We investigated the burden of herpes zoster disease in a population-based register study of one of the largest counties in Sweden between the years 2008 and 2010. The overall incidence for herpes zoster was 2.6–3.3 cases per 1000 person-years, ranging from 1.2–9.2 cases per 1000 person-years, depending on age group. The healthcare costs in 2010 directly related to the diagnosis amounted to at least 1.33 million Euro for the county of Västra Götaland, where 17 % of the nation’s inhabitants live. In accordance with other studies, we observed an increase in herpes zoster incidence over the years of study [10–12], which in some countries has been attributed to the introduction of vaccination against VZV. As the incidence of chickenpox decreases in vaccinating countries, the elderly will not be exposed to a natural booster by their grandchildren, which may increase later herpes zoster incidence in older birth cohorts. This theory could not, however, explain our findings, since VZV vaccination is not part of the child vaccination program in Sweden. Our observed increase could therefore at least in part be explained by other factors, such as improved surveillance and reporting of cases to health authorities. An ageing population and an increasing number of immunosuppressed patients as a result of solid organ or bone marrow transplantation, may also serve to explain this increasing trend, which should be further investigated.
Herpes zoster incidence was generally higher in women than in men, as observed previously [10, 13] and in line with another Swedish study, although the use in that study of prescription proxies, and hospitalization data only, entails that comparison of incidence rates is challenging . Whether this gender difference is due to biological mechanisms and/or detection bias is not known.
Although strongly related to increasing age, we further observed that 30 % of our cases were found in patients below 50 years of age, emphasizing the important distinction that herpes zoster is not only a geriatric affliction [10, 13, 15, 16].
The most frequent complications to herpes zoster were pain, Bell’s palsy and ocular problems. Herpes zoster-related meningitis and encephalitis were very rare, with an incidence of less than 1/100 000 person-years. In a study investigating viral DNA/RNA in cerebrospinal fluid from patients with suspected infection and neurological syndromes in Västra Götaland County, the estimated incidence of VZV central nervous system infections was 1.8/100 000 person-years , as defined by positive PCR-detection of VZV DNA. Our findings as recorded in the Swedish Patient Register may therefore represent a slight underestimation, likely due to meningitis and encephalitis sometimes being coded as “other meningitis and encephalitis”, without reference to the correct B02 ICD code.
When studying the relation between immunosuppressive conditions (IC) and herpes zoster, we found that 5–13 % of our cases had a prescription of an immunosuppressive drug within 90 days before herpes zoster diagnosis, and 6.8–8.2 % had a previous diagnosis of an IC condition, both of which findings confirm results from a UK study where 8 % of hospitalized herpes zoster cases had underlying IC . The latter observation also mirrors the findings by others on a substantially increased risk of herpes zoster in those with cancer and other immunosuppressive diagnoses [16, 19]. We furthermore found that the preceding use of immunosuppressive drugs was more common in our herpes zoster patients than in the general population, even in the ages below 50 years.
It has been proposed that the broader use of corticoids in children is associated with more common affliction of shingles in the same age group . If this applies also to adults, our findings may lend support to this argument, although it is possible that this association is related instead to a higher relative use of healthcare visits/resources.
The proportion of pain-related complications within one year after diagnosis was up to 15 % in the oldest population. The incidence of long-term post-herpetic neuralgia (PHN) caused by herpes zoster varies between studies depending on study population and definitions used. Pain up to 30 days after diagnosis may reflect only acute pain, and not true PHN . We thus present data per time window since diagnosis, to enable a distinction between acute and long-term pain. We partially defined pain/PHN through prescription proxies, and it is not certain whether these analgesics against neuropathic pain were prescribed specifically for pain related to herpes zoster; or actually for some other neuropathic condition. Nevertheless, we focused on reasonable time spans for prescription, and analgesics in line with Swedish guidelines for herpes zoster . Indeed, our observations are in accordance with previous findings, where the condition develops in 8–14 % of patients [23–25].
Herpes zoster may also be related to more severe subsequent outcomes such as stroke , where one potential mechanism could be direct infection of cerebral arteries . We observed an increased risk of both stroke and CVD within a year after herpes zoster, which may be in line with previous reports of VZV-related neurological sequelae [5, 17]. We also found that the youngest population (0–39 years) had a 4-fold higher risk of developing stroke within a year after herpes zoster diagnosis—which may support previous findings of VZV as a risk factor for stroke in children [28–30].
In one study, post-varicella cerebral infarctions in children age 0–6 years were uniformly located to the middle cerebral artery territory  and it may be of relevance to investigate in clinical studies whether stroke after herpes zoster might show a similar regional pattern.
Furthermore, bacteremia has been associated with chickenpox/primary VZV infection in children [31, 32]. We observed an overall increased risk for subsequent sepsis in herpes zoster patients and the largest risk increase (9-fold) was again found in the youngest age group, which may indicate that herpes zoster is a risk factor in young individuals, similar to chickenpox. These analyses do not adjust for potential confounders in terms of co-morbidities and therefore should be interpreted with caution. Nevertheless, even if there is no causal relation, it is conceivable that occurrence of herpes zoster could act as a risk marker for subsequent severe disease in vulnerable populations.
Since this is a register-based study, there are some instances where registration may have been imperfect, and our conclusions affected, as described above. However, we conclude after our chart validation that our use of the diagnosis code B02 is highly valid. If at least half of the unclear cases were actually cases of sub-optimally documented herpes zoster, the verification proportion would be around 86 %, a figure reflected in other studies . Our proportion of false positives therefore appears low, and although we did not assess the proportion of false negatives, our observed incidence is in line with the published literature, which should entail that our approach is valid for the proportion of herpes zoster cases which have merited/triggered health care attention.
Regarding costs, we did not consider costs for complications that were not connected to the ICD-code B02; prescriptions >90 days after herpes zoster diagnosis, or additional treatments for IC patients with herpes zoster. Also, our definition of IC was somewhat limited compared to other studies. Other studies who have considered these and other additional factors observe a higher cost related to herpes zoster treatment [34, 35]. Our estimates of costs should therefore be regarded as conservative.