[ Main ] [ Allergy ]  


Allergy Diagnostic Tests


Total IgE Assay Phadiatop
Specific IgE Paediatric Food Mix Range of Specific IgE Tests
Costs  

When a patient has a heath problem, of any description, whether of an allergy or of some other medical problem, he will then visit his doctor. The doctor will make an investigation of the patient and included in that investigation will be many questions to the patient about the signs and symptoms, occurrence and frequency of his condition.

  

This thorough clinical history is the cornerstone of a confident and reliable diagnosis, whether it be allergy or some other disease process. This clinical history and presentation of symptoms may indicate to the doctor that allergy may be involved. This indication may be very clear-cut or it may be very vague. This is where the detective-work gets really serious !!









Reviews, Recommendations & Endorsements
The information contained in this article has been developed for reading by an educated and informed member of the public, or by medical health care professionals involved in the management of allergic patients. Although intended primarily for South African readers, almost all of the information contained here is applicable in the rest of the world.
  

This text has been conceived and developed by Laboratory Specialities, and has been reviewed by a number of leading expert allergy specialists and opinion leaders in both clinical allergy and laboratory diagnostics. It therefore is fully in accordance with current mainstream medical thinking and opinion on the diagnosis of allergy and the use of the various in vitro allergy diagnostic assays.

  

The use of in vitro diagnostic tests and assays in the diagnosis of allergy and the identification of the causative allergens is endorsed by the Allergy Society of South Africa. All these tests described here are used and recommended by individual opinion leaders, experts and specialists in the field of allergy in South Africa.

  






Initial steps in the Diagnostic Workup
The initial step in the diagnosis of allergy is the differentiation of allergy from other conditions that may mimic the symptoms of allergy. In classical cases it may be relatively easy for the clinician and even the patient to state that the symptoms of asthma, or rhinitis, or conjunctivitis, or dermatitis, or oro-gastro-intestinal conditions, etc., are caused by an allergy to some naturally occurring allergen or some other substance.
  

Usually, however, the association between symptoms and allergy and allergen is less clear-cut and may require some serious detective-work by the clinician and the patient. There are many other clinical conditions that may give the same apparent symptoms as allergy, but in fact the aetiology (the cause) is quite different and the treatment and prognosis (likely outcome) may be also quite different. It is therefore important to reliably establish that a patients symptoms are indeed due to an allergy. The initial step in the diagnostic work-up is therefore to differentiate allergy from other conditions that may mimic the symptoms of allergy; e.g. in middle ear infections, in various respiratory disorders, in various gastro-intestinal problems, in rhinitis, etc.

  

A thorough clinical history remains the cornerstone of a confident and reliable allergy diagnosis. Diagnostic tests are to be used as an adjunct to the history.









Total IgE Assay
Top
After the development of the assay for the measurement of Total IgE, it has been widely used as an indicator of allergy. There are however several clinical limitations and disadvantages to the measurement of Total IgE, that severely restricts its application and value, especially in the South African medical environment.


The normal range, or reference range of Total IgE is dependent on and therefore varies with the age of the patient.
The internationally accepted reference range that has been established over the years is applicable only to the Caucasian population. Practical working experience in South Africa and other countries has shown that this reference range cannot be applied to either Coloured, Indian or Black patients, whose reference ranges are more-or-less higher and more-or-less wider.
The high incidence of parasites in certain sections of the South African population, particularly Ascaris, limits the application of the Total IgE assay as a test for allergy.
The extent of the symptoms and the type of symptoms also affects the level of IgE, with those conditions such as widespread dermatitis commonly causing a greater elevation of Total IgE values than a conjunctivitis or rhinitis.
  

In summary, these factors have all made the use of Total IgE a rather poor screening test or indicator of allergy. Figures of 60% sensitivity (i.e. of 100 patients who are allergic, only 60 will have a raised value of Total IgE) and 60% specificity (i.e. of 100 patients who have a raised value of Total IgE, only 60 are actually allergic) are widely acknowledged, and that really is not good enough to provide a reliable diagnosis of "Allergic" or "not Allergic".

  

There are however a number of clear clinical indications for the assay of Total IgE where it will usually provide valuable diagnostic information:

To predict the development of atopy in new-borns, where a value above 0.7 kU/l IgE indicates a pre-disposition to develop atopy.
For paediatric patients up to approximately 3 years of age (Caucasian only), where the reference range is more narrow and more accurate.
To provide a very approximate indication of "allergen load" , where the higher the value, the greater the range of allergens and degree of sensitivity of the patient.
In cases of contradictory results from clinical history and other tests, such as a positive history or positive Phadiatop result but negative SPT (skin prick tests) or Specific IgE tests, and more information is desirable.
In cases of equivocal results from other tests such as only weakly positive SPT results or Specific IgE test results, and more information is desirable.
  

In line with international clinical trends and developments, the investigation of cases of allergy in South Africa is moving away from the use of this classical "thermometer" of the Total IgE level to indicate whether a patient is allergic or not, to the use of two different screening tests:


Phadiatop assay, for the identification of patients allergic to INHALANT allergens;
Specific IgE Paediatric Food Mix fx5, for the identification of patients allergic to INGESTANT allergens (i.e. foods).
  

These two separate tests can be used singly, where the symptoms are clear-cut and the suspicion is clearly either an inhalant allergy or a food allergy, or they can be used together if the symptoms and the association to allergy and to particular allergens is vague.









Phadiatop
Top
The Phadiatop assay has been increasingly used for several years as an indicator of allergy to various common inhalant allergens. The name Phadiatop is derived from Pharmacia differential atopy test. Phadiatop is a further development of the classical Pharmacia ImmunoCAP® System Specific IgE test, but instead of testing for a single allergen, such as house dust mite, or Bermuda grass, etc., Phadiatop tests for the presence in the serum sample of allergen-specific IgE to a wide range of common inhalant allergens.

The most important inhalant allergens are all included in the range of this test; including the House Dust Mite, Cat, Dog, Horse, cockroach, various grass pollens, weed pollens and tree pollens and mould spores. The Phadiatop assay gives a "Yes" or "No" result with few borderline or equivocal results. Phadiatop results are not affected by age, by race, by parasites, by medication, or by symptoms.

  

The sensitivity of the Phadiatop test is >96%. (i.e. 19 out of 20 patients with an allergy to one or more inhalant allergens will give a positive result with Phadiatop). Similarly the specificity is approximately 94% (i.e. 19 out of 20 patients with a positive Phadiatop result will indeed have allergen specific IgE to one or more inhalant allergens). The use of Phadiatop to identify the inhalant allergic is therefore at least 95% reliable, which is a major improvement over the approximately 60% reliability of the Total IgE assay.

A negative Phadiatop result practically excludes common inhalant allergens and obviates the need for any further testing for them. Instead either other allergens (not common inhalants) or even a non-allergic aetiology, should be considered.


  

A positive Phadiatop result will, when followed up by the laboratory with a small panel of Specific IgE tests on the same serum sample for the locally relevant individual inhalant allergens, almost always lead to the identification of the individual causative allergen(s). These follow-up Specific IgE tests can be either for an Inhalant Allergen Mix of closely related allergens such as several different mould spores, or for single allergens, such as Bermuda grass. There are over 30 different Specific IgE Inhalant Mixes that can be used as screening tests for groups of related allergens, including Grass pollens, Weed pollens, Tree pollens, Moulds, feathers, and Animal Epithelia. Five of these Inhalant Mixes are highly relevant to the South African medical environment:


Specific IgE Grass Mix gx2, with relevant grasses from South Africa,
Specific IgE Weed Mix wx7, with relevant weeds from South Africa,
Specific IgE Tree Mix tx4, with relevant European (Temperate) trees found in South Africa,
Specific IgE Tree Mix tx7, with relevant semi-tropical trees found in South Africa,
Specific IgE Mould Mix mx1, with relevant moulds from South Africa.
  

Specific IgE Tests for individual inhalant allergens are available for a very wide range of over 100 individual inhalant allergens, both naturally occurring pollens and spores of all types and species, as well as numerous epidermal allergens, and various occupational allergens such as industrial chemicals, etc.









Specific IgE Paediatric Food Mix fx5
Top
The Specific IgE Paediatric Food Mix is a screening test to identify the patient allergic to a limited range of foods. It therefore is similar to the Phadiatop assay in concept, the major difference being that Phadiatop is used as a screening test for inhalant allergens, instead of food allergens.

Particularly in connection with foods, it is important to use the correct terminology. An "allergy" is defined as an adverse reaction by a person to a particular food that involves the IgE mechanism. All other adverse reactions to a food are called a "hypersensitivity", and can involve any of the other, (non-IgE mediated), mechanisms, as described below.

  

IgE-mediated allergy is only one of several types of adverse reactions to foods. In fact an allergy to a food represents approximately only half the cases of an adverse reaction to a food, the other 50% of cases have some other non-allergic mechanism. These can be any of the following:


a chemical sensitivity (e.g. to a food additive such as sulphur dioxide);
the food itself may contain histamine (e.g. as found in tuna fish, cheese, red wine);
the food may directly cause the release of histamine in the patient's blood (e.g. strawberries);
the food may contain a toxin, (e.g. a mushroom);
some other known mechanism is involved;
some other unknown mechanism may be involved.
  

To identify the other types of adverse reactions to foods, challenge testing will be necessary, and this can be very complex and time-consuming and laborious for both the patient and the doctor, and may still be fruitless !!. Because the challenge test is so laborious it is rarely done in clinical routine, and so the normal procedure is for the doctor to first of all investigate the possibility of the clinical problem being caused by an IgE mechanism, and thereby requesting the Specific IgE tests.

It can therefore be expected that of all the patients showing a suspected adverse reaction to a food, only half will have a positive Specific IgE result, even if the doctor has chosen the right allergens to test for. The other half of patients will have some other non-IgE mechanism causing their adverse reaction, and of course the Specific IgE tests will be negative. There are a number of other diagnostic tests that are under investigation in both South Africa and around the world that claim to be of use in the diagnosis of non-IgE mediated food hypersensitivity. However they are not officially approved and so cannot yet be recommended for routine clinical use.

  

Avoidance of the causative allergen(s) is the optimal therapy for food allergy, and so it is essential to accurately and reliably identify the individual causative food allergens.

Specific IgE Paediatric Food Mix fx5 covers in one single test the great majority of cases of food allergy in paediatric patients, up to the age of approximately 3 years. This Multi-Allergen screening test covers six of the most important allergenic foods in a baby or infant diet:


egg white;
cow's milk;
fish;
peanut;
soya;
wheat.
  

Cross-reactivity also means that other closely related foods are also covered to a greater or lesser extent. For older children and adults, as the diet is expanded to include a wider range of foods, then other potential allergens are encountered, and these should also be considered by the doctor in the diagnostic work-up of the individual patient.

A negative ImmunoCAP® Specific IgE fx5 result in a paediatric patient reliably (>90%) excludes the common ingestant allergens (i.e. 9 out of 10 patients with a negative result with this test will indeed not be allergic to any of the 6 foods). In this event either other potential food allergens, or some other aetiologic mechanism (not involving IgE) should be considered. In an adult patient, a wide range of other potential food allergens should be considered for investigation.

  

A positive Specific IgE Paediatric Food Mix fx5 result reliably (>90%) demonstrates that the patient has allergen-specific IgE to one or more of the 6 foods covered by the test (i.e. 9 out of 10 patients with an allergy to one or more of these 6 allergens will give a positive result with this test). A positive result should of course be followed up with further tests by the laboratory, using the same serum sample, in order to reliably and accurately identify the offending food allergen(s). Several other Specific IgE Food Screening Tests of groups of related food allergens are available, the most clinically important are:


Specific IgE Nuts Mix fx1
Specific IgE Seafoods Mix fx2
Specific IgE Cereals Mix fx3
  

A negative result reliably (>95%) excludes all the individual relevant allergens, so obviating the need to test for many single food allergens. A positive result with any Specific IgE Mixed Allergen test should be followed up with Specific IgE tests for the individual allergens. Over 160 individual ImmunoCAP® Specific IgE food allergens are available in total. A laboratory will offer a range of 10 to over 100 of the most clinically important. With this very large range of potential food allergens, it is obviously vitally important that the clinician must make a careful choice of the allergens to be tested for, based on the thorough clinical history.









Range of Specific IgE Tests
Top
Over 400 different Specific IgE allergen tests are available from Pharmacia & Upjohn, Diagnostics. This range includes those allergens that have been thoroughly evaluated and documented internationally and are therefore formally approved for routine use in clinical investigations of patients. These Specific IgE allergens have the code number such as f1, g2, e3, etc. In addition there are those Specific IgE allergens which belong to the Pharmacia & Upjohn, Diagnostics Special Allergen Service which are still under international evaluation and are therefore intended only for research investigations. These have the code number such as Rf289, Ri202, etc.

The range of allergens includes the following categories:


Pollens
grasses
weeds
trees
Moulds & Yeasts, including spores
Mites, including various House Dust Mites
Epidermals, including animal proteins, urines, etc.;
Foods
Fruit
Vegetables
Grains
Legumes
Spices
Seeds & Nut
Fish
Crustacea
Molluscs
Meat
Milk
Egg & Fowl
Occupational allergens, including chemicals
Drugs, including anaesthetics and antibiotics
Insects, including venoms
Parasites
Miscellaneous
  

Although these over 400 Specific IgE allergens are manufactured by Pharmacia & Upjohn, Diagnostics, each individual laboratory will stock a range of just 20 to 100 of the most important. Even if your local laboratory does not offer a wide range of Specific IgE allergens, they can certainly refer the patient's blood sample to another co-operating laboratory for more testing for the more unusual Specific IgE allergens.

For further information on theses types of allergens and on the individual allergens, see the section entitled "Available Specific IgE tests".


  

Specific IgE test results are expressed by the laboratory either in semi-quantitative classes, zero to six, indicating increasing levels of allergen-specific IgE to that particular allergen, or as a fully quantitative value of so many kilo-units per litre of specific IgE (kU/l). The latter method of measurement is of course more precise and is therefore preferred.


  


Costs
All these various assays such as Total IgE, Phadiatop, Specific IgE, etc., are available at almost all private and hospital pathology laboratories in South Africa. The laboratories all charge Medical Aid Scheme of Benefits tariffs. All of these tests and assays are fully reimbursed under the Medical Aid Scheme of Tariffs.
It is very important that the doctor makes a wise choice of which tests to use, depending on the individual circumstances of the patient. It is expensive and almost always clinically unnecessary to test for a wide range of Specific IgE allergens; the clinical history and presentation should give clues to what type of allergen(s) or even what individual allergen(s) to test for, without the expense of unnecessary tests.




  


Trademarks
The following names are registered trademarks belonging to
Pharmacia & Upjohn Diagnostics:
ImmunoCAP®®
Specific IgE®
Phadiatop®
Pharmacia UniCAP® System.
  


Further Information
If you would like further information, or clarification, or if you have any questions, please contact Laboratory Specialities by telephone at 011-792-6790 (Mr Charles Duff or Sister Maria Ramsay) or 021-4478998 (Mr Steve Lee).
Brochures for either patients or doctors are available on a variety of topics and can be supplied on request.



[ Main ] [ Allergy ]