Herpes Zoster

01Pathophysiology

Herpes zoster results from the reactivation of latent VZV that has been dormant in the sensory (dorsal root) ganglia since the primary varicella infection, which may have occurred decades earlier. VZV establishes lifelong latency within neuronal cell bodies after retrograde axonal transport from the skin during the initial infection. The virus is kept in check by cell-mediated immunity (predominantly T-cell surveillance), and any decline in this immune function allows the virus to reactivate.

Once reactivated, VZV replicates within the ganglion and travels anterogradely along the sensory nerve back to the skin, producing inflammation and necrosis of the nerve (ganglionitis and neuritis) and subsequently the characteristic vesicular eruption in the corresponding dermatome. This explains the prodromal pain: the neural inflammation begins before the virus reaches the skin, so patients experience dermatomal burning, itching, or lancinating pain for 1 to 5 days before any visible rash appears. This prodromal phase is a frequent source of diagnostic confusion.

The rash follows a strict dermatomal pattern because VZV reactivates from a single ganglion and tracks along its associated sensory nerve. The vesicles do not cross the midline because each dorsal root ganglion innervates only one side of the body. Involvement of two or more noncontiguous dermatomes or disseminated disease (defined as >20 lesions outside the primary dermatome) should raise concern for severe immunocompromise, such as advanced HIV or hematologic malignancy.

The development of postherpetic neuralgia (PHN), the most common complication, is attributed to persistent neuronal damage and aberrant nerve repair after the acute infection. Inflammatory destruction of the nerve fibers leads to central and peripheral sensitization, resulting in chronic neuropathic pain that can persist months to years after the rash resolves.

02Classification and Clinical Manifestation

Complications

03Diagnostic Workup

Herpes zoster is overwhelmingly a clinical diagnosis. The combination of prodromal dermatomal pain followed by a unilateral vesicular eruption confined to a single dermatome is considered sufficient for diagnosis in the vast majority of cases. Laboratory confirmation is reserved for atypical presentations, immunocompromised patients with unusual rash morphology, and suspected zoster sine herpete (pain without rash).

When laboratory confirmation is needed, PCR of vesicular fluid is the test of choice. It is the most sensitive and allows definitive identification of VZV as opposed to HSV, which is important because HSV can occasionally present in a zosteriform pattern. The Tzanck smear, while rapid and inexpensive, should be understood as a nondiagnostic test: it confirms a herpesvirus infection but cannot tell you which one. Exam questions that present a Tzanck smear with multinucleated giant cells are testing whether you know this limitation.

For herpes zoster ophthalmicus, an urgent ophthalmologic examination (slit-lamp exam) is indicated regardless of whether ocular symptoms are present, particularly when the Hutchinson sign is positive. For Ramsay Hunt syndrome, audiometry should be performed to evaluate for sensorineural hearing loss.

04Management & Treatment

The cornerstone of acute treatment is antiviral therapy initiated within 72 hours of rash onset. This 72-hour window is one of the most frequently tested concepts. Antivirals reduce the duration of viral shedding, accelerate lesion healing, and most importantly, reduce the risk and severity of postherpetic neuralgia. Valacyclovir is generally preferred over acyclovir for immunocompetent patients due to its superior bioavailability and simpler dosing schedule (three times daily versus five times daily).

However, antivirals may still be started after 72 hours in the following situations: new vesicles are still appearing, the patient is immunocompromised, or ophthalmic (HZO) or otologic (Ramsay Hunt) involvement is present. This nuance is important because exam questions may present a patient at 4 days into the rash who still has new vesicle formation, testing whether you know that ongoing active disease is an indication to treat.

For immunocompromised patients or those with disseminated zoster, IV acyclovir is the treatment of choice. These patients are at risk for visceral dissemination (pneumonitis, hepatitis, encephalitis) and require inpatient management with contact and airborne isolation precautions (the vesicular fluid contains live virus, and disseminated disease can be transmitted via the airborne route, unlike localized zoster which only requires contact precautions).

Corticosteroids (e.g., prednisone 60 mg/day tapered over 21 days) may be used as adjunctive therapy alongside antivirals in patients over 50 years with moderate to severe pain, to reduce acute pain and improve quality of life. However, corticosteroids do not prevent PHN and should not be used in immunocompromised patients.

For established postherpetic neuralgia, first-line pharmacotherapy includes gabapentin, pregabalin, or a tricyclic antidepressant (nortriptyline or amitriptyline). Topical lidocaine patches are an option for patients who prefer localized therapy or cannot tolerate systemic agents. Opioids are reserved as second or third-line options.

Shingrix (recombinant, adjuvanted zoster vaccine) has replaced the older live-attenuated Zostavax. It is recommended for immunocompetent adults aged 50 and older regardless of prior varicella or zoster history, and for immunocompromised adults aged 19 and older. It is given as a two-dose intramuscular series separated by 2 to 6 months. Because Shingrix is a recombinant (non-live) vaccine, it is safe in immunocompromised patients.

05Differential Diagnosis & Distractors

06Traps & High-Yield Pearls

The most common way students get herpes zoster questions wrong is by failing to recognize the prodromal phase. A vignette describing an older or immunocompromised patient with localized burning or lancinating pain in a band-like distribution, with a normal skin exam at the time of presentation, is designed to test whether you can identify pre-eruptive zoster. Students frequently anchor on cardiac, biliary, or musculoskeletal diagnoses and miss the diagnosis entirely.

A second major trap involves the 72-hour treatment window. Questions will present a patient at various time points after rash onset to test whether you know the indications to treat beyond 72 hours: new vesicle formation, immunosuppression, or ophthalmic/otologic involvement. The wrong answer is to withhold antivirals simply because the patient presents on day 4 or 5.

The Hutchinson sign (vesicles on the nose tip) is a classic exam pearl: its presence in a patient with forehead vesicles mandates ophthalmologic evaluation because it signals nasociliary nerve involvement and a high risk of keratitis and other ocular complications. Students who treat this as routine thoracic zoster and fail to order an ophthalmic exam will lose the point.

Be aware that the Tzanck smear is a distractor test. It confirms herpesvirus but cannot distinguish between VZV and HSV. If the question asks for the most accurate test, the answer is always PCR. If the question asks what the Tzanck smear shows, the answer is multinucleated giant cells, but you must pair that with the knowledge that this finding is shared by HSV.

Finally, know the isolation precautions. Localized herpes zoster requires contact precautions only (covering the rash). Disseminated zoster or zoster in an immunocompromised host requires both contact AND airborne precautions because the virus can become aerosolized. This distinction is a recurring infection control question.

The core competency being tested across herpes zoster questions is threefold: recognizing the dermatomal pattern (including prodromal and atypical presentations), applying the 72-hour antiviral initiation rule with its exceptions, and identifying high-risk variants (HZO, Ramsay Hunt, disseminated disease) that require escalated management.