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Embassy Suites Raleigh-Durham/Research Triangle Cary, North Carolina June 21, 2008 Symposia Series 2 2008
Strategies for Preventing Herpes Zoster and Postherpetic Neuralgia: Are Your Patients Adequately Protected? Kevin P. High, MD, MSc Chief, Section on Infectious Diseases Professor of Medicine Sections on Infectious Diseases, Hematology/Oncology, and Molecular Medicine Co-Director, Molecular Medicine Graduate Program Wake Forest University School of Medicine Winston-Salem, North Carolina
Only 2% of adults ≥60 years of age received herpes zoster vaccination in its first year of availability (2006)
Only 2% of adults aged 18 to 64 years reported receiving Tdap
44% of adults >65 years of age reported receiving tetanus vaccination in the previous decade
Only 10% of women aged 18 to 26 years reported receiving at least 1 dose of the 3-dose human papillomavirus (HPV) vaccine course
CDC and National Foundation for Infectious Diseases news conference, January 23, 2008. Anne Schuchat, MD, Assistant Surgeon General, United States Public Health Service; Director, National Center for Immunization and Respiratory Diseases, CDC. Michael N. Oxman, MD, Professor, University of California, San Francisco; Staff Physician, Infectious Disease Section, VA Medical Center, San Diego. Kristin Nichol, MD, MPH, Chief of Medicine, Minneapolis VA Medical Center; Professor of Medicine and Vice Chair, Department of Medicine, University of Minnesota.
Natural History, Epidemiology, and Health Burden of Herpes Zoster and PHN
Natural History of Herpes Zoster VZV = varicella-zoster virus Adapted from Kost RG, Straus SE. N Engl J Med. 1996;355:32-42; Hope-Simpson RE. Proc R Soc Med . 1965;58:9-20. Age VZV T Cells Varicella Herpes Zoster Zoster Threshold Varicella Exposure Silent Reactivation?
A 61-year-old woman was recently diagnosed with cancer in her left breast and underwent port placement for chemotherapy. Several days later she developed burning, itching, and severe pain on her left chest (near the port site), arm, and back
A few days later, she developed a vesicular rash
She was unable to sleep because of excruciating discomfort
She cannot tolerate even contact with clothing to the affected area
Herpes Zoster Rash Photo provided courtesy of M. Susan Burke, MD, Director, Internal Medicine Clinical Care Center, Lankenau Hospital.
What factors in this patient’s history may have predisposed her to the development of herpes zoster?
Impaired cell immunity due to advancing age, diseases, or immunosuppressive therapy
Lifetime risk of herpes zoster is estimated to be 1 in 5 individuals 1
50% of individuals living until 90 years of age will develop herpes zoster 2
Risk factors for herpes zoster include
Advancing age 1-3 (reduced VZV-specific cell-mediated immunity [CMI])
Global reduction in CMI
Hematologic and neoplastic malignancy 1,2
Bone marrow and organ transplants 1,4
Immunosuppressive therapy 1,2
Psychological stress 5
Physical trauma 5
1 Gnann JW Jr, Whitley RJ. N Engl J Med. 2002;347:340-346; 2 Johnson RW, Whitton TL. Expert Opin Pharmacother . 2004;5:551-559; 3 Levin MJ et al. J Infect Diseases . 2008;197:825-835; 4 Kawasaki H et al. J Pediatr . 1996;128:353-356; 5 Thomas SL, Hall JA. Lancet Infect Dis . 2004;4:26-33.
Incidence of Herpes Zoster Increases With Age Donahue JG et al. Arch Intern Med . 1995;155:1605-1609; Oxman MN et al. N Engl J Med. 2005;352:2271-2284. Estimated 1 million cases in the United States annually, which will likely increase as population ages Rate Per 100,000 Person-Years Age (Years) 1629 876 640 318 194 184 90 54 39 121 1118 1122 495 307 262 201 0 500 1000 1500 2000 0-14 15-24 25-34 35-44 45-54 55-64 65-74 ≥ 75 Women Men
Complications of Herpes Zoster Gnann JW Jr, Whitley RJ. N Engl J Med . 2002;347:340-346; Arvin AM. Clin Microbiol Rev . 1996;9:361-381; Moriuchi K, Rodriguez W. Pediatr Infect Dis J . 2000;19:648-653. Neurologic Ophthalmic
Chronic neuropathic pain that persists or develops after herpes zoster rash has healed 1
Recent definitions include pain 90-120 days after rash onset 1-3
Clinical features of PHN include 2
Constant aching and burning, intermittent lancinating or stabbing pain, allodynia, hyperpathia
Risk factors include 3
Advancing age, severity of acute pain and rash, painful prodrome, and number of affected dermatomes
Frequency and severity increase with advancing age 4
1 Oxman MN et al. N Engl J Med. 2005;352:2271-2284; 2 Wood MJ, Easterbrook P. Shingles, scourge of the elderly. In: Sacks SL et al, eds. Clinical Management of Herpes Viruses . Amsterdam: IOS Press; 1995:193-209; 3 Jung BF. Neurology . 2004;62:1545-1551; 4 Levin MJ et al. J Infect Dis . 2008;197:825-835.
Impact of PHN on Quality of Life in Older Adults Schmader KE. Clin J Pain . 2002;18:350-354; Chidiac C et al. Clin Infect Dis . 2001;33:62-69; Lydick E et al. Qual Life Res . 1995; 4:41-45; Katz J et al. Clin Infect Dis . 2004;39:342-348; Coplan PM et al. J Pain . 2004;5:344-356. Physical Functional
Interference with basic activities of daily living including
Shown to accelerate rash healing and resolution of acute pain (days 1-30) 1
Effective when administered within 72 hours of rash onset; efficacy beyond 72 hours is unknown 1,6
Do not reliably prevent PHN 1,6
1 Kost RG, Straus SE. N Engl J Med. 1996;335:32-42; 2 Gnann JW Jr, Whitley RJ. N Engl J Med. 2002;347:340-346; 3 Zovirax [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2004; 4 Famvir [package insert]. East H an o ver, NJ: Novartis Pharmaceuticals; 2002; 5 Valtrex [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2005; 6 Mounsey AL et al. Am Fam Physician. 2005;72:1075-1080.
Management Strategies: Acute Herpes Zoster CNS = central nervous system; NSAIDs = nonsteroidal anti-inflammatory drugs. Physicians’ Desk Reference. 62th ed. Montvale, NJ: Thomson PDR; 2008; Montes LF et al. Cutis. 1986;38:363-365; Kalibala S et al. AIDS Action. 1990;10:2-3. Treatment Whom to Treat Limitations Oral antivirals Patients with zoster rash Use within 72 hours of rash onset IV acyclovir Selective use in immunosuppressed patients or those with CNS disease May use after 72 hours in immunosuppressed patients Oral corticosteroids Adjunctive therapy for patients with moderate to severe pain (controversial) Side effects: use with caution in patients with underlying illnesses Aspirin, NSAIDs, antihistamines, calamine, silver sulfadiazine Patients with minor pain or itching May not provide adequate pain relief Opioids, opioid-like drugs Patients with moderate to severe pain Significant side effects, potential for addiction
The patient’s rash resolved about 1 month after initial onset, but she is still experiencing discomfort in the same area. She returns to the clinic several times over the course of the next 6 months, during which time gabapentin was titrated up slowly to 2400 mg per day in divided doses and opioid medication was discontinued, as she no longer required it
She presents again 7 months after rash onset because her pain has increased. She ran out of gabapentin 2 weeks ago
Treatments for PHN: Pain Response and Adverse Event Profiles Gabapentin, pregabalin, lidocaine patch 5%, and topical capsaicin are approved by the Food and Drug Administration (FDA) for the treatment of PHN. 1 Rowbotham M et al. JAMA. 1998;280:1837-1842; 2 Dworkin RH et al. Neurology. 2003;60:1274-1283; 3 Pappagallo M, Haldey EJ. CNS Drugs . 2003; 17:771-780; 4 Watson CPN, Babul N. Neurology . 1998;50:1837-1841; 5 Raja SN et al. Neurology. 2002;59:1015-1021; 6 Davies PS, Galer BS. Drugs . 2004;64:937-947. Medication Pain Response and Adverse Event Profile Gabapentin, pregabalin 1,2 33% reduction in pain with gabapentin; 63% of patients receiving pregabalin experience clinically significant pain reduction Adverse events include somnolence, dizziness, and peripheral edema Tricyclic antidepressants 3 47% to 67% of patients report at least moderate pain relief Adverse events include sedation, confusion, urinary retention, dry mouth, postural hypotension, and arrhythmia Opioid analgesics 4,5 38% to 58% of patients report pain relief Adverse events include constipation, nausea, loss of appetite, dizziness, and drowsiness Lidocaine patch 5% 6 60% efficacy (ie, at least moderate pain relief) No systemic adverse events, but local reactions include erythema and skin rash Capsaicin cream Moderate pain relief but often with intolerable burning
Corticosteroids: Patients ≥60 years of age receiving a dose equivalent to 20 mg/d prednisone for >2 weeks should not receive the zoster vaccine for at least 1 month after discontinuation of such therapy
Topical (eg, skin, nasal, inhaled), intra-articular, bursal, or tendon injections are not considered sufficiently immunosuppressive to raise vaccine safety concerns
Immunosuppressive therapy not considered sufficiently immunosuppressive to raise vaccine safety concerns includes:
Methotrexate (≤0.4 mg/kg/week)
Azathioprine (≤3.0 mg/kg/d)
6-Mercaptopurine (≤1.5 mg/kg/d)
Centers for Disease Control and Prevention. MMWR (early release). 2008;57:1-30. CDC Recommendations: Immunocompromised Patients
CDC Recommendations: Herpes Zoster Vaccine and Inactivated Vaccines Can Be Administered Concomitantly
Immunogenicity of zoster and influenza vaccines is not compromised when the 2 are administered simultaneously 1
Zoster and influenza vaccines given concomitantly are generally well tolerated in older adults 2
Simultaneous administration of inactivated vaccines should not result in an impaired immune response or an increased rate of adverse events 1
Therefore, the zoster vaccine can be administered with other indicated vaccines within the same visit (eg, Td, Tdap, PPV)
1. Centers for Disease Control and Prevention. MMWR (early release). 2008;57:1-30; 2. Kerzner B et al. J Am Geriatr Soc . 2007;55:1499-1507.