes zoster in patients with clear indications.
  • Start IV antiviral therapy for herpes zoster for:
    • Immunocompromised patients
    • Disseminated zoster
    • Neurovascular involvement: e.g., VZV encephalitis, VZV vasculopathy, HZO with retinal involvement
  • Antiviral therapy can also be considered in patients without clear indications.
• Rash onset ≥ 72 hours
  • New vesicles continually appearing: same treatment as for rash onset < 72 hours
  • No new vesicles
    • Consider supportive care alone for patients with uncomplicated disease.
    • Consider antiviral therapy for herpes zoster in patients aged ≥ 50 years, with immune deficiency, or evidence of complications (e.g., disseminated zoster, neurological involvement).
• Supportive care
  • Provide routine wound care and adequate analgesia for all patients.
  • Consider adjuvant corticosteroids in select patients.
• Infection control measures ^[16]
  • Use airborne precautions and contact precautions when evaluating or admitting patients with suspected shingles.
  • Advise patients to avoid contact with pregnant or immunocompromised individuals, and infants, until all lesions have crusted over.
  • Trace any at-risk patient contacts for consideration of varicella-zoster immunoglobulin (see “VZIG”).
• Disposition: See “Admission criteria and consultations.”

Patients seeking care for suspected shingles should be placed on both airborne precautions and contact precautions to prevent transmission to other at-risk individuals (e.g., VZV-naive or immunocompromised individuals) until all lesions have crusted over. ^[17]

Antiviral therapy for herpes zoster ^[10][14][16]

Antiviral therapy speeds up the resolution of lesions, reduces viral shedding, reduces the formation of new lesions, and decreases pain. It is most effective if administered within approx. 72 hours or while new lesions are erupting.

• Indications ^[10]
  • Age > 50 years
  • Moderate or severe rash and pain
  • Immunocompromised patients
  • Signs of disseminated zoster and/or neurological complications
  • Nontruncal involvement (e.g., herpes zoster ophthalmicus)
• Regimens ^[10][18]
  • For immunocompetent patients (or mild uncomplicated disease in immunocompromised patients) choose one of the following:
    • Acyclovir ^[10]
    • Valacyclovir ^[10]
    • Famciclovir ^[10]
  • Immunocompromised patients; and/or those with disseminated zoster: IV acyclovir

Antiviral therapy should be initiated as early as possible since the effectiveness of antiviral treatment decreases as the disease progresses.

Anti-inflammatory and analgesic therapy ^[10][14][19]

Pain control is vital to maintain patients' quality of life and prevent postherpetic neuralgia.

• General principles
  • Consider prescribing medication regularly (e.g., every 6 hours) rather than as needed.
  • Reassess frequently to ensure adequate analgesia and consider using standardized scales to monitor pain.
  • For patients requiring opioid analgesia: Change to long-acting formulations once an effective dose is reached.
  • For refractory or severe pain: Consider referral to a pain specialist for possible neural blockade. ^[10]
• Recommended regimens
  • For mild pain, consider one or more of the following: ^[10]
    • Acetaminophen ^[14]
    • NSAIDs, e.g., ibuprofen ^[14]
    • A weak opioid, e.g., tramadol ^[10]
  • For moderate to severe pain, add one of the following: ^[10]
    • A strong opioid, e.g., oxycodone ^[10]
    • Nortriptyline ^[19]
    • Gabapentin ^[10]
    • Pregabalin ^[10]
    • Corticosteroids

Corticosteroids ^[10]

• Consider adjuvant corticosteroids in patients with:
  • CNS involvement
  • Cranial nerve involvement (e.g., facial nerve palsy, herpes zoster oticus)
  • HZO, especially if there is significant periorbital edema
  • Severe pain
• Options
  • Prednisolone ^[14]
  • Prednisone ^[10]

Admission criteria and consultations ^[10]

• Consider hospitalization if:
  • The patient is immunocompromised
  • Symptoms are atypical and/or severe (e.g., refractory or severe pain and rash, involvement of more than two dermatomes, disseminated zoster)
  • There are complications (e.g., signs of myelitis, meningoencephalitis, ophthalmic involvement, or severe bacterial superinfection)
• Consider the following specialist consultations:
  • Infectious diseases: disseminated zoster, pregnant patients, complicated cases
  • Ophthalmology: herpes zoster ophthalmicus
  • Pain specialist: severe or refractory pain
  • Neurology: neurological complications

• Initiate antiviral therapy.
• Pain management and supportive care
• Consider adjunctive corticosteroids.
• Admit to the hospital and administer IV antivirals if there are signs of complicated herpes zoster, immunocompromised state, or disseminated zoster.
• Consider specialist consultation.
• Immunization with zoster vaccine

Postherpetic neuralgia ^[14][20][21]

• Definition: chronic neuropathic pain persisting for at least three months in the area previously affected by the rash
• Epidemiology ^[20]
  • Most common complication (occurs in 10–20% of overall herpes zoster cases)
  • Strong association with age ^[20]
• Risk factors ^[14][20]
  • Age > 50 years
  • Severe infection (severe pain or rash)
  • Ocular involvement
  • Immunosuppression
• Clinical features ^[14]
  • Pain (including allodynia, paresthesias, dysesthesias) in the same dermatome as the rash
  • Duration of symptoms > 3 months but can persist for years
• Treatment ^{[10][14][19][21]}
  • The initial choice of analgesics should be guided by side-effect profiles, the potential for drug interactions, and patient comorbidities.
  • One of the following tricyclic antidepressants: ^[10][19][21]
    • Amitriptyline ^[21]
    • Nortriptyline ^[21]
    • Relative contraindications: patients with heart disease, epilepsy, or glaucoma
    • Should be used with caution in elderly patients
  • One of the following anticonvulsants: ^[10][19][21]
    • Pregabalin ^[21]
    • Gabapentin ^[21]
  • Topical treatments ^[10][19][21]
    • Capsaicin patch or cream ^[21]
    • Lidocaine patch ^[21]
  • Opioids ^[21]
    • Morphine ^[21]
    • Oxycodone ^[21]
    • Tramadol ^[21]
  • Interventional pain therapy: Consider intrathecal glucocorticoid injections and/or neural blockade for severe cases.
• Prognosis: Pain typically continues to decrease over the first year but may last for months to years. ^[21]

Herpes zoster encephalitis ^[10]

• Risk factors ^[10]
  • Immunosuppression
  • More than one prior episode of herpes zoster infection
  • Herpes zoster with cranial nerve involvement
  • Disseminated herpes zoster infection
• Clinical features ^[10]
  • Usually manifests as acute or subacute delirium within days of vesicular eruption
  • Focal neurologic deficits
  • Possible additional features
    • Headache, fever, meningismus
    • Ataxia
    • Seizures
• Diagnostics
  • CSF analysis
    • Mononuclear pleocytosis
    • PCR positive for VZV DNA
  • MRI brain may show:
    • Plaque-like lesions in white matter
    • Signs of demyelination
    • Late findings: hemorrhagic infarcts or ischemia
• Treatment ^[10]
  • Acyclovir ^[10]
  • Corticosteroids (e.g., prednisolone ) ^[10]
• Prognosis
  • Average mortality rate ∼ 10% ^[10]
  • Chronic VZV encephalitis in immunocompromised patients has a very poor prognosis.

Additional complications ^[10]

• Cranial nerve involvement: Facial nerve palsy
• CNS involvement
  • Meningitis
  • Guillain-Barré syndrome
  • Transverse myelitis
  • VZV vasculopathy: persistent postviral inflammation of intracerebral arteries that can increase the risk of stroke ^[22]

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

Routine chickenpox immunization and shingles vaccination (see also “Immunization schedule”) are recommended for all eligible individuals. ^[23][24]

Shingles vaccination ^{[24][25][26][27]}

• General principles
  • Consists of 2 doses of recombinant zoster vaccine (RZV) administered 2–6 months apart
  • At-risk individuals should begin an RZV immunization series regardless of previous shingles outbreak or vaccination.
• Indications
  • All individuals ≥ 50 years of age without contraindications to vaccination
  • Immunocompromised individuals ≥ 19 years of age, including those with HIV ^[27][28]
• Special considerations
  • Avoid vaccination of patients with active herpes zoster infection until symptoms improve. ^[24]
  • Consider deferring vaccination in pregnant individuals until after delivery. ^[29]

RZV is different from the varicella vaccine and should not be administered for the prevention of chickenpox. ^[24]

Screening for evidence of immunity to varicella is not routinely required prior to shingles vaccination. ^[30]