Background Anaphylaxis-related deaths in the United States (US) have not been well characterized in recent years. Objectives To define epidemiological features and time trends of fatal anaphylaxis in the US from 1999 to 2010. Methods Anaphylaxis-related deaths were identified by the 10th clinical modification of the International Classification of Diseases (ICD-10) system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated using census population estimates. Results There were a total of 2,458 anaphylaxis deaths in the US from 1999 to 2010. Medications were the most common cause (58.8%), followed by unspecified anaphylaxis (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug anaphylaxis over twelve years: from 0.27 (95%CI: 0.23-0.30) in 1999-2001 to 0.51 (95%CI: 0.47-0.56) per million in 2008-2010, P<0.001. Fatal anaphylaxis due to medications, food, and unspecified allergens was significantly associated with African-American race and older age, P<0.001. Fatal anaphylaxis to venom was significantly associated with White race, older age, and male gender, P<0.001. The rates of fatal anaphylaxis to foods in African-American males increased from 0.06 (95%CI 0.01-0.17) in 1999-2001 to 0.21 (95%CI 0.11-0.37) per million in 2008-2010, P<0.001. The rates of unspecified fatal anaphylaxis decreased overtime from 0.30 (95%CI: 0.26-0.34) in 1999-2001 to 0.09 (95%CI: 0.07-0.11) per million in 2008-2010, P<0.001. Conclusion There are strong and disparate associations between race and specific classes of anaphylaxis mortality in the United States. The increase in medication-related anaphylaxis deaths likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Up to 5% of the US population has suffered anaphylaxis. Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. Fatal drug anaphylaxis may be increasing, but rates of fatal anaphylaxis to venom and food are stable. Risk factors for fatal anaphylaxis vary according to cause. For fatal drug anaphylaxis, previous cardiovascular morbidity and older age are risk factors, with beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections the commonest triggers. Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk. For fatal venom anaphylaxis, risk factors include middle age, male sex, white race, cardiovascular disease, and possibly mastocytosis; insect triggers vary by region. Upright posture is a feature of fatal anaphylaxis to both food and venom. The rarity of fatal anaphylaxis and the significant quality of life impact of allergic conditions suggest that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

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