The late phase response, as noted, refers to the recrudescence of symptoms after an apparent temporary resolution. Such patients are said to experience biphasic anaphylaxis. Biphasic anaphylaxis is recurrent anaphylaxis occurring 1 to 72 hours after resolution of an initial anaphylactic episode, though an outside limit of 78 hours has also been suggested. Estimates of biphasic anaphylaxis vary from <1% to 20% of patients; These recurrences can occur repeatedly after multiple temporary remissions. Delayed epinephrine administration is also associated with an increased risk of developing a biphasic reaction, i.e., worsening symptoms after a period of improvement.
Biphasic anaphylaxis is associated with;
- a more severe initial presentation of anaphylaxis (odds ratio [OR], 2.11; 95% CI, 1.23-3.61) or
- repeated epinephrine doses (i.e., >1 dose of epinephrine) required with the initial presentation (OR, 4.82; 95% CI, 2.70-8.58)
- wide pulse pressure (OR, 2.11; 95% CI, 1.32-3.37),
- unknown anaphylaxis trigger (OR, 1.63; 95% CI, 1.14-2.33),
- cutaneous signs and symptoms (OR, 2.54; 95% CI, 1.25-5.15), and
- drug trigger in children (OR, 2.35; 95% CI, 1.16-4.76)
Prompt and adequate treatment of anaphylaxis appears central to reducing biphasic anaphylaxis risk. While the possibility of biphasic anaphylaxis should be emphasized in this higher risk group, it is important to educate all patients regarding the chance of a biphasic reaction as well as avoiding known triggers, identification of symptoms of anaphylaxis, the use of auto-injector epinephrine for the treatment of anaphylaxis, and timely follow-up with an allergist.
