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Shingles ( Herpes Zoster )

Shingles ( Herpes Zoster ) is an infection of nerve and the area of skin around it. It is caused by the herpes varicella zoster virus , which is also called chicken pox ( PHE March 2020 ) Primary infection by the VZV ( Varicella zoster virus ) causes chicken pox usually in childhood. VZV is an exclusively human neutrophic alpha herpesvirus- Varicella or chickenpox

 

The virus remains latent in the ganglionic neurons along the entire neuraxis and gets reactivated when the immune system weakens due to any reason as advancing age , immunosuppression- herpes zoster or HZV

 

How common –Any one who had natural infection with wild-type VZV or had varicella vaccination can develop herpez zoster over 95 % of immunocompetent individuals aged > 50 yrs are seropositive for VZV ( indicating primary infection ) and are theoretically at risk of developing HZ In the US an estimated 1 million cases are seen each year In the UK the overall incidence is estimated to be 1.85 – 3.9 cases per 1000 population Incidence increases with age ( reduced cell mediated immunity ) No seasonal variation The estimated lifetime risk of HZ in the general population is about 30 % and this risk increases sharply after 50 yrs ( this rises to nearly 50 % among individuals who are or live beyond 85 yrs of age ) HZ is a significant global health burden that is expected to increase as population ages

 

What happens – VZV is transmitted by droplets , aerosols and direct contact Skin lesions remain infectious until they have crusted over It is believed that HZ arises when cell mediated immunity declines The virus replicates in the sensory ganglia – neuropathic damage of the fibres with intense inflammation and necrosis Virus travels along the sensory nerve ( anterograde axonal transport ) and when it reaches the skin -it causes the characteristic acute vesicular dermatitis with typical unilateral distribution The occurrence of HZ in specific dermatomes corresponds to the varicella lesion density Pain- is caused due to acute neuritis.

 

Risk factors – Immunocompromised status ( e.g HIV / AIDS ) Older age Malignancy ( for e.g leukemia , lymphoma , myeloma ) Transplant patients ( for e.g bone marrow transplant ) Children with a h/o intrauterine varicella or varicella occurring within the 1st year of life Psychological stress Family h/o zoster Physical trauma Presence of co-morbidities as
○ diabetes ○ rheumatoid arthritis ○ CVD ○ chronic kidney disease ○ SLE ( strongest relative risk for HZV ) ○ inflammatory bowel disease ○ COPD ○ asthma ○ depression Female gender ( possibly – reason now known why ) CKS reports that limited evidence suggests that statins may also increase the risk of shingles Diets low in micronutrients Most papers report that people of black race suffer less in comparison to whites.

 

Presentation – unilateral rash , typically restricted to a single dermatome , which is usually accompanied by radicular pain along that dermatome pain can be severe and described as burning , throbbing or stabbing itching and unpleasant sensation ( dysesthesias ) produced by touch ( allodynia ) and decreased sensation in the affected area patients often report prodromal tingling ,itching and pain before the rash headache , malaise also commonly reported rash and pain can develop within few days of each other rash is initially erythematous maculopapular and later evolves into vesicles , pustules and finally scabs ( within 2-4 weeks ) thoracic , cervical and ophthalmic involvement are the most common pain can precede rash by weeks to months residual scarring or pigmentation can happen the acute morbidity related to HZV can last from 2-4 weeks the lesions are not contagious once they have scabbed multi-dermatomal involvement ( disseminated disease ) is common in immunocompromised people and can be the first clue of immunodeficient status.

 

Diagnosis –Note the unilateral distribution dermatomal pattern 
○ zoster can affect any level of neuraxis
○ most common site is the chest with dermatomes T1 to L2 affected the most commonly affected The diagnosis is clinical Lab tests are rarely required but if diagnostic uncertainty persists the following can help
○ immunofluorescent microscopy
○ Real-time PCR
○ Serological testing

 

Differentials – herpes simplex virus contact dermatitis insect bite folliculitis impetigo candidiasis scabies urticaria drug eruptions dermatitis herpetiformis

The pain due to shingle ( prodromal phase ) can often be confused with other conditions as
 acute appendicitis cholecystitis migraine renal calculi.

 

Treatment – Treatment with antivirals like acyclovir ( Zovirax ) , valacyclovir , famciclovir is with the aim of 
○ reduce severity and duration
○ reduce pain and potential complications as PHN The 72 hr guidance is deduced from the finding that acyclovir is most effective when given within 48 hrs of the onset of rash ( most trials of HZV treatment enroll patients within 72 hr of rash ) Acyclovir is considered the gold standard CKS recommends giving antiviral treatment up to 1 week after rash onset if the person is considered to be at higher risk of severe shingles or complications Valacyclovir is a pro-drug of acyclovir and is considered a safe and effective alternative to its parent compound Famciclovir is a prodrug of penciclovir and can be given tds ( rather than 5 times / day ) Children – treatment generally not recommended Topical antivirals are not recommended ( lacks efficacy ) Pregnant or breastfeeding – seek specialist advice Address pain relief Advice not to scratch ( reduce risk of transmission ) calamine lotion can be helpful.

 

Admit if -Shingles in the ophthalmic distribution of trigeminal nerve ( HZO- herpes zoster
ophthalmicus ) watch out for those with
○ watch for people with Hutchinson’s signvisual symptoms
○ unexplained red eye Immunocompromised status Serious complication suspected Confusing situations as intense local pain , altered skin sensation but no rash ( Zoster sine herpete ) Side effects from antiviral treatment as nausea, vomiting or CNS toxicity.

 

Post-herpetic neuralgia – most common and serious complication about 40 % of those aged > 60 will experience PHN ( 10-20 % estimated incidence ) paroxysmal or constant- dermatomal , severe , stabbing or burning dysesthetic pain which can persist for a few months after the onset of rash ( many papers quote > 3 months ) what causes PHN is not known PHN can be challenging to manage PHN can disrupt sleep , mood , work and ADLs , adversely impact QoL and cause social withdrawal and depression First line treatment often used include tricyclic antidepressants , gabapentin , pregabalin , topical lidocaine patches 2nd and 3rd line treatment can include opiates , tramadol ,capsaicin cream , patch In treatment resistant cases – trials of botulinum toxin , epidural steroid injections , spinal cord stimulation , percutaneous peripheral nerve field stimulation have been undertaken with variable results

 

HZ ophthalmicus -virus infects the ophthalmic division of the trigeminal nerve complications as keratitis , corneal ulceration , conjunctivitis , optic neuritis and glaucoma can happen. It may even lead to blindness if untreated.

 

Others – After PHN the most common complications include ( ophthalmic zoster -as above ) , myelitis and secondary bacterial infection , large and small vessel encephalitis and cranial and peripheral nerve palsies ( including Ramsay Hunt syndrome and Bell’s palsy ) Complications can be
○ cutaneous e.g bacterial superinfection
○ Visceral ( neural extension of VZV infection )
○ Neurological ( e.g PHN , aseptic meningitis )
○ Ocular ( e.g keratitis , retinal necrosis )

 

Vaccination – Zostavax ( live vaccine ) and Shingrix ( a recombinant zoster vaccine ) are available – both increase cellular immunity and are given to reduce the incidence and severity of shingles in older people PHE England recommends Zostavax in those
○ aged 70-78 yrs
○ those in their 70s born on or after 2/9/1942 and have never received Zostavax before – they remain eligible to receive the vaccine until their 80th birthday Zostavax can be given any time of the year ( NHS )

 

Specialist advice / referral – Patients who have new vesicles forming or who have cutaneous , motor , neurologic or ocular complications after 7 days of antiviral therapy Rash has not healed in a normal fashion in an immunocompetent patient with HZ 2nd episode of shingles in an immunocompetent 
patient or recurrence of shingles in an immunocompromised patient ( CKS ) Diagnostic uncertainty.

Patient information

Work and shingleshttps://www.healthassured.org/blog/working-with-shingles/

Shingles support society FAQs https://shinglessupport.org.uk/frequently-asked-questions-about-shingles/

Healthcare worker and shingles from NHS Health at Work network https://www.nhshealthatwork.co.uk/chickenpox-shingles.asp

NHS Inform Scot on shingles https://www.nhsinform.scot/illnesses-and-conditions/infections-and-poisoning/shingles

BAD Shingles leaflet https://www.bad.org.uk/shared/get-file.ashx?id=128&itemtype=document

CDC for patients https://www.cdc.gov/shingles/about/index.html

Shingles FAQs from Immunize. Org https://www.immunize.org/catg.d/p4221.pdf

For Healthcare professionals

From CDC https://www.cdc.gov/shingles/hcp/index.html

Shingles vaccination programme from NHS England https://www.england.nhs.uk/south/wp-content/uploads/sites/6/2017/08/good-practice-guide.pdf

 

References

  1. Marra, Fawziah et al. “Risk Factors for Herpes Zoster Infection: A Meta-Analysis.” Open forum infectious diseases vol. 7,1 ofaa005. 9 Jan. 2020, doi:10.1093/ofid/ofaa005
  2. CKS Shingles https://cks.nice.org.uk/topics/shingles/
  3. Mueller, Niklaus H et al. “Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency.” Neurologic clinics vol. 26,3 (2008): 675-97, viii. doi:10.1016/j.ncl.2008.03.011
  4. NHS Shingles vaccine overview https://www.nhs.uk/conditions/vaccinations/shingles-vaccination/
  5. Lisa A. Jackson, Meredith A. Reynolds, Rafael Harpaz, Hospitalizations to Treat Herpes Zoster in Older Adults: Causes and Validated Rates, Clinical Infectious Diseases, Volume 47, Issue 6, 15 September 2008, Pages 754–759, https://doi.org/10.1086/591132
  6. Cohen, Kenneth R et al. “Presentation and management of herpes zoster (shingles) in the geriatric population.” P & T : a peer-reviewed journal for formulary management vol. 38,4 (2013): 217-27.
  7. Johnson, Robert W et al. “Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective.” Therapeutic advances in vaccines vol. 3,4 (2015): 109-20. doi:10.1177/2051013615599151
  8. Kawai KGebremeskel BGAcosta CJ
    Systematic review of incidence and complications of herpes zoster: towards a global perspective
  9. Prevention of herpes zoster and its complications: from the clinic to the real-life experience with the vaccine Giovanni Gabutti1​, Nicoletta Valente1​, Parvanè Kuhdari1​, Silvia Lupi1​, Armando Stefanati JOURNAL OF MEDICAL MICROBIOLOGY Volume 65, Issue 12 https://doi.org/10.1099/jmm.0.000386
  10. Nagel, Maria A, and Don Gilden. “Complications of varicella zoster virus reactivation.” Current treatment options in neurology vol. 15,4 (2013): 439-53. doi:10.1007/s11940-013-0246-5
  11. PHE document on Shingles eligibility https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/766641/Shingles_flowchart_poster.pdf
  12. Nair PA, Patel BC. Herpes Zoster (Shingles) [Updated 2020 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441824/
  13. Fawziah Marra, Kamalpreet Parhar, Bill Huang, Nirma Vadlamudi, Risk Factors for Herpes Zoster Infection: A Meta-Analysis, Open Forum Infectious Diseases, Volume 7, Issue 1, January 2020, ofaa005, https://doi.org/10.1093/ofid/ofaa005
  14. Forbes Harriet JBhaskaran KrishnanThomas Sara LSmeeth LiamClayton TimLangan Sinéad M et al. Quantification of risk factors for herpes zoster: population based case-control study 
  15. Forbes, H.J., Thomas, S.L. & Langan, S.M. The Epidemiology and Prevention of Herpes Zoster. Curr Derm Rep 1, 39–47 (2012). https://doi.org/10.1007/s13671-011-0004-4
  16. The diagnosis and management of herpes zoster and its complications Home > Best Practice Journal > 2014 > BPJ: 59 >

  17. Robert H. Dworkin, Robert W. Johnson, Judith Breuer, John W. Gnann, Myron J. Levin, Miroslav Backonja, Robert F. Betts, Anne A. Gershon, Maija L. Haanpää, Michael W. McKendrick, Turo J. Nurmikko, Anne Louise Oaklander, Michael N. Oxman, Deborah Pavan Langston, Karin L. Petersen, Michael C. Rowbotham, Kenneth E. Schmader, Brett R. Stacey, Stephen K. Tyring, Albert J. M. van Wijck, Mark S. Wallace, Sawko W. Wassilew, Richard J. Whitley, Recommendations for the Management of Herpes Zoster, Clinical Infectious Diseases, Volume 44, Issue Supplement_1, January 2007, Pages S1–S26, https://doi.org/10.1086/510206
  18. Severe Complications of Herpes Zoster Antonio Volpi, Department of Public Health, University of Rome ‘Tor Vergata’, Rome, Italy. • HERPES 14 Supplement 2 2007
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