For 3 days, a 60-year-old woman has
had a tender rash on her forehead. The
lesions erupted 2 days after she sustained
minor trauma to the left side of
the forehead (Figure 1); no scratches
or bleeding were associated with the
injury. She noted a burning sensation
and mild tenderness at the site shortly
before the lesions arose.
The patient has no significant
medical history; she takes no medications
and did not receive the varicella
vaccine. She does not recall any similar
eruptions in the past anywhere on
Vesicles and crusts on an erythematous
base in a linear distribution are
present on the left aspect of the forehead
(Figure 2). The lesions do not cross the
midline. The eyes and the nasal apex
are not affected; lymph nodes are not
Herpes zoster ophthalmicus (HZO)
following trauma to the forehead is
strongly suspected. The diagnosis is confirmed
by polymerase chain reaction
(PCR) for varicella zoster virus (VZV)
DNA. Oral valacyclovir, 1000 mg tid, is
Seven days later, the pain has subsided
and a crust has formed on the
forehead at the site of the vesicles (Figure
3). Post-herpetic neuralgia has not
HZO--cutaneous lesions in the
dermatome associated with the ophthalmic
division of the trigeminal
nerve (cranial nerve V1)--results from
reactivated VZV that travels down the
ophthalmic nerve from the trigeminal
ganglion; the virus reaches the nerve
endings within 3 to 4 days.1,2 Cranial
nerve V1 comprises the frontal nerve;
the lacrimal nerve; and the nasociliary
nerve, which provides sensory innervation
to the cornea, ciliary body,
iris, and conjunctiva. The terminal
branch is the anterior ethmoidal nerve,
which innervates the sides and tip
of the nose. HZO most often involves
the supraorbital and supratrochlear
branches of the frontal nerve, which
innervate the upper eyelid and
Paresthesias or pain along the involved
dermatome may precede the
development of the vesicles. Vesicular
eruption on the forehead, lymph node
enlargement in the drainage areas,
fever, malaise, headache, occasional
neck stiffness, and a reactive conjunctivitis
with or without corneal involvement
follow. Prodromal lymphadenopathy
can be confused with later reactive
adenopathy that is caused by
secondary infection of vesicles.
The presence of VZV vesicles on
the side or the tip of the nose in the
distribution of the nasociliary nerve
(Hutchinson sign) may herald ocular
involvement. However, severe ocular
complications can occur with a vesicular
rash anywhere on the forehead.
Herpes zoster develops in about
20% of persons who were exposed
to VZV during childhood.3 Risk factors
for reactivation of the latent VZV
are diabetes, advancing age, cancer, surgery, radiation, chemotherapy, immunosuppressing
corticosteroid therapy, stress, and
AIDS.1,4 Persons with HIV infection
are at increased risk for herpes zoster
and are more likely to have severe
disease. Thus, suspect HIV infection
in patients younger than 45 years
who present with herpes zoster.5
Trauma to the skin from injury
or sunburn can also cause the VZV
to reactivate, as in this patient. Older
age, prolonged prodromal pain, and
severe acute pain are risk factors for
severe post-herpetic neuralgia.6,7CONFIRMING THE DIAGNOSIS
Several methods are available to
confirm the diagnosis of a herpesvirus
Tzanck smear. A cytologic
smear of scrapings from the base of
a vesicle is prepared with Wright or
Giemsa stain. Multinucleated giant
cells are characteristic of herpes
zoster, varicella, and herpes simplex.
Punch biopsy. This technique
provides more dependable material
for histologic examination, particularly
when a bacterial or fungal infection
is present. Usually, results show multinucleated
giant cells and Cowdry
type A intranuclear inclusion bodies.
Results of the biopsy can confirm the
presence of Herpesviridae but--like a
Tzanck smear--cannot identify the
Viral culture. A viral culture
can distinguish among herpes simplex
1, herpes simplex 2, and VZV.
VZV infection is best confirmed by
isolation of virus in tissue culture.
Often, a positive result is available
within 48 hours of specimen inoculation;
however, cytopathic effects may
take up to 5 days.
assay (DFA). This test uses fluorescein-
tagged antibody directed against
viral antigen. DFA has a higher
sensitivity and specificity than Tzanck
smear in vesicular lesions. This
method yields rapid results and can
differentiate herpes simplex virus
PCR. This method is growing in
use and availability. It is a rapid, sensitive,
and simple technique for diagnosis
of VZV infection.
Post-herpetic complications are
more common in HZO than in other
manifestations of zoster. Without
prompt detection and treatment, eye
involvement threatens the patient's vision.
Iritis, iridocyclitis, glaucoma
secondary to uveitis, keratitis, corneal
neovascularization, corneal tissue ulcerations,
scarring, and secondary
bacterial or fungal infection are possible
sequelae. Immediate intervention
can prevent or ameliorate complications;
however, glaucoma may result
from corticosteroid treatment. Palsy
of the third cranial nerve, and occasionally
of the fourth and sixth cranial
nerves, may occur.2,3 Post-herpetic
neuralgia, which affects more than
half of patients with HZO, may be severe
and long-lasting; it requires intensive
Herpes zoster ophthalmicus.
This disease warrants aggressive
treatment and assiduous follow-up.
Obtain ophthalmologic consultation
early for patients with significant
ocular symptoms. Local therapies
include warm, moist compresses.
Prescribe ocular lubricants to hydrate
the cornea and conjunctivae.
Antiviral agents--initiated within
72 hours of disease onset--are the
cornerstone of systemic treatment.
Acyclovir, 800 mg 5 times daily for 7
days, can reduce pain and hasten resolution
of lesions. This agent can abort
recurrences if initiated immediately
at onset of symptoms. Valacyclovir is a
prodrug that rapidly converts to acyclovir.
Given in the standard oral regimen
of 1000 mg tid for 7 days, valacyclovir
is as effective as acyclovir for
the prevention of ocular complications
of HZO. Patients tolerate both drugs
equally; however, the valacyclovir regimen
may be easier to follow.8
Famciclovir is also a prodrug;
it is biotransformed into the active
metabolite penciclovir. The recommended
oral dose for adults is 500 mg
q8h for 7 days. Famciclovir and valacyclovir
are equally effective in hastening
the resolution of zoster-associated
pain and post-herpetic neuralgia9;
some physicians believe acyclovir may
be comparable to the other agents in
Systemic corticosteroids are
used to ameliorate pain. Oral prednisone,
1 to 2 mg/kg qd (not to exceed
60 mg/d) tapered over 2 weeks,
may be prescribed as symptoms resolve.
The use of these agents is controversial;
they can increase the risk
of visceral and cutaneous dissemination,
especially in immunocompromised
patients.10Post-herpetic neuralgia. For patients
with post-herpetic neuralgia, applications
of capsaicin cream, 4 times
daily, may help deplete pain fibers of
substance P and reduce pain impulses.
Tricyclic antidepressants, such
as amitriptyline, are often helpful, particularly
when the agents are initiated
early in the course of HZO. Analgesics--
including narcotics, acetaminophen,
aspirin, and NSAIDs--
may also be used. When secondary
bacterial infection of the vesicles occurs,
give an antibiotic that covers
gram-positive skin flora.
Studies of patients with acute
herpes zoster who were older than
50 years showed that antiviral therapy
(ie, famciclovir or valacyclovir for 7
days) started within 72 hours of rash
onset and/or low-dose amitriptyline
given for 90 days may reduce the incidence
and duration of post-herpetic
neuralgia. Corticosteroids and analgesics
do not prevent post-herpetic
Persons who have not had chickenpox
are at risk for contracting herpes
zoster; advise such patients to
avoid close contact with persons who
have active zoster lesions. In addition,
varicella can be contracted from exposure
to herpes zoster.
Patients infected with VZV need
to avoid known precipitating factors--
such as sun exposure, stress, and
that can lead to recurrence of the
1. Strauss SE, Oxman MN. Varicella and herpes
zoster. In: Freedberg IM, Eisen AZ, Wolff K, et al,
eds. Fitzpatrick’s Dermatology in General Medicine.
5th ed. New York: McGraw-Hill; 1999:2427-2450.
2. Covucci AL. Paresis of cranial nerves 3, 4 and 6
associated with herpes zoster ophthalmicus: a case
report. Clin Eye Vis Care. 1999;11:159-163.
3. Chang SD, Deluise VP. Herpes zoster. In: Duane
TD. Duane’s Ophthalmology [book on CD-ROM].
Philadelphia: Lippincott-Raven; 1998.
4. Marsh RJ. Herpes zoster ophthalmicus. J R Soc
5. Friedman-Kien AE, Lafleur FL, Gendler E, et al.
Herpes zoster: a possible early clinical sign for development
of acquired immunodeficiency syndrome
in high-risk individuals. J Am Acad Dermatol. 1986;
6. Whitley RJ, Shukla S, Crooks RJ. The identification
of risk factors associated with persistent pain
following herpes zoster. J Infect Dis. 1998;178(suppl
7. Choo PW, Galil K, Donahue JG, et al. Risk factors
for postherpetic neuralgia. Arch Intern Med.
8. Colin J, Prisant O, Cochener B, et al. Comparison
of the efficacy and safety of valaciclovir and acyclovir
for the treatment of herpes zoster ophthalmicus.
9. Tyring SK, Beutner KR, Tucker BA, et al. Antiviral
therapy for herpes zoster: randomized, controlled
clinical trial of valacyclovir and famciclovir
therapy in immunocompetent patients 50 years and
older. Arch Fam Med. 2000;9:863-869.
10. Ernst ME, Santee JA, Klepser TB. Oral corticosteroids
for pain associated with herpes zoster.
Ann Pharmacother. 1998;32:1099-1103.
11. Alper BS, Lewis PR. Does treatment of acute
herpes zoster prevent or shorten postherpetic neuralgia?
J Fam Pract. 2000;49:255-264.