Herpes zoster and Postherpetic neuralgia

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Herpes zoster and Postherpetic neuralgia

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• 1972? ??????????? ??
• 1973? ?????????????? ?????
• 1977? ???????????????
• 1980? ???????????????????(??)
• 1980-2007? ??????????(??????,???)
• 1984? ?????????????????? (1984/071985/06)
• 1993? ?????????????????
• 1995? ?????????????
• 1998? ????????????
• 2001? ??????????????????????,
• 2005? ??????????????????? (??)
• 2008? ????????????

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Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616

• Overall, 34,280 patients were diagnosed with
  zoster (incidence 4.89/1000 person-years)
• A total of 4543 patients (13.3) had persistent
  neuralgia one month after the start of the zoster
  rash (incidence 0.64/1000 person-years),
• 2944 patients (8.6) developed postherpetic
  neuralgia 3 months after the start of the zoster
  rash (incidence 0.42/1000 person-years).
• overall hospitalization rate for zoster was 16.1
  cases per 100,000 person-years.
• The cost for each home care case and per
  hospitalized case were approximately NT1655 and
  NT38,051, respectively

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Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616
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Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616
6
Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616
7
Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616
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Epidemiological Features and Costs of Herpes
Zoster in TaiwanA National Study 2000 to 2006
Acta Derm Venereol 2009 89 612616
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goals of therapy for herpes zosterJ Am Acad
Dermatol 200757S136-42

• The goals of therapy for herpes zoster are
• to accelerate healing,
• limit the severity and duration of pain,
• reduce complications, which include, in addition
  to postherpetic neuralgia, encephalitis,
  myelitis, cranial and peripheral palsies, a
  syndrome of delayed contralateral hemiparesis,
  and acute retinal necrosis.

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Management and prevention of herpes zoster a
Canadian perspective.

• Varicella-zoster virus reactivation leads to
  herpes zoster the main complication of which is
  postherpetic neuralgia (PHN).
• Rapid antiviral therapy initiated within 72 h of
  rash onset has been shown to
• accelerate rash healing,
• reduce the duration of acute pain and,
• to some extent, attenuate the development and
  duration of PHN.

Can J infect dis Med Microbiol 201021(1)45-52.
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Pathogenesis and diagnosis

• Varicella-zoster virus (VZV), a member of the
  Herpesviridae family
• Following an incubation period of 14 to 21 days,
  the primary infection is varicella (chickenpox).
• The virus then migrates via retrograde axonal
  transport to sensory ganglia, where it
  establishes lifelong latency.
• VZV reactivations can be asymptomatic or
  symptomatic leading to the development of zoster,
  which typically occurs many decades after primary
  infection.

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Clinical manifestation of Herpes zoster

• A typical zoster rash in an immunocompetent
  individual involves one or two adjacent
  dermatomes, and usually lasts seven to 10 days.
• Thoracic dermatomes up to 50 of cases,
• Ophthalmic areas in 1 to 10
• About 75 patients report having prodromal pain
  (zoster sine herpete)
• can precede the rash by days to weeks

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Clinical manifestation of Herpes zoster

• Because zoster rash is so typical, diagnosis can
  be made clinically in most instances.
• In very early stage, red edematous plaque may be
  confused with cellulitis or contact dermatitis.
• While few papular lesions only, differentiate
  from herpes simplex virus (HSV) or conditions
  such as impetigo, folliculitis, insect bites
  etc..
• The rash may be atypical dissemination or
  chronicity in immunocompromised patients.

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Laboratory diagnostic test of Herpes zoster

• Swabs and cell scrapings from the base for
• Direct fluorescent antibody staining (DIF), 90
  positive in vesicular stage (DDx VZV/HSV)
• Cell culture 60 to 75, need one week
• Polymerase chain reaction (PCR)
• the mostsensitive diagnostic method to
  distinguish wild-type VZV from the vaccine Oka
  strain
• Tzanck cytology ballooning cells and
  multinucleated giant cells
• Cytopathic viral infection

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Herpes zoster
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Complication of Herpes zoster

• Pain is the most frequent complication.
• Acute pain occurring within 30 days after rash
  onset,
• subacute pain (between 30 days and 90 to 120
  days)
• postherpetic neuralgia (PHN), significant pain
  and persists longer than 90 to 120 days after
  rash onset.
• Keratitis, 2/3 in Hepes zoster ophthalmicus
• neurological complications
• Ramsay Hunt syndrome HZ of the facial nerve,
  with vesicles on the ear, palate or tongue
  leading to facial paresis, hearing loss and
  vertigo.
• Others myelitis, aseptic meningitis, Bells
  palsy, etc..

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Complication of Herpes zoster
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Complication of Herpes zoster

• Visceral dissemination fatality rate of 5 to
  15,even with antiviral therapy
• cellular immunodeficiency HIV, hematological
  malignancies, solid tumours, and following stem
  cell or organ transplantation,
• ????????,????????
• Soft tissue infection, ? After NSAID

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Postherpetic Neuralgia (PNH)

• The risk of PHN, given an episode of zoster,
  increases with age.
• 10 of patients with zoster
• in one-third of zoster patients gt 60 y/o
• incidence of 14 cases per 10,000 person-years
• In addition to advancing age, the severity of
  acute pain and rash, prodromal pain, ophthalmic
  location and possibly female sex are also risk
  factors for PHN

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Antiviral Treatment for Herpes zoster

• The main objectives of antiviral treatment are
• to reduce viral replication,
• To reduce duration of rash and acute pain
• to prevent complications seen mostly in
  immunocompromised patients.
• early antiviral therapy may also attenuate
  development of PHN.

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10.7.1.1. ?????????

• Acyclovir(98/11/1?100/7/1) ??????????????
• ??????
• ????????????????????VI??,?????????
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• ????,???? (??38???) ??? (?X???)
  ????,?????(85/1/1)?
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• ???????? (acute retina necrosis)?
• ???????????????????????????,??????????????(86/1/1?
  87/4/1)?
• ???????????????????acyclovir(87/11/1)
• ????????????
• ?????????????? (TBI) ??????????????
• ???????????????acyclovir?????????14?21??(95/6/1?10
  0/7/1)

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10.7.1.1. ?????????

• 2.Famciclovirvalaciclovir(100/7/1)
• ??????????????
• ????????????????????VI??,?????????
• ??????????????S2??,?????????
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• ???????? (acute retina necrosis)?
• ??????3????????????????????,???5???????????
• ???????????????????acyclovir
• A.????????????
• B.??????????????(TBI)?????????30????
• 3. Acyclovir?Famciclovir?valaciclovirt????????,???
  ????10???,???????????????,???????(95/6/1?100/7/1)

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Antiviral Treatment for Herpes zoster
In Taiwan, the usual dosage for Famciclovir is
250mg TID
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Usage of Famciclovir for Herpes zoster

• Equal efficacy is noted in RCT 559
  immunocompetent adults treated for 7 days
  (initiated within 72 hours of onset of zoster
  skin lesions)
• famciclovir (750 mg QD, 500 mg BID, or 250 mg
  TID)
• acyclovir (800mg x5/day ).
• J Clin Virol 200429248-53
• Famciclovir, like acyclovir, has also been shown
  to reduce the duration of postherpetic neuralgia
  by a median of 2 months. Ann Intern Med
  199512389-96

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Rash severity in herpes zoster Correlates and
relationship to postherpetic neuralgiaJ Am Acad
Dermatol 200246834-9
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BRITISH MEDICAL JOURNAL 293 1529, 1986
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Frequently descriptions in Textbook or Review
Articles

• Antiviral drugs have been consistently found to
  effectively reduce the severity and duration of
  herpes zoster, and are safe and well tolerated
  with minimal adverse effects.
• They do not, however, reliably prevent the
  development of postherpetic neuralgia.

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ANTIMICROB AGENTS CHEMOTHERA 3915461553, 1995
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In Canada

• Oral therapy with one of the three antivirals is
  recommended as first-line treatment for all
  immunocompetent patients who
• consult rapidly (preferably within 72 h of rash
  onset)
• who fulfill any of the following criteria
• 50 years of age or older
• moderate or severe acute pain
• moderate or severe rash
• Nontruncal involvement

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Late antiviral treatment

• Of note, the 72 h inclusion criterion has been
  arbitrarily chosen in randomized clinical trials
  and may not be optimal in clinical practice.
• The presence of new vesicles, which reflect
  active viral replication, may be an alternative
  way to select patients for antiviral treatment.
• Ophthalmic zoster should be treated more
  aggressively, including referral for eye
  assessment and starting of antiviral therapy even
  beyond the 72 h period.

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Usage of corticosteroids in HZ

• Although showing some benefits in acute zoster
  pain, corticosteroids do not provide added value
  over acyclovir in reducing PHN, and are thus not
  recommended in the initial management of HZ .

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Acute pain associated with herpes zoster

• Defined as pain before and during blister
  eruption.
• Prodromal pain can consist of various symptoms,
  e.g. itching, burning, tingling, stubbing,
  tenderness superficial and deep pain.
• Usually moderate-to-severe acute pain caused by
  acute neuritis, can last for nearly a month.
• Pathogenesis of acute pain
• an abnormal discharge in the dorsal horn,
• by the inflammation of the dorsal root ganglion,
• by the extent of the neuritis and the dermal
  vasculitis.

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Use of NSAID in VZV infection
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NSAID may induce more infection
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Use of NSAID in VZV infection

• RESULTS
• In patients with varicella, there were 386 cases
  of severe skin or soft tissue complications (rate
  2.8 per 1000) during the 2month follow-up period
  (mean age 10.7 years). The rate of complications
  associated with exposure to NSAIDs was increased
  (rate ratio 4.9 95 CI 2.1, 11.4).
• In patients with zoster disease, there were 681
  cases of severe skin or soft tissue complications
  (rate 6.3 per 1000) during the 2month follow-up
  (mean age 60.9 years).
• The rate ratio of complications associated with
  exposure to NSAIDs was 1.6 (95 CI 1.1, 2.4). In
  both conditions, there was no increased risk of
  complication associated with a current exposure
  to paracetamol.
• CONCLUSIONS
• The use of NSAIDs is associated with an elevated
  risk of severe skin and soft tissue complications
  of varicella zoster virus infection, mostly in
  children with varicella.

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Zoster-Associated Pain/Postherpetic Neuralgia
pain

• Pain that persists beyond a defined period of
  time is referred to as postherpetic neuralgia.
• from 914, Usually in elder, rare in lt 50y/o
• Although the overall incidence of chronic pain is
  low, its incidence and severity increases with
  rising age.

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BMJ 200032114
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BMJ 200032114
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Journal of Antimicrobial Chemotherapy (1998) 41,
549556
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Zoster Brief Pain InventoryOrigin J Pain
20045344-56.

• 1. Have you had any pain caused by your shingles
  in the last 24 h?
• (yes, no)
• 2. Shade in the areas where you feel pain on the
  diagram (face and back body anatomy diagrams)
• 3. Rate your worst pain in the last 24 h (scale
  of 010)
• 4. Rate your least pain in the last 24 h (scale
  of 010)
• 5. Rate your average pain in the last 24 h (scale
  of 010)
• 6. Rate your current pain
• (scale of 010)

• 7. Are you receiving treatments or medication for
  your shingles pain? (yes, no)
• 8. How much relief have these treatments provided
  in the last 24 h? (scale of 0100)
• 9. How your shingles pain has interfered with
  (last 24 h)
• A. General activity
• B. Mood
• C. Walking ability
• D. Normal work
• E. Relations with other people
• F. Sleep
• G. Enjoyment of life
• (scale of 010 for each item)

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Management of Zoster-assocoated Pain(ZAP)

• ZAP Acute pain associated with rash and PHN.
• ZAP may be described as continuous or paroxysmal,
  evoked or spontaneous, burning or lancinating,
  and other sensory abnormalities in the skin.
• Different (2) pain mechanisms .
• Increased excitability of damaged primary
  afferent neurons causing irritable nociceptors
  and central sensitization, resulting in pain and
  allodynia
• Degeneration of nociceptive neurons in dorsal
  root ganglia or the spinal cord, leading to
  deafferentation with central hyperactivity,
  causing pain but typically without allodynia .

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Treatment regimensRasi et al. - Acyclovir in
treatment of post-herpetic pain J Infect Dev
Ctries 2010 4(11)754-760

• All patients took acyclovir, 800 mg five times a
  day, for the first four days of the first week,
  followed by three treatment-free days. In the
  cases evidence of pain reduction but not CPR, a
  second course of treatment with the same dosage
  was offered. The patients were followed for three
  months without medication

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The efficacy of time-based short-course acyclovir
therapy in treatment of post-herpetic pain J
Infect Dev Ctries 2010 4(11)754-760.

• Group 1 within 72 hrs, Group 2 after 72 hrs
• acyclovir, 800 mg five times a day, x 4 days of
  the first week, followed by three treatment-free
  days. If no complete response, treating again.
• No significant difference (or no therapeutic
  effect ?)

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Management of ZAP

• Perform a medical and psychosocial evaluation and
  targeted physical examination to confirm the
  diagnosis, document comorbid illness and provide
  a basis for treatment.
• Elderly patients may be socially isolated, may
  have cognitive impairment, depression or other
  life stressors that may impact treatment
  compliance and outcome.
• Anxiety or depression may also develop secondary
  to severe ZAP and can influence suffering.

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Management of ZAP

• Patient education and general measures
• The disease and its time course should be
  explained, including the risk of viral
  transmission to individuals who have not had
  varicella.
• The rash should be kept clean and dry to reduce
  the risk of secondary bacterial infection.
• Acute skin discomfort may be reduced by sterile
  wet dressings.
• Topical antibiotic dressings with adhesives that
  can cause irritation and delay rash healing
  should be avoided.

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Management of ZAP

• Pharmacological agents
• ZAP should be assessed early and treatment should
  begin promptly.
• The principles of optimum pain management
• use of standardized pain measures,
• scheduled analgesia,
• consistent and frequent follow-up to adjust
  dosing to the needs of the patient,

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Management of ZAP

• Pharmacological agents
• It is important to recognize that ZAP changes
  over time and can become more severe as the acute
  infection progresses.
• The initial choice of treatment approaches
  depends on the patients pain severity, comorbid
  conditions and on any previous known response to
  specific medications.

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In Taiwan

• 2008 ? Herpes zoser ??
• (ICD 9 053) 6488  ????Neurotin 617?
• (ICD 9 053.1X) 2709  ????Neurotin 320?

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????????

• 1.1.6. Gabapentin?lidocaine???(97/12/1?98/4/1?98/9
  /1)????????????????,???????
• 1.????????????????(NSAIDs)?????????????????????(97
  /12/1?98/4/1)
• 2. Gabapentin??????,????????3,600mg,??????2,400mg?
  ,???????????????,???????????Neurontin?Gapatin?Gati
  ne?Gaty?Carbatin?(97/12/1?98/4/1?98/9/1)
• 3. Lidocaine???,????????3?,??????2??,?????????????
  ??,???????????Lidopat Patch?(98/9/1)
• 4. Lidopat ??????Gabapentin?????????(98/9/1)

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Vaccination for Herpes zoster

• Zoster vaccine licensed for 60 years of age and
  older .
• not licensed for immunocompromised individuals,
  pregnant women or children.
• vaccine is a lyophilized live, attenuated Oka
  VZV strain.
• Boost cellular immunity in older adults through a
  range of subcutaneous doses with a good safety
  profile .
• SPS randomly assigned gt 38,000 people to zoster
  vaccine or placebo .
• reduced the burden of illness by 61,
• Reduce the incidence of zoster by 51
• Reduce the incidence of PHN by 67
• 60 to 69 years of age vs gt 70 years of age
  vaccine efficacy 63.9 versus 37.6,
  respectively
• However, the reduction in incidence of PHN was
  similar in these two age groups.

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Principles of analgesics for postherpetic
neuralgia

• Grade 1 non-opioids as a rule (pain NRS 14)
• Grade 2 nonopioids and/or low potency opioids
  in combination with analgesics (pain NRS 58)
• Grade 3 high potency opioids, individual
  combination with the above mentioned analgesics
  (pain NRS 910)
• NRS numerical rating scale.

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AAN Evidence-Based Guideline Summary of Treatment
for Postherpetic Neuralgia
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