Allergy testing is not yet a precise science and is not suitable for all atopic patients. It must be used with caution and only in the correct circumstances. However, skin prick tests, radioallergosorbent testing (RAST) and patch tests, if interpreted by experts, may make a useful contribution in a range of allergies.
It is essential to understand which type of allergic disease the reaction is (key points) to determine which tests would be appropriate. Not all apparently allergic skin reactions are allergic in origin.
In dermatological disease, allergies are usually type I or IV immune reactions (see box at the bottom). Type I allergy should be investigated using serum IgE, RAST and skin prick testing, while type IV reactions should be investigated using patch testing.
Contact dermatitis can be confirmed by a patch test
Targeted type I testing
Allergy tests for type I disease should always be targeted to a few allergens identified by a careful history and examination. Routine screening with a large battery of allergens is never indicated.
These tests are most valuable in the investigation of patients with respiratory atopic disease.
Serum total IgE testing can be used to gain an indication of whether there is a general atopic state. However, it does not correlate well with severity of allergic disease and varies with age.
RAST is an automated quantitative analysis that detects allergen-specific IgE and may be useful in confirming type I allergy to inhaled allergens and certain food groups, such as nuts and shellfish.
For these allergens, RAST results show good correlation with the degree of reaction to skin prick tests. However, false positive and false negative results are common and patients with very high IgE levels are particularly prone to false positive RAST.
RAST may also be used in atopic eczema patients, where aeroallergens, such as house dust mites, or specific food allergens, such as milk, are suspected. Routine RAST for all atopic eczema patients is not indicated because 20 per cent have normal IgE and negative RAST, and 15 per cent of healthy individuals have raised IgE.
Skin prick testing may be a more reliable method of testing for type I allergy to fruits and drugs than RAST, although for reproducible and reliable results it requires experienced staff who perform the tests regularly. Allergens are applied, diluted or in their normal state, and gently inoculated into the skin. Histamine and normal saline are used as controls.
However, this method is not suitable for patients taking antihistamines, phenothiazines, or calcium-channel blockers, and patients with atopic eczema tend to have hyperreactive skin, leading to false positives. In addition, because there is a small risk of anaphylaxis in cases of severe allergy, the testing should only be done where resuscitation equipment is available.
It is commonly assumed that RAST or skin prick tests may help to find a cause for acute and chronic urticaria, but in fact, they are rarely used by dermatologists for this purpose.
Skin prick testing may occasionally be helpful in acute urticaria if it is particularly important to confirm a drug allergy, but it is not used routinely.
Defined as being of sudden onset and less than six weeks' duration, acute urticaria may have an obvious precipitant, such as penicillin, other drugs, sunlight, cold or heat, or foods. A careful history is vital and may be all that is needed to establish the cause of the urticaria.
It may be important to confirm latex allergy objectively in health workers, or before operations and other medical procedures, and this can be done initially with RAST. Latex allergy may cause angioedema in some patients.
This subcutaneous variant of urticaria, mainly affecting the junctions between skin and mucous membranes, can be severe and leads to anaphylaxis in some highly allergic people, although most cases show milder forms of urticaria.
If the RAST is positive, no further testing is necessary, but if negative, skin prick testing may be carried out under close supervision, to exclude a false negative RAST.
Chronic urticaria (CU) by definition lasts more than six weeks and is rarely due to a type I reaction. Up to 35 per cent of patients may have delayed pressure or other physical urticarias, while 60 per cent of CU patients have histamine-releasing autoantibodies, for which there is no routine clinical or laboratory test.
In addition, 15 per cent may have antithyroid antibodies, compared with 6 per cent in the general population.
Although CU may be provoked or aggravated by a number of drugs and food additives, this is rarely an immunological reaction, but is due to direct action of a 'pseudoallergen' on mast cells, with degranulation and histamine release. Common culprits are salicylates, NSAIDs, opiates and azo dyes. In some cases, there may be an association between occult infections or Helicobacter pylori infection and urticaria. Most patients do not need allergy tests.
- Allergy testing is not recommended for all patients with atopic disease.
- Different kinds of tests should be used to identify the allergens responsible for type I and type IV allergies.
- IgE, RAST and skin prick testing can sometimes identify the cause of acute allergic reactions, such as food allergies, although they have high false negative and false positive rates.
- These tests are not usually suitable for cases of urticaria, although there are some exceptions.
- Patch testing can help distinguish irritant from allergic contact dermatitis and identify allergens involved in contact dermatitis.
Patients with type IV allergies have delayed allergic responses and should be tested using the patch test. This is designed to elicit an immune response using a battery of allergens applied to the back in prescribed concentrations for 48 hours, thereby establishing that the patient has been previously sensitised to one or more of the allergens.
This is a test for delayed hypersensitivity, so the strength of the reaction is quantified after 48 hours when the tests are removed and again after 96 hours. In experienced hands, this is a reproducible method of testing, but false positive and false negative results are possible, and there is a risk of sensitising a patient to new allergens.
The current British Standard series of patch tests contains the 37 most common contact allergens, including metals, rubber chemicals, preservatives, plant extracts and medications. There are also many specialised batteries designed to identify occupational and dental allergens.
Patch testing is used to differentiate between irritant and allergic contact dermatitis and to establish which allergens may be involved in the latter. This may be of crucial importance in patient management.
Once again, the history and examination are extremely important and may yield vital clues, such as the timing and distribution of a rash, and the patient's occupation, social habits and hobbies, which can help in deciding which batteries of patch tests to use.
The results of patch testing must be interpreted with care. Some positive reactions are of doubtful relevance and some important, unsuspected, allergies may be revealed. Patients must be advised on sources of allergens and how to avoid them.
Routine investigation of patients with atopic eczema using patch testing is not indicated, but an unexplained flare of eczema may require it, once the exacerbation has settled.
Atopic patients are more susceptible to developing type IV allergies and irritant dermatitis than the normal population. This may be particularly important in occupational allergen exposure.
- Dr Carr is consultant dermatologist at the department of dermatology, University Hospital of North Durham
- This article was originally published in MIMS Dermatology. To subscribe visit www.hayreg.co.uk/specials
|GELL AND COOMBS CLASSIFICATION OF ALLERGIC DISEASE|
|Classification||Immune mechanism||Clinical disease|
|Type I (immediate hypersensitivity)||Antigen-specific IgE, mast cells, eosinophils, histamine, leukotrienes, interleukins||Urticaria, angioedema, anaphylaxis, allergic rhinitis, allergic asthma|
|Type II||IgG antibody-mediated, direct cytotoxic effect, complement-mediated cell lysis||Autoimmune thyroiditis, haemolytic anaemia, autoimmune|
|Type III||Immune complexes, IgG and IgM antibodies, complement||Serum sickness, hypersensitivity vasculitis, systemic lupus erythematosus|
|Type IV (delayed T-cell mediated hypersensitivity)||T-cell mediated (Th1 and cytotoxic) cytokines, dendritic antigen-presenting cells, macrophages||Allergic contact dermatitis, other eczemas, graft rejection|
|Source: Gell PGH, Coombs REA. Classification of allergic reactions responsible for clinical hypersensitivity and disease. Clinical Aspects of Immunology, 1968.|