053 – Herpes zoster

Zoster, or shingles, is a reactivation of a latent infection with the varicella zoster virus (VZV), a member of the Herpesviridae family. After a primary infection, the virus lays dormant in dorsal root ganglia for life. Reactivation may be triggered by certain medications, other infections, or different forms of physical or emotional stress. The onset of cutaneous zoster typically involves a 1–3 day prodrome of pain or paresthesias in the affected dermatome, followed by the eruption of erythematous papules and vesicles in the same distribution.

Zoster is usually confined to a distinct dermatome but can also be found in multiple contiguous or noncontiguous dermatomes (zoster multiplex). There may be small islands of lesions at a distant location. Disseminated zoster occurs 5–10 days after the onset of dermatomal disease. It is defined as more than 20 lesions outside the initial dermatome of involvement. Associated symptoms can include pain, malaise, and headache. Thoracic dermatomal pain can simulate an acute myocardial infarction.

The most common complication is post-herpetic neuralgia, which is much more frequent in elderly patients with zoster. The pain of post-herpetic neuralgia can be intractable and debilitating, and one of the goals of treatment is to prevent its development. Neuropathies may occur and include peripheral motor neuropathies, neurogenic bladder, and diaphragmatic paralysis. They are usually transient. Zoster encephalitis usually appears in the first 2 weeks after the onset of lesions and has a 10–20% mortality rate. Lesions are also at risk for bacterial superinfection. In extreme cases, necrotizing fasciitis may occur.

There is an increased incidence of zoster in the immunocompromised, including patients with HIV and cancer, transplant recipients, and patients taking systemic corticosteroids or other immunosuppressive drugs. These populations may also have a higher incidence of atypical manifestations, such as zoster multiplex and myelitis.

Zoster should be differentiated from cellulitis based on the presence of umbilicated vesicles in a dermatomal distribution. Patients may report a history of similar attacks.

Grouped vesicles or small bullae on an erythematous base, usually confined to a distinct dermatome and not crossing the midline. The face in the trigeminal, and especially ophthalmic distribution, and the trunk from T3–L2 are most frequently affected.

Early lesions may be urticarial. Vesicles may be confluent, sparse, or discrete. Commonly, vesicles become hemorrhagic or pustular after several days. The lesions typically crust over and resolve after a 7–14 day course. Scarring is common.

Regional adenopathy may be seen. Some patients may suffer acute segmental neuralgia, known as zoster sine herpete, without ever developing a skin eruption.

Post-zoster neuralgia is more common in individuals over the age of 70.

Cellulitis or erysipelas
Herpes simplex virus infection
Herpetic whitlow
Allergic contact or irritant contact dermatitis
Folliculitis
Insect bites
Molluscum contagiosum
Other poxviruses (cowpox, monkeypox)
Pyoderma gangrenosum
Primary varicella infection, and disseminated varicella
During the prodromal phase, herpes zoster pain may mimic acute myocardial infarction or biliary colic.
Urticaria
Bullous fixed drug eruption
Eczema herpeticum
Sweet's syndrome
Vasculitis
Blistering distal dactylitis
Erysipeloid
Orf
Mycobacterium marinum infection
Sporotrichosis
Pasteurella multocida infection

PCR can be useful for detecting viral DNA in difficult or complicated cases (encephalitis, zoster sine herpete), although most disease is diagnosed clinically by typical appearance and distribution of lesions.

The Tzanck smear is the most rapid and least expensive test. A smear is made of cells scraped from the base of a vesicle or bullae, stained and examined under the microscope for multinucleate giant cells.

Direct fluorescence antigen testing (DFA) is a rapid (less than 24 hour) and sensitive test for HSV-1, HSV-2, and VZV. This test is performed by vigorously scraping the base of a vesicle with a sterile cotton-tipped swab or 15 blade and smearing the cells onto a glass slide from a DFA kit. The slide is then fixed (usually contained in a kit) and sent for immunofluorescence analysis. Individual slides must be sent for each virus suspected. Slides can be stored at room temperature for 24 hours after fixation, if needed.

Viral culture may also be performed.

Electron microscopy is also available but rarely used.

Consider the following additional tests based on the clinical scenario:

• HIV testing
• Lumbar puncture with CSF analysis
• MRI of brain and/or spinal cord

Patients with active vesicular lesions can spread the infection to immunocompromised hosts and, if the patient is a health care provider, he/she should take a leave of absence from work.

The following consultations may be needed: dermatology, neurology, and/or infectious disease.

The CDC Advisory Committee on Immunization Practices recommends a single dose of zoster vaccine (Zostavax®) for adults 60 years of age or older, whether or not they have had a previous episode of herpes zoster. The vaccine is contraindicated in the immunocompromised, those with an allergy to gelatin or neomycin, or those with active untreated tuberculosis.

Antiviral therapy (acyclovir and pro-drug forms), if administered in the first 72 hours after symptom onset (and possibly beyond that time), can shorten the length and severity of the acute episode and may help to decrease the likelihood of developing postherpetic neuralgia. A single published study supports the use of amitriptyline (25 mg daily) as an adjunct to an antiviral agent in acute herpes zoster to decrease the incidence of and pain associated with subsequent postherpetic neuralgia. Take into account the risk factors for developing postherpetic neuralgia: old age, severe pain in the acute episode of herpes zoster, and presence and severity of prodromal pain. Corticosteroids do not appear to prevent postherpetic neuralgia.

Aluminum acetate or Burow's soaks can help to alleviate cutaneous symptoms. Patients routinely require oral analgesia. Consider NSAIDs and opioids, including controlled-release oxycodone in patients not rapidly responding to the initial regimen. Simultaneous prescription of stool softeners can prevent opioid-induced constipation. Observe for and promptly treat any secondary bacterial infection.

Antivirals:

• Acyclovir 800 mg p.o. every 4 hours for 7–10 days (frequently given 5 times daily)
• Famciclovir 500 mg p.o. every 8 hours for 7 days
• Valacyclovir 1,000 mg p.o. every 8 hours for 7 days
  • Note: Valacyclovir should not be used in immunosuppressed patients.
• Foscarnet 40 mg/kg IV every 8 hours for 10 days. Given as a 1-hour infusion. This drug is reserved for cases resistant to acyclovir.

Therapies for postherpetic neuralgia:

• Topical lidocaine 5% patch
• Tricyclic antidepressants (eg, nortriptyline, start at 10–20 mg daily)
• Gabapentin 300 mg p.o. 3 times daily
• Pregabalin start at 75 mg at bedtime and then advance to up to 300 daily to twice daily
• Weak opioid agonist analgesics (eg, tramadol 50–200 mg daily)
• Strong opioid agonist analgesics (eg, controlled-release oxycodone)
• Topical capsaicin 0.075% cream

Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 Jun 6;57(RR-5):1-30; quiz CE2-4. PubMed Id: 18528318

Madkan V, Sra K, Brantley J, Carrasco D, Mendoza N, Tyring SK. Human Herpesviruses. In: Bolognia J, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, MO: Mosby/Elsevier; 2008:1204-1208.

Straus SE, Oxman ME, Schmader KE. Varicella and Herpes Zoster. In: Fitzpatrick TB, Wolff K, eds. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008:1885-1898.

Wood SM, Shah SS, Steenhoff AP, Rutstein RM. Primary varicella and herpes zoster among HIV-infected children from 1989 to 2006. Pediatrics. 2008 Jan;121(1):e150-6. PubMed Id: 18086820

Tyring SK. Management of herpes zoster and postherpetic neuralgia. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S136-42. PubMed Id: 18021865

Feller L, Wood NH, Lemmer J. Herpes zoster infection as an immune reconstitution inflammatory syndrome in HIV-seropositive subjects: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Oct;104(4):455-60. PubMed Id: 17604657

Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja M, Betts RF, Gershon AA, Haanpaa ML, McKendrick MW, Nurmikko TJ, Oaklander AL, Oxman MN, Pavan-Langston D, Petersen KL, Rowbotham MC, Schmader KE, Stacey BR, Tyring SK, van Wijck AJ, Wallace MS, Wassilew SW, Whitley RJ. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007 Jan 1;44 Suppl 1:S1-26. PubMed Id: 17143845

Tyler KL, Beckham JD. Management of acute shingles (herpes zoster). Rev Neurol Dis. 2007;4(4):203-8. PubMed Id: 18195672

Katz J, Cooper EM, Walther RR, Sweeney EW, Dworkin RH. Acute pain in herpes zoster and its impact on health-related quality of life. Clin Infect Dis. 2004 Aug 1;39(3):342-8. PubMed Id: 15307000

Nikkels AF, Nikkels-Tassoudji N, Piérard GE. Revisiting childhood herpes zoster. Pediatr Dermatol. 2004 Jan-Feb;21(1):18-23. PubMed Id: 14871320

Plaghki L, Adriaensen H, Morlion B, Lossignol D, Devulder J. Systematic overview of the pharmacological management of postherpetic neuralgia. An evaluation of the clinical value of critically selected drug treatments based on efficacy and safety outcomes from randomized controlled studies. Dermatology. 2004;208(3):206-16. PubMed Id: 15118369

Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med. 2000 Mar 2;342(9):635-45. PubMed Id: 10699164

Decroix J, Partsch H, Gonzalez R, Mobacken H, Goh CL, Walsh L, Shukla S, Naisbett B. Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA). J Eur Acad Dermatol Venereol. 2000 Jan;14(1):23-33. PubMed Id: 10877249

Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage. 1997 Jun;13(6):327-31. PubMed Id: 9204652

Appearance
Patient Appears Ill

Body Location
Abdomen
Anterior Neck
Arm
Back
Breast
Buccal Mucosa
Buttocks
Cheek
Chest
Chin
Dorsal Tongue
Dorsum of Hand
Face
Female Genital
Fingers
Flank
Floor of Mouth
Foot (Feet) or Toes
Forearm
Forehead
Frontal Scalp
Gingival-Alveolar Mucosa
Hand or Fingers
Hard Palate
Inferior Eyelid
Inframammary Fold of Chest
Lateral Neck
Leg
Lips
Lower Back
Lower Leg
Male Genital
Mucosal Lip
Neck
Occipital Neck
Parietal Scalp
Posterior Neck
Sacral Region of Back
Scalp
Shaft of Penis
Soft Palate/Tonsillar
Superior Chest
Superior Eyelid
Temple
Trunk
Upper Arm
Upper Back
Ventral Tongue

Configuration
Grouped

Distribution
Dermatomal
Unilateral

Laboratory
ALT Elevated
AST Elevated
Tzanck Smear Shows Multinucleated Giant Cells

Lesion
Corneal Ulcer (Defect)
Hard Palate Erosion
Hard Palate Ulceration
Lip Mucosa Vesicle
Pustule
Soft Palate Erosion
Soft Palate Ulceration
Soft Palate Vesicle
Tense Vesicle
Umbilicated Vesicle

Medications
Etanercept
Glucocorticoid
Immunosuppressive

Signs and Symptoms
Cranial Nerve Palsy
Fever (Febrile)
Headache
Hearing Loss
Lymphadenopathy
Malaise
No Fever (Afebrile, Apyrexial)
Pain or Itch Precede Rash by Days
Painful Skin Lesions
Paralysis
Pruritus (Itching)
Vertigo

Temporal
Developed Acutely Over Days to Weeks
Developed Rapidly in Minutes or Hours

Medical History
Acquired Immune Deficiency Syndrome (AIDS)
Human Immunodeficiency Virus (HIV) Disease
Immunosuppression/Immunocompromised
Malignancy NOS
S-P Liver Transplant
S-P Organ Transplant NOS
S-P Renal Transplant