Chickenpox in Childhood illness

Varicella-Zoster Virus

    Varicella-zoster virus (VZV) causes chickenpox and herpes zoster (shingles). Chickenpox follows initial exposure to the virus and is typically a relatively mild, self-limited childhood illness with a characteristic exanthem, but can become disseminated in immunocompromised children. Reactivation of the dormant virus results in the characteristic painful dermatomal rash of herpes zoster, which is often followed by pain in the distribution of the rash (postherpetic neuralgia). See the image below.

                           
Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.

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Signs and symptoms

Pain and paresthesia are typically the first symptoms of VZV infection. Until the characteristic vesicular rash erupts, diagnosis may be difficult. A prodromal period during which symptoms may vary is common. Pain occurs in 41% of patients, itching in 27%, and paresthesias in 12%.

During the acute illness, patients may experience the following:

Pain (90%)

Helplessness and depression (20%)

Flulike symptoms (12%)

Herpes zoster (shingles)

The most common presentation is the shingles vesicular rash, which most commonly affects a thoracic dermatome

After a prodromal illness of pain and paresthesias, erythematous macules and papules develop and progress to vesicles within 24 hours

The vesicles eventually crust and resolve

Pain and sensory loss are the usual symptoms

Motor weakness also occurs and is frequently missed on examination

Cases of actual monoplegia due to VZV brachial plexus neuritis have been reported

      Zoster multiplex

    Shingles may appear in multiple dermatomes, both contiguous and noncontiguous, on either side of the body

Immunocompromised individuals are more susceptible

Terminology depends on the number of involved dermatomes and on whether the condition is unilateral or bilateral (eg, zoster duplex unilateralis refers to the involvement of 2 unilateral dermatomes)

Cases of zoster simultaneously occurring in 7 noncontiguous dermatomes have been reported

    Zoster sine herpete

     VZV infection may reactivate without causing cutaneous vesicles. These patients have severe dermatomal pain, possible motor weakness and possible hypesthesia, but no visible rash or vesicles.

     VZV infection may present as acute peripheral facial palsy in 8-25% of patients who have no cutaneous vesicles.       This is more common in immunosuppressed patients who use acyclovir (or other agents) as zoster prophylaxis. ^[1]

      Central nervous system deficits

More common in immunocompromised individuals, but do occur in the general population

      CNS involvement may become apparent 3 weeks after the onset of the initial rash

The manifestations are usually bilateral

The physical findings may progress

The underlying pathology typically progresses for 3 or more weeks

     Progression for 6 months in immunocompromised individuals has been reported

Recurrence is rare but has been reported

     Zoster encephalitis is also rare but is reported in otherwise healthy individuals

      Ramsay-Hunt syndrome

     This syndrome occurs when the geniculate ganglion is involved. The clinical presentation includes the following:

     A peripheral facial palsy

     Pain in the ear and face

Vesicles in the external ear canal (not always present)

Additional auditory and vestibular symptoms in some cases

    Keratitis (herpes ophthalmicus)

     Caused by reactivation of VZV infection in the ophthalmic division of the trigeminal nerve.

    The presentation may include conjunctivitis or corneal ulcers

Complications include blindness

Vesicles do not have to be present

Rarely, the virus migrates along the intracranial branches of the trigeminal nerve, causing thrombotic cerebrovasculopathy with severe headache and hemiplegia 

Physical

Herpes zoster (shingles)

The most common presentation is the shingles vesicular rash, which most commonly affects a thoracic dermatome.

After a prodromal illness of pain and paresthesias, erythematous macules and papules develop and progress to vesicles within 24 hours. The vesicles eventually crust and resolve.

Pain and sensory loss are the usual symptoms, but motor weakness also occurs and is frequently missed on examination. Motor weakness results when the viral activity extends beyond the sensory root to involve the motor root. Cases of actual monoplegia due to varicella-zoster virus (VZV) brachial plexus neuritis have been reported.

Typical zoster in the vicinity of right popliteal fossa in a vertebral nerve L4 distribution.

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Human herpesvirus (HHV) type 3. Intraoral herpes zoster closely resembles recurrent HHV-1 infection, but the lesions generally follow a dermatome and stop sharply at the midline, as shown here. However, the rules for common sites of occurrence of HHV-1 and HHV-3 often do not apply to patients who are immunocompromised. Courtesy of Sheldon 

Differential Diagnoses

• Acute Nerve Injury

• Chronic Fatigue Syndrome

• Electrical Injuries

• Eosinophilic Fasciitis

• Group A Streptococcal Infections

• Herpangina

• Herpes Simplex

• Impetigo

• Lumbar Disc Disease

• Lumbar Spondylosis

• Meningitis

• Meningococcal Infections

• Meningococcemia

• Neurosurgery for Cauda Equina Syndrome

• Poxviruses

• Rehabilitation and Fibromyalgia

• Spinal Cord Abscess

• Spinal Hematoma

• Spinal Stenosis.              

• Laboratory Studies.     When the presentation includes the typical dermatomal rash, additional studies are not required.

• If the diagnosis is in doubt, a Tzanck smear can be performed and has a sensitivity of about 60%. To obtain a Tzanck smear, remove the crust from a vesicle and scrape the underlying moist skin with a No. 15 surgical blade. Smear the cells from the vesicle base onto a slide, fix for 1 minute with absolute alcohol, and stain with Wright stain (other staining methods can also be used).

  The diagnosis can also be confirmed with a culture of vesicular fluid that is positive for varicella-zoster virus (VZV).

  In cases of zoster sine herpete, DNA analysis via polymerase chain reaction (PCR) can be used for early diagnosis if laboratory turnaround time is reasonably short. If not, the decision of whether to start empiric acyclovir must be based on clinical grounds alone.

  In cases of acyclovir-resistant VZV, detections of mutations in thymidine kinase can be determined by PCR and sequence analysis. Acyclovir-resistance may occur in stem cell transplant recipients. ^[5]

  Imaging Studies

  MRI may be useful if myelitis or encephalitis is suspected.

  Procedures

  Lumbar puncture may be helpful if signs suggest myelitis or encephalitis. The cerebrospinal fluid (CSF) shows increased levels of protein and pleocytosis because the inflammatory response involves the leptomeninges. CSF PCR can be used to detect VZV DNA.

  Although seldom necessary, biopsy results provide a definitive diagnosis.

  Histologic Findings

  The varicella zoster virus is a DNA virus with a genome that encodes 70 proteins.

  The Tzanck preparation shows characteristic findings of giant cells with 2-15 nuclei. Recently infected epithelial cells contain a single enlarged nucleus with a thick nuclear membrane.

• Medical Care

  Treatment options are based on the patient's age, immune state, duration of symptoms, and presentation.

  Several studies indicate that antiviral medications decrease the duration of symptoms and the likelihood of postherpetic neuralgia, especially when initiated within 2 days of the onset of rash. In typical cases that involve individuals who are otherwise healthy, oral acyclovir may be prescribed. An important study by Kubeyinje (1997) suggested that the use of acyclovir in healthy young adults with zoster is not clearly justified, especially in situations of limited economic resources. ^[6]

  Acyclovir has 2 limitations—bioavailability and the existence of some resistant strains of varicella-zoster virus (VZV).

  Other medications, including valacyclovir, penciclovir, and famciclovir, are also available. They may have an increasing role in the treatment of typical zoster. Studies suggest that, when compared with oral acyclovir, the new medications may decrease the duration of the patient's pain.

  Varicella zoster immune globulin (VariZIG) is indicated for administration to high-risk individuals within 10 days (ideally within 4 days) of chickenpox (varicella zoster virus) exposure. ^[2]  

  In July 2013, the CDC issued updated recommendations for the use of varicella-zoster immune globulin (VariZIG) to reduce the severity of VZV infection, extending the window for postexposure prophylaxis for those at high risk for severe varicella. ^[7, 8] The FDA's original approval of VariZIG recommended use within 4 days, but subsequent studies have shown that the treatment is effective for up to 10 days after exposure.

  Other recommendations include the use of VariZIG in the following patients:

  • Immunocompromised patients without evidence of immunity
  • Newborn infants whose mothers have varicella symptoms between 5 days before and 2 days after delivery
  • Hospitalized premature infants born at 28 weeks of gestation or later whose mothers do not have evidence of immunity to varicella
  • Hospitalized premature infants born at less than 28 weeks of gestation or who weigh less than 1000 g at birth, regardless of their mothers' evidence of immunity to varicella
  • Pregnant women without evidence of immunity

  Dworkin et al (2009) conducted a randomized, placebo-controlled trial of oral oxycodone and oral gabapentin as potential treatments for acute pain in patients with herpes zoster. They found that controlled-release oxycodone was superior to placebo in the early period of pain (1-14 d). Gabapentin was not shown to yield a significantly greater relief of pain than placebo, although it conferred modest pain relief during the first week. ^[9]

  Surgical Care

  Surgical care may be required for complications of zoster, such as necrotizing fasciitis.

  Consultations

  Consultation with a neurologist is indicated in cases of myelitis or encephalitis.

  Consultation with an infectious disease specialist may be helpful if bacterial superinfection or viral resistance to acyclovir is evident.

  Consultation with an ophthalmologist is indicated upon optic involvement.

  Consultation with a dermatologist may be helpful when the rash is atypical.