Quantification of risk factors for postherpetic neuralgia in herpes zoster patients: A cohort study

Abstract

Objective: To investigate risk factors for postherpetic neuralgia, the neuropathic pain that commonly follows herpes zoster.

Methods: Using primary care data from the Clinical Practice Research Datalink, we fitted multivariable logistic regression models to investigate potential risk factors for postherpetic neuralgia (defined as pain ≥90 days after zoster, based on diagnostic or prescription codes), including demographic characteristics, comorbidities, and characteristics of the acute zoster episode. We also assessed whether the effects were modified by antiviral use.

Results: Of 119,413 zoster patients, 6,956 (5.8%) developed postherpetic neuralgia. Postherpetic neuralgia risk rose steeply with age, most sharply between 50 and 79 years (adjusted odds ratio [OR] for a 10-year increase, 1.70, 99% confidence interval 1.63-1.78). Postherpetic neuralgia risk was higher in women (6.3% vs 5.1% in men: OR 1.19, 1.10-1.27) and those with severely immunosuppressive conditions, including leukemia (13.7%: 2.07, 1.08-3.96) and lymphoma (12.7%: 2.45, 1.53-3.92); autoimmune conditions, including rheumatoid arthritis (9.1%: 1.20, 0.99-1.46); and other comorbidities, including asthma and diabetes. Current and ex-smokers, as well as underweight and obese individuals, were at increased risk of postherpetic neuralgia. Antiviral use was not associated with postherpetic neuralgia (OR 1.04, 0.97-1.11). However, the increased risk associated with severe immunosuppression appeared less pronounced in patients given antivirals.

Conclusions: Postherpetic neuralgia risk was increased for a number of patient characteristics and comorbidities, notably with age and among those with severe immunosuppression. As zoster vaccination is contraindicated for patients with severe immunosuppression, strategies to prevent zoster in these patients, which could include the new subunit zoster vaccine, are an increasing priority.

Figure 1. Adjusted associations between postherpetic neuralgia and demographic risk factors and health behaviors and comorbidities, stratified by whether a patient received antivirals during acute zoster

Adjusted associations between postherpetic neuralgia and (A) demographic risk factors and health behaviors and (B) comorbidities, stratified by whether a patient received antivirals during acute zoster. Analyses are restricted to 69,661 patients for whom antiviral status was most likely to be available. Full results can be found in table e-8. Adjusted for age, sex, socioeconomic status (SES), HIV, leukemia, lymphoma, myeloma, immunosuppressive therapies, rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), asthma, chronic kidney disease, depression, personality disorder, diabetes, recent cancer diagnosis, smoking, and body mass index (BMI) category. Hematopoietic stem cell transplantation and other unspecified cellular immune deficiencies were excluded due to too few numbers. Patients excluded were those with zoster diagnosed in Hospital Episode Statistics (HES) or having a HES visit for zoster 7 days after diagnosis (n = 494), patients who were not HES-linked (n = 45,418), and patients with nontruncal zoster (n = 3,840), as their antiviral use may not be recorded in Clinical Practice Research Datalink. ¹Odds ratios estimate the effect of a 10-year increase in age on postherpetic neuralgia derived, in age groups <50, 50–79, and ≥80 years, from piecewise linear splines. ²Measured by index of multiple deprivation score (IMD1 = least deprived, IMD5 = most deprived). ³Includes patients prescribed a 14-day (or longer) course of high dose (at least 20 mg per day) oral corticosteroids medications in the month before zoster diagnosis, or patients taking other immunosuppressive medications less than 1 month prior to zoster diagnosis. Interaction terms between antiviral use and other risk factors were added to the model one at a time. CI = confidence interval.