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Identifying patients at risk

Immune function and risk

The key risk factors for shingles and its complications are older age and immunocompromised status, both of which are linked to weakened immune function allowing reactivation of varicella zoster virus.1,2 However, there are other risk factors which should also be considered:1,2

Older age3-6

Incidence of shingles increases with age, roughly doubling every decade after 50 years of age.3 This is thought to result from the age-related decline in cell-mediated immunity, known as immunosenescence.2,3 Shingles is less common in children and cases are usually very mild7

An icon of an elderly person with a walking stick

Immunocompromised status5,8-10

Immunocompromising conditions or immunodeficiency can impact cell-mediated immunity and increase the risk of shingles2

Patients receiving immunosuppressive medication, including targeted therapies and biologics that suppress the immune system, have an increased risk of shingles9

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Other risk factors

Other factors that increase risk of shingles include the following:

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Certain acute or chronic conditions5,9,10
Chronic conditions associated with an increased risk of shingles include chronic kidney disease, asthma, diabetes, cardiovascular conditions and chronic obstructive pulmonary disease2

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Female sex5,8-10
Proposed reasons for findings of a higher risk of shingles in women than men include the possibility that women may be more likely to visit their general practitioner with symptoms and a possible impact of the menopause on immune responses10

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Family history of shingles2,9
One mechanism proposed to explain the increased risk observed with a family history of shingles is genomic variation in the genes for human leukocyte antigens (HLA), which are involved in eliciting the immune response3,9

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White race8-10
Possible reasons for the impact of race/ethnicity that have been proposed include differences in genetic risk, household composition, lifetime exposure to varicella (chickenpox), access to healthcare and/or health-seeking behaviours9,10

An icon of a person’s head with the brain highlighted. There is a lightning bolt over the brain.

Psychological factors2,5,9,11,12
Certain life events or psychological factors, including post-traumatic stress disorder, depression, psychological stress and physical trauma, may contribute to an increased risk of shingles2,9,11,12

Spotlight on older age and immunosenescence

Immunosenescence describes the gradual age-related decline of the innate and adaptive immune responses and overall immune function, including the following changes:13

An illustrated drawing of a T cell

Senescent T cells lose proliferative capacity and display downregulated expression of CD27 and CD2814

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B cells show an age-associated decline in clonal diversity and reduced antibody response efficiency14

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Macrophages and neutrophils exhibit diminished capacity for phagocytosis and chemotaxis14

Defining immunocompromised status

Immunocompromised status and immune deficiency are often used interchangeably as terms to indicate that an individual has a weakened immune system with reduced ability to fight infection.15,16 The causes can be categorised into two groups:16

Inborn errors of immunity

Also known as primary immunodeficiencies, these are inherited immune disorders resulting from genetic mutations usually present from birth and diagnosed in childhood.16,17 Examples include X-linked agammaglobulinaemia and severe combined immunodeficiency17

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Secondary immunodeficiency

Secondary immunodeficiency is acquired as a result of disease (such as human immunodeficiency virus) or treatment with drugs that induce immunosuppression (such as chemotherapy)16,18

An icon of a medicine bottle and a virus

Which patients with immunocompromised status are at risk?

Patients with conditions that change cell-mediated immunity are one of the groups at the highest risk of developing shingles2,19

In a study of 621,588 patients with immunocompromising conditions, the overall incidence rate of shingles in the cohort of patients who were immunocompromised was 7.8/1000 person-years compared with 6.2/1000 person-years in a cohort of patients who were not immunocompromised.19 The incidence with individual immunocompromising conditions was documented:

Incidence of shingles in patients with immunocompromising conditions19

A bar graph displaying the overall incidence of shingles per 100 person-years across various immunocompromising conditions.

Chart created using data from Yanni EA et al. 2000-2012. BMJ Open 2018;8:e020528

In this study, shingles risk was evaluated only in a cohort of individuals with selected immunocompromising conditions and a matched cohort of individuals who were immunocompromise free,19 but other chronic conditions have also been identified as risk factors for shingles, including:

  • Asthma and chronic obstructive pulmonary disease9,20
  • Chronic kidney disease20
  • Depression20
  • Type 1 diabetes20
  • Granulomatosis with polyangiitis, previously known as Wegener’s granulomatosis5,6

References

  1. Centers for Disease Control and Prevention. Zoster. https://www.cdc.gov/vaccines/pubs/pinkbook/herpes-zoster.html (accessed February 2024).
  2. Marra F et al. Risk factors for herpes zoster infection: A meta-analysis. Open Forum Infect Dis 2020;7:ofaa005.
  3. Gauthier A et al. Epidemiology and cost of herpes zoster and post-herpetic neuralgia in the United Kingdom. Epidemiol Infect 2009;137:38-47.
  4. Kimberlin DW and Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007;356:1338-1343.
  5. National Institute for Health and Care Excellence. Clinical knowledge summary: Shingles. https://cks.nice.org.uk/topics/shingles/ (accessed February 2024).
  6. Johnson RW et al. Herpes zoster epidemiology, management, and disease and economic burden in Europe: A multidisciplinary perspective. Ther Adv Vaccines 2015;3:109-120.
  7. Primary Care Dermatology Society. Herpes zoster (syn. shingles). https://www.pcds.org.uk/clinical-guidance/herpes-zoster (accessed January 2024).
  8. Le P and Rothberg M. Herpes zoster infection. BMJ 2019;364:k5095.
  9. Kawai K and Yawn BP. Risk factors for herpes zoster: A systematic review and meta-analysis. Mayo Clin Proc 2017;92:1806-1821.
  10. Cadogan SL et al. Prevalence of and factors associated with herpes zoster in England: A cross-sectional analysis of the Health Survey for England. BMC Infect Dis 2022;22:513.
  11. Cohen KR et al. Presentation and management of herpes zoster (shingles) in the geriatric population. P T 2013;38:217-227.
  12. Sinayobye J et al. Prevalence of shingles and its association with PTSD among HIV-infected women in Rwanda. BMJ Open 2015;5:e005506.
  13. Lee KA et al. Immune senescence, immunosenescence and aging. Front Aging 2022;3:900028.
  14. Xu W et al. The untwining of immunosenescence and aging. Semin Immunopathol 2020;42:559-572.
  15. Centers for Disease Control and Prevention. Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html (accessed March 2024).
  16. British Society for Immunology. Immunodeficiency. https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/immunodeficiency (accessed January 2024).
  17. Tangye SG et al. Human Inborn Errors of Immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2020;40:24-64.
  18. Marshall JS et al. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol 2018;14:49.
  19. Yanni EA et al. Burden of herpes zoster in 16 selected immunocompromised populations in England: A cohort study in the Clinical Practice Research Datalink 2000-2012. BMJ Open 2018;8:e020528.
  20. Forbes HJ et al. Quantification of risk factors for herpes zoster: Population based case-control study. BMJ 2014;348:g2911.

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July 2024 | NP-GB-HZU-WCNT-240013 (V1.0)