Herpes zoster

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

17. Disposition

18. Follow Up / Return Precautions

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