Herpes Zoster. Chang Gung Hospital 2014/01/22 Yi-Chun Tsai

Transcription

1 Herpes Zoster Chang Gung Hospital 2014/01/22 Yi-Chun Tsai

2 Outline Introduction Clinical manifestation Epidemiology Pathophysiology Diagnosis Recurrent zoster Treatment Complications Pregnancy Zoster vaccune Summry references

3 Introduction Herpes zoster 中醫稱 纏腰火龍 纏腰火丹 俗稱 蜘蛛瘡 生蛇 皮蛇 民俗療法 : 畫蛇斬蛇 畫蜈蚣 打皮蛇

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5 Introduction Varicella (chickenpox) Varicella-zoster virus(vzv) Latent infection within the sensory dorsal root ganglia Herpes zoster (shingles)

6 Epidemiology CDC in the US: 32% of person in the US experience zoster during their lifetimes. nearly one million individuals annually

7 Epidemiology Immunocompetent hosts: women>men white>black family history Immunocompromised patients: (at increased risk of VZV reactivation) transplant recipients patients receiving selected immunomodulator therapies HIV-infected patients.

8 Epidemiology Risk factors: Age is the most important risk factor. (dramatic increase in disease rates begins to occur after 50 years of age) Malignancy, disorders of cell-mediated immunity, and chronic lung or kidney disease.

9 Pathophysiology Early 1900s: a viral illness that was acquired from personto-person contact 1965: zoster was secondary to reactivation of latent varicella-zoster virus infection

10 Diagnosis Clinical diagnosis Additional diagnostic information Atypical rash in an immunocompromised host Possible disseminated disease in an immunosuppressed host without cutaneous lesions

11 Diagnosis Polymerase chain reaction (PCR) rapid and sensitive (from clinical specimens obtained from skin lesions and selected body fluids.) highly specific; no cross-reactivity was identified when tested against several other viruses Direct fluorescent antibody (DFA) widely available lower cost compared to culture, and is associated with more rapid turnaround time.

12 Diagnosis Viral culture Virus isolation by culture is sometimes available insensitive and associated with low yield (approximately 60 ~ 75%) when compared with PCR testing. Serologic testing The presence of IgG antibodies to VZV correlates both with a history of varicella and protection against subsequent infection. Serologic testing has also been employed in vaccine studies to assess response to immunization.

13 Clinical manifestations Rash- erythematous papules quickly evolve grouped vesicles or bullae (not cross the midline) 3~4 days more pustular or occasionally hemorrhagic lesions crust 7~10 days Scarring and hypo- or hyperpigmentation may persist months to years

14 Clinical manifestations Zoster is generally limited to one dermatome in previously healthy hosts, but can occasionally affect two or three neighboring dermatomes. The lumbar dermatomes are the most comthoracic andmonly involved sites of herpes zoster.

15 Clinical manifestations Acute neuritis- Pain is the most common symptom of zoster approximately 75% of patients have prodromal pain in the dermatome where the rash subsequently appears. deep "burning", "throbbing", or "stabbing" sensation is thought to be related to viral replication, inflammatory changes, and cytokine production leading to neuronal destruction and increased sensitivity of pain receptors Atypical pain without rash zoster sine herpete

16 Recurrent Zoster immunocompetent host: uncommon 5180 unvaccinated patients >60y/o zoster within the previous four years 4.5 years of follow-up only 25 well-documented recurrent cases ( Three or more episodes recurring in the same individual are rare) immunocompromised host: more common HIV-infected patients (mean age 41 years) 282 episodes of herpes zoster were identified in 239 patients 158 were new occurrences of zoster and 124 were recurrent zoster events

17 Treatment Antiviral Therapy The nucleoside analogues: acyclovir, valacyclovir, and famciclovir

18 Treatment Antiviral Therapy initiated within 72 hours of clinical presentation in patients greater than 50 years of age Adverse events: nausea, diarrhea, or headache. Indications for antiviral treatment in patients with herpes zoster Age 50yr Moderate or severe pain Severe rash Involvement of the face or eye Other complications of herpes zoster Immunocompromised state

19 Antiviral Therapy Treatment GOALS OF THERAPY Important goals of antiviral therapy are to: Hasten the resolution of lesions Reduce the formation of new lesions Reduce viral shedding Decrease the severity of acute pain Whether antiviral therapy prevents post-herpetic neuralgia (PHN) is not as clear because of conflicting study results. However, the evidence is limited by different methodologies of pain assessment, definitions of PHN, and length of follow-up.

20 Antiviral Therapy Treatment Nonimmunocompromised persons Drug Bioavailability (oral) Acyclovir 10~20% 800 mg orally 5 times daily for 7 to 10 days Famciclovir penciclovir 77% 500 mg orally 3 times daily for 7 days modest improvement in lesion healing rates (median 5~6 days with low- and high-dose famciclovir) compared with placebo (median 7days) Valacyclovir acyclovir (active drug) 54.5% 1000 mg orally 3 times daily for 7 days 7 or 14 days accelerated the resolution of acute neuritis (median duration of pain 38 and 44 days, respectively) compared with acyclovir (median 51 days).

21 Treatment Antiviral Therapy Immunocompromised persons requiring hospitalization persons with severe neurologic complications Drug Dose Side effect acyclovir 10mg/kg IV Q8H for 7~10 days Reduced time to last new-lesion formation, full crusting, cessation of viral shedding, cession of pain, reduced cutaneous dissemination, reduced visceral herpes zoster Renal insufficiency foscarnet 40mg/kg IV Q8H until lesions are healed (acyclovir-resistant VZV) Not reported (is not approved for this use by the FDA) Renal insufficiency, hypokalemia, hypomagnesemia, nausea, diarrhea, anemia, granulocytopenia, headache

22 Treatment Analgesia for acute neuritis mild pain: NSAIDs. Acetaminophen alone or in combination with a weak opioid analgesic (eg. Codeine or tramadol) moderate to severe pain that disturbs sleep: stronger opioid analgesics (eg, oxycodone or morphine)

23 Treatment Glucocorticoids: a subsequent meta-analysis of five placebo-controlled trials: Acyclovir alone v.s. acyclovir plus glucocorticoids did not demonstrate any benefit of combination therapy on quality of life or the incidence of PHN potentially increase the risk of secondary bacterial skin infection not recommend the routine use of corticosteroids in addition to antiviral therapy.

24 Complications In a review of 859 patients with herpes zoster, 100 patients (12%) developed complications within 60 days. Two 12% Three or More 5% Single complication 83% Patients with one or more complications had more frequent comorbidities (eg, diabetes, cancer, HIV, transplant recipient).

25 Complications including uveitis and keratitis PHN

26 Complications Postherpetic neuralgia(phn) all patients- 10~15% older than 60 y/o- 50% PHN refers to pain persisting beyond 90 days from the initial onset of the rash. The pain may persist for many months or even years. interfere with sleep and daily living

27 Complications Postherpetic neuralgia(phn) TREATMENT A number of modalities have been investigated for the treatment of PHN: 1. Tricyclic antidepressants - nortriptyline, amitriptyline, desipramine - effective, often thought of as the mainstay of therapy. - Side effect: Anticholinergic side effects (principally sedation and dry mouth)

28 Complications Postherpetic neuralgia(phn) In a subsequent prospective, randomized, double-blind, crossover comparison 58 elderly patients with PHN were randomly assigned to six weeks dose amitriptyline 12.5 to 150 mg per day (mean: 65 mg per day) lorazepam (active placebo) 0.5 to 6 mg per day inactive placebo efficacy significantly more effective 47% 15% 16%

29 2. Anticonvulsants Complications Postherpetic neuralgia(phn) Gabapentin Pregabalin Valproic acid 1800 to 3600mg daily 150 to 600 mg daily 1000 mg per day - side effects: dizziness, somnolence, dry mouth, peripheral edema, and weight gain.

30 3. Opioids: Complications Postherpetic neuralgia(phn) - Be effective for pain relief in patients with PHN (1) are associated with a risk of physical dependence, tolerance, addiction, and overdose second or third-line treatment (2) Other experts consider low-dose opioids as a firstline treatment option for select patients with PHN

31 Complications Postherpetic neuralgia(phn) 4. Capsaicin - Limited data suggest that topical application of standard concentration capsaicin is effective for PHN. - burning, stinging, and erythema intolerable in up to one-third of patients. 5. Topical lidocaine - one patch for up to 12hrs per day 6. Intrathecal glucocorticoids - In patients who have PHN affecting nerves other than the trigeminal nerve, intrathecal glucocorticoids may be a reasonable option, particularly if there has been no response to the above measures.

32 Complications Postherpetic neuralgia(phn) 7. NMDA receptor antagonists - eg. Ketamine 8. Cryotherapy - freezing peripheral nerves ; however, the duration of relief was less than two weeks as assessed by questionnaire 9. Surgery 10. Others

33 Complications Postherpetic neuralgia(phn) Combination therapy have been more effective (e.g., gabapentin + nortriptyline) (e.g., gabapentin + opiate) But also confer a greater risk of side effects

34 Complications Herpes zoster ophthalmicus(hzo) VZV reactivation within the V1 distribution of the trigeminal ganglion a serious sight-threatening condition conjunctivitis, episcleritis, eratitis, and/or iritis

35 Complications Herpes zoster ophthalmicus(hzo) Treatment - initiate antiviral therapy to limit VZV replication + use adjunctive topical steroid drops to reduce the inflammatory response and control immuneassociated keratitis and iritis. - Intravenous acyclovir (10 mg/kg three times daily for seven days) is suggested in the patient who is immunocompromised or requires hospitalization for sight-threatening disease

36 Complications Secondary bacterial infection increased erythema, warmth, or purulence surrounding any lesions receive appropriate staphylococcal and streptococcal antibiotic coverage in addition to antiviral therapy

37 Complications Immunocompromised persons can have additional complications: disseminated skin disease acute and progressive outer retinal necrosis chronic herpes zoster with verrucous skin lesions development of acyclovir-resistant VZV the disease can involve multiple organs(e.g., lung, liver, brain, and GI), and patients may present with hepatitis or pancreatitis several days before the rash appears.

38 pregnancy There are no clinical trials examining the role of antiviral therapy in the pregnant woman with herpes zoster infection. However, experience with acyclovir therapy in both HSV infection and varicella pneumonia (10 mg/kg IV every eight hours) suggests that this drug is safe in pregnancy. Passage of varicella zoster virus to the fetus during zoster is rare.

39 Zoster vaccine Zostavax live, attenuated vaccine (Oka/Merck strain of varicella-zoster virus)

40 Zoster vaccine The Advisory Committee on Immunization Practices (ACIP) recommends: Routine vaccination of all patients 60 years of age, including : (1) patients who report a previous episode of zoster (2) patients with chronic medical conditions (e.g., chronic renal failure, diabetes mellitus, rheumatoid arthritis, chronic pulmonary disease) unless those conditions are contraindications (3) residents of nursing homes and other long-term care facilities 60 years of age without contraindications (CDC, 2008). US FDA approved: For prevention of herpes zoster (shingles) in individuals 50 years of age and older.

41 Zoster vaccine The efficacy of the vaccine in preventing herpes zoster Age Efficacy 50~59 y/o 70% 60~69 y/o 64% 70 y/o 38% The efficacy in preventing PHN Age Efficacy 60~69 y/o 66% 70 y/o Undiminished 67% Although the effectiveness of the vaccine to prevent herpes zoster is reduced in persons 70y/o or older, the increased risk of severe disease and the persisting efficacy of the vaccine in preventing PHN in these older persons strongly favor vaccinating them.

42 Zoster vaccine A follow-up study: the reduction in the risk of herpes zoster remained significant for at least 5 years after vaccination, though the effectiveness declined over the time. in vaccinated (as compared with vaccinated) persons in whom herpes zoster developed, pain was significantly shorter in duration and less severe.

43 Zoster vaccine Contraindications History of anaphylactic/anaphylactoid reaction to gelatin, neomycin (excluding contact dermatitis to neomycin), or any other component of the vaccine immunosuppression or immunodeficiency, including - individuals with leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic systems - primary and acquired immunodeficiency states - AIDS or clinical manifestations of HIV those receiving immunosuppressive therapy (including highdose corticosteroids) pregnancy

44 summary Herpes zoster results from reactivation of endogenous latent VZV infection within the sensory ganglia. The presenting clinical manifestations include a dermatomal vesicular rash and acute neuritis. Age is the most important risk factor. Diagnosis: Clinical diagnosis, Serologic testing, PCR, DFA, viral culture.

45 summary Treatment: antiviral therapy(acyclovir, valacyclovir, and famciclovir), Analgesia for acute neuritis, Glucocorticoids. Complications: Postherpetic neuralgia(phn), Herpes zoster ophthalmicus(hzo), Secondary bacterial infection. There are no clinical trials examining the role of antiviral therapy in the pregnant woman with herpes zoster infection. Zoster vaccine: For prevention of herpes zoster (shingles) in individuals 50 years of age and older.

46 References Up to date Treatment of herpes zoster in the immunocompetent host Postherpetic neuralgia Clinical manifestations of varicella-zoster virus infection: Herpes zoster Diagnosis of varicella-zoster virus infection Varicella-zoster virus infection in pregnancy The New England Journal of Medicine Herpes zoster Jeffrey I. Cohen, M.D.

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48 全身性抗疱疹病毒劑 1.Acyclovir:(98/11/1 100/7/1) (1) 使用本類製劑應以下列條件為限 : I. 疱疹性腦炎 II. 帶狀疱疹或單純性疱疹侵犯三叉神經第一分枝 VI 皮節, 可能危及眼角膜者 III. 帶狀疱疹或單純性疱疹侵犯薦椎 S2 皮節, 將影響排泄功能者 IV. 免疫機能不全 癌症 器官移植等病患之感染帶狀疱疹或單純性疱疹者 V. 新生兒或免疫機能不全患者的水痘感染 VI. 罹患水痘, 合併高燒 ( 口溫 38 以上 ) 及肺炎 ( 需 X 光顯示 ) 或腦膜炎, 並需住院者 (85/1/1) VII. 帶狀疱疹或單純性疱疹所引起之角膜炎或角膜潰瘍者 VIII. 急性視網膜壞死症 (acute retina necrosis) IX. 帶狀疱疹發疹三日內且感染部位在頭頸部 生殖器周圍之病人, 可給予五日內之口服或外用藥品 (86/1/1 87/4/1) X. 骨髓移植術後病患得依下列規定預防性使用 acyclovir:(87/11/1) A. 限接受異體骨髓移植病患 B. 接受高劑量化療或全身放射治療 (TBI) 前一天至移植術後第三十天為止 (2) 其中 Ⅰ 與 Ⅵ 應優先考慮注射劑型的 acyclovir 疱疹性腦炎得使用 14 至 21 天 (95/6/1 100/7/1)

49 2.Famciclovir;valaciclovir:(100/7/1 101/5/1) 使用本類製劑應以下列條件為限 : (1) 帶狀疱疹或單純性疱疹侵犯三叉神經第一分枝 VI 皮節, 可能危及眼角膜者 (2) 帶狀疱疹或單純性疱疹侵犯薦椎 S2 皮節, 將影響排泄功能者 (3) 免疫機能不全 癌症 器官移植等病患之感染帶狀疱疹或單純性疱疹者 (4) 帶狀疱疹或單純性疱疹所引起之角膜炎或角膜潰瘍者 (5) 急性視網膜壞死症 (acute retina necrosis) (6) 帶狀疱疹發疹 3 日內且感染部位在頭頸部 生殖器周圍之病人, 可給予 5 日內之口服或外用藥品 (7) 骨髓移植術後病患得依下列規定用於預防復發性生殖器疱疹 :(101/5/1) A. 限接受異體骨髓移植病患 B. 接受高劑量化療或全身放射治療 (TBI) 前一天至移植術後第 30 天為止 3.Acyclovir famciclovir 及 valaciclovir 除上述特別規定外, 使用療程原則以 10 天為限, 口服 注射劑及外用藥膏擇一使用, 不得合併使用 (95/6/1 100/7/1 101/5/1)