Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations

Abstract

Background: Anaphylaxis-related deaths in the United States have not been well characterized in recent years.

Objectives: We sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010.

Methods: Anaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates.

Results: There were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by "unspecified" (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12 years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 to 2001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (P < .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (P < .001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (P < .001). The rates of fatal anaphylaxis to foods in male African American subjects increased from 0.06 (95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI, 0.11-0.37) per million in 2008 to 2010 (P < .001). The rates of unspecified fatal anaphylaxis decreased over time from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001 to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (P < .001).

Conclusion: There are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths caused by anaphylaxis likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Keywords: Fatal anaphylaxis; death certificate; drug; epidemiology; food; venom.

Figure 1

Fatal drug anaphylaxis features. A. Rates by age groups, all races and genders combined. Drug anaphylaxis was significantly associated with age, P<0.001. B. Rates by race and age groups, both genders. Drug anaphylaxis was significantly associated with African-American race, P<0.001. C. Rates over time by race and gender. Fatal anaphylaxis to drug significantly increased over 12 years among all races and both genders, P<0.001. No significant difference was observed between females and males. D: Culprit medications in fatal drug anaphylaxis with specified medications, N=368. E: Culprit medications in fatal algorithm-identified anaphylaxis with specified medications, N=148. The error bars show 95%CI.

Figure 2

Fatal anaphylaxis by geographic region performed as a subset analysis, 1999-2004. A. Drug anaphylaxis rates were lower in Northeast region, P<0.001. B. Venom anaphylaxis rates were higher in the South region, P<0.001. C. There was no significant association with geographic region for food-induced anaphylaxis. D. West region had lower unspecified anaphylaxis rates, P=0.03. Maps were created using an interactive map tool at http://diymaps.net

Figure 3

Fatal venom anaphylaxis features. A. Rates by age groups, all races and genders combined. Venom anaphylaxis was significantly associated with age, P<0.001. B. Rates by race and age groups, both genders. Venom anaphylaxis was significantly associated with White race, P<0.001. C. Rates over time by race and gender. Venom anaphylaxis was significantly associated with male gender, P<0.001.There was no significant increase overtime in fatal anaphylaxis to venom. The error bars show 95%CI.

Figure 4

Fatal food anaphylaxis features. A. Rates by age groups, all races and genders combined. Fatal food anaphylaxis was significantly associated with age, P=0.02. B. Rates by race and age groups, both genders. Food anaphylaxis was significantly associated with African-American race, P<0.001. C. Rates over time by race and gender. There was significant increase overtime in fatal anaphylaxis to food among African-American males, P<0.001. The error bars show 95%CI.

Figure 5

Unspecified fatal anaphylaxis features. A. Rates by age groups, all races and genders combined. Unspecified fatal anaphylaxis was significantly associated with age, P<0.001. B. Rates by race and age groups, both genders. Unspecified anaphylaxis was significantly associated with African-American race, P<0.001. C. Rates over time by race and gender. There was significant decrease overtime in unspecified fatal anaphylaxis, among all races and both genders, P<0.001. The error bars show 95%CI.