Herpes zoster

Meet the patient

A 68-year-old man arrives at 3am with three days of burning across his left flank that the on-call registrar worked up as renal colic — two normal CTs, no stone. This morning a band of red papules appeared over the same strip of skin, and by evening grouped vesicles are tracking from his spine toward his umbilicus, stopping dead at the midline.[1][2]

The pain started before the rash, the rash sits in one dermatome, and the clock for antivirals started seventy-two hours ago. Hold those three facts — pain first, one dermatome, the seventy-two-hour window — and the whole topic falls into place.[1]

One virus, two names — the girdle that comes back

Varicella-zoster virus infects a person twice, under two names. Primary infection is chickenpox (varicella) — a generalised vesicular fever; the virus then retreats into the dorsal-root ganglia of the spinal cord and the sensory ganglia of the cranial nerves (chiefly the trigeminal and the geniculate), where it sits silently for decades, held in check by cell-mediated immunity — CD8 and CD4 T-cells suppressing viral gene transcription.[1][17]

When that T-cell surveillance wanes — with age over fifty, immunosuppression, HIV, transplant, chemotherapy, anti-TNF biologics, JAK inhibitors, prolonged steroids, haematological malignancy, or even local trauma to a ganglion — latency breaks. The virus replicates inside the ganglion, ignites a sensory ganglionitis (the source of prodromal pain), and travels anterograde down the peripheral nerve to erupt in the dermatome that ganglion serves.[1][3]

Etymology for viva gold: zoster is Greek for "girdle" or "belt", because the thoracic eruption wraps the trunk like one; shingles comes from the Latin cingulum, also "girdle". Two languages, one image — and the reason the rash is so often thoracic and unilateral.[2]

The numbers that frame the whole topic:[2]

Pain before the rash — the trap that costs

The single most dangerous feature of zoster is that the pain precedes the rash by days. For one to five days (range two to ten) the patient feels burning, tingling, itching, or hyperaesthesia localised to the dermatome about to erupt — and because the skin is still clear, the diagnosis is whatever that dermatome mimics.[1][3]

Zoster sine herpete is the extreme version of the same problem — dermatomal pain that never produces a rash, confirmed only by VZV PCR of skin, saliva, or CSF, or a rising IgM and IgG. Treat it as zoster once confirmed.[1][5]

Read the dermatome like the consultant does

Three words decide the bedside diagnosis: dermatomal, unilateral, midline-stopping. The eruption sits in the territory of a single dorsal root or cranial sensory nerve, stays on one side of the body, and does not cross the midline — because dermatomes meet at the midline but do not overlap it. Vesicles crossing the midline should make you question the diagnosis or suspect immunocompromise with dissemination.[1][4]

The thoracic dermatomes (T3 to L2) carry the majority of cases, with the trunk the classic site. The lesion timetable is worth memorising because examiners ask it verbatim:[1][3]

• Day 0 to 1 — erythematous macules and papules in the band.
• Day 2 to 3 — grouped vesicles on an erythematous base, the classic drop-like herpetiform cluster.
• Day 4 to 5 — vesicles cloud into pustules.
• Day 7 to 10 — crusting begins; the patient is infectious until every lesion has crusted.
• Weeks 2 to 4 — crusts shed, leaving depigmented scars or persistent dysaesthesia.[1]

Clinical diagnosis is sufficient in the immunocompetent patient with a classic eruption — no test is needed. Reach for VZV PCR of vesicle fluid (the gold standard, sensitivity above 95 percent) when the picture is atypical, when you must distinguish VZV from HSV, or in immunocompromise; CSF PCR is reserved for suspected meningitis, encephalitis, myelitis, or VZV vasculopathy with stroke.[1][5]

Hutchinson's sign and the V1 fork — sight in the balance

A vesicle on the tip of the nose is an ophthalmology emergency until proven otherwise. The ophthalmic division of the trigeminal nerve (V1) carries three branches — frontal, lacrimal, and nasociliary — and the nasociliary branch supplies the eye itself (cornea, iris, ciliary body) plus the tip and side of the nose. So a lesion on the nasal tip means the virus has reached the branch that also feeds the cornea.[1][7]

Hutchinson's sign — vesicles on the tip, side, or root of the nose — predicts ocular involvement in more than half of V1 zoster cases, with a positive predictive value approaching 80 percent when the rash is active. Ophthalmic zoster accounts for 10 to 25 percent of trigeminal zoster, and its complications are sight-threatening: epithelial and stromal keratitis, anterior uveitis, scleritis, optic neuritis, choroiditis, and acute retinal necrosis.[7][8]

Management of herpes zoster ophthalmicus: oral valaciclovir 1 g three times daily or famciclovir 500 mg three times daily for 7 to 10 days, started within 72 hours, plus the urgent eye review and topical antiviral or corticosteroid drops as the ophthalmologist prescribes. Escalate to IV aciclovir 10 mg/kg every eight hours for sight-threatening disease (acute retinal necrosis, optic neuritis, severe uveitis), immunocompromise, or an inability to absorb oral therapy.[7][8]

Ramsay Hunt — the ear that paralyses the face

Ear pain, vesicles in the ear canal, and an ipsilateral facial palsy is Ramsay Hunt syndrome — VZV reactivation in the geniculate ganglion of the facial (VII) nerve, with spread through the nervus intermedius to the chorda tympani (taste, anterior two-thirds of the tongue) and anastomoses to the vestibulocochlear (VIII) nerve.[13][14]

The full picture is a triad plus extras: ipsilateral lower-motor-neurone facial palsy, deep ear pain, and vesicles on the pinna, in the external auditory canal, on the tympanic membrane, or on the anterior tongue and soft palate — with variable sensorineural hearing loss, tinnitus, vertigo, and hyperacusis, and loss of taste in the anterior two-thirds of the tongue. When the facial palsy appears without vesicles, call it Ramsay Hunt sine herpete and treat it the same way.[13][14]

Outcomes are worse than Bell palsy, and the clock is just as unforgiving. Untreated, only about 30 percent recover full facial function (House-Brackmann I or II) by six months; treated with antivirals plus corticosteroids within 72 hours, that figure rises to 70 to 80 percent. Sequelae include synkinesis (blinking twitches the mouth corner), hemifacial spasm, crocodile tears (misdirected parasympathetic regrowth causing lacrimation while eating), and permanent taste loss.[13][14]

The 72-hour window — antivirals and the clock

Antivirals work only if started early, and the magic number is 72 hours from rash onset. Initiated within that window, they accelerate lesion healing, cut viral shedding, reduce acute pain severity, and modestly lower the incidence of post-herpetic neuralgia (number needed to treat roughly 8 to 13).[1][6]

The three oral agents are guanosine analogues activated by viral thymidine kinase, inhibiting viral DNA polymerase. Valaciclovir and famciclovir have three to five times the oral bioavailability of aciclovir and so need less frequent dosing — aciclovir 800 mg five times daily is cheaper but inconvenient, and is the agent most renal-dose adjustments trip on.[1][5]

The corticosteroid caveat examiners love. A tapering course of prednisolone may reduce acute pain and speed rash healing in the immunocompetent adult, but it does not prevent post-herpetic neuralgia — so it is not routine. The one syndrome where the steroid is non-negotiable is Ramsay Hunt, where prednisolone 1 mg/kg/day for 7 days plus IV aciclovir is the standard of care for facial-nerve outcomes.[6][13]

Disseminated zoster — the immunocompromise alarm

More than twenty vesicles beyond the primary dermatome, or any visceral involvement, is disseminated zoster — and it is an alarm bell for immunocompromise. Dissemination means viraemic spread of virus to multiple skin sites and organs, almost always in the immunocompromised: HIV with a low CD4 count, solid-organ or bone-marrow transplant recipients (peaking in the first year), chemotherapy, high-dose corticosteroids, haematological malignancy, and anti-TNF or JAK inhibitor therapy.[12][15]

Recurrent zoster is uncommon in the immunocompetent — a second attack occurs in roughly 5 percent, and each recurrence progressively raises the odds of undetected immunosuppression. A patient under 50 with their second bout of shingles earns an HIV test and an immune workup on the spot.[4][15]

Post-herpetic neuralgia — the complication that outlives the rash

Post-herpetic neuralgia (PHN) is dermatomal pain persisting beyond 90 days from rash onset, and it is the complication patients fear most. The pain is neuropathic: burning, lancinating or shock-like, with allodynia (the touch of clothing or a breeze is agonising) and hyperalgesia. Risk rises steeply with age — uncommon under 40, but affecting 20 to 30 percent of the over-80s — and with severe acute pain, a severe rash, ophthalmic distribution, and immunocompromise.[6][9]

The mechanism is deafferentation: peripheral sensory-axon loss, sodium-channel accumulation driving ectopic firing, dorsal-horn sensitisation (wind-up and microglial activation), and failure of descending inhibition. Trigeminal PHN — particularly V1 — is among the most refractory, because the nerve supply to the face and eye is dense and the allodynia can be disabling.[9][10]

The ladder runs in three steps, all with named drugs at named doses:[1][9]

• Gabapentinoids first — gabapentin (start 300 mg nocte, titrate to 300 to 600 mg three times daily, max 3600 mg/day) or pregabalin (start 75 mg twice daily, titrate to 150 to 300 mg twice daily). Both are alpha-2-delta calcium-channel ligands; both are renally dosed and carry a suicidality warning.
• Tricyclic antidepressants — amitriptyline or nortriptyline 10 to 150 mg nocte; effective but anticholinergic, so check an ECG first in the over-40s or cardiac-risk patient (QT prolongation).
• Topicals for focal disease — lidocaine 5 percent patch (twelve hours on, twelve off) and capsaicin 8 percent patch (a single 60-minute in-clinic application giving up to twelve weeks of relief). Capsaicin needs pre-treatment lidocaine and local cooling.[1][6]

Refractory PHN goes to combination therapy (gabapentinoid plus TCA, or gabapentinoid plus topical), short-course tramadol or oxycodone as rescue, and interventional options through the pain team — nerve blocks, epidural injection, sympathetic blockade, spinal-cord or peripheral-nerve stimulation.[1][9]

Vaccination — Shingrix twice, and win

The recombinant zoster vaccine (Shingrix) is the single most consequential intervention in this topic, and it needs two doses. It is recombinant VZV glycoprotein E antigen plus the AS01B adjuvant (monophosphoryl lipid A and QS-21 saponin in a liposome), given as two intramuscular doses in the deltoid at month 0 and month 2 (range 1 to 6 months if the second is delayed). Two doses are mandatory — single-dose efficacy is markedly lower and not licensed.[11][18]

Because Shingrix is non-live, it is safe and recommended in selected immunocompromised adults — HIV with CD4 at least 200, post-bone-marrow and solid-organ transplant on low-dose immunosuppression, and patients on low-dose corticosteroids — though responses are blunted. ACIP 2022 recommends it for immunocompetent adults 50 and over and immunocompromised adults 19 and over on low-level immunosuppression. Serology is not required first — nearly all adults over 50 in VZV-endemic regions are already seropositive.[11][18]

The older live vaccine (Zostavax) is largely retired. It used live attenuated Oka/Merck VZV at fourteen times the varicella dose, given as a single subcutaneous injection, with 51 percent efficacy against zoster and 67 percent against PHN — efficacy that waned after five to eight years. Because it is live, it is contraindicated in the immunocompromised (HIV with CD4 under 200, transplant, chemotherapy, biologics, high-dose steroids), and it has been withdrawn from the US market. Where Shingrix is unavailable it remains an option for the immunocompetent.[1][11]

An emerging dividend: large observational data suggest recombinant zoster vaccination is associated with a reduced risk of dementia in the years after the dose — a signal that has pushed Shingrix from a pure PHN-prevention tool toward broader protective value, though the mechanism is still being worked out.[18][11]

Pregnancy, immunocompromise, and the special populations

Pregnancy is where the varicella-versus-zoster distinction becomes critical. Primary varicella in the first 20 weeks carries a fetal varicella embryopathy risk — limb hypoplasia, ocular defects, cicatricial skin lesions, and neurodevelopmental delay — and severe maternal varicella near delivery can transmit to the newborn. Maternal shingles, by contrast, does not carry the embryopathy risk — the fetus is already exposed to the mother's VZV antibodies — but a severe maternal zoster near delivery still warrants IV aciclovir, and a seronegative pregnant woman exposed to varicella gets VZIG.[16][17]

Two related complications complete the picture. Motor zoster produces segmental paresis in the affected myotome — diaphragmatic paresis (C3 to C5, look for an elevated hemidiaphragm on the chest film), limb weakness, or sacral involvement causing urinary retention (rule out cauda equina with MRI). VZV vasculopathy produces stroke — a recognised though uncommon complication, especially after V1 zoster — and zoster also carries a measurable short-term rise in cardiovascular and cerebrovascular events in the weeks after the rash.[1][10]

How patients come to harm — the preventable list

• The prodrome worked up as renal colic or appendicitis for two days while the antiviral window closes — the preventable delay.[1]
• An ophthalmic zoster discharged without a slit-lamp review, returning blind in one eye from undiagnosed keratitis or acute retinal necrosis.[7][8]
• A Ramsay Hunt syndrome treated as Bell palsy and sent home without antivirals or steroids — leaving a permanent facial palsy.[13][14]
• A disseminated zoster in a young patient treated as just shingles without an HIV test, missing the underlying diagnosis.[12][15]
• An immunocompromised patient given oral antivirals for disseminated disease that needed IV aciclovir.[12]
• PHN dismissed as expected at this age with no neuropathic agent started, leaving an elderly patient housebound with allodynia for a year.[6][9]
• A pregnant woman with primary varicella not given VZIG and not counselled on embryopathy risk.[16][17]
• A patient eligible for Shingrix who never gets it — the most preventable harm of all, because the vaccine is over 90 percent effective.[11][18]

The mantra, and the mnemonic

The mantra: One dermatome, one side, stops at the midline — antivirals within seventy-two hours, the nose-tip means the eye, the ear means the face, and Shingrix twice to prevent the lot.[1][11]

Ward-round test — three stems, thirty seconds each