Analysis of histiocytosis deaths in the US and recommendations for incidence tracking

We determined the frequency of deaths associated with histiocytosis in the United States (US) for which incidence data are lacking and could be potentially important in understanding outcomes for patients with these disorders.

National death data collected by the US Vital Statistics Reporting System and aggregated using wonder.cdc.gov were analyzed for underlying cause of death due to malignant histiocytosis (MH), Langerhans cell histiocytosis (LCH) and Letterer-Siwe disease (LS, a form of LCH) for 3 periods: 1979-1988, 1989-1998, and 1999-2006. To capture histiocytosis, International Classification of Diseases (ICD)-9 codes 202.3, 202.5, and 277.8 and ICD-10 codes C96.1, C96.0, and D76.0-76.1 were used. Deaths were calculated for US residents stratified according to sex, race, region, and age. Other listed contributing causes of death with a histiocytosis diagnosis were also examined.

A total of 2,416 deaths primarily due to histiocytosis as underlying cause occurred between 1979 and 2006. On comparison of the underlying and contributory cause for the period 1999-2006, histiocytosis mentioned on the death certificate as a contributory cause (N=562) occurs nearly as often as does underlying cause alone (N=648). The age-adjusted (year 2000) death rate was highest for MH (2.62 deaths per 10 million, 95% CI: 2.40-2.83) and for LCH and LS disease (2.17, 95% CI: 1.98-2.36) during the period 1979-1988. Death rates of each type of histiocytosis dropped significantly from 1979 to 1988 to 1999-2006 (p-value <0.0001). Distribution of the conditions showed the majority of deaths were due to LCH and LS (67%) across all time periods. LCH/LS was significantly more common in persons younger than 5 years of age irrespective of gender (p-value <0.0001) whereas death rates from MH were significantly greater in ages >54 years (p-value <0.00001). There were more MH deaths among males than females whereas no gender differences were seen for LCH/LS.

Death due to histiocytosis or histiocytosis-related causes is a rare event that is trackable in the US by person, place and time characteristics. However, a population-based, disease incidence registry has begun to accurately ascertain incidence cases, which will facilitate study of these conditions.