Everything you ever wanted to know about allergies

About 50 million Americans are estimated to have allergies of some kind, approximately 1 in 5 people.  This includes indoor or outdoor allergies, food, medication, latex, insect sting, skin and eye allergies.  All demographics have shown increases since the early 1980s.  Allergy is the fifth most frequent chronic disease in all US age groups, except in children, where it is third most common. 

The most common allergies are environmental, such as pollens, mold spores, dust mites, or animal dander.  Skin allergies, such as eczema and urticaria, are usually triggered by poison ivy and other plants.  Latex allergy is seen in 4% of allergy sufferers, affecting 10% of healthcare workers.  4% of allergy patients have insect allergies (including bee/wasp stings, ant bites, cockroach and dust mites.)  4% have only eye allergies, from the same environmental triggers previously mentioned.

6% of children and 4% of adults in North America have food allergies.  It is the leading cause of anaphylaxis, with 200 deaths in the US every year due to food allergies.  (This figure excludes non-IgE mediated food intolerances, like lactose intolerance, histamine sensitivity, etc.)

Oral allergy syndrome is a mild allergic presentation, causing tingling and itching of mouth and throat.  It is caused by consumption of fresh fruits and vegetables in individuals who are allergic to pollens, which are crossreactive.  People allergic to ragweed may get symptoms from eating bananas or melons, which people allergic to birch may get symptoms from eating carrots, celery or apple.  In these instances, the proteins responsible can be degraded with heat, so these foods can be eaten if cooked.  Allergy skin tests are generally negative to the commercially prepared food extracts but positive to the fresh food.  Progression to systemic symptoms is very rare in oral allergy syndrome.

Allergies have a significant impact on the economy.  They cause more than 17 million office visits, with seasonal allergies responsible for more than half of these.  Food allergies cause 30,000 visits to the emergency room every year.  Latex allergy is responsible for over 200 cases of anaphylaxis a year.  The annual cost of allergies is estimated to be around $14.5 billion, with about 85% of that figure being direct costs (copays, medications, etc) and the remainder being indirect (missed work or school, etc.)

Approximately 400 Americans die each year due to anaphylaxis from penicillin.  Over 200 deaths each year are from food allergies; approximately 100 are from insect allergies; and about 10 from latex allergy.

There are currently two major forms of allergy testing: skin prick testing, in which an allergen in put into the skin and watched for an allergic response; and RAST testing, which detects circulating serum IgE specific to a particular allergen.  Both of these tests depend on the presence of allergen-specific antibodies for a positive result.   

In skin prick testing (SPT), the allergen is introduced into the skin.  Local IgE specific to the allergen binds to mast cells, which degranulate, releasing histamine and other mediators.  This produces a “wheal and flare” response that can be quantitated based upon the size of the reaction. 

IgE serum testing is important for people who have eczema, urticaria, dermatographism, mast cell disease or who take antihistamines and cannot stop therapy.  It is less sensitive and less specific than skin prick testing.  This means that if negative, you still might have the allergy, and if it is positive, you might not have it.  Cut off levels for what constitutes a significant amount of allergen are not uniformly agreed upon.  Low levels of specific IgE antibodies are often detected, with doubtful clinical significance.  In many cases, these results are confusing rather than confirmatory. 

There is another type of skin test called “intradermal testing,” which is more sensitive and less specific than SPT.  The allergen is placed deeper into the skin than in skin prick testing.  However, it is associated with serious systemic allergic reactions, including fatal anaphylaxis in some cases.  It is used primarily to test for Hymenoptera venom and medications.

If the SPT for inhalant allergies is positive, you are truly allergic 70-95% of the time (depending on the allergen.) If negative, you are truly not allergic 80-97% of the time. 

SPT is much less reliable for food allergies.  If positive, you have the allergy anywhere from 30-90% of the time.  If negative, you are not allergic only 20-60%. 

Regarding medications, a positive SPT makes the allergy probable, but a negative SPT does not exclude it.  Penicillin is a notable exception.  In 98.5% of patients with negative SPT, no type I allergic response was observed upon challenge.  The remaining 1.5% of patients had mild reactions.

Let’s look at how the results from serum IgE (RAST test) and skin prick test (SPT) line up.

When RAST positive, SPT is positive 80-100% of the time, depending on the antigen.  When SPT is positive, RAST is positive 16.3-50% of the time.  When RAST is negative, SPT is positive 48.5-69.6% of the time.  When SPT is negative, RAST is positive up to only 5.6% of the time.

The discrepancies between the two methods occur for multiple reasons.  The first is that SPT mimics the natural allergic response in the body, while RAST measures the amount of free IgE antibodies, which does not reflect IgE that is bound to cells.  Another large reason for difference is the quality of allergen extracts.  Cross reactivity, in which another allergen of similar shape is detected, is a problem.  These tests currently do not distinguish between the portion of a substance that is allergenic and that that is not.  Also, several medications can affect the efficacy of skin testing, some obvious (antihistamines) and some not (some antidepressants.)  Patient compliance with stopping these medications is variable, and the time of abstinence needed for a reliable test is sometimes unclear.

There are also non-IgE mediated mechanisms for allergy, though they are much less common.  There is a mechanism for cell mediated allergy, in which T cells are activated directly by the allergen, causing inflammation.  This usually affects the GI tract and skin, and is the mechanism for enterocolitis.  Some disorders are mediated by both IgE and T cell response, like eosinophilic esophagitis.  And, of course, people with mast cell disease frequently react to substances for which they do not have a true IgE allergy due to the unusual mast cell physiology in these people. 

People with allergies/sensitivities due to a non-IgE mechanism (like celiac disease, enterocolitis, mast cell disease) may have negative skin and RAST tests, but fail an exposure test.  Sometimes, these people also have an antigen-specific IgE to the offending substance, but not for all substances. 

If a person tests positive for antibody to an allergen, they are considered “sensitized” to the allergen.  However, presence of these specific antibodies does not always mean that the patient is clinically allergic.

In a University of Manchester study, 79 children with positive skin and blood tests for peanut allergy were food challenged.  60 were found to not be allergic.  These results confirmed results previously seen in studies done at John’s Hopkins and Sydney Children’s. 

In another study, kids who had positive IgE RAST levels for the relevant allergens who were food challenged, 45% had no true allergy to milk; 57% to egg; 59% to peanut; 67% to wheat; and 72% to soy.

In recent years, the use of IgG antibodies for diagnosing food allergies has been marketed extensively.  The use of these tests has become problematic in many communities, notably in Canada, where position statements were issued indicating these tests have no diagnostic value.  The only instance in which food-specific IgG is considered diagnostic is celiac patients who are IgA deficient, and who therefore cannot be accurately diagnosed used the traditional test. 

There is increasing evidence that allergen specific IgG4 is a result of action by T cells to induce immunologic tolerance after prolonged exposure.  This means that sometimes when your body is exposed to a food regularly for a long time, your T cells tell your body that this is a safe food.  It makes an antibody to remember this fact.  The presence of food specific IgG is the result of exposure to and tolerance of that food.  Food specific IgG is found in a large percentage of the healthy population.  Furthermore, there is no correlation between food specific IgG and IgE. 

If you suspect food allergy, food diaries and elimination diets can be helpful in identifying the problem.  Due to the overdiagnosis of food allergies by providers, as well as self-diagnosis by patients, over 20% of adults and children in the US change their diets due to a food allergy that may or may not be real. 

Skin prick testing is the most reliable way to test for allergies.  In the absence of this test, RAST tests can give some answers.  However, the definitive way to diagnose allergies is through exposure challenge.  Positive skin prick tests and RAST tests do not always translate to clinical allergies.  There are rare cases of non-IgE mediated allergies/sensitivities, in which a patient will test RAST and SPT negative, but fail exposure.