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.
Try two board-style Varicella questions
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Question 1Infectious 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?
AShort course of oral prednisone
BVaricella-zoster immune globulin
CCalamine and oral antihistamines
DOral valacyclovir or acyclovir
EIntravenous acyclovir therapy
Reveal answer & full explanation
Correct answer: D — Oral valacyclovir or acyclovir
AShort course of oral prednisone
BVaricella-zoster immune globulin
CCalamine and oral antihistamines
DOral valacyclovir or acyclovir✓
EIntravenous 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
Calamine and oral antihistamines — symptomatic care by itself is appropriate for healthy children younger than 13 with uncomplicated varicella, but this 24-year-old seen within 24 hours of rash onset is at higher risk of severe disease and complications and needs an oral antiviral; calamine and antihistamines relieve itching but do not shorten the illness or reduce complications.
Varicella-zoster immune globulin — 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.
Intravenous acyclovir therapy — reserved for immunocompromised hosts or severe/complicated disease such as varicella pneumonia (including in pregnancy) or encephalitis, whereas uncomplicated varicella in pregnancy is treated orally; this healthy patient has uncomplicated cutaneous disease with stable vitals and clear lungs, so oral therapy suffices.
Short course of oral prednisone — a steroid can seem reasonable for an intensely pruritic, inflamed rash, but systemic corticosteroids impair cell-mediated immunity and are a recognized risk factor for severe, disseminated varicella; they have no antiviral effect, and this adult seen within 24 hours of rash onset needs an oral antiviral.
Question 2Infectious DiseaseEasy
A 6-year-old unimmunized boy has fever and an intensely itchy rash that began on the scalp and face 2 days ago and now involves the trunk. A classmate at his daycare had a similar illness 2 weeks ago. Temperature is 38.6 C (101.5 F). He is well hydrated and playful, and the oropharynx shows a few shallow erosions. Which physical examination finding of the skin lesions is most likely to be present?
AUmbilicated lesions that are all at the same stage of evolution
BHoney-colored crusts with satellite pustules at the lesion margins
CFlaccid bullae that shear with lateral pressure on the skin
DLesions at several stages of evolution present in the same area
EOval gray vesicles on the palms and soles with an erythematous rim
Reveal answer & full explanation
Correct answer: D — Lesions at several stages of evolution present in the same area
AUmbilicated lesions that are all at the same stage of evolution
BHoney-colored crusts with satellite pustules at the lesion margins
CFlaccid bullae that shear with lateral pressure on the skin
DLesions at several stages of evolution present in the same area✓
EOval gray vesicles on the palms and soles with an erythematous rim
Why Lesions at several stages of evolution present in the same area is correct
Primary varicella produces successive crops of lesions, so the defining bedside finding is simultaneous presence of macules, papules, vesicles, and crusts within one anatomic region.
Each crop erupts over several days while earlier lesions are already crusting, which is why the polymorphic appearance is the discriminator rather than the vesicle itself.
The rash begins on the face and scalp and spreads to the trunk, where lesions are most concentrated, with mucosal erosions common and pruritus prominent.
A child remains contagious until every lesion has crusted.
Lesions at several stages of evolution present in the same area — the expected finding in varicella and the classic teaching point.
Why the others are wrong
Umbilicated lesions that are all at the same stage of evolution — the monomorphic synchronous eruption of smallpox and related orthopoxvirus infection, which also favors the face and extremities over the trunk.
Honey-colored crusts with satellite pustules at the lesion margins — nonbullous impetigo from Staphylococcus aureus or Streptococcus pyogenes, which spreads by autoinoculation around crusted plaques, usually without fever or mucosal erosions, and appears in varicella only later as a secondary bacterial infection of scratched lesions.
Flaccid bullae that shear with lateral pressure on the skin — a positive Nikolsky sign seen in staphylococcal scalded skin syndrome and in toxic epidermal necrolysis, neither of which produces discrete pruritic vesicles in crops.
Oval gray vesicles on the palms and soles with an erythematous rim — hand-foot-and-mouth disease, tempting because the fever, daycare exposure, and oral erosions all fit an enterovirus, but its vesicles favor the palms, soles, and buttocks, are usually tender rather than intensely itchy, and do not erupt in successive crops spreading from the scalp and face to the trunk.
Antiviral therapy in an uncomplicated immunocompetent child is optional, while household contacts who are immunocompromised or pregnant warrant post-exposure evaluation.
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Neonatal exposure (maternal rash onset 5 days before to 2 days after 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 or severe/complicated disease (including varicella pneumonia in pregnancy): IV acyclovir 10 mg/kg q8h; uncomplicated varicella in pregnancy: oral acyclovir or valacyclovir
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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