Specific IgE testing: objective laboratory evidence supports allergy diagnosis and treatment

Medical Laboratory Observer, March, 2006 by Lee R. Choo-Kang

CONTINUING EDUCATION

To earn CEUs, see test on page 20.

LEARNING OBJECTIVES

Upon completion of this article, the reader will be able to:

1. Explain how specific IgE blood testing allows primary-care physicians to diagnose and manage allergic diseases in children.

2. Compare specific IgE blood testing--including its methodology, sensitivity, and specificity--with skin testing.

3. Explain how the objective evidence obtained from specific IgE testing contributes to accurate diagnosis and appropriate management of allergic disease.

4. Describe the typical progression of allergic diseases (i.e., the Allergy March).

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Two-and-a-half-year-old Mary is being seen by her pediatrician for a persistent cough. It is February and her parents describe a frequent runny nose, nasal congestion, and cough for the past four months. Mary was the product of an uncomplicated full-term pregnancy. She seemed healthy over her first year of life except for eczema, which has gotten better lately. Since entering daycare last winter, she had an episode of bronchiolitis but did well over the summer. On examination, Mary had nasal drainage and swollen turbinates, as well as bilateral wheezing. Mary's mother reports that she takes over-the-counter medication for allergic rhinitis and wonders if her daughter is developing a similar problem.

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As the prevalence of asthma and atopic disease increases, (1) primary-care clinicians are seeing more young patients for respiratory disease that may have an allergic component. Clinical manifestations of IgE-mediated disease correspond to age. Eczema and gastrointestinal symptoms secondary to food allergy are often the first clinical manifestations of atopy in an infant or young child. As the atopic child grows, he is more likely to present with recurrent and often chronic upper and lower respiratory illnesses. It has been shown that children sensitized to foods at an early age become sensitized to aeroallergens later, (2) and they have a higher risk of developing asthma (3,4) than other children. Yet, without objective diagnostic testing, it is very difficult to differentiate allergic from non-allergic disease on the basis of symptoms, family history, and physical examination alone. In one study, specialists' ability to predict allergic sensitization without diagnostic testing rarely exceeded 50%. (5)

The evolution of specific IgE testing

Two types of tests--in vivo skin-prick testing and in vitro blood testing--have been used to confirm the presence of allergen-specific IgE antibodies in patients with suspected allergy. IgE antibodies are a special class of immunoglobulins that are produced by the immune system in response to antigens. Once secreted by specially programmed B-lymphocytes, IgE circulates in the bloodstream until it becomes attached to the surface membranes of mast cells and basophils present in the epithelial surfaces of the body, such as the respiratory and gastrointestinal tracts and the skin. Upon re-exposure, some allergens cross-link the membrane-bound corresponding specific IgE and trigger the release of several inflammatory mediators including histamine, leukotrienes, prostaglandins, and proteases, thereby producing the familiar signs and symptoms of allergies. (6)

Before the introduction of radioallergosorbent (RAST) blood tests in the 1970s, skin-prick testing was the only method of confirming IgE-mediated disease. In skin testing, skin pricks expose small drops of allergen to reactive skin cells. Positive (histamine) and negative (saline) controls are also used. Sensitized patients will develop a wheal-and-flare reaction within 15 minutes. Results of skin testing are reported subjectively on a number scale, or the wheal diameter measured. (7) Since skin-prick testing depends on the complex interactions among IgE antibodies, immune cells, and the skin, patients must stop taking antihistamines and tricyclic antidepressants (due to their antihistamine properties) seven to 14 days before skin testing. As a consequence of the small but potential risk for anaphylaxis following skin testing, patients should preferably not be taking beta-agonists or monoamine oxidase inhibitors. Skin testing is also contraindicated in pregnant women and patients with unstable asthma. Usually performed by allergists, skin testing requires trained staff, specialized materials, and the ability to manage possibly serious side effects. Medical laboratory personnel were rarely involved in skin-prick testing, unless they prepared the antigens used for skin testing or immunotherapy. The advent of blood-testing technology has moved specific IgE evaluation into the medical laboratory.

First-generation RAST tests yielded a high number of false-negative results and were considered unreliable by allergists and primary-care clinicians. (8) This perception reinforced the commonly held view that skin testing represented the gold standard for specific IgE testing due to its greater sensitivity. A modified RAST assay was introduced in the late 1970s and is still used by some laboratories today. Its sensitivity was increased by lowering cutoff values, doubling the sample volume per test, and increasing the serum incubation to overnight rather than just three hours. Unfortunately, however, the likelihood of false-positives increased, and the results were mostly qualitative. A third generation of assays, introduced in the late 1980s and early 1990s, had improved sensitivity and improved reproducibility due to automation and use of monoclonal antibodies. And for test methods utilizing calibrators directly tied to the World Health Organization Reference Preparation for IgE, these assays delivered the first truly quantitative measurements of IgE.