What is the case fatality rate of drug-induced anaphylaxis?

Case Fatality Rate of Drug-Induced Anaphylaxis

The case fatality rate of drug-induced anaphylaxis is approximately 0.25% to 0.33% of hospitalizations or emergency department presentations for anaphylaxis, with drug-induced anaphylaxis showing increasing rates compared to other causes of fatal anaphylaxis. 1, 2

Epidemiology of Drug-Induced Anaphylaxis

• Drug-induced anaphylaxis is one of the leading causes of anaphylaxis in adults, with medications being the most common trigger (35%) in the general population 1
• Excluding pediatric populations (where food is the most common trigger), medications are the most frequent cause of fatal anaphylaxis in reports from the United States, United Kingdom, Australia, and New Zealand 1
• The incidence of anaphylaxis due to medication triggers has been increasing over time, in contrast to other causes of fatal anaphylaxis 1, 3
• The mortality rate from drug-induced anaphylaxis ranges from 0.004 to 0.56 deaths per million person-years, which is higher than food-induced anaphylaxis (0.002-0.29) 3

Specific Drugs Associated with Anaphylaxis

• Antibiotics are the most common cause of drug-induced anaphylaxis (49.6%), with amoxicillin being the most frequently implicated 4
• Other common triggers include:
  • Muscle relaxants, latex, and anesthetics (15%) 4
  • Nonsteroidal anti-inflammatory drugs (10.2%) 4
  • Acetaminophen (3.9%) 4
  • Iodinated or magnetic resonance imaging contrast media (4.2%) 4
  • Immunotherapy and vaccines (3.9%) 4

Risk Factors for Fatal Drug-Induced Anaphylaxis

• Older age is a significant risk factor for fatal drug anaphylaxis 5
• Previous cardiovascular morbidity increases risk of fatal outcomes 5
• Beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections are the most common triggers of fatal drug anaphylaxis 5
• In perioperative settings, per case mortality was estimated to be one in 26.6 cases in the UK for all causative drugs 1
• Delayed administration of epinephrine is associated with increased mortality 5

Trends in Drug-Induced Anaphylaxis

• The rate of anaphylaxis-related hospitalizations increased from 21.0 to 25.1 per million population between 1999 and 2009 (annual percentage change, 2.23%) 2
• Despite increasing hospitalizations, the case fatality rate among hospitalizations has been decreasing (annual percentage change, -2.35%) 2
• Overall mortality rates from anaphylaxis have remained relatively stable at 0.63 to 0.76 per million population 2
• Fatal drug anaphylaxis may be increasing, while rates of fatal anaphylaxis to venom and food remain stable 5

Clinical Presentation and Management Considerations

• Anaphylactic shock is the most common presentation (76.6%), followed by severe systemic reactions (10.5%), acute laryngeal edema (9%), and severe bronchospasm (2.1%) 4
• Most cases (81.1%) occur in ambulatory settings, with 18.9% occurring during anesthesia 4
• Hospitalization is required in 94.8% of cases, with 23.7% requiring intensive care unit admission 4
• Epinephrine is used in 57.9% of cases 4

Important Caveats and Considerations

• Most fatal anaphylactic reactions are unpredictable - over four-fifths of those dying from drug anaphylaxis had no previous indication of their allergy 6
• Appropriate management after recovery from a severe reaction may be protective against a fatal recurrence 6
• Accurate identification of the cause and effective avoidance is crucial for preventing future reactions 6
• The diagnosis of drug hypersensitivity is most commonly obtained through skin tests (72.9%), with laboratory tests (2.4%) and oral challenges (3.9%) being less frequently used 4
• Despite the potentially life-threatening nature of anaphylaxis, the actual probability of dying is very low 2