INTRODUCTION: Over the last six decades, there has been a steady increase in the number of herpes zoster (HZ, shingles) cases in the United States, including among younger adults.
A 2013 study (Hales et al1) found that rates of shingles have been climbing since the mid-1940s in all age groups. From 1945 to 1949, 0.76 out of every 1,000 people got the disease. Between 2000 and 2007, that number rose to 3.15 people per 1,000. The virus has hit older adults particularly hard. Shingles rates rose 39% from 1992 to 2010 in people over 65. It is now estimated that one in three (1 in 3) people will get HZ during their lifetime.
DISCUSSION: The rise in HZ cases is a complicated issue. Several factors are involved in these cases. As we discussed in a previous Viro Perspective, waning immunity in younger adults or the possible emergence of wild type alleles may be involved with cases seen in those under 50 years of age.
Immunosuppression is a key reason for HZ. Harpaz et al2 discussed the prevalence in immunosuppression in the U.S. They said that the number of immunosuppressed adults in the United States is unknown but thought to be increasing because of both greater life expectancy among immunosuppressed adults due to improvements in medical management, as well as new indications for immunosuppressive treatments.
Immunosuppression increases the risks and severity of primary or reactivation infections. There are many examples of this, such as in the case of a 67-year-old woman with non-Hodgkin’s lymphoma who was undergoing chemotherapy and who presented with an acute alteration of consciousness due to multiple brain lesions3. MRI of the brain revealed multiple and nonspecific lesions of hyperintensity with mild edema in the cortex and subcortex. She was treated with intravenous acyclovir. However, two days after admission, the patient died and was diagnosed with varicella-zoster virus (VZV) encephalitis. This case highlights the risk of VZV reactivation with severe neurological complications in patients undergoing immunosuppressive therapy.
In another example, there was HZ of the trigeminal nerve with multi-dermatomal involvement4. This was an unusual example of HZ with involvement of both the ophthalmic and maxillary divisions of the trigeminal nerve in an immunocompetent patient. Immunocompetence status and age-specific screening should be warranted in case of atypical involvement and according to the patient’s history, while treatment with antiviral drugs should be rapidly initiated in patients at risk. The 2020 pandemic with SARS-CoV-2 is also showing a correlation of COVID-19 infection with the reactivation of VZV, leading to HZ.
CONCLUSION: There is no single cause for the rise in the reactivation of VZV, however it is apparent that the increase in immunosuppression is key. The use of immunosuppressive drugs to prevent other diseases is common, such as in battling cancer. Many other infections also lower the immunocompetence of an individual. It is known that an active immune response producing interferons helps to keep VZV reactivation in check. It is also known that SARS-CoV-2 infections reduce lymphocytes, monocytes, and eosinophils, along with noted reductions of CD4/CD8 T cells, B cells, and natural killer cells. This results in lymphopenia due to the direct infection of lymphocytes with SARS-CoV-2, activation-induced cell death, and impairment to antiviral responses (such as with specific interferons). At some point, it should be investigated if these HZ cases can be reduced using the SHINGRIX vaccine in those under 50.
- Hales, C.M., Harpaz, R., Joesoef, M. R.., and Bialek, S. R. (2013). Examination of Links Between Herpes Zoster Incidence and Childhood Varicella Vaccination. Ann Intern Med 159(11), 739-745. https://doi.org/10.7326/0003-4819-159-11-201312030-00006
- Harpaz, R., Dahl, R.M., Dooling, K.L. (2016). Prevalence of Immunosuppression among US Adults, 2013. JAMA.2016;316(23):2547-2548. https://doi.org/10.1001/jama.2016.16477
- Suzuki, T., Tetsuka, S., Ogawa, T., Hashimoto, R., Okada, S., and Kato, S. (2020). An Autopsy Case of Varicella Zoster Virus Encephalitis with Multiple Brain Lesions. Intern Med 59: 1643-1647. https://doi.org:/10.2169/internalmedicine.3417-19
- Pelloni, L.S., Pelloni, R., and Borradori, L. (2020). Herpes zoster of the trigeminal nerve with multi-dermatomal involvement: a case report of an unusual presentation. BMC Dermatology 20:12 https://doi.org/10.1186/s12895-020-00110-1
By David Kilpatrick, PhD and Abbas Vafai, PhD
MKTG 1060 – Rev A 060321