Introduction

Allergic diseases may affect up to 25% of the population. They are an increasing cause of illness. Laboratory tests can play a useful part in diagnosing allergy and identifying specific allergens. However, the tests are relatively expensive and have to be interpreted with caution. A good clinical history will focus the laboratory testing or remove the need for inappropriate tests. It is important to consider what useful information will be gained from the results obtained from the laboratory tests. The aim of laboratory allergy testing must be to identify potentially harmful substances which can be avoided.

Those requesting the tests should fill in relevant clinical details on the request form and should indicate the specific types of allergens that are suggested by the clinical details.

This laboratory can measure the total level of IgE in a serum sample and can measure IgE against many different specific allergens ( sometimes called RAST tests). These tests can be against single allergens, mixtures of related allergens (e.g nut mix) or against mixtures of the most common allergens of one type e.g the inhaled allergen (aeroallergen) mix or the common food allergen mix.

Total IgE measurements

A “normal” total IgE level ( <75kU/L) IgE usually suggests that the patient is not allergic, particularly when total IgE is less than 20 kU/L. However, occasionally, an allergic patient may have a normal total IgE level (

Provided they have no other cause for a raised IgE e.g. parasitic infection or hyper IgE syndrome, a very high level of total IgE (>5000kU/L) usually indicates that a patient will have high levels of specific IgEs and detectable clinical allergy against numerous specific allergens – the so called ATOPIC STATE.

In general, the higher the total IgE the more likely the presence of clinical allergy and high levels of specific IgEs to multiple allergens.

IgE to specific allergens

These tests are highly specific (in a laboratory sense). IgE responses to more than 1000 allergens can be measured. The specific IgE results are quantitative. Results are expressed as kUA/L IgE. The tests are calibrated using the same standard used for total IgE and thus, at least in theory, the sum of all specific IgEs should equate to the total IgE.

Tests for IgE against specific allergens are very sensitive with a weak positive response defined >0.35k kUA/L. Great care should be taken in assuming that a low level of IgE against a specific allergen, say 1.0 kUA/L is the cause of a reaction to an allergen suggested by the patient. Clearly in a patient with a total IgE of >5000kU/L, 1.0 kUA/L IgE against any allergen represents a tiny proportion of the total IgE suggesting that IgE responses to other allergens could be more likely causes of clinical symptoms.

An atopic patient with a very high level of total IgE will usually have a high level of IgE antibodies to many different specific allergens. Therefore, there is no point in these cases in doing multiple specific laboratory allergen tests, the specific allergens causing symptoms are likely to be defined more efficiently from a good clinical history.

Total IgE levels and focussed specific IgE testing may help to confirm a clinical diagnosis of atopy or allergy based on the patients history of symptoms and possible specific allergen “triggers”.
Although a high level of IgE to a specific allergen may confirm clinical reactions to the allergens, the presence of IgE antibodies does not necessarily mean that the patient will have symptoms related to that allergen. It is not fully understood why clinical symptoms can correlate poorly with IgE levels to specific allergens
Conversely a negative specific allergen IgE RAST test does not always exclude allergy and a patient may have symptoms when no specific IgE can be detected. If a patient has had an allergic reaction to a specific allergen several years previously and has not been exposed to that allergen since, a negative specific IgE antibody level does not exclude allergy.

Single allergens or mixes?

It is often widely assumed by clinicians that measurement of IgE against specific allergens is an efficient way to identify clinically relevant allergens. However, laboratory experience suggests that even in patients giving a reasonably good history, only between 5 and 50% of specific IgE tests are positive, depending on the allergen. Many laboratory requests for IgE against multiple specific allergens give negative results for all tests requested.

Allergy diagnostic manufacturers have shown from extensive studies that mixtures of common food allergens or common inhaled allergens with give a positive result in 80-90% of individuals with appropriate symptoms. In a detailed audit of over 4000 requests to one large laboratory of samples from patients showing possible symptoms of allergy, 48% were negative for all specific allergens; 39% were positive for inhaled allergens, 11 % for both aero and food allergens and only 2% for food allergens only.

In asthma and perennial rhinitis 90% of well characterised subjects will have a positive reaction to mixed inhaled allergens will have antibodies to one or more of the following allergens: house dust mite, cat, dog or pollens. Those with high levels of total IgE will usually be positive to all or most of these.

Similarly most individuals with food allergy or food related excema will be positive for mixed food allergens (egg, milk, fish, wheat, soy, peanut) and will have antibodies to one or more of the component allergens. Those with high levels of total IgE will usually be positive to all or most of them. In general, patients with specific IgE responses to less common food allergens will also have responses to components of the food allergen mix. In the audit described above only 22 out of 1000 samples which had responses to less common food allergens had no reaction to components of the common food allergen mix – most of the 22 had reactions to tree nuts.
There is often little value in asking for IgE against the individual components of mixes, especially where high levels have been detected. In many cases most or all of the components will be positive so will tests for many allergens that have not been investigated.

Total IgE levels and responses to common (food or aero-) allergen mixes represent a cost effective means of ruling out allergy or indicating the likely success of further analysis of responses to specific allergens. Many “allergy” requests give “negative” results for both aero allergen and food allergen mixes and very low levels of total IgE.

Common sense and food allergy

An allergic individual can respond dramatically to an infinitesimally small amount of allergen. As a result food labelling is compulsory and detailed. Nevertheless, we are seldom aware of what is present in our food. Many real or perceived responses to food are not allergic. Perceived responses are often conditioned by external factors particularly the media.

Nut allergy is potentially one of the more serious food allergies. Allergy can be against peanut (which are not really nuts) or tree nuts or both. Most individuals with IgE recognising one tree nut will also have responses to others. This is partly due to crossreacting antigenic sites. Furthermore, allergens from the same nut from different parts of the world may differ. Given the obvious problems with assuming that nuts will not be contaminated with other types of nut it is highly unadvisable to try to identify a “safe” nut in a nut allergic individual.

Cross reactions

The immune system works at a molecular level whereas most people assume their allergy is against something specific e.g a particular fish, a particular fruit etc. Most allergic reactions are to proteins found in many related species. e.g the commonest allergen in fish is found in all fish. Many plant allergens are found in many parts of the plant and in many related plants. Thus pollen can induce allergy to seeds or whole plants. Plants that we eat are related to wild plants which may look nothing like the food. It is also common for there to be cross-reaction between allergens from apparently unrelated plants. This is because unrelated species can have the same carbohydrates. Thus much nut or fruit allergy is triggered by tree pollens. Latex allergy can also cause allergy to fruits that are related and vice versa.

Summary

Although some allergic reactions can be extremely serious, most are irritating or at worst somewhat debilitating. Deaths from anaphylaxis are rare and usually occur in individuals with already recognised serious disease especially asthma. Most common allergens (e.g foods, pets) can be identified and avoided by the patient. In contrast some are extremely difficult to avoid (house dust mite, pollen). Drugs (e.g anti-histamines) used to treat allergy are not affected by the nature of the allergen. In many cases a detailed investigation of the allergens involved will be of limited use in defining the final outcome for the patient.