Allergies, Causes and Allergy Testing
The cause of allergy seems to be an entangled web of many factors. Genetic predisposition, environmental triggers and local protein allergens seem most important.
by Dr Adrian Morris
Features of allergy and tests available
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 hypothesis”, 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!). Vitamin D deficiency has also recently been implicated as an allergy trigger.
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 (first 6 months) having a “protective” effect (for example to cats and dogs). However, minimal allergen exposure during the first year of life is still the recommended “rule of thumb” for allergy prevention.
Factors that seem to reduce the likelihood of developing allergies include:
- A home with 2 or more older siblings living in close proximity (germ swapping).
- Pet ownership (especially dogs & early exposure to animals on farms)
- Exposure to parasite or worm infections (IgE was designed to eradicate worms).
- Exclusive breastfeeding for first 4 months of life (providing immune protection).
- Early introduction of probiotic bifidobacteria bacteria to bowel (acidophilus GG promotes gut immunity)
- Micro-bacteria in spoilt food and drinking water
- Dietary anti-oxidants, folate, fish oils and vitamins (such as Beta carotene)
Factors that seem to promote allergic sensitisation include:
- Lack of older siblings (who carry germs that switch off allergies)
- Advancing parental age (aging genes predispose to allergy)
- Birth by Caesarian section (lacks exposure to “protective” vagina bacteria).
- Sterile Westernised homes (no germs to stimulate the immune system)
- Predominantly sterile indoor environment (no exposure to dirt)
- No household pets (faecal endotoxins & germs switch off allergies)
- Early use of paracetamol and broad spectrum antibiotics (alter immune responses)
- Lack sun exposure (lack of Vitamin D effects genes)
- Obesity and sedentary lifestyle (under-developed lungs cause asthma).
- Parental indoor smoking (maternal during pregnancy and infancy).
- Withholding of potentially allergenic foods such as peanut and egg exposure in early infancy (exposure from 4 months is better than 12 months).
- Diesel exhaust particles (make aero-allergens more potent and carry them deaper into airways)
Reference: Tan T, Ellis JA, Saffery R, Allen KJ. The role of genetics and environment in the rise of childhood food allergy. Clinical and Experimental Allergy 2012 (42) 20-29
The Allergic March
The Allergy March is the term used to describe the chronological and predictable 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.
Immunoglobulin E (IgE) is a universal marker for allergy testing
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 on allergy testing the blood by RAST tests and also with Skin Prick Tests. The role, if any for IgG and IgA as indicators of allergic sensitisation or intolerance is at best uncertain.
Specific types of allergy tend to be age related. Allergy to Cow’s Milk and Hen’s Egg White is common in those under 3 years of age, and tends to naturally resolve with time. Peanut, Nut 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 which rise in later childhood and peak in early adolescence.
What reliable allergy tests are available?
We can perform Skin Prick allergy testing 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 Allergy 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 patient’s allergic symptoms.
The newer ALK Abello, Stallergenes and 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 allergy 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.
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 skin prick 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 allergic 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 accurate allergy blood tests are available?
There is the original old Total serum IgE blood allergy 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 seafood’s 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 indicator.
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 allergy in adults. Total IgE allergy testing 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 isn’t 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 blood 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 doesn’t 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.
Allergy Tests for Food Allergy in Children
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 allergy test 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 identified on allergy testing but there is a considerable amount of cross-reactivity between the diverse botanical nut families. Peanut and nut allergen component tests are also available (Ara h2 etc)
“Pseudo-allergic” or Anaphylactoid 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 and nitrate) 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 allergy testing in food additive, drug and colorant intolerance.
Then we get Physical Urticaria’s – 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.
Confirming 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.