Seasonal Variation and Temporal Trends of Herpes Zoster: A Single-Center Retrospective Cross-Sectional Study

1. Introduction

Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3), is a double-stranded DNA alphaherpesvirus that causes varicella (chickenpox) during primary infection and herpes zoster (shingles) following reactivation of latent virus. Primary VZV infection generally occurs during childhood and is transmitted through respiratory droplets or direct contact with infectious secretions [1]. After initial infection, VZV spreads to the dorsal root or trigeminal nerve ganglia via blood or retrogradely from cutaneous nerves and remains latent there for life [2]. The development of herpes zoster is triggered by reactivation of latent VZV acquired through primary infection or vaccination, usually in the setting of waning immunity [3]. Cell-mediated immunity plays a central role in maintaining VZV latency, and reactivation is generally attributed to a decline in this immune surveillance. Upon reactivation, VZV replicates within cell bodies of neurons [4]. In the subsequent phase, the viral particles are transported from the cell bodies along the nerve axons to the associated dermatome. In the affected dermatome, the virus provokes inflammation and causes a painful, erythematous, vesicular rash [1]. VZV shows a worldwide distribution. Varicella infection in pregnancy can spread via placenta, leading to fetal infection which leads to disseminated life-threatening diseases. But herpes zoster does not pose a risk to a developing fetus due to specific maternal antibodies that are transmitted diaplacental to the fetus [4]. The characteristic cutaneous manifestation of herpes zoster is a painful, grouped vesicular rash that is usually limited to a single dermatomal distribution [5]. In immunocompromised individuals, herpes zoster may present with disseminated disease involving multiple organs, including the brain and liver [2,5]. Herpes zoster may lead to severe complications, resulting in increased hospitalization rates. Herpes zoster is uncommon in the pediatric population [5]. Notable complications of herpes zoster include postherpetic neuralgia, cranial nerve palsies, meningitis, encephalitis, myelitis, stroke, bacterial superinfections, hepatitis, Reye syndrome, and Ramsay Hunt syndrome [1,5]. Although postherpetic neuralgia is the most common neurological complication of herpes zoster, stroke represents one of its most serious complications. A total of 10-20% of patients with herpes zoster suffer from herpes zoster ophthalmicus, the infection of the ophthalmic branch of the trigeminal nerve, which can cause vision loss. The risk of stroke increases after a herpes zoster episode, especially following cases with ocular involvement and in immunocompromised patients. Well-established risk factors for herpes zoster include advanced age (≥50 years), immunodeficiency, acute infections, psychological stress, and female sex [1]. Herpes zoster has traditionally been considered to occur throughout the year without epidemic patterns, reflecting the reactivation of latent endogenous VZV, with most population-based studies reporting no seasonal variation in incidence [6,7]. Herpes zoster can occur at any age, particularly in individuals with impaired cell-mediated immunity due to underlying diseases or immunosuppressive medications [8]. Recent large population-based studies have demonstrated significant seasonal variation with a peak during the summer months [9,10]. To address the inconsistent findings of previous studies on herpes zoster seasonality, this study aimed to evaluate monthly and seasonal variation and temporal trends of herpes zoster and to investigate their potential implications for disease prevention.

2. Materials and Methods

This study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Istanbul Medipol University with protocol code E-10840098-202.3.02-3570 on 4 June 2025. As anonymized routine laboratory data were analyzed in this retrospective study, informed consent for participation was not required in accordance with the Turkish Regulation on Clinical Research, overseen by the Turkish Medicines and Medical Devices Agency, Ministry of Health. The clinical photographs contain no identifiable information, and informed consent was obtained from the patients. A retrospective cross-sectional study design was used, wherein the outpatient records of all patients who visited the dermatology outpatient clinic of our hospital between January 2017 and December 2025 were reviewed. Outpatient clinic records were screened for herpes zoster using the ICD-10 (International Classification of Diseases, 10th Revision) code B02. Medical records of all patients diagnosed with herpes zoster, regardless of age, were retrospectively reviewed. For patients with multiple visits, only the first visit was included in the analysis and was considered the index date. Data on patient age, sex, and the year, month, and season of herpes zoster diagnosis were collected. Because the study was conducted in the Northern Hemisphere, December, January, and February were classified as winter; March, April, and May as spring; June, July, and August as summer; and September, October, and November as autumn. The data obtained from the study were analyzed using IBM SPSS Statistics for Windows, version 30.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics for the sociodemographic and clinical characteristics of the patients were presented as counts (n), percentages (%), medians, and interquartile ranges (IQR). The distributions of herpes zoster cases according to month, season, and year were presented using frequency tables and graphs. Differences in herpes zoster case proportions across months, seasons, and years were evaluated using the chi-square test. When a significant difference was detected, pairwise comparisons of proportions were performed with Bonferroni adjustment for multiple comparisons. A linear-by-linear association test was used to assess the presence of a linear trend across years. To evaluate more recent temporal trends, this analysis was specifically applied to the 2020–2025 period. Statistical significance was set at p < 0.05.

3. Results

During the study period, a total of 1493 patients diagnosed with herpes zoster were evaluated; 784 (52.5%) were female and 709 (47.5%) were male. The patients ranged in age from 1 to 104 years, with a mean age of 53.4 ± 19.0 years and a median age of 56 years. The highest proportion of cases occurred in the 60–69-year age group (21.8%), followed by the 50–59-year age group (21.3%) (Table 1). The numbers of herpes zoster cases and total outpatient visits by year, month, and season are summarized in Table 2. The seasonal and annual variation in the herpes zoster case rate per 1000 dermatology outpatient visits is summarized in Table 3. The monthly and annual variation in the herpes zoster case rate per 1000 dermatology outpatient visits is summarized in Table 4. The overall mean case-to-dermatology outpatient visit rate of herpes zoster was 3.89 cases per 1000 visits. The highest and second-highest monthly case rates were observed in April 2020 and April 2021, at 9.04 and 8.48 cases per 1000 visits, respectively. Monthly mean rates ranged from 3.39 to 4.43 per 1000 visits, with the highest rate observed in November, and the lowest rate in July (Figure 1). However, no statistically significant difference was observed in visit-adjusted case rates across months (p = 0.453) (Table 5). Annual mean rates ranged between 2.72 to 5.21 cases per 1000 dermatology outpatient visits, with the highest rate observed in 2025, and the lowest rate in 2022 (Figure 2). Bonferroni-adjusted post hoc analyses showed that the herpes zoster case rate in 2025 was significantly higher than those in 2017, 2018, 2019, 2022, and 2023, whereas the case rates in 2022 and 2023 were significantly lower than that in 2024. During the 2020–2025 period, a significant linear increasing trend in herpes zoster case rates was observed (Linear-by-Linear Association = 14.431; df (degrees of freedom) = 1; p < 0.001). However, this increase was not continuous over the years; herpes zoster case rates decreased in 2022 and 2023, followed by an increase in 2024 and 2025, reaching the highest rate in 2025 (5.21 per 1000 dermatology outpatient visits) (Table 6). In the seasonal analysis, the highest case rate was observed in autumn, with a rate of 4.14 per 1000 visits. The corresponding rates were 3.82 in winter, 3.80 in spring, and 3.76 in summer (Figure 3). However, the difference between seasons was not statistically significant (p = 0.486) (Table 7).

4. Discussion

Varicella-zoster virus is a highly contagious human herpesvirus that causes varicella during primary infection [1]. VZV can be transmitted via the airborne route or through direct contact with vesicular fluid from varicella or herpes zoster lesions [7]. Following initial replication in the respiratory tract, VZV spreads to the regional lymph nodes, followed by viremia and subsequent dissemination to the skin, where it produces the characteristic vesicular rash of varicella. T lymphocytes play a key role in the systemic dissemination of VZV from the respiratory tract to the skin and sensory neurons. Following primary infection, VZV establishes latency in sensory ganglia and may reactivate decades later, resulting in herpes zoster [1]. Two mechanisms have been proposed for the establishment of VZV latency in sensory ganglia: transport of the virus by infected T cells during varicella-associated viremia and retrograde axonal transport from infected sensory nerve endings in the skin. Upon reactivation, VZV is transported along microtubules within sensory axons to the skin, where it infects epithelial cells [7]. VZV reactivation is associated with impaired cell-mediated immunity, which may occur as part of the natural aging process, as a consequence of an immunocompromising condition, or following immunosuppressive therapy [7,8]. Herpes zoster occurs worldwide and its complications are potentially life-threatening [4]. Evidence regarding the seasonality of herpes zoster remains inconsistent [9]. Given the inconsistent evidence regarding herpes zoster seasonality, the present study aimed to assess monthly and seasonal variations in herpes zoster case rates and to explore their potential implications for disease prevention. A total of 1493 patients with herpes zoster were included in this study, of whom 52.5% were female and 47.5% were male, indicating a slight female predominance. This finding is consistent with the study conducted in Sweden, which provides evidence of the female predominance in herpes zoster disease [11]. The patients in our study ranged in age from 1 to 104 years, consistent with previous reports indicating that herpes zoster can occur across all age groups [8] (Figure 4 and Figure 5). The mean age of the patients was 53.4 ± 19.0 years, with a median age of 56 years. Adults above 50 years are at an increased risk for developing herpes zoster due to immunosenescence associated with advancing age [8]. Age-related immunosenescence is accompanied by a progressive decline in cell-mediated immunity, which may facilitate the reactivation of latent VZV [7]. The greatest proportion of our cases was observed in the 60–69-year age group (21.8%), followed closely by the 50–59-year age group (21.3%); together, these age groups accounted for 43.1% of all cases. This finding is consistent with a multicenter study conducted in our country, in which the largest proportion of herpes zoster cases was observed among individuals aged 60–69 years (24.3%), followed by those aged 50–59 years (20.3%), with these two age groups together accounting for 44.6% of all cases. Herpes zoster is not a notifiable disease in our country, and no nationwide surveillance or registry system is currently available [12]. Consequently, epidemiological data are primarily derived from single-center or multicenter studies rather than population-based studies. The overall mean herpes zoster case rate in our study was 3.89 per 1000 dermatology outpatient visits, while previous studies have reported an annual incidence of approximately 2–3 cases per 1000 patients per year in the general population [7]. In our study, the highest and second-highest monthly case rates were observed in April 2020 and April 2021, coinciding with periods of stringent COVID-19-related public health restrictions in our country. The marked reduction in dermatology outpatient visits during these periods may have contributed to the elevated case rates per 1000 outpatient visits, potentially reflecting pandemic-related changes in healthcare utilization and healthcare-seeking behavior rather than a true increase in herpes zoster occurrence [13,14]. Monthly mean herpes zoster case rates in our study ranged from 3.39 to 4.43 per 1000 dermatology outpatient visits, with the highest rate observed in November and the lowest in July; however, no statistically significant differences were observed across months. This finding is consistent with previous population-based studies reporting no significant association between month and the occurrence of herpes zoster [15,16]. In the seasonal analysis, the highest herpes zoster case rate was observed in autumn, followed by winter, spring, and summer. However, these differences were not statistically significant, indicating no clear evidence of seasonal variation in herpes zoster case rates. A study conducted in 2025 similarly found no statistically significant seasonal variation in herpes zoster occurrence, although the mean number of cases was slightly higher during the summer months [17]. The multicenter study conducted in 2025 and a population-based study conducted in 2014 reported no apparent seasonal variation in herpes zoster occurrence; however, neither study performed a statistical analysis to formally assess seasonality [12,15]. In contrast to our findings, several studies have reported significant seasonal variation in herpes zoster occurrence, with a peak during the summer months [9,10,18]. A recent study from Germany identified two distinct peaks in herpes zoster incidence: one during the summer and another from late December to early January [19]. Two previous studies have reported an increase in herpes zoster cases associated with periods of increased rainfall and humidity [3,20]. One study reported a latitudinal gradient in herpes zoster seasonality, with a strong correlation observed between seasonal ultraviolet radiation levels and herpes zoster incidence [21]. But epidemiological sources have generally considered herpes zoster to occur throughout the year because it represents endogenous reactivation of latent varicella-zoster virus [7]. During the 2020–2025 period, a significant linear increasing trend in herpes zoster case rates was observed in our study. However, this increase was not continuous over the years; herpes zoster case rates decreased in 2022 and 2023, followed by an increase in 2024 and 2025, reaching the highest rate in 2025. The decline in visit-adjusted herpes zoster rates observed in 2022 and 2023 may partly reflect post-pandemic changes in healthcare-seeking behavior, with patients becoming more likely to seek outpatient care for relatively minor complaints [14]. The resulting relative increase in the overall number of dermatology outpatient visits may have increased the denominator, thereby contributing to the lower herpes zoster case rates observed during these years. In our study, the highest herpes zoster case rate was observed in 2025, consistent with the reported global trend toward increasing herpes zoster incidence, which may be partly attributable to population aging [22]. The incidence of herpes zoster may be expected to increase over time as populations age and the use of immunosuppressive therapies becomes more widespread [6]. It has also been hypothesized that reduced exposure to varicella, particularly following the introduction of varicella vaccination programs, may diminish exogenous boosting of VZV-specific immunity and consequently increase the risk of herpes zoster [10]. It is estimated that at least 20-30% of the population and up to 50% of individuals who reach the age of 85 will be affected by herpes zoster [23]. According to data from the Global Burden of Disease database, herpes zoster–associated mortality among individuals aged >65 years ranges from 0.0022 to 82.21 deaths per 100,000 population [4]. A systematic review demonstrated a high incidence of herpes zoster among individuals aged ≥50 years across different geographic regions. Moreover, most studies that evaluated temporal trends reported an increase in herpes zoster incidence over time [24]. Herpes zoster can usually be diagnosed clinically based on the characteristic appearance of the rash. In atypical cases of herpes zoster, laboratory confirmation may be obtained by polymerase chain reaction (PCR), direct immunofluorescence assay, viral culture, or histopathological examination of a skin biopsy (Figure 6 and Figure 7). PCR detection of varicella-zoster virus DNA in vesicular fluid is considered the most sensitive and specific method for confirming herpes zoster. PCR testing can be performed on specimens obtained from skin lesions, blood, plasma, cerebrospinal fluid, and bronchoalveolar lavage fluid [8]. Postherpetic neuralgia is the most common complication of herpes zoster and may substantially impair quality of life, with an impact comparable to that associated with congestive heart failure, depression, acute myocardial infarction, and diabetes mellitus [15]. Antiviral-resistant VZV strains may emerge in immunocompromised patients, particularly during prolonged antiherpesvirus therapy. Amenamevir, a helicase–primase inhibitor with a novel mechanism of action and activity against acyclovir-resistant VZV strains, is approved for the treatment of herpes zoster in Japan. Vaccination may play an important role in preventing varicella and herpes zoster in immunocompromised patients, thereby potentially reducing the risk of antiviral-resistant VZV infections. In older adults, herpes zoster vaccination may provide a more reliable approach to the prevention and mitigation of herpes zoster than prodromal or preemptive antiviral therapy [25]. VZV is thought to have emerged approximately 70 million years ago and is considered to be genetically stable [16]. Herpes zoster vaccination is an effective preventive strategy for reducing the risk of VZV reactivation and subsequent herpes zoster [17]. Two vaccines have been developed for the prevention of herpes zoster: the zoster vaccine live (ZVL), licensed in 2006, and the recombinant zoster vaccine (RZV), introduced in 2017 [1]. RZV is more effective than ZVL in preventing herpes zoster. As a non-live, nonreplicating vaccine, RZV can also be administered to immunocompromised individuals [4]. The incidence of serious adverse events and deaths was similar between RZV and placebo recipients, suggesting that these events were more likely related to the underlying risks associated with an aging population than to vaccination itself. RZV is recommended for immunocompetent adults aged ≥50 years and immunocompromised adults aged ≥18 years. Optimal vaccine efficacy is achieved with two doses administered 2–6 months apart [2]. A meta-analysis found that herpes zoster vaccination was significantly associated with a reduced risk of dementia [26]. Although herpes zoster is uncommon in children, varicella vaccination has been associated with a 64% reduction in the risk of herpes zoster in children [4]. One study reported that, in the post-varicella vaccination era, pediatric herpes zoster occurred at an earlier age but retained a relatively mild clinical phenotype [27]. Individuals with herpes zoster can transmit VZV to susceptible seronegative contacts, resulting in varicella rather than herpes zoster. Childhood varicella vaccination may influence the epidemiology of herpes zoster in two distinct ways. First, as vaccinated children reach adulthood, fewer individuals will harbor latent wild-type VZV, potentially reducing the incidence of herpes zoster. Second, in the short term, reduced exposure to children with varicella may decrease exogenous boosting of VZV-specific immunity in adults with latent VZV. As exogenous boosting is thought to protect against VZV reactivation, its reduction may temporarily increase the incidence of herpes zoster and lower the age at disease onset. Mathematical models suggest that the increase in herpes zoster incidence may persist for more than 30 years [28]. A systematic review noted that several studies reported a decline in herpes zoster incidence in the oldest age groups [24]. A similar pattern was observed in the age distribution of our cohort, with patients aged 70–79 years and ≥80 years accounting for 14.1% and 6.3% of cases, respectively. The largest proportion of herpes zoster cases in our study was observed in the 60–69-year age group (21.8%), consistent with a population-based study that reported the highest herpes zoster incidence in the same age group (22.4 per 1000 person-years) [15]. A population-based study spanning 60 years reported a more than fourfold increase in herpes zoster incidence across all age groups and both sexes. However, the rate of increase did not differ significantly before and after the introduction of varicella vaccination [16]. In our country, a universal single-dose varicella vaccination program for children aged 12 months was introduced in 2013, although a two-dose schedule is recommended for licensed live attenuated varicella vaccines. The recombinant zoster vaccine is available in our country but is not currently included in the national immunization program [29]. Herpes zoster surveillance has been recommended to assess the potential impact of varicella vaccination on herpes zoster incidence [5]. Understanding seasonal patterns and long-term trends in herpes zoster occurrence is important for informing public health planning, optimizing healthcare resource allocation, and guiding preventive strategies [10]. In our study, no significant seasonal variation in herpes zoster case rates was observed. In contrast to our findings, several studies have demonstrated significant seasonal variation, most commonly characterized by a peak during the summer months [9,10,18]. These discrepancies may reflect differences in geographic location, climatic conditions, study populations, and methodological approaches used to assess seasonality. Consistent with our findings, several population-based studies have reported no significant seasonal variation in herpes zoster occurrence, with the earliest published in 1957 and the most recent in 2025 [17,30]. In accordance with these observations, the Centers for Disease Control and Prevention (CDC) Pink Book indicates that herpes zoster does not exhibit a distinct seasonal pattern and occurs throughout the year [31]. More conclusive evidence may be obtained from large-scale, multicountry studies conducted concurrently across diverse populations.

5. Conclusions

Varicella-zoster virus, also known as human herpesvirus 3, is a double-stranded DNA alphaherpesvirus that causes varicella during primary infection and herpes zoster following reactivation of latent virus [1]. Herpes zoster may lead to severe complications, resulting in increased hospitalization rates [5]. Epidemiological sources have generally considered herpes zoster to occur throughout the year because it represents endogenous reactivation of latent varicella-zoster virus [7]. More recent large population-based studies have demonstrated significant seasonal variation with a peak during the summer months [9,10]. In our study, no significant monthly and seasonal variation in herpes zoster case rates was observed. Consistent with our findings, several population-based studies have reported no significant seasonal variation in herpes zoster occurrence, with the earliest published in 1957 and the most recent in 2025 [17,30]. In accordance with these observations, the CDC Pink Book indicates that herpes zoster does not exhibit a distinct seasonal pattern and occurs throughout the year [31]. Herpes zoster is a vaccine-preventable disease that may cause serious complications and shows an increasing trend in occurrence. Our findings suggest that herpes zoster does not exhibit a distinct seasonal pattern and occurs throughout the year, supporting the importance of maintaining year-round preventive strategies, including vaccination.