Herpes Zoster and the Zoster Eye Disease Study ... Herpes Zoster and the Zoster Eye Disease Study (ZEDS)

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  • Herpes Zoster and the

    Zoster Eye Disease

    Study (ZEDS)

    Elisabeth J Cohen, MD

    Professor of Ophthalmology

    New York University SoM

    NYU Langone Medical Center

  • Financial Disclosures

    • I have no financial disclosures or conflicts of interest.

  • Presentations of Varicella Zoster Virus (VZV) Infection •Herpes Zoster (HZ) caused by

    reactivation of latent VZV in

    persons who have had varicella

    •Typical painful, unilateral,

    vesicular, dermatomal rash •Pain pre rash in 74%: unilateral,

    first time ever, moderate to

    severe, stabbing pain • Lee Clin Neurol Neurosurg


    •Herpes Zoster Sine Herpete:

    radicular pain without rash • Lewis BMJ 1958

    •Severe uveitis •Schwab Ophthalmology


    •Stroke due to HZ: only 63% hx

    zoster rash •Nagel Neurology 2008; 70:853-60

    •HZ without rash not very rare!

  • What’s New in Herpes Zoster

    • Increasing incidence of zoster

    •Decreasing age of onset of zoster

    •Risk factors before and after zoster

    •Varicella Zoster Virus (VZV) trigger for temporal/giant cell arteritis

    •Efficacy and safety of vaccines against zoster

    •Ongoing debate regarding timing of vaccination at age 50 or 60

    •I will make the case for age 50 years and above

    •Zoster Eye Disease Study (ZEDS) randomized controlled clinical trial

    to evaluate prolonged suppressive antiviral treatment to reduce

    complications of Herpes Zoster Ophthalmicus, NEI funded fall, 2016

    begins enrollment in spring, 2017

  • Herpes Zoster (HZ) / Shingles

    •Common disease

    •1,200,000 new cases/yr in US • Suaya Open Forum Infect Dis


    •10-20% involve Vth nerve •~99% age 40+ in USA have had varicella, are at risk for HZ

    •1 in 3 in US will have zoster • 1 in 2 age 85

    •More common, severe in immunocompromised persons •> 90% of people with HZ are not immunocompromised

    •Misconception #1 •Healthy people are not at risk for zoster and its potentially disabling sequelae- we are!

  • Increasing Incidence of Zoster Worldwide

    • Increasing incidence of HZ over

    60 yrs in population-based study

    •1945-60 v 1980-2007 in MN

    •59% women

    • Incidence up >4-fold in all ages

    • Increased steadily before and

    after varicella vaccination • Kawai Clin Infect Dis. 2016;jul


    • Increase in Australia

    •2000-2006 v. 2006-2013, pre-

    and post- universal varicella

    vaccination •MacIntrye PLoS One. 2015 Apr


    Age-specific rate of unique zoster cases (national data, by year).

    Rimland D , and Moanna A Clin Infect Dis. 2010;50:1000- 1005

    ©2010 by Oxford University Press

  • Age at Onset of Zoster

    •Rate goes up with age, but

    number of cases highest in 50’s • Yawn Neurology 2013; 81:928 (Figure 1)

    • Insinga J Gen Intern Med 2005;20:748-53 (2)

    • Ghaznawi Ophthalmology 2011;118:2242 (3)

    •CDC study mean age onset 52 yrs

    • Hernandez J Clin Virol 2011; 52:344-8

    •Taiwan population (35,000 HZ)

    •Mean age 55 (Lin Medicine 2016;95)

    •Misconception #2

    •Herpes Zoster is only a

    disease of the elderly- it

    affects large number of

    people in their prime too!








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  • Decreasing Age at Onset of Zoster

    •Age of onset of HZO (Chen Cornea 2015; 34:535)

    •400 pts (58% women) HZO onset 1996-2004 v. 2005-2012

    •Mean age 65 yrs 59 yrs P

  • Role of Varicella Vaccination in Zoster Increase

    •Postponement of HZ: encounters with varicella “boosts” immunity

    (Hope-Simpson Proc R soc Med. 1965;58: 9-20)

    •Many think varicella/chicken pox vaccination cause of increase in zoster

    and decrease in age at onset

    •However rise in zoster began before varicella vaccination • Leung. Clin Infect Dis 2011; 52:332-40, Russell Vaccine 2014;32;6319-24

    • Yawn. Mayo Clin Proc 2007; 82:1341, Kawai Clin Infect Dis 2016; 63:221-6

    •Routine varicella vaccination not widespread in Europe!

    • Increase in rates of HZ reported similar in these countries

    •Cause of increasing incidence of zoster is unknown!

  • Risk Factors for Development of Herpes Zoster

    •Well known : increasing age , immunocompromise, female sex

    •Recent additions to risk factors

    •Family history 3x, depression 4x, stress 3x, history of zoster 80% • Marin Open Forum Infect Dis. 2016 Jun 13;3

    •Heart failure 2x • Wu BMC Infect Dis 2015; 15:17

    •Traumatic brain injury 3x • Tung PLoSOne 2015 Jun 11;10

    •Diabetes 45%, asthma 50%, acute kidney disease 70% • Suava Open Forum Infectious Diseases 2014 Sep; 1(2)

    • Peng J Asthma 2016 Jul 13 [epub]

    • Yang Sci Rep 2015 Sep3;5:13747

    •Statin use 13% inc risk: case control study in UK, N=145,000 HZ,

    •Dose dependent: high dose 27% increase risk

    •Decrease in risk with increased time since use of statin.

    •Consistent with causal effect (Matthews Br J Dermatol 2016; 175:1183-94.)

    • Implications regarding importance of vaccination against zoster in

    patients with wide variety of medical conditions, and statin use

  • Smoking and Zoster

    •Association of cigarette smoking with a past history and incidence of HZ • Ban J Epidemiol Infect. 2017 Jan 16:1-6 [epub ahead of print]

    •Community-based prospective cohort study over 3 years in Japan

    •Baseline survey: > 12,000 with information on smoking and history HZ

    •3 years active surveillance for incidence HZ

    •Past history HZ: current vs never smokers: 0.67 odds ratio

    • Incidence of HZ: current vs never smokers: 0.52 hazards ratio


    •Smoking inversely related to prevalence and incidence of HZ

    •Cellular immunity may be increased in light to moderate smokers

    •Not to encourage smoking

    •Personal comment: Study change in rates of smoking vs. HZ

  • Postherpetic Neuralgia (PHN)

    •Most common complication of zoster

    •Defined as pain beyond 3 months after onset of zoster

    •Occurs in ~30% of HZO with eye involvement, mostly age 65+

    •Systematic reviews of risk factors for PHN

    •Age, severity prodomal and acute pain, rash, HZO • Forbes Pain. 2015 July 25 [epub], Kawai Int J Infect Dis. 2015; 34: 126-31

    •Efficacy of (acute high dose) gabapentin to prevent PHN RCT

    •Prevent central nervous system sensitization •Rullan M Trials 2017; 18:24

    •Zoster risk factor for development major depression • Chen, M. H. Psychosom Med, 2014; 76:285-91.

    •Zoster is most common cause of suicide due to pain in people age 70

    years and older •Hess, TM. Minn Med. 1990; 73:37-40

  • Anecdote

    •My mother worked full time to age 67…She then got very ill with

    Shingles. Her optic nerve was involved and she was in severe pain. You

    could not even touch her hair or face. She suffered for many

    weeks…She was never the same….The chronic pain caused her to

    sleep for most of the day, she resigned as a deacon of the church as

    she could no longer attend services or meetings due to the pain. The

    pain never really went totally away… I received the vaccine about 2

    years ago, and pray I never get the disease. Neither the polio (age 12),

    meningitis (age 41), or RA (age 67 treated with methotrexate) stopped

    my very active mother, but the shingles destroyed her life.

    •KC 2017

  • Zoster Risk for

    Stroke, Heart,

    Vascular Disease

    Zoster long known risk factor for stroke

    •90% inc stroke, especially in younger pts

    •~2x risk neuro complications after HZO

    than HZ elsewhere age 45-64 • Wang PLoS One 2016; 11:e0164019

    • Kwon Clin Microbiol Infect 2016 Jun;22:542-8

    •Meta-analyses of relati