Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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16
Herpes Zoster and Varicella
Danielle M. DeHoratius
I. Definition and Pathophysiology
Infection with the varicella-zoster virus (VZV), a double-stranded deoxyribonucleic acid (DNA) virus, will produce one of two clinical entities. Generalized, highly contagious, and usually benign chickenpox represents primary infection in a nonimmune host, whereas localized and painful zoster (shingles) is recurrence of a latent infection in the partially immune host. Clinical manifestations reflect the interaction between this virus and the host immune mechanisms.
Chickenpox, usually acquired through respiratory droplets, is seen primarily in the winter and spring, has an incubation period of 10 to 23 days, begins abruptly, and the lesions heal or even disappear within 7 to 10 days. Ninety percent of reported cases occur in children <10 years of age. Four percent of infections are subclinical. Almost every individual would have been infected by young adulthood. The disease is communicable 1 day before the appearance of the exanthem to 6 days after; crusts are noninfectious. Signs, symptoms, and complications often become more severe with age; adolescents and adults may become severely ill, particularly with pulmonary involvement. VZV infections during pregnancy can cause a distinct clinical syndrome. There is a 5% risk of fetal damage if intrauterine infection occurs during the first semester or early second trimester, producing the congenital varicella syndrome characterized by limb hypoplasia, muscular atrophy, skin scarring, cortical atrophy, microcephaly, cataract formation, and rudimentary digits. HIV-infected patients may experience atypical varicella, with a small number of disseminated pox-like lesions (1). Viral transmission may also occur through direct contact with the vesicles because of the high viral titers found within.
Zoster results from the reactivation of latent virus in dorsal root or cranial nerve ganglion cells. It is suspected that the virus is transported from the dorsal root or trigeminal ganglia through the myelinated nerves to the skin. As these nerves may terminate at the isthmus of hair follicles, primary infection first occurs in the follicular and sebaceous epithelium and then spreads to the rest of the epidermis. Histologic evidence reveals that herpes infection may occur exclusively in the folliculosebaceous units before the clinical appearance of vesicles (2).
The incidence of zoster shows no seasonal variation. Two thirds of patients are older than 40 years. Lesions erupt for several days and are usually gone within 2 to 3 weeks in children and 2 to 4 weeks in adults. Zoster is a self-limited, localized disease that causes discomfort for several days but usually heals without complications. Postherpetic neuralgia (PHN) is seen with increasing frequency in those older than 60 years of age and can be extremely painful, chronic, and, at times, unremitting.
In patients with serious underlying conditions that alter immunologic competence, more severe disease develops. Lesions may be greater in number and persist for up to 7 months in the immunosuppressed; visceral dissemination can occur in 8% of untreated immunocompromised patients. For children with lymphoma or leukemia, varicella is a life-threatening infection; adults with such diseases often develop zoster, which may then disseminate. Dissemination occurs in only 2% to 4% of zoster cases in normal hosts. However, of all cases of disseminated zoster, approximately two thirds of the patients have malignant disease, including approximately 40% with lymphoproliferative disorders. In Hodgkin’s disease, dissemination occurs in approximately 25% of cases, with a mortality approaching 25%. In patients with any type of malignant disease and in particular Hodgkin’s disease, localized dermatomal zoster also develops more frequently than in age-matched controls. The location of the affected dermatome is often related to a site of prior radiation therapy or to the presence of neoplastic lesions either centrally (lesions in or around the spinal column), causing neural irritation, or peripherally,
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as metastatic deposits. Immunosuppressive therapy for lymphoproliferative diseases or that used in transplantation programs predisposes to recurrence of varicella-zoster infection but not necessarily to dissemination. In patients known to be at risk for AIDS, the occurrence of zoster may be one sign that heralds depression of cellular immunity and may be the first sign of human immunodeficiency virus (HIV) infection.
II. Subjective Data
  • Varicella
    • Varicella in children is preceded by little or no prodrome; there may be only 24 hours of malaise and fever. In adolescents and adults, fever and constitutional symptoms almost always precede the exanthem by 24 to 48 hours. Patients are usually infectious for 1 to 2 days before the development of the rash and for 4 to 5 days following the beginning of the eruption, which is usually when the last vesicular crop has crusted over. Oftentimes, patients experience intense pruritus with the vesicular stage.
    • The appearance of cough, dyspnea, and chest pain within 2 to 5 days after the onset of the rash is indicative of severe pulmonary involvement.
    • Pruritus is the primary and most troublesome feature of chickenpox. Excoriation contributes to secondary bacterial infection and scarring.
  • Zoster. The appearance of zoster lesions is frequently preceded by a mild to severe pre-eruptive pruritus, tenderness, or pain; the last may be generalized over the entire nerve segment, localized to part of it, or referred. Depending on the location, this pain may be confused with that of pleural or cardiac disease, cholecystitis or other abdominal catastrophe, renal or ureteral colic, sciatica, or other ailments. Neurologic changes within the affected dermatome include hyperesthesia, dysesthesia, or hypoesthesia. The interval between pain and eruption may be as long as 10 days but averages 3 to 5 days. In some patients, particularly children, there are no sensory changes. The pain will usually subside within several weeks, but 73% of patients older than 60 years of age have discomfort that persists beyond 8 weeks.
III. Objective Data (See color insert)
  • Chickenpox begins abruptly with the appearance of discrete, erythematous macules and papules located primarily over the thorax, scalp, and mucous membranes; the face and distal extremities remain less involved. Lesions progress rapidly from erythematous macules to 2- to 3-mm clear, tense, fragile vesicles surrounded by an erythematous areola. This appearance is often descriptively coined as “dew drops on a rose pet al.” As the lesions progress, they first become umbilicated and then within hours become cloudy and purulent, with crusts forming in 2 to 4 days. Varicella lesions appear in 3 to 5 distinct crops for up to a 5-day period, and lesions in all stages of development may be seen within one area. This is an important difference from smallpox. Crusts fall off in 1 to 3 weeks. Lesions usually heal without scarring. The most common complications are secondary bacterial infection of the skin lesions, usually staphylococci and streptococci. Adults often have a more complicated course with a more widespread rash, a prolonged fever, and an increased chance of complications, most commonly varicella pneumonia.
  • Zoster lesions first appear posteriorly and progress to the anterior and peripheral distribution of the nerve involved (see dermatome charts on the inside covers). Only rarely will the eruption be bilateral. Erythematous macules, papules, and plaques are seen first, and in most instances grouped vesicles appear within 24 hours, although occasionally blisters never develop. Plaques may be scattered irregularly along a dermatomal segment or may become confluent. Mucous membranes within the dermatomes are also affected. The vesicles become purulent, crust, and fall off within 1 to 2 weeks. The presence of a few vesicles (10 to 25) outside the affected dermatome can occur and does not imply dissemination.
    In >50% of individuals, zoster will involve the thoracic nerves; cervical or lumbar nerve involvement occurs in 15% to 20% of cases. Lesions on the tip of the nose herald involvement of the nasociliary branch of the ophthalmic division of the trigeminal nerve, implying a strong possibility of concomitant keratoconjunctivitis. Paresis and permanent motor damage are more common than previously thought and are found mostly with involvement of the trigeminal and upper cervical and
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    thoracic nerves. Shingles may appear in multiple dermatomes both contiguous and noncontiguous and this is termed zoster multiplex (3), which is more common in immunocompromised individuals. VZV may reactivate without causing cutaneous vesicles but instead present with other symptoms and is termed zoster sine herpete. Overall incidence is 10% to 20%, with >66% of individuals affected with zoster being older than 50 years of age. Twenty-five percent of patients with HIV and 7% to 9% of patients with renal and cardiac transplant experience at least one episode of zoster. Ninety-five percent to 100% of individuals are seropositive for VZV antibodies. The disseminated form of zoster occurs in 2% to 20% of patients with herpes zoster; in contrast, up to 35% of patients with herpes zoster will have a few scattered vesicles in remote sites.
  • Those patients predisposed to more severe disease may show hemorrhagic, bullous, and infarctive-gangrenous lesions, which will heal slowly with scarring.
  • Persistent varicella zoster in an immunocompromised host may present with atypical hyperkeratotic papules.
IV. Assessment
  • Infection may be confirmed by cytologic smear of the vesicle, viral culture, direct immunofluorescence with a monoclonal antibody, biopsy, or serologic methods (see Chap. 15, sec. IV.B). Of 56 patients with typical clinical herpes zoster, 64% had positive Tzanck smears, 55% had positive immunofluorescence assays, and 26% had positive cultures (4).
  • Patients who are more at risk for severe varicella or those with disseminated zoster should be hospitalized and kept under strict precautions—in private rooms and away from seriously ill patients and those with lymphoproliferative disease or on immunosuppressive therapy. All patients with disseminated zoster or those severely ill with varicella should be investigated for underlying neoplastic or immunologic disease.
  • Approximately 50% of adults with varicella show nodular pulmonary infiltrates, but not all will manifest clinical respiratory disease. A chest x-ray is indicated for evaluation.
  • Nonimmune hospital employees who have been exposed to varicella should avoid patient contact for 8 to 21 days following exposure.
V. Therapy
  • Varicella. Most patients with varicella require only symptomatic therapy.
    • Localized itching may be alleviated by application of a drying antipruritic lotion (calamine alone or with 0.25% menthol and/or 1.0% phenol). Lotions with phenol should not be given to pregnant women. Powdered oatmeal baths are also helpful for the itching.
    • Antihistamines may help pruritus. Salicylates should not be used for fever control to avoid Reye’s syndrome.
    • The patient should cut nails short and keep hands clean, and children should wear gloves, if necessary, to prevent excoriation.
    • Mouth and perineal lesions may be treated by rinses or compresses with 1.5% hydrogen peroxide, saline, or other agents (see Chap. 15, sec. V.B).
    • Apply topical antibiotic ointments to locally infected lesions. If infection is widespread, it is most often due to group A β-hemolytic Streptococcus or Staphylococcus, and systemic antibiotics should be used.
    • The American Academy of Pediatrics does not recommend oral acyclovir routinely for the treatment of uncomplicated varicella in otherwise healthy children. This is due to the marginal therapeutic effect, the cost of the drug, and the feasibility of drug administration in the first 24 hours. Acyclovir [20 mg/kg (not to exceed 800 mg) PO q.i.d. for 5 days] is indicated for children over 24 months with chronic cutaneous or pulmonary disorders, as well as adolescents, who are found to have more severe diseases than young children. If the child is over 40 kg, the adult dose is appropriate. Administration of oral acyclovir within 24 hours of onset for 5 to 7 days has been demonstrated to reduce the maximum number of lesions, shorten the time to healing, decrease
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      the number of patients with fever by the second day, and decrease severe itching.
    • Severe varicella, especially in the immunocompromised patient, should be treated with acyclovir as done for disseminated zoster.
    • Antiviral treatment of varicella (800 mg PO q.i.d. for 5 days) in healthy adults, initiated the first day of illness, decreases the time of illness, decreases the time to healing, and lessens symptoms. Valacyclovir and famciclovir have not been extensively studied for use in primary varicella infection.
    • In the immunocompromised or immunosuppressed population, intravenous acyclovir therapy is recommended. This is generally done to decrease the likelihood of life-threatening complications associated with severe disseminated disease such as pneumonia, encephalitis, thrombocytopenia, and purpura. This population may also be complicated by acyclovir-resistant strains of VZV; foscarnet is a potential alternative therapy. The varicella-zoster immune globulin (VZIG) may be indicated in highly susceptible individuals. If given within 96 hours of exposure, the disease is not prevented but the course may be modified. VZIG is indicated for infants born to mothers who experience the onset of chickenpox 5 days before delivery or within 2 days after delivery.
    • In March 1995, the U.S. Food and Drug Administration (FDA) approved the use of the live attenuated varicella vaccine for use in susceptible healthy children and adults. Recommendations include one-dose vaccination for healthy children 12 to 18 months of age and two-dose vaccination, in a 4- to 8-week interval, in adolescents aged 13 years or older who are at high risk for varicella exposure. Prophylactic immunization for all children and adolescents susceptible to varicella is recommended. Long-term immunity of children having received the varicella Oka vaccine strain has been observed to persist 10 years after administration. Nonetheless, the duration of immunity to varicella after childhood vaccination is not yet determined. Similarly, the risk of herpes zoster after vaccination needs to be established. The possibility of vaccine-induced primary varicella or herpes zoster infection is low. Vaccination of susceptible adults, particularly health care workers, international travelers, day care workers, family contacts of immunocompromised patients, and nonpregnant women of childbearing age, should be performed. Adverse reactions to the vaccine include fever, infection-site reactions, and rash. Although rare, the occurrence of vaccine-induced zoster infection in both immunocompetent and immunocompromised individuals has been reported. Two studies found that there is an increased risk of breakthrough varicella if the person has been vaccinated 5 or more years previously (5,6). An ongoing case–control study in Connecticut reported that vaccine effectiveness was 97% within the first 12 months but decreased to 84% thereafter (7). Concerns remain whether varicella vaccine in young children will create a cohort of adults at risk for potentially life-threatening varicella. At present, fewer than 2% of adults older than 30 years in the United States are susceptible to varicella. Mathematic models indicate that if varicella vaccine coverage in children exceeds 90%, a greater proportion of cases will occur at older ages, but the varicella disease burden will decrease for children and adults. The American Academy of Pediatrics strongly encourages physicians to support varicella immunization requirements for childcare and school entry. The effectiveness of a single dose of the vaccine in children under 13 is approximately 80%. A second booster dose may be considered for increased effectiveness, as is done with the measles-mumps-rubella vaccine. Certainly, a combination vaccination of varicella, measles, mumps, and rubella would increase the chances of this booster; however, the immunogenic formulation has been difficult up until this point (8). Kuter et al. showed that over 10 years of follow-up, children who received two doses of vaccine were three times less likely to develop breakthrough varicella as compared with the patients who received a single dose (9). Interestingly, even though there has been a decrease in vaccination-associated varicella, this has not resulted in increased incidence of herpes zoster (10).
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  • Zoster
    • Acyclovir, a purine nucleoside analog, has been proved effective in both localized and disseminated zoster.
      • Administered intravenously for acute zoster, it decreases the duration of pain and the healing time. In the immunocompromised patient, it can also prevent or abort dissemination. Side effects are rare but include a transient recurrence of pain on discontinuing therapy and impaired renal function following rapid infusion.
      • Topical acyclovir (5% in polyethylene glycol applied q4h for 10 days) promotes healing of localized zoster in immunocompromised patients. However, it is ineffective in reducing pain and preventing postherpetic neuralgia.
      • Oral acyclovir (800 mg q4h, five times daily for 7 to 10 days), if started within the first 24 to 48 hours, is capable of shortening the time to lesion crusting, healing, and cessation of pain, and reducing new lesion formation. Treatment within 72 hours at onset may halve the incidence of residual neuropathic pain at 6 months in immunocompetent patients (11). Acyclovir-resistant VZV infection has been reported in patients with AIDS; clinically, they have persistent, generalized hyperkeratotic papules. Two of the drugs listed below (Valtrex and Famvir) are more bioavailable prodrugs of Acyclovir and are therefore more effective. A comparison study between Valtrex and Famvir showed no difference in effectiveness (12).
    • Valacyclovir (Valtrex) is the L-valyl ester and prodrug of acyclovir. It displays improved bioavailability and prolonged half-life compared with acyclovir (see Chap. 15, sec. V.A.1). The current recommended dose of valacyclovir is 1,000 mg by mouth three times a day for 7 days. Valacyclovir is superior in decreasing the duration or PHN and zoster-associated pain compared with acyclovir. Valacyclovir is as effective as famciclovir. The use of valacyclovir is contraindicated in immunocompromised patients. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome have occurred in patients with advanced HIV disease, renal transplant, or bone marrow transplant.
    • Famciclovir (Famvir), another purine nucleoside analogue, was approved for use in herpes zoster in 1994. It displays improved availability compared with acyclovir and valacyclovir (see Chap 15, sec. V.A.2.). The dose is 500 mg three times a day for 7 days; the cost is similar to that of acyclovir. Famciclovir was effective in reducing PHN in individuals older than 50 years old when compared with placebo. Valacyclovir and famciclovir appear to be equally efficacious for the treatment of herpes zoster and both may be superior to acyclovir in decreasing the duration of acute pain as well as PHN. This suggests that both cost and prescription plan availability should be taken into consideration when selecting between the two newer antiviral agents.
    • Foscarnet is a pyrophosphate antagonist that inhibits DNA polymerase. It is approved for use in the treatment of acyclovir-resistant herpes zoster infections. It is administered intravenously, 40 mg/kg every 8 to 12 hours within 7 to 10 days in patients suspected of having acyclovir-resistant herpes zoster infection. Foscarnet is administered for 10 days. The associated side effects include azotemia secondary to nephrotoxicity, hyperphosphatemia, hypocalcemia, anemia, nausea, vomiting, and genital ulceration.
    • Analgesics should be given as necessary. Opiates may be needed.
    • For the vesicular stages, one of the following may be effective:
      • Application of cool compresses with 1:20 Burow’s solution.
      • Painting of lesions with equal parts of tincture of benzoin and flexible collodion or with flexible collodion q12h.
      • Application of a drying lotion containing alcohol, menthol, and/or phenol.
      • Splinting the area with an occlusive dressing is often very useful in relieving pain. Lesions should be covered with cotton and then wrapped with an elastic bandage as for a fractured rib.
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    • When lesions are crusted and/or secondarily infected, Burow’s solution compresses should be applied (see Chap. 40, Wet Dressings, Baths, Astringents, sec. I.B.1) and systemic antibiotics used if appropriate.
    • Ocular involvement should be evaluated by an ophthalmologist. Herpes zoster keratoconjunctivitis is treated with topical ophthalmic corticosteroids. The distinction from herpes simplex keratitis is crucial, because the treatment is quite different (see Chap. 15, sec. V.C).
    • When herpes zoster occurs along the facial nerve and involves the geniculate ganglion—it may be accompanied by symptoms such as hearing loss and a rapid onset of facial pain—one must consider the diagnosis of herpes zoster oticus, also called Ramsay Hunt Syndrome. On physical examination, there may be a unilateral herpetic rash of the pinna and peripheral facial paralysis. Patients may also experience a loss of taste and vertigo.
    • Systemic corticosteroids are thought to decrease the incidence of PHN presumably by inhibiting perineural inflammation and fibrosis in patients older than 50 years of age. The effectiveness of this treatment remains unclear. Several regimens have been proposed, all advocating that treatment is started early (within 5 to 7 days of the eruption), adequate doses are used (40- to 60-mg prednisone PO daily or its equivalent), and treatment be continued for 3 to 4 weeks in a tapering fashion. Acyclovir with prednisone has been shown to be at least as effective as acyclovir alone in reducing the time to healing of the acute eruption (13). While the additional benefit of adding systemic corticosteroids is not significant, the doses used do not increase the risk of dissemination. Corticosteroids decrease the severity of edema and pain and are very useful in patients with severe facial swelling either with or without ocular involvement. The risk–benefit ratio must be determined for each patient. Two larger studies reported that the addition of oral steroids to an antiviral course showed no protective effect against PHN (13,14).
    • Intralesional injections of corticosteroids and/or anesthetics into the affected dermatome may be useful in decreasing the pain of acute zoster. Intralesional corticosteroids also might reduce the incidence of PHN in a fashion similar to their systemic usage. Use of the treatment techniques for injecting the involved skin is an innovative and useful approach (15).
    • Therapy with levodopa and benserazide (a peripheral decarboxylase inhibitor) has been reported to ameliorate the pain of acute zoster and, in elderly patients or those with ophthalmic zoster, to promote healing. Its effect on PHN is unclear.
    • Emetine or its derivative, dehydroemetine, with or without systemic corticosteroids, has also been reported to decrease the pain of acute zoster. Given their cardiotoxic side effects, these agents should be used with caution.
    • The use of a live attenuated vaccine (Oka/Merck) in older adults to prevent herpes zoster and PHN was recently reported in the New England Journal of Medicine. Previous studies show that VZV vaccines can significantly increase a person’s cell-mediated immunity to VZV in immunocompetent older adults (16). In the subpopulation of hematopoietic-cell transplant recipients, the VZV vaccine reduced the incidence and severity of herpes zoster (17). Oxman et al. showed that the burden of illness, defined as the incidence, severity, and duration of the associated pain and discomfort, was reduced by 61.1% (p <0.001) and the incidence of PHN was decreased by 66.5% (p <0.001). The incidence of herpes zoster was reduced by 51.3% (p <0.001). In conclusion, the zoster vaccine markedly reduced morbidity from herpes zoster and PHN among older adults (18).
  • PHN is defined as pain persisting longer than 1 month up to at least 120 days following resolution of the vesicles. When the pain starts within 120 days of the rash, it is defined as subacute herpetic neuralgia. With acute infection there is direct viral damage and inflammatory neuritis of the peripheral nerve fibers, dorsal route ganglia, and the spinal cord. When the inflammatory phase decreases, fibrosis and destruction on nerve tissue begins and affects all levels of the pain pathway (19).
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    PHN occurs in 9% to 14% of patients. Its incidence and severity are directly related to age. The incidence in patients between ages 30 and 50 is 4%, in contrast to 50% in patients over the age of 80. The pain improves from severe to mild in two thirds of cases. Preexisting postherpetic pain is extremely difficult to alleviate, in testimony to which multiple approaches have been suggested. The most important strategy is prevention. Evidence supports the use of low doses of tricyclic antidepressants and phenothiazines. Local physical modalities can be helpful, and neurosurgical procedures remain an option in failed medical cases. Pain clinics can be very helpful in the long-term management of these patients. Researchers in the United Kingdom reported that after 3 months, 15% of patients still had pain and at 1 year roughly 5% to 10% still reported pain. Spontaneous resolution after 1 year is limited (20).
    • Application of capsaicin cream 0.025% or 0.075% (Zostrix) t.i.d. to q.i.d. may cause complete pain relief in 25% and reduction of pain in as many as 80% of patients with PHN. Capsaicin is a derivative of hot chilli peppers and depletes and prevents reaccumulation of the chemomediator substance P in peripheral sensory resources.
    • The use of a combination of a tricyclic antidepressant and a substituted phenothiazine medication may lead to relief of pain within 1 to 2 weeks after institution of therapy. Amitriptyline (Elavil) 75 to 100 mg daily should be used in combination with either perphenazine (Trilafon) 4-mg t.i.d. to q.i.d., fluphenazine hydrochloride (Permitil) 1 mg t.i.d. to q.i.d., or thioridazine (Mellaril) 25 mg q.i.d. Nortriptyline (Aventyl, Pamelor) may be substituted for amitriptyline, with the former being as effective but associated with fewer unpleasant side effects (21). It may be necessary to continue medication for months.
    • Chlorprothixene (Taractan) has been reported twice to be effective in the treatment of PHN. For severe pain, an initial 50 to 100 mg IM injection has been advocated. Otherwise, the dosage is 25 to 50 mg PO q6h. The recommended duration of therapy is 4 to 10 days. Higher doses are unwarranted and frequently result in side effects.
    • Gabapentin (Neurontin) significantly decreases pain scores and sleep interference associated with PHN. An initial dose of 300 mg/day is increased over 4 weeks (900, 1,800, 2,400, 3,600 mg/day divided t.i.d.) until efficacy is obtained or side effects become intolerable. Dose-limiting adverse effects include somnolence, dizziness, ataxia, peripheral edema, and infection (22).
    • Beneficial results have been reported with the combined use of either carbamazepine (Tegretol) 600 to 800 mg/day or phenytoin sodium (Dilantin) 300 to 400 mg/day with 50 to 100-mg nortriptyline (Aventyl, Pamelor) and with the combined use of carbamazepine (Tegretol) up to 1,000 mg/day and clomipramine up to 75 mg/day.
    • Opioids are effective in controlling neuropathic pain; therefore, oxycodone may provide some relief from PHN. In one study, patients treated with oxycodone experienced greater pain relief (p <0.0001) and reduced allodynia (p <0.0004) as compared with the placebo group. The initial dose was oxycodone 10 mg every 12 hours and was increased over 4 weeks to a maximum of 30 mg every 12 hours. Across the oxycodone group, the average dose was 45 mg/day (23).
    • Daily intralesional or subcutaneous injection of triamcinolone 0.2 mg/mL into the affected dermatome achieves pain relief in some patients with acute herpes zoster and in many patients with postzoster neuralgia. Up to 30 mL of the drug diluted in saline can be administered at each session. Injection by tumescent technique may be particularly helpful. Some authors report that when combined with local anesthetic and given over days or weeks the duration of pain is reduced (24).
    • Topical EMLA cream applied for a 24-hour period of time significantly decreased pain scores in PHN.
    • Lidocaine (5%) adhesive patch (Lidoderm) significantly reduces pain intensity. Several of the 10 × 14 cm patches can be used simultaneously to cover the affected area. Minimal systemic absorption of lidocaine occurs (25).
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    • Repeated cryosurgery to limited areas affected by PHN has been reported to reduce the sensitivity of trigger areas and produce long-term relief from pain.
    • Transcutaneous electrical stimulation has brought pain relief to a high percentage of patients.
    • Neurosurgical intervention is occasionally necessary in patients with intractable pain.
    • Pain clinics at major medical centers can be helpful in evaluating and treating these patients. They often employ the use of nerve blocks (26).
    • Intrathecal methylprednisolone has been reported to relieve pain and allodynia. Potential toxicities include arachnoiditis or other neurotoxic event. This treatment may be most appropriately administered by a pain clinic or neurologist (27).
References
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