What is a biphasic reaction in allergic responses?

From the Guidelines

The biphasic reaction in allergies is a potentially life-threatening condition where allergic symptoms recur after initially improving, typically within 1-72 hours after the first reaction, without additional exposure to the allergen. This phenomenon is characterized by an initial allergic reaction that seems to resolve with treatment, only to have symptoms return hours later, often more severely than the first episode 1. Biphasic reactions occur in approximately 5-20% of anaphylactic reactions, with the second phase potentially being more dangerous than the first because patients may no longer be under medical supervision.

Key Characteristics and Risk Factors

• Common symptoms during both phases include hives, swelling, breathing difficulties, drop in blood pressure, and gastrointestinal distress.
• The mechanism involves delayed mast cell and basophil activation, with continued release of inflammatory mediators like histamine, leukotrienes, and cytokines after the initial reaction appears to subside.
• Risk factors include severe initial reactions, delayed administration of epinephrine, and insufficient doses of medications, as well as wide pulse pressure, unknown anaphylaxis trigger, cutaneous signs and symptoms, and drug trigger in children 1.

Management and Prevention

• Administering epinephrine as the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis is crucial, and its administration should not be delayed, as doing so may be associated with higher morbidity and mortality 1.
• Patients with significant allergic reactions should be observed for 4-24 hours depending on reaction severity, and always carry emergency medications including epinephrine auto-injectors (like EpiPen or Auvi-Q) even after symptoms appear to resolve.
• Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis but may be considered as secondary treatment, and their use should be guided by the severity of the reaction and the patient's overall condition 1.

From the Research

Definition and Incidence of Biphasic Reactions

• A biphasic reaction is a type of allergic reaction that occurs in two phases, with an initial reaction followed by a second reaction that can occur hours or even days later 2, 3, 4, 5.
• The incidence of biphasic anaphylactic reactions is highly variable, ranging from 1% to 20% of episodes 2.
• Biphasic reactions can be less severe, equally severe, or more severe than the initial reaction, ranging in degree from mild symptoms to fatal reactions 3.

Risk Factors for Biphasic Reactions

• The severity of the reaction, the time of onset after administration of antigen before the occurrence of symptoms of the primary response, the presence of hypotension or laryngeal edema during the primary response, and the history of a previous biphasic reaction have all been mentioned as risk factors in various studies 2.
• A delay in the administration of epinephrine and too small a dose of epinephrine given for the primary response have also been mentioned as risk factors 2, 5.
• Patients who require higher doses of adrenaline to control their initial symptoms may be at higher risk of developing a biphasic response 4.

Observation and Management of Biphasic Reactions

• The traditional recommended observation time is 4-6 hours after complete resolution of symptoms for every anaphylaxis patient, but some studies suggest that a longer observation period of 8 hours or even 24 hours may be necessary 2, 5.
• Corticosteroids may decrease the incidence of biphasic reactions, but no definitive conclusions can be made at this time 5.
• Patients who receive epinephrine within one hour of symptom onset and who respond to epinephrine with rapid and complete symptom resolution can probably be discharged from the ED with careful return precautions and education without the need for prolonged observation 5.