Chapter 51 Herpes Zoster and Postherpetic Neuralgia

Question 1

Herpes zoster (“shingles”)

Answer 1

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

Question 2

postherpetic neuralgia (PHN) is diagnosed when

Answer 2

herpes zoster pain persists.

Question 3

A fundamental epidemiologic feature of zoster

Answer 3

a marked increase in incidence with aging.

Question 4

incidence of herpes zoster is significantly

increased in patients with

Answer 4

suppressed cell-mediated
immunity—including HIV, AIDS, certain cancers, organ transplants (especially bone marrow transplant), immunemediated
diseases, and immunosuppressive treatments— compared to immunocompetent individuals.

Question 5

The most important condition in the spread of VZV is the

Answer 5

primary chicken pox infection, but latent and reactivated VZV infections

Question 6

important reservoirs

of virus because VZV is more likely to reactivate in these groups

Answer 6

Latently infected elderly adults and immunosuppressed patients

Question 7

When zoster occurs, VZV can be transmitted during

Answer 7

the vesicular phase of the rash and cause primary infection

when there is contact with a seronegative individual

Question 8

A zoster exposure with a seropositive, latently infected individual
may result in a

Answer 8

subclinical reinfection and boost of

humoral and cellular VZV immunity, but it is unlikely to cause varicella or herpes zoster

Question 9

presentation of pain in herpes zoster

Answer 9

a prodrome of dermatomal pain precedes the appearance of the characteristic unilateral
rash.

Question 10

most commonly affected sites in herpes

zoster

Answer 10

Thoracic dermatomes

Question 11

The rash becomes vesicular after

Answer 11

several days, then forms a crust, and loss of all scabs usually
occurs within 2 to 4 weeks

Question 12

This acute herpes zoster pain

gradually resolves

Answer 12

before or shortly after rash healing in

most cases.

Question 13

zoster sine herpete

Answer 13

Dermatomal pain without a rash

Question 14

zoster sine herpete diagnosis

Answer 14

the finding of VZV DNA in the cerebrospinal fluid of patients with prolonged
radicular pain and no rash provides evidence of this syndrome

Question 15

In addition to acute pain, the morbidity of herpes zoster

includes

Answer 15

neurologic disorders and ophthalmologic, cutaneous, and visceral complications.

Question 16

The types of neurologic

complications include

Answer 16

motor neuropathy, cranial polyneuritis,
transverse myelitis, meningoencephalitis, and cerebral
angiitis and stroke after ophthalmic zoster

Question 17

Ophthalmologic

complications

Answer 17

including keratitis, uveitis, iridocyclitis,

panophthalmitis, and glaucoma

Question 18

The main goals of the treatment of herpes zoster are to

Answer 18

relieve acute pain and prevent postherpetic neuralgia.

Question 19

Treatment of herpes zoster patients with

Answer 19

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

Question 20

antiviral therapy

is recommended as first-line treatment in herpes zoster patients who are

Answer 20

aged 50 years and older, have moderate or severe rash, have moderate or severe pain, have ophthalmic
involvement, or are immunocompromised.

Question 21

How then can
acute pain and the risk of chronic pain be further reduced,
beyond that currently achieved by antiviral therapy?

Answer 21

Corticosteroids, opioids, gabapentin, tricyclic antidepressants,
and neural blockade have been investigated or considered as strategies to achieve these goals

Question 22

neural blockade

Answer 22

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.

Question 23

For patients with moderate to severe pain

Answer 23

treatment with a strong opioid analgesic (e.g., oxycodone) is recommended in combination
with antiviral therapy.

Question 24

If moderate to severe pain in patients with herpes zoster has not responded rapidly to
treatment with an opioid analgesic and antiviral therapy, then

Answer 24

the addition of a corticosteroid can be considered.

Question 25

For patients with pain that is inadequately controlled by antiviral agents in combination with oral analgesic medications
and/or corticosteroids,

Answer 25

referral to a pain specialist or pain center is recommended to evaluate eligibility for neural blockade

Question 26

PREVENTION OF HERPES ZOSTER

Answer 26

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

Question 27

POSTHERPETIC NEURALGIA

Answer 27

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

Question 28

pain associated with herpes zoster has three

phases

Answer 28

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

Question 29

pain in PHN compared to herpes zoster

Answer 29

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.

Question 30

risk factors for PHN

Answer 30

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

Question 31

PATHOPHYSIOLOGY of PHN

Answer 31

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

Question 32

mechanisms may

contribute to PHN

Answer 32

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

Question 33

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

Answer 33

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.

Question 34

a first-line treatment for patients with PHN

Answer 34

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

Question 35

The initial choice of these medications for PHN should be guided
by

Answer 35

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

Question 36

Gabapentin

Answer 36

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.

Question 37

Side effects of gabapentin

Answer 37

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

Question 38

To reduce side effects and increase patient compliance with treatment, gabapentin should be

Answer 38

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.

Question 39

High-concentration capsaicin patch.

Answer 39

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.

Question 40

Lidocaine patch 5%

Answer 40

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.

Question 41

Treatment with the lidocaine patch 5% consists of

Answer 41

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.

Question 42

The lidocaine patch 5% is not approved for patients with

Answer 42

herpes zoster, and it should
not be used in patients with open lesions because the available
formulation is not sterile

Question 43

Opioid analgesics

Answer 43

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.

Question 44

The most common side effects of opioid analgesics

Answer 44

constipation, sedation, and nausea, as well as cognitive
impairment and problems with mobility can occur in
elderly patients.

Question 45

tolerance

Answer 45

a reduction in analgesic

benefit over time)

Question 46

physical dependence

Answer 46

withdrawal symptoms develop with abrupt discontinuation

or rapid dose reduction

Question 47

dosing of opioid

Answer 47

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.

Question 48

Pregabalin

Answer 48

similar in structure to gabapentin and has demonstrated efficacy in PHN

Question 49

common adverse effects of pregabalin

Answer 49

Dizziness, somnolence, peripheral edema,

amblyopia, dry mouth and gait disturbances

Question 50

Pregabalin doses

Answer 50

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

Question 51

Tramadol

Answer 51

a norepinephrine and serotonin reuptake inhibitor with a major metabolite that is a mu
opioid agonist

Question 52

side effects of tramadol

Answer 52

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

Question 53

Serotonin

syndrome may occur if tramadol is used concurrently with

Answer 53

other serotonergic medications, especially selective serotonin
reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors

Question 54

Tramadol may cause or exacerbate cognitive

impairment

Answer 54

in the elderly, and dosage adjustment is necessary in patients with renal or hepatic disease

Question 55

To decrease the likelihood of side effects, tramadol

should be initiated at

Answer 55

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

Question 56

Tricyclic antidepressants

Answer 56

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

Question 57

amitriptyline is poorly tolerated and contraindicated in

Answer 57

elderly patients

Question 58

Despite the efficacy of TCAs in the treatment of PHN, their cardiac toxicity and side effect profile require considerable caution

Answer 58

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

Question 59

Side Effect of TCA

Answer 59

Dry
mouth is the most common side effect, and constipation,
sweating, dizziness, disturbed vision, and drowsiness

Question 60

To decrease side effects, all TCAs should be initiated at

Answer 60

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.

Question 61

selective serotonin reuptake inhibitors and selective serotonin and norepinephrine
reuptake inhibitors tx in PHN

Answer 61

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

Question 62

combination therapy

Answer 62

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

Question 63

Invasive treatments may be considered when patients have

failed to obtain adequate relief from other treatment approaches

Answer 63

These include sympathetic nerve blocks, which may provide temporary relief in patients with PHN but
typically do not provide longer-lasting benefits

Question 64

intrathecal administration of methylprednisolone

Answer 64

not approved by the FDA and the wellknown
risks of intrathecal steroids include neurologic
complications and adhesive arachnoiditis