Herpes Zoster and Post Herpetic Neuralgia dr. Semuel A. Wagiu, SpS Siang Klinik RSUD dr. M. Haulussy Ambon, 13 Pebruari 2010

VARICELLA ZOSTER VIRUS VZV is a DNA virus belongs to the Herpes Virus Family Causes two clinically distinct forms of disease.  Chicken-pox (Varicella)  Primary infection  usually in childhood  Herpes Zoster (shingles)  secondary manifestation of an earlier infection  later in life Brief…

V ARICELLA - CHICKENPOX benign and self limiting illness. Incubation period is d Skin lesions appear by day 14 in crops of vesicles, pustules and crusted papules on face, trunk, and extremities spread by respiratory droplets or direct contact with skin lesions. highly contagious: 48 h prior to onset of rash until skin lesions have fully crusted. New lesion formation stops within 4 d most lesions have fully crusted by day 6 Immunosupresed host: susceptible to disseminated varicella severe morbidity and higher Mt rates (7-14%) Typically, the lesions of varicella are in different stages of development

V ARICELLA - TREATMENT Symptomatic : Antihistamines, Acetaminophen, prevent scratching Acyclovir : reduces duration and severity of sy within first 24 h of rash onset recommended in healthy adults, and immunocompromised not recommended routinely in otherwise healthy children. After h no effect on the course of illness IV-Acyclovir for immunocompromised host even > 24 h of symptom onset Primary infection with VZV causes chicken pox

V ARICELLA VACCINE Recommended for all children months A two-dose schedule may be warranted in Canada in the future Children who are nonimmune in whom vaccine is not contraindicated should be offered postexposure vaccination preferably within 96 h (four days). Nonimmune children at risk for serious disease who are not candidates for vaccine should be offered VZIG as soon as possible and within 96 h of exposure A child with mild illness should be allowed to return to school or daycare as soon as he or she is well enough to participate normally in all activities, regardless of the state of the rash.

P ATHOPHYSIOLOGY OF HZ Following primary infection, the virus lies dormant in the sensory nerve ganglia, dorsal root, and cranial nerve ganglia, until reactivated in later in life causing Herpes Zoster. Reactivation occur in the presence of stress, surgery, or injury. linked to an age-related diminished cell-mediated immunity, therefore HZ develops mainly in elderly people and immunocompromised. The virus travels at a possible rate of mm per hour., reaches the skin in ~48-96 hours.

H ERPES ZOSTER - CLINICAL PRESENTATION Presents with rash and acute neuritis. The rash starts as small papules which quickly evolve into vesicles grouped on an erythematous base. Rash is painful, unilateral and usually occurs in a restricted dermatomal distribution Rash of HZ has been described as "dew drops on a rose petal."

H ERPES ZOSTER - CLINICAL PRESENTATION Contagious for those who have not had varicella or have not received the varicella vaccine Lesions crust in 7-10 days and are no more infectious. Without complications HZ typically lasts 2-4 weeks.

D IAGNOSIS OF HERPES ZOSTER Clinical: dermatomal distribution of rash PCR-most sensitive and specific Viral culture -low sensitivity Direct immunofluorescent antigen staining- test (when PCR not available) Tzank test

COMPLICATIONS OF HERPES ZOSTER Postherpetic neuralgia Bacterial infection of skin lesions Ocular complication: (conjunctivitis corneal scarring, vision loss) Encephalitis Bells Palsy (Zoster sine herpetic) Cochlear vesicular involvement (Ramsey hunt syndrome) Loss of taste

P OSTHERPETIC NEURALGIA Pain along cutaneus nerves of involved dermatome persisting > 30 d after the lesions have healed Incidence of PHN increases with age and is uncommon in pt < 60 yo AFP 2005 Helgason, S. et al. BMJ 2000;321:794

Skema definisi nyeri pada Herpes Zoster NYERI ZOSTER Nyeri fase akutNeuralgia pasca herpes Onset RuamRuam SembuhNyeri Sembuh > 1bln

P OSTHERPETIC NEURALGIA Pain may last months or in a few cases over a year. Pain is described as lacinating, burning, shooting, stabbing, paroxysmal or electrical. Allodynia occurs.( pain in reaction to a non- noxious stimuli, light touch, clothing). Pain ↑ through out the day Pain can be debilitating and interfere with daily functioning ), Pain (2006) JAMA (2005), Pain (2006)

Risk factors for development of PHN: Advancing age Site of HZ involvement Lower risk - Jaw, neck, sacral, and lumbar Moderate risk - Thoracic Highest risk - Trigeminal (especially ophthalmic division), brachial plexus Severe prodromal pain (with HZ) Severe rash

OPHTHALMIC HERPES ZOSTER Affects the ophthalmic branch of the trigeminal nerve Causes severe and lasting pain, particularly among elderly pt. Can be complicated by various eye disorders in about 50 % of all the pt if not treated Might result in blindness if not diagnosed and treated adequately

OPHTHALMIC HERPES ZOSTER HERPES ZOSTER OPHTHALMICUS Ophthalmologist referral recommended for emergency assessment & treatment Antiviral drugs at first sign of infection recommended for all pt with ophthalmic herpes zoster “irrespective of their age or the severity of symptoms” Anterior segment of the left eye showing the supra-temporal area of scleromalacia

T REATMENT OF HERPES ZOSTER Management of acute Herpes Zoster infection Treatment of ophthalmic Herpes Zoster Prevention of Postherpetic neuralgia Management of Postherpetic neuralgia

MANAGEMENT OF ACUTE HZ 1. Antiviral medications: Acyclovir (800 mg 5xd/7-10) decreases pain especially in pt > 50 less expensive Famcyclovir ( 500 or 750 mg 3xd/7xd) within first 72 h, decreases duration of rash by 1-2 d, decreases pain only in pt with > 50 skin lesions Valacyclovir and Famcyclovir have similar effect more preferred since dosing is 3 x d, compared to Acyclovir 5 x d more expensive  There are no data examining the effect of Antiviral Tx >72 h of rash onset 2. Steroidal treatment

A NTIVIRAL T REATMENT OF A CUTE HZ The “ rule” can be used as a guide for antiviral treatment: 50 h or less since onset of lesions, 50 y or older More than 50 lesions American Family Physician 2005

S TEROID TREATMENT OF A CUTE HZ INFECTION Studies have found that CS combined with ACV Caused greater reduction of pain in 1st 2 wks but no difference > 2 wks Did not affect cutaneous healing Resulted in significant benefit in quality of life at 30 days “Treatment of herpes zoster with Antiviral meds appear to be more effective than treatment with steroids.”

P REVENTION OF HERPES ZOSTER Varicella vaccine – live attenuated vacc containing 1350 plaque forming units Zoster vaccination - contains plaque forming units compared to varicella vac A study of varicella vaccine in pt > 60 yo showed these results: 61 % reduction in pain and discomfort 51 % reduction in incidence of HZ 67 % reduction in incidence of PHN The vaccine has been approved for use US (by FDA in May 2006 for adults > 60 yo) Europe, and Australia

ANTIVIRAL THERAPY IN PREVENTION OF PHN Acyclovir ( 7-10 d) : reduces the incidence of pain at 1 to 3 M, but no difference > 3M does not influence the incidence or duration of PHN Famcyclovir (for 7 d) no effect on incidence of PHN did reduce duration of pain Valacyclovir compared to ACV No difference on incidence of PHN but pain lasted longer among pt in ACV group. Famcyclovir and Valacyclovir showed similar results in reducing the duration of PHN

P REVENTION OF POSTHERPETIC NEURALGIA Steroid therapy have no effect on preventing PHN TCA 25 mg, initiated within 48 h of rash, and continued for 90 d  reduced the risk or PHN by 50 %

M ANAGEMENT OF POSTHERPETIC NEURALGIA TCA - amitriptyline desipramine Anticonvulsants: gabapentin Potent analgesic opioids: oxycodone Lidocaine patch Topical capsaicin Intrathecal methylprednisolone (for persistent neuralgia nonresponsive to oral and topical therapy).

AAN 2004

K EY RECOMMENDATIONS FOR PRACTICE (A) Physicians should treat acute herpes zoster with antiviral medication within 72 hours of symptom onset to increase the rate of healing and decrease the pain. (A) Physicians should treat HZ with antiviral medications to decrease the incidence and duration of PHN. (A) TCA and gabapentin should be used to decrease the pain of PHN. (B) Amitriptyline should be used to decrease the risk of PHN in older patients (B) The lidocaine patch, capsaicin and opioids should be used to decrease the pain from post herpetic neuralgia. A = consistent, good quality patient-oriented evidence B = evidence: inconsistent or limited-quality patient-oriented evidence American Family Physician 2005