Title: Hilton IrvineOrange County Airport
12008
Symposia Series 1
Hilton Irvine/Orange County Airport Irvine,
California March 29, 2008
1
1
2Strategies for Preventing Herpes Zoster and
Postherpetic Neuralgia Are Your Patients
Adequately Protected?
- M. Susan Burke, MD
- Clinical Assistant Professor of Medicine
- Thomas Jefferson University
- Philadelphia, Pennsylvania
- Director, Internal Medical Clinical Care Center
- Lankenau Hospital
- Wynnewood, Pennsylvania
3Do you routinely recommend and administer the
herpes zoster vaccine to your patients who are
60 years of age?
?
KEY QUESTION
- Yes
- No
- Use your keypad to vote now!
4Do you routinely recommend and administer the
herpes zoster vaccine to your patients who are
60 years of age?
Use your keypad to vote now!
5Faculty Disclosure
- Dr Burke advisory board Merck Co., Inc.
speakers bureau Merck Co., Inc., Pfizer Inc.
6Learning Objectives
- Discuss the natural history and public health
burden of herpes zoster and postherpetic
neuralgia (PHN) - Review the benefits and limitations of current
treatment options for herpes zoster and PHN - Evaluate clinical trial data on the efficacy and
safety of herpes zoster vaccination
7Low Adult Immunization Rates
- 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 gt65 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.
8Natural History, Epidemiology, and Health Burden
of Herpes Zoster and PHN
9Natural History of Herpes Zoster
VZV varicella-zoster virus Adapted from Kost
RG, Straus SE. N Engl J Med. 199635532-42
Hope-Simpson RE. Proc R Soc Med. 1965589-20.
10Case Study
11Case Study 1
- 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
12Herpes Zoster Rash
Photo provided courtesy of M. Susan Burke, MD,
Director, Internal Medicine Clinical Care Center,
Lankenau Hospital.
13What factors in this patients history
may have predisposed her to the
development of herpes zoster?
?
DECISION POINT
- Impaired cell immunity due to advancing age,
diseases, or immunosuppressive therapy - Psychological stress
- Physical trauma
- All of the above
- None of the above
- Use your keypad to vote now!
14What factors in this patients history may have
predisposed her to the development of herpes
zoster?
- Impaired cell immunity due to advancing age,
diseases, or immunosuppressive therapy - Psychological stress
- Physical trauma
- All of the above
- None of the above
Use your keypad to vote now!
15Risk of Herpes Zoster
- Lifetime risk of herpes zoster is estimated to be
1 in 5 individuals1 - 50 of individuals living until 90 years of age
will develop herpes zoster2 - Risk factors for herpes zoster include
- Advancing age1,2
- Reduced VZV-specific cell-mediated immunity
- HIV/AIDS1,2
- Hematologic and neoplastic malignancy1,2
- Bone marrow and organ transplants1,3
- Immunosuppressive therapy1,2
- Psychological stress4
- Physical trauma4
1Gnann JW Jr, Whitley RJ. N Engl J Med.
2002347340-346 2Johnson RW, Whitton TL. Expert
Opin Pharmacother. 20045551-559 3Kawasaki H
et al. J Pediatr. 1996128353-356 4Thomas SL,
Hall JA. Lancet Infect Dis. 2004426-33.
16Incidence of Herpes Zoster Increases With Age
Estimated 1 million cases in the United States
annually, which will likely increase as
population ages
2000
Women
1629
Men
1500
1122
1118
Rate Per 100,000 Person-Years
1000
876
640
495
500
318
307
262
201
194
184
121
90
54
39
0
0-14
15-24
25-34
35-44
45-54
55-64
65-74
75
Age (Years)
Donahue JG et al. Arch Intern Med.
19951551605-1609 Oxman MN et al. N Engl J Med.
20053522271-2284.
17Complications of Herpes Zoster
Gnann JW Jr, Whitley RJ. N Engl J Med.
2002347340-346 Arvin AM. Clin Microbiol Rev.
19969361-381Moriuchi K, Rodriguez W. Pediatr
Infect Dis J. 200019648-653.
18Postherpetic Neuralgia
- Chronic neuropathic pain that persists or
develops after herpes zoster rash has healed1 - Recent definitions include pain 90-120 days after
rash onset1,3 - Clinical features of PHN include2
- Constant aching and burning, intermittent
lancinating or stabbing pain, allodynia,
hyperpathia - Risk factors include3
- Advancing age, severity of acute pain and rash,
painful prodrome, and number of affected
dermatomes - Incidence and duration increase with advancing
age4
1Oxman MN et al. N Engl J Med. 20053522271-2284
2Wood MJ, Easterbrook P. Shingles, scourge of
the elderly. In Sacks SL et al, eds. Clinical
Management of Herpes Viruses. Amsterdam IOS
Press 1995193-209 3Jung BF. Neurology.
2004621545-1551 4 Kost RG, Straus SE. N Engl J
Med. 199635532-42.
19Impact of PHN on Quality of Lifein Older Adults
Schmader KE. Clin J Pain. 200218350-354
Chidiac C et al. Clin Infect Dis. 20013362-69
Lydick E et al. Qual Life Res. 1995 441-45
Katz J et al. Clin Infect Dis. 200439342-348
Coplan PM et al. J Pain. 20045344-356.
20Diagnosis of Herpes Zoster
21Acute Herpes Zoster Clinical Manifestations
- Prodrome of dermatomal pain 2-5 days
- Rash characteristics
- Initially maculopapular, then vesicular with an
erythematous base - Unilateral, although can slightly overlap midline
- Usually involves 1 or 2 dermatomes
- May be associated with pain or other abnormal
sensations - Evolves over 7-10 days, healing over next 2-4
weeks - Reactivation may involve pain without rash
(zoster sine herpete)
Oxman MN. Clinical manifestations of herpes
zoster. In Arvin AM, Gershon AA, eds.
Varicella-Zoster Virus Virology and Clinical
Management. Cambridge, UK Cambridge University
Press 2000246-275.
22Acute Herpes Zoster Rash
Order of rash progression Vesicles Pustular
lesions Lesions crust over Resolution
of rash
Photo and slide courtesy of John W Gnann, Jr, MD.
23Herpes Zoster Rash
Photo provided courtesy of Dr. Kenneth Schmader,
Associate Professor of Medicine Geriatrics,
Duke University School of Medicine.
24Trigeminal Zoster
Photo provided courtesy of M. Susan Burke, MD,
Director, Internal Medicine Clinical Care Center,
Lankenau Hospital.
25Pitfalls in Diagnosis
- Prodrome of acute pain and paresthesias may be
mistaken for other painful conditions - Migraine, glaucoma, myocardial infarction,
pleurisy, duodenal ulcer, cholecystitis,
appendicitis, and biliary or renal colic - Rash can appear similar to other rashes
- Zosteriform herpes simplex is the most frequent
error in diagnosis - Can be linear, but heals more rapidly, is likely
to have less pain, and may recur in same area - If indicated, only reliable way to distinguish
between the two is with laboratory testing (PCR,
culture, IFA) - Occasional confusion with contact dermatitis
HSV herpes simplex virus IFA
immunofluorescent assay PCR polymerase chain
reaction. Oxman MN. Clinical manifestations of
herpes zoster. In Arvin AM, Gershon AA, eds.
Varicella-Zoster Virus Virologyand Clinical
Management. Cambridge, UK Cambridge University
Press 2000246-275 Rubben A et al. Br J
Dermatol. 1997137256-261 Gershon AA et al.
Varicella-zoster virus. In Murray PR et al, eds.
Manual of Clinical Microbiology. 6th ed.
Washington, DC ASM Press 1995884-894.
26Recurrent Herpes Simplex
Photo provided courtesy of M. Susan Burke, MD,
Director, Internal Medicine Clinical Care Center,
Lankenau Hospital.
27Contact Dermatitis
Reprinted with permission from DermNet. Available
at http//dermnet.com. Accessed February 4, 2008.
28Treatment Strategies for Herpes Zoster and PHN
29Case Study 1 (contd)
- The patient was started on
- Valacyclovir 1000 mg 3 times per day for 7 days
- Oxycodone 10 mg/acetaminophen 650 mg every 4-6
hours as needed - Gabapentin 300 mg, titrated up to 300 mg tid
over the next 2 weeks - Silver sulfadiazine cream applied 1-2 times per
day, and diphenhydramine 25 mg every 6 hours as
needed for itching
30Antiviral therapy administered within 72 hours
of rash onset can reliably prevent PHN
?
DECSION POINT
- True
- False
- Unsure
- Use your keypad to vote now!
31Antiviral therapy administered within 72 hours
of rash onset can reliably prevent PHN.
Use your keypad to vote now!
32Pharmacologic Management of Herpes Zoster
Antivirals
- Most widely used treatment
- Nucleoside analogs block viral replication1 and
promote rash healing2 - 3 agents available
- Acyclovir3 800 mg 5x per day, 7-10 days
- Famciclovir4 500 mg q8h, 7 days
- Valacyclovir5 1000 mg 3x per day, 7 days
- 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
unknown1,6 - Do not reliably prevent PHN1,6
1Kost RG, Straus SE. N Engl J Med.
199633532-42 2Gnann JW Jr, Whitley RJ. N Engl
J Med. 2002347340-346 3Zovirax package
insert. Research Triangle Park, NC
GlaxoSmithKline 2004 4Famvir package insert.
East Hanover, NJ Novartis Pharmaceuticals
2002 5Valtrex package insert. Research
Triangle Park, NC GlaxoSmithKline 2005
6Mounsey AL et al. Am Fam Physician.
2005721075-1080.
33Management StrategiesAcute 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.
198638363-365 Kalibala S et al. AIDS Action.
1990102-3.
34Case Study 1 (contd)
- The patients 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
35Treatments 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. 1Rowbotham M et al. JAMA. 19982801837-1842
2Dworkin RH et al. Neurology. 2003601274-1283
3Pappagallo M, Haldey EJ. CNS Drugs. 2003
17771-780 4Watson CPN, Babul N. Neurology.
1998501837-1841 5Raja SN et al. Neurology.
2002591015-1021 6Davies PS, Galer BS. Drugs.
200464937-947.
36Limitations of PHN Treatments
- PHN is difficult to treat
- Therapy does not work for every patient
- Effect of therapy is often modest
- Therapy must be individualized
- Introduce and modify treatments sequentially to
determine their efficacy and tolerability - Titrate dose so benefits exceed side effects
- Introduce treatments separately
Comorbid illness, the risk of drug interactions,
and side effects must be considered when treating
elderly patients with PHN
Adapted from Kost RG, Straus SE. N Engl J Med.
199633532-42.
37Case Vignette
38Reducing the Incidence and Severity of Herpes
Zoster and PHN With Herpes Zoster Vaccination
39Herpes Zoster Vaccination
Varicella Exposure
Silent Reactivation?
ZosterVaccination
VZV T cells
Zoster Threshold
Varicella
Age
Adapted from Kost RG, Straus SE. N Engl J Med.
199635532-42 Hope-Simpson RE. Proc R Soc Med.
1965589-20.
40Shingles Prevention Study
- A VA Cooperative Study to determine whether
zoster vaccine decreased the incidence and/or
severity of herpes zoster and PHN - Randomized, double-blind, placebo-controlled
- 22 US sites (VA and university medical centers)
- Enrolled 38,546 adults 60 years of age
- 46 70 years of age (gt6.6 80 years of age)
- Study end points
- Reduction in burden of illness (composite of
incidence, severity, and duration of herpes
zoster) - Incidence of herpes zoster and PHN
VA Department of Veterans Affairs. Oxman MN et
al. N Engl J Med. 20053522271-2284.
41Herpes zoster vaccination reduces
the burden of illness associated
with zoster by
?
KEY QUESTION
- 31
- 41
- 61
- 100
- Use your keypad to vote now!
42Herpes zoster vaccination reduces
the burden of illness associated
with zoster by
Use your keypad to vote now!
43Vaccine Efficacy for Herpes Zoster
Burden of Illness
9
Plt.001
8
Vaccine
7
Placebo
6
Herpes Zoster Burden of Illness
5
4
3
2
1
0
All
60-69
?70
CI confidence interval Oxman MN et al. N Engl J
Med. 20053522271-2284.
Age (Years)
44Herpes Zoster Vaccination Reduces Incidence of
Herpes Zoster and PHN
Oxman MN et al. N Engl J Med. 20053522271-2284.
44
45CDC RecommendsHerpes Zoster Vaccination in Adults
- October 25, 2006 ACIP recommends that the
zoster vaccine be given to all people 60 years
of age, including those who have had a previous
episode of herpes zoster1 - October 2007 CDC includes zoster vaccine in
adult immunization schedule for adults 60 years
of age, including those who have had a previous
episode of herpes zoster2
ACIP Advisory Committee on Immunization
Practices CDC Centers for Disease Control and
Prevention. 1CDCs Advisory Committee Recommends
Shingles Vaccination press release. Atlanta,
GA CDC Press Office October 26, 2006
2Advisory Committee on Immunization Practices.
Recommended adult immunization schedule United
States, October 2007September 2008. Ann Intern
Med. 2007147.
46Contraindications to Herpes Zoster Vaccine
- History of anaphylactic/anaphylactoid reaction to
neomycin - Serious current illness (or T 38.5C)
- History of immunodeficiency states including
- Leukemia, lymphomas, or other malignant neoplasms
affecting the bone marrow or lymphatic system - AIDS or other clinical manifestations of
infection with HIV - Immunosuppressive therapy, including high-dose
corticosteroids - Active untreated tuberculosis
- Known or suspected pregnancy
ZOSTAVAX package insert. Whitehouse Station,
NJ Merck Co., Inc. 2006.
47Barriers to Vaccination
- Patient-related issues
- Lack of knowledge about immunizations
- Fear of needles
- Vaccine access
- Vaccine coverage
- Physician-related issues
- Missed opportunities to vaccinate
- Unfamiliar with vaccination guidelines
- Lack of insight as to the importance of
vaccination
Adapted from Burns IT, Zimmerman RK. J Fam Pract.
200554S58-S62.
48Strategies to Improve Vaccination Rates
- Communicate effectively with patients
- Provide education and information about risks and
benefits of vaccination - http//www.cdc.gov/vaccines/pubs/vis/vis-facts.htm
- Develop office protocols
- Assess each patients vaccination status
- Administer and document vaccinations properly
- Implement strategies to improve vaccination rates
- eg, patient reminders
- Facilitate patient access to recommended
vaccinations - Identify and minimize office barriers
- If needed, refer patients to other facilities
offering vaccines - Health centers, travel clinics, infectious
disease specialists
Poland GA et al and the National Vaccine
Advisory Committee. Am J Prev Med.
200325144-150.
49Case Study
50Case Study 2
- A 72-year-old man with a history of chronic
obstructive pulmonary disease, coronary artery
disease, and mild renal insufficiency arrives at
the clinic for his yearly flu shot - Medical history includes a history of herpes
zoster (V-1 dermatome with ocular involvement
and 18 months of PHN) 9 years ago - Medications inhaled corticosteroids, beta
agonist, ASA, and ACE inhibitor - Because of his prior severe case of shingles, the
patient has read about the herpes zoster vaccine
and wants to receive it today
ACE angiotensin-converting enzyme ASA
aspirin.
51Does this patient meet the criteria to
receive the herpes zoster vaccine,
and can it be given with
his flu shot?
?
DECISION POINT
- Yes, he should receive it, but should not get it
at the
same time as his flu shot - Yes, he should receive it,
and can get the flu shot
at the same time - No, he does not meet
criteria to receive the zoster
vaccine
because his medications
include inhaled corticosteroids - Unsure
- Use your keypad to vote now!
52Does this patient meet the criteria to
receive the herpes zoster vaccine,
and can it be given with
his flu shot?
- Yes, he should receive it, but should not get it
at the
same time as his flu shot - Yes, he should receive it,
and can get the flu shot
at the same time - No, he does not meet
criteria to receive the zoster
vaccine
because his medications
include inhaled corticosteroids - Unsure
Use your keypad to vote now!
53ACIP Guidance on What Constitutes Being Immune
Suppressed
- Corticosteroids a dose equivalent to either gt2
mg/kg of body weight or 20 mg/d of prednisone for
gt2 weeks raises concern about the safety of
vaccination with live-virus vaccines - Individuals receiving chemotherapy or radiation
for leukemia, other hematopoietic malignancies,
or solid tumors - Live-attenuated vaccines should not be
administered for at least 3 months after such
immunosuppression or chemotherapy
ACIP General Recommendations on
ImmunizationDecember 2006.
54The Herpes Zoster Vaccine and Inactivated
Influenza Vaccine Can Be Administered
Concomitantly
- Herpes zoster vaccine can be given with the
influenza vaccine - Clinical data have shown both vaccines to
demonstrate immunogenicity when administered
concomitantly compared with individual
administration
Kerzner B et al. J Am Geriatr Soc.
2007551499-1507.
55Case Study
56Case Study 3
- A 61-year-old woman, born and raised in Irvine,
California, arrives at the clinic for routine
followup - Active problems hypertension, type 2 diabetes
- Social history investment banker, unmarried,
no children - Medical history no prior herpes zoster claims
she has never had chickenpox
57Which of the following is a true statement
concerning this patient?
?
DECISION POINT
- She should not receive the herpes zoster vaccine
- She should not receive the herpes zoster vaccine
until she receives 2 doses of the varicella
vaccine - She should have varicella titers taken first and,
if positive,
may receive the herpes zoster
vaccine - She may receive the herpes zoster vaccine today
- Use your keypad to vote now!
58Which of the following is a true statement
concerning this patient?
- She should not receive the herpes zoster vaccine
- She should not receive the herpes zoster vaccine
until she receives 2 doses of the varicella
vaccine - She should have varicella titers taken first and,
if positive, may receive the herpes zoster
vaccine - She may receive the herpes zoster vaccine today
Use your keypad to vote now!
59Should the Herpes Zoster Vaccine Be Given to
Patients With Unknown Chickenpox History?
- VZV seropositivity rate among Americans 60 years
of age is gt991 - Most patients who do not recall history of
chickenpox are VZV seropositive - Serologic testing was not an entry requirement
for the Shingles Prevention Study - Data have shown herpes zoster vaccination to be
safe in VZV-seronegative patients2 - VZV serologic testing is not recommended prior
to receiving herpes zoster vaccine
1Kilgore PE et al. J Med Virol. 200370(suppl
1)S111-S118. 2Macaladad N et al. Vaccine.
2007252139-2144.
60Q A
61PCE Takeaways
62PCE Takeaways
- Incidence and severity of herpes zoster increase
with advancing age to produce substantial
negative effects on quality of life - Antiviral therapy may reduce the incidence and
severity of acute herpes zoster, but does not
reliably prevent PHN - Herpes zoster vaccination offers a safe and
highly effective method of reducing the public
health care burden of herpes zoster and its
complications
63PCE Takeaways (contd)
- The ACIP recommends vaccination of
immunocompetent individuals 60 years of age
regardless of previous history of herpes zoster - The CDC has included the herpes zoster vaccine
in the 2007-2008 Recommended Adult Immunization
Schedule
64Do you now plan to routinely recommend and
administer the herpes zoster vaccine to your
patients who are 60 years of age?
?
KEY QUESTION
- Yes
- No
- Use your keypad to vote now!
64
65Do you now plan to routinely recommend and
administer the herpes zoster vaccine to your
patients who are 60 years of age?
Use your keypad to vote now!
662008
Symposia Series 1
Hilton Irvine/Orange County Airport Irvine,
California March 29, 2008
66