Primary VZV infection producing pruritic vesicular rash in successive crops; vaccine-preventable; reactivates years later as herpes zoster.
Also known as: chickenpox, VZV, varicella zoster virus, primary varicella
Overview
Primary infection with varicella-zoster virus (VZV, human herpesvirus 3) characterized by fever and a generalized pruritic vesicular eruption in successive crops. After resolution, VZV remains latent in sensory ganglia and can reactivate as herpes zoster.
Epidemiology
Universal vaccination (introduced in US in 1995) reduced incidence by >97%. Pre-vaccine: nearly all US adults were immune by age 30. Now seen primarily in unvaccinated children, vaccine breakthroughs (milder), and susceptible adults. Highly contagious by airborne and contact routes.
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Question 1Infectious DiseaseMedium
A 35-year-old immunocompetent man presents with a painful vesicular rash in the T5-T6 dermatomal distribution on his left chest that does not cross the midline. He reports significant burning pain that started 3 days before the rash appeared. Which of the following is the most likely diagnosis?
AContact dermatitis
BHerpes zoster
CBullous impetigo
DCellulitis
Reveal answer & full explanation
Correct answer: B — Herpes zoster
AContact dermatitis
BHerpes zoster✓
CBullous impetigo
DCellulitis
Why Herpes zoster is correct
Herpes zoster is varicella-zoster virus (VZV) reactivation from a dorsal root or cranial nerve ganglion after primary varicella.
Classic features are a painful, grouped vesicular rash in a single dermatome that does not cross the midline.
A prodrome of burning or neuritic pain typically precedes the rash by 2-3 days, exactly as described here.
Antiviral therapy started within 72 hours of rash onset (valacyclovir 1000 mg TID or famciclovir 500 mg TID for 7 days) shortens the course and reduces complications.
Postherpetic neuralgia (pain persisting more than 3 months) is the most common complication; risk rises with age and immunosuppression and is treated with gabapentin, pregabalin, TCAs, or lidocaine patches.
Why the others are wrong
Contact dermatitis — Produces symmetric, non-dermatomal eczematous patches at sites of allergen contact; confused-with because both cause vesicles, but it never respects a single dermatome or the midline.
Bullous impetigo — Superficial staphylococcal infection with flaccid bullae and honey-colored crusting; confused-with vesicular disease, but it is not dermatomal and lacks the neuritic prodrome.
Cellulitis — Poorly demarcated warm erythema without vesicles; right-concept-wrong-setting, as it is a spreading dermal infection rather than a banded vesicular eruption.
Additional high-yield points
Systemic corticosteroids are NOT routine therapy for herpes zoster; they may modestly reduce acute pain but do NOT reduce the risk of postherpetic neuralgia and are not recommended for prophylaxis against it.
The recombinant zoster vaccine (RZV/Shingrix), 2 doses 2-6 months apart, is recommended for all immunocompetent adults 50 and older, and is also recommended for immunocompromised adults beginning at age 19.
RZV is preferred and can be given to immunocompromised patients because it is non-live (recombinant), with efficacy over 90% in immunocompetent adults.
Question 2Infectious DiseaseMedium
A 24-year-old man presents with 1 day of fever, malaise, and a pruritic rash that appeared this morning. He has no chronic illnesses, takes no medications, and is not immunocompromised. On examination, lesions are present on the scalp, face, and trunk in multiple stages simultaneously — erythematous macules, papules, and several clear vesicles described as "dewdrops on a rose petal." Vital signs are stable and his lungs are clear to auscultation. Which of the following is the most appropriate initial management?
ALive attenuated varicella vaccine
BOral valacyclovir or acyclovir
CVaricella-zoster immune globulin
DIntravenous acyclovir therapy
Reveal answer & full explanation
Correct answer: B — Oral valacyclovir or acyclovir
ALive attenuated varicella vaccine
BOral valacyclovir or acyclovir✓
CVaricella-zoster immune globulin
DIntravenous acyclovir therapy
Why Oral valacyclovir or acyclovir is correct
This is a classic primary varicella presentation: a short febrile prodrome with a generalized pruritic vesicular rash showing lesions in multiple stages at once ("dewdrop on a rose petal").
For immunocompetent adolescents (>=13 years) and adults, oral acyclovir 800 mg five times daily for 7 days, or valacyclovir 1 g three times daily, is guideline first-line because adults have more severe disease and higher complication rates than children.
Benefit is greatest when antiviral therapy is started within 24 hours of rash onset; this patient's rash appeared the same morning, so he is an ideal candidate.
Healthy children under 13 with uncomplicated disease typically receive only supportive care (calamine, antihistamines, acetaminophen; never aspirin, due to Reye syndrome).
Why the others are wrong
Intravenous acyclovir therapy is reserved for immunocompromised hosts, pregnant patients, or severe/disseminated disease such as varicella pneumonia or encephalitis; this healthy patient has uncomplicated cutaneous disease with stable vitals and clear lungs, so oral therapy suffices.
Varicella-zoster immune globulin is post-exposure prophylaxis for susceptible high-risk contacts (pregnant women, immunocompromised patients, exposed neonates) given within 10 days of exposure; it does not treat established active infection.
Live attenuated varicella vaccine is used for primary prevention or post-exposure prophylaxis in susceptible immunocompetent contacts within 3-5 days of exposure; a live vaccine has no role in treating an active varicella infection.
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Neonatal exposure (mother varicella ±5 days of delivery)
Pathophysiology
Virus enters via respiratory tract, replicates in regional lymph nodes, undergoes primary viremia to liver/spleen, then secondary viremia seeds skin and mucosae. Infection of basal epidermal cells produces the characteristic 'dewdrop on a rose petal' vesicles. Latency is established in dorsal root and cranial nerve ganglia.
Clinical presentation
Symptoms
Prodrome (1-2 days, mild in children, severe in adults): fever, malaise, headache, anorexia
Rash begins on the scalp, face, and trunk and spreads peripherally
Lesions progress over hours: macule → papule → vesicle ('dewdrop on a rose petal') → pustule → crust
Successive crops mean lesions in all stages are present simultaneously — a key diagnostic feature
Intense pruritus
Signs / physical exam
200-500 lesions in a typical case; fewer in vaccinated breakthroughs
Oral and genital mucosal vesicles
Patient is contagious from 2 days before rash until all lesions crust
Adults often have more lesions and higher fever
Classic findings
Lesions in multiple stages (papules, vesicles, crusts) simultaneously over the trunk and face.
Differential diagnosis
Smallpox (historical) — Uniformly aged lesions in a single stage, centrifugal distribution; vesicles deep-seated and umbilicated
Disseminated herpes zoster — Dermatomal vesicles with scattered satellite lesions in an immunocompromised host
Hand-foot-mouth disease (coxsackievirus) — Vesicles on hands, feet, oropharynx without generalized rash
Disseminated HSV — Grouped vesicles on an erythematous base, often mucocutaneous; PCR distinguishes
Bullous impetigo — Honey-colored crust, localized, S. aureus
Drug eruption — Generalized maculopapular rather than vesicular
Diagnostic workup
Diagnostic criteria
Clinical presentation of generalized vesicular rash with lesions in multiple stages; confirm with PCR or DFA if uncertain or in immunocompromised.
Labs
Diagnosis is usually clinical
VZV PCR of vesicular fluid — most sensitive when needed
Direct fluorescent antibody (DFA) of scraped vesicle base
Tzanck smear: multinucleated giant cells (does not distinguish VZV from HSV)
VZV IgG to document immunity
Imaging
Chest x-ray if pneumonia suspected (especially adults, smokers, immunocompromised)
Diagnostic algorithm
flowchart TD
A[Exposure] --> B{Susceptible?}
B -->|Immune| Z[No action]
B -->|Yes - immunocompetent| C[Varicella vaccine<br/>within 3-5 d]
B -->|Yes - high risk| D[VariZIG within 10 d<br/>± pre-emptive acyclovir]
E[Clinical varicella] --> F{Host}
F -->|Healthy child <13| G[Supportive<br/>no aspirin]
F -->|Adolescent/adult| H[Oral acyclovir<br/>≤24 h of rash]
F -->|Immunocompromised<br/>or severe| I[IV acyclovir]
Varicella exposure and disease management algorithm.
Treatment
First-line
Healthy children <13 years: supportive care — calamine, oral antihistamines, cool baths; keep nails trimmed to prevent superinfection; antipyretics with ACETAMINOPHEN (AVOID aspirin — Reye syndrome) and AVOID systemic NSAIDs given association with severe soft tissue infection
Adolescents ≥13 years and adults: oral acyclovir 800 mg 5x/day for 7 days (or valacyclovir 1 g TID) — start within 24 h of rash for best benefit
Immunocompromised, pregnant, or severe disease: IV acyclovir 10 mg/kg q8h
Varicella vaccine (live, 2-dose schedule) — primary prevention; first dose 12-15 months, second 4-6 years
Post-exposure prophylaxis
Susceptible immunocompetent contacts: varicella vaccine within 3-5 days of exposure
High-risk susceptible contacts (immunocompromised, pregnant, neonates exposed near delivery): VariZIG within 10 days of exposure
If VariZIG unavailable, IVIG or pre-emptive acyclovir starting day 7-10 post-exposure
Pregnancy
Avoid live varicella vaccine in pregnancy
Maternal varicella: oral acyclovir if within 24 h; IV acyclovir for pneumonia or severe disease
Maternal rash within 5 days before to 2 days after delivery → administer VariZIG to neonate plus IV acyclovir if symptomatic
Second-line / adjunct
Treat secondary bacterial skin infection (commonly group A strep or S. aureus) — beta-lactam coverage; consider necrotizing fasciitis with disproportionate pain
Airborne + contact precautions for hospitalized patients
Complications
Bacterial superinfection of skin lesions (group A strep, S. aureus, including necrotizing fasciitis and toxic shock)
Varicella pneumonia (most common cause of mortality in adults)
Cerebellar ataxia (most common neurologic complication in children; usually self-limited)
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