Management of Herpes Zoster

Herpes zoster (shingles) is a common viral cutaneous eruption that is estimated to affect 300,000 persons a year in the United States. Most cases represent reactivation of the varicella-zoster virus (VZV). The incidence increases with age and degree of host immunosuppression. A community-based study found 100 cases per 100,000 person-years between the ages of 15 to 35 years, with a rise each decade to 450 cases per 100,000 by age 75 years. Lifetime risk is estimated at 30%. The seasonal variation seen with varicella does not occur with zoster; shingles is rarely an epidemic illness. Shingles may present as a pain syndrome without vesicles and pose a diagnostic problem. The primary physician must recognize zoster, make the patient comfortable, and prevent complications.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5 and 6)

Pathophysiology and Epidemiology

Varicella, or chickenpox, usually affects people early in life; the virus then lies dormant in a nerve ganglion in a genomic state until reactivation occurs. It is suspected that every person who has had chickenpox harbors latent virus. Estimates are that 50% of all people who live to the age of 85 years will have an attack of zoster and that approximately 10% will have at least two attacks.

The nerve root changes consist in necrosis and sometimes cyst formation. A decrease in cellular immunity may allow the latent virus to reactivate and spread along the nerve; clinical zoster is the result. Helper T cells and several lymphokines produced by other T-cell subsets usually protect the host from reactivation. The disorder occurs with increased frequency among immunocompromised patients and the elderly, probably as a consequence of defects in cellular immunity. Humoral immunity does not appear to be an important factor; even severely infected patients show significantly elevated antibody titers to zoster, and fewer than 5% of persons born in the United States do not possess varicella antibody. Occasional outbreaks may result from trauma to a nerve in which the virus is latent.

The risk for transmission is low despite the fact that zoster skin lesions contain large amounts of virus. However, immunosuppressed patients and those who have never had chickenpox are at risk for transmission from persons with zoster. Although a tenuous suggestion has been made that persons with zoster are at somewhat higher than average risk for some cancers (e.g., colon cancer) due perhaps to reduced cellular immunity, the observed relative cancer risk of latent cancer is only 1.1 times that of the general population.

Clinical Presentation

The presentation is one of radicular pain followed by the appearance of tense, grouped vesicles on an erythematous base (“dew drops on a rose petal”) in a dermatomal distribution. The pain is also dermatomal and may begin as an itch or tenderness that precedes the cutaneous lesion by 1 to 7 days. Patients describe sensations of burning, tingling, and sharp, knifelike pricking or of deep, boring discomfort. More than half of patients have a unilateral involvement of one or more thoracic dermatomes. The cranial dermatomes account for approximately 15% of cases, and cervical and lumbar dermatomes each accounts for approximately 10%.

The cutaneous eruption becomes pustular within a few days; crusting and healing then follow during 14 to 21 days. The crust is often dark, almost black. Scarring and atrophy can occur if the lesions are deep. Malaise, low-grade fever, and adenopathy
accompany severe eruptions. The total length of the course is related to the duration of new vesicle development; vesicle formation for several days usually predicts a 2- to 4-week course, whereas vesicle formation persisting for more than 1 week predicts a longer course.

Complications

About one in eight patients experiences at least one complication; risk is higher in the elderly (approaching 50%) and in those who are immunocompromised. Major complications include postherpetic neuralgia, keratitis, uveitis, motor deficits, infection, and systemic involvement, such as meningoencephalitis, pneumonia, deafness, and dissemination.

Postherpetic Neuralgia.

Postherpetic neuralgia is most prevalent in persons older than the age of 50 years. The pain is often excruciating and can be refractory (see later discussion). The incidence exceeds 40% in zoster patients older than the age of 60 years; the risk is also high in those with HIV infection or other immunocompromised states.

Ocular Complications.

Persons with involvement of the first division of the trigeminal nerve have a nearly 50% risk of developing eye complications such as keratitis, keratopathy, episcleritis, and iritis. Vesicles on the tip of the nose were believed to indicate definite nasociliary involvement (putting the eye at risk), but recent data do not confirm this traditional view.

Disseminated Disease.

The presence of more than 10 lesions outside a single dermatome of distribution is early evidence of dissemination. Patients with HIV/AIDS may have VZV infection as part of the AIDS-related complex. In most HIV cases, VZV infection presents as a typical dermatomal illness; occasionally, it is disseminated and can be complicated by hepatitis, pneumonia, meningitis, or proctitis. In immunocompromised hosts, VZV and herpes simplex infections may present in similar and atypical fashion, sometimes in unusual distributions or even without vesicles.

DIAGNOSIS (2,7,8)

The diagnosis is generally not difficult if the characteristic dermatomal rash and pain are present. The most serious diagnostic problem occurs during the prodromal phase, when patients present with a pain syndrome. Periorbital headache, unexplained back pain, or chest wall pain may represent the prodromal period of herpes zoster. Prodromal zoster pain has been mistaken for myocardial infarction, cholecystitis, and appendicitis. The characteristic eruption may not appear until 2 to 5 days later.

In patients with the characteristic rash, a Tzanck preparation demonstrating the presence of multinucleated giant cells provides strong supportive evidence of zoster. The Tzanck preparation has been found to be superior to viral isolation in the diagnosis of early lesions. In persons with atypical presentations (e.g., immunocompromised patients), confirmation may be required. Culture, although slow, allows for confirmation, but the VZV virus can be hard to recover from the swab. More sensitive, rapid, and less expensive than culturing is subjecting the sample obtained from a swab to immunofluorescence staining, which uses fluorescein-conjugated monoclonal antibodies against VZV. Finally, the diagnosis can be confirmed by the demonstration of a rising antibody titer, but this requires two separate determinations separated in time.

Rapid molecular diagnostic assays that detect DNA sequences of VZV by polymerase chain reaction assay are available for severely ill persons who present with acute but nonspecific symptoms (e.g., meningeal infection). Their high cost makes them best reserved for prompt diagnosis in inpatient settings.