The diagnosis of skin diseases is usually based on the patient's history and clinical presentation.
The interpretation requires experience. Test results should always be interpreted in relation to the patient's symptoms.
Specific IgE antibody tests or skin prick tests are used to investigate IgE-mediated immediate allergy, which predominantly causes respiratory tract symptoms. They are rarely indicated in the diagnosis of skin diseases (e.g. contact urticaria, severe atopic dermatitis in young children and food allergies).
Epicutaneous tests (patch tests) are used to diagnose delayed contact allergy (allergic contact dermatitis).
Skin prick tests (prick-testing)
Investigation of immediate (IgE-mediated) allergy
The patient's skin is pierced with a lancet to introduce the allergen to be studied. Histamine solution is used as a positive control and the diluent used for the allergen extract as a negative control (picture 1).
A characteristic sign of a positive immediate reaction (IgE-mediated sensitisation) is a wheal, usually attended by pruritus, at the site of the skin prick.
The test is read at about 15 minutes when the reaction is usually at its maximum.
The test series should include outdoor and indoor allergens reflecting the geographical region.
For example, the standard series used in Finland includes the following allergens: birch (Betula sp.), timothy (Phleum pratense), meadow fescue (Festuca pratensis), mugwort (Artemisia vulgaris), Cladosporium herbarum -mould, dog, cat, horse and house dust mite (D. pteronyssimus).
The test is usually performed on the arm and therefore topical medications (e.g. glucocorticoids) should not be applied to the arm in the three days before the test.
Antihistamines prevent the occurrence of reactions, and they should therefore be stopped 5 days before testing. Cough medicines (e.g. diphenhydramine), anti-nausea drugs (meclozine, cyclizine) or sleeping pills (doxylamine) may also have an antihistamine effect.
A small amount of a systemic glucocorticoid (less than 20 mg/day prednisone in adults) does not influence the test results.
Specific IgE antibodies
Used like prick tests in the investigation of immediate (IgE-mediated) allergy.
Specific antibodies against allergens are measured in the patient's serum.
Either group tests (usually as screening tests) containing several allergens (e.g. dust analysis), or tests identifying antibodies against single allergens can be used.
The result is reported as the concentration of kilo-units (kU/l). The clinically significant IgE antibody level varies from patient to patient and also depending on the symptom (e.g. respiratory symptom, food allergy) and the used allergen.
Medications used by the patient do not have an impact on the results of specific IgE antibody tests, and the tests are usually more easily available than prick tests.
Indications
Adult atopic dermatitis Atopic Eczema (Atopic Dermatitis) in Adults is not directly linked with IgE-mediated allergies, and on its own it is not an indication for allergy investigations.
In some patients, IgE-mediated allergies (e.g. for food substances, animals, pollen) may worsen atopic dermatitis, in which case carrying out prick testing or measuring IgE antibodies may be indicated. The sensitization must, however, always be interpreted in relation to the patient's symptoms.
Indications in small children (below 1 year) include atopic dermatitis that is either widespread or tends to flare up Atopic Dermatitis in Children: Clinical Picture, Diagnosis and Treatment and has not improved with appropriate topical treatment. In some children below one year of age with severe atopic dermatitis, the underlying cause may be allergy to cow's milk, cereals or eggs, and in such cases allergy investigations (skin prick, specific IgE or challenge tests) may be warranted.
The tests are also used in the diagnostic workup of contact urticaria, protein contact dermatitis and some drug allergies, e.g. allergy to microbial drugs or local anaesthetics.
Interpretation
Skin prick testing and determination of specific IgE antibodies aim to answer two questions:
Has the patient developed IgE-mediated sensitization to an allergen that causes him/her symptoms (e.g. a single food substance or an animal)?
Does the patient have atopic tendency (sensitization to common respiratory allergens)?
A positive test result does not prove a causal relationship with the patient's symptoms. A positive test result alone does not indicate that the patient has a clinically significant, symptomatic allergy; it merely demonstrates that the person has been sensitised to the allergen in question. The test results must always be viewed in relation to the symptoms, and interpretation requires experience.
The wheal diameter (the mean of the longest diameter and the diameter perpendicular to it [D+d]/2) is reported.
The lower limit of a positive reaction is 3 mm, reactions smaller than that are not reported.
The intensity of the reaction in relation to the histamine-induced reaction: the diameter of a significant wheal must be at least half of the diameter of the wheal produced by the histamine control.
At the same time the negative control must be negative.
The standard series includes about 30 chemicals. It covers 70-80% of all contact allergies.
Other test series are available to cover other allergens, e.g., conditioners and preservatives, cosmetics, plastics, glues, chemicals used in hairdressing, dental products, etc.
In special cases, substances supplied by the patient can also be tested.
Various patch test chambers are commercially available. When using the Finn Chamber® system the substances to be tested are incorporated into petroleum jelly or other vehicle substance and placed in 8 mm diameter aluminium chambers. The chambers are attached with acrylic adhesive tape to the skin of the back (upper arms) for 2 days. An allergic reaction is slow to develop and the test areas are usually monitored for 4-5 days.
Antihistamines do not alter the results. Topical glucocorticoids weaken the reactions, but a small amount of systemic glucocorticoids (less than 20 mg/day prednisone in adults) does not affect test results.
Interpretation
Patch tests demonstrate sensitisation to tested allergens.
However, a positive test result does not prove a causal relationship with the patient's skin problem.
Testing is supervised and interpreted by a dermatologist.
Phototesting
The diagnostic workup of photodermatitis Photodermatitis is principally based on the patient's history supported by clinical presentation and targeted laboratory tests. Conditions that need to be excluded: lupus erythematosus and porphyrias (antinuclear antibody and extractable nuclear antigen antibody analysis and a qualitative test of plasma porphyrins). Phototesting is indicated only in special cases.
Phototesting and interpretation are carried out in specialized care.
The skin areas to be tested (back, upper arms) are irradiated with gradually increasing UVB and UVA doses.
The threshold dose for erythema is tested by determining the lowest UV dose that will cause visible erythema (MED = minimal erythema dose). The threshold dose for erythema is reduced in photosensitivity: for example, the threshold for UVA doses needed to provoke MED is often reduced in drug phototoxic reactions.
Solar urticaria responds immediately (within 10-30 minutes), but other types of photodermatitis generally develop within 1-3 days.
Reproduction of the response (photo provocation test) may be indicated in cases of polymorphous light eruption (the most common type of photodermatitis) and discoid lupus erythematosus; the same skin area is irradiated on several consecutive days and monitored for 5-7 days.
Photopatch testing
Used where photoallergic contact dermatitis is suspected Photodermatitis.
Photopatch testing and interpretation are carried out by a dermatologist.
The testing is carried out in the same way as ordinary patch testing but the allergens are applied in duplicate sets. The test strips are removed after 2 days, and one set is irradiated with light (UVA 5-20 J/cm2 ). The results are read 2-5 days after testing started.
Photopatch testing identifies both standard contact allergy and photoallergic contact dermatitis.
A positive reaction only on the irradiated group indicates photoallergic contact dermatitis, and a positive result on both groups indicates standard contact dermatitis.
The cornerstone of diagnosis is the patient's history, challenge testing is rarely needed.
All patients with chronic urticaria or pruritus should be tested for dermographism.
Dermographism
Scratch the skin on the back with a blunt instrument (e.g. a spatula) and wait for 5 minutes. The test result is positive if raised hives develop over the scratched skin areas (pictures 3). Antihistamines prevent the reaction.
Test for cold urticaria
Ice cubes (in a plastic bag) are applied to arm skin for 1-10 minutes. Wheal formation will be noted either whilst the ice cubes are applied or immediately after they are removed.
The exposure time is used to assess the patient's sensitivity to cold. A wheal that develops after 1-2 minutes' exposure indicates that the patient is very sensitive to cold exposure.
In localised cold urticaria, testing must target the symptomatic areas.
Test for heat urticaria
A test tube, or other vessel, with water at +42°C is applied to arm skin. Alternatively, a hand and arm may be immersed in +42°C water for 10 minutes. In heat urticaria, a raised wheal will develop on the exposed area.
Cholinergic urticaria
Sweat production is induced by asking the patient to walk up and down stairs or to run on a treadmill. When clothing is removed, the patient's upper body and flanks will typically reveal large numbers of tiny wheals.
Challenge tests
Open application test
A test for immediate contact allergy
In contact urticaria and protein contact dermatitis, the suspected substance is applied and gently rubbed onto forearm skin. The result is read after 15-20 minutes.
Repeated open application test, ROAT
An application test for delayed contact allergy
The suspected substance is applied twice daily for 7 days on forearm skin. Allergic contact dermatitis will usually develop on the second to fourth day after the start of the test.
Oral challenge test
Performed in order to exclude drug Hypersensitivity to Drugs or food hypersensitivity Food Allergy in Adults. Oral exposure is used to test suspected substances. Whenever possible testing should use a double blind method.
Suspected food allergies in children: if there is a suspicion that the symptoms are caused by nutritionally important foods or if severe symptoms are anticipated, a supervised challenge test is performed after a period of avoidance of approximately two weeks' duration. Challenge tests performed at home are sufficient in the investigation of mild symptoms caused by nutritionally less important food.
Subcutaneous challenge
Indicated, in addition to other tests, in cases of suspected allergy to certain drugs (e.g. local anaesthetics)
A dose of 0.5-1 ml of the suspected allergen is injected subcutaneously, and the result is monitored for 1 hour, if necessary for up to 24 hours.
References
Johansen JD, Aalto-Korte K, Agner T et al. European Society of Contact Dermatitis guideline for diagnostic patch testing - recommendations on best practice. Contact Dermatitis 2015;73(4):195-221. [PubMed]
Johnston GA, Exton LS, Mohd Mustapa MF et al. British Association of Dermatologists' guidelines for the management of contact dermatitis 2017. Br J Dermatol 2017;176(2):317-329. [PubMed]
Mothes-Luksch N, Jordakieva G, Hinterhölzl L et al. Allergy diagnosis from symptoms to molecules, or from molecules to symptoms: a comparative clinical study. World Allergy Organ J 2018;11(1):22. [PubMed]
Griffiths RLM, El-Shanawany T, Jolles SRA et al. Comparison of the Performance of Skin Prick, ImmunoCAP, and ISAC Tests in the Diagnosis of Patients with Allergy. Int Arch Allergy Immunol 2017;172(4):215-223. [PubMed]