Herpes Zoster (Shingles)
Reactivation of latent VZV in a dorsal root ganglion → painful unilateral dermatomal vesicular eruption.
Also known as: herpes zoster, shingles, zoster, postherpetic neuralgia, zoster ophthalmicus
Overview
Reactivation of varicella-zoster virus (VZV) latent in dorsal root or cranial nerve ganglia, producing a painful unilateral vesicular eruption confined to one or two adjacent dermatomes.
Epidemiology
Lifetime risk ~30% in the US; incidence rises sharply after age 50. ~1 million US cases annually. Increased severity, duration, and risk of postherpetic neuralgia (PHN) with age and immunosuppression.
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Risk factors
- Age >50 (declining cell-mediated immunity)
- Immunosuppression: HIV, malignancy (especially hematologic), transplant, chemotherapy, biologics, chronic corticosteroids
- Stress, trauma
- Female sex (slightly higher risk)
- Family history of zoster
Pathophysiology
Primary varicella infection establishes lifelong latency in sensory ganglia. Decline in VZV-specific cell-mediated immunity allows reactivation → viral replication in ganglion → axonal transport down sensory nerve → cutaneous vesicular eruption in dermatomal distribution. Neural damage produces acute neuritis and, in some, chronic postherpetic neuralgia.
Clinical presentation
Symptoms
- Prodromal pain, burning, paresthesia in dermatomal distribution 1-5 days (occasionally weeks) before rash
- Acute neuritic pain — sharp, burning, lancinating, allodynia
- Malaise, low-grade fever, headache
- Pruritus, tingling in affected area
Signs / physical exam
- Unilateral grouped vesicles on erythematous base in a dermatomal distribution — does NOT cross midline (except small overlap)
- Most common dermatomes: thoracic (T3-L2), trigeminal (especially V1 — ophthalmic), cervical, lumbar
- Lesions progress: erythematous macules/papules → vesicles → pustules → crusts over 7-10 days; complete healing 2-4 weeks (longer in elderly)
- Zoster ophthalmicus (V1): involvement of forehead, upper eyelid, tip of nose (Hutchinson sign = nasociliary nerve = high risk of ocular involvement)
- Ramsay Hunt syndrome (CN VII + VIII): facial palsy + vesicles in ear canal/auricle + vertigo + hearing loss + ageusia
- Disseminated zoster: >20 lesions outside primary dermatome, especially in immunocompromised
- Zoster sine herpete: dermatomal pain without rash — diagnosis of exclusion, PCR confirms
Classic findings
Painful unilateral vesicular rash respecting the midline in a dermatomal distribution.
Differential diagnosis
- Herpes simplex (zosteriform HSV) — Recurrent vesicles in fixed location, not strictly dermatomal; PCR/culture differentiates
- Contact dermatitis — Geometric/linear borders match contactant; pruritus dominant; no prodromal pain
- Cellulitis — Diffuse warmth, erythema, no vesicles or dermatomal distribution
- Impetigo — Honey-colored crusts, not dermatomal
- Bullous pemphigoid — Tense bullae on urticarial base, widespread, older adult; DIF positive
- Cardiac ischemia or appendicitis (prodromal pain) — Pain without rash in early prodrome can mimic visceral disease; rash emerges 1-5 days later
Diagnostic workup
Diagnostic criteria
Clinical: prodromal pain + unilateral dermatomal vesicular rash; PCR confirms in atypical cases.
Labs
- Clinical diagnosis sufficient in most cases
- PCR of vesicle fluid (most sensitive and specific; preferred when confirmation needed)
- Direct fluorescent antibody (DFA) — rapid
- Tzanck smear shows multinucleated giant cells (does not distinguish HSV from VZV)
- Viral culture (low yield)
- HIV testing in young adults with zoster
- Workup for underlying malignancy not routinely indicated in immunocompetent adults but consider in disseminated or recurrent disease
Imaging
- Slit-lamp examination by ophthalmology for any V1 involvement
- MRI brain if encephalitis, myelitis, or stroke (varicella vasculopathy) suspected
Diagnostic algorithm
| Scenario | Key Management Step |
|---|---|
| Standard zoster <72 h | Valacyclovir 1 g TID × 7 d + analgesia |
| Hutchinson sign / V1 involvement | Antiviral + urgent ophthalmology |
| Ramsay Hunt (CN VII) | Antiviral + prednisone taper + ENT/audiology |
| Immunocompromised / disseminated | IV acyclovir + airborne/contact isolation |
| Postherpetic neuralgia | Gabapentin/pregabalin, lidocaine patch, TCA |
| Prevention | Recombinant zoster vaccine (Shingrix) 2 doses, age ≥50 |
Treatment
First-line
- Antiviral therapy within 72 hours of rash onset (still beneficial if vesicles still forming or in immunocompromised): valacyclovir 1 g PO TID × 7 days, OR famciclovir 500 mg PO TID × 7 days, OR acyclovir 800 mg PO 5x/day × 7-10 days (valacyclovir/famciclovir preferred due to better bioavailability and dosing)
- Renal dose adjustment for all antivirals
- Pain control: acetaminophen, NSAIDs for mild; gabapentin or pregabalin titrated up for moderate-severe neuritic pain; opioids short-term if needed (codeine, tramadol, oxycodone)
- Tricyclic antidepressants (nortriptyline, amitriptyline) for acute pain and PHN prevention
- Local: cool compresses, calamine lotion, topical lidocaine 5% patch (after lesions crust)
- Vaccination: recombinant zoster vaccine (Shingrix) — 2 doses 2-6 months apart, age ≥50, including those with prior zoster (wait until acute episode resolves)
Zoster ophthalmicus
- Same antiviral as above PLUS urgent ophthalmology referral within 24 hours
- IV acyclovir if sight-threatening keratitis, iritis, retinal involvement
- Topical antivirals and steroids only under ophthalmology direction
Ramsay Hunt syndrome
- Antiviral + oral corticosteroid (prednisone 60 mg/day tapered over 1-2 weeks) — improves facial nerve recovery
- ENT referral; audiometry
Disseminated / immunocompromised
- IV acyclovir 10 mg/kg q8h until clinical improvement, then PO antiviral to complete 14 days
- Airborne + contact isolation (disseminated disease can transmit varicella to non-immune contacts)
Postherpetic neuralgia
- First-line: gabapentin or pregabalin titrated to effect; topical lidocaine 5% patch; topical capsaicin 8% patch
- Second-line: TCAs (nortriptyline, amitriptyline), SNRIs (duloxetine, venlafaxine)
- Third-line: opioids, intrathecal corticosteroids, nerve blocks
Second-line / adjunct
- Systemic corticosteroids — controversial for typical zoster; may speed acute pain resolution but do not prevent PHN; useful in Ramsay Hunt and severe cases
- Recombinant zoster vaccine (Shingrix) recommended for immunocompromised adults ≥19 years per CDC ACIP 2022
Complications
- Postherpetic neuralgia (PHN) — pain persisting >90 days after rash onset; affects 10-18% of all zoster patients, ~30% of those >80 years; antiviral therapy reduces but does not eliminate risk
- Bacterial superinfection of skin lesions
- Zoster ophthalmicus: keratitis, uveitis, scleritis, acute retinal necrosis, secondary glaucoma, vision loss
- Ramsay Hunt syndrome: facial palsy (worse prognosis than Bell's palsy), hearing loss, vertigo
- CNS: meningoencephalitis, myelitis, varicella vasculopathy → stroke
- Disseminated visceral zoster (pneumonitis, hepatitis) in immunocompromised
- Motor zoster (segmental muscle weakness)
- Transmission of varicella to non-immune contacts (especially neonates, pregnant women, immunocompromised) from active lesions
PANCE pearls
- Hutchinson sign (vesicles on tip of nose) predicts ocular involvement in zoster ophthalmicus — urgent ophthalmology referral.
- Antiviral therapy is most effective if started within 72 hours of rash onset, but still consider in ongoing vesicle formation, ocular involvement, immunocompromised, or severe pain.
- Recombinant zoster vaccine (Shingrix) is preferred over the older live attenuated vaccine (no longer marketed in the US) and is recommended for all adults ≥50 and immunocompromised adults ≥19.
- Zoster in a young adult should prompt HIV testing.
- Pre-emptive gabapentin/pregabalin within the first weeks of acute zoster may reduce the incidence and severity of postherpetic neuralgia.
References
- CDC ACIP 2022 — Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years (Anderson et al., MMWR 2022)
- AAFP 2017 — Herpes Zoster and Postherpetic Neuralgia: Prevention and Management (Saguil et al., Am Fam Physician 2017)
- Cochrane 2014 — Antiviral Treatment for Preventing Postherpetic Neuralgia (Chen et al., Cochrane Database Syst Rev 2014)
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