Herpes zoster affects some 600,000 to 900,000 mostly elderly or immunocompromised people in the United States each year (16,64). Its annual incidence is
approximately 5 to 6.5 per 1,000 at age 60, increasing to 8 to 11 per 1,000 at age 70 (16).

Herpes zoster usually begins with a prodromal phase characterized by pain, itching, paresthesias (numbness/tingling), dysesthesias (unpleasant sensations), and/or sensitivity to touch (allodynia) in one to three dermatomes. A few days later, a unilateral maculopapular rash appears on the affected area, which then evolves into vesicles. These vesicles usually scab over in 10 days, after which the lesions are not contagious. Multiple dermatomes or a generalized infection are more likely to be involved in immunosuppressed patients, such as patients with a hematologic malignancy or iatrogenic immunosuppression. Rarely, the prodrome is not followed by typical zoster lesions (zoster sine herpete), making diagnosis difficult. In most patients, the disappearance of the skin lesions are accompanied by decreased pain, with complete resolution of pain within 4 to 6 weeks.

Herpes zoster can affect any level of the neuraxis, including cranial nerves, but is most frequently seen in thoracic dermatomes followed by lesions on the face, typically in the ophthalmic distribution of the trigeminal nerve [herpes zoster ophthalmicus (HZO)]. HZO is often accompanied by zoster keratitis, resulting in blindness if unrecognized and not treated. Thus, if visual symptoms are present in patients with ophthalmic distribution zoster, a slit-lamp examination by an ophthalmologist is imperative, especially if skin lesions extend to the medial side of the nose (Hutchinson sign). Herpes zoster can also affect the cranial nerve VII (geniculate) ganglion, causing weakness or paralysis of ipsilateral facial muscles with skin lesions in the external auditory canal/tympanic membrane (zoster oticus) and/or anterior two thirds of the tongue or hard palate. This peripheral facial weakness and zoster oticus constitutes the Ramsay Hunt syndrome [reviewed by Sweeney and Gilden (57)]. Additional cranial nerves may be involved, leading to tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. Less common presentations of herpes zoster include optic neuritis/neuropathy from optic nerve involvement (10,38); ophthalmoplegia from cranial nerves III, VI, and IV involvement (5,10,34,55); and osteonecrosis and spontaneous tooth exfoliation from involvement of the maxillary and mandibular distribution of the trigeminal nerve (22,37,63). Lower motor neuron-type weakness in the arm or leg may also follow cervical or lumbar distribution zoster, respectively [reviewed by Merchet and Gruener (40) and Yoleri et al. (68)]. Diaphragmatic weakness following cervical zoster (4) and abdominal muscle weakness, leading to abdominal herniation, following thoracic zoster (59) have also been reported.

Diagnosis of herpes zoster is straightforward based on the clinical presentation, characteristic rash, and pain/altered sensation. However, there are cases in which rash does not follow the prodrome (zoster sine herpete), making the diagnosis more challenging. Patients may only present with dermatomal distribution pain that does not cross the midline or unilateral facial or limb weakness. In these cases, a fourfold rise in serum antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva (20) may assist with diagnosis. Cerebrospinal fluid (CSF) can also be examined for the presence of VZV DNA and anti-VZV immunoglobulin (Ig) G antibody.

Treatment of herpes zoster is based on the patient’s immune status and age; however, no universally accepted protocol exists. In immunocompetent individuals under age 50 years, analgesics (nonsteroidal anti-inflammatory agents, opioids) and topical treatments (calamine lotion, petroleum jelly, local anesthetic creams, occlusive bandages) are used to relieve pain (Fig. 27-1). Oral antivirals (acyclovir 800 mg five times a day for 10 days; famciclovir 500 mg orally three times daily; or valacyclovir 1,000 mg three times daily for 7 days) are not required but will speed the healing of rash and resolution of pain. These antivirals are generally well tolerated. Side effects include nausea, headache, diarrhea, and vomiting. It has also been reported that treatment of herpes zoster with 800 mg/day of oral acyclovir within 72 hours of rash onset may reduce the incidence of residual pain at 6 months by 46% in immunocompetent adults (32). Thus, in immunocompetent individuals over the age of 50, treatment with both analgesics and antivirals are recommended and are essential in patients with ophthalmic distribution zoster. Similarly, treatment of patients with the Ramsay Hunt syndrome within 7 days of onset appears to improve recovery (21,42). In addition to antivirals, prednisone (60 mg orally for 3 to 5 days) has also been used to reduce the inflammatory response, although double-blind, placebo-controlled studies to confirm additional efficacy are lacking. In immunocompromised patients, intravenous acyclovir, 10 mg/kg every 8 hours for 7 to 14 days, is recommended.

The most common complication of herpes zoster is PHN, which is characterized by constant, severe, stabbing or burning, dysesthetic pain that persists for >3 months and sometimes years after resolution of the zoster skin lesions. As many as 1 million individuals are affected in the United States (8). The occurrence of PHN is closely associated with age. It is rare in patients younger than 50 years of age but is seen in up to 40% of patients with zoster who are older than 60 years (50). Other risk factors for PHN include severe pain during zoster and a prodrome of severe
dermatomal pain prior to rash. Symptoms tend to improve over time, with less than 5% of patients still having pain at 1 year. However, during this period, pain can be quite debilitating, and the patient’s quality of life can be severely affected, leading to depression. The cause of PHN is unknown, but two non-mutually exclusive theories have been proposed—that the excitability of ganglionic or spinal cord neurons is altered after zoster and that low-grade virus infection persists in ganglia despite resolution of the skin lesions (36,62).

Treatment of PHN is aimed at symptomatic pain relief with use of analgesics, including opiates and neuroleptic drugs, but no universal treatment exists. For topical treatment, lidocaine is administered as 5% patches, with up to three patches applied to the affected area at one time, for up to 12 hours within a 24-hour period (Fig. 27-2). As an alternative, capsaicin 0.075% can also be applied topically three to four times a day, but local skin irritation can limit its use. For systemic treatment of chronic pain, nonsteroidal anti-inflammatory drugs can be used in conjunction with neuroleptics and other agents if pain is refractory. Gabapentin is widely used, with a starting dose of 300 mg daily and gradually titrating up as needed to a maximum of 3,600 mg/day (divided into three doses daily) (49,51). Pregabalin is given at 75 to 150 mg orally twice daily or 50 to 100 mg orally three times a day (150 to 300 mg/day). If minimal relief is obtained at 300 mg daily for 2 weeks, the dose can be increased to a maximum of 600 mg/day in two or three divided doses. Tricyclic antidepressants, including amitriptyline (10 to 25 mg orally at bedtime with a maximum dose of 150 to 200 mg/day), nortriptyline, and desipramine, lessen the pain of PHN. Newer anticonvulsants, such as topiramate, levetiracetam, lamotrigine, and oxcarbazepine are also being used. Oxycodone (controlled release, 10 to 40 mg orally every 12 hours) or controlled-release morphine sulfate can also be used (17). Levorphanol produces morphinelike analgesia at a dose of 2 mg orally every 6 to 8 hours as needed, with maximum doses of 6 to 12 mg daily (52). Combination treatment with morphine and gabapentin also decreases pain better than either drug alone or placebo (26).