Appropriate use of allergy testing in primary care
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An allergic reaction is a result of hypersensitivity of the immune system to an allergen. Generally, for an allergy to be considered a “true” allergy, there are two factors that need to be present:
- Clinical features – i.e. the development of specific signs and symptoms on exposure to that allergen AND
- Sensitisation – as shown by the presence of allergen-specific IgE
The exceptions to the definition of true allergy are the non-IgE-mediated food-induced allergic disorders, which are only rarely encountered in general practice, e.g. food protein-induced enterocolitis syndrome.
An intolerance is an adverse reaction to a substance, not involving the immune system.
It is estimated that approximately 30% of people in New Zealand are affected by an allergic condition during their lives.1 The symptoms and signs of allergy vary widely from very mild reactions to life threatening situations (anaphylaxis).
The diagnosis of allergy in primary care is often based on the clinical picture rather than on the results of investigations.
Take a detailed history
A detailed clinical history should include information about:
- Type, severity and duration of the symptoms
- Onset of the symptoms and the timing in relation to the presumed allergen
- Relationship of the symptoms to place, time (of day, season), work or hobbies
- What the patient thinks is the likely allergen
- Personal and family history of atopy
- Any exposure to new foods, pets or plants
- Any medicines that are being taken, including all over-the-counter treatments
Physical examination is guided by the clinical history
In general this should include an examination of the:
- Skin – for signs of urticaria or other rash, dry skin, eczema or dermatitis, excoriations
- Head and neck – in particular eyes (e.g. swelling, tearing, redness, allergic “shiners” in children), nose and sinuses for congestion, mouth and tongue, cervical lymph nodes
- Lungs – laboured breathing, wheezing (high-pitched sounds produced by narrowed airways when a person exhales) or the presence of rhonchi (sounds that resemble snoring when air is blocked or becomes rough through the large airways). Abnormal sounds can sometimes be heard without a stethoscope.
The majority of patients with allergy can be adequately managed with medicines, appropriate advice and reassurance, without it being necessary to specifically identify the allergen. If medical treatment is inadequate to control symptoms, and it is thought that identifying the likely causative allergens would benefit the management of that patient, then allergy testing for some conditions may be indicated. The two allergy tests that can be requested in general practice for IgE mediated allergies are:
- Skin prick tests (in vivo)
- Serum allergen-specific IgE tests (in vitro)
The results of both of these allergy tests must be interpreted in the context of the clinical history as a positive result only reflects sensitisation and not necessarily allergic disease if there is no history of symptoms. For example, a patient might display a high response to peanuts when allergy tested, yet have no clinical reaction after eating peanuts. Therefore that person is NOT allergic to peanuts.2 Positive allergy tests may also be clinically irrelevant if the patient is unlikely to have been exposed to that allergen, in which case it cannot be the cause of their current allergy symptoms.
Patch testing is not available within the primary care setting (but may be available in specialist allergy clinics and within secondary care). It is usually considered for difficult cases of allergic contact dermatitis, e.g. caused by nickel, rubber or cosmetics.
If laboratory investigation of allergy is required, skin prick testing is preferred. Skin prick testing should not be requested if the result of the test is unlikely to improve the management of the patient, e.g. confirming an allergy to pollen in a patient with obvious seasonal allergic rhinitis, whose symptoms are well controlled, is unlikely to be helpful.
Skin prick testing detects IgE bound to mast cells in the skin. Small amounts of the suspected allergens are introduced into the epidermis and superficial dermis and interact with any specific IgE bound to skin mast cells. If this occurs, histamine and other mediators are released, leading to a visible “wheal-and-flare” reaction which is maximal after about 15 to 20 minutes.
The extent of the reaction on the patient’s skin is assessed to give a positive or negative skin prick test result. If the diameter of the wheal is ≥ 3 mm more than the negative control, this is considered a positive result. The degree of sensitivity of the patient to the allergen is reflected in the size of the wheal, but this should be interpreted relative to the age of the individual. For example, in children aged under five years, a much smaller wheal size can be clinically significant.
The following wheal sizes in adults gives some guidance as to the relative sensitivity to the allergen and the likelihood of being allergic:
|Size of wheal||Clinical significance|
|> 15 mm||Very sensitive|
|10 to 15 mm||Moderately sensitive|
|5 to 10 mm||Mildly sensitive|
|< 3 mm||Negative result|
N.B. The size of the wheal (and therefore the degree of sensitivity) is not an indication of the severity of symptoms for that patient.3 Sufficient clinical information should be included on the request form so that the results of skin prick testing are able to be interpreted appropriately in relation to the patient’s symptoms.3
In some patients, swelling, heat and itch may develop in the testing spots one to two hours after application of the allergens (rather than within the first 15–20 minutes). This is referred to as a late phase cutaneous reaction. Although these reactions are IgE dependent they do not appear to relate to the clinical situation for the patient and have no diagnostic value.4
Negative and positive controls
In addition to application of the suspected allergens, both a positive and negative control are also used.
The negative control is a saline solution, to which no response is expected. If a patient reacts to a negative control, then this will indicate that the skin is extremely sensitive and that the results may be unreliable, e.g. patients with dermographism can develop wheals to all allergens as well as to the negative control.
The positive control solution contains histamine, to which everyone is expected to react (i.e. develop a small raised wheal with a red surrounding flare). Failure to react could mean that the patients may have taken medicines that are blocking the response to the histamine and allergens.
Selecting patients for skin prick testing
Skin prick testing may not be reliable for older adults. Skin reactivity (and the size of the wheal) increases with age until age 50–60 years when it begins to decline again.1,3 People with darker pigmented skin appear to develop larger wheals than people with paler skin.1
If skin prick testing is required for a child aged under two years, this should ideally be performed at a specialist allergy clinic, as it is more difficult to interpret the results in this age group (there is often a small wheal but a large erythematous flare).
Pregnant women should only have skin prick testing if detection of an allergy and subsequent treatment outweighs the risks – in rare cases, uterine contractions may occur as a result of a systemic reaction.4
Indications for skin prick testing
Patients who may benefit from skin prick testing include those with:3,5,6
- Significant asthma, eczema and allergic rhinitis – where avoidance of specific allergens or immunotherapy (desensitisation) may improve the condition
- When major allergen avoidance measures are being considered such as removal of carpets or the family pet or avoidance of specific foods from the diet
- Acute urticaria* and angioedema (often related to food allergy)
- Significant systemic symptoms following a bee or wasp sting (not localised reactions to stings) – especially if immunotherapy (desensitisation) is being considered
Contraindications for skin prick testing
Skin prick testing is contraindicated in the following clinical situations:2
- Patients with a history of recent anaphylaxis. Skin prick testing should not be performed within four to six weeks of an anaphylactic episode because the results may be falsely negative.
- Skin prick testing should be used with caution in people with significant co-morbidities such as cardiovascular disease or arrhythmias and also in elderly people
- Patients with skin conditions such as dermographism, because the results may be falsely positive. Any skin condition, e.g. widespread atopic dermatitis, that affects the skin cell structure or requires topical medicines for treatment may also make interpretation of the results difficult.
- Patients taking medicines that may interfere with skin prick testing and that cannot be discontinued should not undergo skin prick testing (see box below for a list of these medicines)
Choosing appropriate allergens for skin prick testing
It is important that the allergens tested are relevant to both the patient’s clinical condition and to their exposure. In general a small number of allergens (e.g. three to four) is required in a patient with a clear history of reactions to specific allergens (e.g. foods) and more allergens (up to 25) in a patient with rhinitis, eczema or asthma.2,3
Considerations when interpreting skin prick testing results
Wheal size results can be affected leading to false positives and false negatives: A positive reaction from one test site may falsely affect the result of a neighbouring test site (this is why test sites need to be at least 2 cm apart). In addition irritant reactions can cause false positive skin prick test results.3 Negative skin prick test results can occur even in the presence of true IgE-mediated allergy, due to inadequate representation of allergenic proteins in certain extracts,5 or if the patient has taken antihistamines prior to testing.
Sensitivity does not equal allergy: Positive skin prick test results (sometimes even with large wheal size) can occur without any clinical response occurring on contact with that same allergen. The skin prick test result indicates only whether IgE to a specific allergen is present or not. Therefore a test may be technically positive, but if symptoms do not occur on exposure to that allergen, it is referred to as “clinically silent sensitisation”, or a “clinical false positive” test result (however, this individual may still be classified as atopic).5
A negative skin prick test result to foods such as peanut has a negative predictive value of >95%, however, the positive predictive value is significantly lower, reaching only 60% in patients with a convincing history of an allergic reaction. A recent study from the United Kingdom reported a 22.4% prevalence of clinical peanut allergy among people with sensitivity demonstrated on testing.8
Skin prick testing may also be positive when a patient has a previous history of allergy that has since resolved, e.g. hay fever may remit in adults but pollen skin tests often remain positive throughout life.5
Lack of sensitivity does not mean that allergy can be ruled out: When the skin prick test result is equivocal or does not correlate with the history, a controlled challenge (by an allergy specialist) with the suspected allergen may be required (if clinically indicated and practical).5
Wheal size cannot predict the severity of an allergic reaction: Some patients with anaphylactic sensitivity to insect venom or latex, may have a wheal size as small as 3 mm while, in contrast, others may have wheals of 10 mm or greater to inhalant and other food allergens but show little or no allergic signs if they are exposed to these allergens. In addition, a positive skin prick test result does not predict the nature of the allergic symptoms.5
Wheal size has some correlation with likelihood of clinical response: Despite wheal size not automatically correlating with clinical response, wheal size does have some correlation with the likelihood that the patient is clinically reactive to that allergen, i.e. people with a larger wheal size are more likely to clinically react to that allergen upon challenge than those with a smaller wheal size.5
Medicines that can interfere with skin prick testing
Medicines that may interfere with skin prick testing include:3,5
- Antihistamines (H1-blockers) – decrease the reactivity of the skin and should be stopped at least 72 hours prior to skin prick testing
- Topical corticosteroids – should not be used in the area of the testing site for two to three weeks prior because they have been shown to reduce skin reactivity. Oral or inhaled steroids do not appear to alter the reaction to skin prick testing and can be continued.
- Other medicines – such as tricyclic antidepressants, phenothiazines, benzodiazepines, quetiapine and mirtazapine may also reduce the reactivity of the skin. Skin prick testing should generally only be requested if these medicines are able to be discontinued temporarily.
Histamine receptor -2 blockers (e.g. ranitidine) work mainly in the stomach instead of the skin but have in the past been included among the medicines which should be avoided prior to skin prick testing. However, a recent report showed minimal interference with allergy testing in patients who were taking H2 blockers at the time of testing.7
Advantages of skin prick testing include:
- The cost – skin prick testing is relatively inexpensive costing approximately $24 for a panel (compared to a cost of $40–$50 per single allergen tested for using serum allergen-specific IgE testing)6,9
- Skin prick testing has a greater sensitivity (and consequently high negative predictive value) than serum allergen-specific IgE tests and is relatively specific
- The results are available quickly (results are known within 15–20 minutes)
Disadvantages of skin prick testing include:
- In rare cases, skin prick testing can trigger anaphylaxis. The risk is higher in younger children and in situations where a systemic reaction has occurred as a result of exposure to, for example, a food, latex or a stinging insect.10
- Not all allergens are available for skin testing
- Skin prick testing takes approximately 30 minutes or more to perform at a community laboratory.
Serum allergen-specific IgE tests are used to detect the presence of allergen specific IgE antibodies produced in the serum when it is mixed with a series of allergens.
Serum allergen-specific IgE tests were formerly known as RAST tests (radioallergosorbent test), however, this test is now done by enzyme allergosorbent testing.
Indications for serum allergen-specific IgE tests
Serum allergen-specific IgE tests can be useful when skin prick testing is considered unsuitable, for example:13
- When the patient’s skin is unsuitable for skin prick testing (e.g. in patients with widespread dermatitis or dermographism)
- When the patient is unable to discontinue a medicine such as an antihistamine (as this does not affect serum testing)
- In rural areas where skin prick testing may be unavailable
- When the suspected allergen is not available for skin prick testing (depending on the clinical need)
- If the history strongly suggests allergy to a specific allergen but skin prick testing is negative
- Where there are specific safety concerns due to past anaphylaxis (e.g. an anaphylactic reaction to nuts)
- For the prediction of allergy persistence or resolution of food allergies in children
Although serum allergen-specific IgE tests are less sensitive than skin prick tests, false positives are less common with serum testing, and so the positive predictive value is greater.6
Selecting allergens for serum IgE tests
Serum allergen-specific IgE tests should be requested for an individual allergen or allergen mix (where available) based on the patient’s clinical history. They should not be used as general screening tests.14 The cost for this form of testing is per allergen tested (approximately $40–$50) and therefore testing for multiple allergens incurs a significant cost (to the laboratory). Results of serum allergen-specific IgE tests can take one to two weeks.9
Availability of allergens for testing varies throughout the country. Contact your local community laboratory for specific information.
Some allergens are related, whereby a patient who is sensitive to one allergen also reacts to other similar allergens, even if they have never have been exposed them. This is known as cross-reactivity.5
Common related allergen groups include:11,12
- Brazil nut, walnut, hazelnut, cashew, almond
- Apple, pear
- Kiwifruit, avocado, banana, latex
- Melon, watermelon, tomato
Oral allergy syndrome typically occurs in adults with allergic seasonal rhinitis (hay fever), especially those allergic to birch pollen.1 It is characterised by allergic symptoms localised to the inside of the mouth after ingesting certain fruits, nuts or vegetables (usually only if raw). This is due to cross reactivity between pollen and pollen remnants found in these foods.
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