Varisela (Cacar Air)

01Pathophysiology

Varicella-zoster virus enters through the upper respiratory mucosa and the conjunctiva, inhaled as aerosolized virus from a shedding contact. This airborne route is why a single case in a waiting room can infect children who never touched the patient, and why the isolation answer is airborne plus contact rather than droplet.

The virus replicates first in local mucosal epithelium and regional lymphoid tissue. Infected T lymphocytes carry it into the bloodstream in a primary viremia around days 4 to 6, seeding the liver, spleen and other reticuloendothelial organs, where a second round of replication occurs. This silent amplification phase explains the long incubation period of 10 to 21 days. A secondary viremia near day 14 delivers virus-laden T cells to the skin. That two-wave kinetic is the mechanistic reason for two clinical facts that are heavily tested: the prodrome and infectivity begin before any rash is visible, and post-exposure prophylaxis has a narrow window because it must be given before the secondary viremia is established.

At the skin, virus is transferred from T cells to epidermal keratinocytes. Cell-to-cell fusion produces multinucleated giant cells and ballooning degeneration, and intraepidermal edema lifts the roof of the epidermis to form a thin-walled vesicle sitting on a base of dermal inflammation and vasodilation. That histology is the direct explanation of the "dewdrop on a rose petal" appearance and of why varicella vesicles are fragile and rupture easily, unlike the deep, firm, umbilicated lesions of smallpox and mpox. Because the virus arrives at the skin in successive waves of viremia over 3 to 5 days, new crops erupt while earlier crops are already pustular or crusted. This is the origin of the single most discriminating exam sign: lesions at different stages of evolution within the same anatomic region.

The distribution follows viral delivery and skin temperature. Highly perfused, warmer central skin (trunk, face, scalp) is seeded most heavily, giving a centripetal or central distribution with relative sparing of the palms and soles. Involvement of the mucous membranes reflects the same hematogenous seeding of stratified epithelium; the oral vesicles rupture within hours and appear as shallow ulcers, which is why a child may present with refusal to eat.

The itch comes from keratinocyte injury with release of histamine and other mediators into an inflamed dermis. Scratching breaches the epidermal barrier at the moment when the skin is colonized by Staphylococcus aureus and group A Streptococcus, and this is the mechanism behind the most common complication overall: bacterial superinfection, ranging from impetiginization to cellulitis, necrotizing fasciitis, bacteremia and streptococcal toxic shock syndrome. A vignette in which fever resolves and then recurs on day 4 to 6, with a lesion that becomes tender, indurated and surrounded by expanding erythema, is testing this sequence.

Control of the infection depends on cell-mediated immunity. Where T-cell function is impaired (leukemia on induction chemotherapy, transplant recipients, high-dose corticosteroids, advanced HIV), viremia is not contained and the illness becomes progressive varicella: continued high fever, hundreds of new lesions past day 5, hemorrhagic vesicles, coagulopathy, and visceral dissemination to lung, liver and brain. The same principle explains why corticosteroids are a risk factor and why the live vaccine is contraindicated in severe immunocompromise.

Varicella pneumonia results from viral replication in alveolar and bronchiolar epithelium with an interstitial mononuclear infiltrate and alveolar hemorrhage. It is the leading cause of death in adults with chickenpox, and the risk is amplified by adult age, smoking, pregnancy (especially the third trimester) and a high lesion count. Cough, dyspnea and hypoxemia appearing 1 to 6 days after the rash, with a widened $A-aA-a$ gradient and diffuse nodular infiltrates, is the pattern to recognize.

Neurologic complications follow two different mechanisms. Acute cerebellar ataxia is a post-infectious, largely immune-mediated demyelinating process appearing about 1 week after the rash in a child who otherwise looks well; it is self-limited and resolves over weeks. Encephalitis is a diffuse, more ominous direct and immune-mediated process with altered mental status and seizures, carrying real mortality. Reye syndrome, mitochondrial injury with hepatic steatosis and cerebral edema, is triggered by salicylates given during varicella or influenza, presenting with intractable vomiting followed by encephalopathy, raised transaminases and hyperammonemia with normal bilirubin.

In pregnancy, transplacental viremia before 20 weeks of gestation can damage developing tissue and, characteristically, the fetal dorsal root ganglia. Denervation of a limb bud produces hypoplasia of that limb with cicatricial scarring in the same dermatome, together with chorioretinitis, cataracts, microcephaly and cortical atrophy: congenital varicella syndrome. Near delivery the mechanism is different and is about antibody timing. If the mother develops rash from 5 days before to 2 days after delivery, the newborn receives virus transplacentally but not enough maternal IgG, and develops overwhelming neonatal varicella with mortality up to 30 percent.

Finally, the virus is never cleared. It travels along sensory nerves to establish latency in dorsal root and cranial nerve ganglia, from which it reactivates decades later as herpes zoster when cell-mediated immunity wanes. Treating the primary infection with acyclovir does not prevent this.

02Classification and Clinical Manifestation

Complications, listed by the population in which they are tested

03Diagnostic Workup

In an unvaccinated child with a generalized pruritic vesicular eruption in crops, lesions at different stages, and a documented exposure 2 weeks earlier, the best initial step is clinical diagnosis alone. No confirmatory testing is required, and a question that offers "PCR of vesicle fluid" against "diagnose clinically and begin symptomatic care" in a textbook pediatric case is testing whether you order tests you do not need. Isolation precautions are the action item, not laboratory confirmation.

Confirmatory testing is required when the clinical picture is not classic or when the answer changes management. That covers four situations: a vaccinated patient with breakthrough disease whose sparse maculopapular rash resembles an insect bite reaction; an immunocompromised or pregnant patient in whom antiviral and immune globulin decisions turn on certainty; a neonate; and any case where herpes simplex, mpox or a drug eruption is a serious alternative. In all of these, the correct sequence is to select the newest, intact, fluid-filled vesicle, unroof it, and swab the base of the lesion vigorously, because the diagnostic material is cellular. That sample goes for PCR, which is the most accurate test. If the lesions have already crusted, the crust itself can be lifted and submitted; PCR remains the highest-yield option.

Serology answers a different question. IgG establishes immunity and belongs to exposure management and occupational screening, not to acute diagnosis. When a pregnant woman reports exposure and cannot recall chickenpox or vaccination, the correct first step is not to give immune globulin blindly but to send varicella IgG, provided the result can be obtained rapidly; a positive result ends the workup, while a negative result makes immune globulin the next step. In an immunocompromised patient after exposure, the sequence is compressed because the risk is high and time is short.

Complication-directed testing is layered on top. Any adult with chickenpox and a cough, dyspnea, or oxygen saturation below the expected range needs a chest radiograph and pulse oximetry; the finding of diffuse nodular infiltrates confirms varicella pneumonia and converts management to intravenous therapy. A child who develops gait instability roughly a week after the rash, with a normal level of consciousness and no fever, has acute cerebellar ataxia and needs reassurance and observation rather than an urgent scan; imaging and lumbar puncture become appropriate when the sensorium is altered, seizures occur, there are focal deficits, or the picture could be meningitis. Persistent vomiting with encephalopathy in a child who received aspirin prompts transaminases, ammonia, glucose and coagulation studies for Reye syndrome.

Findings that confirm or reframe the diagnosis: a positive vesicle PCR confirms it outright; multinucleated giant cells support a herpesvirus but do not name it; negative IgG with a compatible exposure identifies a susceptible host requiring prophylaxis; new lesions continuing beyond day 7 with hemorrhagic change identifies progressive varicella and demands hospitalization.

04Management and Treatment

Acute stabilization starts with two questions: is this host at risk of severe disease, and are they already showing signs of it? A well-appearing, immunocompetent child under 12 needs no antiviral agent. Trials in this group show only about one less day of fever and modestly fewer lesions, which does not justify treating everyone, and the exam consistently rewards symptomatic care with pruritus control, hydration and infection-control counseling. What matters instead is the negative instruction: no salicylates because of Reye syndrome, and avoid ibuprofen because of the reported association with invasive group A streptococcal soft tissue infection during chickenpox. Acetaminophen is the antipyretic of choice.

For everyone outside that low-risk group, oral acyclovir within 24 hours of rash onset is the answer: age over 12 years, chronic pulmonary or cutaneous disease, long-term salicylate therapy, corticosteroid use, and secondary household cases. In immunocompromised hosts, in pneumonia, in encephalitis and in neonatal disease, the route changes rather than the drug: intravenous acyclovir, admission, and supportive care. Generous hydration is part of the prescription because acyclovir precipitates in renal tubules, and the dose is reduced in renal impairment.

The next best step in several classic branch points:

• Adult smoker on day 3 of the rash with new dyspnea and hypoxemia: obtain a chest radiograph and pulse oximetry, then admit for intravenous acyclovir and supportive oxygen.

• Child whose fever resolved and then returned on day 5 with a tender, expanding erythematous lesion: this is bacterial superinfection, and the next step is antibiotics against Staphylococcus aureus and group A Streptococcus, with surgical assessment if pain seems out of proportion or systemic toxicity is present.

• Non-immune pregnant woman exposed 3 days ago: check varicella IgG if it can be resulted quickly, then give varicella-zoster immune globulin if she is susceptible. Never the live vaccine.

• Immunocompromised patient exposed: immune globulin, not the vaccine, and not simply observation.

• Neonate whose mother developed rash 2 days before delivery: immune globulin at birth, with intravenous acyclovir if disease develops.

• Susceptible healthy college roommate exposed yesterday: vaccinate within 3 to 5 days.

Long-term management is really prevention and counseling. The illness itself is self-limited and confers lifelong immunity against a second episode of chickenpox, but the virus persists in sensory ganglia and can reactivate as herpes zoster decades later. Antiviral treatment of the primary illness does not reduce that risk. Adults aged 50 and older should be counseled about the recombinant zoster vaccine at the appropriate time, which is a distinct product from the childhood varicella vaccine. Scarring is usually the result of scratching and superinfection, which is why nail care and pruritus control are more than comfort measures.

Contraindications to standard therapy deserve their own attention. The live attenuated vaccine is contraindicated in pregnancy, in severe cellular immunodeficiency, in untreated advanced HIV, in patients on high-dose corticosteroids, and in anyone with anaphylaxis to gelatin or neomycin; pregnancy should be avoided for 1 month after vaccination. Household contacts who are pregnant or immunocompromised are not a contraindication to vaccinating a healthy child, since transmission of vaccine strain is rare and only from a vaccine-associated rash. Acyclovir requires renal dose adjustment and adequate hydration, and in renal failure the interval is lengthened rather than the drug abandoned. Salicylates are contraindicated in children with varicella. Corticosteroids should not be given for uncomplicated varicella, and a patient on chronic corticosteroids who develops varicella needs the dose reduced where safely possible along with antiviral therapy.

05Differential Diagnosis And Distractors

06Traps And High-Yield Pearls

The most frequent way this topic is missed is not failing to recognize chickenpox but failing on the management branch point after recognition. Students correctly identify the rash and then treat every patient the same way. The competency being tested is risk stratification: a healthy 5-year-old gets calamine and a school exclusion, a 25-year-old smoker gets oral acyclovir started within 24 hours and a chest radiograph if short of breath, and a child on induction chemotherapy gets admitted for intravenous acyclovir. Answer choices are built so that "oral acyclovir" is right for one patient and wrong for the patient in the next question.

The second common trap is the exposure question, where the reflex is to reach for the vaccine. The rule is that the live vaccine goes to susceptible immunocompetent hosts within 5 days, while immune globulin goes to those who cannot receive a live vaccine: pregnant non-immune women, the significantly immunocompromised, neonates whose mothers developed rash from 5 days before to 2 days after delivery, and preterm infants. Giving the live vaccine in pregnancy is the classic wrong answer, and so is giving immune globulin to a healthy vaccinated adult who needs nothing at all.

Third, the analgesic trap. Aspirin during varicella produces Reye syndrome, and the vignette signals it with a child who was "given a chewable tablet for fever" and returns with vomiting and confusion, transaminase elevation and hyperammonemia with a normal bilirubin. Ibuprofen is the subtler version of the same trap, given its reported link to invasive group A streptococcal infection during chickenpox. Acetaminophen is the only clean choice.

Fourth, stage synchrony is the single detail that separates varicella from smallpox and mpox. Varicella lesions in one body region sit at different stages at once because seeding occurs in waves. Smallpox and mpox lesions in one region are all at the same stage, are deep and umbilicated, and involve palms and soles. If a question describes uniform deep lesions on the palms with lymphadenopathy, the diagnosis is not chickenpox no matter how convincing the fever and the vesicles look.

Fifth, breakthrough varicella in a vaccinated child is written to look like insect bites: 20 sparse maculopapular lesions, no fever, and a parent insisting the child is fully immunized. Vaccination reduces severity, not the possibility of infection, and the child is still contagious. This is where PCR of a lesion base earns its place, and where isolation until no new lesions for 24 hours applies even though nothing ever crusts.

Sixth, isolation type. Varicella requires airborne plus contact precautions, not droplet precautions, and it continues until every lesion has crusted. A non-immune exposed inpatient is isolated from day 8 to day 21 after exposure, and to day 28 if immune globulin was given, which reflects the incubation period extended by passive antibody.

Seventh, do not confuse acute cerebellar ataxia with encephalitis. A well-appearing child with a wide-based gait a week after chickenpox needs reassurance and observation, not an antiviral drip and an urgent scan; a patient with altered mental status or seizures needs the opposite.

Finally, the timing traps in pregnancy are worth memorizing as two windows. Infection before 20 weeks risks congenital varicella syndrome with dermatomal cicatricial scarring and limb hypoplasia. Maternal rash from 5 days before to 2 days after delivery risks fatal neonatal varicella and mandates immune globulin for the newborn. Maternal rash more than 5 days before delivery is the reassuring scenario, because transplacental maternal IgG has had time to reach the fetus.

The core competencies here are recognizing an evolving polymorphic vesicular exanthem, separating it from synchronous-lesion mimics, stratifying hosts by risk to decide whether and how to treat, and applying post-exposure prophylaxis rules that hinge entirely on whether the exposed person can safely receive a live vaccine.