Burden of herpes zoster: the direct and comorbidity costs of herpes zoster events in hospitalized patients over 50 years in France

The current PMSI 2011 analysis identified 2,571 stays of patients aged over 50 years hospitalized for HZ corresponding of 0.9 % of the 2011 recorded total stays, while diabetes represented 95,204 stays (62 times more) and degenerative disease represented 48,291 stays (19 times more). The HZ represents a subsequent economic burden of approximately 11 million€ in global Health Assurance expenses and quality management may reduce the total amount spent for HZ treatment. The total annual costs of B029 “HZ without complications” and B023 “Zoster Ocular Disease” care were responsible for 29 % and 16 % of total HZ annual costs respectively. The HZ stay mean cost is 4,206€ ranging between 3,480€ for HZ without complications to 8,893€ for Zoster encephalitis. The Zoster Ocular Disease stay mean cost of 3,516€ is similar to the cost observed in HZ without complications. The absence of cost impact between these two HZ is due to the classification DRG system. In the case of Zoster Ocular Disease stays, the DRG are mainly distributed in the Major Diagnostic Category (MDC) 02 therefore the HZ without complications stays are mainly distributed in the MDC 09. The DRG tariffs relevant to the MDC 02 are lower than the DRG tariffs of MDC 09.

Clinical and costs input data were derived from a cohort of 2,392 patients, with 60 % of women and with a mean age of 76.3 years. Death occurs in 1.6 % of cases of patients hospitalized with zoster. B020 “HZ encephalitis” and B021 “HZ meningitis” stays characteristics involved older patients, longer LOS, higher rates of transfer to another health care institution and higher death rates even though the related number of extracted stays was the lowest (63 and 44 stays respectively).

When present as only comorbidity in hospitalizations for other hospitalization causes, HZ significantly increases the LOS at hospital and subsequent economic burden for the French health system whereas death rates were not linear as expected and do not stand a classical conclusion. Comorbidity indicates the co-occurrence of preexisting age-related health conditions in reference to an index disease [27]. Advanced age is associated with increased vulnerability to chronic health problems. Given the complexity and heterogeneity involved in comorbidity, however, no single definition or measure would serve all research and clinical purposes. The level of comorbidity correlates with the magnitude of immune response in older adults (decrease in T cell proliferation and IL-12 production and increase in IL-10 production in response to PHA stimulation) [28]. Until recent published papers, comorbidities were not taken into account in the management and prognosis of herpes zoster [29]. Risk of herpes zoster has been found in patients with chronic obstructive pulmonary disease [30], kidney disease [31, 32], rheumatoid arthritis [33], inflammatory bowel disease [34], type II diabetes [35]. In addition, some authors report a risk of cancer after infection by herpes zoster [36, 37]. Few data analyzed impact of comorbidities on the management and the cost of herpes zoster.

A Spanish study has been conducted by Gil-Prieto et al. in 2011, describing the disease burden of patients aged ≥50 years hospitalized with HZ (in DP or DAS) between 1998 and 2004 who presented Chronic Obstructive Pulmonary Disease (COPD), cardiovascular disease and/or diabetes [38]. The annual number of hospitalization was 2,289 stays with a mean LOS of 12.4 days. Death rates were 3.7 % and increased to 4.7 % for patients with comorbidity even though death rates were 2.1 % for the cohort without comorbidities. Death rates were higher due to a higher death probability in the treatment of COPD, cardiovascular disease and/or diabetes as the cohort involved patients hospitalized for another primary diagnosis (COPD, cardiovascular disease and/or diabetes).

The study shows only than more women than men with HZ are hospitalized and hospitalization is prevalent in older ages, which is in line with epidemiological studies. As reported by Gonzalez Chiappe et al. [20] and by Chang et al. two decades ago for an Asian population [39], the predominance of HZ in women might be ascribed to a higher proportion of females in the older population. Moreover, Thomas et al. added, in 2004, that women might be more likely to seek medical advice, thereby causing higher reporting rate [32]. Pinchinat et al. review stated, in 2013, that HZ incidence increases sharply with age for the European population [12, 40].

The present study method included a check step by analyzing the age and sex characteristics and their statistical differences in both groups with HZ and without HZ in each of the five pathologies. This check step conclusion determined the need of matching for further analyses to neutralize the confounding factors.

This study highlighted the impact of an associated diagnosis of HZ for patients aged 50 years and older with chronic conditions. When associated to one of the 5 most common chronic diseases, HZ significantly increased the LOS. Herpes Zoster significantly increases length of hospitalization (p < 0.001) leading to subsequent economic burden for the French health system. It is expected that this extension of LOS also has an impact on the cost of the management of the disease. Herpes Zoster doesn’t significantly increase the number of deaths.

This review has various limitations. First of all, PMSI database is the basis of hospital funding and not an epidemiological register. The prospective payment is directly linked to the coding process leading to optimize this latter. Nevertheless the high exhaustiveness and quality of information (including some medical information) allows using the PMSI database to estimate various indicators by disease, like the number of patients hospitalized annually, the number of stays per patient and the total cost of hospitalization [24‐26]. Using hospitals and death records generate limitations: codes were not necessarily accurate; i.e., misclassification or diagnosis errors by coding as a different herpes [41], under reporting of pre-existing conditions such as stroke [42]; inadvertent omissions, the unavailability of medical records to certifying physician and difficulties in determining the underlying cause of death and hospitalization when several disease processes were involved [43, 20].

Further investigations to study the impact of HZ comorbidty in other categories, to provide up-to-date analyses (PMSI 2013 follow-up) in the following 5 to 10 years, will allow a long-term projection of clinical characteristics, economic evaluation and trend over time.