Allergies, IgE and Unexplained Symptoms: Could There Be a Connection?

An in-depth look at allergy mechanisms and modern IgE blood testing

Allergy is often discussed in everyday life, yet many people are unsure what it truly means from a medical perspective. For some, allergy is obvious: rapid swelling after eating peanuts, or wheezing when exposed to cats. For others, the link is subtle and symptoms blend into day-to-day life: blocked nose, intermittent rashes, digestive problems after meals, or coughing fits that appear without a pattern.

It is therefore unsurprising that many patients begin to question whether allergy could be contributing to their symptoms, even when earlier assessments have not provided answers.

This article explores what IgE-mediated allergy is, how it differs from other conditions that can mimic allergy, and why some individuals and clinicians are now considering broader IgE allergy panels, including newer tests such as the ALEX² 295 Allergen IgE panel, when the clinical picture is unclear.

The purpose is not to convince every reader to pursue testing, but to offer a clearer understanding of the science and the situations in which deeper investigation may be appropriate.

What exactly is an allergy?

In clinical terms, allergy refers to a hypersensitivity reaction initiated by the immune system. A specific group of allergic reactions involves a type of antibody called Immunoglobulin E (IgE).

IgE has a very particular role: it binds to receptors on mast cells and basophils (immune cells found in the skin, airways, and gut). When an allergen attaches to IgE, these cells release mediators such as histamine, which can lead to symptoms including:

• Itching or hives

• Runny or blocked nose

• Sneezing or itchy eyes

• Wheezing or shortness of breath

• Nausea, vomiting or abdominal pain

• Swelling of lips, face or throat

This is why some individuals respond to specific allergens within minutes, while others may not have symptoms at all.

IgE allergy is not the same as food intolerance

Due to overlapping symptoms, people often assume that all reactions to food represent “allergy”, when many are actually non-IgE-mediated food intolerances or gastrointestinal conditions.

A simplified comparison is below:

Examples of intolerance include lactose intolerance, FODMAP sensitivity and histamine intolerance. These are not detected by IgE blood tests.

Why are some allergy cases difficult to identify?

Patients often describe symptoms that are suggestive but not definitive. Common challenges include:

• Multiple potential food triggers, making elimination diets difficult

• Year-round nasal symptoms that may be allergy or non-allergic rhinitis

• Eczema flares that may be environmental, dietary or unrelated to allergy

• Asthma that worsens in certain places or seasons

• Digestive symptoms that overlap with IBS or intolerance

• Reactions to fruits and vegetables, sometimes due to pollen cross-reactivity rather than the food itself

In these complex presentations, clinicians may look beyond single-allergen tests and consider broader assessments when appropriate.

Modern IgE testing and the ALEX² 295 Allergen Panel

Traditional allergy testing often focuses on one allergen at a time, based on the patient’s history. This works well when the trigger is obvious, for example, immediate facial swelling after a specific nut.

However, when patterns are unclear, broader panels can be helpful.

What does the ALEX² panel include?

The ALEX² Allergy Explorer evaluates IgE sensitivity to approximately:

• 120 allergen extracts (such as peanut, cat dander, grass pollen)

• 170 molecular allergen components, which provide more refined information such as:

  • whether a nut reaction may relate to storage proteins (often higher risk)

  • or is more consistent with pollen-associated cross-reactivity

Why components matter

For example:

• A person who reacts to hazelnuts may only be sensitised to a birch-related protein, sometimes causing mild oral symptoms.

• Another may react to storage proteins linked with a higher likelihood of systemic reactions.

This level of insight is not available in simpler IgE panels.

When might broader IgE testing be considered?

Each patient requires individual assessment, but circumstances in which clinicians may consider wider allergy screening include:

• Symptoms involving more than one body system (skin, gut, airways)

• Reactions to multiple foods without a clear pattern

• Eczema, asthma or rhinitis suspected of having an allergic component

• Suspected pollen-food syndrome or cross-reactivity

• Symptoms where initial allergy or intolerance tests have been inconclusive

• Patients who have undergone unvalidated IgG food tests and require an evidence-based alternative

Testing should be aligned with clinical history and used to support, not replace, professional evaluation.

What allergy testing cannot do

It is important to be realistic about the role of IgE testing. It does not:

• Diagnose lactose intolerance, FODMAP sensitivity, coeliac disease or IBS

• Predict the exact severity of a reaction

• Stand alone without clinical correlation

• Replace the need for urgent medical care in suspected anaphylaxis

A positive IgE result does not always mean a clinically relevant allergy, and a negative result does not completely exclude one if the history is strongly suggestive.

Potential next steps after testing

Depending on findings and symptoms, outcomes may include:

• Targeted allergen avoidance where appropriate

• Discussion of medication options such as antihistamines or inhalers

• Environmental control strategies for dust mites, pets or mould

• Consideration of specialist referral in higher-risk cases

• Dietetic input when food allergens are identified

• Emergency action planning for those at risk of anaphylaxis

Why patient-led information matters

Many individuals live with symptoms for years, believing there is no explanation. Others eliminate foods unnecessarily, impacting quality of life. Some rely on tests that are not recommended for diagnosing allergy, such as IgG food sensitivity tests.

Understanding when IgE allergy is a possibility can guide more appropriate healthcare decisions and reduce uncertainty.

Further guidance

If you are reading this because you have symptoms and are unsure what to do next, sensible first steps may include:

• Keeping a structured symptom diary

• Reviewing past reactions and possible triggers

• Considering whether symptoms relate to foods, seasons, animals or environments

• Seeking clinical advice if symptoms are recurring or severe

Broader IgE testing is not required for everyone, but it can be a useful tool in selected situations and should ideally be interpreted with clinical support.