VARICELLA-ZOSTER VIRUS INFECTION/ CHICKEN POX/ HERPES ZOSTER/ SHINGLES/

POSTHERPETIC NEURALGIA

†††† Infection with the highly contagious herpesvirus varicella-zoster leads to both an acute infection and a also a chronic form of infection with periods of recurrence and latency.† The virus is transmitted via airborne droplets.† Most cases of acute infection occur in the pediatric population although acute infection in adults has a higher associated mortality.† Once acute infection resolves, the virus remains latent in the dorsal spinal ganglia and cranial nerves until reactivation occurs.

†††† Symptoms of acute infection (chickenpox) manifest after a two to three week incubation period and are characterized by a generalized macular rash which progresses to vesicular and/or pustular lesions.† The vesicles eventually rupture and then crust over.† The rash begins on the trunk and progresses to include the face and extremities.† Children usually do well without complications or residual symptoms; whereas, adults are prone to pneumonitis or encephalitis.† The most common complication encountered in pediatric patients is secondary bacterial skin infection due to Staphylococcus aureus or Streptococcus pyogenes.† Immunocompromised patients are at an increased risk of complications and should be treated aggressively.† Young patients require no therapy.† Older adolescents and adults may be treated with oral acyclovir but this is controversial and the decision should be made depending on the individual case.† Immunocompromised patients definitely require treatment with intravenous acyclovir.† Intravenous foscarnet is indicated for the treatment of acyclovir-resistent strains in immunocompromised patients.

†††† Once acute infection resolves, patients generally manifest no symptoms until they become elderly or immunocompromised.† Reactivation of varicella-zoster infection, termed herpes zoster or shingles, is characterized by vesicular lesions and pain distributed in a unilateral dermatomal pattern.† Patients often present in the prodromal period and complain of pain or a discomfort in a localized region which will then be followed by the development of vesicles.† During the eruption of vesicles, patients are highly contagious to persons who are not immune and remain so until the vesicles become crusted over.

†††† The Ramsey Hunt syndrome is a form of shingles characterized by seventh nerve paresis, periauricular pain, and a vesicular rash.† Patients may also experience vertigo and taste abnormalities.† Ramsey Hunt syndrome may be confused with Bellís palsy secondary to the associated unilateral facial paralysis.† Osteonecrosis and exfoliation of teeth may occur when zoster affects the maxillary or mandibular divisions of the trigeminal nerve.† Cervical zoster may be associated with upper extremity weakness or less commonly diaphragmatic paralysis.† Ophthalmic herpes zoster (herpes zoster ophthalmicus) represents a medical emergency due to the potential complications of corneal ulceration, corneal neovasculariztion, uveitis, keratitis, iritis, and iridocyclitis.† Symptoms of herpes zoster ophthalmicus include vesicular lesions on the forehead, regional lymphadenopathy, fever, malaise, headache, stiffness/soreness of the neck, and conjunctivitis.

†††† A more common complication of shingles is secondary bacterial infection of the skin lesions.† Treatment with oral acyclovir (800 mg PO 5 times/day for 7 to 10 days), valacyclovir hydrochloride (1,000 mg PO TID for 7 days) or famciclovir (750 mg PO QD, or 500 mg PO BID or 250 mg PO TID for 7 days) should be started as soon as possible.† Mildly immunocompromised adults may be treated with oral acyclovir as above; however, severely immunocompromised adults require intravenous acyclovir 500 mg/m2 Q8 hours for 7-10 days.† Analgesics may also be required for pain control. This disorder is completely preventable with vaccination of patients at age 60 years-old. Shingles occurs in patients who have previously been exposed to varicella usually decades earlier but suffer wanning immunity and thus reactivation of the dormant virus from the dorsal root ganglia in the spine. Zostavax 0.65 mL subcutaneously is an effective therapy to prevent shingles and thus post herpetic neuralgia.

†††† Central nervous system complications are more common in immunocompromised patients.† Potential complications include myelitis, encephalitis and arteritis.† Myelitis presents as paraparesis and sphincter impairment, and in immunocompromised patients, may progress to a fatal condition.† When the diagnosis is suspected, a search for varicella-zoster viral DNA or antibodies in the cerebrospinal fluid (CSF) establishes the diagnosis.† Once the diagnosis is established, aggressive acyclovir therapy is indicated.† Varicella encephalitis is secondary to a vasculopathy.† Large vessel disease occurs in immunocompetent patients predominantly and manifests as an acute stroke weeks to months after zoster of the contralateral trigeminal distribution.† Therapy entails intravenous acyclovir (10-15 mg/kg TID x 7-10 days) along with prednisone (60-80 mg QD x 3-5 days).† Whereas, small vessel disease occurs in immunocompromised patients weeks or months after a zoster outbreak and manifests as hemiplegia, aphasia, headache, fever, vomiting, mental status changes, seizures, focal deficits or visual-field deficits.† The finding of varicella-zoster virus DNA or antibodies is suggestive of the diagnosis.† Intravenous acyclovir (15-30 mg/kg QD x 10 days) is recommended although therapy may need to be prolonged in the severely immunocompromised.

†††† Following resolution of the vesicles of herpes zoster, patients may enter a chronic stage (postherpetic neuralgia).† Persistent burning or lancinating pain in a dermatomal distribution compatible with the area of prior vesicular eruption is the only symptom of the chronic stage.† Patients may complain of hyperesthesia (exaggerated sensory perception in response to light stimuli), allodynia (the perception of pain in response to normally nonpainful stimuli), or hyperalgesia (an exagerrated sensation in response to normally painful stimuli).† The incidence of postherpetic neuralgia increases with increasing age and in the immunocompromised patient population.† Occurrence is rare in patients younger than 50 years of age but frequent in patients greater than 60 years old.† If treatment with an antiviral was not initiated during herpes zoster reactivation, a trial of acyclovir, valacyclovir hydrochloride or famciclovir in the dosages stated above may be employed but may not be effective.† Amantidine (100 mg PO BID) may be effective.† Acute pain control may require the use of tramadol (50 to 100 mg PO Q 4 to 6 hours), opiods, NSAIDs, or acetaminophen.† Amitriptylline (25 mg QHS and titrated to 100 mg or effect) may prove an effective therapy for controlling persistent pain; however, frequent side effects limit use.† It may be effective if started early when patients over 60 years of age manifest herpes zoster lesions.† The dosage should start at 10-25 mg and increased as needed.† Once pain is controlled for at least 2 months, the dose may be tapered and eventually discontinued.† Patients less than 60 years of age can be treated if they develop chronic pain.† The tricyclics nortriptyline or desipramine may be better tolerated and as efficacious.† Gabapentin (starting with single 300 or 400 mg tablet QD titrating up to 3600 mg/day divided TID) or pregabalin are effective alternatives with fewer side effects than the tricyclic antidepressants.† Other treatment options include capsaicin cream (initially will cause increased pain; however, after repeated applications pain control may achieved), phenytoin (200-300 mg divided BID to TID), carbamazepine (100 mg QD titrating up to 800 mg QD or to effect), or a lidocaine patch (Lidoderm 5% patch 1-3 patches applied to intact skin in area of pain for no more than 12 hours/day).† A TENS unit or physical therapy may prove effective.† Refractory cases may require referral to a pain specialist for nerve blocks or intrathecal drug therapy (narcotic, anesthetic, or clonidine).† Associated pruritis may respond to calcamine lotion, oral antihistamines, or over the counter topical analgesic creams.

†††† Persons who have been exposed to infected patients (chicken pox and herpes zoster patients) should be questioned if they have had prior infection.† Patients with a negative history of prior infection may be considered for varicella-zoster immune globulin (VZIG).† All children (regardless of their immune status) without a history of chicken pox should receive VZIG.† All bone marrow recipients should receive VZIG immediately upon exposure regardless of their or the marrow donors past infection history.† Susceptible immunocompromised children and adults should receive VZIG within 72 to 96 hours if antibody titers are not available.† Immunocompetent adults who deny a past history of infection should undergo serologic testing.† If the results indicate a lack of immunity, VZIG should be administered.† VZIG is administered intramuscularly at a dose of 125 mg/10 kg of body weight up to a maximum of 5 vials.

†† ††The following patient populations should receive the varicella virus vaccine: healthcare workers, household contacts of immunocompromised patients, employees of educational institutions and daycare centers, college students, military personnel, prison inmates, prison employees, nongravid women of childbearing age, and international travelers.† Varivax is the live attenuated varicella virus vaccine.† Varivax is administered as a 0.5 ml dose subcutaneously which is repeated again in 4-8 weeks for adult patients and adolescents 13 years of age and older.† The vaccine is contraindicated in children less than 12 months old.† In the pediatric population between the ages of 1 and 12 years, the vaccine is administered as a singles 0.5 ml dose subcutaneously.† There is an extensive list of contraindications to the vaccine and the PDR should be consulted prior to its use.† Some of the contraindications include: pregnancy, hypersensitivity to gelatin or neomycin, malignancies of the blood or bone marrow, patients receiving immunosuppressive agents, immunocompromised patients, patients with concomitant active untreated tuberculosis, patients who have received VZIG within the past 5 months, and patients who have received a blood transfusion within the past 5 months.

Brody M. and Moyer D.† Varicella-zoster virus infection: The complex prevention-treatment picture.

††††† Postgraduate Medicine.† Jul. 1997; 102/1: 187-194.

Forbes C. and Jackson W.† A colour atlas and text of clinical medicine.† London.† Wolfe Publishing,

††††† 1993:29-30.

Galloway G.† Postherpetic neuralgia.† Internal Medicine.† Jan 2000; 21/1: 20-22.

Gilden D., Kleinschmidt-DeMasters B., LaGuardia J., Mahalingam R., and Cohrs R.† Neurologic

††††† complications of the reactivation of varicella-zoster virus.† NEJM.† Mar. 2000; 342/9: 635-643.

Joseph P.† Treatment regimens for postherpetic neuralgia.† Emergency Medicine.† Oct. 2000; 32/10:

††††† 12-22.

Landow K.† Acute and chronic herpes zoster.† Postgraduate Medicine.† Jun. 2000; 107/7: 107-118.

Rowbotham M., Harden N., Stacey B., Bernstein P., and Magnus-Miller L.† Gabapentin for the treatment

††††† of postherpetic neuralgia.† JAMA.† Dec. 1998; 280/21: 1837-1842.

Severson J.† Management of shingles.† Cortlandt Forum.† Apr. 2000; 13/4: 189-196.

von Lichtenberg F.† In: Robbins pathologic basis of disease 4th ed.† Philadelphia.† W.B. Saunders Co, 1989:

††††† 320-321.