Herpes zoster infection
BMJ 2019; 364 doi: https://doi.org/10.1136/bmj.k5095 (Published 10 January 2019) Cite this as: BMJ 2019;364:k5095
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What is the recurrence rate of shingles? Should recurrence suggest looking for underlying undiagnosed immunosuppression?
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I was surprised that this article failed to mention Giant Cell Arteritis (GCA) as an important differential diagnosis, particularly before the appearance of the rash (and rarely there may not be a rash), as the authors state "Approximately 20% of patients present with systemic symptoms such as fever, headache, malaise, or fatigue.” Missing GCA could result in sudden and irreversible blindness due to anterior ischaemic optic neuropathy. Cranial nerve palsies can also occur in both conditions.
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The nasociliary branch of the trigeminal nerve innervates the apex and lateral aspect of the nose, as well as the cornea. Therefore, lesions on the side or tip of the nose should raise suspicion of ocular involvement.
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"Treatment aims to ... reduce the risk of post-herpetic neuralgia."
However, the most recent Cochrane review of this topic concluded (in 2014) that there was "high quality evidence that oral aciclovir does not reduce the incidence of postherpetic neuralgia significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments". (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006866.pub3/...)
This is referenced in the most recent NICE guideline for shingles (May 2018) (https://cks.nice.org.uk/shingles#!scenariobasis:2).
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The article on herpes zoster provides a useful practice update. However, the guidance on management approaches for Post-Herpetic Neuralgia (PHN) seems to be out of step with currently recommended practice. This is important as it is the commonest complication of herpes zoster (9-30% incidence) and can be the cause of considerable persisting pain and suffering. PHN is a classical neuropathic pain condition and if simple analgesics do not suffice (as will often be the case) then institution of anti-neuropathic pain medications rather than strong opioids should be the next step. This is in line with NICE guidance which advocates either a tricyclic antidepressant in low dose or a gabapentinoid as first line therapies (https://cks.nice.org.uk/post-herpetic-neuralgia). If these are unsuccessful and pain symptoms are persisting then a referral to a pain clinic for consideration of other treatment approaches such as topical capsaicin or combination therapies should be considered before or alongside the introduction of strong opioids. The evidence base supporting the use of strong opioids in PHN is relatively weak (as it is for most neuropathic pain) and the evidence of harms is increasingly apparent in the shape of the current prescription opioid crisis (see for example Godlee's editorial https://www.bmj.com/content/359/bmj.j4828).
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Dear Editor
It is 18 years since I and a few others took your editorial writer to task for recommending the referral of patients with shingles to a pain clinic without giving the reader any hint of what might be reasonably expected of such a facility (1). Half a professional lifetime later I am dismayed that you continue to publish articles that express expertise but which do not attempt to understand the views of colleagues working within the same field. Is it really the case that pain clinics and those who work in them are so obscure? Have you not yet considered that even pain clinic staff (and these days commissioners) might await the arrival of the weekly BMJ with the hope that it may offer them useful advice on the management of those under their care?
1) https://www.bmj.com/rapid-response/2011/10/28/why-burden-pain-clinic
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Though recurrent Zoster is not that rare, it is usually at a different site and my experience is when someone gets recurrent tingling and a blistering rash it is nearly always Herpes simplex (which can occur anywhere on the body and usually recurs in the same place). Early treatment does seem to limit the rash, as does early treatment of Zoster.
Treatment of the first episode of shingles before a rash appears on the basis of dermatome pain, especially on the face (as well as considering giant cell arteritis, etc), is one of those clinical decisions but Acyclovir is pretty safe and not expensive.
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I was saddened to read the suggestion of using Oxycodone for post herpetic pain. This is at a time when we are recognising the iatrogenic epidemic of narcotic addiction. In the UK I think Oxycodone is still not used to the extent that it is in the USA. I personally have never yet met a patient with post herpetic pain in whom I felt the need to narcotics beyond short term codeine. My understanding of the pathophysiology of chronic pain is that early neuropathic pain management (with traditionally triclcylics) may prevent the development of chronicity whereas narcotics are likely to have the opposite effect.
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Dear BMJ
I have just read the article regarding treatment of the above. I believe, where a patient has had herpes zoster infection before, and they have the tingling/pain signalling the reactivation of herpes zoster infection that they recognise from previous infections, that acyclovir oral should be prescribed at that point.
I am aware that many doctors would not prescribe until the rash presents, and I believe this puts patients at unnecessary risk of long term post shingles pain for no reason.
From the article, I believe overall it gives the impression that prescribing should happen on presentation of the rash. Can this be clarified?
Thank you
Eileen Hoogduyn
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Re: Herpes zoster infection. Interplay between herpes zoster infection and COVID-19
Dear Editor
The present article on herpes zoster provided a beneficial update on zoster reactivation. However, we should be aware that the incidence and presentation of zoster seems to have changed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. In the past, the occurrence of shingles in a previously healthy young or middle-aged individual had been thought to be the result of an underlying immunosuppressive state including human immunodeficiency virus (HIV) or lymphoma and necessitated further immunologic workup(1, 2). However, the today stressful era has made zoster prevalent even in immunocompetent individuals. Accordingly, COVID-19, which has been among the most fearsome problems of the current century, may have triggered the evolution of zoster. In fact, being infected with the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) may have become a precipitating factor for herpes zoster infection. Moreover, SARS-CoV-2 vaccination is also associated with abundant cases of zoster reactivation(3).
The pathophysiologic mechanism underlying COVID-associated zoster includes virus-induced immunosuppression (decreased number of natural killer cells and absolute lymphocytes), the iatrogenic immunosuppression imposed by corticosteroid use for management of SARS-CoV-2 infection, and, last but not least, the psychological stress imposed by the illness(4, 5). In contrast, the underlying mechanism for zoster reactivation following SARS-CoV-2 vaccination includes vaccine-induced immune system stimulation, cellular response and changes in interferon responses(6, 7).
Although the mean age of zoster onset is over 60 years, zoster following both SARS-CoV-2 infection and SARS-CoV-2 vaccination has been demonstrated in younger ages(8). Most of these cases occur within 7-10 days following SARS-CoV-2 infection or vaccination. In addition, recurrent herpes zoster has also been reported following COVID vaccination in immunosuppressed patients(9-11).
The post-COVID zosters usually have similar characteristics of those unrelated to SARS-CoV-2 infection (including painful, unilateral vesicular lesions in dermatomal distribution); however, they may present with atypical or severe manifestations, such as necrotic or haemorrhagic herpetic eruptions, multi-dermatomal or disseminated lesions, trigeminal dermatome involvement or accompaniment of severe neuralgia, all related to impaired immune response(12, 13). The COVID-vaccine related zosters also can present atypically. There have been cases of COVID vaccine-associated atypical zoster arising in the oral cavity and hard palate without skin involvement(14).
All the aforementioned issues suggest that the COVID pandemic has opened a new window to all traditional characteristics of any disease; this has included zoster incidence and clinical manifestations, which should be taken into account in looking after patients in primary care.
1. Cho S-F, Wu W-H, Yang Y-H, Liu Y-C, Hsiao H-H, Chang C-S. Longitudinal risk of herpes zoster in patients with non-Hodgkin lymphoma receiving chemotherapy: a nationwide population-based study. Scientific Reports. 2015;5(1):14008.
2. Mohseni Afshar Z, Goodarzi A, Emadi SN, Miladi R, Shakoei S, Janbakhsh A, et al. A comprehensive review on HIV‐associated dermatologic manifestations: from epidemiology to clinical management. International Journal of Microbiology. 2023;2023(1):6203193.
3. Afshar ZM, Aryanian Z, Tabavar A, Hatami P, Janbakhsh A, Goodarzi A, et al. A Comparison of SARS-CoV-2 Infection-related and COVID-19 Vaccine-related Herpes Zoster; A Narrative Review. Journal of Pharmaceutical Negative Results. 2022:734-8.
4. Afshar ZM, Barary M, Ebrahimpour S, Hasanpour A, Janbakhsh A, Sayad B, et al. Impact of corticosteroid use in COVID-19 infection: A rapid clinical review. Authorea Preprints. 2024.
5. Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. The Journal of infectious diseases. 2020;221(11):1762-9.
6. Babazadeh A, Miladi R, Barary M, Shirvani M, Ebrahimpour S, Aryanian Z, et al. COVID‐19 vaccine‐related new‐onset lichen planus. Clinical case reports. 2022;10(2):e05323.
7. Mohseni Afshar Z, Barary M, Hosseinzadeh R, Karim B, Ebrahimpour S, Nazary K, et al. COVID-19 vaccination challenges: A mini-review. Human vaccines & immunotherapeutics. 2022;18(5):2066425.
8. Iwanaga J, Fukuoka H, Fukuoka N, Yutori H, Ibaragi S, Tubbs RS. A narrative review and clinical anatomy of Herpes zoster infection following COVID‐19 vaccination. Clinical Anatomy. 2022;35(1):45-51.
9. Desai HD, Sharma K, Patoliya JV, Ahadov E, Patel NN. A rare case of varicella-zoster virus reactivation following recovery from COVID-19. Cureus. 2021;13(1).
10. Bostan E, Yalici‐Armagan B. Herpes zoster following inactivated COVID‐19 vaccine: a coexistence or coincidence? Journal of cosmetic dermatology. 2021;20(6).
11. Song J-H, Park S-Y. A Case of Recurrent Herpes Zoster after Coronavirus Disease-2019 (COVID-19) Vaccination. The Journal of Korean Medicine Ophthalmology & Otolaryngology & Dermatology. 2021;34(4):181-97.
12. Nofal A, Fawzy MM, Deen SMSE, El‐Hawary EE. Herpes zoster ophthalmicus in COVID‐19 patients. International Journal of Dermatology. 2020;59(12):1545.
13. Shors AR. Herpes zoster and severe acute herpetic neuralgia as a complication of COVID-19 infection. JAAD Case Reports. 2020;6(7):656-7.
14. Katsikas Triantafyllidis K, Giannos P, Mian IT, Kyrtsonis G, Kechagias KS. Varicella zoster virus reactivation following COVID-19 vaccination: a systematic review of case reports. Vaccines. 2021;9(9):1013.
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