1. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. in the clinic Herpes Zoster

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3. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. Who should receive the vaccine against varicella zoster?  Immunocompetent ≥60 years (regardless prior HZ)  Zostavax (concentrated version of chickenpox vaccine)  Single, subcutaneous dose in the deltoid of arm  Don’t use antivirals 24h before until 14d after vaccination  Can be given at same time as flu vaccine

4. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What are risk factors for herpes zoster?  Occurs at any age in persons with previous varicella  Risk factors  Being older than age 60  Being immunocompromised from disease or medical Rx  Having varicella before 1 yr of age  Proximate cause rarely established  Recurrence uncommon

5. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. Who should not receive the vaccine against varicella zoster (a live-virus vaccine)?  Those with a life-threatening or severe allergic reaction to gelatin, neomycin, or another component of vaccine  Those with leukemia, lymphoma, or another blood or bone cancer  Those with HIV/AIDS who have T-cell counts <200  Those treated with drugs that affect the immune system, including high-dose steroids  Women who are or might be pregnant

6. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What is the evidence that the vaccine works? Shingles Prevention Study  Double-blind RCT: 38,546 people ≥60y with Hx of varicella  315 HZ cases among vaccine recipients vs. 642 with placebo  27 cases of postherpetic neuralgia among vaccine recipients vs. 80 among placebo recipients  Vaccine more effective preventing HZ in those <70 but more effective preventing postherpetic neuralgia in those ≥70  Effective for at least 6 years Observational study  75,761 vaccinated and 227,283 unvaccinated people ≥60y  Vaccine reduced frequency of HZ and involvement of the eye and hospitalizations for HZ

7. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What are the barriers to vaccination?  Fewer than 10% eligible people in U.S. receive vaccine  Costs $100 to $300  Most expensive vaccine for older adults  Many physicians unaware Medicare pays for it through Part D instead of Part B

8. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. When should clinicians consider low- dose acyclovir to prevent herpes zoster?  Low-dose acyclovir recommended for:  Immunocompromised patients who can’t receive the VZV vaccine because it contains a live virus  Including patients receiving bortezomib and recipients of allogenic transplants of peripheral blood stem cells  Comparable dose of valacyclovir / famciclovir can be used  Note: For patients receiving anti-TNF-α therapy, low-dose acyclovir not yet recommended

9. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. CLINICAL BOTTOM LINE: Prevention…  Herpes zoster (shingles) occurs most commonly in…  People >60y with age-related immune system weakening  People who are immunocompromised  Live-virus vaccine recommended to prevent varicella in children and adults w/o antibodies against VZV  Concentrated formulation of the vaccine against varicella recommened to prevent herpes zoster in adults ≥60y  Vaccine contraindicated if immune system weakened  Use low-dose acyclovir instead

10. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. Can serologic tests help guide decisions about vaccination for herpes zoster?  To establish whether immunity present  Obtain titers of serologic antibodies against VZV  However, screening before vaccination unneeded  Safe to vaccinate immune persons  Postvaccination serologic testing not recommended

11. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. CLINICAL BOTTOM LINE: Screening…  Screening for serologic antibodies to VZV before vaccination  Generally not required  Safe to vaccinate people already immune to the disease  However, screening provides information on immunity status  Might be useful to some people

12. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What symptoms are typical?

13. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What symptoms are typical?  Erythematous, maculopapular rash  Band-like distribution corresponds to affected nerve  Does not cross the midline  Isolated lesions outside primary dermatome not unusual  Rash is followed by clear vesicles for 3 to 5 days, pustulation, and scabbing  Other possible symptoms  Generally feeling unwell, malaise  Photophobia, headache  Significant fever is rare

14. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What conditions can be confused with herpes zoster?  Contact dermatitis cutaneous reaction to topical Rx  Especially from exposure to toxic plants  Localized HZ-like rash doesn’t usually conform to dermatomal distribution  Consider an alternative diagnosis if  The patient has a rash without pain  Rash doesn’t conform to a dermatomal distribution  Neuralgic pain persists without typical skin eruption  Zosteriform herpes simplex, especially in sacral area  Painful skin vesicles with distribution that may mimic HZ  Patients with >2 episodes HZ should have virologic testing to distinguish between HSV and varicella zoster virus

15. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. When should clinicians consult a specialist to help diagnose herpes zoster?  Infectious disease specialist or dermatologist  For assistance recognizing atypical presentations  For assistance with procedures such as skin biopsy  Ophthalmologist  Eye involvement (herpes zoster ophthalmicus)  Otolaryngologist  Facial nerve involvement (Ramsay-Hunt syndrome)

16. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. CLINICAL BOTTOM LINE: Diagnosis…  Characteristic rash in the involved dermatome  Erythematous maculopapular rash followed by clear vesicles for 3 to 5 days, pustulation, and scabbing  Sensations may range from mild itching or tingling to severe pain preceding the development of skin lesions  Clinical appearance of fully developed HZ is quite distinct  When diagnosis isn’t obvious, order confirmatory lab tests  Differential Dx: contact dermatitis; HSV infection  Consult specialists when presentation is atypical or complex

17. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What complications should the clinician anticipate?  Vision and hearing impairments  Neurologic complications  Vasculopathy, myelitis, cranial and peripheral nerve palsies, and polyradiculitis  Bacterial infection of cutaneous lesions  Varicella zoster infection of lungs and CNS  In immunocompromised persons  Postherpetic neuralgia  Pain >3 months after rash has resolved  Intensity varies from trivial to debilitating  More frequent with age, severe acute pain, larger rash

18. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What antiviral drugs are available to treat herpes zoster?  For those presenting within 72h of lesion onset:  Start antiviral drug: famciclovir; valacyclovir; or acyclovir  Reduces pain duration  Shortens new lesion formation duration  Accelerates healing + reduce duration of viral shedding  Role in postherpetic neuralgia less clear  For those presenting >72h after lesion onset:  Use antivirals if new vesicle formation continuing or patient has complications (cutaneous, motor, neurologic, ocular)  Despite lack of evidence on effectiveness

19. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. When should intravenous antivirals be given?  CNS involvement, especially myelitis  Manifestations where active viral replication less certain  For example, delayed contralateral hemiparesis  Dissemination of herpes zoster to liver, lungs, or other visceral organs

20. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What drugs can be used for control of acute pain?  Even with limited skin involvement, pain can be severe  Early pain relief may reduce risk of postherpetic neuralgia  Start with OTC pain relief (acetaminophen, ibuprofen)  Have low threshold for adding a short-acting narcotic  Prescribe on a regular schedule, not “as-needed”  Consider adding gabapentin or tricyclic antidepressant  Be aware some tricyclic antidepressants (amitriptyline) can cause serious problems in older adults

21. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What is the role of corticosteroids in treating herpes zoster?  Corticosteroids don’t reduce frequency or severity of postherpetic neuralgia  But provide other benefits: early healing and less acute pain  Prescribe 10 to 14 days of tapering oral prednisone for patients >50y with moderate-to-severe pain  Prescribe only if you also prescribe antiviral drugs

22. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What nondrug therapies should be considered when managing herpes zoster?  Keep cutaneous lesions clean and dry  Wash rash with soap and water and pat dry  Warm or cool astringent soaks may be soothing  Consider using sterile, occlusive, nonadherent dressing to protect lesions and promote healing  Wear loose-fitting clothing  Topical creams and ointments provide no benefit

23. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. When should patients be hospitalized?  If patient has disseminated herpes zoster  If patient has ocular involvement  For observation, supportive care, and IV acyclovir

24. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. When should a specialist be consulted?  Pain specialist  When treating postherpetic neuralgia  Neurologist  When patient develops vasculopathy or myelitis  Ophthalmologist  All patients with herpes zoster ophthalmicus  Infectious disease specialist  For managing antiviral drugs

25. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What should patients know about their herpes zoster?  How to soothe and protect involved skin  What to expect regarding potential for chronic  Dosing regimen for pain medicines  Risk of transmitting virus to others and causing chickenpox (varicella)  Avoid contact with susceptible infants, small children, pregnant women, and immunocompromised individuals  Virus transmits primarily through direct contact, but also through the air

26. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. What other complications should a clinician look for after an episode of herpes zoster?  Contralateral hemiparesis  VZV can induce CNS angiitis and result in stroke-like symptoms  Hemiparesis contralateral to antecedent trigeminal zoster  Multifocal vasculopathy  Consider if altered mental status or focal neurologic findings during / after episode  Acute retinal necrosis  Consider in patients w/ acute visual changes and Hx of HZ  Most cases occur in patients w/ AIDS  Herpes zoster not associated with increased cancer risk

27. © Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (5): ITC3-1. CLINICAL BOTTOM LINE: Treatment…  Use antiviral drugs: famciclovir, valacyclovir, acyclovir  Add oral corticosteroids for beneficial anti-inflammatory effects  Treat pain early and aggressively  To reduce acute and postherpetic neuralgia  Start with OTC pain relievers and add short-acting narcotic analgesics if needed  Use on scheduled rather than an as-needed basis  Use conservative measures to soothe and protect involved skin  Hospitalize for disseminated HZ infection or ocular involvement  Consult a specialist if Dx or management unclear or complicated