Chapter 51 Herpes Zoster and Postherpetic Neuralgia Flashcards
KEY POINTS 1. Herpes zoster (shingles) is caused by reactivation of the varicella-zoster virus (VZV), which establishes latency in sensory ganglia after primary infection (chicken pox). 2. The characteristic unilateral dermatomal vesicular rash of herpes zoster heals within 2 to 4 weeks and is accompanied by pain in the majority of patients. 3. Older age is associated with an increased risk of herpes zoster because of an age-associated decline in VZVspecific cell-mediated immunity. 4. Antivi
Herpes zoster (“shingles”)
a viral infection that is accompanied by acute pain. Following a primary chicken pox infection, the varicellazoster virus (VZV) establishes latency in sensory ganglia
throughout the nervous system. Herpes zoster is the reactivation of the virus and its spread from a single dorsal root or cranial nerve ganglion to the corresponding
dermatome and neural tissue of the same segment
postherpetic neuralgia (PHN) is diagnosed when
herpes zoster pain persists.
A fundamental epidemiologic feature of zoster
a marked increase in incidence with aging.
incidence of herpes zoster is significantly
increased in patients with
suppressed cell-mediated
immunity—including HIV, AIDS, certain cancers, organ transplants (especially bone marrow transplant), immunemediated
diseases, and immunosuppressive treatments— compared to immunocompetent individuals.
The most important condition in the spread of VZV is the
primary chicken pox infection, but latent and reactivated VZV infections
important reservoirs
of virus because VZV is more likely to reactivate in these groups
Latently infected elderly adults and immunosuppressed patients
When zoster occurs, VZV can be transmitted during
the vesicular phase of the rash and cause primary infection
when there is contact with a seronegative individual
A zoster exposure with a seropositive, latently infected individual
may result in a
subclinical reinfection and boost of
humoral and cellular VZV immunity, but it is unlikely to cause varicella or herpes zoster
presentation of pain in herpes zoster
a prodrome of dermatomal pain precedes the appearance of the characteristic unilateral
rash.
most commonly affected sites in herpes
zoster
Thoracic dermatomes
The rash becomes vesicular after
several days, then forms a crust, and loss of all scabs usually
occurs within 2 to 4 weeks
This acute herpes zoster pain
gradually resolves
before or shortly after rash healing in
most cases.
zoster sine herpete
Dermatomal pain without a rash
zoster sine herpete diagnosis
the finding of VZV DNA in the cerebrospinal fluid of patients with prolonged
radicular pain and no rash provides evidence of this syndrome
In addition to acute pain, the morbidity of herpes zoster
includes
neurologic disorders and ophthalmologic, cutaneous, and visceral complications.
The types of neurologic
complications include
motor neuropathy, cranial polyneuritis,
transverse myelitis, meningoencephalitis, and cerebral
angiitis and stroke after ophthalmic zoster
Ophthalmologic
complications
including keratitis, uveitis, iridocyclitis,
panophthalmitis, and glaucoma
The main goals of the treatment of herpes zoster are to
relieve acute pain and prevent postherpetic neuralgia.
Treatment of herpes zoster patients with
the antiviral agents acyclovir, famciclovir, valacyclovir, and brivudin inhibits viral replication and has been shown to reduce the duration of viral shedding, hasten rash healing, and decrease the severity and duration of acute pain. Famciclovir, valacyclovir and brivudin offer more convenient dosing and
higher and more reliable blood levels of antiviral activity compared to acyclovir
antiviral therapy
is recommended as first-line treatment in herpes zoster patients who are
aged 50 years and older, have moderate or severe rash, have moderate or severe pain, have ophthalmic
involvement, or are immunocompromised.
How then can
acute pain and the risk of chronic pain be further reduced,
beyond that currently achieved by antiviral therapy?
Corticosteroids, opioids, gabapentin, tricyclic antidepressants,
and neural blockade have been investigated or considered as strategies to achieve these goals
neural blockade
Although treatment of herpes zoster patients with multiple epidural
injections or continuous epidural infusions is unlikely to be feasible in most settings, these data suggest that aggressive
analgesia can be effective in patients with herpes zoster
and ongoing moderate to severe pain.
For patients with moderate to severe pain
treatment with a strong opioid analgesic (e.g., oxycodone) is recommended in combination
with antiviral therapy.
If moderate to severe pain in patients with herpes zoster has not responded rapidly to
treatment with an opioid analgesic and antiviral therapy, then
the addition of a corticosteroid can be considered.
For patients with pain that is inadequately controlled by antiviral agents in combination with oral analgesic medications
and/or corticosteroids,
referral to a pain specialist or pain center is recommended to evaluate eligibility for neural blockade
PREVENTION OF HERPES ZOSTER
A live attenuated zoster vaccine induces significant increases
in the cellular immune response to VZV in older adults. cellular immunity to VZV declines with age
POSTHERPETIC NEURALGIA
any pain persisting after
rash healing to pain that has persisted at least 6 months after rash onset. PHN is a chronic pain syndrome that can last for years
and cause substantial suffering and reduction in quality of life
pain associated with herpes zoster has three
phases
an acute herpetic neuralgia that accompanies the rash and lasts for approximately 30 days after rash onset,
a subacute herpetic neuralgia that lasts from 30 to 120 days
after rash onset, and PHN, defined as pain that persists for at
least 120 days after rash onset
pain in PHN compared to herpes zoster
Sharp, stabbing pain was found to be more common in patients with zoster than in patients with PHN, whereas burning pain was more common in PHN patients and much less likely to be reported by patients with zoster.
risk factors for PHN
Older age is the most well-established risk factor for PHN. patients with more severe acute pain are at greater risk for PHN. patients have a painful prodrome before their rash appears and they have a greater risk of PHN than patients who did not have a prodrome. Greater severity and duration of the herpes
zoster rash are additional risk factors for the development of PHN
PATHOPHYSIOLOGY of PHN
More severe zoster
infections are accompanied by greater neural damage, and
it has been proposed that this neural damage contributes
prominently to the development of PHN
mechanisms may
contribute to PHN
the mechanism of allodynia in PHN is abnormal activity in preserved primary
afferent nociceptors that have been damaged by the varicella- zoster virus but that remain in continuity with their
central targets. Activity in these “irritable” nociceptors may initiate and then maintain a state of central sensitization in which input from large fiber afferents that respond to nonpainful mechanical stimuli causes allodynia
As opposed to patients with prominent allodynia, PHN patients with predominantly continuous pain were found to have sensory loss in the areas where they have the most
pain. This suggests that
continuous pain in PHN is caused by a different mechanism than allodynia, possibly involving central structural and functional changes accompanying
deafferentation. These may include a structural reorganization of the spinal cord that involves abnormal synaptic connections, as well as functional abnormalities resulting from deafferentation involving hyperexcitability
of dorsal horn neurons.
a first-line treatment for patients with PHN
tricyclic antidepressants (TCAs). gabapentin, high-concentration capsaicin patch, lidocaine patch 5%, pregabalin whereas opioid analgesics, TCA ,and tramadol are more typically 2nd-line treatments because they generally require greater caution in the often elderly patient with PHN
The initial choice of these medications for PHN should be guided
by
the adverse event profiles, potential for drug interactions, and patient comorbidities and treatment preferences, especially because there are no replicated data demonstrating superior effectiveness of one drug over another
Gabapentin
second-generation antiepileptic drug, was associated with a statistically significant reduction in daily pain ratings as well as improvements in sleep, mood, and quality of life at daily dosages of 1800 to 3600 mg in two large clinical trials.
Side effects of gabapentin
somnolence, dizziness, and (less often) mild peripheral edema, which
requires monitoring and possibly dosage adjustment but usually not treatment discontinuation. Gabapentin may
cause or exacerbate gait and balance problems and cognitive
impairment in the elderly
To reduce side effects and increase patient compliance with treatment, gabapentin should be
initiated at low dosages—100 to 300 mg in a single dose at bedtime or 100 mg 3 times daily—and then titrated by 100 mg 3 times
daily as tolerated.
High-concentration capsaicin patch.
a single treatment application may be associated with sustained reductions in pain that last for 2 to 3 months, the high-concentration capsaicin patch has the
potential to provide a novel addition to existing treatments
for PHN, which are typically administered 1 or more times each day.
Lidocaine patch 5%
a topical preparation that has excellent safety and
tolerability, and the only side effects involve mild skin reactions m(e.g., erythema, rash). Systemic absorption is minimal but must be considered in patients receiving oral Class I antiarrythmic drugs such as mexiletine.
Treatment with the lidocaine patch 5% consists of
application of a maximum of three patches daily for a
maximum of 12 hr applied directly to the area of maximal
PHN pain and allodynia, which typically overlaps the affected dermatome.
The lidocaine patch 5% is not approved for patients with
herpes zoster, and it should
not be used in patients with open lesions because the available
formulation is not sterile
Opioid analgesics
oral opioid analgesics
in PHN, controlled-release oxycodone titrated to a maximum dosage of 60 mg daily provided statistically significant benefits on pain, disability, and allodynia and controlled-release morphine titrated to a maximum dosage of 240 mg daily provided statistically significant benefits
on pain and sleep but not on physical functioning and mood.
The most common side effects of opioid analgesics
constipation, sedation, and nausea, as well as cognitive
impairment and problems with mobility can occur in
elderly patients.
tolerance
a reduction in analgesic
benefit over time)
physical dependence
withdrawal symptoms develop with abrupt discontinuation
or rapid dose reduction
dosing of opioid
treatment can begin with a shortacting medication at morphine oral equianalgesic dosages
of 5 to 15 mg every 4 hr as needed. After 1 to 2 weeks of treatment, the total daily dosage can be converted to an equianalgesic dosage of one of the available longacting opioid analgesics (i.e., controlled-release morphine, controlled-release oxycodone, transdermal fentanyl, levorphanol, and methadone) while the patient continues taking the short-acting medication on an as needed basis.
Pregabalin
similar in structure to gabapentin and has demonstrated efficacy in PHN
common adverse effects of pregabalin
Dizziness, somnolence, peripheral edema,
amblyopia, dry mouth and gait disturbances
Pregabalin doses
Pregabalin should be initiated at 150 mg/day in two or three divided doses. Frail older patients may require lower starting doses. The dose may be increased to 300 mg/day in two or three divided doses within 1 week depending on clinical response and any adverse effects. The maximum dose of 600 mg/day in two or three divided doses can be considered if the patient does not have adequate pain relief at the risk of significantly higher frequency of adverse effects
Tramadol
a norepinephrine and serotonin reuptake inhibitor with a major metabolite that is a mu
opioid agonist
side effects of tramadol
dizziness, nausea, constipation, somnolence, and
orthostatic hypotension. There is an increased risk of seizures in patients
treated with tramadol who have a history of seizures or who are also receiving antidepressants, opioids, or other drugs that can reduce the seizure threshold
Serotonin
syndrome may occur if tramadol is used concurrently with
other serotonergic medications, especially selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors
Tramadol may cause or exacerbate cognitive
impairment
in the elderly, and dosage adjustment is necessary in patients with renal or hepatic disease
To decrease the likelihood of side effects, tramadol
should be initiated at
low dosages—50 mg once or twice daily—and then titrated every 3 to 7 days by 50 to 100 mg/
day in divided doses as tolerated. The maximum dosage of tramadol is 100 mg 4 times daily; in patients aged over 75, the maximum dosage of tramadol is 300 mg daily
in divided doses
Tricyclic antidepressants
Amitriptyline
is clinically the most widely used TCA in PHN. nortriptyline demonstrated equivalent efficacy to amitriptyline but was better tolerated.
desipramine may be used in patients who experience excessive
sedation with nortriptyline
amitriptyline is poorly tolerated and contraindicated in
elderly patients
Despite the efficacy of TCAs in the treatment of PHN, their cardiac toxicity and side effect profile require considerable caution
when treating older patients with PHN. All TCAs must be used very cautiously in patients with a history of cardiovascular disease, glaucoma, urinary retention, and autonomic neuropathy, and a screening EKG to check for cardiac conduction abnormalities is recommended before beginning TCA treatment, especially
in patients over 40 years of age. TCAs must be used cautiously
when there is a risk of suicide or accidental death from overdose, and TCAs may cause balance problems and
cognitive impairment in the elderly
Side Effect of TCA
Dry
mouth is the most common side effect, and constipation,
sweating, dizziness, disturbed vision, and drowsiness
To decrease side effects, all TCAs should be initiated at
low dosages—10 to 25 mg in a single dose at bedtime— and should then be slowly titrated as tolerated. TCAs should
be titrated to dosages of at least 75 to 150 mg daily. For titration above 100 to 150 mg daily, blood levels and the
EKG should be monitored.
selective serotonin reuptake inhibitors and selective serotonin and norepinephrine
reuptake inhibitors tx in PHN
either selective serotonin reuptake inhibitors (e.g., fluoxetine, paroxetine) or selective serotonin and norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine) in PHN and so it is unknown whether these classes of antidepressant medications are efficacious in PHN
combination therapy
may provide
additional pain relief in some individuals with PHN who have responded to one or another agent. Disadvantages
of combination therapy include an increased risk of adverse effects as the number of medications is increased
Invasive treatments may be considered when patients have
failed to obtain adequate relief from other treatment approaches
These include sympathetic nerve blocks, which may provide temporary relief in patients with PHN but
typically do not provide longer-lasting benefits
intrathecal administration of methylprednisolone
not approved by the FDA and the wellknown
risks of intrathecal steroids include neurologic
complications and adhesive arachnoiditis
