Summary: Herpes Zoster or Shingles, is a viral infection caused by the Varicella Zoster Virus and results from the reactivation of the dormant virus. It commonly occurs in immunocompromised adults and manifests as a painful rash along a single dermatome. Special presentations include Herpes Zoster Ophthalmicus and Herpes Zoster Oticus (Ramsay Hunt syndrome). Post-Herpetic Neuralgia (PHN) is a common complication, featuring persistent pain lasting over three months. Management of PHN includes medications like pregabalin and tricyclic antidepressants, along with topical therapies. Shingles vaccines such as Zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV), are approved for prevention, offering protection for several years. Booster doses for vaccines are not currently recommended. Understanding and managing Shingles and its complications are crucial for healthcare professionals.
Keywords: Herpes Zoster; Shingles; Shingles Vaccine; postherpetic neuralgia; Ramsay-Hunt syndrome
What is Shingles?
Herpes Zoster, commonly known as “shingles” is a viral infection caused by the Varicella Zoster Virus (VZV). It occurs due to the reactivation of the dormant virus from the cranial nerve sensory ganglia or the dorsal root ganglia of the spinal nerves. The initial infection of this virus is known as Varicella or “chickenpox” and it usually occurs during childhood or adolescence [1].
Shingles is thus seen in patients who had a prior infection with VZV and it commonly occurs in immunocompromised adults. The underlying cause of immunosuppression could be immunosuppressive drug use, cancer, cancer therapy, autoimmune disorders and human immunodeficiency virus (HIV) infection [1][2].
Shingles manifests clinically as a viral prodrome of fever, headache, photophobia, weakness and burning pain followed by the appearance of a crop of vesicles distributed unilaterally over a single dermatome. The thoracic dermatomes are most commonly involved with the lesser involvement of the cervical, trigeminal and lumbosacral respectively [1]. There are three clinical stages of shingles commonly recognised [1][3]:
Pre-eruptive stage: This stage is usually seen 2 days prior to the eruption of the characteristic skin rash. It involves symptoms of a viral prodrome and burning pain within the affected dermatome.
Eruptive stage: This stage is characterized by the eruption of the skin rash and usually lasts for two to four weeks. The lesions begin as macules, may morph into papules and ultimately transform into painful, umbilicated vesicles. The pain is described as excruciating and unresponsive to nonsteroidal anti-inflammatory drug (NSAID) therapy. Patients are highly infectious during this stage.
Chronic stage: This stage is characterized by excruciating pain lasting for more than four weeks in duration. Neurological pain manifesting with paraesthesias and dysesthesias may be crippling in nature. This stage may last for a year or even longer.
Image 1.0: Unilateral rash of shingles in a thoracic dermatome
Author: Fisle
License: WikipediaCommons
Special presentations of Shingles
Herpes Zoster Ophthalmicus: This is the involvement of the eye in Zoster due to the involvement of the ophthalmic division of the trigeminal nerve. It can manifest as conjunctivitis, uveitis, retinitis but usually involves the cornea producing keratitis and a corneal ulcer. This presentation is dangerous as there is a significant risk of visual loss [3].
Image 2.0: Herpes Zoster Ophthalmicus of the left eye
Author: Jonathan Trobe, M.D. - University of Michigan Kellogg Eye Center
License: WikipediaCommons
Herpes Zoster Oticus or Ramsay Hunt syndrome: This is the involvement of the ear in Zoster due to the involvement of the facial nerve and the geniculate ganglion. It can manifest as unilateral facial paralysis, earache and painful vesicles in the ear canal and the pinna. There may be additional involvement of the auditory nerve leading to hearing loss, vertigo and tinnitus [3].
Image 3.0: Ramsay hunt syndrome- vesicles in the ear canal and unilateral facial palsy
Author: Worme M, Chada R, Lavallee L
Attribution: WikipediaCommons
Central Nervous System Herpes Zoster: There is central nervous system involvement in some patients, particularly those with concomitant HIV/AIDS infection. It can manifest as confusion, headache, personality changes and ataxia.
Post-Herpetic Neuralgia
The most common chronic complication of Shingles is postherpetic neuralgia (PHN). PHN refers to burning pain distributed in a unilateral dermatomal pattern lasting for more than equal to 3 months after a Zoster infection. Since the duration is longer than 3 months, the characteristic rash is usually not seen, however history of preceding rash may be elucidated and skin scarring in the affected dermatome may be seen [4].
Patients usually manifest with altered skin sensation over the affected dermatome including hypoaesthesia or hyperaesthesia, pain on non-painful stimuli such as light touch known as allodynia and altered autonomic supply to the affected skin manifesting as hyperhidrosis.
While the exact cause of PHN is not known, it has been hypothesized to be due to myelin and axonal damage in the peripheral nerves and the central nervous system [4].
Diagnosis of PHN is usually clinical however some tests may be used to support the diagnosis. Serological testing for VZV IgG and IgM may be done however they are non-specific. Viral DNA PCR and CSF viral culture can be used [4].
Due to the disabling nature of the symptoms and the lack of complete resolution of symptoms on treatment, the effective management of PHN is a must-know for clinicians. First line management consists of pregabalin and tricyclic antidepressants. Topical therapies such as a 5% lignocaine patch and capsaicin patches and creams can also be used. Second-line treatment options include invasive modalities such as botulinum toxin injections, local anesthetic injections, spinal cord stimulation, and extradural and intrathecal injections [4].
Prevention of Shingles
There are two shingles vaccines approved in the United States - A zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). Initially, ZVL was only FDA approved for prophylaxis of all immunocompetent adults older than 60 years and was later on FDA approved for all immunocompetent adults over 50 years of age. On the other hand, RZV which has a greater efficacy than ZVL was initially FDA approved for all immunocompetent adults over 50 years of age and was later on FDA approved for persons over 18 years at risk of immunosuppression [5].
ZVL is administered as a single dose subcutaneously in the upper arm and has a protective effect of about eight years while RZV is administered as a two dose regimen intramuscularly in the upper arm 2 to 6 months apart and it offers protection for about 10 years (studies still ongoing). Side effects of both vaccines are mild and consist predominantly on injection site reactions [5].
The vaccines have been shown to boost cell mediated immunity against VZV and are capable of reducing the risk of Herpes Zoster, hospitalisations for Zoster, Herpes Zoster Ophthalmicus and postherpetic neuralgia. While the immune response declines with both vaccines over the years following administration, booster doses are currently not recommended [5].
Author: Dr. Dhruv Gandhi, MBBS, KJ Somaiya Medical College and Research Centre, Mumbai, India.
Editor: Dr. Sidhant Ochani, MBBS, Khairpur Medical College, Khairpur, Pakistan.
References
[1] Nair PA, Patel BC. Herpes Zoster. [Updated 2023 Sep 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441824/
[2] Koshy, E., Mengting, L., Kumar, H., & Jianbo, W. (2018). Epidemiology, treatment and prevention of herpes zoster: A comprehensive review. Indian journal of dermatology, venereology and leprology, 84(3), 251–262. https://doi.org/10.4103/ijdvl.IJDVL_1021_16
[3] Patil, A., Goldust, M., & Wollina, U. (2022). Herpes zoster: A Review of Clinical Manifestations and Management. Viruses, 14(2), 192. https://doi.org/10.3390/v14020192
[4] Gruver C, Guthmiller KB. Postherpetic Neuralgia. [Updated 2023 Apr 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493198/
[5] Harbecke, R., Cohen, J. I., & Oxman, M. N. (2021). Herpes Zoster Vaccines. The Journal of infectious diseases, 224(12 Suppl 2), S429–S442. https://doi.org/10.1093/infdis/jiab387