All About Chicken Pox (Varicella)

Primary infection with varicella-zoster virus (VZV) causes varicella (chickenpox). The virus establishes latent infection in dorsal root ganglia; its reactivation causes herpes zoster (shingles).

ETIOLOGY.

VZV is a human herpesvirus; it is classified as an alpha herpesvirus because of its similarities to the prototype for this group, which is herpes simplex virus (HSV). VZV is an enveloped, double-stranded DNA virus; the viral genome encodes more than 70 proteins, including proteins that are targets of immunity and a viral thymidine kinase, which makes the virus sensitive to inhibition by acyclovir and related antiviral agents.

VZ-Virus

PATHOLOGY.

Varicella begins with mucosal inoculation of virus transferred in respiratory secretions or by direct contact with skin lesions of varicella or herpes zoster. Inoculation is followed by an incubation period of 10–21 days, during which subclinical viral spread occurs. Widespread cutaneous lesions result when the infection enters a viremic phase; peripheral blood mononuclear cells carry infectious virus, generating new crops of vesicles for 3–7 days. VZV is also transported back to respiratory mucosal sites during the late incubation period, permitting spread to susceptible contacts before the appearance of rash. The transmission of infectious virus by respiratory droplets distinguishes VZV from other human herpes viruses. Visceral dissemination of the virus follows the failure of host responses to terminate viremia, which results in infection of lungs, liver, brain, and other organs. VZV becomes latent in dorsal root ganglia cells in all individuals who experience primary infection. Its reactivation causes a localized vesicular rash that usually involves the dermatomal distribution of a single sensory nerve; necrotic changes are produced in the associated ganglia, sometimes extending into the posterior horn. The histopathology of varicella and herpes zoster lesions is identical; infectious VZV is present in herpes zoster lesions, as it is in varicella lesions, but is not released into respiratory secretions. Varicella elicits humoral and cell-mediated immunity that is highly protective against symptomatic reinfection. Suppression of cell-mediated immunity to VZV correlates with an increased risk of VZV reactivation as herpes zoster.

EPIDEMIOLOGY.

In the United States and other temperate climates, 90–95% of individuals acquire VZV in childhood. Annual varicella epidemics occur in winter and spring. Wild-type VZV strains that cause the annual epidemics of varicella do not exhibit changes in virulence as judged by the clinical severity of primary VZV infections from year to year. Household transmission rates are 80–90%; more casual contact, such as school classroom exposure, is associated with attack rates of 30% or less. Varicella is contagious from 24–48 hr before the rash appears and while uncrusted vesicles are present, which is usually 3–7 days. Susceptible children acquire varicella after close, direct contact with adults who have herpes zoster; this route of transmission maintains the circulation of the virus in the population. For unexplained reasons, varicella is much less common in tropical areas, so that susceptibility rates among adults are as high as 20–30%. Herpes zoster shows no seasonal variation in incidence because it is due to the reactivation of endogenous, latent virus. Despite anecdotal reports, epidemiologic studies demonstrate that exposure to varicella does not cause herpes zoster. Herpes zoster is very rare in children younger than 10 yr except among those given immunosuppressive therapy for malignancy or other diseases, those who have human immunodeficiency virus (HIV) infection, and those who have been infected in utero or during the first year of life. The risk of severe or life-threatening primary or recurrent VZV infection is related primarily to host factors rather than variations in the pathogenicity of VZV strains.

CLINICAL MANIFESTATIONS OF VARICELLA.

Although the incubation period of varicella ranges from 10–21 days, the illness usually begins from 14–16 days after exposure. Almost all exposed, susceptible children experience a rash, but it may be limited to fewer than 10 lesions. Prodromal symptoms are common, particularly in older children; fever, malaise, anorexia, headache, and occasionally mild abdominal pain occur 24–48 hr before the rash appears. Temperature elevation is usually moderate, ranging from 100–102º F but may be as high as 106º F; fever and other systemic symptoms persist during the first 2–4 days after the onset of the rash. Varicella lesions appear first on the scalp, face, or trunk. The initial exanthem consists of intensely pruritic erythematous macules that evolve to form clear, fluid-filled vesicles. Clouding and umbilication of the lesions begin in 24–48 hr. While the initial lesions are crusting, new crops form on the trunk and then the extremities; the simultaneous presence of lesions in various stages of evolution is characteristic of varicella.

  

Typical rash in varicella

 

Pustular rashes and hemorrhagic rashes

 

 Hemorrhagic form of varicella

Ulcerative lesions involving the oropharynx and vagina are common; many children have vesicular lesions on the eyelids and conjunctivae, but serious ocular disease is rare. The average number of varicella lesions is about 300, but healthy children may have from fewer than 10 to more than 1,500 lesions. In secondary household cases and cases involving older children, more days of new lesion formation and more lesions are likely. The exanthem is more extensive in children with skin disorders, such as eczema or recent sunburn. Hypopigmentation of lesion sites persists for days to weeks in some children, but scarring is unusual.

 

 An element on the palate

Varicella Convalescent

The differential diagnosis of varicella includes vesicular rashes caused by other infectious agents, such as enterovirus or Staphylococcus aureus, drug reactions, contact dermatitis, and insect bites.

COMPLICATIONS OF VARICELLA.

Secondary bacterial infections, usually resulting from S. aureus or Streptococcus pyogenes (group A b{beta}-hemolytic streptococcus), are the most common complication of varicella. Cellulitis, lymphadenitis, and subcutaneous abscesses also occur. Varicella gangrenosa, usually resulting from S. pyogenes, is a rare but potentially life-threatening consequence of secondary infection. Acute bacterial sepsis is uncommon, but transient bacteremia may cause focal infections, including staphylococcal or streptococcal pneumonia, arthritis, or osteomyelitis. Encephalitis and cerebellar ataxia are well-described neurologic complications of varicella; the incidence of central nervous system morbidity is highest among patients younger than 5 yr and older than 20 yr. Meningoencephalitis is characterized by seizures, altered consciousness, and nuchal rigidity; patients with cerebellar ataxia have a more gradual onset of gait disturbance, nystagmus, and slurred speech. Neurologic symptoms usually begin from 2–6 days after the onset of the rash but may occur during the incubation period or after resolution of the rash. VZV-related encephalitis and cerebellar ataxia may be immune mediated; the severe hemorrhagic encephalitis caused by HSV is very rare in children with varicella. Clinical recovery is typically rapid, occurring within 24–72 hr, and is usually complete. Before the association of salicylates was documented, some children with varicella had neurologic symptoms caused by the encephalopathy associated with Reye syndrome. Varicella hepatitis is relatively common and is usually subclinical, but some children have severe vomiting, which must be differentiated from that associated with Reye syndrome. Acute thrombocytopenia, accompanied by petechiae, purpura, hemorrhagic vesicles, hematuria, and gastrointestinal bleeding, is a rare complication that is usually self-limited. Other rare complications of varicella include nephritis, nephrotic syndrome, hemolytic-uremic syndrome, arthritis, myocarditis, pericarditis, pancreatitis, and orchitis.

Progressive disease caused by primary VZV infection occurs in otherwise healthy adolescents and adults, immunocompromised children, pregnant women, and newborn infants. Varicella pneumonia is very rare in children, but this complication accounts for most of the increased morbidity and mortality in high-risk populations. Respiratory symptoms, which may include cough, dyspnea, cyanosis, pleuritic chest pain, and hemoptysis, usually begin within 1–6 days (average, 3 days) after the onset of the rash. Hypoxemia is often much more severe than is suggested by the physical findings; the chest radiograph may be normal or may show diffuse bilateral infiltrates. Varicella pneumonia is often transient, resolving completely within 24–72 hr, but in severe cases, the interstitial pneumonitis progresses rapidly to cause respiratory failure. Hemorrhage into the cutaneous lesions is a sign of severe varicella in high-risk patients, as is severe abdominal or back pain, although its pathogenesis is uncertain.

The risk of progressive varicella is highest in children with malignancy if chemotherapy was given during the incubation period and the absolute lymphocyte count is less than 500 cells. In one large series, the mortality rate without antiviral therapy was 7%, and all varicella-related deaths occurred within 3 days after the diagnosis of varicella pneumonia. Hepatitis, encephalitis, and disseminated intravascular coagulopathy are other frequent complications. The syndrome of inappropriate antidiuretic hormone secretion may accompany disseminated varicella with or without clinical encephalitis. Children who acquire varicella after organ transplantation are also at risk for progressive VZV infection. Children on long-term, low-dose steroid therapy usually have no complications, but fatal varicella has occurred in patients receiving high-dose steroids. Untreated varicella is severe or fatal in children with congenital immunodeficiency disorders, especially involving cell-mediated immunity. Unusual clinical findings of varicella, including lesions that develop a unique hyperkeratotic appearance and chronic new lesion formation for weeks or months, have been described in children with HIV infection.

In rare instances, maternal varicella results in the congenital varicella syndrome, associated with unusual cutaneous defects, atrophy of an extremity, microcephaly, ocular defects, and damage to the autonomic nervous system. Infants who are born within 4 days after or 2 days before the onset of maternal varicella may acquire progressive varicella.