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Herpes Zoster & Varicella

Key Points

  • Primary varicella infection (chickenpox) and herpes zoster are both caused by varicella zoster virus (VZV).
  • Herpes zoster (shingles) represents activation of varicella zoster virus from cranial or dorsal root ganglion, thus affecting the skin in a dermatomal distribution. It can disseminate and can have internal organ involvement.
  • The hallmark lesion of primary varicella and herpes zoster is a vesiculopustule. In zoster, multiple lesions are grouped and/or present within a dermatomal distribution.
  • A potential complication of herpes zoster is post-herpetic neuralgia (PHN), the development of persistent pain and/or dysesthesia at the sites previously affected by herpes zoster. There is limited evidence to support a definitive intervention to prevent the development of PHN. Management of PHN includes nerve-directed therapies.
  • Primary varicella infection and disseminated zoster can be a dermatologic emergency in patients who are immunocompromised, including pregnant women.

Introduction

Primary varicella

Varicella zoster virus (VZV) is a herpes family virus that causes primary varicella infection and herpes zoster. Prior to the introduction of varicella vaccination, the lifetime prevalence of primary varicella was approximately 90%, with most cases occurring during childhood. This highly contagious virus is spread through respiratory and salivary secretions and results in nonspecific symptoms (fever, headache, malaise) followed by a generalized pruritic vesiculopustular eruption. Infection with primary varicella leads to lifelong immunity in approximately 90% of cases; the lifetime prevalence of having additional infections with primary varicella is estimated at 13%. Since the introduction of childhood varicella vaccination, the rates of primary varicella infection have been dramatically reduced. Typically, primary varicella infection is self-limited and requires only symptomatic treatment. However, infection of adults may be severely debilitating, requiring systemic antiviral medication and possibly hospitalization. Primary varicella infection of pregnant individuals may result in intrauterine infection (especially in the first or second trimesters of pregnancy), resulting in congenital varicella syndrome, a syndrome marked by significant morbidity and mortality to both mother and child.

Herpes zoster

Herpes zoster represents the reactivation of VZV from the cranial or dorsal root ganglion with presentation of a painful vesicular rash in a dermatomal distribution. Prior to the development of the zoster vaccine, the lifetime prevalence of zoster in the adult American population was 10-20% with increased risk with advancing age; the prevalence of zoster approached 50% in individuals over the age of 85. Zoster vaccination, generally recommended for individuals over the age of 60, is safe and significantly reduces the risk of zoster reactivation. Patients with cranial nerve V1 involvement require ophthalmic evaluation to rule out the possibility of ocular involvement. In very severe cases, herpes zoster may be systemically disseminated, resulting in a generalized vesicular eruption with possible internal organ involvement; immunocompromised and immunosuppressed individuals are at high risk for disseminated zoster. Cases of disseminated zoster with central nervous involvement may be fatal. Patients with disseminated zoster are highly contagious, and shed virus through respiratory and salivary secretions in addition to skin, requiring both contact and respiratory isolation.

In localized (single dermatome involvement) herpes zoster, treatment with systemic antivirals is the standard of care, especially in patients presenting with early lesions; early intervention with systemic antivirals may thwart the development of vesicular lesions. Patients are considered infectious through direct viral shedding from skin lesions until these lesions crust over and thus require strict contact precautions (especially from immunocompromised, pregnant patients, and patients who have never had varicella before). Although there is excellent data that systemic antivirals reduce the duration of zoster lesions, reduce associated pain, and reduce viral shedding, there is limited evidence to support a definitive intervention to prevent the development of post-herpetic neuralgia (PHN), including zoster vaccination. PHN is the development of persistent pain and/or dysesthesia at the sites previously affected by herpes zoster. In one study, the incidence of PHN at 9 years (defined by pain within the past 12 months at the site affected by herpes zoster) following herpes zoster was 21%, and risk factors associated with the development of PHN included: pain preceding the development of cutaneous rash by >72 hours, moderate to severe pain with rash, severity of rash, and female gender. Management of PHN includes nerve-directed therapies.

Initial Evaluation

Herpes zoster (shingles)

Note that vesicles and papulovesicular lesions are grouped with an erythematous to hemorrhagic base.

Primary varicella infection

Differential diagnosis

Herpes simplex virus (oral)

Note that the vesiculopustular lesions of HSV are also grouped, as in zoster.

Herpes simplex virus (genital)

Eczema herpeticum

Erythema multiforme

Treatment

Herpes zoster

First-line therapy: The first-line therapy for herpes zoster includes the treatment of the acute eruption and therapy for herpetic neuralgia and post-herpetic neuralgia. Confirmation of herpes zoster by viral direct fluorescence assay (DFA) is recommended in most cases, especially in disseminated cases or cases involving immunocompromised or pregnant patients. Contact and respiratory isolation may be required (see Introduction).

The management of herpes zoster is dependent upon the age of the patient, the location of the eruption, the immune competence of the patient, and the presence of coexistent diseases contraindicating steroid usage (e.g., active tuberculosis, diabetes mellitus, and at times hypertension, osteoporosis, psychiatric disorders, and peptic ulcer disease).

First steps (general measures for all patients)

  • For blistering lesions, compresses of 5% aluminum acetate (i.e., Domeboro’s solution) up to four times daily will speed drying of the lesions and removal of the crusts.
  • Refer all patients with ophthalmic (VI) zoster (lesions around the eye or on the nose) to an ophthalmologist within 24 hours.
  • Advise the patient to avoid contact with immunosuppressed persons and persons who have not had varicella (chicken pox) until all lesions are crusted.
  • Perform a review of symptoms for previously undetected malignancy or immunocompromise. No additional laboratory tests beyond those suggested by the physical examination and review of symptoms are required. HIV serologic testing and examination for findings of HIV infection are indicated, especially in persons under the age of 50 and those with risk factors predisposing to HIV infection.

Patients under 50 years, immunocompetent

Most immunocompetent younger patients are not benefited by antiviral therapy. Infections of the ophthalmic branch (V1) of the trigeminal nerve and the Ramsey-Hunt syndrome (facial palsy and herpes zoster oticus) are exceptions where oral antiviral therapy is indicated. Significant zoster neuralgia is also a relative indication for antiviral therapy in the younger patient (for medications and dosages, see below).

Patients over 50 years, immunocompetent

  • Patients over 50 are at higher risk for post-herpetic neuralgia and therefore therapy is indicated.
  • Oral acyclovir 800 mg orally 5 times per day; or valacyclovir 1 g 3 times daily, or famciclovir 500 mg 3 times daily; all for 7 days. Correct the dosages for renal function. If the renal function of the patient is unknown, order a creatinine, or begin valacyclovir or famciclovir at twice daily and obtain a creatinine.
  • If there is significant neuralgia, and if there is no contraindication, a course of systemic antiviral medication combined with 3 weeks of oral prednisone may alleviate neurologic symptoms (but will not impact the risk of developing post-herpetic neuralgia): prednisone 0.5-1 mg daily for the first week, with tapered dosing over two additional weeks.

Immunosuppressed patients

Except for those who are severely immunosuppressed, the risk of cutaneous dissemination is low and visceral dissemination is uncommon. These patients do tend to have a more prolonged course, more pain, more extra-dermatomal lesions, and more scarring. Oral antiviral therapy (as outlined above) should be given to all immunocompromised patients, unless absolutely contraindicated. The duration of therapy should be open-ended and continued until all lesions have crusted over and no new lesions appear.

  • In severely immunosuppressed patients who are at high risk or who have dissemination only, intravenous acyclovir (10 mg/kg every 8 hours) for 7 days can be guaranteed to reach adequate tissue levels to prevent or treat disseminated zoster. Correct the dosage for renal function.
  • Isolate (contact and respiratory isolation) hospitalized patients from other immunosuppressed persons. Staff without a prior history of varicella or varicella immunization should not enter their rooms.
  • Since the risk of dissemination is enhanced by steroid therapy in the immunosuppressed, steroid therapy is relatively contraindicated in the setting of immunosuppression. Consider whether steroids are to be used on a case-by-case basis, depending on age, severity of pain, and degree of immunosuppression. If systemic steroids are administered to an immunosuppressed patient, an effective antiviral agent must be given.

Management of acute herpes zoster pain

  • Topical therapy with drying soaks followed by the application of lidocaine ointment may provide mild benefit. For thoracic and extremity lesions, occlusion with light compression of the involved area may significantly reduce the discomfort.
  • Lidocaine patches may be applied to the affected dermatome.
  • Acetaminophen, salicylates, and NSAIDs (nonsteroidal anti-inflammatory drugs) are sometimes adequate and may be tried initially. The latter two agents may induce hemorrhage into the blisters.
  • Systemic corticosteroids are sometimes beneficial and may be used in the non-immunosuppressed patient (see above).
  • Acyclovir may reduce the acute pain, especially if given intravenously. For the hospitalized patient, severe pain may be an indication for intravenous acyclovir.
  • Amitriptyline beginning at 25 mg nightly and increasing by 25 mg every night to a maximum of 75 mg per night is often of great benefit. This may be the best oral therapy for acute and chronic zoster neuralgia.
  • Gabapentin in doses from 300 mg to 600 mg 3 times daily may be added to tricyclic therapy above for additional pain relief (maximum dose 3600 mg daily).
  • Intradermal injections in the involved area with a long-acting anesthetic (bupivacaine 0.25%) may reduce acute pain.
  • Even a brief respite from the pain is welcomed by the patient, and often when the pain returns it is much less severe. Early referral of patients with severe pain to an anesthesiologist or a pain clinic for a nerve block, ganglion block, or epidural block is extremely rewarding.

Pitfalls

  • Occasionally herpes simplex will appear in a zosteriform pattern. Culture these lesions (for herpes simplex virus) or test by DFA, especially if recurrent, as the acyclovir dosage requirements are different.
  • Begin antiviral and pain control therapy as soon as possible. Early aggressive treatment works best.
  • Intravenous acyclovir may result in psychosis or altered mental status in immunocompromised individuals.

Primary varicella infection

In adults and adolescents, early treatment of varicella with effective antivirals shortens disease duration and prevents complications. This is also true of secondary childhood cases within a household, where early treatment is possible. All immunosuppressed persons with varicella should be treated with effective antiviral therapy. Varicella immune globulin (VZIG) may be considered in high-risk individuals within four days after exposure (CDC hotline: 800-232-2522). VZIG is not the standard used in the treatment of varicella.

First steps

  • Acyclovir 800 mg 5 times daily for 5-7 days.
  • Severe disease, immunosuppressed: Intravenous acyclovir 10 mg/kg 3 times daily for 7-10 days. In pregnant women, a dose of 7.5 mg/kg 3 times daily has been recommended. Monitor renal function.
  • All high-risk individuals with certain types of exposures should receive varicella-zoster immune globulin (VZIG) within the first 96 hours after exposure.

Alternative steps

Valacyclovir 1000 mg or famciclovir 500 mg both 3 times daily for 7 days. These agents have a higher bioavailability and could be considered in persons if compliance is an issue and in patients with borderline immune function who are not being admitted for intravenous antiviral treatment. All patients with significant immune suppression should be evaluated for treatment with intravenous acyclovir.

Pitfalls

  • Secondary staphylococcal infection of varicella is common, and may be easily overlooked.
  • Reye’s syndrome may follow varicella, especially in children in whom aspirin is used as an antipyretic. Aspirin should never be given to treat the fever of varicella in children.
  • To avoid post-varicella scarring, treat pruritus (with systemic antihistamines such as hydroxyzine) and secondary infection aggressively.
  • Live attenuated varicella vaccine is recommended for all children over 1 year of age who have not had varicella. Adults, especially those involved in patient care, should also be immunized if they have not had varicella. Children should not take aspirin for 6 weeks after the varicella vaccine.

When to refer to a dermatologist

  • If the diagnosis of primary varicella or herpes zoster is not clear.
  • For management of highly symptomatic cutaneous eruption.
  • For management of post-herpetic neuralgia.
  • For diagnosis and management, or hospital consultation, of a patient with disseminated zoster.

Clinical Cases

Case 1

  • 68-year-old healthy male
  • No significant past medical history (normal renal function)
  • Review of systems is noncontributory
  • History of primary varicella infection as child
  • No sick contacts
  • Presents for management of 3 days’ history of thoracic pain preceding 1 day of a painful, pruritic linear vesicular eruption

Initial evaluation

  • Healthy appearing male
  • Normal vital signs
  • Thoracic dermatomal band of vesicles on an erythematous base
  • Diagnosis: localized herpes zoster
  • Recommend acyclovir 800 mg 5 times daily for 7 days
  • Recommend application of aluminum acetate compresses 3-4 times daily
  • Recommend contact precautions until lesions crust over
  • Follow-up in 2 weeks

2-week follow-up evaluation

  • No active vesicular lesions
  • Minimal hyperpigmented macules marking prior sites of cutaneous involvement
  • Patient denies neurologic symptoms in the previously affected skin

Case 2

  • 7-year-old healthy female
  • No significant past medical history
  • No history of varicella vaccination
  • No known sick contacts
  • Presents for evaluation and management of generalized “blisters” for 2 days
  • Also with mild fever, malaise

Initial evaluation

  • Healthy appearing girl
  • Widespread vesiculopustular eruption
  • Diagnosis: primary varicella infection
  • Oral acyclovir 4 times daily for 5 days
  • Recommend contact and respiratory isolation until lesions crust over
  • Recommend hydroxyzine to alleviate nighttime pruritus
  • Recommend aluminum acetate compresses 4 times daily to hasten drying of lesions
  • Follow-up in 6 weeks (lesions resolved with only mild postinflammatory pigmentary changes)

References

Bruxelle J, Pinchinat S (2012) Effectiveness of antiviral treatment on acute phase of herpes zoster and development of post herpetic neuralgia: review of international publications, Med et Mal infectieuses (English), 42:53-58.

Chen N, Li Q, Zhang Y, Zhou M, Zhou D, He L (2011) Vaccination for preventing postherpetic neuralgia, Cochrane Database Sys Rev, 3, CD007795.

Lamont RF, Sobel JD, Carrington D, Mazaki-Tovi S, Kusanovic JP, Vaisbuch E, Romero R (2011) Varicella-zoster virus (chickenpox) infection in pregnancy, Brit Journal Ob Gyn, 118:1152-1162.

McKendrick MW, Ogan P, Care CC (2009) A 9 year follow-up of post herpetic neuralgia and predisposing factors in elderly patients following herpes zoster, J Infection, 59:416-420.

Weinberg JM (2007) Herpes zoster: epidemiology, natural history, and common complications, JAAD, 57: S130-135.