Diagnosing Allergic Diseases

Careful diagnosis of allergy can lead to a very grateful patient.

Allergic disease is one of the 3 most common reasons why patients attend their family physician. Respiratory diseases represent about 25% of all visits to general practitioners and about 80% of patients with recurrent presentations are found to be allergic.

Allergies are a significant cause of morbidity. For some patients the inconvenience of their hay fever, the embarrassment of their eczema and the time off work and school because of asthma is the most significant problem in their life.

There is also a definite mortality attached to allergic diseases. The previous high death rate from asthma in New Zealand, despite all the modern drugs available, made it clear that we needed to change our tack in the management of this disease, and now it is becoming increasingly recognised that allergic factors play a significant role in the pathogenesis of this disease. Research and educational programs in allergic triggers, e.g. house dust mite, was long overdue. Allergen identification, avoidance, and environmental control should be as important in the overall management plan for asthma as drug therapy, peak flow monitoring and patient education.

The prevalence of food anaphylaxis along with all other allergic diseases has also increased dramatically over the last 20 years. Identifying the correct food early in case of food anaphylaxis and the correct venom in insect sting anaphylaxis, so that specific immunotherapy can be instituted, could actually save lives.

The increase in allergy awareness increases in New Zealand has created an increased demand for "Allergy Tests," as families see the need to diagnose atopy early, so they can start Primary Allergy Prevention measures. It is important to be aware of all the tests available, and emphasize the merits of the proven, useful tests, so that patients will not be forced to resort to Alternative (Unproven) Allergy Tests.

The intention of this article is to increase awareness of methods available for diagnosing allergies and highlight the pitfalls of interpretation of these results, hopefully dispelling the misconception that ‘doing allergy tests is a waste of time’, and finally improving the overall management of allergic patients.

Case History

A careful history is the basis for the diagnosis and management of allergic diseases. The principle of history taking is the same for any medical problem (When, Where & What). General points of particular importance are:

  • Family history of allergies (Atopy)
  • The patient’s perception of precipitating factors
  • The home environment, e.g. pets, carpet in bedroom, mildew
  • The work environment, e.g. chemicals, irritants
  • Dietary factors e.g. hives within 1 hour of eating
  • Timing of symptoms, e.g. day, night, seasonal, at work, at home
  • Hobbies and interests, e.g., horse allergy in keen rider
  • Medication, especially less obvious OTC preparations.

Pitfalls in History

  • Absence of known contact with pets does not exclude sensitization to animals or symptoms on exposure. Several recent studies show very high level of cat allergens in homes without cats, at school, in offices, cinemas and even doctor’s office.
  • Patients with perennial disease have most of their symptoms in the bedroom during the early morning although the causal agent is not necessarily in the bedroom.
  • Patients who have strong aeroallergen sensitivity and chronic low dose exposure to the allergen, e.g., house dust mite or cat will not notice immediate symptoms at home, but will notice symptoms from irritants (due to a nonspecific nasal hyperactivity) like smoke, cold air and perfumes. The patient will then assume these are the allergens, when they are merely secondary irritant triggers. Therefore the case history is rarely informative with regards to house dust mite allergy. A carefully taken history should be followed by an appropriate physical examination.

Skin Prick Test

  • This is the best test for immediate hypersensitivity (Type 1 allergy). It demonstrates tissue bound IgE and identifies the atopic state.
  • Prick test are the in vivo counterpart of the serum specific antibodies (RAST test) although the results do not always parallel each other.
  • Skin test can provide useful confirmatory evidence for a diagnosis made on clinical grounds. A positive skin prick test merely identifies sensitization to a particular allergen it does not predict clinical relevance independent of the history.

    A carefully performed and correctly interpreted prick test with a concentrated extract of high quality allergen is a simple, quick, cheap and safe method with a high degree of specificity and sensitivity. Therefore prick testing with a battery of routine allergens is still the first and basic procedure in diagnosing allergic diseases.

Indications for Doing a Skin Prick Test

  • To demonstrate atopy, i.e. an increased tendency to react to environmental agents by producing IgE antibodies, manifesting clinically one or more of the characteristic disorders of asthma, eczema, or hay fever, multiple positive skin tests and a family history of allergic diseases. There is a good argument for performing skin prick tests as part of the routine work-up of all patients presenting with asthma, eczema and rhinitis — for proper management of these conditions the identification of allergenic triggers is essential before deciding on a long-term program.
  • It is pointless requesting a test if the result will not affect the management of that patient, e.g. testing to confirm pollen sensitivity in someone with obvious spring time hay fever seems pointless unless desensitisation is contemplated (since pollen exposure is unavoidable).
  • Acute urticaria and angioedema – rarely of value in chronic urticaria.
  • Insect sting, bee and wasp, especially if immunotherapy contemplated.
  • Anaphylaxis – test should be timed for 6 weeks after reaction
  • Educational value, provide a clear illustration for patient that may reinforce verbal advice.
  • Essential when expensive or time-consuming allergen avoidance measures, removal of a family pet, or removing carpets from the bedroom are being contemplated

What Allergen Should We Test For?

Based on the pattern of skin reactivity, the success of allergen avoidance measures and immunotherapy (desensitisation), the allergens should be included in a standard battery of skin prick tests. Foods and other allergens should be selected on an individual basis, as dictated by the history. There is a potential to cause systemic reactions with food allergens. Skin prick test with peanuts, eggs or latex should only be done in a specialised clinic/hospital setting in patients who have had anaphylactic reaction to these agents.

Relevant Inhalant allergens in New Zealand in the skin prick test

  • House dust mite 1 (D. pteronyssinus)
  • House dust mite 2 (D. farinae)
  • Perennial rye
  • Cat
  • Macrocarpa
  • Oak
  • Birch
  • Cedar
  • Plantain
  • Moulds (Individually) – Alternaria, Aspergillus
  • Dog

Food allergens reliably tested by skin prick test

  • Milk
  • Eggs
  • Peanut
  • Wheat
  • Soy
  • Fish & shellfish

Cross Reactivity between Allergens

Using new immunoglobulin assays, the sera of affected people have shown strong antigen cross-reactivity among aeroallergens.

Amongst the trees, the cedar, juniper, beech and birch families show strong antigen cross-reactivity within families but not between the different families. Major allergens are shared to such a degree between the birch family (birch, alder, hazel, hornbeam), that test or treatment with birch allergen alone should cover the rest. By way of contrast, there is strong cross-reactivity between the family group of willow, poplar, and aspen as well as olive, ash and privet, respectively.

All of the important grass pollens show considerable cross-reactivity. Similar cross-reactivity is evident between moulds but the extent is less well defined. It exists between some species of Cladosporium and Alternaria and some species of Penicillium and Aspergillus.

It is important to know that laboratory cross-reactions do not equate to clinical sensitivity.

Many children who are peanut allergic will have positive skin tests to several other legumes, but will have on reaction if these legumes are eaten.

Pitfalls for Choosing Allergens for Skin Tests

  • The extracts used should reflect the local aeroallergens. No point using commercial extracts of allergens that are only common in the supplier’s home country.
  • Mixed Moulds: Mixing moulds (and possibly pollens) causes dilution and degradation and hence loss of potency. Also, because the cross-reactivity is so ill defined, mixed mould skin test results are very unreliable.
    Nevertheless some, including Alternaria, Cladosporium, Aspergillus and Penicillium, have been shown on the skin test and challenge to be potent allergens triggering asthma and rhinitis in susceptible patients. In a group of asthmatics, skin test reactivity to Alternaria was found to be associated with a 200-fold increase in the risk of respiratory arrest.
  • Complicated mixes of unrelated pollens should not be recommended since in the case of a positive reaction it does not indicate which pollen(s) are responsible and, in the case of a negative reaction, it fails to indicate whether the individual pollens at full concentration would give a positive result.
  • Fruits & Vegetables are very unreliable when commercial extracts are used. The shelf life is too short. Much better results are obtained using fresh fruits and vegetables. This should be done in a setting where resuscitation is possible, as anaphylaxis has been reported by this method.

Cockroach Hypersensitivity

Numerous studies in the USA, Asia, Africa and Australia have shown that cockroach is an important indoor aeroallergen and is a significant cause of asthma and rhino conjunctivitis.

Subjects with cockroach-sensitive asthma appear to be a distinct sub-group characterised by chronicity and elevated serum IgE antibody levels with fewer aeroallergen skin sensitivities.

More studies are needed to get a more accurate picture of the relevance of cockroach sensitivity in New Zealand.

Techniques of Skin Prick Testing

Skin Prick Testing

Pricking skin with lancet.

Clean the arm with soap and water or alcohol. The inner aspect of forearm is marked off with a skin-marking pen. The dots can be numbered to correspond to the number of allergens being tested. Dots are usually at least 2cm apart.

Allergens are placed alongside the dots using dropper from allergen vial. A sterile prick lancet is used to make a small prick through the drop and a new lancet is used for each allergen used.

After this, the excess allergen is removed by laying a tissue on the arm (not by wiping). The test is then read at 15 minutes. Positive wheals are those exceeding 3mm in diameter greater than the negative control.

Interpretation of Prick Test

Prick Test

Measuring wheals after 15 minutes.

Reactions are assessed by the degree of erythema and the size of wheal produced. Allowance must be made for any positive response to the glycero-saline control.

There may be confusion if the extent of the reaction is graded using the ‘+’ scale (very few labs still use this old grading). Note that there is a 0+ but no 1+! It is included in 2+. For this reason it is better if the grading is done according to the size of the wheal.

Wheal measurement compared with the old system
0+ = < 4mm
2+ = 5-10mm
3+ =10-15mm
4+ = > 15mm

A positive test is 2mm or more greater than the negative control. However, a skin wheal 6mm or more across is more likely to be clinically relevant.
A wheal > 15mm diameter suggests patient is very sensitive.
A wheal 10 to 15mm diameter suggests patient is moderately sensitive
A wheal 5 to 10mm diameter suggests patient is mildly sensitive.
It is important that these reactions are interpreted in conjunction with the clinical history.

Advantage of Prick Test

The advantage of performing prick tests rather than intradermal skin tests are as follows:

  • Glycerinated stock solution is much more stable than the aqueous dilution used for ID tests.
  • They are easy to carry out and repeat if necessary.
  • They are virtually painless so that young children do not object.
  • The risk of systemic allergy reaction is very low due to a small volume inoculated (0.000003ml is introduced with lancet prick).
  • Even in multi-sensitive patients the whole testing program can be finished in 1 hour.

Clinical Significance

The value of any diagnostic procedure depends upon the knowledge of its interpreter.

To be informative, the skin prick tests must be related to the clinical context of the patient’s history and the physical examination. The selection of the antigens and the administration of tests require experience and knowledge. A skin test may be positive both before the allergy is clinically apparent and years after cessation of symptoms.

The physician must be aware of the many reasons for false-positive and false-negative reactions to properly interpret test results.

Common errors in prick testing

  • Tests too close together (< 2cm)
  • Induction of bleeding, leading possibly to false-positive results
  • Insufficient penetration of skin by lancet leading to false-negative
  • Spreading of allergen solutions during the tests.

Causes of false-positive skin prick tests

  • Irritant reaction
  • Nonspecific enhancement through axon reflex from nearby strong reaction. Place tests at least 2cm apart.

Causes of false-negative skin prick tests

  • Extract of diminished potency (especially foods)
  • Medications modulating allergic reaction
  • Diseases attenuating the skin response, e.g. eczema
  • Decreased reactivity of the skin in infants and elderly patients
  • Too soon after systemic anaphylactic reaction

Use of positive control may over come some false negative results.

Positive skin tests in symptom-free subjects are regarded as evidence of latent or sub-clinical allergy. A positive grass pollen skin test in an asymptomatic subject indicates a 10-fold increase in the risk of hay fever.

It is important not to interpret the results of skin tests without knowledge of the patient’s history. As many atopics have specific IgE antibodies without symptoms. Probably about one third of atopics (with positive skin prick tests) will have symptoms

A skin test is immunologically the most constant and quantitatively reproducible test in vivo. It is not affected by nonspecific hyper-reactivity in the mucous membrane, as are nasal and bronchial provocation tests.

If all tests are negative (except the positive control) the patient is unlikely to have atopic disease. Particular caution should be used when interpreting skin tests for foods. Not only are they much less reliable than tests with inhalant allergens, but also only a fraction of patients with positive food skin tests will react during a food challenge. (1,2) Therefore food allergen avoidance should never be based only on skin test results.

Factors Affecting Skin Tests

Area of the Body

Reactivity to both allergen and histamine varies according to the part of the body. The mid and lower back are more reactive than the forearm. The back as a whole is more reactive than the forearm. The antecubital fossa is the most reactive part of the arm, whereas the wrist is the least reactive. The ulnar side of the arm is more reactive than the radial.

Age

Skin reactions vary according to age. Infants react predominantly with large erythematous flare and a small wheal. Using prick test, a significant wheal is detectable after 3 months of age in most infants tested with either histamine or allergen extracts. (3) The mean wheal size is significantly smaller than later in life. (4) It is therefore possible to perform skin tests to diagnose allergic disorders in infancy, but the size of the wheal is often smaller and the criteria of positivity should always compare the size of the wheal induced by allergen extracts with that elicited by positive control solutions.

Skin test wheals increase in size from infancy to adulthood and then decline after the age of 50. (5) The reactivity to histamine is parallel to that of allergens.

Sex

There is no sex difference in skin test reactivity. Women have the weakest histamine whealing capacity during the first day of the menstrual cycle, but this is clinically insignificant.

Race

The whealing capacity to histamine is significantly greater in healthy non-atopic Blacks with darkly pigmented skin than it is in Whites with light skin pigmentation. (6) Flare measurement is also different. My experience is that this seems to be the case in Polynesians as well.

Circadian Rhythm

Circadian variation of histamine, bradykinin or allergen whealing capacities have been shown. There are clinically insignificant peaks in the late evening and a decreased reactivity in the morning.

Seasonal Variation

Seasonal variations related to specific IGE antibody synthesis have been demonstrated in pollen allergy. Skin sensitivity is increased after the pollen season and then declines until the next season. This is significant in patients with low sensitivity.

A recent study in AAA&I (April 2001) concluded, "Although skin reactivity may be slightly greater to tree pollen during the pollen season, the timing of skin testing is not a critical determinant in patients with pollen allergy"

Pathological Condition

Eczema is known to decrease the skin reactivity to histamine. Peripheral nerve abnormality, like diabetic neuropathy shows a decreased reaction to skin test. Also, in the case of previous systemic anaphylactic reaction, a delay of at least 1 week is preferable before skin testing.

Drugs/Medications

Antihistamines:

The H1-antagonists, which block the capillary effect of histamine, inhibit the wheal-and-flare reaction to histamine allergen and mast cell secretagogue. The duration of this inhibitory effect is related to the half-life of the drug and its metabolites. The duration of the inhibitory activity varies from 3 to 10 days for cetrizine, loratadine and terfenadine to up to 60 days for astemizole. (7) This fact is probably the commonest cause of a false-negative test and again stressing the importance of doing positive controls. In practice, apart from astemizole, 72 hours off antihistamines seems an adequate length of time to wait before skin testing.

Corticosteroids:

Short-term (< 1 week) administration at therapeutic doses in asthmatics does not modify skin prick test. Conversely, long-term steroid treatment does not alter histamine-induced vascular reactivity in skin but affects skin mast cell responses (8 modifies skin texture, therefore making the interpretation of immediate skin tests difficult. It is recommended that low-dose oral corticosteroids (< 15mg of prednisone per day) should not be discontinued, whereas high-dose should be reduced, if possible, before performing skin tests. Application of topical corticosteroids for a period of 1 week reduces both the immediate and late-phase skin reaction induced by allergens. (9)

Intradermal Skin Tests

These are more sensitive than SPT, but they are also much more dangerous. There have been several reports of anaphylaxis following intradermal tests. They are usually indicated for diagnosing some drugs and venom allergy. Intradermal skin testing is not recommended for the evaluation of food allergy.

Scratch tests are no longer recommended.

Provocation — Challenge Testing

The skin tests and RAST test are indirect assays of an allergic state. A positive result only indicates that the individual is sensitized to that allergen, it does not give any information of clinical reactivity. Many patients will still have a positive skin prick test result even after they have clinically outgrown their allergy.

Direct challenge, either by inhalation or ingesting antigens, may be of great diagnostic use. In addition to antigen challenge, the general hyper-responsive state of the airway associated with asthma may be evaluated by exercise or by inhalation of chemicals to which asthmatics are more sensitive than non-asthmatics.

Nonspecific Tests

Exercise

Physical exercise is a major precipitant of bronchial asthma. The diagnosis of asthma can probably be made after 6 to 8 minutes of exercise and pre- and post-pulmonary function testing. In patients with exercise-induced asthma (EIM) 6 to 8 minutes exercise is generally followed by a 20% or greater fall in the FEVI.

Bronchial Challenges

Asthma is characterised by enhanced bronchial hyper-reactivity. This hyper-reactivity can be manifested clinically by the asthmatic adverse response to cold air, cigarette smoke, fumes, weather changes, and other stimuli that have little or no effect on a non-asthmatic patient. In the doctor’s office setting, airway hyper-reactivity can be demonstrated by the patient’s response in a bronchial challenge such as the inhalation of a methacholine solution at a concentration of less than 25 mg/ml is indicative of a positive response.

Specific Tests

Nasal Provocation Tests (NPT)

To date, NPT has been used primarily as a research tool for the investigation of allergic and non-allergic rhinitis. Standardized nasal provocation testing has the potential to become a more frequently used clinical test in the diagnosis of allergic and occupational rhinitis and for determination of the appropriate and focused therapy.

Nasal provocation begins with administration of a diluent solution such as phosphate-buffered saline with 0.4% phenol or normal saline into one or both nostrils using a metered dose delivery device. This challenge will detect nonspecific responses. Over the next 15 minutes sneezes are counted, nasal discharges are collected, and pruritus, rhinnorrhea, nasal blockage, and ocular symptoms are scored. If there are no clinical symptoms or significant changes on rhinomanometric measurements then allergen is deposited into the nose. During allergen deposition the patient should hold their breath to avoid inhaling allergen into lower airways. The dose of allergen is increased at 15-minutes interval until symptoms or signs develop.

Bronchial Challenges

Because skin test results generally correlate well with bronchial provocation tests they are generally not necessary in everyday practice. There may be special instances, however, such as in occupational asthma or in investigative work, when specific challenge is indicated.

Oral Food Challenges

In instances when an adverse food reaction is suspected, an oral challenge can be performed. The challenge can either be open, in which case both the physician and the patient know the content of the ingested substance, or single-blinded, with only the doctor knowing the content of the challenge or double-blind and Placebo-controlled, where neither the patient nor the doctor know the content of the challenge. This Double-blind Placebo-Controlled Food Challenge (DBPCFC) is considered the "gold standard" in diagnosing IgE-mediated (true) food allergy.

Indications for DBPCFC:

  • Research Studies
  • Chronic disorders like asthma and eczema when foods are suspected as triggers
  • Multiple food allergies suspected
  • Situations where patient’s perception may bias accurate symptom assessment (i.e. subjective complaints, such as abdominal pains and headaches)

Patients with histories of life-threatening anaphylaxis should be challenged only when the causative agent cannot be determined conclusively by history, skin and RAST or if you suspect (from tests) that the allergy is "outgrown"

The selection of foods to be tested by oral challenge is determined by history, skin prick tests or RAST results.

Foods implicated by SPT or RAST, but unlikely to provoke food-induced allergic reactions, may be screened with open challenges.

Technique in Food Challenges:

  • Should only be conducted in clinic or hospital setting with resuscitation equipment at hand.
  • Suspected food allergens should be eliminated for 7-14 days before challenge in IgE-mediated disorders and up to 12 weeks in some gastrointestinal disorders.
  • Antihistamines should be stopped for 72 hours and other medications minimized
  • In some asthmatics short courses of steroids may be necessary to get FEV1>70% predicted value
  • Food challenge administered in fasting state
  • The food can be administered whole (masked in infant formulae or pureed) or in a lyophilised preparation contained in an opaque capsule.
  • In suspected IgE-mediated reactions food dose is doubled every 15-60 minutes
  • Once 10g lyophilized food tolerated clinical reactivity can be ruled out
  • Negative blind challenge should always be followed by open feeding under observation
  • In non-Ige-mediated disorders challenge may need to be given over a 2-3 day period

The evaluation of many "delayed" reactions (eg most IgE-negative gastrointestinal allergies) can be conducted safely on an outpatient basis.

In cases when patient’s symptoms are largely subjective, a cause-and-effect relationship is established only after 3 cross-over trials demonstrate exacerbation of symptoms only during allergen ingestion

Non-Food Oral Challenges

Oral challenge can also help diagnose sensitivity to aspirin, sulphites and other drugs, in which the sensitivity is not on an IgE basis. In such circumstances skin testing or RAST testing would be of no use.

Blood Tests

IgE

IgE levels are often elevated in cases of allergic disease but these levels cannot be considered pathogonomic signs of allergy. A normal IgE level does not exclude allergy, while definitely elevated levels may be seen in non-atopic people.

Specific IgE (RAST) and Immuno CAP RAST

The radioallergosorbent test (RAST) measures the amount of IgE that is directed to a specific allergen. RAST tests for particular allergens may be appropriate in those patients who present with a good history of sensitivity to a particular allergen, and yet produce consistently negative skin test results. Skin tests are generally considered to be more sensitive than RAST assay and it is rare though not unknown for a patient to be skin test negative and RAST positive. The usual explanation is that the extracts used for skin testing were defective.

For inhalant allergies, the sensitivity of the RAST system is 60-80% and the specificity is higher than that of the skin prick tests.

A recent study published in April 2001, Vol, 86, No.4 of AAA&I, ‘Precision of Commercial labs ability to classify positive and negative allergen- specific IgE results’, shows that not all commercial labs provide reproducible and accurate results.

The Pharmacia CAP RAST (a modified RAST system) was found to be the best.

Indications for RAST (over skin prick test)

  • Severe generalized eczema.
  • When a patient demonstrates demographism.
  • When a patient is on antihistamines, which for some reason cannot be temporarily discontinued.
  • Patients apprehensive about skin prick test.
  • Patients suspected to be acquisitively sensitive to certain foods

A recent study using Pharmacia CAP-RAST in children with atopic dermatitis demonstrated that quantification of food-specific IgE provided increased positive predictive accuracies for milk, egg, peanut, and fish sensitivity compared to skin prick tests. As shown below a patient with a serum food allergen-specific IgE level in excess of the 95% predictive value may be considered reactive, and an oral food challenge would not be considered necessary. These tests are also useful in predicting when follow-up challenges are likely to be negative (i.e. when patients "outgrow" their food allergy)

CAP-RAST 95% positive predictive values:
(Adapted from Sampsom, H A, J Allergy Clin Immun)

Food 95% PPV Sensitivity Specificity  
  (kUa/l) (%) (%)  
Egg 6 72 90  
Milk 32 51 98  
Peanut 15 73 92  
Fish 20 40 99  

Choice of Allergens

The choice of allergens selected to some extent depends on the age of the patient. The allergic child under 2 should always have IgE to milk, egg, wheat, peanut and soy estimated. In this age group foods rather than inhalant pattern is seen. As the child reaches school age an inhalant pattern begins to appear. By the time the child is a teenager the pattern is usually one of a pure inhalant allergy.

Insect Venom Sensitivities

RAST, ELISA or EAST tests may be necessary to complement skin tests to determine an individual patient sensitivity to bee and/or wasp venom before desensitisation is considered.

Intra-dermal testing is considered to be more diagnostic for venom allergies

The results of positive skin tests alone or RAST are considered sufficient to obtain the Supplementary Pharmaceutical Benefit from the Department of Health.

Complement Levels and C1-Esterase Inhibitor Levels

In a patient presenting with angioedema, if an allergic trigger is not obvious from the history, and especially if there is a family history of angioedema or unexplained abdominal pains, it is worth doing complement levels and C1-esterease inhibitor levels to rule out hereditary angioedema or acquired angioedema.

Patch Testing

Patch testing is the diagnostic test of allergic contact dermatitis and differentiates it from irritant dermatitis. Allergic contact dermatitis is a cell mediated (Type 4) reaction that produces an eczematous reaction initially confined to the site of contact. The cell-mediated response appears 7 to 14 days after initial sensitisation and reactivates within 2 to 5 days of re-exposure. Patch testing is used to identify the sensitising substance. Once identified, strict avoidance is necessary to avoid further skin reaction. The ‘memory’ for the reaction is usually carried by the skin for life.

Clinical Indications:

  • To differentiate allergic contact dermatitis from irritant dermatitis
  • Atopic dermatitis, especially in adults with chronic hand eczema, eyelid eczema or eczema confined to the lips and perioral regions, head and neck regions and feet.
  • Occupational contact dermatitis. The vast majority of occupational skin diseases are caused by contact dermatitis and 90% of this is due to irritation and not sensitisation. This can be important in medico-legal cases. Occupations that carry a high risk of skin irritations include hairdressing, domestic work, floral workers, nursing, mechanics, printers, bar tending and food processing.

Technique

Test doses of allergens are placed under occlusion and left in situ for 48 hours. The test is usually read at 48 hours and again at 72 hours. The precise technique varies from centre to centre. Experience in patch testing is essential if correct interpretation and reliable and reproducible results are to be obtained. All or part of a standard battery can be applied and any other allergen considered relevant for the patient concerned. As mentioned before a careful history is paramount in trying to identify potential allergens.

The antigens are applied to a patch (adhesive tape) and the patch is applied to the upper back. The patches are kept on for 48 hours. Reactions are read and classified as negative, + (weak) erythema only, ++ erythema and vesiculation, +++ strong reaction, erythema vesiculation and oedema. There are commercially available patch test strips that are smaller and easier to apply, but these are much less sensitive than the Finn Chamber method.

sneezing

Preparing for Patch testing
chemicals added to Finn chambers.

sneezing

Strips of Patch test chambers
applied to the back.

Some common Allergens (causing contact dermatitis) used in Patch Testing:

Allergen Sources
Nickel Jewellery
Balsam of Peru Perfumes, citrus fruits
Dichromate Cement, leather, matches
Paraphenylenediamine Hair dyes, clothing
Rubber chemicals Shoes, clothing, gloves
Colophony Sticking plasters
Benzocaine Topical anaesthetics
Neomycin Topical medicaments
Parabens Preservatives in cosmetics, creams
Epoxy resins Glues
Formaldehyde Clothing, cosmetics, paper
Wool alcohol Lanolin, cosmetics, creams

Mast Cell Tryptase Test

Mast cell tryptase is a protease that is found in mast cell granules and secreted upon stimulation of the cell together with histamine and many other mediators. The assay of tryptase offers significant advantages over other methods of monitoring mast cell activation and anaphylaxis because:

  • It can performed on serum samples.
  • It has a long serum half-life.
  • It is more specific than histamine.
  • Levels may be elevated for several hours after the reaction.

Tryptase is released into the circulation after precipitation of systemic anaphylaxis caused by drugs, venom, allergen, allergen immunotherapy and aspirin and may be used to distinguish mast cell-dependant anaphylaxis from other systemic events such as septic shock, cardiogenic shock, or vasovagal reactions.

It should be noted, however, that serum tryptase is rarely shown to rise after food-induced allergic reaction.

The specimen should be taken within 6 hours of a suspected anaphylactic event. This assay is available in Auckland.

Diagnosis of Food Allergy

This is the subject of much confusion, controversy and misconceptions.

Ingestion of foods, commonly fish, shrimps, nuts (especially peanuts), eggs, milk and strawberries may elicit allergic symptoms such as angio-oedema, urticaria, asthma or severe systemic anaphylactic reactions within minutes. These immediate reactions based on Type 1 allergy can be diagnosed from the history and confirmed by RAST or skin testing if necessary.

Food skin prick test and RAST have a very high negative predictive value for immediate hypersensitivity, but a very low positive predictive value (<50% compared to DBPCFC)

A negative prick skin or RAST test predicts with about 97% accuracy that the test food was not the cause of symptoms but only in atopic disorders and where immediate hypersensitivity food reactions are involved. They have no predictive role in other food reactions like food additives.

Both skin and RAST tests measure the same thing. RAST tests have no advantage over skin tests. Overall combining the results of both tests does not increase accuracy.

Food allergen extracts currently available are not standardised and may show instability. Allergen extracts, such as from fruits and legumes are rapidly degraded so that testing with fresh food extracts avoids false negative results. An alternative is the prick-prick test with raw fresh foods. This method is often used in my practice, with strongly positive results after the commercial extracts were negative.

Of children with atopic dermatitis, one third have adverse reactions to foods, of which egg, peanut, cow’s milk, soybean, fish, and wheat are the most common causes. Caution is necessary in patients with anaphylactic reaction to foods. In these patients, skin prick tests should only be done in a specialised clinic/hospital setting.

The ‘gold standard’ for diagnosing food allergy is avoidance and challenge (preferably double-blind Placebo-controlled).

Unproven Tests in Allergy

  • Applied Kinesiology – Muscle Testing
  • Cytotoxic Food Testing
  • Electrodermal skin test – VEGA Test
  • ELISA/ACT
  • Hair Analysis
  • IgG Antibodies to food
  • Iridology
  • Pulse Test

References

  1. Onorato J, et al. Placebo-controlled double-blind food challenge in asthma. J Allergy Clin Immunol 1990;78:1139
  2. Metcalfe DD, Sampson HA. Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. J Allergy Immunol 1990;86:421
  3. Menardo JL, et al. Skin test reactivity in infancy. J Allergy Clin Immunol 1985;75:646
  4. Matheson A, et al. Reactivity of the skin of the newborn infant. Paediatrics 1952;10:181
  5. Skassa-Brociek W, et al. Skin tests reactivity to histamine from infancy to elderly. J Allergy Clin Immunol 1987;80:711
  6. Van Nierkerk CH, Prinsloo AEM. Effect of skin pigmentation on the response to intra-dermal histamine. Int Arch Allergy Appl Immunol 1985;76:73
  7. Tyolahti H, Lahti A. Start and end of the effects of terfinadine and astimazole on histamine induced wheals in human skin. Acta Derm Venerol 1989;69:269
  8. Olson R, et al. Skin reactivity to codeine and histamine during prolonged corticosteroid therapy. J Allergy Clin Immunol 1990;86:153
  9. Anderson M, Pipkorn U. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J Allergy Clin Immunol 1987;79:345
  10. Onorato J, et al. Placebo-controlled double-blind food challenge in asthma. J Allergy Clin Immunol 1990;78:1139
  11. Metcalfe DD, Sampson HA. Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. J Allergy Immunol 1990;86:421
  12. Menardo JL, et al. Skin tests reactivity in infancy. J Allergy Clin Immunol 1985;75:646
  13. Matheson A, et al. Reactivity of the skin of the newborn infant. Paediatrics 1952;10:181
  14. Skassa-Brociek W, et al. Skin test reactivity to histamine from infancy to elderly. J Allergy Clin Immunol 1987;80:711
  15. Van Nierkerk CH, Prinsloo AEM. Effect of skin pigmentation on the response to intra-dermal histamine. Int Arch Allergy Appl Immunol 1985;76:73
  16. Tyolahti H, Lahti A. Start and end of the effects of terfinadine and astimazole on histamine induced wheals in human skin. Acta Derm Venerol 1989;69:269
  17. Olson R, et al. Skin reactivity to codeine and histamine during prolonged corticosteroid therapy. J Allergy Clin Immunol 1990;86:153
  18. Anderson M, Pipkorn U. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J Allergy Clin Immunol 1987;79:345
  19. Szeinbach S, et al. Precision and accuracy of commercial laboratories’ to classify positive and/or negative allergen-specific IgE results

Useful link – JCAAI : Allergy Testing
http://www.jcaai.org/Param/Aller.htm

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