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INTRODUCTION
1. The
History and Physical Examination
2.
Evaluation of the Patient's Environment
a) House dust Mite Analysis
b) Detection of Pollen and Mould Allergens
i.) Regional Pollen and Mould Counts
ii.) Home Air Sampling
iii.) Mould Plate Cultures
3.
Identification of the Atopic Patient
a.)
Cord Blood IgE
b.)
Total IgE
c.) The
Phadiatop Test
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4.
Identification of the Causative Allergen by measurement of Allergen Specific IgE
a.) In
Vivo Tests
Skin Prick Tests
b.) In
Vitro Tests
i.) The Radio-Allergo-Sorbent Technique (RAST)
ii.) RAST Mixed-Allergen Tests
iii.) RAST Tests for Individual Allergens
Pollen allergy
Mould allergy
Food allergy
Diagnosis of
Venom Allergy
Diagnosis of
Drug Allergy
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4. Identification of the Causative Allergen by measurement of Allergen Specific IgE
Specific allergy testing should be guided by the history, clinical examination, environmental assessment of the patient and an assessment of atopy. Specific allergy tests are classified into in vivo and in vitro tests.
a.) In Vivo Tests
Index
Skin Prick Tests
Skin tests are reliable, easy to perform, give rapid results and are cost effective. They can be performed by any practitioner trained in the technique and in the interpretation of results. Skin tests are generally reliable for the identification of aero-allergens. For the diagnosis of food allergy they are more useful for their negative predictive value with currently available stored food extracts. Their sensitivity increases for food allergy if fresh extracts are used. They may result in severe local and rarely even anaphylactic reactions and should therefore always be conducted in a facility where emergency and resuscitation facilities are available.
Skin tests are commercially available in South Africa only from Bayer. The standard skin test kit has 8 aero-allergens plus a positive and negative control. The 8 allergens in the standard kit are as follows: house dust mite, cat saliva, dog epithelium, feathers, Bermuda grass, Maize pollen, grass mix and tree mix. A large range of additional individual allergens can be ordered through Bayer. (Telephone 011-921 5717; Fax 011-921 5524). In view of safety considerations, skin testing for inoculant allergens such as bee venom and horse antigens and for drugs such as penicillin should only be performed by specialists in a hospital environment. The technique of skin testing is described in Appendix IX.
When skin tests are performed, strict attention must be given to storage of the reagents, the results of positive and negative controls and the reading of the result. Patients must be co-operative and should not be on certain medications for the times indicated in Appendix IX (on page 204), since these will block the wheal and flare reaction. Skin testing is conveniently recorded and graded in millimetres measuring the wheal and flare size. A positive skin test is a wheal 2mm greater than the negative control and may be expressed as a percentage of the positive histamine control response. The response of the skin testing should be recorded in the patient’s clinical notes. The most accurate method is to transfer the outline of the wheal and erythema with transparent tape and calculate the area, but a semi-quantitative grading of 0-4 is usually adequate for practical purposes.
Skin testing is dangerous for some allergens particularly if non-standardised, fresh, undiluted or highly purified extracts are used. Patients who report apparent exquisite sensitivity to certain allergens (e.g. peanut, egg, penicillin, crustaceans) should never be challenged directly. In such patients, confirmation or follow-up evaluation of allergen sensitivity should be made using RAST tests.
It is usually unnecessary to follow up skin prick tests with intradermal tests, but this may be important when performing skin tests for drug or venom hyper-sensitivity. The risk of systemic reactions is greater with intradermal testing. Intradermal tests should be conducted at 1:100-1:1000 the concentration used for skin prick tests.
Skin prick tests conducted at 6 month intervals have been shown to be useful in monitoring specific responses in patients undergoing immunotherapy.
A recent position statement by the American Academy of Allergy and Clinical Immunology summarises the state of the art of skin testing (Ref.6).
b.) In Vitro Tests
Index
i.) The Radio-Allergo-Sorbent Technique (RAST)
It is possible to test in the laboratory for IgE-mediated sensitivity to over 420 individual allergens, using either the first generation Phadebas
â RAST test from Pharmacia, or the second generation Pharmacia ImmunoCAPâ RASTâ test. These are listed in Appendix X on pages 205-211 and available at most pathology laboratories in the R.S.A. Many unusual or specialised allergen tests are available at the University of Cape Town Allergology Unit.
The RAST test can be used for single individual allergens, or for mixes of similar, related allergens.
ii.) RAST Mixed-Allergen Tests
In practice, patients may react to groups of allergens, to cross-reacting allergens or only to specific individual allergens within a particular group. For this reason, RAST Mixed-allergen tests have been developed. Mixed-allergen RASTs are mixes of certain groups of similar allergens for which one can screen cost-effectively. A positive result reliably indicates that the patient has allergen-specific IgE to one or more of the constituent allergens, and the serum sample should be further investigated with individual RAST tests to identify the responsible individual allergens. A negative result with the RAST Mixed-allergen test reliably excludes any of the component allergens, thereby obviating any further testing for these allergens. The use of RAST Mixed-allergen tests can therefore be ver cost-effective when used correctly.
RAST Mixed-allergen tests are available for a number of allergen groups e.g. different nut mixes, different fish mixes, different fruit mixes, different animal mixes, different grass mixes, different tree mixes, different mould mixes, different spice mixes and different cereal mixes. Mixed RAST tests are listed in Appendix XI, on pages 212-213. Of the 66 available Mixed-allergen RAST tests, 40 are for routine clinical use and a further 26 are intended for research purposes.
The most useful Mixed allergen RAST is the RAST Paediatric Food Mix fx5 which contains a mixture of common food allergens, i.e. cow’s milk, egg white, codfish, wheat, peanut and soya bean. The fx5 is particularly useful in screening for food allergy in small children, in whom food allergy is more common. In fact, in children under the age of three years, a combination of an IgE test plus a fx5 test is most useful in identifying the atopic child.
Obviously, if the patient has a strongly suspected allergy or history that simply requires confirmation, then screening with RAST Mixed-allergen tests is not required.
iii.) RAST Tests for Individual Allergens
The Phadebas RAST test from Pharmacia of Uppsala, Sweden, has for years been the gold standard for in vitro allergy testing. However, this first generation RAST test was not as sensitive as skin testing.
The second generation Pharmacia ImmunoCap RAST has now almost completely replaced RAST tests in South Africa and throughout the world. It is a technically improved development of the original RAST, and the major advantage is that its sensitivity now approaches that of skin testing. The CAP RAST is currently utilised for more than 93% of all RAST samples in the allergy laboratories of South Africa. A few remaining laboratories still utilise the original Phadebas RAST test.
The range of over 420 individual RAST allergens (see Appendix X) and include the following types of allergens:
- grass pollens
- weed pollens
- tree pollens
- animal danders, epithelia, feathers & body fluids
- house dust mites & other mixes
- mould spores
- drugs & chemicals
- occupational allergens
- food allergens, such as vegetables, fruits, nuts, meats, fish, crustacea, spices, dairy products, etc.
- insects and insect venoms
- parasites
- house dusts
- other miscellaneous allergens
With the Pharmacia ImmunoCap RAST, results from the laboratory can be expressed in terms of classes (1-6) or in fully quantitative units of kU/l IgE.
Of the 420 individual RAST allergens available in the Pharmacia ImmunoCAP RAST Assay System, 235 are for routine diagnostic use, and a further 185 allergens are available as part of Pharmacia's’Special Allergen Service. These allergens are not yet fully documented and so are intended for research purposes only.
Plate 3 on pages 124 and 125 shows a "generic" Laboratory Test Request Form for the various IgE-based assays that can be utilised by laboratories and clinicians.
As the range of allergens is so large, testing must be made selectively. The decision about which individual allergens to test for is dictated firstly by the patient’s history, and taking into consideration his geographical location (particularly with respect to aero-allergens). Thus, if a patient lives on the South African coast and gives a perennial history, it is essential to test for house dust mite, and if he lives in Natal, one should also test for cockroach allergy. If the patient lives on the highveld or inland and there is a seasonal variation in symptoms, it is important to test for grasses. If the patient's symptoms are worse indoors or during the wet months, mould allergy, or cat and dog allergy should be investigated.
The pathologist involved in vitro allergy testing should be able to assist the clinician with information on locally prevalent and important allergens. It should be borne in mind that the sensitivity of RAST tests is very good for aero-allergens and also good for certain foods, e.g. Egg, Shrimp and Cod, whereas for fruit and vegetables the clinical sensitivity is much lower.
Index
Pollen | |
allergy |
may be due to grass pollen or weed pollen and only rarely to tree pollen. Allergy to grasses is the most important, particularly for highveld patients. The very long grass season in South Africa often results in prolonged symptoms both at the coast and inland. Local studies have shown that common allergenic grasses in South Africa are Bermuda allergenic. In screening for grass allergy, the most appropriate grass mix is the RAST Grass Mix gx2, since this includes Bermuda grass. The Panicoidiae grass family appears to be important in Southern Africa. However, in view of cross-reactivity among grasses, testing individually for both Bermuda grass and Rye grass or Timothy grass specific IgE will detect most grass allergic subjects. There is a high level of cross-reactivity among grasses, with the exception of Bermuda grass that must be individually identified, and if immunotherapy is to be given then Bermuda grass should be included.
In South Africa, unlike the USA where Ragweed is common, allergy to weed pollens is fairly uncommon.
Allergy to tree pollen is common in Sweden (birch) and in Mediterranean countries (cedar), but uncommon in South Africa. The trees to which patients may react include oak, plane, willow, poplar, acacia species and prosopis tree (particularly in Namibia). There is a clear seasonality with tree pollen, with various trees pollinating during limited periods of the early spring in different regions of the country. At the University of Cape Town, we have recently confirmed that Port Jackson pollen also induces IgE antibodies. |
Index
Mould | |
allergy |
is an important cause of symptoms, and mould allergens include Aspergillus fumigatus, Cladosporium herbarium, Alternaria alternata and Epicoccum. Unlike grass allergy, mould allergens do not, in general, cross-react and need to be tested individually. A RAST Mould Mix mx1 is often a useful screening test before following-up with RAST tests for individual mould allergens. If the patient shows a positive response to a particular mould, the source and presence of the mould should be sought in the patient’s home, using mould culture plates. Recently allergy to the fungus Pitysporum orbicularis has been shown in patients with chronic eczema. |
Index
Food | |
allergy | is generally one of the most difficult areas of allergy diagnosis. It is also the most difficult area of in vitro diagnostic tests. In vitro RAST tests usually have a very good correlation with the clinical history when the reaction is immediate, and so the allergen is already identifiable by the history (e.g. peanut, crustaceans, egg, and milk allergy). However, when the history of food allergy is vague and symptoms may be more chronic such as occurs in patients with eczema, the in vitro RAST tests are less useful. Some false positive results can be encountered when panels of food allergy tests are performed. In such instances positive responses of greater than 3+ CAP RAST class (out of a maximum of 6 classes) should be considered as candidates for food elimination/challenge studies; positive responses of 1+ or 2+ may well be clinically false positives.
Identifying sensitivity to food allergens is more important in small children where food allergy is commonly encountered, and for these children the RAST Paediatric Food Mix fx5e is a very useful first line screening test before RAST testing for the individual component allergens. Even for adult food allergy, this test is a useful screen which may be complemented by other food allergens normally found in the adult diet.
For small children with cow's milk allergy it is always important to know whether they are reacting to casein and/or alpha lactalbumin and/or beta lactoglobulin and/or soya, so that appropriate milk substitutes can be safely advised.
A number of new and exotic food allergies has been reported both overseas and in South Africa; these include allergy to kiwi fruit, pine nut, passion fruit, melon, mango and egg plant. Several pateints who are allergic specifically to food spices (e.g. cinnamon, nutmeg, fennel, oregano, tarragon, paprika and thyme) have been identified recently. For such patient, it is usually cost-effective to screen with a RAST Mixed Spices test prior to testing individual spices. Patients have also been reported to be highly allergic to tetramin fish feed, trout, squid and oyster.
When an in vitro food allergy test has been performed to confirm a known sensitivity (e.g. peanuts), it is extremely important that challenge tests are not carried out, due to the risk of anaphylaxis. However, when a food allergen is first identified as a result of in vitro screening, it should always be regarded as a "candidate allergen", until sensitivity has been proven by controlled challenge studies. The gold standard for the diagnosis of food allergy remains the double blind placebo controlled food challenge (DBPCFC).
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Index
Diagnosis of Venom Allergy
| Allergy to bees (Hymenoptera) is the most important venom allergy in South Africa. Patients who are allergic to wasps are very uncommon in South Africa, unlike Europe and America.
Bee venoma hypersensitivity may be confirmed using the CAP RAST test but the level of IgE antibodies to bee venom does not necessarily correlate with the degree of patient sensitivity. CAP RAST’s are also available for wasp venom. Patients with anaphylactoid sensitivity to bee venom or wasp venom should be treated with immunotherapy by a specialist in allergy. Skin testing for venom allergy is reliable but in view of risk of anaphylaxis as a result of the skin test, they should only be conducted in specialised allergy units. |
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Diagnosis of Drug Allergy
| A practical approach to the investigation and diagnosis of specific drug allergies is given in the chapter devoted to drug allergy.
RAST tests and skin tests are available for many drugs but the sensitivity, specificity and predictive value of these tests is extremely variable for different drugs. A knowledge of the individual sensitivity and specificity profiles is necessary for each drug and for many drugs this data is not yet currently available.
Reliable skin testing can be performed for the following: Penicillin, toxoids, antisera, insulin, ACTH and egg protein vaccines. RAST's are available for alcuronium, suxamethonium, ampicillin, amoxycillin, Penicilloyl G, Penicilloyl V, insulin, thiopentone, procaine, cephalosporins and trimethoprim.
A low sensitivity of RAST tests for drugs limits their usefulness in drug allergy but they are, in general, highly specific and thus a positive result is always useful and indicative of specific IgE sensitivity.
Mast cell tryptase measurement is extremely useful if measured or serum samples taken within hours of an anaphylactic reaction due to drugs, particularly during anaesthesia.
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Index
