VARICELLA (Chicken pox) INFECTION & TROPICAL MEDICINE DIVISION

Definition : Varicella is a common contagious disease caused by primary infection with varicella-zoster virus (VZV). It is characterized by a short or absent prodromal period and by a pruritic rash consisting of crops of papules, vesicles, pustules, and crusting Etiology : Varicella zoster virus (VZV)  Herpesvirus group

Epidemiology : worldwide distribution, usually endemic in large cities Epidemiology : worldwide distribution, usually endemic in large cities. The mostly age distribution is 5-9 year old. Transmission by direct contact, droplet. The patient can transmit the disease 1 day before the rash appeared until crusted was dried. In mild cases, crusted was completed until 5 days, and in severe cases until 10 days.

Epidemiology of primary varicella 90% of cases occur at <10 years of age; maximum incidence ages 1-6 Older children more likely to have prodromal symptoms [Whitney RJ (1990) Antiviral agents and viral diseases of man. Raven Press, NY] Higher risk of herpes zoster in healthy children infected with VZV during infancy [Kakourou T et al.(1998) JAAD 39, 207-10; Baba K et al. (1986) J Pediatr 372-7.] Highly contagious, with >90% household transmission rate [Ross AH (1962) NEJM 267, 369-76.] 10-35% transmission rate with secondary contacts like school [Ross AH (1962) NEJM 267, 369-76.]

Pathogenesis :

Primary varicella Days 2-4: initial viral replication in regional lymph nodes Days 4-6: primary viremia Subsequent second round of viral replication in liver, spleen, other organs Secondary viremia seeds capillaries and then epidermis by day 14-16

Herpes zoster VZV spreads from skin/mucosa into sensory nerve endings Virus travels to dorsal root ganglion and becomes latent Reactivation occurs with decreased cell-mediated immunity Initial replication occurs in affected DRG after reactivation

Ganglionitis ensues, with inflammation and neuronal necrosis Pain ensues with travel of the virus down the sensory nerve

Clinical manifestations : Incubation period 14-16 days (10-21 days). The disease begins with low-grade fever, malaise, and the appearance of rash. In children the exanthem and symptoms usually occur simultaneously.

Rash : The typical vesicle of chickenpox is superficially located in the skin. The lesion appear in crops that generally involve the trunk, scalp, face, and extremities. The distribution typically central especially on trunk and face.

The rash is more profuse on the proximal parts of the extremities than on the distal parts. A distinctive manifestation of the eruption is the presence of lesions in all stages in any one general anatomical area; macules, papules, vesicles, pustules, and crusts are usually located in proximity to each other. In summary, the rash characterized by (1) a rapid evolution of macule to papule to vesicle to pustule to crust, (2) a central distribution of lesions that appear in crops, and (3) the presence of lesions in all stages in any one anatomical area.

Fever : The height of the fever usually paralels the severity of the rash. When the eruption is sparse, the temperature is usually normal or slightly elevated. Other symptoms : headache, malaise, and anorexia usually accompany the fever. The most distressing symptom is pruritus, which is present during the vesicular stage of the disease.

Unusual manifestations : Hemorrhagic, progressive, and disseminated varicella  in immunompromised host and a potencially fatal outcome. Our department had been reporting 3 cases with varicella hemorrhagic, two in immunocompromised child and the other in normal child. Congenital varicella syndrome is extremely rare. Manifestations of this syndrome include a hypoplastic extremity, zosteriform skin scarring, microphthalmia, cataracts, choreoretinitis, and abnormalities of the CNS.

Severe or fatal varicella in 5 to 10 day-old infants may occur when their mothers have varicella 5 days or less before delivery.

Diagnosis : 1. Confirmatory clinical factors, (1) development of a pruritic papulovesicular eruption concentrated on the face and trunk associated with fever and mild constitutional symptoms;

(2) the rapid progression of macules to papules, vesicles, pustules, and crusts; (3) the appearance of these lesions in crops, with a predominant central distribution including the scalp; (4) the presence of shallow white ulcers on the mucous membranes of the mouth; and (5) the eventual crusting of the skin lesions. 2. Detection of the causative agent from vesicular fluid 3. Serological tests : ELISA, FAMA, RIA, LA

Differential diagnosis : Impetigo Insect bites, papular urticaria, and urticaria Scabies Dermatitis herpetiformis Rickettsialpox Eczema herpeticum and other forms of HSV infection Steven-Johnson syndrome Smallpox

Chickenpox versus smallpox 14-21 day incubation Mild to no preceding illness Lesions most numerous on trunk Palms and soles spared Lesions at varying stages of development Scabs form 4-7 days after rash appears Vesicles do collapse on puncture SMALLPOX 7-17 day incubation Fevers, severe systemic symptoms precede rash by 2-3 days Lesions most numerous on face, arms, legs Palms and soles involved Lesions at same stage of development Scabs form 10-14 days after rash appears Vesicles do not collapse on puncture

Complications : are not common Secondary bacterial infection Encephalitis Varicella pneumonia Reye’s syndrome Disseminated varicella Prognosis : usually a benign disease, clears spontaneously without sequaelae.

Complications and mortality in varicella In healthy children aged 1-14, mortality rate estimated at 2/100,000 [Mehta PN (2004) eMedicine online] Bacterial superinfection is most common complication; Staph exotoxin can result in bullous varicella [Melish ME (J Pediatr (1973) 83, 1019-21]

CNS is most common extracutaneous site; symptoms include Reye’s syndrome, acute cerebellar ataxia, encephalitis, myelitis [McKendall and Kiawans (1978) Handbook of clinical neurology. Elsevier Press] Rare complications: myocarditis, appendicitis, glomerulonephritis, hepatitis, pancreatitis, vasculitis, arthritis, keratitis, iritis, optic neuritis Whitney RJ (1990) Antiviral agents and viral diseases of man. Raven Press, NY]

Immunity : an attack of chickenpox usually confers lasting immunity. Treatment : self limited disease 1. Symptomatic  acetaminophen for high fever; oral antihistamines and local applications of of calamine lotion may help control the itching. Fingernails should be kept short and clean in an attempt to minimize secondary skin infections. For same reason, daily bathing also recommended during chickenpox.

2. Treatment of complications : (1) bacterial infections (2) encephalitis 3. Specific antiviral : 20 mg/kg of acyclovir four times daily for 5 days (max 800 mg) Preventive measures : Zoster immunoglobulin (ZIG) 5 ml/IM within 72 hours of a household exposure to children with underlying leukemia. Live attenuated varicella vaccine.