Is Anaphylaxis Possible Even If Your Allergy Test Came Back Negative?

While allergy tests help diagnose allergies, there are still risks of false positives and negatives. A negative food allergy test does not always guarantee immunity to severe allergic reactions like anaphylaxis. In the rare event of a false negative allergy test, particularly a food allergen skin test, the FDA has issued warnings about life-threatening anaphylaxis following allergen exposure.

Understanding Allergy Tests and Their Limitations

Allergy tests, such as skin prick or blood tests, are designed to identify common allergens and their severity. The different types of allergy tests will test for food allergens, insect stings, medications, and latex allergies.

Healthcare providers perform these tests in a controlled setting to see how the body reacts to common allergens. Allergy testing detects the presence of higher-than-normal allergen-specific immunoglobulin E (IgE) antibodies in the blood. The immune system produces Immunoglobulin E (IgE) to fight off allergens, and it plays a significant role in the development of allergic diseases.

Allergy tests can have limitations, including false negatives, delayed reactions, and emerging or delayed allergies.

False Negatives

If an allergy test fails to detect an existing allergy, this is known as a false negative. A false negative allergy test could result from a testing error, the body’s reaction being mediated by non-IgE mechanisms, or the allergen not included in the test panel.

If someone receives a false negative allergy test, they could still be at potential risk of experiencing an allergic reaction, including anaphylaxis. While false negatives are relatively rare regarding allergy tests, they can still occur.

Delayed Allergic Reactions

Allergic reactions, including anaphylactic reactions, might be caused by mechanisms other than IgE antibodies, such as cell-mediated responses. Cell-mediated immune reactions involve regulatory T (Treg) cells, which sustain immune tolerance to allergens and can delay allergic reactions.

Emerging Allergies

Allergies can develop over time due to genetics, environmental factors, and immune system changes. If the immune system has not developed detectable levels of IgE antibodies against specific allergens, an allergy test result might be negative. The American College of Allergy, Asthma, and Immunology (ACAAI) recommends getting allergy tests every two years, as new allergy symptoms and responses may develop.

Can Anaphylaxis Occur Without A Positive Allergy Test?

The simple answer is yes; anaphylaxis can happen even if your allergy results come back negative. False negatives, emerging allergies, and delayed, non-IgE-mediated reactions can all influence anaphylaxis without a positive allergy test. Uncommon allergens and triggers, idiopathic anaphylaxis, and non-allergic anaphylaxis can all trigger an anaphylactic response in individuals with negative allergy tests.

Idiopathic Anaphylaxis

Idiopathic anaphylaxis is a rare disorder that poses life-threatening symptoms similar to that of other forms of anaphylaxis. The cause of idiopathic anaphylaxis remains unknown due to a lack of strong evidence and research.

The triggers of idiopathic anaphylaxis cannot be identified without thorough diagnostic testing, physical examination, and clinical history of the individual. Even with extensive testing, the etiology of idiopathic anaphylaxis remains uncertain.

Non-Allergic Anaphylaxis

Non-allergic anaphylaxis, also referred to as anaphylactoid reactions or non-immunoglobulin E (IgE)-mediated hypersensitivity reaction, does not involve the immune system. Anaphylactoid reactions can be triggered by physical exercise, nonsteroidal anti-inflammatory drugs (NSAIDs), and radiocontrast agents.

Exercise-induced anaphylaxis is typically triggered by physical exercise; however, for some, it only occurs during exercise after exposure to a specific food allergen. This type of anaphylaxis is known as food-dependent, exercise-induced anaphylaxis.

Uncommon Triggers

Allergy test panels, such as blood tests, oral food challenges, and skin prick tests, typically test for the most common allergens. However, standard tests may not include rare or unusual triggers, such as environmental factors, food additives, spices, and chemicals.

Someone with a rare allergy may not know they’re allergic until they experience mild symptoms or life-threatening anaphylaxis. Other uncommon triggers of anaphylaxis may include direct mast cell activation, opioid medications, and environmental factors like heat and cold.

Identifying the Signs and Symptoms of Anaphylaxis

Knowing the symptoms to look for can be life-saving in cases of anaphylaxis, whether you have received a negative or a positive allergy test. Anaphylaxis symptoms can affect several organ systems, including the skin, lungs, gut, and heart.

The most common signs and symptoms of anaphylaxis include:

• Hives or itching
• Difficulty breathing or wheezing
• Swelling of the face, tongue, lips, or throat
• Rapid heartbeat
• Low blood pressure
• Nausea, vomiting, or diarrhea
• Dizziness
• Tightness of the throat
• Airway constriction
• Loss of consciousness

Even if you don’t have allergies or are not at risk of anaphylaxis, it’s critical to be aware of the signs and symptoms in an emergency. If you experience any of these anaphylaxis symptoms or suspect a risk of a false negative test, consult an allergist or immunologist.

Anaphylaxis treatment should not be delayed when symptoms occur. Epinephrine is the first-line treatment for severe allergic reactions like anaphylaxis and should be administered when symptoms appear.

Anaphylaxis Education Resources

Anaphylaxis and allergic reactions can occur even when allergy tests come back negative. Understanding the limitations of allergy tests like skin prick or blood tests and working closely with healthcare professionals can help manage potential reactions. Anaphylaxis is a life-threatening, severe allergic reaction that should not be underestimated, even with a negative allergy test.

If you suspect that you may be at risk of severe allergic reactions like anaphylaxis, always be prepared for emergencies by carrying an epinephrine auto-injector. Consider lifestyle adjustments to prevent anaphylactic reactions by minimizing exposure to potential triggers, including foods, environmental factors, latex, or insect bites.

The KeepSmilin4Abbie Foundation was created in memory of Abbie Benford, who lost her fight to an anaphylactic reaction to a food allergen. The foundation funds research to identify early signs of anaphylaxis to enable early intervention to help save millions of lives at risk of sudden death like Abbie’s.

Consider getting involved by donating, becoming a sponsor, or joining one of our local road race teams. Together, we can fight to #stopanaphylaxis®.

References:

• U.S. Food & Drug Administration, 2023. FDA Requires Warning about Anaphylaxis Following False Negative Food Allergen Skin Test Results in the Prescribing Information for All Allergenic Extracts for Diagnosis of Food Allergy.
• Cleveland Clinic, 2024. Allergy Testing.
• GoodRx, 2024. How Accurate Are Allergy Tests? Plus Some to Avoid at All Costs.
• Frontiers in Immunology, 2019. Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses.
• The Journal of Allergy and Clinical Immunology, 2016. Regulatory T cells in allergic diseases.
• The American College of Allergy, Asthma, & Immunology. Allergy Testing.
• Current Treatment Options in Allergy, 2017. Idiopathic Anaphylaxis.
• The Journal of Allergy and Clinical Immunology, 2021. Non-IgE-mediated anaphylaxis.
• The Journal of Allergy and Clinical Immunology, 1998. Definitions of anaphylaxis and anaphylactoid events.
• Medscape, 2022. Exercise-Induced Anaphylaxis.