Biphasic Anaphylaxis: The Sneaky Second Wave of Allergic Reactions
Biphasic anaphylaxis is a secondary wave of anaphylaxis symptoms that occurs hours after the initial reaction resolves without further allergen exposure. While biphasic reactions have relatively mild symptoms, they can be as severe as the first anaphylactic reaction. The exact cause of biphasic anaphylactic reactions remains unclear, but it is believed to involve a delayed response to an allergen or inadequate epinephrine administration.
What Is Biphasic Anaphylaxis?
Biphasic anaphylaxis, or protracted anaphylaxis, is a secondary phase of anaphylactic symptoms. This second wave emerges without further exposure to an allergen, complicating prevention and treatment strategies. Anaphylaxis is a severe, immediate, life-threatening reaction to an allergen, with symptoms ranging from skin rash and hives to difficulty breathing and hypotension.
After the initial anaphylactic response resolves and symptoms subside, biphasic anaphylaxis can occur anywhere from 1 to 72 hours from the first reaction. The exact mechanism behind biphasic anaphylaxis is not fully understood, but studies show that it often involves a delayed release of inflammatory mediators.
Symptoms of Biphasic Anaphylactic Reactions
The signs and symptoms of biphasic anaphylaxis are similar to those of the first wave of anaphylaxis, including:
- Hives or rash
- Swelling of the throat, tongue, or lips
- Difficulty breathing
- Dizziness or fainting
- Nausea, vomiting, or diarrhea
- Stomach pain
- Low blood pressure (hypotension)
The severity of biphasic allergic reactions can range anywhere from mild to life-threatening, making it unpredictable and potentially dangerous.
Treatment for Biphasic Anaphylaxis
Treating biphasic anaphylactic reactions is similar to primary anaphylaxis treatment. These options include:
- Epinephrine (adrenaline)
- Antihistamines
- Corticosteroids
- Oxygen therapy
Epinephrine, also known as adrenaline, is the first-line treatment for severe allergic reactions, such as anaphylaxis and biphasic anaphylaxis. Antihistamines can relieve some symptoms of anaphylaxis, such as hives and itching, but they should not be used in place of epinephrine.
Corticosteroids have been discussed as a way to reduce the second wave of anaphylaxis, but only one study reported a beneficial effect. In severe cases involving respiratory distress from anaphylaxis, oxygen therapy alongside adrenaline (epinephrine) is recommended.
What Causes Biphasic Anaphylaxis?
The exact cause of biphasic anaphylaxis is not definitive but is suspected to involve a delayed immune response to an allergen. Unlike the initial wave of anaphylaxis, which is an immediate hypersensitivity reaction, the secondary phase is thought to proceed from complex immunological mechanisms.
While there are unique factors that can influence one’s risk of biphasic anaphylaxis, anyone who experiences anaphylaxis is at risk. Individuals who have severe allergies, require multiple doses of epinephrine, or experience a delay in treatment are highly susceptible.
Severity of the Initial Reaction
Severe anaphylactic reactions are more likely to be associated with biphasic anaphylactic responses. When the initial reaction to an allergen produces intense symptoms, such as airway constriction or fainting, the immune system may be primed for a second surge. Those who experience mild anaphylaxis will likely experience mild biphasic responses, whereas those who have severe anaphylactic episodes will have severe biphasic reactions.
Individuals who experience severe anaphylaxis symptoms, particularly multiorgan involvement, are more susceptible to experiencing biphasic reactions. Severe gastrointestinal, skin, respiratory, and cardiac anaphylaxis symptoms amplify the risk of a second wave of anaphylaxis.
Delayed Release of Inflammatory Mediators
When exposed to an allergen, immune cells such as basophils and mast cells release inflammatory mediators. These histamines, leukotrienes, and prostaglandins may be released in two waves during an allergic reaction. The initial release of inflammatory mediators triggers primary anaphylaxis, and a second release may occur hours later from residual allergens in the body or lingering immune activation.
Tree Nut and Peanut Allergies
Peanut and tree nut allergies are the most common food allergens that have triggered biphasic anaphylaxis. Due to residual allergens in the body, people who experience anaphylactic symptoms after exposure to a peanut or tree nut may experience a biphasic response hours later.
Inadequate or Delayed Treatment of Epinephrine
Suboptimal or delayed treatment of anaphylaxis in the first wave increases the likelihood of a biphasic response. Studies show that individuals who did not receive epinephrine administration or received it late were more likely to experience biphasic reactions. Insufficient antihistamines or corticosteroids might fail to entirely suppress the inflammatory process, potentially causing a second wave of anaphylaxis.
Individual Risk Factors
Some individuals with allergies are predisposed to biphasic anaphylaxis due to asthma, heart disease, genetics, and age. Uncontrolled asthma can amplify the severity and recurrence of allergic reactions and anaphylaxis, and underlying health conditions such as heart disease can cause them.
Variations in immune system genes may influence the likelihood of biphasic responses. People with a history of multiple or severe allergies and previous anaphylactic episodes are more likely to experience protracted anaphylaxis.
Biphasic Anaphylaxis Awareness and Prevention
While it is impossible to prevent biphasic anaphylaxis completely, taking proactive steps can help you stay prepared and safe. Timely medical intervention, prolonged observation, epinephrine administration, and proactive management are essential for mitigating the risks of biphasic reactions.
If you or a loved one is at risk of anaphylaxis or has severe food allergies, understanding the potential for a sneaky second wave can be lifesaving.
The KeepSmilin4Abbie Foundation was created in remembrance of Abbie Benford, who was almost sixteen years old when she died from anaphylaxis. Our mission is to fund research into the early detection of anaphylaxis to save millions from life-threatening allergic reactions.
Visit our website to see how you can participate in the fight to #stopanaphylaxis®.
References:
- Annals of Allergy, Asthma, & Immunology, 2005. Biphasic anaphylactic reactions.
- Acute Medicine and Surgery, 2021. Incidence and timing of biphasic anaphylactic reactions: a retrospective cohort study.
- Healthline, 2020. Everything You Should Know About Biphasic Anaphylaxis.
- Harvard Health Publishing, 2020. Epinephrine is the only effective treatment for anaphylaxis.
- American Academy of Allergy Asthma & Immunology, 2018. Corticosteroids for treatment of anaphylaxis.
- Allergo Journal International, 2014. Guideline for acute therapy and management of anaphylaxis.
- The Journal of Allergy and Clinical Immunology, 2020. Risk Factors and Characteristics of Biphasic Anaphylaxis.
- Food Allergy Research & Education, 2021. Biphasic Reactions Are More Likely When Symptoms of Initial Reaction Are Severe.
- Acute Medicine and Surgery, 2021. Association between biphasic reactions and the systems of symptoms and treatment in patients with anaphylaxis hospitalized from the emergency department.
