Drug Reactions Largest Factor in Fatal Anaphylaxis

Ricki Lewis, PhD

October 03, 2014

Medications are the leading cause of anaphylaxis-related deaths, especially among older individuals and blacks, according to a study published online September 30 in the Journal of Allergy and Clinical Immunology.

The United States does not maintain a national registry to track fatal anaphylaxis. To understand the temporal patterns and demographic associations of such fatalities, Elina Jerschow, MD, from the Department of Medicine, Allergy/Immunology Division, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, and colleagues analyzed death certificates from the US National Mortality Database covering 1999 to 2010, using International Classification of Diseases, 10th Revision, coding (which began in 1999).

The investigation revealed that fatal drug-induced anaphylaxis rose from 0.27 (95% confidence interval [CI], 0.23 - 0.30; P < .001) per million from 1999 through 2001 to 0.51 (95% CI, 0.47 - 0.56; P < .001) per million from 2008 through 2010. Most deaths (58.5%) were in inpatient facilities.

The most common cause of anaphylaxis death was drugs (58.8%, or 1446 deaths out of 2458), with no significant difference between the sexes. The researchers hypothesize that this trend may reflect increased drug use, improved diagnosis, and coding changes. Nearly three quarters of cases did not specify the medications.

Of deaths from identified drugs, 149 were antibiotics (most commonly penicillins, followed by cephalosporins, and then sulfa drugs and macrolides), followed by 100 deaths from radiocontrast agents used in diagnostic imaging, and then 46 deaths from cancer chemotherapy. The remaining medications were serum, opiates, antihypertensives, nonsteroidal anti-inflammatory drugs, and anesthetics.

After drugs, the next most common causes were unspecified allergens (19.3%), venom (15.2%), and food (6.7%). The only factor to show a geographic association was venom in the southern United States as a result of greater exposure to venomous insects.

Blacks and older individuals faced higher risk for anaphylaxis caused by drugs, food, and unspecified allergens, whereas older white men were more likely to die from anaphylaxis from venom than blacks.

Rates of fatal anaphylaxis from foods among black males rose 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 investigators hypothesize that contributing factors include more comorbidities, greater medication use, and less access to healthcare among blacks.

Limitations of the study include underreporting and misreporting of anaphylaxis on death certificates, coding confusion for venom and food-related events, and no information on attempts to halt anaphylaxis.

The researchers call for a national registry for fatal anaphylaxis, similar to the one for food allergies. They conclude that "[u]nderstanding the patterns of fatal anaphylaxis might help in identifying specific risk factors and formulating preventative approaches," emphasizing the importance of identifying antibiotic allergies.

This publication was supported by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. The authors have disclosed no relevant financial relationships.

J Allergy Clin Immunol. Published online September 30, 2014. Abstract

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