eMedicine Specialties > Dermatology > Viral Infections

Herpes Zoster

Author: Joseph S Eastern, MD, Clinical Assistant Professor, Department of Internal Medicine, Section of Dermatology, University of Medicine and Dentistry of New Jersey
Contributor Information and Disclosures

Updated: Jul 2, 2009

Introduction

Background

Zoster is a common, predominantly dermal, and neurologic disorder caused by the varicella-zoster virus (VZV), a virus morphologically and antigenically identical to the virus causing varicella (chickenpox). Difference in clinical manifestations between varicella and zoster apparently depends on the immune status of individual patients; those with no prior immunologic exposure to varicella virus, most commonly children, develop the clinical syndrome of varicella, while those with circulating varicella antibodies develop a localized recrudescence, zoster.

Zoster probably results most often from a failure of the immune system to contain latent varicella-zoster virus replication. Whether other factors such as radiation, physical trauma, certain medications, other infections, or stress also can trigger zoster has not been determined with certainty. Nor is it entirely clear why circulating varicella antibodies and cell-mediated immune mechanisms do not prevent recurrent overt disease, as is common with most other viral illnesses.

Pathophysiology

Zoster most commonly manifests in 1 or more posterior spinal ganglia or cranial sensory ganglia, presumably because viral particles have been preserved within these ganglia in a dormant state since the original episode of varicella. This results in pain and characteristic cutaneous findings (see History) along the corresponding sensory dermatomes of the involved ganglia. Less often, involvement of anterior and posterior horn cells, leptomeninges, and peripheral nerves is observed, with consequent muscle weakness or palsy, pleocytosis of spinal fluid, and/or sensory loss. Rarely, myelitis, meningitis, encephalitis, or visceral involvement may occur.

Frequency

United States

The incidence of zoster is estimated at 2-3 cases per 1000 per year (approximately 750,000 cases per year). Actual incidence may be significantly higher since many relatively mild cases do not come to the attention of health care workers and remain undiagnosed. Generally, approximately 10-20% of the US population eventually develops 1 or more cases of zoster. The incidence in individuals who are immunocompromised or in elderly persons is much higher, probably close to 50%.

International

Internationally, the incidence of zoster has not been well studied, but probably it is in the same range of 2-3 cases per 1000 persons per year.

Mortality/Morbidity

• Zoster is rarely, if ever, fatal, although in individuals who are severely debilitated, zoster may be considered a contributing factor to death.
• Morbidity usually is confined to pain within the affected dermatome, which can be severe and can persist well beyond the duration of active disease (postherpetic neuralgia [PHN]). Eye involvement (zoster ophthalmicus) can cause temporarily or permanently decreased visual acuity or blindness. Complications such as secondary infection and meningeal or visceral involvement can produce further morbidity in the form of infections and scarring.

Race

Blacks are reported to have a significantly lower risk of developing zoster than whites; however, zoster has been reported as an early manifestation of HIV infection in young Africans.

Sex

No sex predilection is reported for varicella-zoster virus reactivation.

Age

Almost 50% of individuals who live beyond age 80 years can expect to develop zoster. Zoster is rare in children and young adults, with the exception of younger patients with AIDS, lymphoma, other malignancies, and other immune deficiencies, and patients who are recipients of bone marrow and kidney transplants. In addition, patients with these associated factors are at greater risk of developing zoster regardless of age.

Clinical

History

• Zoster may begin with a systemic response, eg, fever, anorexia, and lassitude, although symptoms frequently are mild and may not be associated by either patient or physician with the classic zoster signs and symptoms that follow.
• Symptoms typically include prodromal sensory phenomena along 1 or more skin dermatomes lasting 1-10 days (averaging 48 h), which usually are noted as pain or, rarely, paresthesias.
  • Prodromal pain typically is described as muscle or toothachelike in origin but may simulate headache, iritis, pleurisy, brachial neuritis, cardiac pain, appendicitis or other intraabdominal disease, or sciatica, which can result in incorrect tentative diagnoses.
  • The prodromal interval of pain prior to onset of cutaneous findings has been believed to represent spread of viral particles along sensory nerves; however, approximately 10% of patients report onset of pain and rash simultaneously.
• After the onset of prodromal symptoms, the following signs and symptoms occur:
  • Patchy erythema, occasionally accompanied by induration, appears in the dermatomal area of involvement.
  • Regional lymphadenopathy may appear at this stage or subsequently.
  • The classic finding of grouped herpetiform vesicles develops upon the erythematous base. At this point, the virus usually has induced significant inflammation of the involved sensory nerve causing severe pain, which led 19th-century French physicians to refer to zoster as "the band of roses from hell."
  • Cutaneous findings classically appear unilaterally (for unknown reasons), stopping abruptly at the midline of the limit of sensory coverage of the involved dermatome. Vesicles initially are clear, but eventually, they cloud, rupture, crust, and involute. This evolution often is accelerated greatly by treatment.
  • After vesicular involution, remaining erythematous plaques slowly resolve, typically without visible sequelae; however, scarring can occur if deeper epidermal and dermal layers have been compromised by excoriation, secondary infection, or other complications.
• Unfortunately, resolution of the associated pain does not always accompany resolution of erythema and vesiculation. PHN, which usually is confined to the area of original dermatomal involvement, can persist for weeks, months, or years and often is severe. The reason some patients with zoster, and not others, experience PHN is not understood fully, but patients who are older (>60 y), particularly patients who are debilitated or arteriosclerotic, are affected far more frequently than patients who are younger. In addition, PHN is observed more frequently after cases of herpes zoster ophthalmicus and in instances of upper body dermatomal involvement. Other less common postherpetic sequelae include hyperesthesia, or more rarely, hypesthesia or anesthesia in the area of involvement.
• The virus that causes zoster is morphologically and antigenically identical to the virus that causes varicella. In one study involving the recently released high-potency, live attenuated varicella-zoster virus vaccine developed by Merck, a reduction in the incidence rate of herpes zoster of 51.3% during 3 years of follow-up was noted.

Physical

Classic physical findings of zoster include painful grouped herpetiform vesicles on an erythematous base confined to the cutaneous surface innervated by a single unilateral sensory nerve. Regional lymphadenopathy may be present. Vesicles initially are clear but eventually cloud, rupture, crust, and involute.

Many clinical variations are possible as follows:

• Herpes zoster ophthalmicus (HZO) constitutes 10-15% of zoster cases.¹ HZO results from viral invasion of the Gasserian ganglion.
  • For unknown reasons, involvement of the ophthalmic branch of the fifth cranial nerve (CN; termed CN V1) is 5 times as common as involvement of the maxillary (CN V2) or mandibular (CN V3) branches. HZO is recognized easily by vesicular and erythematous involvement of the CN V1 dermatome, ipsilateral forehead, and upper eyelid.
  • Ipsilateral preauricular and, occasionally, submaxillary nodal involvement is a common prodromal event in HZO and often is valued equivalently with pain, vesiculation, and erythema in establishing a diagnosis.
  • Prodromal lymphadenopathy should not be confused with later reactive adenopathy caused by secondary infection of vesicles.
  • Headaches, nausea, and vomiting also are common prodrome symptoms.
  • Signs of meningeal irritation may be present; therefore, meningitis must be excluded.
  • The ophthalmic branch of the fifth CN (with ciliary ganglion) sends branches to the tentorium (recurrent nerve of Arnold) and to the third and sixth (and occasionally fourth) CNs, which may account for the frequency of meningeal signs and, occasionally, the CN III and CN VI nerve palsies associated with HZO.
  • HZO requires particularly aggressive treatment and follow-up monitoring because of the possibility of involvement of the eye, which occurs in approximately one half of patients with HZO.
  • Traditionally, involvement of the nasociliary branch, characterized by vesicles at the tip of the nose, has indicated that eye involvement is present or imminent (termed the Hutchinson rule). However, in recent years, clinicians with extensive experience in the treatment of HZO have disputed this, claiming that eye and nasociliary branch involvement can be present with or without distal nasal vesiculation. In the author's experience, eye lesions are rare in the absence of distal nose lesions.
  • Eye involvement poses a risk to vision in the absence of prompt detection and treatment. The presence of orbital edema is an ophthalmologic emergency, and patients must be referred immediately for specialized ophthalmic evaluation and treatment. Iritis, iridocyclitis, glaucoma, and corneal tissue ulcerations are possible in these cases. Involvement of the area below the palpebral fissure alone, without upper eyelid or nasal involvement, is considered less likely to result in ocular complications since the superior maxillary nerve innervates the lower eyelid.
  • Postherpetic complications are more common in HZO than in other manifestations of zoster. In particular, PHN is observed in well over one half of patients with HZO and can be severe and long lasting. Scarring also is more common, probably as a result of severe destructive inflammation. Palsy of the third CN, and occasionally of the fourth and sixth CNs, may occur. Rarely, simultaneous involvement of other CNs has been reported. The most common of these is seventh CN involvement, which may produce facial palsy.
• Zoster of the maxillary branch of the fifth CN (CN V2): Involvement is localized to the ipsilateral cheek, lower eyelid, side of the nose, upper eyelid, upper teeth, mucous membrane of the nose, nasopharynx, tonsils, and roof of the mouth. At times, only the oral mucus membrane is involved without skin manifestations. Early preeruptive herpetic pain can simulate a severe toothache and result in unnecessary oral surgery or dental treatment.
• Zoster of the mandibular branch of the fifth CN (CN V3): Areas of involvement include the side of the head, external ear and external auditory canal, lower lip, and a portion of the oral mucosa. As in other fifth CN branch involvement, prodromal pain in affected areas can result in incorrect diagnoses.
• Zoster oticus (also termed geniculate zoster, zoster auris, Ramsay-Hunt syndrome, Hunt syndrome): This form of zoster is considered rare but more likely is recognized rarely. It often is mistaken for eczema, Ménière disease, Bell palsy, stroke, and abscess of the ear. Classically, it begins with otalgia and herpetiform vesicles on the external ear canal with or without features of facial paralysis resulting from facial nerve (CN VII) involvement, auditory symptoms (eg, deafness), and vestibular symptoms in variable combinations. The syndrome also may result from zoster of ninth or tenth CN origin since the external ear has complex innervation by branches of several CNs (CN V, CN VII, CN IX, CN X), as well as vertebral nerve C2 and possibly C3.
• Glossopharyngeal and vagal zoster (herpes pharyngis, herpes laryngis): This variation of zoster involves the jugular and petrosal ganglia, which are adjacent and often involved in some combination; however, individual involvement of both ganglia has been observed. Painful vesicular rash typically involves the palate, posterior tongue, epiglottis, tonsillar pillars, and, occasionally, the external ear. A unilateral distribution can distinguish this variation of zoster from herpes simplex and herpangina.
• Herpes occipitocollaris (vertebral nerves C2 and C3 involvement): Involvement includes the posterior scalp, nuchal area, portions of the ear, and portions of the lower mandible and anterior neck. Vertebral nerves C2 and C3 often are involved together. Branches of vertebral nerves C2 and C3 communicate with the seventh and tenth CNs, sometimes causing CN VII and CN X symptoms as well. Nuchal and/or scalp involvement occasionally is confused with folliculitis, furunculosis, cellulitis, erysipelas, or acne keloidalis nuchae. The painful prodrome can result in confusion and misdiagnosis until the classic vesicular rash appears.
• Zoster encephalomyelitis (meningoencephalitis): Localized mild leptomeningitis in the region of neurologic involvement is more common than generally is recognized and often results in pleocytosis (25-50 lymphocytes) in the spinal fluid.
  • Leptomeningitis most likely occurs when CNs (especially fifth) are involved because of the presence of the recurrent nerve of Arnold, branching from CN V1 to the tentorium. For this reason, meningeal symptoms (headache, changes in sensorium, fever, stiffness of neck) are most common with HZO.
  • Rarely, symptoms of meningoencephalitis may be significant and, at times, severe enough to cause death. Reports exist of zoster encephalomyelitis being mistaken for acute poliomyelitis. Spread of varicella virus to the central nervous system also may occur during suppression of host resistance by neoplasms, by cytotoxic drugs, and, possibly, by radiation therapy.
• Zoster myelitis: That varicella-zoster virus can produce encephalomyelitis is well documented. More rarely, the myelitis lesion predominates or is the sole feature. The clinical picture is one of acute onset of paraplegia resulting from a diffuse involvement of the spinal cord. The picture is that associated with acute transverse myelopathy.
• Disseminated zoster: Dissemination usually is defined as a generalized eruption of more than 10-12 extradermatomal vesicles occurring 7-14 days after the onset of classic dermatomal zoster. Disseminated zoster typically is indistinguishable clinically from varicella (chickenpox).
  • Dissemination occurs in approximately 2% of zoster cases in the general population, but it has been observed in as many as 35% of patients who are hospitalized and/or immunocompromised.
  • Dissemination often is an indication of depressed cell-mediated immunity caused by various underlying clinical situations, which include malignancies, radiation therapy, cancer chemotherapy, organ transplants, and the chronic use of systemic corticosteroids. However, the short-term use of low-to-moderate doses of corticosteroids has been shown not to increase the incidence of dissemination.
  • Patients in whom zoster has disseminated must be observed carefully for the development of pneumonitis and encephalitis, which can be life threatening.
• Bilateral zoster: On rare occasions, zoster manifests bilaterally. The reason this occurs is unknown, as is the reason zoster typically occurs unilaterally. A popular superstition among lay people states that "if shingles occurs on both sides and meets in the middle, you will die." While some cases of bilateral zoster have been reported in patients who are extremely debilitated and in whom bilateral presentation cannot be considered a favorable sign, a fatal prognosis is not necessarily indicated for all patients. In cases of bilateral zoster, it is not unusual for 1 or 2 adjacent dermatomes to be involved. Unlike examples of multiple dermatomal involvement in unilateral disease, involvement in adjacent dermatomes is not typically a sign of underlying disease (eg, malignancy).
• Multiple dermatomal involvement: Involvement of more than 1 dermatomal distribution in unilateral zoster is rare and usually is considered a harbinger of significant compromise of the immune system caused by AIDS, malignancy, chemotherapy, and other factors.
• Recurrent zoster: Recurrences, while rare, are not unheard of and have not been shown to represent any specific event. Most reputed cases of recurrent zoster involve other entities, usually herpes simplex in a linear distribution.
• Zoster involving the urinary bladder: Rarely, zoster involving the dermatomes of the buttock area (vertebral nerves L1, L2, S2, S3, S4) may be associated with vesicles in the bladder, which can cause severe dysuria and urinary frequency. This picture can be mistaken easily for cystitis. If vesicles rupture in the bladder, hematuria (another common symptom of cystitis) may occur. Transient bladder paralysis resulting from zoster involving the gluteal and sacral regions and lumbar sympathetic segments has been reported, and acute urinary retention is possible if a motor component exists.
• Other internal manifestations: Vesicular involvement has been reported in bronchi, pleural spaces, and the gastrointestinal tract. Zoster pneumonia also has been reported. Such involvement frequently is found in individuals with significantly compromised immune systems. Pain in these areas, as on the cutaneous surface, may be referred pain and does not necessarily indicate the presence of vesicles.
• Motor complications: While zoster classically invades only sensory nerves (for unknown reasons), viral particles occasionally cross over to the anterior horn of the involved ganglion, resulting in motor symptoms.
  • Paresis may be seen in extraocular muscles, any area of facial innervation, and anywhere along the spinal cord, including the phrenic nerve. Paresis most commonly is observed when muscles of an arm or leg are involved; however, this may be because it is detected most easily at those locations.
  • Truncal motor involvement may be more common than generally is believed, because both physician and patient easily may overlook a small area of muscle weakness of the central trunk.
  • Motor symptoms can range from weakness to total paralysis, depending on how many roots of the involved nerve plexus are affected. While most motor involvement (like most sensory involvement) is self-limited, partial or complete paresis can persist indefinitely, particularly when CN V, CN VII, phrenic, and upper or lower extremity nerves are affected.
  • Paralysis of abdominal musculature can cause a hernial bulge.

Causes

• Reactivation of varicella virus that has remained dormant within dorsal root ganglia, often for decades after the patient's initial exposure to the virus in the form of varicella (chickenpox), causes zoster. Exactly what triggers this reactivation has not yet been determined precisely, but likely candidates include external reexposure to the virus, acute or chronic disease processes (particularly malignancies and infections), medications of various types, and emotional stress. More than 1 or all of these factors, plus others, possibly are capable of triggering zoster. The reason 1 dorsal root ganglion experiences reactivation of its stored viral load preferentially over other ganglia is unclear.
• Zoster can be a presenting symptom of hyperparathyroidism, and it occurs twice as often (rate, 3.7%) among patients with hypercalcemia compared with age-matched cohorts of patients older than 40 years who have normal calcium levels.²
• The cause of PHN also remains a mystery. Rapid initiation of treatment has been shown to decrease the incidence of PHN significantly, which can be explained by the theory that incessant pain of active zoster sets up a positive feedback loop within the thalamus and the cortex, creating a central pain syndrome similar to phantom leg pain. Prompt treatment breaks the loop by providing pain-free periods early in the disease course.

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