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Why did I become Allergic?

by Dr Adrian Morris

Features of allergy and tests available.

The cause of allergy seems to be an entangled web of 3 factors - genetic predisposition, environmental triggers and locally found protein allergens.

Your genetic background plays a major role - we know that a family history of allergies or "Atopy" is highly significant, smaller families with fewer children favour the development of allergy. Males are more likely to develop allergies than females, and prenatal maternal diet and smoking seem to play a role. A number of genes linked to allergy and which carry the "allergy predisposition" have been identified on Chromosomes 5 and 11 - this is the "atopy phenotype".  Obesity also seems to be a risk factor for developing allergies.

The home environment in the first year of life is pivotal. Parental cigarette smoking triggers allergy, Infant diet and early introduction of allergenic foods play a role. Air Pollution has been implicated; early use of day-care institutions, early use of broad spectrum antibiotics and birth just before the spring pollen season all seem to promote allergic sensitisation. Factors that seem to prevent allergies developing include certain viral illnesses such as Hepatitis A and Measles exposure, living on a farm especially livestock farming, intestinal microflora such as Lactobacilli and the use of certain vaccines such as BCG. This highlights the "hygiene theory", whereby children living the so-called "clean western lifestyle" are at greater risk for developing allergy. Recent studies suggest that heavy exposure to dog and cat allergens in the home may actually prevent allergies developing in infants (they suggest having two or more pets in the home!)

And finally, modest exposure to the common aeroallergens and allergenic foods in conjunction with these other factors leads to sensitisation in early life and clinical allergy then develops. Modest early exposure seems to be the key to triggering sensitisation, as evidence now exists for very high allergen exposure during early life having a "protective" effect (for example to cats and dogs). However, minimal exposure during the first year of life is still the recommended "rule of thumb" for allergy prevention.

The Allergic March

The Allergic March is the term used to describe the chronological progression of one clinical manifestation of allergy to the next. Early life allergy under the age of 3 years usually involves eczema and food allergy, this usually resolves as asthma develops in the middle childhood years. As asthma begins to stabilise, allergic rhinitis becomes a common manifestation of allergy in the adolescent years. Asthma often returns at about the age of 40 just as Hayfever is settling down.

The Natural History of IgE

Specific Allergy related Immunoglobulin E (IgE) is the antibody found in our blood and tissues which mediates allergy. Allergy sufferers have raised levels of IgE and it can be measured in the blood by RAST tests and also with Skin Prick Tests.  The role of IgG and IgA in allergic sensitisation is at present uncertain.

Specific types of allergy tend to be age related. Allergy to Milk and Egg White is common in those under 3 years of age, and tends to naturally resolve with time. Peanut and Fish allergy tends to persist throughout life and levels of specific peanut IgE remain high in peanut allergic people. Just as respiratory allergies develop later, we also see parallel rises in Specific IgE to Tree and Grass Pollen rise in later childhood to peak in early adolescence.

What allergy confirmatory tests are available to us?

We can perform Skin Prick tests for common Inhalant and Food allergens or measure Total IgE in the blood. Then there are the Phadiatop inhalant screen, Food Allergy screens and over 450 individual RAST tests available. We can measure another allergy cell, the eosinophil in the blood, in the sputum and also in nasal samples. Lung function tests are handy in asthma diagnosis, and include Peak Flow (PF), Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity (FVC).  We can measure Nitric Oxide (NO) in exhaled air as a marker of allergic inflammation.

Another way of determining if someone is allergic to a substance, is to directly challenge him or her with that substance. Provocation tests are the Gold Standard in Allergy but can only practically be done in the hospital environment as they can be dangerous and trigger severe allergic reactions. These include bronchial and nasal challenges with the suspected allergen and Double Blind Placebo Controlled Food Challenge tests for suspected food allergy.

Skin Prick Testing.

This is one of the oldest allergy tests and is the cornerstone of primary allergy diagnosis. It was first performed by Dr Charles Blackley who was a Manchester GP and Homeopath, to identify grass pollen as the cause for Hayfever in 1865. This test is still the most highly sensitive allergy test available. It tests for specific IgE antibodies to inhalants including Housedust mite, pollen, cat and dog dander but can also be used to test for food, venom and drug allergy. A positive result is a typical raised wheal and red flare reaction on the skin. It is used to either diagnose or exclude a specific IgE mediated cause for the patientís allergic symptoms.

The newer ALK Abello and Diagenics (Allergopharma) glycerol based extracts are highly standardised and accurate. They are cheap, safe and simple to perform if someone in your surgery has been trained to use them and the results are then immediately available. These tests are useful to demonstrate to the patient the acute inflammatory nature of allergy. They are particularly accurate in diagnosing the cause of asthma and rhinitis. Other international manufacturers of reputable skin prick test reagents include Allergy Therapeutics, Stallergens, Allergopharma and Dome Hollister.

Prick and Prick tests for food allergy are performed using a drop of the fresh food.  The skin is pricked through the drop of fresh extract ( for example in diagnosing allergy to apple).

How are the tests performed?

We use standardised glycerinated extracts of the various allergen extracts such as housedust mite, cat and dog dander, tree, grass and weed pollen and fungal spores. There is also a negative saline and positive histamine control (for reference).

A drop of each extract is placed on the inner aspect of the forearm about 3cm apart and we prick through the drop at 90 degrees to the skin using a specially modified lancet. Using firm controlled pressure and making sure not to draw blood.

The reactions are read after 15 to 20 minutes and a positive reaction should have at least 3mm of raised wheal. All oral antihistamines should be avoided for 2 - 3 days before hand, as they suppress skin reactivity. The kit has a six-month shelf life and should be stored in a refrigerator.

What allergy-confirming blood tests are available?

There is the original old Total serum IgE blood test, which has been superseded by the newer multi-allergen screening tests. The inhalant allergy screen is called a ImmunoCAP Phadiatop, then there are various ImmunoCAP food allergy screening panels such as the fx5 for common paediatric food allergens, fx1 for nuts, fx2 for seafoodís and fx3 for cereals.

There are over 450 individual RASTs available for everything from sheep dander to sesame seeds. These are now called Immunocap RAST tests by Phadia(UK).

Total serum IgE in blood as an allergy test

Total Serum IgE was the original screening test for allergy, but has been superseded by newer more specific tests. However a Total IgE level exceeding 100kU/l is highly suggestive of atopy in adults. Total IgE has a good predictive values in children under 3 years of age and may be used as a screening test in this group. We used to measure Total Cord IgE on newborn babies umbilical cord blood as a predictor of allergy, but this isnít an accurate parameter and is no longer recommended.

Remember that Total IgE may also be raised in parasitic infections, immune diseases,cigarette smokers, with alcohol consumption and in certain cancers. It is not 100% specific to allergy. Total IgE levels depend on the size of the organ affected with allergies - being relatively low in nose allergy, but very high in extensive skin allergy such as eczema. Levels naturally increase from infancy to adolescence when they plateau and then slowly decrease with old age. There is a seasonal variation in Total IgE with levels peaking in spring for pollen allergic individuals.

The Phadiatop Inhalant allergy screen

The Phadiatop (which stands for Phadia Differential Atopy Test) is a multi-allergen inhalant allergy screening test - very useful for assessing if inhalant allergy is present in conditions such as asthma and rhinitis. It doesnít tell us which individual allergens are implicated but rather whether there is respiratory allergy or not.

The screening panel has extracts of Housedust Mite, Cat and Dog dander, Mould spores, Tree Grass and Weed Pollen and can be adapted to include locally implicated aero-allergens such as Cockroach.

Blood Tests for Paediatric Food Allergy

The fx5 food allergy screen

The fx5 is the common Paediatric Food Allergy screening test that includes the commonest 6 implicated allergy-provoking foods. These are Cows Milk Protein, Hens Egg white, Wheat, codfish, Peanut and Soya bean. These foods account for 90% of IgE mediated food allergy in children. The test is therefore a useful screening test in children when no individual food is obviously implicated or when multiple food allergies are suspected

fx1 Nut Allergy Screen

In older children and adults, nut allergy and anaphylaxis is an ever-increasing problem. The fx1 is a very useful screen for nut and peanut allergy and the screening panel includes Peanut, Hazelnut, Brazil nut, Almond and Coconut. In clinical practice, Peanut and Brazilnut account for most nut allergies but there is a considerable amount of cross-reactivity between the diverse botanical nut families.

 

"Pseudo-allergic Reactions"

Not all adverse food reactions are IgE mediated.

Reactions to food additives such as Colourants (for example the azo-dye tartrazine), Preservatives (such as sulphites, benzoate's and anti-oxidants) and Flavourings (such as MSG and Aspartame) are not IgE mediated, their mechanism is largely unknown. Vaso-active amines such as histamine, serotonin and tyramine can occur naturally in food and precipitate pseudo-allergic reactions as can salicylate found in spices and fruit skins. Certain drugs are known to directly trigger histamine release from mast cells without IgE and these include aspirin, opiates, radiocontrast, dextran and Local anaesthetics.  The Cellular Allergen Stimulation Test (CAST) seems to have a good diagnostic predictability for food additive, drug and colorant intolerance.

Then we get Physical Urticariaís - where a stimulus such as pressure, heat, sun and cold can cause histamine release into the skin. Dermatographism (raised wheals after firm rubbing of the skin) is a well-documented harmless example of Pressure Urticaria.

Identifying the allergen is important!

Allergy Management is greatly helped by identifying the cause for the allergic symptoms. Once the triggering allergen has been identified, we can then institute avoidance measures and try to remove the allergen from the environment. This will reduce symptoms. In addition, symptom control may be attained with the aid of preventer and reliever medications. Desensitisation Immunotherapy or "Allergy Shots" using allergen extracts are also an increasingly attractive treatment option and is the only possible method for curing a specific allergy

 

Copyright Dr Adrian Morris    Find out more about the Surrey Allergy Clinic

November 2007

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