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SETH JOHN STANKUS, MAJ, MC, USA, MICHAEL DLUGOPOLSKI, MAJ, MC, USA, and DEBORAH PACKER, MAJ, MC, USA, Eisenhower Ar ! Medi"a# Cen$er, %or$ Gordon, Geor&ia
Am Fam Physician. '((( A)r *+,-*./01'2345'2226 Patient information: See re#a$ed hando7$ on shin&#es, wri$$en 8! $he a7$hors o9 $his ar$i"#e6
Herpes zoster (commonly referred to as “shingles”) and postherpetic neuralgia result from reacti ation of the aricella!zoster irus ac"uired during the primary aricella infection# or chic$enpo%& 'hereas aricella is generally a disease of childhood# herpes zoster and post! herpetic neuralgia (ecome more common )ith increasing age& *actors that decrease immune function# such as human immunodeficiency irus infection# chemotherapy# malignancies and chronic corticosteroid use# may also increase the ris$ of de eloping herpes zoster& +eacti ation of latent aricella!zoster irus from dorsal root ganglia is responsi(le for the classic dermatomal rash and pain that occur )ith herpes zoster& ,urning pain typically precedes the rash (y se eral days and can persist for se eral months after the rash resol es& 'ith postherpetic neuralgia# a complication of herpes zoster# pain may persist )ell after resolution of the rash and can (e highly de(ilitating& Herpes zoster is usually treated )ith orally administered acyclo ir& -ther anti iral medications include famciclo ir and alacyclo ir& .he anti iral medications are most effecti e )hen started )ithin /0 hours after the onset of the rash& .he addition of an orally administered corticosteroid can pro ide modest (enefits in reducing the pain of herpes zoster and the incidence of postherpetic neuralgia& -cular in ol ement in herpes zoster can lead to rare (ut serious complications and generally merits referral to an ophthalmologist& Patients )ith postherpetic neuralgia may re"uire narcotics for ade"uate pain control& .ricyclic antidepressants or anticon ulsants# often gi en in lo) dosages# may help to control neuropathic pain& 1apsaicin# lidocaine patches and ner e (loc$s can also (e used in selected patients&
Herpes zoster results from reactivation of the varicella-zoster virus. Unlike varicella (chickenpox), herpes zoster is a sporadic disease with an estimated lifetime incidence of 10 to 20 percent. The incidence of herpes zoster increases sharply with advancing age, roughly doubling in each decade past the age of 50 years. Herpes zoster is uncommon in persons less than 15 years old. In a recent study, patients more than 55 years of age accounted for more than 30 percent of
herpes zoster cases despite representing only 8 percent of the study population. In this same study, children less than 14 years old represented only 5 percent of herpes zoster cases. The normal age-related decrease in cell-mediated immunity is thought to account for the increased incidence of varicella-zoster virus reactivation. Patients with disease states that affect cell-mediated immunity, such as human immunodeficiency virus (HIV) infection and certain malignancies, are also at increased risk. Chronic corticosteroid use, chemotherapy and radiation therapy may increase the risk of developing herpes zoster. The incidence of herpes zoster is up to 15 times higher in HIV-infected patients than in uninfected persons, and as many as 25 percent of patients with Hodgkin's lymphoma develop
5 About 20 percent of patients with herpes zoster develop postherpetic neuralgia. The varicella-zoster virus genome has been identified in the trigeminal ganglia of nearly all seropositive patients. pathologic studies have demonstrated damage to the sensory nerves. The prodrome generally lasts one to two days but may precede the appearance of skin lesions by up to three weeks. 3 Race may influence susceptibility to herpes zoster. as well as endogenous and exogenous boosting of the immune system periodically throughout life. burning dysesthesias or pruritus along the affected dermatome(s). the virus gains entry into the sensory dorsal root ganglia. How the virus enters the sensory dorsal root ganglia and whether it resides in neurons or supporting cells are not completely understood. The occurrence of herpes zoster in HIV-infected patients does not appear to 2. . 9 1linical Presentation Herpes zoster typically presents with a prodrome consisting of hyperesthesia. Although herpes zoster is not as contagious as the primary varicella 4 infection.herpes zoster. a history of prodromal pain before the appearance of skin lesions and an immunocompromised state. Household transmission rates have been noted to be approximately 15 percent. 7 The virus remains latent for decades because of varicella-zoster virus–specific cell-mediated immunity acquired during the primary infection. paresthesias. Reactivation of the virus occurs following a 8 decrease in virus-specific cell-mediated immunity. persons with reactivated infection can transmit varicella-zoster virus to nonimmune contacts. Blacks are one fourth as likely as whites to develop this condition. this complication occurs nearly 15 times more often in patients more than 50 years of age. The pathophysiology of postherpetic neuralgia remains unclear. Other possible risk factors for the development of post-herpetic neuralgia are ophthalmic zoster. The reactivated virus travels down the sensory nerve and is the cause for the dermatomal distribution of pain and skin lesions. 6 Pathophysiology Varicella-zoster virus is a highly contagious DNA virus. However.3 increase the risk of acquired immunodeficiency syndrome (AIDS) and is less dependent on the CD4 count than AIDS-related opportunistic infections. During the primary infection. the sensory dorsal root ganglia and the dorsal horns of the spinal cord in patients with this condition. The most established risk factor is age. There is no evidence that herpes zoster 2 heralds the onset of an underlying malignancy. Varicella represents the primary infection in the nonimmune or incompletely immune person.
” may further complicate the eventual diagnosis. Although any vertebral dermatome may be involved. *234+5 6& T!)i"a# der a$o a# rash wi$h he orrha&i" :esi"#es on $he $r7n. Ocular complications occur in approximately one half of patients with involvement of the ophthalmic division of the trigeminal nerve. commonly referred to as a “belt-like pattern. pleurisy.During the prodromal phase. keratitis and anterior uveitis. and as many as one in seven with viremia may die. fourth and sixth cranial nerves may occur. These complications include mucopurulent conjunctivitis. o9 a )a$ien$ wi$h her)es <os$er6 Pain is the most common complaint for which patients with herpes zoster seek medical care. The vesicles eventually become hemorrhagic or turbid and crust over within seven to 10 days. Cranial nerve palsies of the third. Of these patients. affecting extraocular motility. herpes zoster may be misdiagnosed as cardiac disease. Indeed. This situation. Twenty or more lesions outside the affected dermatome reflect generalized viremia. episcleritis.” The maculopapular rash evolves into vesicles with an erythematous base (Figure 1). and their development is often associated with the occurrence of anxiety and flu-like symptoms. known as “zoster sine herpete. The pain may be described as “burning” or “stinging” and is generally unrelenting. patients may have insomnia because of the pain. The skin lesions begin as a maculopapular rash that follows a dermatomal distribution. . T5 10 and T6 are most commonly affected. a herniated nucleus pulposus or various gastrointestinal or gynecologic disorders. The prodromal phase is followed by development of the characteristic skin lesions of herpes zoster. Some patients may have prodromal symptoms without developing the characteristic rash. As the crusts fall off. approximately one half manifest other neurologic or visceral involvement. The most frequently involved cranial nerve dermatome is the ophthalmic division of the trigeminal nerve. patients are generally left with scarring and pigmentary changes. The vesicles are generally painful.
the prototype antiviral drug. is administered three times daily. Other antiviral agents. is a DNA polymerase inhibitor. these benefits have only been demonstrated in 12 patients who received antiviral agents within 72 hours after the onset of rash. Antiviral agents. Compared with acyclovir. but they are unlikely to be helpful after lesions have crusted. Based on the findings of multiple studies. Acyclovir may be given orally or intravenously. Acyclovir. Patients may also complain of pain in response to nonnoxious stimuli. appear to be at least as effective as acyclovir. valacyclovir may be slightly better at decreasing the severity of pain associated with herpes zoster. Postherpetic neuralgia is generally a self-limited disease. Symptoms tend to abate over time. bedsheets or wind may elicit pain. (2) treatment of the acute pain associated with herpes zoster and (3) prevention of postherpetic neuralgia. The effectiveness of antiviral agents in preventing postherpetic neuralgia is more controversial. and fewer than one in 20 has pain at one year. Major drawbacks of orally administered acyclovir include its lower bioavailability compared with other agents and its dosing frequency (five times daily).S Antiviral agents have been shown to decrease the duration of herpes zoster rash and the severity of pain associated with the rash. Numerous studies evaluating this issue have been conducted. 7N. Valacyclovir. oral corticosteroids and adjunctive individualized painmanagement modalities are used to achieve these objectives. a prodrug of acyclovir. . Even the slightest pressure from clothing. as well as the duration of postherpetic neuralgia. Valacyclovir is also more bioavailable 14 . Pain that persists for longer than one to three months after resolution of the rash is generally accepted as the sign of postherpetic neuralgia. acylovir (Zovirax) therapy appears to produce a moderate reduction in the development of postherpetic neuralgia. However. Less than one quarter of patients still experience pain at six months after the herpes zoster eruption.282+79 735N. but the results have been variable. lancinating 11 pain that may be radicular in nature.reatment of Herpes Zoster The treatment of herpes zoster has three major objectives: (1) treatment of the acute viral infection. Antiviral agents may be beneficial as long as new lesions are actively being formed. 13 specifically valacyclovir (Valtrex) and famciclovir (Famvir).The most common chronic complication of herpes zoster is postherpetic neuralgia. Affected patients usually report constant burning. Intravenously administered acyclovir is generally used only in patients who are severely immunocompromised or who are unable to take medications orally.
and oral administration produces blood drug levels comparable to the intravenous administration of acyclovir. famciclovir and valacyclovir are provided in Table 1. The advantages of famciclovir are its dosing schedule (three times daily). Prednisone used in conjunction with acyclovir has been shown to reduce the pain associated with herpes zoster.reatment -ptions for Herpes Zoster Medication A"!"#o:ir . . Famciclovir is also a DNA polymerase inhibitor.—Antiviral therapy has been shown to be bene#icial only when patients are treated within /+ hours o# onset o# the herpes 0oster rash. -ost to the patient will be higher" depending on prescription #illing #ee6 . &ontvale" '. $hen *+ $hen 46+ & $wi"e dai#! on da!s *+ $hro7&h '* '0 9or da!s *+ $o '* IV = intravenously6 *—Estimated cost to the pharmacist based on average wholesale prices rounded to the nearest dollar!" #or seven days o# therapy" in $ed boo%. Antiviral agents are not used in combination" and selection o# an agent is based on dosage schedule and cost6 1—Acyclovir can be administered IV to severely immunocompromised patients or patients who are unable to ta%e medications orally6 1-+.=o:ira>0? %a "i"#o:ir ..(. even though clinical trials have shown variable results. its longer intracellular half-life compared with acyclovir and its better bioavailability compared with acyclovir and valacyclovir.%a :ir0? @a#a"!"#o:ir .' $o 20 9or da!s * $hro7&h 4 ' . The likely mechanism involves 15 decreasing the degree of neuritis caused by active infection and. decreasing residual damage to affected nerves..) &edical Economics *ata" +. All three antiviral agents are generally well tolerated.. possibly. TABLE * .De#$asone0 Dosage Average cost (generic)* /(( & ora##! 9i:e $i es dai#! 9or 4 $o *( da!s B*42 $o '2/ . The choice of which antiviral agent to use is individualized.* $o da!sA +(( & ora##! $hree $i es dai#! 9or 4 da!s *. vomiting. The most common adverse effects are nausea.21-S.5+-2:S Orally administered corticosteroids are commonly used in the treatment of herpes zoster.& I@ e:er! / ho7rs 9or 4 $o *( *2( /2 ' . & $wi"e dai#! on da!s / $hro7&h *2.than acyclovir.@a#$re>0? Prednisone . Dosing schedule and cost may be considerations.*'C $o '((0 *( & )er .((( 3( & ora##! $hree $i es dai#! 9or 4 da!s & ora##! $wi"e dai#! on da!s * $hro7&h 4.* $o 30 9or da!s / $hro7&h *2 * . The recommended dosages for acyclovir. headache. dizziness and abdominal pain.
.18 16. demonstrated no benefit. When herpes zoster involves the eyes.Some studies designed to evaluate the effectiveness of prednisone therapy in preventing postherpetic neuralgia have shown decreased pain at three and 12 months. Patients with mild to moderate pain may respond to over-the-counter analgesics. When analgesics are used. The recommended dosage for prednisone is given in Table 1. The morbidity and mortality of herpes zoster could be reduced if a safe and effective preventive treatment were available. Once the lesions have crusted over. despite questionable evidence for its benefits in decreasing the incidence of postherpetic neuralgia.17 Other studies have If the use of orally administered prednisone is not contraindicated. Pain therapy may include multiple interventions. including loss of vision.285 . P+585N. Although most patients with ocular herpes zoster improve without lasting sequelae. 15 7N7935S21S The pain associated with herpes zoster ranges from mild to excruciating. 15. such as topical medications.+57. Lotions containing calamine (e. it can last indefinitely. Treatment is directed at pain control while waiting for the condition to resolve. Patients with more severe pain may require the addition of a narcotic medication. Given the theoretic risk of immunosuppression with corticosteroids. Studies are currently being conducted to evaluate the efficacy of the varicella-zoster vaccine in preventing or modifying herpes zoster in the elderly.. tricyclic . the same as involvement elsewhere. ophthalmologic consultation is usually recommended. -1497+ 2N8-985M5N.g.M5N. adjunctive treatment with this agent is justified on the basis of its effects in reducing pain. some may develop severe complications. Ocular herpes zoster is treated with orally administered antiviral agents and corticosteroids. Topically administered lidocaine (Xylocaine) and nerve blocks have also been reported to be effective in reducing pain. a regular dosing schedule results in better pain control and less anxiety than “as-needed” dosing. It is unusual for a patient to develop herpes zoster more than once. over-the-counter analgesics. some investigators believe that these agents should be used only in patients more than 50 years of age because they are at greater risk of developing postherpetic neuralgia.reatment of Postherpetic Neuralgia Although postherpetic neuralgia is generally a self-limited condition. capsaicin cream (Zostrix) may be applied. suggesting that the first reactivation of varicella-zoster virus usually provides future immunologic protection. Caladryl) may be used on open lesions to reduce pain and pruritus. with or without a narcotic.
Dr7& #e:e#s 9or "#ini"a# 7se are no$ a:ai#a8#e60 *—Additional modalities include transcutaneous electric nerve stimulation 2E'3!" bio#eedbac% and nerve bloc%s6 7N7935S21S & $hree $i es dai#! or res)onse is adeE7a$e6 Capsaicin. Patients must be counseled about the need to apply capsaicin regularly for continued benefit.s 7n$i# res)onse is adeE7a$e.2( $o /( F o# )er L06 *(( & ora##! a$ 8ed$i e.s 7n$i# res)onse is adeE7a$e.Nor)ra in0 res)onse is adeE7a$e. Trials have shown this drug 19 to be more efficacious than placebo but not necessarily more so than other conventional treatments.Te&re$o#0 Ga8a)en$in .s 7n$i# .Pa e#or0 I i)ra ine . Dosage recommendations are provided in Table 2.$o*' F& )er L .s 7n$i# res)onse is adeE7a$e. capsaicin cream must be applied to the affected area three to five times daily. 20 Substance P. Analgesia occurs when substance P is depleted from the nerve fibers. in"rease dosa&e 7n$i# res)onse is adeE7a$e Car8a a<e)ine .=os$ri>0 Lido"aine Dosage A))#! $o a99e"$ed area $hree $o 9i:e $i es dai#!6 A))#! $o a99e"$ed area e:er! 2 $o *' ho7rs as needed6 . is currently the only drug labeled by the U.opical agents Ca)sai"in "rea .'+62 $o +(6/ F o# )er L06 *(( $o 3(( & ora##! a$ 8ed$i e. TABLE ' . Food and Drug Administration for the treatment of postherpetic neuralgia. or $o a>i 7 dosa&e o9 *+( & )er da!6 7nticon ulsants Phen!$oin . To achieve this response. in"rease dosa&e 8! *(( $o 3(( da!s 7n$i# dosa&e is 3(( $o C(( .reatment -ptions for Postherpetic Neuralgia. in"rease dosa&e 8! '+ & e:er! ' $o 2 wee. a neuropeptide released from pain fibers in response to trauma. Occasionally.Ne7ron$in0 or 8#ood dr7& #e:e# is *( $o '( F& )er L .D!#o"aine0 )a$"h . or $o a>i 7 dosa&e o9 *+( & )er da!6 *( $o '+ & ora##! a$ 8ed$i e. an extract from hot chili peppers. is also released when capsaicin is applied to the skin. Patients . in"rease dosa&e 8! *(( & e:er! 3 da!s 7n$i# dosa&e is '(( & $hree $i es dai#!. producing a burning sensation.ricyclic antidepressants A i$ri)$!#ine . in"rease dosa&e 8! '+ & e:er! ' $o 2 wee. anticonvulsants and a number of nonmedical modalities. in"rease dosa&e 8! '+ & e:er! ' $o 2 wee.antidepressants.To9rani#0 Desi)ra ine & ora##! a$ 8ed$i e.Di#an$in0 *(( $o 3(( & ora##! a$ 8ed$i e.E#a:i#0 *( $o '+ Nor$ri)$!#ine .S. narcotics may be required. in"rease dosa&e 8! '+ & e:er! ' $o 2 wee. or $o a>i 7 dosa&e o9 *'+ & )er da!6 '+ & ora##! a$ 8ed$i e. or $o a>i 7 dosa&e o9 *+( & )er da!6 '+ & ora##! a$ 8ed$i e. res)onse is adeE7a$e or 8#ood dr7& #e:e# & e:er! 3 is . They also need to be counseled that their pain will likely increase during the first few days to a week after capsaicin therapy is initiated. Medication .
A recent double-blind. their chronic use is discouraged except in the rare patient who does not adequately respond to other modalities. 7N. These drugs are best tolerated when they are started in a low dosage and given at bedtime. lasting only four to 12 hours with each application. 22 Tricyclic antidepressants commonly used in the treatment of postherpetic neuralgia include amitriptyline (Elavil). the effect was temporary.g. placebo-controlled study showed gabapentin to . with minimal systemic absorption. a clinical trial of at least three months is required to judge a patient's response. such as sedation.. 21 Over-the-counter analgesics such as acetaminophen (e. These agents most likely lessen pain by inhibiting the reuptake of serotonin and norepinephrine neurotransmitters.S 20 Phenytoin (Dilantin). Because of the addictive properties of narcotics. Treatment with tricyclic antidepressants can occasionally lead to cardiac conduction abnormalities or liver toxicity. Although lidocaine was efficacious in relieving pain. The dosage is increased every two to four weeks to achieve an effective dose. .S Tricyclic antidepressants can be effective adjuncts in reducing the neuropathic pain of postherpetic neuralgia. nortriptyline tends to produce fewer anticholinergic effects and is therefore better tolerated. dry mouth.2:5P+5SS7N. The potential for these problems should be considered in elderly patients and patients with cardiac or liver disease.+21<1921 7N. carbamazepine (Tegretol) and gabapentin (Neurontin) are often used to control neuropathic pain. Because tricyclic antidepressants do not act quickly. The onset of pain relief using tricyclic antidepressants may be enhanced by beginning treatment early in the course of herpes zoster infection in conjunction with antiviral medications. lidocaine patches reduced pain intensity.should wash their hands thoroughly after applying capsaicin cream in order to prevent inadvertent contact with other areas. One study found that compared with no treatment. postural hypotension. imipramine (Tofranil) and desipramine (Norpramin). The tricyclic antidepressants share common side effects. blurred vision and urinary retention. Tylenol) and nonsteroidal antiinflammatory drugs have not been shown to be highly effective in the treatment of post-herpetic neuralgia. Nortriptyline and amitriptyline appear to have equal efficacy. these agents are often useful for potentiating the pain-relieving effects of narcotics in patients with severe pain.21-N849S7N. however. Patches containing lidocaine have also been used to treat postherpetic neuralgia. However. nortriptyline (Pamelor).
prevention of postherpetic neuralgia. electrolyte abnormalities. *inal 1omment Herpes zoster and postherpetic neuralgia are relatively common conditions. tricyclic antidepressants and anticonvulsants. Approaches to management include treatment of the herpes zoster infection and associated pain. modalities to consider include transcutaneous electric nerve stimulation (TENS). . biofeedback and nerve blocks. 23 The anticonvulsants appear to be equally effective. Primary treatment modalities include antiviral agents. treatment can be frustrating for the patient and physician.be effective in treating the pain of postherpetic neuralgia. as well as the often associated sleep disturbance. primarily in elderly and immunocompromised patients. which can then be slowly titrated upward. Although the diagnosis of the conditions is generally straightforward. liver toxicity and thrombocytopenia. Effective treatment of postherpetic neuralgia often requires multiple treatment approaches. corticosteroids. There are no specific contraindications to using anticonvulsants in combination with antidepressants or analgesics. and control of the neuropathic pain until the condition resolves. including sedation. Lack of response to one of these medications does not necessarily portend a poor response to another. However. memory disturbances. the risk of side effects increases when multiple medications are used. In addition to medications. Anticonvulsants are associated with a variety of side effects. The dosages required for analgesia are often lower than those used in the treatment of epilepsy. and drug selection often involves trial and error. Side effects may be reduced or eliminated by initiating treatment in a low dosage.
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