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



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continuing education
 or adult education

Any form of learning provided for adults. In the U.S. the University of Wisconsin was the first academic institution to offer such programs (1904).
 

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).

**********

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 runny nose Vox populi → medtalk Rhinorrhea , nasal congestion nasal congestion ENT Difficulty in nasal breathing, due to an ↑ vascular thickness of nasal mucosa. See Nasal stuffiness. , 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 Bronchiolitis Definition

Bronchiolitis is an acute viral infection of the small air passages of the lungs called the bronchioles.
Description

Bronchiolitis is extremely common.
 but did well over the summer. On examination, Mary had nasal drainage and swollen turbinates, as well as bilateral wheezing Wheezing Definition

Wheezing is a high-pitched whistling sound associated with labored breathing.
Description

Wheezing occurs when a child or adult tries to breathe deeply through air passages that are narrowed or filled with mucus as a
. Mary's mother reports that she takes over-the-counter medication for allergic rhinitis Allergic Rhinitis Definition

Allergic rhinitis, more commonly referred to as hay fever, is an inflammation of the nasal passages caused by allergic reaction to airborne substances.
 and wonders if her daughter is developing a similar problem.

[ILLUSTRATION OMITTED]

As the prevalence of asthma and atopic atopic /atop·ic/ (a-top´ik) (ah-top´ik)
1. ectopic.

2. pertaining to atopy; allergic.


atopic

1. displaced; ectopic.

2. pertaining to atopy.
 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 food allergy Allergy medicine A condition, the incidence of which–0.3-7.5%–is obscured by controversial data and differing disease definitions; food-induced reactions of immediate-hypersensitivity type are common and include anaphylaxis, angioedema,  are often the first clinical manifestations of atopy atopy /at·o·py/ (at´ah-pe) a genetic predisposition toward the development of immediate hypersensitivity reactions against common environmental antigens (atopic allergy), most commonly manifested as allergic rhinitis but also as  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 sensitized /sen·si·tized/ (sen´si-tizd) rendered sensitive.

sensitized

rendered sensitive.


sensitized cells
see sensitization (2).
 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 Diagnostic testing
Testing performed to determine if someone is affected with a particular disease.

Mentioned in: Von Willebrand Disease
, 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 sensitization /sen·si·ti·za·tion/ (sen?si-ti-za´shun)
1. administration of an antigen to induce a primary immune response.

2. exposure to allergen that results in the development of hypersensitivity.
 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 in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment.

in vi·tro
adj.
In an artificial environment outside a living organism.
 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 immune system

Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders.
 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 Mast cells
A type of immune system cell that is found in the lining of the nasal passages and eyelids, displays a type of antibody called immunoglobulin type E (IgE) on its cell surface, and participates in the allergic response by releasing histamine from
 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 Leukotrienes
A class of small molecules produced by cells in response to allergen exposure; they contribute to allergy and asthma symptoms.

Mentioned in: Leukotriene Inhibitors

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 allergen /al·ler·gen/ (al´er-jen) an antigenic substance capable of producing immediate hypersensitivity (allergy).allergen´ic

pollen allergen
 to reactive skin cells. Positive (histamine) and negative (saline) controls are also used. Sensitized patients will develop a wheal-and-flare reaction wheal-and-flare reaction
n.
The characteristic immediate reaction to an injected allergen in a skin test, in which an irregular blanched wheal appears, surrounded by an area of redness. Also called wheal-and-erythema reaction.
 within 15 minutes. Results of skin testing are reported subjectively on a number scale, or the wheal wheal (hwel) a localized area of edema on the body surface, often attended with severe itching and usually evanescent; it is the typical lesion of urticaria.

wheal
n.
 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 Antihistamines Definition

Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H1
 and tricyclic antidepressants Antidepressants, Tricyclic Definition

Tricyclic antidepressants are medicines that relieve mental depression.
Purpose

Since their discovery in the 1950s, tricyclic antidepressants have been used to treat mental depression.
 (due to their antihistamine antihistamine (ăn'tĭhĭs`təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine.  properties) seven to 14 days before skin testing. As a consequence of the small but potential risk for anaphylaxis anaphylaxis (ăn'əfəlăk`sĭs), hypersensitive state that may develop after introduction of a foreign protein or other antigen into the body tissues.  following skin testing, patients should preferably not be taking beta-agonists or monoamine oxidase inhibitors Monoamine Oxidase Inhibitors Definition

Monoamine oxidase inhibitors (MAO inhibitors) are medicines that relieve certain types of mental depression.
. 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 Side effects

Effects of a proposed project on other parts of the firm.
. 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.

The technology of blood testing

Specific IgE assays differ in their binding capacity, the source, quality, and availability of antigens, reagent stability, and degree of automation. (8) In the laboratory, serum samples from patients are first incubated with allergens bound to a liquid-phase or solid support. (9) In early RAST tests, a paper disk served as the support. Later assays improved binding capacity by using cellulose sponges, polystyrene, or liquid-phase carriers. The most commonly used method today utilizes a patented high-capacity reaction vessel, which contains an allergen-coated, porous cellulose sponge that greatly increases the surface area available for the specific IgE in question. The IgE finds and interacts with bound allergen, forming specific antibody-antigen complexes. Allergens attach to the sponge with a robust covalent co·va·lent
adj.
Of or relating to a chemical bond characterized by one or more pairs of shared electrons.
 chemical bond that survives the vigorous washing used to sweep away non-specific IgE. Then labeled anti-IgE monoclonal antibodies are added, resulting in the formation of anti-IgE antibody-antibody-allergen complexes. Finally, unbound unbound

said of electrolytes, e.g. iron and calcium, and other substances which are circulating in the bloodstream and are not bound to plasma proteins so that they are available immediately for metabolic processes. See also calcium, iron.
 anti-IgE-antibody is washed away, and the remaining complexes measured. Early specific IgE methodologies detected these complexes with radiolabeling radiolabeling

incorporation of a radioactive element into a compound in order to investigate its metabolism, fate and utilization.
, which has been replaced with enzyme (fluorescent, colorimetric col·or·im·e·ter  
n.
1. Any of various instruments used to determine or specify colors, as by comparison with spectroscopic or visual standards.

2.
) or chemiluminescent chem·i·lu·mi·nes·cence  
n.
Emission of light as a result of a chemical reaction at environmental temperatures.



chem
 labeling. The whole process is often highly automated, which contributes to improved reproducibility, depending on the solid phase and the system in use.

Almost all modern assays claim to report quantitative results, although the results may be obtained by extrapolation (mathematics, algorithm) extrapolation - A mathematical procedure which estimates values of a function for certain desired inputs given values for known inputs.

If the desired input is outside the range of the known values this is called extrapolation, if it is inside then
 rather than by calibration to zero. (10) Very low levels of specific IgE can be reported using a calibration curve that includes zero, though the clinical significance of such low levels is not known. Precise low-level detection may offer an early warning of sensitization, which increases the risk for developing more allergic sensitivities. The clinical significance and predictive value pre·dic·tive value
n.
The likelihood that a positive test result indicates disease or that a negative test result excludes disease.



predictive value

a measure used by clinicians to interpret diagnostic test results.
 of low-level IgE sensitization in children is currently being investigated.

The source, quality, and selection of allergens used in specific IgE testing certainly influences the clinical usefulness of results. Establishing sensitivity to an allergen the patient is not likely to encounter, for example, does nothing to guide clinical management or improve the patient's symptoms but does increase the cost of care. Representative allergen profiles, containing a limited selection of allergens, can provide sufficient evidence to rule out allergy in non-allergic patients and identify pertinent sensitivities in allergic patients. (10) The profiles should include a selection of indoor allergens, outdoor allergens matched to specific geographic regions, and allergens frequently associated with allergic disease. A typical childhood profile would include food and indoor-inhalant allergens, as sensitivities to outdoor allergens take several seasons to develop. An adult profile might include house mite dust (Dermatophagoides farinae), dog and cat dander dander /dan·der/ (dan´der) small scales from the hair or feathers of animals, which may be a cause of allergy in sensitive persons.

dan·der
n.
, plus outdoor allergens, such as grasses, pollens, and molds typical of the region. Testing for large numbers of allergens is rarely necessary. As the link between asthma and allergy continues to be demonstrated, the inclusion of indoor allergens most likely to trigger asthma symptoms rounds out the contents of the test profiles. Some regional respiratory profiles of major inhalant inhalant /in·hal·ant/ (in-hal´ant)
1. something meant to be inhaled; see inhalation (def. 3).

2. a class of psychoactive substances whose volatile vapors are subject to abuse.
 allergens (indoor and outdoor) have been found to accurately identify atopy in up to 99% of cases. (11)

Today's third-generation technology for blood testing allows primary-care clinicians to approximate the diagnostic precision of allergists. (12) Wood and colleagues evaluated skin-prick, intradermal intradermal /in·tra·der·mal/ (-der´mal)
1. within the dermis.

2. intracutaneous.


in·tra·der·mal
adj.
Within or between the layers of the skin.
, and blood testing for specific IgE, comparing their relative sensitivity, specificity, positive and negative predictive value The negative predictive value is the proportion of patients with negative test results who are correctly diagnosed. Worked example
Relationships among terms:

Condition
(as determined by "Gold standard")

True False
, and efficiency (a combined measure of sensitivity and specificity). (13) Results from the skin prick and blood tests were comparable (see Table 1). Poon poon  
n.
Any of several trees of the genus Calophyllum, of southern Asia, having light hard wood used for masts and spars.



[Sinhalese p
 and colleagues, in a review of the scientific literature, came to the same conclusion. (14) They noted that without an independent gold standard for detecting inhalant allergens, "it is not possible to determine which test is more accurate." They also found that blood testing offered more standardization than skin testing, a finding endorsed in a recent editorial written by Portnoy in the Annals of Allergy, Asthma & Immunology. (15)

With blood testing, there can also be variations in results among laboratories, testing technologies, and allergens. Williams and associates conducted a well-controlled study of the accuracy and precision of specific IgE blood tests on 26 masked serum samples sent to six laboratories that used five testing procedures for 17 aeroallergens. (16) Analysis of 12,708 test results showed that one third-generation technology used in two laboratories proved consistently superior to other commercially available assays. This technology measured specific IgE antibodies over a large range with precision and accuracy. The authors--and other allergy experts--support its use as the current standard for quantitative measurement of specific IgE. (17)

The Diagnostic Allergy Proficiency Survey, administered by the College of American Pathologists This article or section needs sources or references that appear in reliable, third-party publications. Alone, primary sources and sources affiliated with the subject of this article are not sufficient for an accurate encyclopedia article. , is one means of evaluating diagnostic performance. In addition, the Clinical and Laboratory Standards Institute (18) publishes standards for quality-control and minimal-performance targets, including recovery of antibodies, precision, linearity, and parallelism over the measuring range. Assay manufacturers can also be consulted regarding recommended validation and calibration procedures. Henry Homburger, MD, a pathologist at Mayo College of Medicine, recently published an excellent review of specific IgE testing that includes practical recommendations about whom should be tested, which tests should be ordered, and what the results mean. (19)

Reporting results

Quantitative results for specific IgE testing are most often measured in kilo units per liter (k[U.sub.A]/L, where [.sub.A] represents the amount of antibody), and calibration should be linked to the World Health Organization 75/502 IgE standard. Many laboratories also categorize k[U.sub.A]/L measurements using a simplified class system with reactions ranging from Class 0 (no reaction) to Class VI (very high specific IgE levels). This antiquated method of grouping results by class is slowly being phased out in favor of quantitative specific IgE results. This is an important direction for the presentation of specific IgE results, because the results of assays from various manufacturers are not interchangeable, although the class system tends to create that impression. (8,20) Consequently, an increasing number of experts believe the class system should be abolished. In fact, in 1992, the Executive Committee of the American Academy of Allergy and Immunology recommended "the arbitrary reference systems with myriad class-scoring schemes should be abandoned in favor of quantitative-reporting methods where test results are reported in units that are proportional to antibody content." (21)

Just as history and physical examination alone are insufficient for a definitive diagnosis, specific IgE test result must be interpreted in the context of symptoms and clinical signs. For example, low levels of specific IgE for one allergen certainly have less clinical significance than higher levels for multiple allergens. In individuals with a positive result, identifying specific allergens guides management. Because the clinical effect of any number of allergens is dependent upon cumulative exposure, rather than an all-or-nothing phenomenon, the avoidance of certain key allergens may lower an individual's allergic burden sufficiently to relieve or eliminate symptoms.

The value of a negative result should not be overlooked either. Many non-allergic conditions, such as vasomotor rhinitis vasomotor rhinitis
n.
Congestion of nasal mucosa without infection or allergy.


vasomotor rhinitis ENT Rhinitis characterized by intermittent episodic sneezing, rhinorrhea, and congestion of nasal mucosa, attributed to
 or infection, mimic allergic respiratory conditions. As many as two-thirds of patients who present with allergy-like symptoms test negative for specific IgE. (22,23) For these non-allergic patients, the search for other etiologies should continue. A thorough diagnostic work-up can spare them unnecessary, ineffective, or costly treatment.

The clinical benefits of specific IgE testing

A definitive diagnosis of confirmed allergic disease offers several benefits for patients. First, specific IgE test results can be used to predict the course of atopic disease. IgE antibodies can be measured by three months of age, before clinical symptoms appear. Infants who develop food sensitization are much more likely than other children to later develop sensitivities toward inhalant allergens. (24,25) So, back when little Mary's eczema was more acute, her pediatrician could have used the results of specific IgE blood testing to determine if it had a potentially avoidable food trigger as well as to predict if she was at risk for subsequent respiratory problems, such as allergic rhinitis and asthma.

Second, early intervention ear·ly intervention
n. Abbr. EI
A process of assessment and therapy provided to children, especially those younger than age 6, to facilitate normal cognitive and emotional development and to prevent developmental disability or delay.
 allows better management of allergic disease. Although the majority of children who wheeze wheeze (hwez) a whistling type of continuous sound.

wheeze
v.
To breathe with difficulty, producing a hoarse whistling sound.

n.
A wheezing sound.
 with respiratory infections under three years of age are likely to outgrow outgrow verb To change the relationship with a condition or structure by dint of ↑ age or size; while children outgrow clothing, and certain behaviors, they rarely outgrow diseases–eg, asthma  this tendency, there is a subgroup of children who will have persistent asthma. (26) These at-risk children can be identified by their propensity for allergic sensitization. (27) Furthermore, observations of children with asthma suggest that treatment in the first five years of life is necessary to minimize progressive loss of lung function. (28) Clinical evidence suggests that early diagnosis followed by appropriate treatment may interrupt or ameliorate the progression of allergic disease. (29-31) Implementing avoidance, which can reduce the need for medications, (32) is impractical if specific allergens have not been identified. If Mary's specific IgE results are positive, her pediatrician can use those results to recommend avoidance of specific inhalant allergens or use pharmacotherapy pharmacotherapy /phar·ma·co·ther·a·py/ (-ther´ah-pe) treatment of disease with medicines.

phar·ma·co·ther·a·py
n.
Treatment of disease through the use of drugs.
 to prevent or treat symptoms.

Finally, negative results can prevent unnecessary trials of allergy medication, direct further diagnostic efforts, and spare the inconvenience of avoidance for patients who would not benefit. A negative specific IgE result for Mary would prompt her pediatrician to look for other causes of her symptoms and reassure her mother that she is at less risk of developing chronic childhood asthma. By providing an accurate definitive diagnosis, specific IgE testing supports early, appropriate, and targeted therapy, greater patient satisfaction, and better control of costs.

Lee R. Choo-Kang, MD, is the director of Pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.

pe·di·at·ric
adj.
Of or relating to pediatrics.
 Pulmonary and Sleep Medicine at St. John's Mercy Medical Center in St. Louis, MO.

References

1. Downs SH, Marks GB, Sporik R, Belosouva EG, Car NG, Peat JK. Continued increase in the prevalence of asthma and atopy. Arch Dis Child. 2001;84:20-23.

2. Nickel R, Lau S, Niggemann B, et al. Messages From the German Multicentre Allergy Study. Pediatr Allergy Immunol. 2002; 13 (suppl 15):7-10.

3. Strachan DP, Butland BK, Anderson HR. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift . 1996;312:1195-1199.

4. Kotaniemi-Syrjanen A, Reijonen TM, Romppanen J, Korhonen K, Savolainen K, Korppi M. Allergen-specific immunoglobulin E immunoglobulin E
n. Abbr. IgE
The class of antibodies produced in the lungs, skin, and mucous membranes and responsible for allergic reactions.
 antibodies in wheezing infants: the risk for asthma in later childhood. Pediatrics. 2003;111:e255-e261.

5. Williams PB, Ahlstedt S, Barnes JH, Soderstrom L, Portnoy J. Are our impressions of allergy test performances correct? Ann Allergy Asthma Immunol. 2003;91:26-33.

6. Naclerio R, Solomon W. Rhinitis Rhinitis Definition

Rhinitis is inflammation of the mucous lining of the nose.
Description

Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common feature is the location of their symptoms.
 and inhalant allergens. JAMA JAMA
abbr.
Journal of the American Medical Association
. 1997;278(22):1842-1848.

7. Ownby DR, Adinoff AD. The appropriate use of skin testing and allergen immunotherapy allergen immunotherapy Desensitization, hyposensitization, immunotherapy Allergy medicine A modality that attempts to ↓ IgE-mediated hypersensitivity to various substances, by administering ever-increasing amounts of an antigen–eg urushiol in poison ivy,  in young children. J Allergy Clin Immunol. 1994;94:662-665.

8. Williams PB. Specific IgE systems for the laboratory. Advance/Laboratory. 2005:36-40.

9. Fromer LM. Clinical rationale for obtaining a precise diagnosis. J Fam Pract. 2004;(suppl):S4-S14.

10. Killingsworth LM. Advancing Allergy Diagnostics in the Lab: In vitro allergy testing allergy testing See Patch testing, RAST, Skin testing.  offers a unique opportunity to expand your lab's services. Advance for Administrators of the Laboratory. 2005;14(9):44.

11. Nalebuff DJ. Use of RAST screening in clinical allergy: a cost-effective approach to patient care. Ear Nose Throat J. 1985;64(3):107-121.

12. Crobach MJ, Hermans J, Kaptein AA, Ridderikhoff J, Petri H, Mulder JD. The diagnosis of allergic rhinitis: how to combine the medical history with the results of radioallergosorbent tests and skin prick tests. Scand J Prim Health Care. 1998;16:30-36.

13. Wood RA, Phipatanakul W, Hamilton RG, Eggleston PA. A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy. J Allergy Clin Immunol. 1999;103(5 pt 1):773-779.

14. Poon AW, Goodman CS, Rubin FJ. In vitro and skin testing for allergy: comparable clinical utility and costs. Am J Manag Care. 1998;4:969-985.

15. Portnoy J. Diagnostic testing for allergies. Ann Allergy Asthma Immunol. 2006;96:3-4.

16. Williams PB, Barnes JH, Szeinbach SL, Sullivan TJ. Analytic precision and accuracy of commercial immunoassays for specific IgE: establishing a standard. J Allergy Clin Immunol. 2000;105(6 pt 1):1221-1230.

17. Johansson SGO SGO Society of Gynecologic Oncologists
SGO Student Government Organization
SGO Surgeon General's Office
SGO Standard Garrison Organization
SGO St George, Queensland, Australia - St George (Airport Code)
SGO Office of the Secretary General
. ImmunoCAP[R] Specific IgE test: an objective tool for research and routine allergy diagnosis. Expert Rev Mol Diagn. 2004;4(3):273-279.

18. Review Criteria for the Assessment of Allergen-Specific Immunoglobulin E (IgE) in In Vitro Diagnostic Devices Using Immunological Methods. Washington: Public Health Service; 2000:1-18.

19. Homburger HA. Diagnosing allergic disease in children: practical recommendations for consulting pathologists. Arch Pathol Lab Med. 2004;128:1028-1031.

20. Dolen WK. IgE antibody in the serum--detection and diagnostic significance. Allergy. 2003;58:717-723.

21. Lockey R, Lichtenstein L, Bloch K, Kaliner M, Zweiman B, Rochelesky G. Position statement. The use of in vitro tests for IgE antibody in the specific diagnosis of the IgE-mediated disorders and in the formulation of allergen immunotherapy. J Allergy Clin Immunol. 1992;90:263-267.

22. Green SA, Martin D. Is every sneeze sneeze, involuntary violent expiration of air through the nose and mouth. It results from stimulation of the nervous system in the nose, causing sudden contraction of the muscles of expiration.  an allergy? Diagnosing and treating allergic vs nonallergic rhinitis. Am J Nurse Pract. 2003;7(5):9-18.

23. Szeinbach S, Boye Boye may refer to:
  • Anker Boye (born 1950), Danish politician
  • Jan Boye (born 1962), Danish politician
  • Karin Boye (1900-1941), Swedish poet and novelist
  • Mame Madior Boye (born 1940), former Prime Minister of Senegal
 M, Muntendam P, O'Connor R. Diagnostic assessment and resource utilization in patients prescribed non-sedating antihistamines. Paper presented at: Annual Meeting of AIAIS; October 16, 2000.

24. Sasai K, Furukawa S, Muto T, Baba M, Yabuta K, Fukuwatari F. Early detection of specific IgE antibody against house dust mite house dust mite Dermatophagoides farinae, D pteronyssoides A mite that feeds on household detritus, which is often highly allergenic; exposure to HDMs can be measured by RAST  in children at risk of allergic disease. J Paediatr. 1996;128:834-840.

25. Sigurs N, Hattevig G, Kjellman B, Kjellman NI, Milsson L, Bjorksten B. Appearance of atopic disease in relation to serum IgE antibodies in children followed up from birth for 4 to 15 years. J Allergy Clin Immunol. 1994;94:757-763.

26. Martinez FD, Wright AL, Taussig LM, Holberb CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. N Engl J Med. 1995 Jan 19;332(3):133-138.

27. Guilbert TW, Morgan WJ, Zeiger RS, Bacharier LB, Boehmer SJ, Krawiec M, Larsen G, Lemanske RF, Liu A, Mauger DT, Sorkness C, Szefler SJ, Strunk RC, Taussig LM, Martinez FD. Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. J Allergy Clin Immunol. 2004;114(6):1282-1287.

28. Busse WW, Lemanske RF Jr. Asthma. New Engl J Med. 2001;344(5):350-362.

29. Wahn U. What drives the allergic march? Allergy. 2000;55:591-599.

30. ETAC ETAC Ethyl Acetate
ETAC Early Treatment of the Atopic Child (UCB Pharma)
ETAC Environmental Technical Applications Center
ETAC Enlisted Terminal Attack Controller
ETAC Everyday Technologies for Alzheimer's Care
 Study Group. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised Adj. 1. randomised - set up or distributed in a deliberately random way
randomized

irregular - contrary to rule or accepted order or general practice; "irregular hiring practices"
, placebo-controlled trial: first results of ETAC[R]. Pediatr Allergy Immunol. 1998;9:116-124.

31. Chan-Yueng M, Ferguson A, Watson W, et al. The Canadian childhood asthma primary prevention study: outcomes at 7 years of age. J Allergy Clin Immunol. 2005;116:49-55.

32. Halken S, Host A, Niklassen U, et al. Effect of mattress and pillow encasings on children with asthma and house dust mite allergy. J Allergy Clin Immunol. 2003;111:169-176.

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1. IgE becomes attached to the surface membranes of mast cells and basophils present in the ______ of the body.

a. skeletal muscle tissue

b. primary immune organs (bone marrow and thymus thymus

Pyramid-shaped lymphoid organ (see lymphoid tissue) between the breastbone and the heart. Starting at puberty, it shrinks slowly. It has no lymphatic vessels draining into it and does not filter lymph; instead, stem cells in its outer cortex develop into
)

c. lung and kidney tissues

d. epithelial surfaces (skin and respiratory and gastrointestinal tracts)

2. Pro-inflammatory mediators released by cross-linked IgE molecules on the surfaces of mast cells include all but

a. complement.

b. histamine.

c. leukotrienes.

d. prostaglandins.

3. When performing skin-prick testing for IgE responses to specific allergens, ______ is used as the negative control.

a. histamine

b. deionized water

c. albumin solution

d. saline

4. Skin-prick testing should not be performed on

a. pregnant women.

b. patients currently taking antihistamine.

c. patients with unstable asthma.

d. Any of the above.

5. Data from a study of Wood, et al, comparing skin-prick testing, specific IgE blood testing, and intradermal skin testing indicated that

a. all three testing methods produced comparable results.

b. skin-prick testing was superior to the other two methods in specificity and positive predictive value Positive predictive value (PPV)
The probability that a person with a positive test result has, or will get, the disease.

Mentioned in: Genetic Testing

positive predictive value 
.

c. skin-prick and specific IgE blood testing were comparable, while intradermal skin testing is less sensitive, specific, and predictive.

d. specific IgE blood testing and intradermal skin testing were superior to skin-prick testing for sensitivity, specificity, and predictive value.

6. The most commonly employed method of specific IgE blood testing today uses ______ to support the reagent allergens.

a. polystyrene carriers

b. porous cellulose sponges

c. paper disks

d. agarose agarose

more highly purified form of agar with similar uses to agar and widely used in the separation of nucleic acid fragments.
 gel

7. Non-radioactive labels used in today's specific IgE blood testing methods include

a. enzyme conjugates.

b. fluorescent conjugates.

c. chemiluminescent conjugates.

d. Any of the above.

8. A proposed advantage of specific IgE blood-testing methods that have the capability to detect very low levels of IgE with precision is

a. providing an early warning that sensitization to allergens has occurred.

b. the ability to detect allergy in immunodeficient patients.

c. the ability to monitor seasonal fluctuations in IgE levels.

d. tracking genetic predisposition genetic predisposition Molecular medicine The tendency to suffer from certain genetic diseases–eg, Huntington's disease, or inherit certain skills–eg, musical talent  for allergy development in families.

9. Which of the following allergens, commonly used when testing adults, may be eliminated when performing specific IgE blood testing on children less than two years of age?

a. Grasses and pollens.

b. House mite dust.

c. Cat dander.

d. Dog dander.

10. Compared to skin-prick testing, specific IgE blood testing offers greater capability for

a. sensitivity.

b. negative predictive value.

c. efficiency.

d. standardization.

11. Specific IgE blood levels should be reported in

a. mg/dL.

b. IU/L.

c. % of normal reference.

d. k[U.sub.A]/L.

12. When the results of specific IgE blood levels is positive (elevated),

a. the test should be repeated.

b. the sample should be retested using an alternate automated method.

c. the specific allergens to which the IgE is directed should be identified.

d. no further testing is recommended.

13. The benefits of performing specific IgE blood testing include

a. the ability to predict the course of atopic disease.

b. the ability for early intervention to better manage allergic disease.

c. prevention of unnecessary procedures on patients for whom negative results are obtained.

d. All of the above.

14. The correct sequence of the pattern known as the Allergy March is

a. food sensitivities, seasonal asthma, and inhalant sensitivities to indoor allergens.

b. food sensitivities, inhalant sensitivities to indoor allergens, and inhalant sensitivities to outdoor seasonal allergens.

c. eczema, asthma, food allergies Food Allergies Definition

Food allergies are the body's abnormal responses to harmless foods; the reactions are caused by the immune system's reaction to some food proteins.
, and allergic rhinitis.

d. recurrent otitis media, asthma, food allergies, and skin sensitivities.

15. The highest incidence of hypersensitivity hypersensitivity, heightened response in a body tissue to an antigen or foreign substance. The body normally responds to an antigen by producing specific antibodies against it. The antibodies impart immunity for any later exposure to that antigen.  to food allergens in children is found at around the age of

a. six months.

b. one year.

c. two years.

d. five years.

16. Risk factors for the development of allergic asthma include

a. total serum IgE of >100 kU/L before six years of age.

b. smoking.

c. family history of allergy.

d. All of the above.

17. Manifestations of hypersensitivity to food allergens include all but

a. glomerulonephritis glomerulonephritis: see nephritis. .

b. dermatitis.

c. colic colic, intense pain caused by spasmodic contractions of one of the hollow organs, e.g., the stomach, intestine, gall bladder, ureter, or oviduct. The cause of colic is irritation and/or obstruction, and the irritant and/or obstruction may be a stone (as in the gall .

d. chronic otitis otitis

Inflammation of the ear. Otitis externa is dermatitis, usually bacterial, of the auditory canal and sometimes the external ear. It can cause a foul discharge, pain, fever, and sporadic deafness.
.

18. A conservative intervention strategy recommended in children for ameliorating the progression of allergic disease is

a. immunosuppressive therapy.

b. implementing avoidance of the specific troublesome allergen.

c. removal of the thymus gland thymus gland (thī`məs), mass of glandular tissue located in the neck or chest of most vertebrate animals. In humans, the thymus is a soft, flattened, pinkish-gray organ located in the upper chest under the breastbone. .

d. stem-cell donation from an HLA-matched sibling.

19. Specific IgE levels directed to seasonal outdoor allergens typically are not yet developed in very young children because

a. the immune system of infants and toddler is rudimentary.

b. only older children and adults have predilection towards developing allergies to outdoor allergens.

c. exposure to outdoor allergens and development of specific IgE levels occurs over several seasons.

d. None of the above.

20. Reporting specific IgE blood levels by using a class system with 0 indicating "no reaction" to VI meaning "very high levels" is

a. the preferred reporting method.

b. an objective alternative to providing quantitative results.

c. considered arbitrary with recommendations that it be abandoned.

d. a new and upcoming reporting method.

[GRAPHIC OMITTED]

By Lee R. Choo-Kang, MD

RELATED ARTICLE: The progression of allergic disease

Atopic children, probably genetically predisposed to allergic disease, develop symptoms in a predictable pattern known as the Allergy March. The formation of IgE antibodies begins early in life and sensitization can often be detected before clinical symptoms appear. Sensitization usually occurs first to food allergens, such as cow's milk, egg white, wheat, and soy. Sasai and associates demonstrated a positive predictive value of hen's egg antibodies in children as young as six months of age. (1) In the youngest patients, hypersensitivity to food allergens can manifest itself as atopic dermatitis, gastrointestinal symptoms (colic), chronic otitis, or rarely, wheezing. (2) These allergic conditions typically have their highest incidence at age two. In children younger than age three, atopy can be diagnosed with positive IgE results to food allergens and perennial inhalants inhalants,
n.pl 1. chemical vapors that are inhaled for their mind-altering effects.
2. in herbology, volatile herbal compounds that are delivered by holding a soaked pad to the nose and mouth, by placing the herbs in steaming water, or
 such as dust mites, as sensitization to outdoor seasonal allergens rarely occurs before then. Even prior to the onset of wheezing, the significance of early atopy is important, as there is an inherent risk of later developing asthma. For example, young children who have atopic dermatitis and a positive family history of asthma have a 40% risk of later developing asthma. (3) Nevertheless, it is important to recognize that food allergies themselves are not entirely the cause of later inhalant allergic sensitization but merely serve as a clinical marker in a child who is genetically predisposed for atopic disease.

[GRAPHIC OMITTED]

In children older than three years, food sensitivities tend to decrease and sensitization to inhalant allergens typically increases during the preschool years. (4) In most children with asthma, symptoms commence before age five. Sensitization to perennial allergens, such as house dust mites, dog and cat dander, occurs before sensitization to seasonal allergens. Risk factors for development of allergic asthma include a family history of allergy, sensitization to food allergens, total serum IgE > 100 kU/L before age six, living in an allergen-rich environment, and smoking. (5) Understanding the progression of allergic disease lays the foundation for early intervention, a strategy shown to improve the long-term prognosis. (6)

References

1. Sasai K, Furukawa S, Muto T, Baba M, Yabuta K, Fukuwatari F. Early detection of specific IgE antibody against house dust mite in children at risk of allergic disease. J Pediatr. 1996;128:834-840.

2. Homburger HA. Diagnosing allergic disease in children: practical recommendations for consulting pathologists. Arch Pathol Lab Med. 2004;128:1028-1031.

3. Kulig M, Bergmann R, Tacke U, Wahn U, Guggenmoos-Holzmann I. Long-lasting sensitization to food during the first two years precedes allergic airway disease. Pediatr Allergy Immunol. 1998;9:61-67.

4. Hahn EL, Bacharier LB. The atopic march: the pattern of allergic disease development in childhood. Immunol Allergy Clin North Am. 2005;25:231-246.

5. Dykewicz MS, Fineman S. Executive summary of joint task force practice parameters on diagnosis and management of rhinitis. Ann Allergy Asthma Immunol. 1998;81(5 pt 2):463-468.

6. Chan-Yueng M, Ferguson A, Watson W, et al. The Canadian childhood asthma primary prevention study: outcomes at 7 years of age. J Allergy Clin Immunol. 2005;116:49-55.

By Lee R. Choo-Kang, MD
Table 1. Comparison of results from skin-prick and blood tests for
specific IgE

                     Skin-prick  Specific-IgE    Intradermal
                     testing     blood testing*  skin testing

Sensitivity (%)      93.6        87.2            60
Specificity (%)      80.1        90.5            32.3
Positive predictive  90.1        91.1            12
  value (%)
Negative predictive  87.1        86.4            84.6
  value (%)
Efficiency           89.2        88.8            36.8

* Study processed with ImmunoCAP technology
COPYRIGHT 2006 Nelson Publishing
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2006 Gale, Cengage Learning. All rights reserved.

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Title Annotation:Immunoglobulin E
Author:Choo-Kang, Lee R.
Publication:Medical Laboratory Observer
Geographic Code:1USA
Date:Mar 1, 2006
Words:4952
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