News
Is it really hay fever?
Wednesday 9th June 2021
Dr John Rees
It's that time of the year again when, for most of the UK, pollen levels are off the scale and many of us reach for the antihistamines and steroid spray hay fever remedies, but for the majority of people allergies cause symptoms all year round. But is it hay fever or perhaps a common cold? Both have similar symptoms but are treated in different ways - so, can a new 10 minute allergy test help tell the difference?
What are allergens?
It sounds obvious but allergens are the things that trigger allergies. Allergens are in the main highly water soluble proteins, usually with molecular weights between 10 to 100kDa. Allergens are found in diverse biological materials from moulds, plants, animals including insects and arachnids. Many allergens are enzymes but the key characteristic of allergens is their ability to stimulate the immune system to generate Immunoglobulin E (IgE) antibodies in those people who are genetically predisposed.
Allergic sensitisation
First, to become allergic, a person needs to be sensitised to a specific allergen. Certain individuals are genetically predisposed (atopic) to sensitisation - this is an inherited trait for the ability to produce IgE. However, not everyone who has the tendency to be atopic will necessarily go on to develop an allergic disorder but this could result in the development of symptoms later on in life.
The risk of whether you become predisposed to allergies is dependent on your parents. If neither parent is allergic then the risk of allergy is around 10 to 20%, if one parent has allergies then the risk to the child is about 50%. However, if both your parents have sensitivities then the risk can be as high as 80%. It is thought that antenatal events and in utero exposure to allergens could impact early on whether a child will develop an allergy.
The allergic reaction
The allergic response consists of a cascade of reactions involving immune cells, antibodies, allergens and inflammatory mediators but the end result is chiefly rhinitis (hay fever symptoms), asthma or eczema.
Allergies occur when a person who has become previously sensitised to an allergen is re-exposed to the same allergen. The sensitised person will already have developed some IgE antibodies. These antibodies occur free in the blood and also bound to IgE receptors fixed on mast cells and basophils. The subsequent cross-linking by an allergen through adjacent specific IgE antibodies fixed via their Fc component to IgE receptors on these mast cells is the trigger for degranulation and release of inflammatory mediators (e.g. histamine) into the surrounding tissues - that's why antihistamines can be an effective treatment for many. These inflammatory mediators are responsible for causing the symptoms of the allergy either by further recruitment of inflammatory cells to the area or by direct action on target tissues e.g. airways in asthma. These inflamed tissues may also become more sensitive to non-specific irritant triggers including air pollution.
Allergies can change through life
Allergies frequently progress in a characteristic way. In babies the major sensitivities are, as expected, to foods such as egg and cows milk - either fed directly to the child e.g. formula feeds, through the presence of the allergens in breast milk, or even earlier sensitisation before birth. Allergies in the baby and small child often develop into eczema. In the same older child the sensitivity pattern changes to that of inhalant allergens from pets, dust mites and pollens and the manifestation of disease also characteristically changes from eczema to asthma and rhinitis. Food allergies affect about 3% of children but only 1% of adults.
Allergy Testing
In all aspects of allergy testing the clinical history of the patient is paramount. If there is no clinical history of a specific sensitivity then a positive test result is unlikely to be of immediate use.
There are three main reasons for allergy testing;
1. To advise on appropriate avoidance measures
2. To identify the trigger(s) so that immunotherapy (immunization against an allergen) can be instigated - this is not so common in the UK but has been shown to be an effective method for controlling allergies. Unfortunately, there is always a risk when you inject allergens into a patient known to be sensitive that the procedure itself may trigger an adverse reaction.
3. The need to know by the patient of what is causing their symptoms
Basically, allergy tests are either conducted in vivo (mostly skin prick tests) or in vitro (blood tests). Alternative practitioners of medicine have an array of incredible wares to "diagnose" allergy including analysing samples of hair or measuring muscle weaknesses (kinesiology) - none of these methods have been proven but anecdotal evidence and the current inadequate provision of NHS allergy services drives an unhealthy demand for alternatives by allergy sufferers desperate for help.
Skin Prick Tests
The skin prick test is simple in principle and involves eliciting an inflammatory response in the skin of the patient by applying a drop of an allergen solution to the forearm or back - then pricking through the skin and allergen drop with a needle. If the patient is sensitive to the specific allergens then 30 minutes later the area of the pin prick will display a small bump surrounded by an area of redness (wheal and flare). If the bump is significantly larger than that elicited by a control solution such as saline, then the result is regarded as positive.
Pitfalls of the skin prick test
Standardisation of allergen extracts has always been difficult due to the complexity of the raw materials. However, even with well defined pharmaceutical preparations further issues exist;
False negative results - Skin prick tests are sensitive to inhibition by anti-allergy drugs such as anti-histamines which can block the allergic response giving false negative results.
False positive results - Extracts of some allergens may contain irritants or chemicals that mimic an allergic response. Other conditions such as severe eczema or dermatographism may also render skin prick testing inappropriate - some people will react to the "pricking procedure" even when saline is used instead of an allergen solution.
The outcome of a skin prick test can also be affected by the;
- storage conditions of the aqueous allergens solutions
- complexity of the allergen extracts (these are often quite crude extracts of plants or animals containing multitudes of proteins, carbohydrates, lipid and nucleic acids)
- relative concentrations of the allergens within the extract will also affect the potency as well as the overall allergen concentration
- person performing the test may not perform the test in exactly the same way as someone else - e.g. differences in needle pressure and/or interpretation of the results
Interpretation of skin prick test results
A completely negative result (no bump) or large wheal (>5mm in diameter) is unlikely to be misinterpreted. However, borderline responses where a wheal is around the "cut-off" size of about 3mm can potentially incorrectly classify the patient as positive or negative.
Other concerns regarding skin prick testing
As allergens are "injected" into the patient during the skin prick procedure this could trigger an anaphylactic response. Although this risk is low, as a precaution basic resuscitation facilities should be available to clinics providing skin prick testing. Skin testing may also be impractical and stressful for small children due to the discomfort caused both by the procedure and the resulting reactions.
Blood tests
The measurement of IgE poses significant problems for the medical test developer;
- the IgE antibody is produced in only minute quantities (µg/L) - even in people with severe allergies compared with g/L quantities of other antibody isotypes such as IgG present in g/L
- we not only need to measure the total level of IgE but also specific IgE sub-populations that have specific reactivity with allergens, so tests need to be even more sensitive.
Even then, most of the reactivity is frequently directed to only a small component of the allergen source, any blood test for detecting specific IgE reactivity has to be both highly sensitive and specific for both human IgE and the allergen component. When detecting very small quantities of IgE with an anti-human IgE antibody the specificity of this antibody is paramount as even a small cross-reactivity with IgG or other antibody isotypes could easily make the test useless.
Despite these difficulties, simple blood tests are available from diagnostic companies allowing us to provide a safe and clinically relevant alternative to skin prick tests.
The Radioallergosorbent test (RAST)
In vitro tests for allergen specific IgE were established in the late 1960's with radioimmunoassay. The test was refined into the RAST® (radioallergosorbent test) procedure to consist of activated paper discs to which were irreversibly bound allergen extracts. A patients serum sample would then be incubated with the allergen disc and any allergen specific antibodies present would bind to the allergens coupled to the disc. Unbound IgE and other serum components could be washed away leaving only the specific antibodies bound to the disc. The quantity of bound IgE was estimated by incubating the disc with radio-labelled (125I) anti-human IgE. The early RAST® procedure took days just to get a result - due to long incubation times and slow gamma counters. Now, the whole process can be completed in less than an hour with non-radioactive immunoassays.
In 1998, a particle based lateral flow assay was developed and patented in the UK which reduced the time for a result from up to 3 days to just 30 minutes using just a couple of drops of blood. This became the world's first self test kit to reliably identify allergies to common allergens such as dust mites, pollens, pet allergies, egg and milk as well as a general allergy self test that measured the total level of allergy antibodies known as a total IgE test. This test was at least a million times more sensitive than current COVID antibody tests, and one version gave three separate results for three different allergen just on the one device. A new lateral flow test can now detect high levels of total IgE in just 10 minutes.
Advantages of blood tests
All that is required is a small blood sample and clinical history to establish the likely allergens contributing to the patients symptoms.
- Results obtained by in vitro blood testing compare well to skin prick testing and is more convenient for both the patient and the clinician
- Multiple tests can be performed on one blood sample and some manufacturers provide rapid point of care tests that provide results in the same time it takes to develop the reaction in skin prick testing
- Blood tests also allow the level of Immunoglobulin E in the blood to be quantified
- No interference with anti-histamine drugs
Total IgE - a general allergy test
Total IgE measurement must be taken in context with the patient's history. The diagnostic value of total IgE measurement is questionable, particularly if the value of the total IgE score is between 20 and 100kU/L. The average level of total IgE in healthy population is around 13kU/L but the distribution is markedly positively skewed towards higher values.
However,
- rarely is specific allergen sensitivity observed when the adult total IgE is lower than 20kU/L
- most patients with a total IgE level greater than 100kU/L are likely to have one or more specific IgE sensitivities eg. to common allergens such as house dust mite (Dermatophagoides pteronyssinus or D. farinae), cat or dog hair/ epithelium, grass pollens and moulds
Sensitivity to foods in adults is rare compared to sensitivity to these inhalant allergens - quite contradictory to popular belief where a large proportion of the general public insist their lives are burdened by food allergies. What is of major concern is that food sensitivity in older children to anaphylactic allergens such as peanuts appears to be increasing in prevalence. There are some non-allergy causes for high levels of IgE including intestinal parasites.
The SELFCheck Allergy Test is a general allergy test that detects high levels of total IgE (>150kU/L). This means that anyone with a positive result is highly likely to have allergy sensitivities and might benefit from further specific allergy tests through their doctor. However, it is still possible for some people with lower levels of IgE to have sensitivities but more likely to just one or a few allergens rather than multiple sensitivities. It is therefore crucial that a total IgE result is considered in the context of symptoms. It is probably pointless for most people to take an allergy test if they do not have symptoms.
Allergen specific IgE tests - specific allergy tests
Blood tests for specific IgE fall into two main categories; those that screen for sensitivity to many allergens simultaneously and single allergen systems. Simple single tests also exist that test for sensitivity to defined mixtures of allergens - often referred to as atopy tests. A positive clinical history together with a high total IgE or a positive atopy test result is likely to make confirmation of specific sensitivities worthwhile.
a) single allergen systems
Single allergen systems offer the greatest flexibility for the clinician and laboratory allowing specific testing for hundreds of single allergens. This is most useful when only a small number of allergens are suspected or where a sensitivity to less common allergens need to be investigated. However, if more than a handful of allergens are implicated from the clinical history then the use of a screening panel of allergens could be more cost effective.
b) allergy screen panels
Allergy screen panels are offered by a number of IVD manufacturers and are most useful for;
a) young children - where only a small blood sample is available and repeated blood sampling is inappropriate for the baby or small child
b) when it is suspected that more than a few allergens are implicated from the clinical history
Allergen panels are most cost effective when tests for more than 4 or 5 allergens are requested on one occasion and reduces the need for further single allergen tests. In many laboratories there will be a need for both single allergen systems for maximum flexibility and allergy screening systems for gaining a comprehensive overview. Most allergy screening systems don't need expensive capital equipment but some IVD manufacturers are now supplying automation for those laboratories requiring higher throughput of patient samples.
Blood tests for allergen specific IgE
The most common format for an allergy test is;
a) An allergosorbent
The allergosorbent is usually supplied with allergens already irreversibly bound to a solid phase support. However, some commercial immunoassays work with the formation of the allergosorbent during the assay procedure through a ligand coated solid phase, ligand labelled liquid allergens and an anti-ligand added during the incubation steps. The solid phase to which the allergens are bound can be for example, an activated paper disc, coated tube, thread, nitrocellulose membrane or an activated sponge material. Whatever the materials used, the aim is to form an allergosorbent where specific allergens are irreversibly bound to a solid support to aid the removal of unbound reactants during the immunoassay.
b) Patient sample
A serum or plasma sample is added to the allergosorbent followed by an incubation during which time specific antibodies if present in the sample will bind to the allergosorbent. This can include large quantities of specific IgG antibodies as well as IgE. Unbound materials are washed away from the solid phase.
c) Detection of the bound specific IgE antibodies
The bound IgE antibodies can then detected in a variety of ways;
1) direct detection eg. Fluorescent labelled anti-human IgE antibodies or through the accumulation of coloured particles, such as colloidal gold, labelled with anti-human IgE such as those used in lateral flow type immunoassays (SELFCheck)
2) indirect detection eg. Enzyme, chemiluminescent assays where a further reagent is required to be added to provide a measurable signal
Some manufacturers use an amplification step prior to adding a substrate/chromogen such as using a biotinylated anti-human IgE followed with a streptavidin conjugate to increase the sensitivity of the assay.
Summary
Allergies are a common trigger of asthma, eczema and rhinitis as well as having the potential to trigger severe, life threatening systemic reactions (anaphylactic shock) in patients susceptible to certain foods, insect stings, antibiotics and anaesthetics.
An accurate diagnosis of the allergy causes derived from a clear clinical history and backed up with confirmation from laboratory tests will save clinical resources, improve quality of life and in some circumstances can be critical.
If you have allergy symptoms speak with your pharmacist who can provide you with a range of anti-allergy medications including steroid sprays and antihistamines without the need for a prescription. Of course, if you are concerned about your symptoms always speak with your doctor.
The SELFCheck Allergy Test kit is a simple and reliable, 10 minute allergy blood spot test to find out if your total IgE level is high or in the normal range, for further information please click here