Makindo Medical Notes

Related Subjects: |Herpes Varicella-Zoster (Shingles) Infection |Chickenpox Varicella Infection |Varicella Cerebral Vasculopathy |Herpes Viruses |Herpes Zoster Ophthalmicus (HZO) Shingles

🚨 OPHTHALMIC EMERGENCY: Herpes Zoster Ophthalmicus (HZO) is shingles affecting the ophthalmic division (V1) of the trigeminal nerve. Start oral antivirals within 72 hours of rash onset to reduce complications. Urgent same-day ophthalmology referral for any eye involvement, visual symptoms, or Hutchinson's sign (vesicles on nose tip).

👁️ Definition

• HZO: Reactivation of varicella-zoster virus (VZV) in the ophthalmic division (V1) of the trigeminal nerve, causing dermatomal rash and potential ocular complications.
• Epidemiology: Accounts for 10–25% of all herpes zoster (shingles) cases. Incidence: 1.2 per 1000 person-years, increasing with age.
• Significance: Up to 50% develop ocular complications without prompt treatment. Risk of permanent vision loss if untreated.

🧬 Pathophysiology

• Primary infection: Varicella-zoster virus (VZV) causes chickenpox (varicella) in childhood → virus becomes latent in dorsal root ganglia and cranial nerve ganglia (especially trigeminal ganglion).
• Reactivation: Declining cell-mediated immunity (age, immunosuppression, stress) allows viral reactivation → virus travels along ophthalmic division (V1) sensory nerves.
• V1 distribution: Supplies forehead, upper eyelid, cornea, conjunctiva, nose (via nasociliary branch).
• Hutchinson's sign: Vesicles on nose tip/ala/root indicate nasociliary branch involvement → 75% risk of ocular disease (nasociliary branch also innervates cornea).
• Ocular damage mechanism: Direct viral invasion of ocular tissues + immune-mediated inflammation → keratitis, uveitis, vasculitis.

⚠️ Risk Factors

• Age: >60 years (peak incidence 60–80 years). Risk doubles each decade after age 50.
• Immunosuppression (strongest risk factor):
  • HIV/AIDS (especially CD4 <200 cells/μL).
  • Haematological malignancies (lymphoma, leukaemia).
  • Solid organ or bone marrow transplantation.
  • Chemotherapy, immunosuppressive drugs (azathioprine, methotrexate).
  • High-dose corticosteroids (>20 mg prednisolone daily for >2 weeks).
  • Biological therapies (TNF-α inhibitors).
• Chronic diseases: Diabetes mellitus, chronic kidney disease, COPD, rheumatoid arthritis.
• Other: Physical/emotional stress, recent trauma/surgery to V1 distribution, female gender (slightly higher risk).

📸 Clinical Images

🔴 Clinical Presentation

Prodromal Phase (1–4 days before rash)

• Fever, malaise, headache (may mimic meningitis).
• Hyperaesthesia, tingling, burning, or stabbing pain in V1 distribution (forehead, scalp).
• Pain may precede rash by several days, causing diagnostic confusion.

Acute Phase (Rash Appearance)

• Classic dermatomal rash: Strictly unilateral, does not cross midline, follows V1 distribution (forehead, upper eyelid, scalp to vertex).
• Rash evolution:
  • Day 0–1: Erythematous macules.
  • Day 1–3: Grouped vesicles on erythematous base ("dew drops on a rose petal").
  • Day 3–7: Vesicles become pustular, may coalesce.
  • Day 7–14: Crusting begins (infectious until crusted).
  • Weeks 2–4: Crusts fall off, may leave scarring/pigmentation changes.
• Hutchinson's sign (⚠️ KEY FINDING): Vesicles on tip, ala, or root of nose → 75% risk of ocular involvement (nasociliary branch supplies both nose tip and cornea).
• Pain: Severe, burning, lancinating, often out of proportion to rash. May persist as post-herpetic neuralgia (PHN).
• Eyelid involvement: Oedema, vesicles on upper lid, ptosis (due to oedema or CN III involvement).

👁️ Ocular Complications (in order of frequency)

🔴 Anterior Segment (most common, 50–70%)

• Conjunctivitis (60%): Follicular or papillary conjunctivitis. Usually mild, self-limiting. Red eye, discharge, chemosis.
• Keratitis (50%, most serious):
  • Punctate epithelial keratitis: Fine dendritic lesions (early).
  • Pseudodendrites: Raised, mucous plaques (unlike HSV true dendrites with terminal bulbs). Stain poorly with fluorescein.
  • Nummular keratitis: Coin-shaped subepithelial infiltrates (immune-mediated, weeks after rash).
  • Disciform keratitis: Central stromal oedema with endothelial inflammation (similar to HSV).
  • Neurotrophic keratopathy: Reduced corneal sensation → epithelial breakdown, ulceration, perforation risk.
  • ⚠️ Key clinical sign: Reduced/absent corneal sensation (distinguishes HZO from HSV, which has normal sensation).
• Anterior uveitis (40%):
  • Granulomatous inflammation common (keratic precipitates, iris nodules).
  • Elevated intraocular pressure (IOP) in up to 50% due to trabecular inflammation.
  • Hypopyon, hyphaema in severe cases.
  • Iris atrophy, posterior synechiae (adhesions between iris and lens).
• Episcleritis/Scleritis (30%):
  • Episcleritis: Sectoral redness, mild discomfort, self-limiting.
  • Scleritis: Deep, boring pain, blue-red discolouration, risk of scleromalacia/perforation.

👁️ Eyelid & Adnexal Complications

• Ptosis: Upper lid droop (oedema or CN III palsy).
• Lid scarring: Notching, cicatrization.
• Entropion/ectropion: Eyelid malposition from scarring.
• Chronic blepharitis: Persistent lid margin inflammation.
• Exposure keratopathy: If incomplete eyelid closure.

🔴 Posterior Segment (less common, <10%, more in immunocompromised)

• Acute retinal necrosis (ARN): Necrotizing retinitis, retinal vasculitis. Sight-threatening. Requires IV aciclovir.
• Progressive outer retinal necrosis (PORN): Rapidly progressive, seen in severe immunosuppression (AIDS). Poor prognosis.
• Optic neuritis: Vision loss, swollen optic disc, RAPD.
• Retinal vasculitis: Vessel sheathing, haemorrhages.

🧠 Neuro-Ophthalmic Complications

• Cranial nerve palsies: CN III (oculomotor), IV (trochlear), VI (abducens) → diplopia, ptosis, ophthalmoplegia. CN VII (facial) → facial palsy.
• Optic neuropathy: Vision loss, disc swelling or atrophy.
• Horner's syndrome: Miosis, ptosis, anhidrosis (sympathetic involvement).

⏱️ Late Complications (weeks to months after acute infection)

• Glaucoma: Secondary to trabeculitis, synechiae, steroid use.
• Cataract: From chronic uveitis or steroid use.
• Corneal scarring: Reduced vision, may require corneal transplant.
• Chronic dry eye: Lacrimal gland involvement.
• Post-herpetic neuralgia (PHN): Persistent pain >90 days after rash (10–15% of cases, higher in elderly).

💥 Systemic Complications

• Post-herpetic neuralgia (PHN, 10–20%): Persistent pain >90 days after rash. More common in elderly, severe acute pain, delayed antiviral treatment.
  • Treatment: First-line: Gabapentin 300–1200 mg TDS or Pregabalin 75–150 mg BD. Second-line: Amitriptyline 10–75 mg nocte. Topical: Capsaicin 0.075% cream or lidocaine patches. Consider pain clinic referral.
• Central nervous system:
  • Encephalitis (rare but serious): Confusion, seizures, altered consciousness. Requires LP, MRI, IV aciclovir.
  • Meningitis: Headache, neck stiffness, photophobia. Usually aseptic, self-limiting.
  • Cerebral vasculitis: Stroke from VZV arteriopathy (weeks to months post-rash). Treat with antivirals + steroids.
  • Myelitis: Spinal cord inflammation, limb weakness.
• Motor neuropathy: CN III, IV, VI, VII palsies (usually resolve spontaneously in weeks to months).
• Disseminated zoster: >20 lesions outside primary/adjacent dermatomes. Seen in immunocompromised. Risk of visceral involvement (pneumonitis, hepatitis). Requires IV aciclovir.
• Ramsay Hunt syndrome: VZV reactivation in geniculate ganglion (CN VII) → facial palsy + ear vesicles + hearing loss.

🔍 Differential Diagnosis

• Herpes simplex keratitis (HSV):
  • True dendrites with terminal bulbs (not raised mucous plaques).
  • Normal corneal sensation (key difference).
  • No dermatomal rash, recurrent episodes common.
  • Stains brightly with fluorescein.
• Preseptal/orbital cellulitis: No dermatomal distribution, no vesicles. Diffuse periorbital erythema/oedema. May have fever, proptosis (orbital).
• Allergic contact dermatitis: Itchy (not painful), bilateral, no neuralgia or prodrome. History of allergen exposure.
• Impetigo: Golden/honey-coloured crusts, no dermatomal pattern, more superficial. Common in children.
• Erysipelas: Well-demarcated raised border, no vesicles. Streptococcal infection.
• Trigeminal neuralgia: Paroxysmal facial pain, no rash. Triggered by touch/eating.
• Cluster headache: Unilateral periorbital pain with autonomic features, no rash.

🩺 Investigations

• Clinical diagnosis: Usually sufficient based on characteristic unilateral dermatomal rash + vesicles in V1 distribution.
• Slit-lamp examination: Essential for all suspected HZO to assess cornea, anterior chamber, IOP.
• Corneal sensation testing: Use cotton wisp or corneal aesthesiometer. Reduced/absent in HZO (normal in HSV).
• Fluorescein staining: Reveals epithelial defects (pseudodendrites stain poorly compared to HSV dendrites).
• Intraocular pressure (IOP): Tonometry to detect glaucoma.
• Laboratory confirmation (if needed):
  • PCR: Swab vesicle fluid or corneal scraping for VZV DNA (high sensitivity/specificity).
  • Direct fluorescent antibody (DFA): Rapid test on vesicle fluid.
  • Serology: Rising VZV IgM/IgG titers (less useful acutely, takes weeks).
  • Anterior chamber tap: PCR for VZV in aqueous humour if uncertain diagnosis (rare).
• Imaging (if CNS complications suspected): MRI brain (encephalitis, vasculitis), LP (CSF PCR for VZV).
• HIV test: Consider in young patients or severe/recurrent disease.

💊 Acute Management

🦠 Antiviral Therapy (START WITHIN 72 HOURS)

• Oral antivirals (first-line for immunocompetent):
  • Aciclovir 800 mg 5× daily (every 4 hours while awake) × 7–10 days.
  • Valaciclovir 1 g 3× daily × 7 days (better bioavailability, preferred).
  • Famciclovir 500 mg 3× daily × 7 days (alternative).
  • Benefits: Reduces acute pain, accelerates rash healing, reduces risk of ocular complications and PHN by ~50%.
  • Start even after 72 hours if: New vesicles still forming, immunocompromised, or ocular involvement.
• IV aciclovir 10–15 mg/kg 8-hourly (indications):
  • Immunocompromised patients.
  • Disseminated zoster.
  • Severe ocular disease (ARN, PORN, optic neuritis).
  • CNS complications (encephalitis, myelitis).
  • Unable to tolerate oral therapy.
  • Duration: 7–14 days IV, then switch to oral to complete 14–21 days total.
  • Caution: Adjust dose in renal impairment. Monitor U&E. Ensure adequate hydration (crystalline nephropathy risk).

💊 Symptomatic Management

• Analgesia (acute pain):
  • Regular paracetamol 1 g QDS + NSAIDs (ibuprofen 400 mg TDS or naproxen 500 mg BD).
  • Severe pain: Add weak opioids (codeine 30–60 mg QDS, tramadol 50–100 mg QDS) or strong opioids (morphine, oxycodone).
  • Neuropathic adjuncts: Gabapentin or pregabalin (start early to prevent PHN).
• Topical skin care:
  • Cool compresses (not ice) to reduce pain/itch.
  • Calamine lotion for itch.
  • Keep rash clean and dry to prevent secondary bacterial infection.
  • Avoid topical aciclovir cream (not effective for HZ, may cause contact dermatitis).
• Eye protection:
  • Preservative-free lubricating drops (e.g., hypromellose) QDS and ointment (e.g., Lacri-Lube) nocte.
  • Avoid eye rubbing.
  • Eye padding/moisture chamber if exposure keratopathy.

👁️ Ophthalmology-Directed Management

• Keratitis:
  • Preservative-free lubricants frequently (hourly if severe).
  • Topical steroids (e.g., dexamethasone 0.1% QDS) for nummular/disciform keratitis (only under ophthalmology supervision, never for epithelial defects).
  • Prophylactic topical antibiotics if epithelial defect (chloramphenicol QDS).
  • Bandage contact lens for neurotrophic ulcer.
• Anterior uveitis:
  • Topical corticosteroids (prednisolone acetate 1% 2-hourly initially, then taper).
  • Cycloplegics (cyclopentolate 1% TDS or atropine 1% BD) to prevent posterior synechiae and reduce pain.
• Elevated IOP/glaucoma:
  • Topical antihypertensives: Beta-blockers (timolol 0.5% BD), alpha-agonists (brimonidine 0.2% BD), carbonic anhydrase inhibitors (dorzolamide 2% TDS).
  • Oral acetazolamide 250 mg QDS if severe elevation.
• Scleritis: High-dose oral NSAIDs or systemic steroids (prednisolone 1 mg/kg daily). Consider immunosuppression if refractory.
• Posterior segment disease (ARN/PORN): IV aciclovir 10–15 mg/kg 8-hourly + intravitreal antivirals (ganciclovir, foscarnet) + oral antivirals + topical/oral steroids. May require laser or surgery for retinal detachment.
• Surgical interventions:
  • Tarsorrhaphy (temporary eyelid closure) for severe exposure keratopathy.
  • Penetrating keratoplasty (corneal transplant) for severe scarring/perforation.
  • Glaucoma surgery if medically uncontrolled IOP.

🚨 Referral Criteria

⚠️ URGENT SAME-DAY OPHTHALMOLOGY REFERRAL

• Any ocular symptoms: Red eye, eye pain, photophobia, blurred vision, floaters, visual field loss.
• Hutchinson's sign (vesicles on nose tip/ala/root).
• Periorbital/eyelid rash (V1 involvement).
• Reduced visual acuity.
• Corneal opacity or fluorescein uptake.
• Fixed/dilated pupil.

⚠️ OTHER URGENT REFERRALS

• Hospital admission (consider): Immunocompromised (for IV aciclovir), disseminated zoster, severe pain uncontrolled, suspected CNS involvement, unable to take oral antivirals.
• Neurology: Suspected encephalitis, myelitis, stroke, CN palsies not improving.
• Pain clinic: Severe acute pain or established PHN refractory to initial management.

🛡️ Prevention

💉 Vaccination (Primary Prevention)

• Shingrix (recombinant zoster vaccine, RZV):
  • Preferred vaccine: Non-live, more effective (>90% efficacy vs 50% for Zostavax).
  • Schedule: 2 doses, 2–6 months apart (IM deltoid).
  • Indications: All immunocompetent adults ≥50 years. Can be given to immunocompromised (unlike Zostavax).
  • NHS England (2023): Routine for ages 65 and 70, catch-up for 71–79.
  • Side effects: Injection site pain (common), myalgia, fatigue, headache (usually mild, self-limiting).
• Zostavax (live attenuated zoster vaccine):
  • Single dose, less effective than Shingrix.
  • Contraindicated: Immunocompromised, pregnancy, allergy to vaccine components.
  • Being phased out in many countries in favour of Shingrix.
• Timing: Can give vaccine during acute HZ episode or after recovery (no minimum interval required, but usually wait until rash resolved).

🦠 Infection Control

• Contagiousness: Contagious from rash onset until all lesions crusted (usually 7–10 days). Can transmit VZV to susceptible individuals (non-immune to chickenpox) → chickenpox, NOT shingles.
• Transmission route: Direct contact with vesicle fluid (not airborne like chickenpox).
• Precautions:
  • Cover rash with dressing.
  • Avoid contact with pregnant women (especially 1st/2nd trimester), newborns, immunocompromised, non-immune individuals.
  • Healthcare workers: Follow infection control policies, cover lesions.

💉 Post-Exposure Prophylaxis

• VZ immunoglobulin (VZIG): For exposed susceptible individuals at high risk of severe varicella:
  • Immunocompromised patients.
  • Pregnant women (non-immune).
  • Neonates (mother developed chickenpox 7 days before to 7 days after delivery).
  • Timing: Within 10 days of exposure (ideally within 96 hours).
• Varicella vaccination: Can prevent/attenuate chickenpox if given within 3–5 days of exposure to susceptible individuals (not for immunocompromised).

📋 Follow-Up & Monitoring

• Acute phase (weeks 1–2): Review response to antivirals, monitor for complications, ensure adequate analgesia.
• Ophthalmology follow-up: Patients with ocular involvement require serial slit-lamp exams until inflammation resolved (weeks to months).
• Long-term (months to years): Monitor for late complications (glaucoma, cataract, corneal scarring). Annual eye exams recommended if had uveitis/keratitis.
• PHN management: If pain persists >90 days, optimize neuropathic agents, consider pain clinic referral.

💡 Clinical Pearls

• 🔴 Hutchinson's sign = red flag: 75% risk of ocular involvement. Always refer urgently.
• ✋ Reduced corneal sensation is the key clinical sign that distinguishes HZO keratitis from HSV keratitis (HSV has normal sensation).
• ⏰ 72-hour window: Start antivirals within 72 hours for maximum benefit, but still start after 72h if new lesions forming or high-risk patient.
• 💉 IV aciclovir indications: Immunocompromised, disseminated disease, posterior segment involvement, CNS complications.
• 👁️ Never use topical steroids without ophthalmology supervision: Risk of worsening epithelial disease or causing superinfection.
• 🧠 Think CNS: Severe headache, confusion, focal neurology → consider encephalitis/vasculitis. Needs LP, MRI, IV aciclovir.
• 📈 Long-term surveillance: Patients with uveitis/keratitis need ongoing ophthalmology follow-up for glaucoma and cataract.
• 💊 Start gabapentin/pregabalin early: May prevent PHN development (start during acute phase for severe pain).
• 🔄 Recurrent HZO: Rare. If occurs, consider immunodeficiency (HIV test).
• ⚠️ Bilateral HZO: Very rare, suggests severe immunosuppression. Requires urgent investigation and IV therapy.

🎯 Summary Algorithm

• HZO suspected (V1 rash)? → Start oral antivirals within 72h + analgesia.
• Hutchinson's sign OR any eye symptoms? → Urgent same-day ophthalmology referral.
• Immunocompromised OR disseminated? → IV aciclovir + hospital admission.
• Pain persists >90 days? → PHN: Optimize neuropathic agents ± pain clinic.
• Patient ≥65 years? → Offer Shingrix vaccination after recovery to prevent recurrence.

📚 References & Guidelines

• NICE CKS (2019): Shingles. Antivirals within 72 hours, urgent ophthalmology referral for ocular involvement.
• American Academy of Ophthalmology (2019): Preferred Practice Pattern: Herpes Zoster Ophthalmicus. Systemic antivirals reduce ocular complications.
• CDC (2018): Shingrix preferred over Zostavax for all immunocompetent adults ≥50 years.
• Royal College of Ophthalmologists (2021): Guidelines for Management of HZO.
• BMJ Best Practice (2024): Herpes Zoster (Shingles).

✅ Key Takeaways: HZO is an ophthalmic emergency requiring prompt recognition and treatment. Start oral antivirals within 72 hours. Hutchinson's sign (vesicles on nose tip) predicts ocular involvement in 75% → urgent same-day ophthalmology referral. Reduced corneal sensation distinguishes HZO from HSV keratitis. Vaccinate eligible patients (Shingrix ≥65 years) to prevent this potentially sight-threatening condition.