Herpes zoster (shingles)
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Classification
- localized Herpes zoster: involvement of 1 or 2 dermatomes
- disseminated Herpes zoster: involvement >= 3 dermatomes
Etiology
- reactivation of latent Varicella zoster
- not a marker of underlying malignancy[2]
- risk may be increased in patients with chronic disease[15]
- risk factors among younger patients (< 50 years)[23]
- patients with contraindications to Herpes zoster vaccine (lymphoma, HIV1) at highest risk[23]
- immunocompromise due to chemotherapy[2]
- association of reactivation (shingles) with trauma is tentative[19]
- methotrexate in combination with a biological response modifier increases risk of Herpes zoster (22 vs 9 per 1000 person-years)[24]
Epidemiology
- primarily occurs in the elderly & immunocompromised
Incidence of shingles (no shingles vaccine)[8]
| annual incidence | age (years) | |
|---|---|---|
| 0.2% | < 50 | |
| 0.5% | 50-60 | |
| 0.7% | 60-70 | |
| 1.0% | 70-80 | |
| 1.2% | >= 80 |
- may occur in children & young adults[3]
- 7 times more frequent in homosexual men with HIV than in HIV-negative controls
- no gender or race predilection
- unlike chickenpox, shingles has no seasonal variation
- may occur in children infected in-utero
- risk independent of childhood varicella vaccination[6] or varicella vaccination programs in general[19]
- recurrence within 3 years 1.4%[8]
- recurrence within 8 years 6.2%[10]
- patients with shingles may spread the varicella virus via direct contact with open shingles lesions or inhalation of aerosolized respiratory droplets[36]
- disseminated Herpes zoster may involve the respiratory tract[2]
Pathology
- ballooning degeneration of epidermal cells
- intra-epidermal vesicle
- histology indistinguishable from Herpes simplex
- latent in dorsal root ganglion after primary infection
- VZV reactivates presumptively with a decline in immunity
- disseminated Herpes zoster may involve the respiratory tract[2]
Clinical manifestations
- often presents as group vesicles on an erythematous base within a single dermatome[2]
- pain
- generally precedes skin manifestations by several days
- pain is generally sharp, burning, may be severe
- distribution may or may not be dermatomal
- hyperesthesia may be present
- pain may persist after resolution of lesions (post Herpetic neuralgia)
- pain may occur in the absence of rash (zoster sine herpete)
- rash
- erythematous maculopapules appear initially
- grouped lesions become vesicular in 12-24 hours
- distribution of lesions
- linear clustering
- unilateral distribution
- rash stops at the midline
- distribution or rash is dermatomal
- adjacent dermatomes may be involved
- lesions may become pustular or hemorrhagic
- weeping followed by crusting over 10-12 days
- resolution of crusts, frequently with scarring within 2-3 weeks
- lesions appear in various stages of development & healing[11]
- regional lymphadenopathy may be observed[36]
- 5% of cases with non-specific prodrome
Laboratory
- diagnosis generally clinical, no laboratory tests usually required
- Tzanck smear, direct antigen test, viral culture of lesion[4]
- skin biopsy
- HIV testing
- patients under 50 years of age, especially if lesions disseminate outside of the primary dermatome
- recurrent Herpes zoster[2]
- see ARUP consult[12]
Complications
- disseminated Herpes zoster with visceral involvement (liver, lung, brain) in immunocompromised patients[2][26]
- involvement of >= 3 dermatomes & respiratory tract
- pneumonia
- cranial nerve palsies, segmental zoster paresis
- partial facial nerve paralysis[38]
- transverse myelitis
- aseptic meningitis,m encephalitis
- cerebral vasculitis
- superinfection of lesions
- post herpetic neuralgia
- ophthalmic Herpes zoster (Herpes zoster ophthalmicus)
- ophthalmic branch of the trigeminal nerve is affected
- forehead extending over upper eyelid
- unilateral cheek with ipsilateral side of nose
- nasociliary branch of the ophthalmic nerve innervates tip of nose & cornea[43]
- acute retinal necrosis may occur in patients with AIDS
- ophthalmic branch of the trigeminal nerve is affected
- Herpes zoster oticus (Ramsay-Hunt syndrome)
- involvement of cranial nerve VII & cranial nerve VIII
- patients with HIV have a higher incidence of shingles, but not of complications
- shingles is contagious especially in early phase[3] Varicella may be transmitted to susceptible individuals
- risk factor for cardiovascular event in weeks after episode of shingles[20][22]
- MI (RR = 1.5), TIA (RR= 2.4), stroke (RR = 1.6-1.7)
- risk greatest in the 1st 4 weeks
- risk declines to baseline after 26 weeks[22]
- risk my persist for 1 year[33]
- Herpes zoster ophthalmicus & Herpes zoster in other branches of the trigeminal nerve increase stroke risk 3-fold relative to Herpes zoster in other dermatomes[22]
- antiviral lowers risk of stroke[22]
- not associated with increased risk of cancer[14]
- not associated with increased risk of dementia[39]
- associated with a slight decreased risk of dementia[39]
- patients with CNS involvement with increased risk of dementia (RR~2)[39]
Differential diagnosis
- before eruption of rash, differential is broad
- rash may resemble rash of Herpes simplex*
- post herpetic neuralgia*
* may masquerade as recurrent shingles[37]
Management
- supportive
- symptomatic relief of pain
- neuropathic pain
- gabapentin or pregabalin ineffective[35]
- amitriptylline or duloxetine
- acetaminophen
- NSAIDS: ibuprofen
- opiates: hydrocodone, morphine, dilaudid
- radicular nerve blocks
- transcutaneous electrical nerve stimulation (TENS)
- consult pain management specialist
- neuropathic pain
- prevention of secondary infection
- keep lesions clean
- contact precautions & airborne precautions for disseminated Herpes zoster[2]
- contact precautions alone for localized Herpes zoster[2]
- symptomatic relief of pain
- referral to specialist
- lesions in distribution of the ophthalmic nerve, CN-V1 (zoster ophthalmicus): consult an ophthalmologist
- ear vesicles, diminished taste on the anterior 2/3 of the tongue, ipsilateral facial paralysis = Ramsay-Hunt syndrome: refer to ENT[2]
- when >= 3 dermatomes involved consider referral to infectious disease for treatment of disseminated varicella-zoster
- antiviral agents
- antiviral therapy if initiated within 72 hours of rash onset[2][36] can:
- lessen Herpes zoster pain
- expedite healing of lesions
- diminish incidence & severity of postherpetic neuralgia
- mild to moderate cases
- famciclovir (Famvir) 500 mg TID for 7 days (post herpetic neuralgia)
- acyclovir (Zovirax) 800 mg PO 5x/day for 7-10 days
- valacyclovir 1 g PO TID for 7 days
- within 72 hours of onset
- severe cases (CNS involvement, immunocompromised, multiple dermatomes)
- acyclovir 12.4 mg/kg IV infusion over 1 hour every 8 hours for 5-7 days
- vidarabine (Vira-A) 10 mg/kg/day infusion over 12 hours for 5-7 days
- antiviral therapy for zoster ophthalmicus even if > 72 hours after lesion onset
- both contact precautions & airborne precautions[2]
- foscarnet for acyclovir resistant Herpes zoster (rare)
- topical antiviral agents not useful
- antiviral therapy if initiated within 72 hours of rash onset[2][36] can:
- oral glucocorticoids
- symptomatic relief
- do not reduce incidence of post-herpetic neuralgia
- do not use without concomitant antiviral therapy[2]
- evidence insufficient to support use (do not use)[2]
- acupucture
- reduces incidence if postherpetic neuralgia & shortens treatment[40]
- no effect on pain[40]
- quarantine until all lesions heal to minimize transmission of Varicella zoster
- contact precautions for localized zoster if immunocompetent & involvement of single dermatome[2]
- contact precautions & airborne precautions if immunocompromised or disseminated zoster/involvement of multiple dermatomes[2]
- Herpes Zoster vaccine
- cuts risk of shingles in elderly in 1/2[5]
- diminishes incidence & severity of postherpetic neuralgia
- endorsed by CDC for patients > 60 years of age
- if lesions become superinfected, antibiotics with Staphylococcus coverage (clindamycin, Keflex + Septra)
- for ulceration, Restore dressing may be useful
- be aware of post-herpetic neuralgia
- patient education
- pain usually resolves over weeks-months
- expect scarring
- notification of contact - transmission will result in chickenpox in susceptible individuals
More general terms
More specific terms
- Herpes zoster mandubularis
- Herpes zoster ophthalmicus
- Herpes zoster oticus; Ramsay Hunt syndrome type 2
- segmental zoster paresis
Additional terms
- cerebral granulomatous angiitis
- chickenpox
- Herpes zoster (shingles) vaccine (Zostavax, Shingrix)
- post Herpetic neuralgia
- Varicella [Herpes] zoster virus (VZV); human herpesvirus 3 (HHV3)
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 864-67
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2021
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 3.0 3.1 3.2 Prescriber's Letter 10(11):64 2003
- ↑ 4.0 4.1 Takahashi S, In: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 5.0 5.1 Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005 Jun 2;352(22):2271-84. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15930418
- ↑ 6.0 6.1 Journal Watch 25(16):131, 2005 Jumaan AO, Yu O, Jackson LA, Bohlke K, Galil K, Seward JF. Incidence of herpes zoster, before and after varicella- vaccination-associated decreases in the incidence of varicella, 1992-2002. J Infect Dis. 2005 Jun 15;191(12):2002-7. Epub 2005 May 12. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15897984 <Internet> http://www.journal.uchicago.edu/JID/journal/issues/v191n12/33867/33867.html
Whitley RJ. Changing dynamics of varicella-zoster virus infections in the 21st century: the impact of vaccination. J Infect Dis. 2005 Jun 15;191(12):1999-2001. Epub 2005 May 12. No abstract available. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15897983 <Internet> http://www.journal.uchicago.edu/JID/journal/issues/v191n12/34420/34420.html - ↑ Hornberger J and Robertus K Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Ann Intern Med 2006, 145:317 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16954357
- ↑ 8.0 8.1 8.2 Yawn BP et al, A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc 2007, 82:1341 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17976353
- ↑ Harpaz R, Ortega-Sanchez IR, Seward JF; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 Jun 6;57(RR-5):1-30; quiz CE2-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18528318
- ↑ 10.0 10.1 Yawn BP et al. Herpes zoster recurrences more frequent than previously reported. Mayo Clin Proc 2011 Feb; 86:88. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21220354
- ↑ 11.0 11.1 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
- ↑ 12.0 12.1 ARUP Consult: Varicella-Zoster Virus - VZV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/varicella-zoster-virus
- ↑ Prescriber's Letter 19(9): 2012 COMMENTARY: Treatment of Shingles Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280922&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 14.0 14.1 Wang Y-P et al. Risk of cancer among patients with herpes zoster infection: A population-based study. CMAJ 2012 Sep 17 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22988158 <Internet> http://www.cmaj.ca/content/early/2012/09/17/cmaj.120518
- ↑ 15.0 15.1 Joesoef RM et al. Chronic medical conditions as risk factors for herpes zoster. Mayo Clin Proc 2012 Oct; 87:961. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23036671
- ↑ Zhang JX et al. Association of physical trauma with risk of herpes zoster among Medicare beneficiaries in the United States. J Infect Dis 2013 Mar 15; 207:1007. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23307932
- ↑ Bond D, Mooney J. A literature review regarding the management of varicella-zoster virus. Musculoskeletal Care. 2010 Jun;8(2):118-22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20301227
- ↑ Whitley RJ, Volpi A, McKendrick M, Wijck Av, Oaklander AL. Management of herpes zoster and post-herpetic neuralgia now and in the future. J Clin Virol. 2010 May;48 Suppl 1:S20-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20510264
- ↑ 19.0 19.1 19.2 Hales CM et al Examination of Links Between Herpes Zoster Incidence and Childhood Varicella Vaccination. Ann Intern Med. 2013;159(11):739-745 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24297190 <Internet> http://annals.org/article.aspx?articleid=1784289
- ↑ 20.0 20.1 Breuer J et al Herpes zoster as a risk factor for stroke and TIA: A retrospective cohort study in the UK. Neurology. Jan 2, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24384645 <Internet> http://www.neurology.org/content/early/2014/01/02/WNL.0000000000000038.full.pdf+html
- ↑ Rice AS et al EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo- controlled phase 2 clinical trial. The Lancet, Early Online Publication, 5 February 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24507377 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962337-5/abstract
- ↑ 22.0 22.1 22.2 22.3 22.4 Langan SM et al Risk of Stroke Following Herpes Zoster: A Self-Controlled Case-Series Study. Clin Infect Dis. 2014 Jun;58(11):1497-503 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24700656 <Internet> http://cid.oxfordjournals.org/content/early/2014/03/25/cid.ciu098.full.pdf+html
- ↑ 23.0 23.1 23.2 Forbes HJ et al Quantification of risk factors for herpes zoster: population based case-control study. BMJ 2014;348:g2911 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25134101 <Internet> http://www.bmj.com/content/348/bmj.g2911
- ↑ 24.0 24.1 Shalom G Systemic Therapy for Psoriasis and the Risk of Herpes Zoster. A 500,000 Person-year Study. JAMA Dermatol. Published online March 22, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25797026 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=2174887
- ↑ Beste RM, Bellolio MF Disseminated Zoster. N Engl J Med 2015; 372:1150. March 19, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25785972 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMicm1404522
- ↑ 26.0 26.1 Cohen JI Clinical practice: Herpes zoster. N Engl J Med. 2013 Jul 18;369(3):255-63 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23863052
- ↑ 27.0 27.1 Janniger CK, MD; Elston DM (images) Medscape: Herpes Zoster http://emedicine.medscape.com/article/1132465-overview
- ↑ Frisch S, Guo AM. Diagnostic methods and management strategies of herpes simplex and herpes zoster infections. Clin Geriatr Med. 2013 May;29(2):501-26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23571042
- ↑ 29.0 29.1 Kwon HJ et al. Asthma as a risk factor for zoster in adults: A population- based case-control study. J Allergy Clin Immunol 2015 Dec 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26739414 <Internet> http://www.jacionline.org/article/S0091-6749%2815%2901641-3/abstract
- ↑ Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS. Varicella zoster disease of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine. J Infect Dis. 2011 Feb 1;203(3):316-23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21177308 Free PMC Article
- ↑ Cohen JI. Herpes zoster. N Engl J Med. 2013 Oct 31;369(18):1766-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24171531 Free PMC Article
- ↑ 32.0 32.1 Brady MP (images) Cutaneous and Mucosal Manifestations of Viral Diseases. Medscape. March 2017 http://reference.medscape.com/features/slideshow/viral-skin
- ↑ 33.0 33.1 Kim MC, Yun SC, Lee HB et al Herpes Zoster Increases the Risk of Stroke and Myocardial Infarction. J Am Coll Cardiol. 2017. July 70(2):293 http://www.onlinejacc.org/content/70/2/295
- ↑ Schmader K. Herpes Zoster. Clin Geriatr Med. 2016 Aug;32(3):539-53. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27394022
- ↑ 35.0 35.1 Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019 Mar 25; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30907944 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2728959
- ↑ 36.0 36.1 36.2 36.3 James W. Fast Five Quiz: Herpes Zoster Facts vs Fiction. Medscape - Sep 22, 2021 https://reference.medscape.com/viewarticle/959182
Janniger CK, Elston DM Herpes Zoster Medscape. July 22, 2021 https://emedicine.medscape.com/article/1132465 - ↑ 37.0 37.1 Sax PE Five Quick Questions from Our Course " ID in Primry Care" HIV and ID Observations. Nov 7, 2022 https://blogs.jwatch.org/hiv-id-observations/index.php/five-quick-questions-from-our-course-id-in-primary-care/2022/11/07/
- ↑ 38.0 38.1 James W Rapid Review Quiz: Herpes Zoster Medscape. July 28, 2022 https://reference.medscape.com/viewarticle/977316
- ↑ 39.0 39.1 39.2 39.3 Johannesdottir Schmidt SA, Veres K, Sorensen HT et al Incident Herpes Zoster and Risk of Dementia: A Population-Based Danish Cohort Study. Neurology. 2022 Jun 8;99(7):e660-e668 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35676090 PMCID: PMC9484607 Free PMC article https://n.neurology.org/content/99/7/e660
- ↑ 40.0 40.1 40.2 Qi T, Lan H, Zhong C et al Systematic review and meta-analysis: the effectiveness and safety of acupuncture in the treatment of herpes zoster. Ann Palliat Med. 2022 Feb;11(2):756-765 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35249352 Free article
- ↑ 41.0 41.1 Xue S Yang WJ, Cao ZX, Sun T. Comparing the efficacy and safety of short-term spinal cord stimulation and pulsed radiofrequency for zoster-related pain: A systematic review and meta-analysis. Medicine (Baltimore). 2022 Mar 18;101(11):e29073. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35356934 Free article
- ↑ Schmader K. Herpes zoster. Ann Intern Med. 2018;169:ITC19-ITC31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30083718
- ↑ 43.0 43.1 A Man with a Rash on the Scalp and Face. NEJM Resident 360. April 21, 2021 https://resident360.nejm.org/clinical-pearls/a-man-with-a-rash-on-the-scalp-and-face
- ↑ NINDS Shingles Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Hemifacial-Spasm-Information-Page