Writing about food allergies from a pediatric allergist's perspective

Biphasic Anaphylaxis: What You Should Know

Biphasic anaphylaxis is a type of anaphylaxis that we should all be aware of. AllergyHome proudly presents Dr. Anne K. Ellis.  Dr. Ellis is an Associate Professor in the Department of Medicine at Queen’s University, Chair of the Division of Allergy & Immunology, and Director of the Allergy Research Unit of Kingston General Hospital. She has extensive expertise in biphasic anaphylaxis and we are excited for her to share with us.

Biphasic Anaphylaxis: What You Should Know

Written by Dr. Anne K. Ellis

What is anaphylaxis?

Anaphylaxis is a serious allergic reaction that is rapid in onset and potentially fatal. It is caused by exposure to various allergens, including food (for example peanuts), medications, insect venom, and others. Signs and symptoms of anaphylaxis are variable, with common signs including: difficulty breathing; tightness in the throat; wheezing, nasal congestion, or coughing; nausea, abdominal pain, or vomiting; a faster heartbeat or pulse; and skin itching, tingling, redness, or swelling. The severity of symptoms increases rapidly, and it is critical for those experiencing an anaphylactic episode to be treated promptly with epinephrine (likely first administered by self or bystander via an epinephrine auto-injector) and be taken by emergency medical services to an emergency department for further treatment and observation. It had been recently estimated that anaphylaxis occurs in 1.2% to 15% of the US population, and causes an estimated 1500 deaths a year.

What is biphasic anaphylaxis?

A variant of the usual monophasic (single phase) anaphylaxis, biphasic anaphylaxis is a well recognized presentation of the anaphylaxis syndrome. It consists of a recurrence of symptoms after an asymptomatic window in which patients seem to successfully recover from the first reaction. The second onset of anaphylaxis occurs without subsequent allergen exposure.

How common is biphasic anaphylaxis?

While an accepted complication, traditionally the prevalence and severity of biphasic reactions was underplayed. As time progresses, however, medical professionals and researchers are increasingly describing it in the literature, and we now know that it occurs more frequently than originally recognized. Variability in epidemiological studies has made it difficult to report an exact incidence rate for biphasic anaphylaxis, however the true incidence rate likely lies between 10-20%. As well, though often reported to be equal or more mild in severity than the original anaphylactic episode, several studies have reported life-threatening second phase reactions.

When will we see biphasic anaphylaxis?

Even more importantly, however, is our ability to accurately predict the likelihood of these potentially fatal complications. In this regard, it is clear that, in addition to its occurrence and severity, the length of time to an individual’s second onset of symptoms is also variable. The duration of the asymptomatic window is critical in determining the optimal post-anaphylaxis observation period. While the most common treatment recommendation is to observe patients for four to six hours prior to discharge from the emergency department, many studies have reported recurrent symptoms developing after discharge, with many reported intervals of 10 hours, and some as long as 26, 40, and 72 hours! The inherent variability in these responses has therefore led us to suggest for some cases, extending post-anaphylactic observation times to 24 hours, and as a minimum, guaranteeing immediate access to self-injectable epinephrine and emergency medical services for the following 48-72 hours post-discharge.

Who will have a biphasic reaction?

The ability to screen for those at high risk from suffering an adverse outcome if discharged inappropriately early may help to resolve the aforementioned issue of post-treatment observation. Selecting those only at highest risk for second responses to undergo extended observation would maximize the utility of hospital admission. Though unfortunately a universal predictor of biphasic anaphylaxis has not yet been determined, patterns are emerging. Specifically, management strategies and initial severity of reaction appear to be associated with the occurrence of biphasic responses. Initial presentation requiring more than one dose (or higher does) of epinephrine, those who have more severe or life-threatening initial symptoms, and those who take longer to stabilize are likely at higher risk for a severe second anaphylactic episode. Other risk factors have only been described in isolated cases and are unlikely to be as predictive as those above. Although studies suggest that steroids and antihistamines do not prevent biphasic anaphylaxis, it is standard practice for many providers to “cover” patients with these medications for varied periods of time after an initial reaction. These treatments certainly do help to decrease the discomfort from any ongoing skin symptoms such as itch and hives. Further prospective studies will prove useful in helping to discern a single clinical feature as a predictor for biphasic reactions.

How should we prepare for biphasic anaphylaxis?

When taking care of family members post-anaphylaxis, being aware of the possibility of a second reaction post-discharge from the emergency department is crucial for their safety. Following the resolution of anaphylactic symptoms and discharge, it is important to possess an epinephrine auto-injector and know how to properly use it, as well as to ensure that you or your family member has access to ready and prompt emergency medical services for return to the hospital if necessary. Knowing the signs of anaphylaxis, and being prepared to treat an unexpected biphasic response, can make a critical difference in effectively treating what could be a potentially fatal biphasic complication.


Ellis, A.K. (2010) Biphasic Anaphylaxis: A Review of the Incidence, Characteristics and Predictors. The Open Allergy Journal. 3, 24-28.

Ellis, A.K. Day JH. (2007) Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol. 2007 Jan;98(1):64-9.

Dr. Anne EllisDr. Anne K. Ellis is an Associate Professor in the Department of Medicine with a cross-appointment to the Department of Biomedical and Molecular Sciences at Queen’s University, having joined the Faculty in August 2008. Her position is one of a Clinician Scientist with 70% protected time for research.

She has served as the Chair of the Division of Allergy & Immunology since May 2010, and is the Director of the Allergy Research Unit of Kingston General Hospital; the flagship of this research program being the Environmental Exposure Unit (EEU), an internationally recognized and validated controlled allergen challenge model of allergic rhinitis. She is also the Co-Director of the Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC), a National multi-centre network of allergic rhinitis researchers, which receives federal funding via AllerGen NCE.

She additionally runs a basic science research program centered on the Kingston Allergy Birth Cohort study, a prospective birth cohort that has enrolled over 400 pregnant women to date, in order to study umbilical cord blood biomarkers that could be predictive of future atopic disease in childhood. She has gained particular expertise in the evaluation of epigenetic modifications as they relate to atopic risk and also epigenetic changes that occur as a result of allergic inflammation.



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