Allergy Conditions

Skin – Laboratory Investigation of Skin Allergies

Written by Prof. P.C. Potter

The skin, with its rich vascular supply common connective tissue mast cells and contact with the external environment, is a target for many allergic disease processes through exposure to allergens via the cutaneous route, or via the oral or injected routes ¹.

Classical allergic Type I hypersensitivity diseases involving the skin include acute systemic allergic urticaria, contact allergic urticaria, the oral allergic syndrome, atopic dermatitis and cutaneous allergic responses to drugs, foods and insect venoms. The skin may also be involved in delayed hypersensitivity reactions of the Gel & Coombs type II, III and IV, as part of autoimmune and infective processes. This article will focus on the use of the laboratory to investigate Type I reactions.

A. History: The Key

Laboratory investigations of allergic diseases should not be embarked upon without a detailed clinical history and a working clinical diagnosis². Some laboratory allergy tests are highly sensitive, and confirmation of an allergy using a laboratory test will often be straightforward and cost effective, if the test is performed selectively with due regard to the history. The practice of blind screening for possible allergies using large panels of allergens is expensive and unrewarding. Properly selected, laboratory confirmation of an allergy is specific, safe for the patient and provides a quantitative level for specific IgE which may be important for follow up purposes.

The history should in particular take into consideration the patients family history, geographical location, a full description of the patient’s symptoms, dietary preference including foods, drug ingestion (includes over the counter medicines) hobbies, work, pets and travel. The history should be followed by a thorough clinical examination.

Laboratory investigation of the allergic patient may include the following:

determination of the level of patient’s environmental allergens, (eg. housedust mite, cockroaches, moulds), using ELISA tests, confirmation that the patient is atopic, identification of specific allergens causing the symptoms and monitoring the effects of treatment and allergen avoidance on the inflammatory response.

B. Identification of Atopy

B. (a) New borns

The family history is the most useful predictor of future allergic disease in young infants. A Cord blood IgE level of greater than 0.7 ku/l is associated with an increased risk of allergic disease. Although specificity is high, its sensitivity even in Caucasians is only of the order of 42%.

New borns with an elevated cord IgE and a family history of atopy are candidates for the institution of measures which will prevent or postpone the onset of atopic dermatitis and food allergy in the first few years of life. These include breast feeding, delayed introduction of solid foods, avoidance of cows milk products and strict environmental avoidance of housedust mites³.

B. (b) In children and adults

The best screen for atopy over the age of 2 is the Phadiatop CAP RAST. This test will detect specific IgE in the patients serum to a panel of common inhaled allergens (eg. housedust mites, grass pollen, trees, mould, dog and cats). Although useful for patients with inhaled allergies, it is less useful in dermatological diseases where food allergens play a more important pathogenic role.

For small children with atopic dermatitis, the Fx5e CAP food allergy screen is extremely useful. This test detects specific IgE to the common foods (eg. milk, egg, peanut, wheat, fish, soya) which are known to play a role in the disease process. In children less than 2 years the Fx5e is particularly useful. Unlike total IgE, the Phadiatop test is not influenced by parasite infestation.

C. Total Serum IgE

Total serum IgE is usually markedly elevated in children with atopic dermatitis, particularly in these with severe disease. When the total serum IgE is markedly elevated, specific IgE RASTs may also be elevated, but the clinical significance of elevated allergen specific IgE in these cases is best evaluated by an allergist. This will involve elimination – challenge testing when food RASTs are positive ⁴ and requires a knowledge of food families and immunological cross reactions and relationships.

It is incorrect to assume that a patient is clinically allergic to all the positive RASTs without clinical evaluation by elimination challenge. The positive RAST in this context identifies a candidate food for specific evaluation. A negative RAST has a much better predictive value.

A total serum IgE is a useful determination when the Phadiatop test and Fx5e is negative but the clinical presentation still suggests allergy.

Children with atypical facies, eczema and recurrent deep seated cutaneous infections, neutrophil dysfunction and lymphocyte dysfunction should be investigated for the hyper IgE syndrome. In these patients the IgE level often exceed 20,000 ku/l and they typically have elevated specific IgE to Staphylococcus aureus.

D. Allergen Specific IgE

Allergen specific IgE is conveniently determined by the Immuno CAP RAST test, available in 90% of laboratories around South Africa. RASTs are available for over 420 allergens, of which 235 are for routine diagnostic use and 185 allergens are available as part of a special allergen service ².

Since the range of allergens is so large, testing must be selective and based on history of exposure knowledge of allergen cross reactivity and allergen families and candidates allergens relevant to the patient under investigation.

“Routine” allergens of importance in skin diseases include food allergens, housedust mite, animal danders, drugs, chemicals (eg. latex) occupational allergens and parasites.

Specific allergy testing is particularly useful in the diagnosis of the cause of acute intermittent urticaria where in 20-30% of cases a specific allergen can be identified (usually a food allergen). Specific IgE testing is also useful for the identification of the allergen responsible for the oral allergy syndrome, particularly for nuts or fish or egg, since these are stable allergens. CAP RASTs are less sensitive when the allergen is a fresh fruit (eg, kiwi, avocado, peach or melon). Skin prick testing is more sensitive for unstable allergens such as fruits, vegetables and certain plants.

The sensitivity and specificity of CAP RAST testing is variable depending on the chemical nature and composition of the allergen being tested. Thus for stable food allergens eg. for cod fish, peanut, egg and shrimps, CAP RASTs are highly sensitive.

For drugs eg. Penicillin, Cephalosporins and Sulphonomides the CAP RAST has a sensitivity below 50%. However even when the sensitivity is low the specificity of the CAP RAST is always high (80-90%). The Latex CAP RAST has a sensitivity of between 70-80% and is a safe test for patients with suspected Latex allergy.

E. Mixed Allergen Tests

In clinical practice, where the history is unclear or bizarre, patients may be reacting to a group of allergens or to cross-reacting allergens. For example patients with Latex allergy may also react to avocado, bananas and chestnuts. This is because there are common or cross-reacting biological elements in these somewhat unrelated foods.

Mixed allergen tests have been developed to enable the practitioner to screen cost effectively for the presence of specific IgE to groups of similar allergens e.g. fish mixes (Fx2), spice mixes (Fx70, Fx71, Fx72) or grain mixes (Fx3). If the mixed allergen test is positive specific CAP RASTs of the component allergens will identify the culprit.

F. Eosinophilia and Eosinophilic Cationic Protein

An Eosinophilia is a characteristic in patients with allergic skin disease e.g. eczema, drug induced urticaria. Eosinophil counts may decrease as the patients go into remission or are removed from the allergen responsible for their symptoms of if systemic steroids are used in their treatment.

Recently the determination of eosinophilic cationic protein (ECP) has become available as an ancillary test for the monitoring of allergic inflammation. ECP measures the level of activation of eosinophils by cytokines. Although a place for this marker is clearly positioned for the monitoring of steroid dependant asthmatic subjects, its role in the day to day management of patients with skin disorders is still being defined⁵.

G. Serum Tryptase

Tryptase is secreted exclusively by MAST cells. Tryptase is not normally detectable in the serum of healthy or allergic individuals. In situation where there has been massive MAST cell activation eg. Anaphylaxis or mastocytosis, the determination of tryptase levels may have diagnostic implications. Tryptase is stable and may even be determined on post mortem serum (up to 24 hours) if anaphylaxis is suspected as the cause of death.

H. Autoantibodies to the Ige Receptor

Certain patients with unrelenting chronic urticaria who are unresponsive to conventional treatment with H1 and H2 blockers may have an auto-immune aetiology, via IgG auto antibodies to the IgE receptor on Mast cells or basophils. Auto antibodies are determined in the laboratory by incubating the patients serum with sensitised basophils from control allergic subjects and determining histamine release. These patients may respond to steroids or plasmaphoresis.

I. Other Laboratory Investigations

The investigations enumerated above have
focussed on screening for Atopy, the demonstration of specific IgE, the determination of Mast cell Tryptase or Eosinophil activation products (ECP) and the determination of environmental allergens (eg. Housedust mite ELISA).

In some patients with unusual or more complex allergic manifestations other tests may be required. These patients should have a full blood count, differential count, ESR or C-reative Protein. In these patients with recurrent infections, neutrophil phagocytosis and chemotaxis, Immunoglobulin A and Immunoglobulin G subclasses should be determined.

In allergic patients with joint involvement or renal involvement an auto immune laboratory work up should be performed and in these patients with unusual swellings, complement CH50 and C1 esterase inhibitor levels should be determined. In patients with drug allergy, liver function tests should be performed.

Urinary histamine determination may be useful for the investigation of patients with mastocytosis or unexplained intermittent urticarial or flushing syndromes ⁶, particularly to distinguish these from other syndromes eg. the Carcinoid syndrome.

Thus with considered and selective use the laboratory can greatly assist the dermatologist or allergist in the diagnosis, management and further monitoring of the patient with allergic disease of the skin.

References

Potter PC. Allergy and the Skin. Diseases of the skin. Vol 8 (5), 5-6, 1994.

Potter PC, Buys C. Investigating the Allergic patient. “The ALLSA Handbook of Practical Allergy”, Creda Press 1st Ed, Potter PC, Lee S. Chapter 1, 1-16, 1994.

Hide DW. The Isle of Wight Study, an approach to Allergy Prevention. Paediatric Allergy Immunol 5 (Suppl) 1, 61-64, 1994.

Potter PC. Diagnosis and Management of Food Allergy. C.M.E./VMO, Vol 12 No 1, 51-56, 1994.

Potter PC. Clinical Applications for ECP monitoring in asthma. Current Allergy and Clinical Immunology. Vol 8 no 3, 305, 1995.

Potter PC. Urticaria. Specialist Medicine. vol XVII (9) 16-24, 1995.