I have written about anaphylaxis before (in the form of a video) and also shared a Why We Do What We Do on Epinephrine. Perhaps appropriately so, here is a “delayed” post on biphasic reactions, which the actual occurrence of, or the potential for lead to further ED observation and admissions for children with anaphylaxis.

Generally, a biphasic reaction means that there has been an asymptomatic period of ≥1 hour with a subsequent resumption of symptoms without further antigen exposure. Though it is hard to precisely estimate the incidence Stark followed a group of 25 patients prospectively and Ellis followed 103, both noting rates of about 20%. A larger retrospective review from Alqurashi noted a rate of 14.7%. These were ED based. However, children receiving oral food challenges according to Järvinen in J Allergy Clin Immunol and Lee in Allergy Asthma Proc saw rates much lower (1.5-2%). So the bottom line is that we don’t really know.

In general the second phase is usually less severe than the first. Urticaria is more common, and is many times the only symptom per Ellis. As is the case with many understudied phenomena there are case reports of fatalities as well. Recurrent symptoms generally appear in the first 4-6 hours, but can occur out to 72 hours. However, most will be within 24-30 hours.

With regard to specific risk factors for biphasic reactions in children I wanted to highlight one study that reviewed nearly 500 patients with anaphylaxis  the aforementioned retrospective review from Alqurashi. Overall in their database from two Canadian Pediatric Emergency Departments 71/484 (14.7%) visits developed biphasic reactions. It is interesting that 49/71 (69%) had respiratory and/or cardiovascular manifestations (different than Ellis) and 35/71 (49%) got epinephrine. Alqurashi also identified five independent predictors for biphasic reactions, and if you take anything home from this post I want this to be it:

  • Age 6 to 9 years – OR 3.60 (95% CI 1.5-8.58)
  • Delay in presentation to the ED >90 min after the onset of the initial reaction – OR 2.58 (95% CI 1.47-4.53)
  • Wide pulse pressure at triage – OR 2.92 (95% CI 1.69-5.04)
  • Treatment of the initial reaction with >1 dose of epi – OR 2.7 (95% CI 1.12-6.55)
  • Treated with inhaled β-agonists in the ED – OR 2.39 (95% CI 1.24-4.62)

What should you do with this info? Well, asymptomatic children at 4 to 6 hours can be discharged home. Any child that has developed biphasic reaction or is still symptomatic should not go home. I would strongly consider admitted/observing children with the above five predictors as well.


Alqurashi W, Stiell I, Chan K, Neto G, Alsadoon A, Wells G. Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis. Ann Allergy Asthma Immunol. 2015 Sep;115(3):217-223

Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol 2007; 98:64.

Järvinen KM, Amalanayagam S, Shreffler WG, et al. Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children. J Allergy Clin Immunol 2009; 124:1267.

Lee J, Garrett JP, Brown-Whitehorn T, Spergel JM. Biphasic reactions in children undergoing oral food challenges. Allergy Asthma Proc 2013; 34:220.

Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J Allergy Clin Immunol 1986; 78:76.