|
INTRODUCTION |
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Background: Herpes zoster was
known to the ancient Greeks and Romans, but it was not until 1885 that von Bokey
noted the association between varicella zoster virus (VZV) and shingles. VZV is
the causative agent of both varicella (chickenpox) and herpes zoster (shingles).
Chickenpox is the primary infection, whereas herpes zoster represents
reactivation of previous infection.
Chickenpox is a common and generally benign illness of childhood that is
characterized by an exanthematous vesicular rash. Approximately 90% of US
children are exposed by age 15 years. Following this primary infection, VZV
becomes latent in dorsal root ganglia. Generally, a decrease in cellular
immunity is believed to trigger the reactivation of the virus.
Herpes zoster presents as a vesicular rash in a dermatomal distribution that
usually is associated with pain. After resolution of the acute eruptive phase,
patients may develop postherpetic neuralgia, a sometimes incapacitating pain
that can last for months.
ˇ@
Pathophysiology: VZ belongs to the herpes family, which
includes the herpes simplex viruses (HSV), cytomegalovirus (CMV), Epstein-Barr
virus (EBV), and human herpes viruses 6 and 7. It is the most infectious of the
human herpes viruses.
Once attached to target cells via specific receptors, the capsid penetrates
through the cell wall and releases the viral genome. Upon completion of viral
double-stranded DNA replication, capsid and membrane synthesis take place. After
the primary infection, the virus migrates along sensory nerve fibers and becomes
latent in satellite cells of dorsal root ganglia. It remains there for the
remainder of the patient's life. Zoster is caused by reactivation of the dormant
virus.
Reactivation typically occurs in elderly and immunocompromised patients when
cellular immunity is decreased. VZ reappears in neurons and satellite cells and
spreads to the skin through peripheral nerves. Skin biopsy specimens during the
acute phase of shingles reveal inflammation and partial denervation.
Inflammation, hemorrhagic necrosis, and neuronal loss also are observed in
dorsal root ganglia.
Inflammation in involved peripheral nerves can persist for months and lead to
demyelination, wallerian degeneration, and sclerosis. This can lead to scarring
of the dorsal root ganglia, peripheral nerves, and skin. In addition,
degenerative and inflammatory changes also can occur in the central nervous
system.
ˇ@
Frequency:
ˇ@
- In the US: Cumulative incidence is 20%, or an annual rate
of 3-5 cases per 1000 persons. Incidence increases with age and impaired
immune status. Second episodes occur in immunosuppressed hosts but are rare in
immunocompetent people. Most recurrent herpes zoster episodes actually are
dermatomal HSV. Immunosuppressed adults (human immunodeficiency virus [HIV]
infection and malignancy) have a much higher risk of zoster. Incidence in
adults with HIV infection is estimated at 3-4 episodes per 100 patient-years.
Approximately 45% of bone marrow transplant recipients have cutaneous or
visceral dissemination.
- Internationally: No accurate data are available, but
incidence likely is similar to that in the United States. Varicella tends to
occur at an older age in the tropics. In sub-Saharan Africa and south and
Southeast Asia, incidence of herpes zoster virus in association with HIV is
increasing.
Mortality/Morbidity: Cutaneous herpes zoster very rarely
causes fatality in patients who are immunocompetent but can be life threatening
in immunocompromised patients.
- Bone marrow recipients with visceral dissemination have a mortality rate
of approximately 10%.
- Long-term complications of ophthalmic zoster with corneal involvement
occur in over 20% of such patients and may result in blindness.
- Morbidity associated with postherpetic neuralgia increases with age.
Race: No clear predominance exists among any race or ethnic
group.
Sex: Although no significant sex predominance has been
observed in HZ, women may have increased risk of postherpetic neuralgia.
Age: All ages can be affected, but zoster primarily is a
disease of elderly people. Incidence and severity increase with age.
- People younger than 20 years - 0.4-1.6 cases per 1000 persons
- People aged of 20-50 years - 2.0-3.0 cases per 1000 persons
- People older than 80 years - 4.5-11.0 cases per 1000 persons
|
CLINICAL |
ˇ@ |
History: The clinical
manifestations of herpes zoster can be divided into the pre-eruptive phase
(pre-herpetic neuralgia), acute eruptive phase, and chronic phase (postherpetic
neuralgia).
- This phase is characterized by unusual skin sensations.
- As many as 80% of patients experience burning, itching, or paraesthesia
that typically is localized to a dermatomal distribution. These symptoms
usually last for several days but occasionally can last for longer than a
week before the cutaneous eruption appears.
- The burning pain prior to the characteristic eruptions may present a
diagnostic dilemma because it can simulate any number of painful conditions,
including migraine headache, cholecystitis, hepatitis, renal colic,
appendicitis, pleurisy, pulmonary embolism, or myocardial ischemia.
- During this time, patients also may experience malaise, myalgia,
headache, and fever.
- These symptoms may precede the eruptive phase by several days to a week
or more and gradually resolve as cutaneous eruptions appear.
- This phase is marked by the emergence of vesicular eruptions and
possible constitutional symptoms.
- Almost all adult patients experience pain (acute neuritis) during the
eruptive phase. A few experience severe pain, without any evidence of a
vesicular eruption (zoster sine herpete), and a small number of patients
have a characteristic eruption but do not experience pain.
- Crust formation and drying occur over 7-10 days and are followed by
resolution at 14-21 days.
- Patients are infectious until lesions are dried. Anyone who has not
previously had varicella is at risk of acquiring this readily transmitted
virus. Pregnant women and immunosuppressed patients have the highest risk of
serious sequelae.
- Herpes zoster may be the earliest clinical sign of acquired
immunodeficiency syndrome (AIDS); therefore, patients should be assessed for
HIV risk factors. HIV testing should be considered in patients younger than
40 years.
- Patients are not more likely to have an underlying malignancy.
- Chronic phase (postherpetic neuralgia)
- Postherpetic neuralgia is persistent or reoccurring pain lasting 30 or
more days after the acute infection or after all lesions have crusted.
- Pain resolves gradually in most patients but can persist for years.
- Most people report a deep, burning or aching pain, paraesthesia,
dysesthesia, hyperesthesia, or electric shock-like pains.
- The pain can be extremely severe and incapacitating, leading to
depression and even suicide.
- Postherpetic neuralgia and intractability of pain increase with age,
from 27% of untreated adults aged 55 years to 47% of untreated adults aged
60 years to 73% of untreated adults aged 70 years.
- Pain lasting for more than 1 year occurs in 48% of patients older than
70 years.
Physical: Presentation with a characteristic rash
facilitates making the diagnosis of herpes zoster. Other findings can include
lymphadenopathy and sensory changes.
- Paraesthesia or other sensory changes over a dermatomal distribution
- The initial rash presents as a swath of patchy, erythematous, swollen
plaques from which clusters of small vesicles arise. This eruption is
virtually diagnostic of shingles.
- The extent of dermatomal involvement varies among patients and may
involve all or part of a dermatome.
- It usually affects a single dermatome and rarely crosses the body
midline. Eruptions in a bilateral distribution are very rare.
- Patients may have as many as 25 vesicles distributed outside the
primarily affected dermatome; more than 25 lesions in noncontiguous
dermatomes suggests disseminated zoster.
- The vesicles arise in clusters and many become purulent by day 4.
Variation in size is common.
- Only be a few vesicles may be present initially, but successive
eruptions for 5-7 days may occur.
- Vesicles either umbilicate or erupt prior to drying and crusting. Crusts
will fall off within 3 weeks.
- In elderly and immunocompromised patients, the eruptive phase is longer
and more extensive. It occasionally results in hemorrhagic blisters, skin
necrosis, and secondary bacterial infections.
ˇ@
- Typically affected dermatomes include thoracic (56%), cervical (17%),
trigeminal nerve (12%), lumbar (10%), and sacral (5%).
ˇ@
- Hematogenous dissemination to the viscera or extradermatomal skin occurs
in 1-2% of immunocompetent patients but is more frequent in
immunocompromised patients.
- Herpes zoster ophthalmicus
- The trigeminal nerve (CN V) has 3 branches—ophthalmic, maxillary, and
mandibular. The ophthalmic nerve further divides into frontal, lacrimal, and
nasociliary nerves.
ˇ@
- Herpes zoster ophthalmicus occurs if involvement of any of the
ophthalmic branches occurs, and it accounts for approximately 7-10% of all
zoster cases.
ˇ@
- Furthermore, HZ may be confined to a single branch of the trigeminal
nerve.
- When the nasociliary branch is involved, vesicles appear on the tip or
side of the nose (Hutchinson sign). This presentation often is associated
with more serious complications and may lead to orbital involvement.
ˇ@
- Involvement of other sensory branches of the trigeminal nerve usually
results in periocular distribution with sparing of the orbit.
ˇ@
- Involvement of the eye presents with acute lesions of the globe and
orbit that develop within 3 weeks of the rash. They may rapidly resolve or
become chronic. These lesions can reappear years after the initial episode.
ˇ@
- Approximately 28% of people develop long-term sequelae.
ˇ@
- Complications resulting from inflammatory changes include keratitis,
episcleritis, iritis, ischemic papillitis, and orbital vasculitis.
ˇ@
- Nerve damage can include ocular motor palsies and neuralgia.
ˇ@
- Tissue scarring can include lid deformities, neuralgia, and lipid
keratopathy.
- Central nervous system involvement
- Latent VZV is restricted to the sensory ganglia.
ˇ@
- During reactivation, a direct invasion of adjacent structures may occur.
This may lead to involvement of the anterior horn neurons, resulting in
muscular weakness, cranial nerve palsies, diaphragmatic paralysis,
neurogenic bladder, and colon pseudo-obstruction.
ˇ@
- A further local invasion may result in myelitis with secondary
paraparesis, urinary retention, and other visceral motor neuropathies.
ˇ@
- The cerebrospinal fluid (CSF) may have pleocytosis and increased protein
content suggestive of CNS inflammation. While some of these patients may
have very mild encephalitis, most have only a headache. Significant
meningoencephalitis is rare.
- Also known as herpes zoster oticus, geniculate neuralgia, or herpes
zoster auricularis, it is caused by VZV reactivation involving the facial
and auditory nerves.
ˇ@
- It may present with hearing impairment; vertigo; facial nerve palsy
(mimicking Bell palsy); and vesicular eruptions on the pinna, in the
auditory canal, on the tympanic membrane, or occasionally on the hard
palate.
ˇ@
- Patients may lose taste sensation in the anterior two thirds of the
tongue.
ˇ@
- It accounts for more than 50% of the cephalic motor neuropathies.
ˇ@
- It may be unnoticed and difficult to diagnose, especially in elderly
patients.
- It is characterized by pain in a dermatomal distribution without vesicle
eruptions or other forms of rash.
ˇ@
- Prevalence is difficult to estimate because definitive diagnosis is
problematic.
ˇ@
- Viral detection by a polymerase chain reaction may be helpful in
establishing the diagnosis.
Causes:
- The cause of herpes zoster is the reactivation of VZV.
- No identifiable environmental, genetic, or social factors exist.
|
DIFFERENTIALS |
ˇ@ |
Herpes Simplex
Impetigo
Other Problems to be Considered:
Atopic dermatitis
Atypical measles
Poison ivy
|
WORKUP |
ˇ@ |
Lab Studies:
ˇ@
- Although usually diagnosed clinically, several laboratory tests are
available for confirmation, differentiation, and subtyping.
- Provides an inexpensive and rapid means for confirming suspected
infection and can be obtained readily in the office or at the bedside. It
does not distinguish between HZV and HSV.
- It is most sensitive when obtained from a new vesicle, followed by a
pustule, then by a crusted lesion. If a crusted lesion is used for smear
preparation, it will be necessary to remove the crust and make the smear by
scraping the base of the lesion.
- The slide can be fixed in alcohol and Papanicolaou stain. Other stains
include methylene blue, toluidine blue, Giemsa, and Wright.
- Under light microscopy, the pathognomonic triad includes multinucleated
giant cell formation, ground glass appearance of the nuclear chromatin, and
nuclear contours that appear molded together.
- A 1992 study demonstrated that, in the hands of experienced
dermatologists, a Tzanck smear has 84% sensitivity.
- Very sensitive in experienced hands
- Does not distinguish between HZV and HSV
ˇ@
- Not readily available due to cost and therefore has a limited role in
diagnosis
- Direct immunofluorescence with fluorescein-tagged antibody directed
against viral antigen
- Improved sensitivity and specificity as compared to the Tzanck smear in
vesicular lesions but is less sensitive in crusted lesions
ˇ@
- Rapid results
ˇ@
- Can differentiate HSV and HZV
ˇ@
- Requires a fluorescence microscope and an experienced technician
ˇ@
- Must be submitted frozen or fixed
- Immunoperoxidase techniques
- Can distinguish between HZV and HSV
ˇ@
- Relatively inexpensive and rapid
ˇ@
- Can be performed on both fixed and fresh specimens
ˇ@
- More labor intensive and less sensitive (sensitivity of 67%) than
immunofluorescence
- Serologic tests include Western blot analysis, complement fixation, and
neutralization test.
- Limited role in diagnosis
ˇ@
- Evaluation for VZV antibodies can be performed to verify immune status
but are not of diagnostic value in either varicella or zoster diagnosis.
- Viral culture remains the criterion standard for diagnosis of herpes
zoster.
ˇ@
- A high false-negative rate (20-80%) is due to inappropriate transport
conditions, sampling the wrong area of the lesion, and inadequate viral
concentration.
ˇ@
- Due to the poor sensitivity and lack of readily available virology
laboratories with VZV culture capability it generally is not useful.
- Polymerase chain reaction
- Polymerase chain reaction is rapid and highly sensitive.
ˇ@
- It can diagnose infection from a wide spectrum of specimens, such as
Tzanck smear debris, vesicle fluid, crusts, fixed tissue specimens, and CSF.
ˇ@
- Reported sensitivity is 97-100% but is somewhat lower with fixed-tissue
specimens.
ˇ@
- Contamination can lead to false-positive results. This can be minimized
by using controls and meticulous laboratory techniques.
ˇ@
- Due to its high sensitivity and specificity, rapid turn around time, and
versatility with a variety of specimens, it eventually may replace the older
laboratory tests for the diagnosis of herpes zoster.
Imaging Studies:
ˇ@
- Imaging studies are not useful in the diagnosis of shingles.
Procedures:
ˇ@
- Punch biopsy is useful when lesions are atypical.
- It is easier to interpret than the Tzanck smear.
- Punch biopsy is more invasive.
- Overall sensitivity and specificity are similar to the Tzanck smear.
Histologic Findings: During the acute phase, significant
inflammation of the skin, dorsal root ganglia, and peripheral nerves is present.
Evidence for early denervation of skin tissue, hemorrhagic necrosis, and
neuronal loss in dorsal root ganglia is present. Inflammatory changes may
persist for months and lead to scarring.
|
TREATMENT |
ˇ@ |
Medical Care: Medical therapy will
be discussed in 3 scenarios that include the treatment of acute herpes zoster,
prevention of postherpetic neuralgia, and treatment of postherpetic neuralgia.
- Topical therapy can include cool tap water compresses several times a
day, especially with extensive eruptions.
ˇ@
- Corticosteroids: Use is controversial because no conclusive evidence
indicates that steroids shorten the course of acute infection, decrease
pain, or have any effect on postherpetic neuralgia. One study demonstrated
that acute neuritis resolved more quickly in patients receiving high doses
of prednisone compared to patients who received a placebo or acyclovir.
Because corticosteroids have demonstrated some improvement in the quality of
life, their administration in combination with antivirals should be
considered for high-risk patients with no contraindications. The addition of
antiviral agents provides a reasonable safeguard against
corticosteroid-induced enhancement of viral replication.
ˇ@
- Injections: Lidocaine injections may eliminate pain during the eruptive
stage. Use higher concentrations (1%) for more severe pain. A combination of
triamcinolone and lidocaine has also been successful.
ˇ@
- Nerve blocks: Sympathetic nerve blocks are useful for treating pain. A
series of 3 injections with 0.25% bupivacaine is administered. Usually, fast
improvement in pain occurs, with total resolution by the third injection.
Although effective for immediate pain relief, no evidence indicates that
they prevent or treat postherpetic neuralgia.
ˇ@
- Antiviral therapy: Antiviral therapy is effective for acute cutaneous or
ophthalmic herpes zoster in immunocompetent patients. Therapy should be
initiated within 72 hours of onset.
ˇ@
- Acyclovir: Both oral and IV acyclovir have been shown to decrease
inflammation, vesicle formation, viral shedding, and pain during the acute
phase of infection. It is most effective when started within 48 hours of
onset. It always is indicated with ocular involvement or with
immunosuppressed and debilitated patients with extensive cutaneous
involvement. In immunocompromised patients, IV acyclovir is effective in
the treatment of disseminated herpes zoster. Therapy can be changed to
oral as they improve. Immunocompromised patients who receive long-term
acyclovir are predisposed to acyclovir-resistant herpes zoster. If
acyclovir resistance is suspected, obtain cultures for sensitivity testing
and treat with foscarnet.
ˇ@
- Valacyclovir: It is the prodrug of acyclovir with very high
bioavailability. It is as effective as acyclovir in during the acute
phase. It has a more convenient dosing regimen than acyclovir.
ˇ@
- Famciclovir: It is a prodrug of penciclovir. When taken orally, it is
as effective as acyclovir for treating uncomplicated cases. Like
valacyclovir, it provides the advantage of 3 times a day dosing, which may
improve compliance.
- Prevention of postherpetic neuralgia
- Analgesics: Some patients obtain relief from aspirin, NSAIDs, and
narcotic medications, but they generally have a limited role in the
treatment of neuropathic pain. In anecdotal reports, topical formulations of
aspirin; indomethacin and lidocaine; and locally injected lidocaine,
procaine, and mepivacaine have provided relief.
ˇ@
- Capsaicin: It is a chemical that depletes substance P (pain impulse
transmitter) and prevents its resynthesis with nerves. It is available
without a prescription. It can be applied daily but may cause moderate
burning during application. It has been shown to decrease postherpetic
neuralgia pain by 21% after 4 weeks.
ˇ@
- Neuroactive agents: Tricyclic antidepressants have an established role
in the treatment of postherpetic neuralgia. Amitriptyline provides
moderate-to-excellent pain relief. Desipramine also is effective. Early
treatment is almost twice as successful as late treatment. Treatment should
be started at low doses at bedtime and increased weekly until pain resolves
or adverse effects become unacceptable. Full results may not be evident for
weeks after the onset of treatment. Serotonin-selective reuptake inhibitors
and lorazepam have been studied but are of limited use.
ˇ@
- Anticonvulsant drugs: Agents such as phenytoin, valproate, carbamazepine,
and gabapentin have shown some benefit in the reduction of shooting pain but
no reduction of continuous pain. Nontraditional therapies such as
acupuncture, nerve stimulation, hypnosis, and biofeedback may be effective
with intractable pain. Emotional support is very important. Patients with
postherpetic neuralgia may become depressed and withdrawn.
Surgical Care:
- Surgical care should be reserved as the last treatment option.
- Candidates include patients with severe postherpetic neuralgia pain who
do not respond to any conventional therapy.
- In extreme cases of neuropathic pain when all other forms of medical
therapy fail, rhizotomy (surgical separation of pain fibers) may be
considered.
Consultations:
- Consultation with a dermatologist or infectious disease specialist should
be obtained if diagnosis is in doubt.
- Consult a pain specialist for severe postherpetic neuralgia.
Diet: No specific dietary changes are recommended.
Activity:
- Patients with shingles can perform activities as tolerated.
- During the acute phase, avoid direct skin contact with immunocompromised
persons, pregnant women, and individuals with no history of chickenpox
infection.
|
MEDICATION |
ˇ@ |
The goal of drug therapy is to suppress
inflammation, pain, and infection. Multiple drug regimens have been studied for
the treatment of acute herpes zoster and the neuropathic pain that persists
after the resolution of cutaneous eruptions (postherpetic neuralgia).
ˇ@
Drug Category: Antivirals -- Reduce pain and
time to lesion resolution during the acute phase of shingles and may reduce risk
or duration of postherpetic neuralgia.
Drug Name
ˇ@ |
Acyclovir (Zovirax) -- Synthetic purine
nucleoside analogue with inhibitory activity against HSV types 1 and 2 and
VZV.
Adjust dosage in patients with renal insufficiency.
|
Adult Dose |
800 mg 5 times per d PO for 7-10 d
500 mg/m2 IV or 10 mg/kg IV q8h for 7 d
|
Pediatric Dose |
Immunocompromised children:
250-600 mg/m2 PO 4-5 times per d PO for 7-10 d
500 mg/m2 IV or 7.5-10.0 mg/kg IV q8h for 7 d
|
Contraindications |
Documented hypersensitivity |
Interactions |
Concomitant use of probenecid or
zidovudine prolongs half-life and increases CNS toxicity of acyclovir |
Pregnancy |
B - Usually safe but benefits must
outweigh the risks. |
Precautions |
Exercise caution in renal failure or
when using nephrotoxic drugs |
Drug Name
ˇ@ |
Valacyclovir (Valtrex) -- Prodrug
rapidly converted to the active drug acyclovir. More expensive but has a
more convenient dosing regimen than acyclovir. |
Adult Dose |
1000 mg PO tid for 7 d |
Pediatric Dose |
Not established |
Contraindications |
Documented hypersensitivity |
Interactions |
Probenecid, zidovudine, or cimetidine
coadministration prolongs half-life and increases CNS toxicity of
valacyclovir |
Pregnancy |
B - Usually safe but benefits must
outweigh the risks. |
Precautions |
Caution in renal failure and
coadministration of nephrotoxic drugs; associated with onset of hemolytic
uremic syndrome; allogenic bone marrow transplant recipients and renal
transplant recipients |
Drug Name
ˇ@ |
Famciclovir (Famvir) -- After
ingestion, drug is rapidly biotransformed into active compound penciclovir
and phosphorylated by viral thymidine kinase. By competition with
deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral
polymerase.
Adjust dose in patients with renal insufficiency or hepatic disease.
|
Adult Dose |
500 mg PO q8h for 7 d |
Pediatric Dose |
Not established |
Contraindications |
Documented hypersensitivity |
Interactions |
Coadministration of probenecid and
cimetidine may increase toxicity of penciclovir; coadministration increases
bioavailability of digoxin |
Pregnancy |
B - Usually safe but benefits must
outweigh the risks. |
Precautions |
Adjust dose in renal insufficiency or
hepatic disease; not studied in immunocompromised patients or disseminated
disease |
Drug Name
ˇ@ |
Foscarnet (Foscavir) -- Pyrophosphate
analogue that is a noncompetitive inhibitor to viral DNA polymerase. Does
not require activation by thymidine kinase.
Adjust dosage for patients with renal insufficiency. |
Adult Dose |
Patients with normal creatine
clearance:
40 mg/kg IV q8h for 14-28 d as induction
|
Pediatric Dose |
Not established; 40 mg/kg IV q8-12h
suggested; benefits must outweigh risks
Do not exceed recommended dosage
|
Contraindications |
Documented hypersensitivity; creatine
clearance <0.4 mL/min/kg |
Interactions |
Avoid use of foscarnet in combination
with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV
pentamidine) unless potential benefits outweigh risks; coadministration with
IV pentamidine may cause hypocalcemia; pentamidine increases hypocalcemia
|
Pregnancy |
C - Safety for use during pregnancy has
not been established. |
Precautions |
May cause decline in renal function;
for correct dosing, obtain 24-h serum creatinine at baseline and continue to
monitor (discontinue if serum creatinine is <0.4 mL/min/kg); hydration may
reduce nephrotoxicity; carefully monitor electrolytes (eg, calcium,
magnesium); assess for electrolyte and mineral level abnormalities if mild
perioral numbness, paresthesias symptoms, or seizures occur;
granulocytopenia and anemia may occur (regularly monitor CBC); infuse
foscarnet solutions into veins with adequate blood flow to avoid local
irritation; to avoid toxicity do not administer by rapid or bolus IV
injection |
Drug Category: Corticosteroids -- Have
anti-inflammatory properties and cause profound and varied metabolic effects. In
addition, these agents modify the body's immune response to diverse stimuli. May
help reduce pain, but reports are inconclusive.
Drug Name
ˇ@ |
Prednisone (Deltasone) -- Decreases
inflammation by suppressing neutrophils and reversing increased capillary
permeability. Also suppresses immune system. |
Adult Dose |
10-50 mg PO qd |
Pediatric Dose |
Not established |
Contraindications |
Documented hypersensitivity; viral
infection; peptic ulcer disease; hepatic dysfunction; connective tissue
infections; fungal or tubercular skin infections |
Interactions |
Coadministration with estrogens may
decrease prednisone clearance; when used with digoxin, digitalis toxicity
secondary to hypokalemia may increase; phenobarbital, phenytoin, and
rifampin may increase metabolism of glucocorticoids (consider increasing
maintenance dose); monitor for hypokalemia with coadministration of
diuretics |
Pregnancy |
B - Usually safe but benefits must
outweigh the risks. |
Precautions |
Abrupt discontinuation of
glucocorticoids may cause adrenal crisis; hyperglycemia, edema,
osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis,
euphoria, psychosis, myasthenia gravis, growth suppression, and infections
may occur with glucocorticoid use |
Drug Category: Topical anesthetics -- Decrease
pain associated with postherpetic neuralgia.
Drug Name
ˇ@ |
Capsaicin (Dolorac, Capsin, Zostrix) --
Derived from plants of the Solanaceae family. May render skin and joints
insensitive to pain by depleting substance P in peripheral sensory neurons.
|
Adult Dose |
Apply to affected area tid/qid |
Pediatric Dose |
<2 years: Not recommended
>2 years: Administer as in adults
|
Contraindications |
Documented hypersensitivity; broken or
irritated skin |
Interactions |
None reported |
Pregnancy |
C - Safety for use during pregnancy has
not been established. |
Precautions |
For external use only; avoid contact
with eyes, mucous membranes, wounds, or damaged skin; do not use tight
bandage; discontinue use if condition worsens or symptoms persist for 14-28
d |
Drug Category: Tricyclic antidepressants --
Have been shown to have a role in the treatment of postherpetic neuralgia.
Drug Name
ˇ@ |
Amitriptyline (Elavil) -- Blocks
reuptake of norepinephrine and serotonin. Decrease pain by inhibiting spinal
neurons involved in pain perception. |
Adult Dose |
10-100 mg PO hs; dose can be titrated
slowly up to 300 mg PO hs |
Pediatric Dose |
0.1 mg/kg PO hs; may be increased
slowly to a maximum of 2 mg/kg PO hs |
Contraindications |
Documented hypersensitivity; taking
MAOIs in past 14 d; history of seizures; cardiac arrhythmias; glaucoma;
urinary retention |
Interactions |
Phenobarbital may decrease effects;
coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine and
quinidine) may increase amitriptyline levels; amitriptyline inhibits
hypotensive effects of guanethidine; may interact with thyroid medications,
alcohol, CNS depressants, barbiturates, and disulfiram |
Pregnancy |
D - Unsafe in pregnancy |
Precautions |
Caution in cardiac conduction
disturbances, history of hyperthyroidism, and renal or hepatic impairment;
avoid using in elderly patients |
Drug Name
ˇ@ |
Desipramine (Norpramin) -- Tricyclic
antidepressants block reuptake of norepinephrine and serotonin. Decrease
pain by inhibiting spinal neurons involved in pain perception. |
Adult Dose |
75 mg PO qd divided tid/qid initially;
gradually increase to a maximum dose of 300 mg qd
Elderly patients: 10-25 mg qd initially
|
Pediatric Dose |
1.5 mg/kg PO qd or in 2-4 equally
divided doses |
Contraindications |
Documented hypersensitivity;
narrow-angle glaucoma; recent postmyocardial infarction; patients currently
receiving MAOIs or fluoxetine patient who have taken them in the previous 2
wks |
Interactions |
Increases effect of sympathomimetics
and benzodiazepines; decreases effect of clonidine, phenytoin, carbamazepine,
and barbiturates; increases toxicity of anticholinergics, MAOIs, cimetidine,
CNS depressants, and alcohol |
Pregnancy |
C - Safety for use during pregnancy has
not been established. |
Precautions |
Caution in cardiovascular disease,
conduction disturbances, seizure disorders, urinary retention,
hyperthyroidism, and patients receiving thyroid replacement therapy |
|
FOLLOW-UP |
ˇ@ |
Further Inpatient Care:
ˇ@
- Inpatient care is recommended for immunocompromised patients, debilitated
patients with severe cutaneous involvement, and ophthalmic zoster.
- Any patient at risk for dissemination or requiring IV medications should
be admitted.
Further Outpatient Care:
ˇ@
- Follow up until symptoms resolve.
- Inform patients about the natural progression of herpes zoster and its
potential complications.
- Pain relief should be a primary concern.
- Patients who develop postherpetic neuralgia should be seen regularly and
should receive emotional support in addition to medical therapy.
Transfer:
ˇ@
- Patients with disseminated disease, severe immunosuppression, or those
unresponsive to therapy should be transferred to a higher level of care.
- If consultation is required but not available at the initial facility,
patients should be transferred to a tertiary-care medical center.
Complications:
ˇ@
- Although no clear predictive factors exist, this severe intractable pain
is the main cause of morbidity.
ˇ@
- It occurs in 73% of patients older than 70 years; incidence increases
with age.
ˇ@
- Most patients will improve eventually, but the pain may persist for
months to years.
- Immunocompromised patients are especially likely to develop disseminated
zoster.
ˇ@
- Mortality rates approach 25%.
ˇ@
- Besides cutaneous involvement, these patients may develop dissemination
to the brain, lungs, and other organs.
- Although acute lesions involving the globe or orbit of the eye can
resolve within a few weeks of treatment, they can become chronic.
ˇ@
- Patients can develop keratitis, episcleritis, iritis, papillitis,
vasculitis, ocular motor palsies, and nerve damage.
- Cranial nerve palsies, peripheral muscle weakness, diaphragmatic
dysfunction, neurogenic bladder, colonic pseudo-obstruction, and other
visceral neuropathies are possible complications.
ˇ@
- Significant encephalitis, although rare, carries a 10-20% mortality
rate.
ˇ@
- Minimally symptomatic aseptic meningitis is common.
- Immunosuppressed, elderly, and debilitated patients have a higher risk
of bacterial superinfections.
ˇ@
- More extensive skin involvement may result in hypertrophic scarring and
disfiguration.
Prognosis:
ˇ@
- The prognosis for younger and otherwise healthy patients is excellent.
- Elderly people have a significantly increased risk of complications,
including postherpetic neuralgia, bacterial infections, and scarring.
Patient Education:
ˇ@
- During the acute phase, patients are infective to others and should be
instructed to avoid contact with elderly people, people who are
immunocompromised, pregnant women, or people with no history of chickenpox
infection.
- Patients should be instructed to not scratch the lesions, which may
predispose to bacterial infections.
|
MISCELLANEOUS |
ˇ@ |
Medical/Legal Pitfalls:
ˇ@
- Misdiagnosis or failure to treat patients with involvement of the
trigeminal nerve may lead to long-term ophthalmic complications.
- Take special care with immunocompromised and debilitated patients. Err on
the side of admitting immunosuppressed patients and those with eye or
symptomatic CNS involvement.
|
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ˇ@ |
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