Unrecognized risk factors clearly exist for HZ, and it is crucial to identify these risk factors to interpret the epidemiology of HZ, target prevention and treatment strategies, and, in the future, monitor the effect of the HZ vaccination program. This is the first study, to our knowledge, that has examined several common chronic conditions as possible risk factors for HZ and assessed the effect of multiple chronic conditions on the risk of developing HZ. Five of the 10 chronic conditions that we found to be associated with HZ (hyperlipidemia, allergic rhinitis, hypothyroidism, osteoarthritis, and chronic obstructive pulmonary disease) have never been previously reported as HZ risk factors. Although we found significant associations between HZ and 8 of the 10 chronic conditions we investigated, the strength of the associations and their attributable fractions was small. On the basis of this analysis, it seems that chronic conditions do not substantially explain why many persons without recognized risk factors (ie, age and immunosuppression) experience HZ or why the incidence of HZ is increasing.
Estimation of attributable fraction assumes that associations of chronic conditions and HZ are causal and that removing chronic conditions has no effect on the distribution of other competing risk factors for HZ.24,25
Our estimates of attributable fraction should be interpreted cautiously because these assumptions may not be met, especially on the causal associations of chronic conditions and HZ. However, whether the assumptions for estimating attributable fraction are fully met or not, the findings suggest that the prevalent chronic conditions we investigated do not explain or contribute substantially to the burden or increasing incidence of HZ.
We chose this data source because it allowed for parsimonious investigation of a previously unexplored hypothesis. However, our ability to detect an association between HZ and prevalent chronic medical conditions may have been limited by our data source and study design. Because this analysis was limited to a single year of claims data, we could only identify cases of HZ that occurred during that period. It is likely that a portion of persons with chronic diseases included in our control population had had HZ before the study period, leading to an underestimate of the association between chronic diseases and HZ. The time at which individuals with chronic disease come to medical attention and receive a diagnosis of that condition varies with their health care–seeking behavior. Individuals with chronic medical conditions may be more likely to seek medical care for HZ or more likely to have it diagnosed during a medical visit because they have more medical conditions and are more inclined to seek medical care. This differential in health care–seeking behavior may lead to spurious associations between HZ and chronic conditions. If those with chronic medical conditions were more inclined to seek medical care for HZ, we would expect on average the number of medical claims among cases with chronic conditions to be higher than among controls with chronic conditions. However, we found that the median number of claims for cases and controls among those with chronic medical conditions was similar. We also adjusted the association between HZ and chronic conditions with the number of claims. Thus, in our study population, the differential of health care–seeking behavior among cases and controls with chronic conditions would not likely alter the findings of the association between HZ and chronic conditions.
Finally, each of the chronic conditions we examined included a broad spectrum of disease. It is possible that the risk of HZ is increased only among persons with longer duration and greater severity of the condition. Claims data do not always allow patients to be categorized by disease severity.
Our findings have several limitations. Ascertainment of HZ through claims data is only possible if patients seek medical care for the condition. Evidence suggests that most persons with HZ seek medical care.26
In addition, there is no mechanism to validate MarketScan diagnostic codes with medical record reviews. However, other studies have used medical record review to report the validity of administrative data in accurately identifying various acute and chronic diagnoses and procedures, including HZ.27-31
Our finding that immunosuppressed persons are at increased risk of HZ provides an additional degree of internal validity for our study methods.
There may be underascertainment of some of the chronic conditions we examined, especially those conditions that are commonly treated with over-the-counter medications, such as allergic rhinitis, without involving a health care encounter. Physicians may not routinely record a patient's chronic conditions on each medical claim, especially if the patient is being seen for an unrelated medical condition.32
In addition, the underascertainment may vary, depending on the existence of other chronic conditions. For example, persons with allergic rhinitis and other chronic conditions who access medical care for those other conditions may be more likely to have their allergic rhinitis brought to medical attention or, if they have multiple and more severe chronic conditions, may have the visit coded for the more severe conditions and with the allergic rhinitis not coded at all. The underascertainment of these kinds of chronic conditions may result in a spurious lowering of the estimate of the association with HZ. Because corticosteroid use may not be as fully captured in the MarketScan databases, chronic conditions with heavy use of corticosteroids might spuriously increase the estimate of the association with HZ.
Lastly, the MarketScan databases have limited data on sociodemographic characteristics, which limited our ability to control for potential covariates, such as race and income, in our analysis. The enrollees in the MarketScan databases differ from the general population, and our study does not include persons 65 years and older, but it is unlikely that the magnitude of the association of the study risk factors and HZ (or the corresponding attributable fractions) would be increased to a substantial degree by age, race, or income.