Varicella, also known as chickenpox, is a highly contagious acute primary infection caused by the varicella-zoster virus. It is characterized by the rapid onset of pruritic eruptions that occur in successive waves and consist of a mixture of papules, vesicles, pustules, and crusts. ICD-10 code is B01.9.
Chickenpox is more common in countries with moderate climates, with the peak of the disease occurring during the winter and spring months. In the United States, 3-4 million cases of chickenpox are reported each year. Chickenpox is most commonly found in children under the age of 10, with less than 5% of cases occurring in those over 15 years old. In the United Kingdom, the disease is mainly observed in preschool-aged children.
Chickenpox is highly contagious, as evidenced by the high rate of secondary infection among household contacts (>90%). It is transmitted primarily by airborne droplets and less commonly by direct contact with the lesions of chickenpox or shingles. A patient is contagious 1-2 days before the rash appears and remains contagious until all lesions have crusted over, which typically occurs by day 6. Natural infection with chickenpox usually confers long-lasting immunity, although clinical recurrences are more common than commonly recognized.
Varicella-zoster virus is controlled by a specific humoral and cellular immune response, which helps to control viremia. Disease control appears to be primarily mediated by cell-mediated immunity. Patients with impaired cell-mediated immunity tend to have more severe cases of chickenpox compared to those with impaired humoral immunity. The varicella-zoster virus can enter a latent state in the dorsal root ganglia or other sensory ganglia, and its reactivation can cause herpes zoster (shingles).
Following an average incubation period of 14-17 days (ranging from 3 to 23 days), the disease begins with prodromal symptoms such as fever, chills, malaise, anorexia, headache, and back or abdominal pain. These symptoms are usually mild or absent in children but more pronounced and prolonged in adults. The fever is typically moderate, although it can occasionally reach 40°C.
The rash initially appears on the scalp or trunk and spreads centrifugally to the face, trunk, and proximal parts of the limbs. The rash typically appears more prominently in covered areas and areas of chronic skin inflammation. At first, the lesions present as individual erythematous patches that quickly develop into papules and then into clear vesicles. These vesicles are surrounded by an irregular erythematous halo, resembling the classic image of "dewdrops on a rose petal". The vesicles become cloudy and develop a depression in the center as they progress into pustules and eventually crusts. The crusts will fall off within 1-3 weeks without leaving scars.
The development of the rash from the macular stage to the crust stage takes approximately 8-12 hours. A characteristic feature of chickenpox is the appearance of rash clusters in successive waves. As a result, different stages of rash development can be observed on any area of the skin. This feature is pathognomonic for varicella. Lesions (vesicles that develop into ulcers) may also occur on mucous membranes, especially in the oral cavity (palate) or genital organs. Moderate to severe itching is common during the vesicular stage.
Complications of Chickenpox
In healthy children, chickenpox is usually mild and clears up on its own. Complications are rare, but can be classified as viral or bacterial. Bacterial skin and soft tissue infections (impetigo, furuncles, cellulitis, erysipelas, necrotizing fasciitis/pyomyositis) are caused primarily by Staphylococcus aureus or Streptococcus pyogenes and are the most common. These infections are often triggered by scratching and can lead to the formation of pock-like scars.
On the other hand, the following patient groups are at high risk for severe disease, which can be associated with life-threatening conditions:
- Otherwise healthy adults and adolescents
- Pregnant women
- Newborns
- Patients with malignancies on a background of immunodeficiency or patients with leukemia or cancer undergoing immunosuppressive chemotherapy or radiation therapy
- Patients with iatrogenic immunodeficiency due to treatment with cytotoxic or immunosuppressive drugs or systemic or intranasal corticosteroids
- Organ transplant recipients under immunosuppression, especially bone marrow transplant recipients
- HIV-infected individuals.
In adults and immunocompromised patients, the most common complication of chickenpox is primary varicella pneumonia (PVP). In one study, radiographic evidence of PVP was confirmed in 16% of healthy adult males, while clinical symptoms were present in only 4%. PVP typically begins 1-6 days after the onset of the rash and presents with cough, dyspnea, cyanosis, and pleuritic pain, but may be asymptomatic. Physical signs are usually mild, but chest X-rays show diffuse bilateral nodular opacities. Mortality rates are 10-30%.
Neurological complications, including encephalitis, acute cerebellar ataxia, acute ascending or transverse myelitis, Guillain-Barré syndrome, and others, occur less frequently than in 1 in 1000 cases. Complete recovery is generally expected. In contrast, mortality from encephalitis in adults can be as high as 35%. Reye's syndrome is an acute encephalopathy associated with fatty degeneration of internal organs, especially the liver. The pathogenesis of the disease associated with salicylates is not fully understood. Although this complication is rare in healthy children, it accounts for up to 40% of deaths from varicella.
Mild hepatitis is typical. Other complications involving internal organs include nephritis, orchitis, pericarditis, myocarditis, and pancreatitis. Multiple organ involvement is more likely in individuals with compromised immune function. Hemorrhagic complications range from transient thrombocytopenia to hemorrhagic chickenpox (fulminant purpura).
Atypical forms of varicella, such as verrucous varicella, have been described in HIV-positive patients. The most common complications in these individuals are recurrent and protracted forms of the disease.
Varicella during pregnancy poses a threat to both the mother and the fetus. The incidence of varicella in pregnant women is estimated to be 1-7 cases per 10,000 pregnancies. The mother is at increased risk for disseminated chickenpox or severe primary varicella pneumonia. Maternal viremia may lead to intrauterine infection. Early embryonic infection may result in abortion. The risk of fetal abnormalities is 2% or less and peaks between 7 and 20 weeks of gestation.
Chickenpox in newborns can occur if the mother is infected during the first two trimesters of pregnancy, resulting in congenital varicella syndrome. This syndrome is characterized by limb hypoplasia, skeletal abnormalities, neurological and ocular defects, skin scarring, and low birth weight. Vertical transmission in later stages of pregnancy may result in premature labor or stillbirth. Maternal chickenpox during the perinatal period can cause severe and even fatal illness in the newborn. If the mother develops the rash less than 5 days before delivery or within 2 days after delivery, the newborn may develop chickenpox between the 5th and 10th day of life. At this time, the newborn's immune system is immature, and the baby is born before a sufficient amount of protective maternal antibodies can cross the placenta to modify the infection. Perinatal chickenpox is associated with a 20% mortality rate due to progressive internal organ involvement.
- Smallpox
- Monkeypox
- Disseminated herpes simplex or disseminated herpes zoster
- Bullous impetigo
- Vesicular exanthems caused by Coxsackie and ECHO viruses or vesicular rickettsiosis
- Drug eruptions
- Erythema multiforme
- Insect bites
- Scabies
- Papular urticaria
General therapeutic recommendations for the treatment of varicella can be divided into symptomatic and etiologic (antiviral) therapy.
Symptomatic therapy is aimed primarily at alleviating itching and fever and provides relief for all patients.
- Itching can be relieved by applying a drying and antipruritic lotion, such as calamine lotion, alone or in combination with 25% menthol and/or 1% phenol. Cool water compresses or bathing with room temperature water and baking soda (1/2 cup per bath) may also help relieve pruritus. Systemic antihistamines are effective for generalized itching.
- Antipyretics may be needed to control elevated body temperature. Aspirin is contraindicated because of a suspected association with Reye's syndrome.
- Oral and genital lesions may be treated with mouth rinses or compresses with 1.5% hydrogen peroxide, isotonic solution, or other preparations.
- Topical corticosteroids should be avoided.
- Topical antibiotics such as mupirocin ointment or bacitracin-polymyxin may be used to treat bacterial superinfections of skin lesions. If the infection is widespread, systemic antibiotics such as erythromycin, dicloxacillin, or cephalexin may be prescribed.
- Good hygiene is important. Baths, use of soothing compresses, isolation in a well-ventilated room with regular changes of bedding, and a light diet are recommended.
- Etiologic therapy targets the varicella-zoster virus. Several antiviral drugs, mostly nucleoside analogues, are available that interfere with the replication of the virus by inhibiting specific stages of the replication process. Antiviral drugs have a virustatic effect by inhibiting viral replication.
Note: Specific antiviral medications and their dosages should be determined by a healthcare professional based on the individual patient's condition.
Recommended Treatments
Acyclovir (ACV)
ACV is the drug of choice for treatment. ACV (a guanosine analog) is selectively phosphorylated by viral thymidine kinase to form ACV monophosphate, which is further converted by cellular enzymes to ACV triphosphate. ACV triphosphate inhibits viral DNA polymerase and stops the synthesis of viral DNA. ACV has been used safely and effectively to treat herpes simplex virus infections for more than 10 years. ACV treatment should be initiated within 24-48 hours after the onset of the rash. It is administered orally at a dose of 20 mg/kg, up to a maximum of 800 mg, four times daily for 5 days in children or 800 mg five times daily for 5 days in adults. For disseminated or complicated chickenpox, intravenous administration at a dose of 10 mg/kg every 8 hours for 7-10 days or until no new lesions appear for 48 hours is recommended.
Placebo-controlled, randomized trials have shown that oral acyclovir reduces the severity and duration of cutaneous and systemic signs and symptoms in healthy children, adolescents, and adults with an excellent safety profile. In addition, intravenous administration of ACV has been effective in preventing the spread of chickenpox, significantly reducing complications from internal organ involvement, viral shedding time, and duration of lesion healing in high-risk patients. Adequate hydration and dose adjustment based on decreased creatinine clearance are necessary in patients with renal insufficiency.
Recommendations for the use of acyclovir (modified based on the American Academy of Pediatrics, 1993).
Considering the limited therapeutic effect and the potential for drug elimination from the body, systemic administration of ACV is not recommended for the treatment of uncomplicated chickenpox in otherwise healthy children. These patients only require symptomatic therapy. Systemic acyclovir administration is optional for the following high-risk patient groups with severe chickenpox:
- Healthy individuals aged 13 years and older, including non-pregnant women of childbearing age.
- Individuals who had secondary exposure to the patient at home.
- Children older than 12 months with chronic skin or lung diseases (e.g., cystic fibrosis) or diabetes, as well as patients receiving prolonged salicylate therapy or periodic steroids.
- The following patient groups should be given intravenous acyclovir as soon as possible:
- Patients with malignant diseases (leukemia, lymphoproliferative disorders, metastatic tumors, etc.).
- Patients with congenital T-cell immunodeficiency or HIV infection
- Patients receiving high doses of steroids.
- Recipients of bone marrow and organ transplants.
- Newborns with chickenpox whose mothers had the disease within 5 days before delivery or within 2 days after delivery.
- Patients with complications involving internal organs, such as primary chickenpox pneumonia or encephalitis.
- Patients receiving cytostatic or immunosuppressive chemotherapy should temporarily discontinue treatment if possible and resume it after 7 days when all lesions have crusted. Steroid doses should also be gradually reduced during the incubation period.
- Systemic acyclovir administration can be beneficial for pregnant women with chickenpox, but there are still differing opinions regarding the safety of this therapy for the fetus.
Resistance to ACV is very rare in immunocompetent individuals. However, the increased clinical use of ACV has been associated with the emergence of drug-resistant strains of varicella-zoster virus, particularly in immunocompromised patients. Resistance results from mutations at the thymidine kinase (TK) level. In such cases, antiviral treatment with foscarnet (40 mg/kg IV every 8 hours) is administered. Foscarnet is a direct inhibitor of viral DNA polymerase and does not require activation by viral TK. Recently, strains resistant to foscarnet and sensitive to cidofovir, an acyclic nucleotide phosphonate, have been reported. Only cellular enzymes are required to convert cidofovir to its phosphorylated derivative, which inhibits viral DNA polymerase.
Vidarabine and Interferon-alpha
Intravenous vidarabine (10 mg/kg every 12 hours for 5 days) is an alternative antiviral treatment for severe chickenpox. It is as effective as ACV but is more toxic. Interferon-alpha (3.5 × 105 IU/kg daily for 2 days, followed by 1.75 × 105 IU/kg daily for 3 days) or infusion of irradiated lymphocytes from healthy donors who have recovered from varicella have also been used with satisfactory results.