Summary
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 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
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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.
Etiology
- 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 immunocompromized individuals.
- Decline in immune function with advancing age
- Malignancy
- HIV infection
- Immunosuppressive therapy
- Malnutrition
- Chronic stress
Pathophysiology
- 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]
Clinical features
-
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.
-
Pain [5]
-
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 dyspnoea, tachypnoea, chest pain, hemoptysis
- Imaging shows nodular interstitial infiltrates
- Hepatitis
- Meningoencephalitis
- Acute retinal necrosis
-
Pneumonia [8]
- Typically seen in immunocompromised patients
-
Herpes zoster characterized by > 20 extradermatomal lesions, involvement of ≥ 3 dermatomes, and/or visceral organ involvement [6][7]
-
Atypical presentation: may be seen in immunocompromised individuals
- No rash
- Recurrent herpes zoster
- Disseminated zoster
Subtypes and variants
Herpes zoster ophthalmicus [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 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
-
Complication
- Can result in blindness, if not treated properly
- Glaucoma
Herpes zoster oticus [11]
- 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 → facial paralysis
- Diagnosis: tone audiometry
Herpes zoster, herpes zoster oticus, and herpes zoster ophthalmicus present with identical rashes.
Diagnostics
Clinical presentation is usually sufficient for a diagnosis. [10][12]
- PCR of VZV DNA [10][13]
-
Additional tests to consider [10][13]
- Serologic assay of VZV (IgM and IgG): can be used to identify active or passive immunity and diagnose primary VZV infection [14]
- 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).
Treatment
Antiviral therapy [10][12][14]
Antiviral therapy speeds up the resolution of lesions, reduces viral shedding, reduces the formation of new lesions, and decreases pain. Antiviral therapy 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 ophthalmicus)
-
Regimens
-
For immunocompetent patients, choose one of the following: [10]
- Acyclovir [10]
- Valacyclovir [10]
- Famciclovir [10]
-
Immunocompromised patients and/or those with disseminated zoster [10]
- IV acyclovir [10]
-
For immunocompetent patients, choose one of the following: [10]
Antiviral therapy should be initiated as early as possible since the effectiveness of antiviral treatment decreases as the disease progresses.
Supportive care [10][12][15]
Patients should receive routine wound care. Pain control is vital to maintain patients' quality of life and prevent postherpetic neuralgia.
Anti-inflammatory and analgesic therapy [10][12][15]
- For mild pain, consider one or more of the following: [10]
- Acetaminophen [12]
- NSAIDs, e.g., ibuprofen [12]
- Tramadol [10]
- Oxycodone [10]
- For moderate to severe pain, add one of the following: [10]
- Nortriptyline [15]
- Gabapentin [10]
- Pregabalin [10]
- Corticosteroids (see below)
- For refractory or severe pain: Consider pain specialist consultation for possible neural blockade. [10]
Corticosteroids [10]
Consider an adjuvant corticosteroid taper in patients with CNS complications (e.g., Bell palsy or vasculopathy) and/or severe pain.
- Prednisolone [12]
- Prednisone [10]
Admission criteria and disposition [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
- Neurology: neurological complications
- Pain specialist: severe or refractory pain
- Ophthalmology: herpes zoster ophthalmicus
Acute management checklist
- 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
Complications
Postherpetic neuralgia [12][16][17]
- Definition: chronic neuropathic pain persisting for at least three months in the area previously affected by the rash
-
Epidemiology [16]
- Most common complication (occurs in 10–20% of overall herpes zoster cases)
- Strong association with age [16]
-
Risk factors [12][16]
- Age > 50 years
- Severe infection
- Ocular involvement
- Immunosuppression
-
Clinical features [12]
- Pain (including allodynia, paresthesias, dysesthesias) in the same dermatome as the rash
- Duration of symptoms > 3 months but can persist for years
-
Treatment [10][12][15][17]
- 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][15][17]
- Amitriptyline [17]
- Nortriptyline [17]
- Relative contraindications: patients with heart disease, epilepsy, or glaucoma
- Should be used with caution in elderly patients
- One of the following anticonvulsants: [10][15][17]
- Pregabalin [17]
- Gabapentin [17]
- Topical treatments [10][15][17]
- Topical capsaicin patch or capsaicin cream [17]
- Lidocaine patch [17]
- Opioids [17]
- 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. [17]
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
-
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
-
CSF analysis
-
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: Bell palsy
- CNS involvement
We list the most important complications. The selection is not exhaustive.
Prevention
-
Chickenpox [18]
-
Live varicella vaccine is recommended for all healthy people with no evidence of immunity to varicella.
- Children: 1st dose at 12–15 months, 2nd dose at 4–6 years (see “Immunization schedule.”)
- Adolescents (≥ 13 years of age) and adults with no evidence of immunity: 2 doses, 4–8 weeks apart
- Contraindications include immunosuppression, known allergy to the vaccine, pregnancy, and transfusion of blood products in the last year.
-
Live varicella vaccine is recommended for all healthy people with no evidence of immunity to varicella.
-
Shingles [19]
-
Recombinant herpes zoster vaccine
- Recommended for individuals ≥ 50 years of age (regardless of previous chickenpox status)
- Administered in 2 doses, 2–6 months apart
- Contraindications include severe allergies to gelatin, neomycin, or any other component of a shingles vaccine.
-
Recombinant herpes zoster vaccine
The live herpes zoster vaccine is contraindicated in immunosuppressed individuals.