Herpes zoster results from reactivation of latent varicella-zoster virus (VZV) in dorsal root or cranial nerve ganglia, producing a painful, unilateral, dermatomal vesicular eruption. There are >1 million cases annually in the United States, with a lifetime risk of ~30% that rises sharply with age. [1-2]
1. History
- Prodrome (2–3 days before rash): malaise, headache, low-grade fever, localized burning/tingling/itching in the affected dermatome [3-4]
- Characterize pain: burning, lancinating, sharp, constant vs. intermittent; severity on 0–10 scale
- Timing of rash onset — critical for antiviral window (<72 hours from rash onset is ideal) [1]
- Progression: erythematous macules → papules → clear vesicles → cloudy/pustular → crusting over 7–10 days [3][5]
- Associated symptoms: allodynia, hyperesthesia, dysesthesia in the dermatome [6]
- Ask about eye symptoms (pain, redness, blurred vision, photophobia) if V1 distribution [7]
- Ask about ear symptoms, facial weakness, hearing loss, vertigo (Ramsay Hunt) [8-9]
- Important negatives: bilateral rash, diffuse/non-dermatomal distribution, systemic toxicity
2. Alarm Features
- Herpes zoster ophthalmicus (HZO): V1 dermatome involvement, Hutchinson sign (vesicles on tip of nose) — risk of keratitis, uveitis, vision loss; requires urgent ophthalmology referral [4][6-7]
- Ramsay Hunt syndrome: facial palsy + vesicles in external ear canal ± hearing loss/vertigo — poorer prognosis than Bell's palsy [6][8-9]
- Disseminated zoster: >20 vesicles outside the primary and adjacent dermatomes; suggests immunocompromise [1][5]
- Neurologic complications: encephalitis, myelitis, stroke (VZV vasculopathy), transverse myelitis [1][6][10]
- Visceral dissemination (immunocompromised): hepatitis, pneumonitis, pancreatitis — may precede rash by days [1]
- Motor weakness in the affected segment (zoster paresis), bladder/bowel dysfunction with sacral involvement [6][10]
- Secondary bacterial superinfection including MRSA [9]
3. Medications
Antiviral therapy (start within 72 hours of rash onset; consider beyond 72 hours if new lesions still forming or complications present): [1]
- Valacyclovir or famciclovir preferred over acyclovir due to better bioavailability, simpler dosing, and superior pain reduction (median pain duration 38 vs. 51 days, P=0.001) [1][9]
- Foscarnet for acyclovir-resistant VZV in immunocompromised patients [1]
- Pain management: acetaminophen/NSAIDs for mild pain; opioids for moderate-severe acute pain; gabapentin or pregabalin as adjuncts; tricyclic antidepressants (amitriptyline 25 mg nightly) may reduce PHN risk [1][13-14]
- Corticosteroids: controversial; may improve acute quality of life when combined with antivirals but do not prevent PHN [13][15]
- Renal dose adjustment required for all antivirals — ensure adequate hydration to prevent crystalline nephropathy [16]
- Caution: avoid corticosteroids in immunocompromised patients without antiviral coverage
4. Diet
- No specific dietary triggers or restrictions
- Adequate hydration is essential, particularly with antiviral therapy, to reduce risk of renal toxicity [16]
- Ensure adequate nutrition in elderly patients — pain and malaise may cause anorexia and weight loss [1]
5. Review of Systems
- Dermatologic: unilateral vesicular rash, pruritus, pain
- Ophthalmologic: eye pain, redness, visual changes, photophobia (if V1 involvement) [7]
- Otologic/Neurologic: hearing loss, vertigo, tinnitus, facial droop (Ramsay Hunt) [8-9]
- Neurologic: headache, focal weakness, urinary retention (sacral zoster), altered mental status (encephalitis) [6]
- Constitutional: fever, malaise, fatigue
- Respiratory: cough, dyspnea (disseminated disease with pneumonitis in immunocompromised) [4]
6. Collateral History and Family History
- Varicella history: prior chickenpox or varicella vaccination status
- Vaccination status: Shingrix (recombinant zoster vaccine) — 2-dose series
- Immunosuppressive medications: chemotherapy, biologics, JAK inhibitors, chronic corticosteroids [17]
- Family history: family history of herpes zoster is an independent risk factor [1]
- Contacts: identify susceptible household contacts (pregnant women, neonates, immunocompromised individuals who have not had varicella or vaccination) [1]
7. Risk Factors
- Age >50 years — strongest risk factor; incidence rises dramatically after age 60 [1][3]
- Immunocompromised states: HIV (especially CD4 <200), hematopoietic stem cell transplant (highest risk, OR 4.51), solid organ transplant, hematologic malignancies, chemotherapy [4][18-19]
- Autoimmune diseases: SLE, rheumatoid arthritis, IBD [18][20]
- Immunosuppressive medications: JAK inhibitors, anifrolumab, chronic corticosteroids, biologics [17]
- Chronic conditions: COPD, asthma, CKD, diabetes, depression — even in younger adults (30–49 years), these comorbidities confer HZ risk comparable to immunocompetent adults aged 50–59 [20-21]
- Female sex, White race [1]
- Stress and psychological trauma [21]
8. Differential Diagnosis
- Herpes simplex virus (HSV): can mimic zoster, especially in recurrent cases; typically smaller cluster, may cross dermatomes; PCR differentiates [4]
- Contact dermatitis: vesicular, pruritic, but bilateral and follows exposure pattern, not dermatomal
- Cellulitis/erysipelas: erythema and pain without vesicles (early zoster before vesicle formation can mimic)
- Impetigo: superficial, honey-crusted lesions; culture positive for Staph/Strep
- Dermatitis herpetiformis: bilateral, symmetric, intensely pruritic papulovesicles (associated with celiac disease)
- Zosteriform cutaneous metastasis: rare; persistent nodular lesions in dermatomal pattern without vesicles
- Zoster sine herpete: dermatomal pain without rash — a diagnostic challenge; requires PCR or serology [6]
9. Past Medical History
- Prior varicella or varicella vaccination
- Previous episodes of herpes zoster (recurrence rate ~5% in immunocompetent, 20–30% in HIV) [4][6]
- History of immunosuppressive conditions or therapies
- Chronic pain conditions (may complicate PHN assessment)
- Renal impairment (affects antiviral dosing)
10. Physical Exam
- Vital signs: low-grade fever possible; tachycardia from pain
- Skin: unilateral, dermatomal distribution of erythematous macules/papules/vesicles/crusts; lesions in different stages of development; does not cross midline (classically) [3-5]
- Most common sites: thoracic (40–50%), cranial nerve (20–25%), cervical (15–20%), lumbar (15%), sacral (5%) [4]
- Hutchinson sign: vesicles on the tip/side of the nose → nasociliary branch involvement → high risk of ocular complications [4][6]
- Cranial nerve exam: facial symmetry (CN VII for Ramsay Hunt), extraocular movements (CN III, IV, VI), hearing [6][8]
- Eye exam: visual acuity, pupillary response, conjunctival injection, fluorescein staining if available
- Assess for dissemination: >20 lesions outside primary dermatome [5]
- Motor exam: segmental weakness in the affected myotome [6][10]
- Lymphadenopathy: regional lymph nodes may be tender
11. Lab Studies
- Diagnosis is clinical in the vast majority of cases [1][9]
- PCR of vesicular fluid — most sensitive and specific confirmatory test for atypical or uncertain presentations [4][22]
- Direct fluorescent antibody (DFA) testing of vesicle scraping — rapid but less sensitive than PCR [4]
- Viral culture — low sensitivity, slow turnaround; rarely needed
- Labs to consider in complicated cases:
- CBC, CMP — baseline renal function before antivirals; evaluate for immunocompromise
- HIV testing — if zoster occurs in a young patient (<50) or is disseminated/recurrent [4]
- CSF analysis with VZV PCR — if meningitis, encephalitis, or myelitis suspected [4][23]
12. Imaging
- Not routinely indicated for uncomplicated dermatomal zoster
- MRI brain/orbits: indicated for neuro-ophthalmic complications (optic neuropathy, cranial nerve palsies, suspected VZV vasculopathy/stroke) [23-24]
- High-resolution MRI with vessel-wall imaging: can identify perineuritis, myositis, cavernous sinus involvement, and VZV vasculopathy in severe HZO [24]
- CT/MRI brain: if stroke symptoms — VZV vasculopathy can cause TIA/stroke weeks to months after zoster [6][10]
- Chest imaging: if pneumonitis suspected in disseminated disease
13. Special Tests
- Hutchinson sign — clinical predictor of ocular involvement in V1 zoster [4][6]
- Slit-lamp examination — mandatory for all patients with ophthalmic zoster to evaluate for keratitis, uveitis, and increased intraocular pressure [4][6]
- Fluorescein staining — corneal dendrites or pseudodendrites
- Tzanck smear — multinucleated giant cells (low specificity; cannot distinguish VZV from HSV)
- VZV IgG/IgM serology — limited utility in acute diagnosis; may help confirm retrospectively or in zoster sine herpete [4]
14. ECG
- Not routinely indicated
- Consider ECG if using tricyclic antidepressants (amitriptyline, nortriptyline) for pain management — risk of QT prolongation, arrhythmia, especially in elderly
- Consider if chest wall pain from thoracic zoster mimics cardiac chest pain — ECG to rule out ACS
15. Assessment
Herpes zoster is a clinical diagnosis based on the characteristic unilateral, dermatomal, painful vesicular rash. [1][9] Key assessment points:
- Severity stratification: mild (young, immunocompetent, limited rash) vs. severe (elderly, immunocompromised, ophthalmic/otic involvement, disseminated, neurologic complications)
- Timing: determine rash onset to guide antiviral initiation (within 72 hours ideal; still treat beyond 72 hours if new lesions forming or complications present) [1]
- Complications: PHN develops in 10–50% depending on age (13–40% prevalence of pain at 6 months in patients >60 years); ophthalmic zoster in ~15% of cases; Ramsay Hunt in <1% [1][9]
- Atypical presentations: immunocompromised patients may have prolonged, multidermatomal, or disseminated disease; verrucous or necrotic lesions; visceral involvement [1][5]
The following figure illustrates the natural history and neurologic complications of VZV reactivation, stratified by immune status:
16. Treatment Plan
Acute antiviral therapy
- Valacyclovir 1 g PO TID × 7 days or famciclovir 500 mg PO TID × 7 days — preferred agents [1]
- Start as early as possible, ideally within 72 hours of rash onset [1][12]
- Extend to 7–10 days (or longer) in immunocompromised patients or if lesions resolve slowly [4]
- IV acyclovir 10 mg/kg q8h for disseminated disease, severe immunocompromise, or CNS involvement [1][4]
Pain management
- Mild: acetaminophen ± NSAIDs
- Moderate-severe: short-course opioids (e.g., oxycodone); add gabapentin 300 mg TID (titrate up) or pregabalin for neuropathic pain [1][14]
- Consider early amitriptyline 25 mg nightly — one trial showed reduced pain at 6 months [13]
- Topical lidocaine 5% patch for localized pain
Wound care
- Keep lesions clean and dry; calamine lotion for comfort
- Cover lesions to reduce transmission risk
Ophthalmology referral
Vaccination (prevention of recurrence)
- Shingrix (recombinant zoster vaccine, 2-dose series) recommended for adults ≥50 years [25]
- Defer vaccination ~3 years after acute episode in immunocompetent patients (natural boost to VZV immunity) [1]
17. Disposition
Discharge (majority of cases)
- Immunocompetent patients with uncomplicated dermatomal zoster
- Adequate pain control achievable with oral medications
- Able to tolerate oral antivirals and maintain hydration
Admission criteria
- Disseminated zoster or visceral involvement
- Severe immunocompromise with extensive disease
- CNS complications (encephalitis, myelitis, stroke)
- Severe ophthalmic zoster requiring IV antivirals
- Intractable pain unresponsive to oral analgesics
- Inability to tolerate oral medications or maintain hydration
Specialist consultation triggers
- Ophthalmology: any V1 involvement or eye symptoms [1][7]
- ENT/Neurology: Ramsay Hunt syndrome [8]
- Neurology: suspected VZV vasculopathy, stroke, encephalitis, myelitis [6]
- Infectious disease: immunocompromised patients with complicated disease, acyclovir-resistant VZV [1]
- Pain management: refractory acute pain or established PHN [26]
18. Follow Up / Return Precautions
Follow-up timing
- Primary care follow-up within 1–2 weeks to assess healing and pain control
- Ophthalmology follow-up even if initial eye exam is normal in HZO — stromal keratitis and uveitis may develop weeks to months after skin lesions heal [4]
Return precautions — advise patients to return immediately for:
- New or worsening eye symptoms (pain, redness, vision changes)
- Facial weakness or hearing loss
- Spreading rash beyond the original dermatome
- Fever, confusion, headache, or neck stiffness
- Weakness in an arm or leg
- Difficulty urinating
Patient counseling
- Contagious via direct contact with vesicular fluid until all lesions have crusted — avoid contact with pregnant women, neonates, and immunocompromised individuals who lack VZV immunity [1]
- Not airborne in localized zoster (unlike varicella), but covering lesions is recommended
- Expected course: new vesicles for 3–5 days, crusting by 7–10 days, complete healing in 2–4 weeks [3-4]
- PHN risk: pain may persist beyond rash resolution, especially in patients >50 years; early treatment and follow-up are key [1][9]
- Discuss Shingrix vaccination at appropriate interval to prevent recurrence [1][25]
References
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