The development and course of herpes zoster depend on contributions
from both the virus and the host. The disease can progress in three
stages, with virus and host factors interacting at each stage (Table
Table 40-1 Stages of Herpes
Zoster ||Download (.pdf)
Table 40-1 Stages of Herpes
|Stage I||Viral replication|
|Loss of immune surveillance|
|Stage II||Clinical syndrome (acute herpes zoster)|
|Viral effect on ganglion-nerve-dermatome|
|Antiviral immune response by the body|
|Cytolysis from virus and host inflammatory reaction|
|Stage III||Sequelae of herpes zoster|
|Central nervous system and visceral spread|
|Antiviral immune response|
Acute herpes usually has pain that is localized to the dermatomal
distribution of one or more affected posterior root ganglia. The
pain may be accompanied by fever and malaise. It usually is mild
at first, but it may grow more severe over the succeeding few days.
It can be dull, sharp, burning, aching, or shooting. Commonly, paresthesia
also is present. Skin lesions usually appear 4 to 5 days later,
but they may appear immediately.
At first, there is a local redness and swelling followed by red
papules that progress through vesicles, blebs, pustules, and then
to the crusting stage over the succeeding 2 to 3 weeks. The lesions characteristically
are unilateral, running along the dermatome in a band. In mild cases,
the skin lesions may not affect the whole dermatome, but sensory
involvement of the whole dermatome usually is present. In severe
cases, larger blebs usually cover the entire dermatome and tend
to coalesce. The area is likely to be extremely painful; the pain
is aggravated by contact or movement.
The lesions appear in thoracic dermatomes in more than 50% of
patients. The next region where they commonly are seen is the trigeminal
distribution, with an incidence of 3% to 20%.
The ophthalmic division is involved in 75% of these patients.
Lumbar and cervical eruptions occur in 10% to 20% of
patients, with a sacral distribution being much less common. With
advancing age, the incidence of trigeminal (ophthalmic) zoster increases
and that of spinal zoster declines. Bilateral zoster occurs in less
than 1% of patients. Recurrent zoster has been reported
in 1% to 8% of patients; approximately one half
of the recurrences are at the site of the previous eruption (Table 40-2).
Table 40-2 Site and Incidence
of Acute Herpes Zoster ||Download (.pdf)
Table 40-2 Site and Incidence
of Acute Herpes Zoster
|Site of Herpes Zoster||Incidence (%)|
|Recurrent at the site of previous herpes zoster||50|
Occasionally, motor paralysis in the intercostal and abdominal
muscles, arms, legs, and muscles innervated by cranial nerves may
be associated with herpes zoster. These motor deficits may be reversible
over a period of years.
If the trigeminal (gasserian) ganglion is affected, the symptoms
usually include pain in the nerve distribution, headache, weakness
of the eyelid muscles and, occasionally, an Argyll Robertson pupil.
Lesions may appear on the face, cornea, mouth, and tongue. Scarring
and anesthesia of the cornea may occur. The first division of the
trigeminal nerve most often is affected. If there is involvement
of the geniculate ganglion, there may be Bell’s palsy,
vertigo, disorders of hearing, and lesions of the external ear and
canal and the anterior portion of the tongue.
The crusts generally fall off at approximately 5 weeks, leaving
irregular pink scars. These scars eventually become hypopigmented
and anesthetic. They form characteristic pocks, which usually are
surrounded by mottled pigmentation and may last for years. The hyperesthesia
and pain usually subside and disappear at approximately the same
time the crusts fall off.
Risk factors for severe, persistent pain associated with acute
herpes zoster include prodromal symptoms, age greater than 50 years,
or moderate or severe pain at presentation.10 The
duration of pain has been shown to correlate with severity of lesions
at worst phase and the involved region, with age over 60 years and
those with trigeminal involvement most likely to have significantly
longer duration of pain.11
In 10% to 50% of patients with herpes zoster,
pain and hyperesthesia persist after the lesions are healed. This
condition, called postherpetic neuralgia, may improve slowly, but
after it has been present for 6 months, complete spontaneous cure
The discomfort of postherpetic neuralgia is of two types: pain
and dysesthesia. The persistent intractable pain, which is constant
and never varies, often is associated with a feeling of heat. It
is described variously as burning, shooting, twisting, lancinating,
pressing, and gripping. A feeling of tightness also may be present.
Relief usually is found during sleep. In chronic postherpetic neuralgia,
the patient commonly has hyperpathia, often associated with damage
to a peripheral nerve, the spinothalamic tract, or the thalamus.
It may be caused by a reduction in the number and proportion of
conducting nerve fibers.
Dysthesia often is interpreted as pain. Uncomfortable unpleasant
sensations make the patient unable to bear the lightest contact
with the skin. Some patients even cut holes in their clothing to minimize
the problem. A slight breath of wind can incite a paroxysm of pain.
Curiously, most patients can tolerate firm pressure on the affected
area but not light pressure. They may wear especially tight clothing
or keep their hands pressed over the painful region. Patients may
complain about a feeling of worms under the skin or of ants crawling
over the skin (formication).
The goals of treatment are early resolution of the acute disease
and prevention of postherpetic neuralgia. The earlier the institution
of treatment, the less likely is the development of postherpetic
Pain should be treated aggressively, especially in elderly patients
and immunosuppressed patients, who are prone to postherpetic neuralgia.14,15 After
postherpetic neuralgia is established, there is no reliable treatment
for this syndrome. Unfortunately, no treatment regimen is fully
effective; this has led to many different treatments with varying
Some physicians do not treat acute herpes zoster because they
believe it will resolve spontaneously if left alone. They institute
treatment only if postherpetic neuralgia develops. This is a great disservice
to the group of patients with intractable pain from postherpetic
neuralgia. Treatment during the early stages of acute herpes zoster
is the best means of preventing needless pain and suffering.21,22
There is no available treatment that is effective in all cases.
Success is usually limited with any method. Many methods of management
have been tried for acute herpes zoster and postherpetic neuralgia.
The various drugs used in the treatment of the acute stage of
herpes zoster are summarized in Table 40-4.
Table 40-4 Drug Therapy
for Acute Herpes Zoster
Antiviral agents are now standard therapy for herpes zoster.
The varicella-zoster virus, like all viruses, is a parasite that
takes over healthy cells and uses their DNA to reproduce itself.
It is believed that, if viral DNA synthesis can be slowed or inhibited,
then specific host immune systems might have more time to help control
the viral infection. Some substances that grossly inhibit DNA synthesis
were developed as possible anticancer drugs and have been found
to have a more significant antiviral than anticancer activity. Theoretically,
these agents could either kill the virus or alter its replication.
To be effective, the agents must be given before significant tissue damage
occurs. Such agents include acyclovir, cytarabine, vidarabine, idoxuridine,
sorivudine, famciclovir, valaciclovir, and brivudine.
Experimental trials using systemic administration of cytarabine
in various dose schedules gave conflicting results, ranging from
apparent success in early, uncontrolled studies to no benefit or apparent
worsening of infection in controlled trials. Controlled studies
of vidarabine in the treatment of herpes zoster in immunosuppressed
patients have been promising. Therapy was most successful when administered
early and to patients younger than 38 years of age or to those with reticuloendothelial
malignancy. Cutaneous healing was accelerated, pain was relieved
acutely, and the incidence of postherpetic neuralgia was low.
Acyclovir masquerades as one of the building blocks of the DNA
needed by the herpesvirus to reproduce itself. This stops the chain,
and the virus ceases to replicate. Although acyclovir accelerates
cutaneous changes in herpes zoster, the intensity and duration of
acute herpetic neuralgia appear to be directly related to time of
therapy initiation (not later than 6 days after onset).21 The author
of a meta-analysis of 30 clinical trials in immunocompetent patients
found five homogeneous, randomized, placebo-controlled trials that
showed that oral acyclovir, 800 mg/day within 72 hours
of rash onset, may reduce the incidence of residual pain at 6 months
by 46%.22 However, at an estimated cost
of from $250 to $300 for 7 days’ treatment
with oral acyclovir, use of this antiviral agent may not be economically
justified in immunocompetent younger patients, especially in developing
Some ophthalmologists have used idoxuridine for treating herpetic
lesions of the conjunctiva and cornea. Prompt treatment is necessary,
and best results are obtained when the drug is used within 4 or
5 days of the onset of infection. This drug’s effects are
variable, and it will not prevent postherpetic neuralgia. Varying
concentrations of idoxuridine in dimethyl sulfoxide have been used in
New Zealand to treat patients with herpes zoster, and it has been
shown that pain decreased faster and that fewer vesicles developed
after topical applications. Early initiation of treatment is necessary.
Similar positive results have been reported from Denmark. Idoxuridine
in dimethyl sulfoxide 35% to 40% has been used
in Great Britain on herpes zoster skin lesions. Faster healing of
lesions and a shorter duration of postherpetic neuralgia have been
reported, and late sequelae are uncommon. Success depends on early
institution of treatment. The solvent decreases inflammation and
edema and has a bacteriostatic action. It is an extremely strong
solvent that has not been approved by the Food and Drug Administration
for this use.
Thymidine analogues have been found to have some inhibitory effect
on certain strains of varicella-zoster virus.
Although acyclovir has been shown to be effective in shortening
duration of zoster pain, other newer agents may offer some advantages.
Sorivudine has compared favorably with acyclovir in terms of accelerating
cutaneous healing24 and preventing recurrences
and new episodes.25 Valaciclovir may be more efficacious
than acyclovir in shortening time to complete resolution of herpes
zoster–associated pain26,27 and appears
to offer cost benefits.28 Famciclovir has been
shown to be efficacious in treating herpes zoster.29–31 It
has also been shown to accelerate healing of genital herpes in humans,32–34 in
preventing further outbreaks of genital herpes (unpublished data
on file, SmithKline Beecham, 1998, Philadelphia) in humans, and
in preventing herpes simplex virus-1 latency in mice.35–37 Famciclovir
may be as or more effective than acyclovir in prevention of latency
for genital herpes.38,39 Intravenous foscarnet
is the current treatment of choice for acyclovir-resistant zoster.40,41
Interferon, which is produced by the body’s immune system,
appears to play a role in the control of disease. It seems to work
more effectively in tandem with other components of the body’s immune
system. Large doses, however, can cause adverse effects. It has
been reported that interferon production in the vesicle fluid of
patients with disseminated herpes zoster is delayed in comparison
with that of patients with localized disease. When human leukocyte
interferon has been administered, it has been shown to increase
circulating interferon. It may, therefore, be used in cases where
there might be a risk of herpetic dissemination.
Zoster immune globulin is not effective in altering the clinical
course of herpes zoster in immunocompromised adults. It is used
currently, however, for the passive protection of susceptible leukemia
patients who have been exposed to chickenpox. It also is recommended
for use in immunocompromised children at risk for chickenpox.
Adenosine monophosphate given intramuscularly also has been used
in the treatment of acute herpes zoster. The exact mechanism by
which it provides certain therapeutic benefits is not understood.
It may correct underlying biochemical imbalances or defects at the
cellular level. Beneficial effects also may occur as a result of
the vasodilating effect of the drug and its ability to decrease
tissue edema and inflammation.
I believe that the ultimate answer to the problem of herpes zoster
and its sequela, postherpetic neuralgia, lies in the field of antiviral
therapy. An antiviral agent is needed that will kill the virus safely
and reliably before there is neurologic damage. Investigation is
still needed to find the most effective antiviral agents against
the varicella-zoster virus.
Analgesics are an important adjunctive therapy. They may be categorized
as nonaddictive, moderately addictive, or strongly addictive agents.
Selecting the optimal agent for a specific patient involves consideration
of various factors, the most important of which are quality, intensity,
duration, and distribution of pain.
Non-narcotic, nonaddictive drugs are used for the control of
mild pain. Oral aspirin and acetaminophen are effective drugs with
a low incidence of side effects. However, they are not effective
in controlling severe pain. Evidence suggests that topical application
of acetylsalicyclic acid markedly reduces the spread of infection
and produces an analgesic effect.42,43
Codeine, propoxyphene, pentazocine, and oxycodone are examples
of moderately addicting drugs. The incidence of addiction is relatively
low, but dependence may occur with these agents. They are good analgesic
agents, but they sometimes produce adverse side effects (such as
When used properly, the strongly addictive narcotics are effective
in the treatment of severe refractory pain, providing relief to
varying degrees. In acute herpes zoster, strong medication may be
needed to control severe pain. Because the acute stage is short,
strongly addictive drugs may be used for a limited period. In such
cases, the narcotic is tapered off as treatment decreases the degree
of pain. When pain is at a level that can be controlled by non-narcotic
drugs, the narcotics should be discontinued. Examples of strongly
addictive drugs are morphine, hydromorphone, and meperidine.
The effects of corticosteorid therapy on herpes zoster are still
unclear, but reports are encouraging. Results of recent, limited
studies suggest that corticosteroids such as prednisone are well
tolerated and may significantly reduce the duration of acute neuralgia
and improve quality of life; however, they have not been shown to
be efficacious in preventing postherpetic neuralgia.44 Inflammation
and scarring are reduced with anti-inflammatory agents. Despite
the uncertain effects of corticosteroid therapy on herpes zoster,
these drugs have been used extensively to treat this infection.
The role of anti-inflammatory drugs in acute herpes zoster is
controversial. If host responses contribute significantly to tissue
injury, then attenuation of these responses may be beneficial. Unfortunately,
the host defenses that cause tissue injury may be inseparable from
those that eliminate or prevent the spread of infection. Currently,
dissociation of protective from harmful host responses to the virus
has not been demonstrated clearly. However, in the immunocompetent
individual, a vigorous antiviral response is altered only very mildly
by corticosteroids. Similarly, in the presence of potent antiviral
therapy, even in the immunosuppressed patient, a reduction in the
inflammatory response eventually may be safe and have a salutary
effect. These are important issues for future investigation.
These drugs usually are administered in the first 10 days and
continued for as long as 3 weeks. Prednisone is usually the agent
of choice. It may be given orally in doses of 60 mg/day
the first week, 30 mg/day the second week, and 15 mg/day
the third week.
Corticosteroids also have been administered by subcutaneous injection
under affected skin, with and without a local anesthetic. Enthusiastic
anecdotal reports of large numbers of patients claim 80% to
100% success in treating acute herpes zoster, with a rapid
resolution of pain and diminished incidence of postherpetic neuralgia.
The experience of others has been less enthusiastic.
Major depression has been associated with a marked decline in
varicella-zoster virus–specific cellular immunity.1 Antidepressants
have two actions: they can relieve pain, and they can relieve depression.
Tricyclic drugs are known to block serotonin reuptake. Therefore,
they would be expected to enhance the action of this neurotransmitter
at synapses, and such enhancement can produce analgesia in laboratory
animals. One of the mechanisms active in central pain states is
some defect in the transmission system in the neuraxis; specifically,
a deficit in serotonin.
There is a strong consensus among clinical investigators that
centrally active antidepressants should be tried in any patient
who is not obtaining pain relief, whether or not he or she appears depressed.
Tricyclics and anxiolytics frequently are given together because,
although depression is not common in acute herpes zoster, many patients
experience anxiety along with the severe pain. The most widely used
combination is amitriptyline and fluphenazine. Amitriptyline alone has
been shown to significantly reduce pain in older patients by more
than one half, making a strong argument for its use with an antiviral
in this group of patients.45 In addition to their
antidepressant and analgesic properties, tricyclics are also sedatives
(for sleep regulation).
Amitriptyline and doxepin may correct the sleep disturbance,
frequent awakening, and early morning awakening that are common
in severe chronic pain states. Adverse side effects of tricyclic
antidepressants include hypotension or hypertension, tachycardia,
arrhythmias, drowsiness, confusion, disorientation, dry mouth, blurred
vision, increased intraocular pressure, urinary retention, and constipation.
It is thought that the host immune system is incompetent during
the acute outbreak. Vitamins, minerals, and improved general nutrition
may help improve the immunologic state or replace a missing element.
In a large group of patients, subcutaneous injections of triamcinolone
0.2% in normal saline have been administered under areas
of eruption and sites of pain and itching, with excellent results
and reduction of postherpetic neuralgia to a negligible percent.
Subcutaneous injections of corticosteroids and local anesthetics
offer an effective treatment for acute herpes zoster. The procedure
is not associated with any significant complications, the Y technique
is simple and inexpensive, and the response to treatment is fairly
predictable, as borne out by our own experience.
Because nerve root involvement is suspected in acute herpes zoster,
somatic nerve blocks have been used in its treatment. These can
include brachial plexus, paravertebral, intercostal, and sciatic
blocks. They are of limited value in the acute phase and of no value
in the postherpetic stage.
As understanding of the pathology of herpes zoster developed,
attention was directed toward the sympathetic ganglia. Sympathetic
blocks have been used to relieve the vasospasm that was thought
to cause the pain and nerve damage. Evidence suggests that sympathetic
blockade during the acute phase of herpes zoster can help the immediate
pain problem, often dramatically. Of greater value, however, is
the possibility that it can prevent the development of postherpetic
neuralgia. Although the evidence for this is less compelling, it
is probably a worthwhile prophylactic measure that should be used
as early as possible.
Trigeminal herpes zoster has been treated with a bupivacaine
block of the ipsilateral stellate ganglion.
Sympathetic blocks have been very successful in treating herpes
zoster, with just one block often proving to be effective. However,
success depends on administration within the first 2 or 3 weeks after
onset of the outbreak. The incidence of success decreases thereafter.
This therapy also apparently prevents lesions from progressing into
the postherpetic syndrome, at least in younger patients.
Epidural blocks using local anesthetic have been successful in
acute herpes zoster.46 The duration of the infection
is shorter, the lesions dry faster, and the pain is relieved.
Spinal blocks usually are not indicated because they are not
as specific as epidural blocks. A patient who has had a laminectomy
in the affected area would be an exception to this general rule. The
use of lumbar plexus blockade has been reported to relieve pain
in an elderly patient for whom other approaches were contraindicated.47
Neurolytic blocks are not indicated in acute herpes zoster.
Complications that may result from any nerve block procedure
include pain, local hemorrhage, infection, needle soreness, sterile
abscess (usually in the immunosuppressed patient), vertigo, and Cushing’s
Because the acute phase of herpes zoster is short, psychological
interventions are not mandatory. However, some patients (especially
those with severe anxiety and fear) benefit from a support program.
Some studies show that interventions such as psychotherapy can also
positively affect certain components of the immune response.48–50 A
regimen consisting of psychological support, administration of antiviral
agents, and patient education has been described by one author as
the “. . best available option for
the management of herpes virus infections.”51
Usually, transcutaneous electrical nerve stimulation (TENS) is
not used in the treatment of acute herpes zoster. However, results
of a preliminary, randomized, single-blind study suggest that a new
form of electroanalgesia—percutaneous electrical nerve
stimulation—may be useful in treating acute herpes zoster
lesions.52 Ice therapy is a counterirritation technique
based on the gate-control theory. It sometimes is used alone in
the acute stage to cool the area. Acupuncture and hypnosis usually
are not used in the treatment of acute herpes zoster because other
conventional methods are more appropriate. Surgery and neurosurgery
are not indicated. The acute stage is self-limited and does not
require such drastic measures. Autohemotherapy has been shown to
be effective in eliminating clinical sequelae of herpes zoster,
but this alternative method requires further investigation.53
It is useful to categorize affected patients according to their
immune status and age (Table 40-5). This allows the clinician to
direct efforts toward all or either antiviral, anti-inflammatory,
or antinociceptive effects, based on the probability of success
and risk factors involved. These patients can be categorized into
four groups: (1) immunocompetent young, (2) immunocompetent older, (3)
immunosuppressed young, and (4) immunosuppressed older patients.
Table 40-5 Therapeutic
Strategy for Acute Herpes Zoster ||Download (.pdf)
Table 40-5 Therapeutic
Strategy for Acute Herpes Zoster
|Type of Patient||Age (years)||Antiviral||Anti-inflammatory||Pain Relief|
|Young immunocompetent||< 50||–||–||Sympathetic block|
|Older immunocompetent||> 50||–||+||Epidural, somatic, and/or sympathetic block—helpful|
|Young immunosuppressed||< 50||++||–||Systemic narcotics|
|Within 72 h|
|Older immunosuppressed||> 50||+||±||Nerve blocks + systemic oral analgesics; adjuvant oral analgesics|
|Within 72 h|
Patients in this group have no defined underlying illness, are
younger than 50 years of age, and have normal immunologic responsiveness.
Although they have acute herpes zoster, their reaction to the infection
is brisk, enabling them to confine the rash in the initial unit.
Likewise, postherpetic neuralgia does not occur. The acute morbidity
is low, and healing is rapid. The rationale for treatment of this
group of patients is to relieve their intolerable pain and prevent
inflammatory damage of the tissues. Antiviral agents administered
during the first 72 hours may be helpful in stopping the replication
of the virus and spreading the infection to the peripheral nerves.
Anti-inflammatory agents (i.e., corticosteroids administered locally
or systematically) are useful in decreasing tissue damage and keeping
the inflammatory reaction of the host to a minimum. The obligatory
treatment is to decrease the severe pain of neuralgia. This is best
done using sympathetic or epidural blocks in the first 3 to 4 weeks
after onset of infection. Antidepressant agents also are helpful
as adjuvant agents.
The major objective of therapy in this group is to prevent postherpetic
neuralgia. Although suffering no underlying disease, the response
to varicella-zoster virus in this group may be less vigorous than
in young patients, leading to a slower viral clearance and perhaps
a higher incidence of spread beyond the initial unit of infection.
Nonetheless, nervous system and visceral complications are still
infrequent and, by themselves, probably do not warrant the use of
potentially toxic therapy at this time. However, both antiviral
and anti-inflammatory therapies may be valuable in preventing postherpetic
neuralgia. Of these, the latter has been shown prospectively to
be effective in this group of patients. It is reasonable on the
basis of the current evidence to treat older patients with acute
herpes zoster who are immunologically normal with a limited course
of corticosteroids (e.g., 60 mg of prednisone or its equivalent
daily for 5 days, tapering the dose over the following 2 weeks).
The value of antiviral agents in this group of patients has not
been tested carefully, although one trial suggested no effect in
the incidence of persistent pain in patients treated with acyclovir despite
an effect on acute pain. This issue deserves careful study. A four-treatment-arm
study of the individual and combined effects of antivirals and corticosteroids
is needed. At this point, antiviral therapy in this group probably
is indicated only in an investigative setting. Pain relief should be
addressed in these patients. Conventional narcotics should be avoided
because these patients are usually older and frail. In addition,
there is a high incidence of postherpetic neuralgia. Non-narcotic
analgesics in association with nerve blocks (epidural and sympathetic
blocks or local intracutaneous infiltration with bupivacaine and
corticosteroids) are recommended.
The principal concern in immunodeficient younger patients is
the spread of the virus in and outside the primary ganglion-nerve-dermatome
unit. Postherpetic neuralgia is not a major issue. Therapy, therefore,
is directed at confining the viral infection. Currently, acyclovir
is available, is of proven efficacy, and can be recommended for
patients. It seems reasonable to recommend hospitalization for patients
in this group who are at greatest risk of developing complications,
particularly those with lymphoproliferative disease or early dissemination.
It also must be emphasized that, if therapy is given, every effort
should be made to start treatment early. When newer agents become
available, they will require similar consideration, with their convenience,
cost, and toxicity weighted against the magnitude of their potential
benefit. It can be predicted, however, that, when other oral drugs
are introduced, their efficacy proved, and their toxicity demonstrated
to be low, the indications for treatment will expand. The clinical
decision to administer these drugs to this group of patients would
be an easy one, with virtually all patients in this group routinely receiving
such treatment. Pain relief in such patients should be obtained
by the techniques that are common for acute pain management.
In this group of patients, therapeutic objectives include prevention
of both viral spread and postherpetic pain. As discussed previously,
antiviral therapy may be helpful in both respects. Acyclovir has
been effective in reducing infection, and it may reduce postherpetic
pain. The latter requires additional confirmation. More importantly,
because of the risk of viral dissemination, patients in this group
require antiviral treatment. However, the use of corticosteroids
to prevent postherpetic neuralgia warrants separate comment. In
older immunocompetent patients, corticosteroids appear to cause
no special risk and to be therapeutically beneficial; but in the
immunosuppressed individual, greater caution is required. These
patients are more susceptible to viral spread and central nervous
system and visceral complications. Corticosteroids may impair their
remaining defenses below a critical level, increasing the risk of
these complications. Data from a collaborative study suggest that
corticosteroids did not protect against postherpetic pain in this
group. This issue must be investigated separately, particularly
to consider the effects of combined antiviral and corticosteroid
therapy. If potent antiviral coverage were available, corticosteroids
might be safe. Pain relief is best provided by nerve blocks.
purpose governs the role of drug therapy in the patient with postherpetic
neuralgia: (1) to provide analgesia for pain, (2) to reduce depression
and anxiety, and (3) to decrease insomnia. Because a considerable
degree of depression, anxiety, and insomnia accompany all chronic pain
syndromes, hypnotics, tranquilizers, antidepressants, and anticonvulsants
frequently have been used as analgesic adjuvants in the management
of postherpetic neuralgia. These include the barbiturates, rauwolfia
alkaloids, phenothiazine derivatives, benzodiazepines, amphetamines,
tricyclic antidepressants, phenytoin, and carbamazepine.
Table 40-6 Drug Therapy for Postherpetic Neuralgia
It is important to warn the patient of the potential side effects
of any drug. The patient is less likely to stop taking the prescribed
medication if he or she knows that certain unpleasant effects are
expected as a normal occurrence and that they usually are not permanent.
However, it is equally important for the physician to adopt a
positive approach regarding the medication. On average, 35% of
patients benefit significantly from the placebo effect. This can
be used to advantage by describing enthusiastically the desirable
effects of each drug which, with time, may be obtained. Patients
also are less likely to stop taking their medication before it has had
time to provide the desired effect.
As a rule, antiviral agents are inappropriate in the treatment
of postherpetic neuralgia. An exception may include their use to
prevent the possible recurrence of herpes zoster infection in a
susceptible patient. For example, the patient with Hodgkin’s
disease is predisposed to recurrent herpes zoster; antiviral agents
may be given before treatment of the primary disease (chemotherapy
and radiation therapy) when reactivation of the virus is most likely.
These drugs may be required to control the severe intractable
pain of postherpetic neuralgia. Narcotics should be used with extreme
caution, if at all, because (1) they are addictive; (2) the problem
is chronic; (3) these patients usually are not terminally ill; (4)
the side effects, such as nausea, loss of appetite, and constipation,
usually make these patients miserable; (5) there may be adverse drug
interactions with antidepressants and other drugs; and, (6) most
importantly, adequate pain relief may be obtained with other drugs.
The temporary initial use of narcotics to relieve extreme pain may
be necessary, however, until the patient begins to respond to therapy.
Antidepressants and tranquilizers frequently are used in conjunction
with analgesics. Some patients become depressed as a reaction to
their pain. The signs of depression may be so subtle that they easily
are missed. As many as 90% of patients may be depressed.
Approximately 85% of these patients will respond to antidepressant
Tricyclic antidepressants are the most commonly used drugs, and
they are the most effective single drug class used in the management
of postherpetic neuralgia. Antidepressants may act at a higher level
than the neurotransmitters, perhaps on pressure molecules in the
hypothalamus or pituitary. This could explain why only some depressed
patients fit the catecholamine hypothesis (i.e., a deficit of serotonin
or norepinephrine is the cause of the problem). Both chronic pain
and depression may represent neurotransmitter deficiencies, and
the antidepressants may restore these to normal levels. These drugs
should be given in appropriate doses, and several should be tried before
concluding that there is no response.
Topical application of a local anesthetic plus a tricyclic antidepressant
can be effective.14,15
Tricyclics and anxiolytics commonly are given together because
many patients have anxiety with their depression. This feeling may
be caused by anticipation of painful spasms, social obligations that
may exacerbate the pain by increasing stress, fear of having a painful
episode in public, or fear that the pain may never leave. Many patients
who did not obtain relief with tricyclics alone may benefit when
a phenothiazine is added. For lasting pain relief, treatment must
be continued throughout life. The usual recommended doses are as
follows: amitriptyline, 50 to 75 mg/day, and fluphenazine,
1 mg three or four times a day.
As a last resort, immediate relief has been obtained in some
hospitalized patients who had not responded to any other therapy
with a short course of high-dose chlorprothixene, 50 mg every 6 hours
for 5 days. Because this protocol requires hospitalization and is
associated with adverse effects, this treatment is recommended only
if all other methods fail and if the pain is severe, because pain
often returns in a few weeks or months.
Anticonvulsants sometimes are useful when other medications have
failed. Phenytoin, 100 mg three to four times a day, or carbamazepine,
500 to 1000 mg daily in three to four divided doses, can be used
to relieve sharp pain.
Sodium valproate, 200 mg twice a day, and amitriptyline, 10 to
25 mg twice a day, have been successful. If the stabbing component
of pain continues, the dose of amitriptyline can be increased. The
dull-ache component of the pain is most resistant to therapy. If
it persists, the scar can be infiltrated with a local anesthetic
and corticosteroids, or TENS, can be started.
Gabapentin has been shown to effectively reduce pain and sleep
interference and improve mood and quality of life in patients with
postherpetic neuralgia and those with painful neuropathy.54,55 Maximum
dosage administered was 3,600 mg/day.
The side effects of anticonvulsants tend to limit their use.
These include bone marrow depression, ataxia, diplopia, nystagmus,
abnormal liver function tests, nausea, lymphanadenopathy, confusion,
This drug depletes substance P from sensory nerve endings in
the skin and has been used topically for various dermatologic diseases.
Intravenous lidocaine has been advocated for the treatment of
many types of chronic neurogenic pain, including postherpetic neuralgia.
The oral antiarrhythmics (e.g., mexiletine) have been tried, and
reports are encouraging. However, definitive studies on the efficacy
of oral antiarrhythmics for the treatment of postherpetic neuralgia
The pathogenesis of postherpetic pain is unknown. Autopsy studies
have shown that the entire sensory pathway, including the brain
and sympathetic ganglia, may be involved. There appear to be multiple
areas along this pathway that can initiate pain. This provides a
rationale for the various methods of treatment and an explanation
of treatment failures.
Analgesic blocks can be used as prognostic, therapeutic, and
prophylactic tools in managing pain. As prognostic tools, blocks
help predicts the effects of prolonged interruption of nerve pathways achieved
through injection of neurolytic agents or surgery. By interrupting
pain pathways, therapeutic blocks influence the autonomic response
to noxious stimulation. They break the cycle of this disease. Patients
with severe intractable pain who are not suited to other treatment
regimens may be relieved by blocks with neurolytic agents.
Subcutaneous infiltration of corticosteroids has been used; pain
relief was obtained in approximately 64% of patients. A
solution of triamcinolone 0.2% in normal saline was injected
daily under all areas of pain, burning, or itching until the desired
effect was obtained. Maximum benefit was achieved in the first 12
treatments. In a comparison study, subcutaneous infiltration of
bupivacaine 0.25% and triamcinolone 0.2% was used,
alone or in conjunction with systemic medication and sympathetic
blockade. Overall results showed moderate to significant improvement
in 70% of patients. A difference in response to treatment
was noticed in relation to duration of symptoms; patients with symptoms
for less than 1 year responded better (85% success) than
patients with symptoms for more than 1 year (55%).
Subcutaneous infiltration of corticosteroids can offer an effective
treatment for postherpetic neuralgia. No significant complications
have been recorded, the technique is simple and inexpensive, and
the response to treatment is fairly predictable. Most importantly,
it offers relief for some patients with postherpetic neuralgia of
many months’ duration.
The total number of such treatments ranges from one to ten (average,
four to six injections). In acute herpes zoster, treatments usually
are given two or three times weekly and tapered to one per week,
if the patient is responding well.
Nerve root involvement is an obvious characteristic of postherpetic
neuralgia, and sensory nerve blocks were used in early attempts
to relieve its pain. The results were limited, depending primarily
on the duration of the blocks, although there were some reports
of success in managing pain in the early stages of the disease.
Coincidental spontaneous resolution may have been responsible. Nerve
blocks primarily are used in postherpetic neuralgia for diagnosis
and prognosis, especially as a prognostic block before neurolytic
block. Corticosteroids injected around the dorsal nerve have had
unpredictable and limited success.
Sympathetic blocks are sometimes helpful in alleviating pain,
although results are sometimes temporary and may only be obtainable
in patients with neuralgia of less than 2 months’ duration. Sympathetic
blocks of the stellate ganglion and trigeminal branch blocks often
are used to treat trigeminal zoster.
Epidural corticosteroid administration has been successful in
treating various lumbosacral conditions. For instance, epidural
nerve blocks often are used to treat zoster in the fifth cervical
Neurolytic blocks may be considered when other blocks have not
given the patient significant relief. They should be performed only
after a prognostic block has shown that an effective block of the
appropriate can be achieved. Neurolytic agents are used in cases
of prolonged destruction of nerves. These blocks include ethyl alcohol
50% in aqueous solution, absolute alcohol 95% in aqueous
solution, and phenol 6%. Ethyl alcohol causes a higher
incidence of neuritis than phenol. This is primarily a result of
incomplete peripheral nerve block after inaccurate needle placement or
spillage of the agent on somatic nerve fibers. The duration of effects
may vary from days to years, but usually it ranges from 2 to 6 months.
Ammonium compounds also can be used for peripheral nerve block.
Pain relief follows selective destruction of unmyelinated C fibers
by the ammonium ion. A solution of ammonium sulfate 10% in
lidocaine 1% or ammonium chloride 15% is used.
The duration of action ranges from 4 to 24 weeks. Neuritis does
not occur with either ammonium sulfate or chloride. The most annoying
side effect is numbness, which can be as bad as the pain for some
Cryoanalgesia also has been used as a means of producing long-term
It is especially important in patients with postherpetic neuralgia
to treat the whole patient and not just an area of the skin. The
emotional stability of the patient almost always is affected, and
the stresses involved for the patient and all members of the household
require thoughtful management.
Severe depression is seen in more than 50% of these
patients and, as previously noted, suicide commonly is considered
by those with long-term intractable pain. Counseling by a psychologist or
clinical social worker who is experienced in pain management is
a valuable adjunct to drug therapy. Training the patient in stress
management and relaxation techniques is important. Anxiety and stress
can exacerbate and prolong the pain. By practicing these techniques,
the patient may be able to control pain to some degree.
In some patients, the pain-tension-anxiety cycle can convert
acute pain symptoms into a chronic condition. Often, no matter what
is done to treat these patients, the pain is not relieved unless
the stress factors also are removed. Basically, two types of persons
are susceptible to chronicity: the tense, hard-driving, conscientious
perfectionist, and the dependent individual unable to cope with life
but burdened with repressed anger and hostility. Reinforcement of
the patient’s response to pain (such as moaning, grimacing,
asking for medication, and remaining in bed) or favorable consequences
of the pain (such as attention and expressions of sympathy, perhaps
also the occasion to manipulate others) may lead to chronic behavior
that, eventually, is independent of the original underlying pathologic
The most important guideline in preventing chronicity is complete
honesty. Make patients aware of the relationship between the psyche
and pain, and relieve them of the fear of organic disease. After
the patient fully accepts the emotional causes of pain, he or she
can learn to relieve the pain by controlling anxiety and tension.
Family and friends should be included in counseling sessions.
They, too, must cope with the pain a loved one is experiencing.
The counselor not only can ease their anxiety but also can teach
them how to provide effective emotional support to help the patient
endure an extremely difficult period. Concentrating on the special
needs of families may require extra effort on the part of the staff,
but it should result in a greater number of patients who recover
with the physical and emotional well-being of the family intact.
Many patients are elderly and live alone. They are unable to
turn to family and friends to provide the assistance they need for
routine daily tasks. The counselor should contact appropriate social service
agencies to provide transportation and other necessities (such as
prepared meals, grocery shopping, housework, and regular contact
with the patient to check on his or her well-being).
Because many patients continue to have some residual pain of
varying degrees that can be aggravating, they may require management
with other techniques. The following techniques are used when all
others fail (Table 40-7).
Table 40-7 Other Therapies
for Postherpetic Neuralgia ||Download (.pdf)
Table 40-7 Other Therapies
for Postherpetic Neuralgia
|Transcutaneous electrical nerve stimulation|
|Cryocautery with dry ice|
|Surgery and neurosurgery|
This has been used in an attempt to relieve the intractable pain
of postherpetic neuralgia. Although the success rate is low, relief
can be sufficient to permit a return to normal activity without
Ice and Other
Ice is applied to the skin for 2 to 3 minutes several times a
day, starting with the least sensitive area and approaching the
most sensitive area. A vibrator then is used in the same manner
in conjunction with psychotropic drugs. Ethyl chloride, or other
cold sprays, can be used alone as treatment. Fluid is sprayed over
the entire painful area, beginning at the upper area and working
down. Evaporation cools the area. The procedure is repeated twice
at 1-minute intervals until the skin is thoroughly cooled. When
beneficial, these treatments will relieve pain for varying lengths
of time. When pain returns to near its former intensity, the treatment
can be repeated. If the patient responds satisfactorily, the pain
is relieved by two or three sets of sprays per day. Good-to-excellent
pain relief has been maintained in patients with refractory postherpetic
pain using cryocautery with a stick of solid carbon dioxide (dry
ice) applied directly to the hyperesthetic sites.
Significant pain relief has been obtained in patients with postherpetic
neuralgia treated with acupuncture. Further investigation is underway.
Hypnosis acts at the level of the cerebral cortex. Impulses are
sent down from higher centers to close the neurophysiologic gate
that controls pain. Pain relief through hyponosis is sometimes complete
but, more often, it is not. Hypnotism is reported to be helpful
in patients with chronic unbearable pain; this changes to bearable
discomfort by breaking up patterns of suffering.
The treatment value of this agent in postherpetic neuralgia is
unknown. It may be tried as a benign last resort. Only a few states
have approved this solvent for medical use.
Surgery is the last resort for the treatment of severe intractable
postherpetic pain. It is not always successful. More effective management
techniques learned in recent years have limited this option further.
Surgery usually attacks the pain pathway in stages at progressively
higher divisions. Because it was suspected that the origin of the
pain lay in the scar and peripheral receptors, wide excision and
skin graftings were tried. This was not found to be effective and
rarely is used today.
Rhizotomy of the somatic afferents and sensory root ganglia also
has had poor results. Investigators who have had some success recommended
that ablation include several segments above and below the affected
area. Sympathectomy has not been successful in treating postherpetic
Cordotomy has been used with good results. In most cases, however,
the pain returns. Early recurrence has been blamed on failure to
ablate all the nerves in the pathway, which resume function after
the swelling has decreased. Stereotactic ablation of the conducting
paths in the thalamus and mesencephalon and frontal lobotomy have
been used. These should be tried only in patients with short life
expectancies who have not had success with any other methods.
Because of the finality of surgery and the unpredictable results,
many surgeons in recent years have taken advantage of technologic
advances in other areas to replace destructive procedures. These
include electronic stimulators used to block transmission of nerve
impulses. An implantable electrode placed over the dorsal columns
of the spinal cord has been tried with some success. Deep brain
stimulators, which are patient activated, have been applied to the
mesencephalic medial lemniscus to block the pain-conducting systems
and stimulate endorphin secretion, the body’s natural pain
reliever. Good pain relief has been achieved in many patients.