Biphasic Reactions: The “Second Wave” of Anaphylaxis
Anaphylaxis is often understood as a single, sudden, severe allergic reaction that resolves once treatment is given.
However, for many people, this assumption can be dangerously misleading. In some cases, symptoms return hours after the initial reaction appears to have resolved — a phenomenon known as biphasic anaphylaxis.
This second phase can occur without any further exposure to the allergen and may be as severe, or even more severe, than the initial reaction.
Understanding this risk is essential for anyone responsible for responding to allergic emergencies.
What Is a Biphasic Reaction?
A biphasic reaction is defined as the recurrence of anaphylactic symptoms after an initial resolution, without re-exposure to the triggering allergen.
The second phase can occur anywhere from 1 to 72 hours after the first reaction, although most occur within the first 8–12 hours.
Clinical studies suggest that biphasic reactions occur in approximately 5–20% of anaphylaxis cases, with variability depending on patient age, trigger, and severity of the initial episode.
A lack of early symptoms isn’t a reliable sign that recurrence won’t happen.
Why Biphasic Reactions Are Clinically Dangerous
The biggest issue with biphasic anaphylaxis is the false reassurance - After treatment with adrenaline, symptoms may appear to resolve completely, leading patients or caregivers to believe the emergency has passed.
Unlike the initial reaction, which often prompts immediate medical attention, the delayed nature of biphasic anaphylaxis means it can occur after a patient has already left medical care, increasing the risk of delayed treatment and poorer outcomes.
However, inflammatory mediators (your body’s internal defence system) may continue to circulate or be released in secondary waves, triggering renewed airway swelling, bronchospasm, or cardiovascular collapse.
Studies have shown that patients experiencing biphasic reactions may require additional doses of adrenaline and, in some cases, advanced airway or circulatory support.
Delayed administration of adrenaline during a second reaction has been associated with increased fatality. This reinforces the need for ongoing observation following anaphylaxis and easy-access for repeat treatment if symptoms recur.
Immediate access to emergency medication is crucial in the event of anaphylaxis - that’s why our Kitts are designed to be a defibrillator’s next-door-neighbour, installed in over 2,000 venues across the UK.
Why One Dose of Adrenaline May Not Be Enough
Clinical guidelines consistently emphasise the importance of access to more than one dose of adrenaline - both because the first dose may misfire or be expired, and because biphasic reactions are unpredictable.
Once a first dose of adrenaline has been given, if symptoms do not fully resolve within 5 minutes of the first dose, or if they return after initial improvement, additional doses are normally advised to be administered (as is on the instructions inside our Anaphylaxis Kitts).
This is why many emergency action plans and allergy organisations recommend that individuals at risk carry two or more adrenaline auto-injectors. The presence of a second dose can be lifesaving, particularly when emergency medical services are delayed or when symptoms re-emerge unexpectedly.
Why Observation and Medical Review Are Essential
Even when symptoms appear to resolve completely, medical evaluation is essential following an anaphylactic episode. You always need to call 999 regardless of whether the patient is getting better or worse after the first dose of adrenaline.
Observation allows healthcare professionals to monitor for recurrence, manage delayed symptoms, and determine whether further treatment or investigation is required.
Clinical guidelines consistently advise against “treat and release” approaches, particularly in moderate to severe cases. The unpredictable nature of biphasic reactions means that patients should be observed for an appropriate period and discharged only when clinically stable and appropriately counselled.
Just like a defibrillator, but for allergies, Kitt Medical provide wall-mounted emergency Kitts, with a subscription supply of emergency adrenaline pens and online CPD-accredited training.
References
Anaphylaxis UK (2023). Anaphylaxis: Signs and Symptoms. Anaphylaxis UK. Available at: https://www.anaphylaxis.org.uk/fact-sheet/anaphylaxis-signs-and-symptoms/. Grunau, B.E., Li, J., Yi, T.W., Stenstrom, R., Grafstein, E., Wiens, M.O. and Scheuermeyer, F.X. (2014) ‘Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis’, Annals of Emergency Medicine, 63(6), pp. 736–744. doi:10.1016/j.annemergmed.2013.10.007.Lee, S. and Hess, E.P. (2018) ‘Biphasic anaphylaxis: A review of the literature’, Current Allergy and Asthma Reports, 18(3), pp. 1–8. doi:10.1007/s11882-018-0769-3.Resuscitation Council UK (2021) Emergency treatment of anaphylactic reactions: Guidelines for healthcare providers. Available at: https://www.resus.org.ukTurner, P.J., Jerschow, E., Umasunthar, T., Lin, R., Campbell, D.E. and Boyle, R.J. (2017) ‘Fatal anaphylaxis: Mortality rate and risk factors’, Journal of Allergy and Clinical Immunology, 139(2), pp. 448–454. doi:10.1016/j.jaci.2016.06.031.