What is a biphasic reaction in the context of anaphylaxis?

Biphasic Reaction in Anaphylaxis

A biphasic reaction is a recurrence of anaphylaxis symptoms after complete resolution of the initial reaction, without re-exposure to the triggering allergen, typically occurring within 8 hours but potentially up to 72 hours after the initial reaction. 1

Definition and Characteristics

Anaphylaxis can follow three distinct time courses:

• Uniphasic reaction: Occurs immediately after exposure and resolves within minutes to hours without recurrence
• Biphasic reaction: Initial symptoms resolve completely but then recur without additional allergen exposure
• Protracted reaction: Continuous anaphylaxis that lasts for hours or days 1

Key features of biphasic reactions:

• Occurs in approximately 1-20% of anaphylactic episodes 1
• Median time to onset is approximately 11 hours after initial symptom resolution 2
• Can range from 1-78 hours after initial reaction resolution 1
• May be less severe, equally severe, or more severe than the initial reaction 3
• Requires the same treatment approach as the initial reaction 1

Risk Factors for Biphasic Reactions

Several factors increase the risk of developing a biphasic reaction:

• Severe initial anaphylaxis, particularly with hypotension (OR 2.18,95% CI: 1.14-4.15) 1, 2
• Unknown trigger for the initial reaction (OR 1.72,95% CI: 1.0-2.95) 2
• Delayed administration of epinephrine (60-190 minutes after symptom onset) 4, 5
• Requiring multiple doses of epinephrine to resolve initial symptoms (OR 4.82,95% CI: 2.70-8.58) 1, 4
• History of drug anaphylaxis (OR 14.3,95% CI: 2.4-85.8) 6

Interestingly, food-triggered anaphylaxis is associated with a decreased risk of biphasic reactions (OR 0.62,95% CI: 0.4-0.94) 2.

Clinical Implications

Observation Period

The optimal observation period after anaphylaxis remains debated:

• For patients with resolved non-severe anaphylaxis who had prompt response to epinephrine and have reliable access to medical care, a 1-hour observation may be reasonable 1
• For patients with severe initial anaphylaxis or requiring multiple doses of epinephrine, extended observation (4-6 hours) is appropriate 1
• The negative predictive value for biphasic anaphylaxis after ≥6 hours of observation is 97.3% 1

Treatment

• Treatment for biphasic reactions is identical to initial anaphylaxis management 1
• Prompt administration of epinephrine is critical for both initial and biphasic reactions 1, 5
• The role of corticosteroids in preventing biphasic reactions remains unclear, with limited evidence suggesting possible benefit 6, 4

Important Clinical Considerations

• Biphasic reactions can be difficult to distinguish from reactions that never fully resolved or from new exposures to the allergen
• Neurological symptoms like facial tingling and blurry vision may occur in anaphylaxis, and 10-20% of anaphylaxis cases may have no cutaneous manifestations 7
• All patients with anaphylaxis should be prescribed an epinephrine auto-injector and educated about the possibility of biphasic reactions before discharge 1
• Referral to an allergist is recommended after anaphylaxis to identify triggers and develop a management plan 1

Pitfalls to Avoid

• Premature discharge: Patients with severe initial reactions or delayed epinephrine administration should be observed longer due to increased biphasic reaction risk
• Failure to educate: All patients must understand the possibility of symptom recurrence and when to use epinephrine
• Misdiagnosis: Biphasic reactions can be misinterpreted as a new allergic reaction or anxiety
• Delayed treatment: Prompt epinephrine administration for the initial reaction may reduce biphasic reaction risk 5