Shingles (Herpes Zoster)

Background

The varicella zoster virus is the cause of this painful disease. It is a close relative of the herpes virus. After initial infection, the virus remains dormant in the dorsal root ganglia. During periods of stress or immunocompromised states, the virus may be reactivated and shingles (Herpes zoster) is the result. It is important to remember that a person with a shingles outbreak is infectious to anyone who has not been previously exposed to the virus. Since over 90% of adults in the United States have had evidence of chicken pox infection, they are all at risk for being afflicted by this disease.

Patients may have a prodrome of headache, malaise, photophobia, and rarely fever. Before the actual skin lesions occur, there may be tingling, itching (paresthesias) or pain. However, within 3-5 days, the rash of shingles will occur. At first, it is a slightly raised and reddish rash, having a characteristic clustering of clear small blisters. Within a few days these small blisters may become pustules, ulcerate, and evenutally crust over. The healing process may take up to 2-4 weeks and scarring may occur. Because the virus is reactivated within the sensory nerves, it travels down these nerves in what is known as a dermatomal distribution. Occasionally, two or more nerves are involved but as a rule, does not cross the midline.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/
Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Herpes zoster

INCIDENCE 1.5-3.0 cases/1000 person in USA
500,000 cases annually in USA

Lifetime risk estimated at 10-20%

AGE RANGE-MEDIAN Increasing age more common
Incidence in patients>75 years >10 cases/1000 person-years

DISEASE ASSOCIATIONS CHARACTERIZATION

AIDS

Zoster in patients infected with HIV: a review.

Vafai A, Berger M.

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Am J Med Sci 2001 Jun;321(6):372-80 Abstract quote

Varicella-zoster virus (VZV), a member of the human herpesvirus family, causes childhood chickenpox (varicella), becomes latent in sensory ganglia, and reactivates years later in immunocompromised and elderly persons to produce shingles (herpes zoster). Early in the AIDS epidemic, zoster was noted in adults and children infected with HIV. Severe and debilitating zoster-associated dermatological, ophthalmic, and neurological complications may occur in patients infected with HIV. Antiviral therapy can modify the duration of zoster and alleviate its attendant complications.

Varicella vaccine may boost the immunity and prevent virus reactivation. VZV immune globulin (VZIG) prevents or modifies clinical illness in persons who have been exposed to varicella or zoster.

PATHOGENESIS CHARACTERIZATION

HERPES ZOSTER VIRUS

LABORATORY/
RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

EMG

Herpes zoster of the head and limbs: electroneuromyographic and clinical findings in 158 consecutive cases.

Mondelli M, Romano C, Rossi S, Cioni R.

Servizio di EMG, ASL 7, Siena, Italy.
Arch Phys Med Rehabil 2002 Sep;83(9):1215-21 Abstract quote
OBJECTIVES: To quantify electromyographic and neurographic changes and to correlate them with the clinical data of outpatients with herpes zoster.

DESIGN: Prospective case series.

SETTING: Outpatient department.

PATIENTS: A consecutive, unselected series of 158 outpatient cases (88 women, 70 men; mean age, 64y) of herpes zoster of the head and limbs.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Blink reflex and electromyography and motor and sensory nerve conduction velocities of nerves and muscles corresponding to affected dermatomes.

RESULTS: Postherpetic neuralgia (PHN), segmental zoster paresis, and polyneuropathy were found in 31%, 19%, and 2.5% of cases, respectively. Absence or reduction of sensory action potential amplitudes, blink reflex areas, and compound muscle action potential amplitudes were found in 60%, 31%, and 18% of cases, respectively. Sensory and motor conduction velocities and motor and blink reflex latencies were nearly always normal or only slightly slowed. Electromyographic signs of abnormal spontaneous activity were found in 36% of the cases. Electrophysiologic alterations were correlated among themselves, with age, with presence of segmental zoster paresis, and with absence of antiviral therapy. The extent of the skin rash (number of dermatomes affected by herpes zoster) was the only variable predictive of disappearance or improvement of PHN.

CONCLUSIONS: Sensory axonal neuropathy, often associated with similar motor involvement, can be shown by classical electrophysiologic methods in herpes zoster. The severity of damage to motor fibers was related to damage to sensory fibers, but no relation was found between peripheral axon damage and PHN. The site of motor system damage may be the ventral roots, plexus, or peripheral nerve. The probability of complications and the severity of sensory and motor peripheral axonal damage were increased in older patients. Appropriate antiviral therapy seems to reduce the incidence of segmental zoster paresis and the severity of damage to the peripheral fibers. A reduced extent of herpetic rash was the only factor to correlate with a good outcome of PHN.

LABORATORY MARKERS

ELVIS

ELVIS: a new 24-hour culture test for detecting herpes simplex virus from ocular samples.

Kowalski RP, Karenchak LM, Shah C, Gordon JS.

Charles T. Campbell Ophthalmic Microbiology Laboratory,University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Arch Ophthalmol 2002 Jul;120(7):960-2 Abstract quote
OBJECTIVE: To compare ELVIS (Enzyme Linked Virus Inducible System) (BioWhittaker, Walkersville, Md), a new, simple, 24-hour cell culture test for detecting herpes simplex virus (HSV), with standard cell culture and Herpchek (NEN, Boston, Mass) for detecting HSV in ocular specimens.

METHODS: Retrospectively, 36 true-positive frozen-stock ocular samples that were cell-culture positive for HSV, and 25 true-negative samples (varicella-zoster virus, adenovirus, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus viridans) were tested with ELVIS. Herpchek was processed at the time of initial clinical laboratory testing. Prospectively, 422 patients were tested for HSV with standard cell culture, ELVIS, and Herpchek. The sensitivity, specificity, positive and negative predictive values, and efficacy of ELVIS based on positive and negative cell cultures were determined.

RESULTS: Retrospectively, ELVIS was 86.1% sensitive (31/36), 100% specific (25/25), and 91.8% efficient (56/61). The positive predictive value was 100% (31/31), and the negative predictive value was 83.3% (25/30). The sensitivity of ELVIS was equivalent to Herpchek (80.5%, 29/36) (P =.53). Prospectively, the sensitivity of ELVIS (84.8%, 28/33) was equivalent to that of Herpchek (84.8%, 28/33).

CONCLUSIONS: ELVIS is an easy HSV diagnostic test that can provide faster positive culture results than standard cell culture, and it is equally sensitive but less time-consuming than Herpchek.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

PENIS

Herpes zoster of the penis: An unusual location for a common eruption.

Spray A, Glaser DA.

Department of Dermatology, St. Louis University School of Medicine.
Am Acad Dermatol 2002 Aug;47(2 Pt 2):S177-9 Abstract quote
Herpes zoster is an acute vesiculobullous eruption estimated to affect 10% to 20% of the population.

The diagnosis usually can be based on clinical features alone, but laboratory studies may be needed for definitive diagnosis, particularly in atypical presentations.

POST-HERPETIC NEURALGIA

Rash severity in herpes zoster: Correlates and relationship to postherpetic neuralgia.

Nagasako EM, Johnson RW, Griffin DR, Dworkin RH.

Department of Anesthesiology, University of Rochester School of Medicine and Dentistry; the Department of Anesthesiology, University of Bristol and Bristol Royal Infirmary; and GlaxoSmithKline.
J Am Acad Dermatol 2002 Jun;46(6):834-9 Abstract quote
Baseline and follow-up data from 4 samples of immunocompetent patients with herpes zoster who participated in clinical trials of the antiviral agent famciclovir were examined (N = 1778).

In both univariate and multivariate analyses, severe rash (ie, >50 lesions, defined as papules, vesicles, or crusted vesicles) was significantly associated with older age, male sex, severe pain, primary involvement of nontrigeminal dermatomes, and a greater number of affected dermatomes. In addition, severe rash predicted the presence of pain 3 months later.

The results indicate that severe rash is more common in patients with herpes zoster who are older and who have more severe acute pain and confirm that severe rash is a risk factor for prolonged pain.

RAMSAY HUNT SYNDROME

Ramsay Hunt syndrome.

Sweeney CJ, Gilden DH.

Department of Neurology, Mail Stop B182, University of Colorado Health Sciences Center

J Neurol Neurosurg Psychiatry 2001 Aug;71(2):149-54 Abstract quote

The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth.

J Ramsay Hunt, who described various clinical presentations of facial paralysis and rash, also recognised other frequent symptoms and signs such as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained these eighth nerve features by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of clinical variations of the syndrome now bearing his name led to his recognition of the general somatic sensory function of the facial nerve and his defining of the geniculate zone of the ear.

It is now known that varicella zoster virus (VZV) causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken. In the only prospective study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy. Further, Bell's palsy is significantly associated with herpes simplex virus (HSV) infection. In the light of the known safety and effectiveness of antiviral drugs against VZV or HSV, consideration should be given to early treatment of all patients with Ramsay Hunt syndrome or Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for 3-5 days).

Finally, some patients develop peripheral facial paralysis without ear or mouth rash, associated with either a fourfold rise in antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy.

VISCERAL ZOSTER

Visceral zoster as the presenting feature of disseminated herpes zoster.

Stratman E.

Department of Dermatology, Marshfield Clinic
J Am Acad Dermatol 2002 May;46(5 Pt 1):771-4 Abstract quote
Visceral dissemination of herpes zoster may follow cutaneous dissemination in immunocompromised patients. The skin is not necessarily the only organ affected and may not even be the presenting organ. Immunohistochemical stains available for routine paraffin-embedded tissue biopsy specimens allow for rapid diagnosis of varicella zoster virus.

We describe a patient in whom gastric dissemination of herpes zoster was proven by immunohistochemistry. Unexplained hepatitis, pancreatitis, gastritis, or complaints of abdominal pain in immunocompromised patients with herpes zoster should prompt a high degree of suspicion for visceral zoster and immediate treatment with intravenous acyclovir.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

VARIANTS

INCOGNITO

Herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive!

Boer A, Herder N, Blodorn-Schlicht N, Falk T.

Dermatologikum Hamburg, Stephansplatz 5, 20354 Hamburg, Germany.

Am J Dermatopathol. 2006 Apr;28(2):181-6. Abstract quote

Infections of the skin by herpesviruses do not always present themselves in typical fashion. Conventional microscopy is used routinely to confirm infection by herpesviruses, but sometimes typical signs such as multinucleated epithelial cells or "ghosts" of them are not encountered in a specimen (so-called herpes incognito).

We studied 35 patients in whom infection with herpesviruses was differentially diagnosed clinically but in whom a biopsy specimen had been taken for confirmation. Only those patients in whom histopathologic findings had been interpreted as being "not diagnostic" of herpesvirus infection by 2 independent dermatopathologists were included. Clinical and histopathologic findings were correlated with results from polymerase chain reaction studies on formalin-fixed paraffin-embedded tissue. Polymerase chain reaction revealed herpesvirus-specific DNA in 12 of 35 specimens, 10 being varicella zoster virus (VZV) positive, 1 herpes simplex virus (HSV)-2 positive, and 1 HSV-1 positive. Ten of these 12 cases presented themselves in very similar fashion (8 VZV, 1 HSV-1, 1 HSV-2).

All lesions were macular or papular and typified mostly by dense perivascular and sparse interstitial superficial and deep infiltrates of lymphocytes, sometimes assuming a patchy lichenoid pattern. Infiltrates were prominent in and around adnexal structures, often peppering follicles, sebaceous glands, and eccrine glands. Lymphocytes were also found in the lower part of the epidermis accompanied by a combination of spongiosis and vacuolar alteration. The papillary dermis was often edematous; extravasated erythrocytes in variable numbers were a common finding. Lymphocytes sometimes had large and polygonal nuclei. Neutrophils and nuclear dust were present occasionally; eosinophils were rare.

We conclude that herpes incognito most commonly is herpes zoster and its histopathologic pattern is distinctive.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT Acyclovir, Famciclovir, and Valacyclovir

FAMCICLOVIR

Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients.

Dworkin RH, Boon RJ, Griffin DR, Phung D.

Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
J Infect Dis 1998 Nov;178 Suppl 1:S76-80 Abstract quote
New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are reviewed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials.

The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia (PHN), which was defined as pain persisting after rash healing, pain persisting > 30 days after study enrollment, or pain persisting > 3 months after study enrollment; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN; the impact of famciclovir treatment on the duration of PHN, while controlling for significant covariates; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment.

The results of these analyses indicated that greater age, rash severity, and acute pain severity are risk factors for prolonged PHN. In addition, they demonstrated that treatment of acute herpes zoster patients with famciclovir significantly reduces both the duration and prevalence of PHN.

CORTICOSTEROIDS

Corticosteroids for herpes zoster: what do they accomplish?

Santee JA.

School of Pharmacy, Division of Pharmacy Practice, University of Missouri-Kansas City, 2411 Holmes, Kansas City, MO 64108, USA.
Am J Clin Dermatol 2002;3(8):517-24 Abstract quote
For some patients, herpes zoster infections not only result in acute pain but serious consequences, including postherpetic neuralgia and damage to ocular tissues. Some authors have recommended corticosteroids for the treatment of these acute symptoms and complications.

The literature concerning the use of corticosteroids for herpes zoster, however, either provides conflicting results or includes recommendations based on clinical experience rather than clinical trials. The author performed a search of the literature to address the question of whether corticosteroids are well tolerated and effective for the treatment/prevention of the acute pain of herpes zoster, postherpetic neuralgia, and/or the ocular complications resulting from herpes zoster. While smaller trials found oral corticosteroids beneficial for preventing postherpetic neuralgia, larger, better designed trials have not found oral corticosteroids to be more efficacious than placebo in preventing postherpetic neuralgia.

Trials investigating the effect of oral corticosteroids for the acute pain of herpes zoster have found that corticosteroids provide a statistically significant improvement. Whether these improvements are clinically significant is uncertain. Thus, oral corticosteroids may confer a slight benefit for initial symptoms as long as the patient is not at risk for complications resulting from corticosteroid therapy. Most trials of topical and injectable corticosteroids are limited by several shortcomings. Therefore, topical and most forms of parenteral corticosteroids have yet to be proven effective for the treatment of acute pain or prevention of complications.

Two controlled, blinded trials investigating the use of intrathecal corticosteroid administration for intractable postherpetic neuralgia suggest that corticosteroid administration results in a significant improvement in pain.

Despite this, several authors have voiced concern over possible serious adverse events with the intrathecal administration of corticosteroids. Intrathecal corticosteroids may provide a benefit for intractable postherpetic neuralgia, but because of risks of serious complications, this is a last-line option and should only be administered by experienced personnel.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
EMG
Herpes zoster of the head and limbs: electroneuromyographic and clinical findings in 158 consecutive cases. Mondelli M, Romano C, Rossi S, Cioni R. Servizio di EMG, ASL 7, Siena, Italy.	Arch Phys Med Rehabil 2002 Sep;83(9):1215-21 Abstract quote OBJECTIVES: To quantify electromyographic and neurographic changes and to correlate them with the clinical data of outpatients with herpes zoster. DESIGN: Prospective case series. SETTING: Outpatient department. PATIENTS: A consecutive, unselected series of 158 outpatient cases (88 women, 70 men; mean age, 64y) of herpes zoster of the head and limbs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blink reflex and electromyography and motor and sensory nerve conduction velocities of nerves and muscles corresponding to affected dermatomes. RESULTS: Postherpetic neuralgia (PHN), segmental zoster paresis, and polyneuropathy were found in 31%, 19%, and 2.5% of cases, respectively. Absence or reduction of sensory action potential amplitudes, blink reflex areas, and compound muscle action potential amplitudes were found in 60%, 31%, and 18% of cases, respectively. Sensory and motor conduction velocities and motor and blink reflex latencies were nearly always normal or only slightly slowed. Electromyographic signs of abnormal spontaneous activity were found in 36% of the cases. Electrophysiologic alterations were correlated among themselves, with age, with presence of segmental zoster paresis, and with absence of antiviral therapy. The extent of the skin rash (number of dermatomes affected by herpes zoster) was the only variable predictive of disappearance or improvement of PHN. CONCLUSIONS: Sensory axonal neuropathy, often associated with similar motor involvement, can be shown by classical electrophysiologic methods in herpes zoster. The severity of damage to motor fibers was related to damage to sensory fibers, but no relation was found between peripheral axon damage and PHN. The site of motor system damage may be the ventral roots, plexus, or peripheral nerve. The probability of complications and the severity of sensory and motor peripheral axonal damage were increased in older patients. Appropriate antiviral therapy seems to reduce the incidence of segmental zoster paresis and the severity of damage to the peripheral fibers. A reduced extent of herpetic rash was the only factor to correlate with a good outcome of PHN.
LABORATORY MARKERS
ELVIS
ELVIS: a new 24-hour culture test for detecting herpes simplex virus from ocular samples. Kowalski RP, Karenchak LM, Shah C, Gordon JS. Charles T. Campbell Ophthalmic Microbiology Laboratory,University of Pittsburgh Medical Center, Pittsburgh, PA, USA.	Arch Ophthalmol 2002 Jul;120(7):960-2 Abstract quote OBJECTIVE: To compare ELVIS (Enzyme Linked Virus Inducible System) (BioWhittaker, Walkersville, Md), a new, simple, 24-hour cell culture test for detecting herpes simplex virus (HSV), with standard cell culture and Herpchek (NEN, Boston, Mass) for detecting HSV in ocular specimens. METHODS: Retrospectively, 36 true-positive frozen-stock ocular samples that were cell-culture positive for HSV, and 25 true-negative samples (varicella-zoster virus, adenovirus, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus viridans) were tested with ELVIS. Herpchek was processed at the time of initial clinical laboratory testing. Prospectively, 422 patients were tested for HSV with standard cell culture, ELVIS, and Herpchek. The sensitivity, specificity, positive and negative predictive values, and efficacy of ELVIS based on positive and negative cell cultures were determined. RESULTS: Retrospectively, ELVIS was 86.1% sensitive (31/36), 100% specific (25/25), and 91.8% efficient (56/61). The positive predictive value was 100% (31/31), and the negative predictive value was 83.3% (25/30). The sensitivity of ELVIS was equivalent to Herpchek (80.5%, 29/36) (P =.53). Prospectively, the sensitivity of ELVIS (84.8%, 28/33) was equivalent to that of Herpchek (84.8%, 28/33). CONCLUSIONS: ELVIS is an easy HSV diagnostic test that can provide faster positive culture results than standard cell culture, and it is equally sensitive but less time-consuming than Herpchek.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
PENIS
Herpes zoster of the penis: An unusual location for a common eruption. Spray A, Glaser DA. Department of Dermatology, St. Louis University School of Medicine.	Am Acad Dermatol 2002 Aug;47(2 Pt 2):S177-9 Abstract quote Herpes zoster is an acute vesiculobullous eruption estimated to affect 10% to 20% of the population. The diagnosis usually can be based on clinical features alone, but laboratory studies may be needed for definitive diagnosis, particularly in atypical presentations.
POST-HERPETIC NEURALGIA
Rash severity in herpes zoster: Correlates and relationship to postherpetic neuralgia. Nagasako EM, Johnson RW, Griffin DR, Dworkin RH. Department of Anesthesiology, University of Rochester School of Medicine and Dentistry; the Department of Anesthesiology, University of Bristol and Bristol Royal Infirmary; and GlaxoSmithKline.	J Am Acad Dermatol 2002 Jun;46(6):834-9 Abstract quote Baseline and follow-up data from 4 samples of immunocompetent patients with herpes zoster who participated in clinical trials of the antiviral agent famciclovir were examined (N = 1778). In both univariate and multivariate analyses, severe rash (ie, >50 lesions, defined as papules, vesicles, or crusted vesicles) was significantly associated with older age, male sex, severe pain, primary involvement of nontrigeminal dermatomes, and a greater number of affected dermatomes. In addition, severe rash predicted the presence of pain 3 months later. The results indicate that severe rash is more common in patients with herpes zoster who are older and who have more severe acute pain and confirm that severe rash is a risk factor for prolonged pain.
RAMSAY HUNT SYNDROME
Ramsay Hunt syndrome. Sweeney CJ, Gilden DH. Department of Neurology, Mail Stop B182, University of Colorado Health Sciences Center	J Neurol Neurosurg Psychiatry 2001 Aug;71(2):149-54 Abstract quote The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth. J Ramsay Hunt, who described various clinical presentations of facial paralysis and rash, also recognised other frequent symptoms and signs such as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained these eighth nerve features by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of clinical variations of the syndrome now bearing his name led to his recognition of the general somatic sensory function of the facial nerve and his defining of the geniculate zone of the ear. It is now known that varicella zoster virus (VZV) causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken. In the only prospective study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy. Further, Bell's palsy is significantly associated with herpes simplex virus (HSV) infection. In the light of the known safety and effectiveness of antiviral drugs against VZV or HSV, consideration should be given to early treatment of all patients with Ramsay Hunt syndrome or Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for 3-5 days). Finally, some patients develop peripheral facial paralysis without ear or mouth rash, associated with either a fourfold rise in antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy.
VISCERAL ZOSTER
Visceral zoster as the presenting feature of disseminated herpes zoster. Stratman E. Department of Dermatology, Marshfield Clinic	J Am Acad Dermatol 2002 May;46(5 Pt 1):771-4 Abstract quote Visceral dissemination of herpes zoster may follow cutaneous dissemination in immunocompromised patients. The skin is not necessarily the only organ affected and may not even be the presenting organ. Immunohistochemical stains available for routine paraffin-embedded tissue biopsy specimens allow for rapid diagnosis of varicella zoster virus. We describe a patient in whom gastric dissemination of herpes zoster was proven by immunohistochemistry. Unexplained hepatitis, pancreatitis, gastritis, or complaints of abdominal pain in immunocompromised patients with herpes zoster should prompt a high degree of suspicion for visceral zoster and immediate treatment with intravenous acyclovir.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Herpes zoster
INCIDENCE	1.5-3.0 cases/1000 person in USA 500,000 cases annually in USA Lifetime risk estimated at 10-20%
AGE RANGE-MEDIAN	Increasing age more common Incidence in patients>75 years >10 cases/1000 person-years

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT	Acyclovir, Famciclovir, and Valacyclovir
FAMCICLOVIR
Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients. Dworkin RH, Boon RJ, Griffin DR, Phung D. Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA.	J Infect Dis 1998 Nov;178 Suppl 1:S76-80 Abstract quote New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are reviewed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials. The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia (PHN), which was defined as pain persisting after rash healing, pain persisting > 30 days after study enrollment, or pain persisting > 3 months after study enrollment; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN; the impact of famciclovir treatment on the duration of PHN, while controlling for significant covariates; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment. The results of these analyses indicated that greater age, rash severity, and acute pain severity are risk factors for prolonged PHN. In addition, they demonstrated that treatment of acute herpes zoster patients with famciclovir significantly reduces both the duration and prevalence of PHN.
CORTICOSTEROIDS
Corticosteroids for herpes zoster: what do they accomplish? Santee JA. School of Pharmacy, Division of Pharmacy Practice, University of Missouri-Kansas City, 2411 Holmes, Kansas City, MO 64108, USA.	Am J Clin Dermatol 2002;3(8):517-24 Abstract quote For some patients, herpes zoster infections not only result in acute pain but serious consequences, including postherpetic neuralgia and damage to ocular tissues. Some authors have recommended corticosteroids for the treatment of these acute symptoms and complications. The literature concerning the use of corticosteroids for herpes zoster, however, either provides conflicting results or includes recommendations based on clinical experience rather than clinical trials. The author performed a search of the literature to address the question of whether corticosteroids are well tolerated and effective for the treatment/prevention of the acute pain of herpes zoster, postherpetic neuralgia, and/or the ocular complications resulting from herpes zoster. While smaller trials found oral corticosteroids beneficial for preventing postherpetic neuralgia, larger, better designed trials have not found oral corticosteroids to be more efficacious than placebo in preventing postherpetic neuralgia. Trials investigating the effect of oral corticosteroids for the acute pain of herpes zoster have found that corticosteroids provide a statistically significant improvement. Whether these improvements are clinically significant is uncertain. Thus, oral corticosteroids may confer a slight benefit for initial symptoms as long as the patient is not at risk for complications resulting from corticosteroid therapy. Most trials of topical and injectable corticosteroids are limited by several shortcomings. Therefore, topical and most forms of parenteral corticosteroids have yet to be proven effective for the treatment of acute pain or prevention of complications. Two controlled, blinded trials investigating the use of intrathecal corticosteroid administration for intractable postherpetic neuralgia suggest that corticosteroid administration results in a significant improvement in pain. Despite this, several authors have voiced concern over possible serious adverse events with the intrathecal administration of corticosteroids. Intrathecal corticosteroids may provide a benefit for intractable postherpetic neuralgia, but because of risks of serious complications, this is a last-line option and should only be administered by experienced personnel.