Laboratory Section - Allergy Tests of Uncertain Efficacy

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

DESCRIPTION

Allergy refers to an acquired potential for developing adverse reactions that are mediated by the immune system (via IgE antibodies).  Allergic disease represents the clinical manifestations of these adverse immune responses. An allergen is any substance that can cause an allergic reaction. Allergens are often common, usually harmless, substances such as pollens, mold spores, animal danders, dust, foods, insect venoms, latex, and drugs. (2)

The optimum management of the allergic patient should include a careful history and physical examination and may include confirming the cause of the allergic reaction by information from allergy tests. The following allergy tests are considered clinically useful for allergy confirmation by the American Academy of Allergy, Asthma, and Immunology (AAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) in the diagnosis and management of the allergic patient:

• Bronchial challenge test
• Double-blind food challenge test
• Intradermal skin testing
• Patch test
• Percutaneous skin tests such as the scratch, prick, or puncture tests
• Photo patch test
• Specific IgE in vitro tests such as Radioallergosorbent Test (RAST), Multiple Radioallergosorbent Tests (MAST), Fluorescent Allergosorbent Test (FAST), Enzyme-linked Immunosorbent Assay (ELISA), and the ImmunoCAP IgE test
• Total serum IgE concentration

Once an allergy-causing agent is identified, treatment is provided by avoidance, medication or immunotherapy.

This policy addresses only allergy tests of uncertain efficacy and those used primarily in research settings. Tests which may be considered useful in the clinical setting, as noted above, are not addressed in this policy.

Allergy Tests of Uncertain Efficacy

Antigen leukocyte cellular antibody (ALCAT) automated food test

The ALCAT automated food test measures whole blood leukocytes by a proprietary process that identifies allergens which cause an increase in leukocyte activity. An electronic counter measures the change in number and size of white blood cells which have been incubated with purified food or mold extracts. A histogram is produced based on cell count and cell size.  Individually processed test samples are compared with a "Master Control" graph.  Scores are generated by relating these effective volumetric changes in white blood cells to the control curve.

Applied Kinesiology (or muscle strength test)

Muscle strength in the extremities is measured before and after a person is exposed to an allergen. Strength in the opposing arm is measured as a person holds a container of allergen extract in the opposite hand or ingests an allergen. A decrease in strength indicates the presence of disease and various nutritional supplements may be recommended.

Cytotoxic food tests

This test involves the response of specially collected white blood cells to the presence of food extracts to which the patient is allergic. A technician observes the unstained cells for changes in shape and appearance of the leukocytes. Swelling, vacuolation, crenation, or other cytotoxic changes in cell morphology are taken as evidence of allergy to the food.

Electrodermal testing (also known as electro-acupuncture)

Electrodermal testing measures changes in skin resistance while a person is exposed to an allergen; either food or inhalant .This allergy-testing device uses a galvanometer to measure the electrical resistance of the skin. A drop in the resistance of the skin is believed to indicate the presence of allergy.  

Hair analysis

Hair is analyzed for the presence (or lack) of various minerals and toxins. Findings are correlated to nutritional deficiencies or disease. Recommendations for diet and supplements are provided based on the analysis.  

Iridology

According to the AAAI, iridology attempts to relate the anatomical features in the iris to various systemic diseases.

IgG/IgG4 antibody test and food specific IgG/IgG4 tests

There are four subclasses of immunoglobulin G. Selective deficiencies in one or more of the four IgG subclasses are seen in some patients with repeated infections. Measurements of IgG and specifically IgG4 antibodies have been used in research settings as diagnostic and prognostic tests to determine response to allergy treatments.

Passive transfer of P-X (Prausnitz-Kustner) test  

This technique involves prick, scratch, or intradermal transfer of serum from a sensitized individual into a nonallergic volunteer. The volunteer is then challenged with the allergen by skin testing. A wheal or a flare response indicates a positive reaction. This procedure is now considered obsolete and has been replaced by the Radioallergosorbent Test (RAST) test.

Provocative-neutralization tests for food (or food additive allergy test)

This procedure is performed by injecting (intradermal or subcutaneous), or placing under the tongue (sublingual), dilute extracts of the suspected food or inhalant allergen and observing the patient’s response or reaction. A symptomatic response indicates an allergy to that food or inhalant, and the reaction can be neutralized by application of a similar extract of a lesser dilution.

Rebuck skin window test

This is a type of skin testing where the skin surface is stripped or broken to cause serious oozing. This area is then covered by a glass plate, coated with the allergen to be tested, and taped in place for 24 hours. At the end of that time the plate is removed, and the cells under the plate and the surrounding skin are checked for any changes. An eosinophilic exudate typical of an allergic reaction appears in the area of the stripped epidermis. The results are very difficult to interpret and are not practical for general use. The procedure is no longer in use.

Allergy Tests In the Research Setting

Conjunctival challenge test

With conjunctival testing, an allergenic extract is placed into the conjunctival sac of the eye followed by observation for redness, itchiness, tearing of the eye, and other similar symptoms.   According to the AAAI, these tests are often used in research protocols that require an objective standard for evaluating clinical sensitivity to an allergen.

Leukocyte Histamine Release Test (LHRT)

In this testing, leukocytes from the serum of an allergic individual are observed for histamine release in the presence of an antigen  The commercial availability of simplified and automated methods of laboratory analysis have renewed interest in the clinical applications of LHRT in the evaluation of food, inhalant, and drug allergies. The AAAI guidelines for this test indicate it is primarily used in a research setting.

Nasal challenge test

This test provides precise measurements of changes in nasal airway resistance along with observations such as number of sneezes and measurement of inflammatory mediators in the nasal secretions after exposure to an allergen. The more commonly known "sniff test," uses a visual assessment of mucosal swelling and rhinorrhea after a small amount of dry pollen is inhaled.

POLICY/CRITERIA

The following allergy tests are considered investigational as the scientific evidence does not permit conclusions regarding their effects on health outcomes:

1. Antigen leukocyte cellular antibody (ALCAT) automated food test
2. Applied kinesiology allergy test
3. Conjunctival challenge test (ophthalmic mucous membrane test)
4. Cytotoxic food tests  
5. Electrodermal testing (also known as electro-acupuncture)
6. Hair analysis
7. IgG/IgG4 allergen specific antibody test and food tests
8. Iridology
9. Leukocyte histamine release test (LHRT)
10. Nasal challenge test
11. Passive transfer or P-X (Prausnitz-Küstner) test (now considered obsolete-and replaced by Radioallergosorbent tests)
12. Provocation-neutralization food or food additive allergy test
13. Rebuck skin window test (no longer in use)

POSITION SUMMARY

This policy is based on the 2008 updated clinical practice guidelines published by the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) and literature reviews of the available evidence. The policy focuses on the following allergy tests which are determined to be of uncertain efficacy because evidence is lacking concerning the diagnostic validity and clinical utility of the tests.

• Antigen leukocyte cellular antibody (ALCAT) test 
• Applied kinesiology 
• Cytotoxic tests
• Electrodermal testing
• Hair analysis  
• IgG and IgG4 allergen specific antibody or food test  
• Iridology  
• Passive transfer or P-X test 
• Provocation- neutralization tests  
• Rebuck skin window test 

In contrast to the AAAI and ACAAI practice guidelines the following tests, which are primarily used in research protocols, have insufficient evidence to determine their clinical utility (e.g. sensitivity, specificity, or positive and negative predictive values) and their role in the management of patient health outcomes is uncertain.

• Conjunctival challenge test,
• Leukocyte histamine release test (LHRT)
• Nasal challenge tests

Effectiveness

The following tests have no randomized, controlled clinical trials documenting outcomes and impact on treatment decisions and/or results from clinical trials are inconclusive or contradictory:(1-3,11-14)

• Antigen leukocyte cellular antibody (AlCAT) test
• Applied kinesiology,
• Cytotoxic tests,
• Electrodermal testing ,
• Hair analysis,
• IgG and IgG4 allergen specific antibody or food test,
• Iridology,
• Passive transfer or P-X test,
• Provocation- neutralization,
• Rebuck skin window test

The following tests are primarily used in the research setting and evidence is insufficient to permit conclusions on their clinical utility or effectiveness for improving health outcomes.

Leukocyte Histamine Release Test (LHRT)

Overall, the evidence is not sufficient to permit conclusions on the diagnostic accuracy of LHRT Studies are potentially prone to spectrum bias, referral bias, ascertainment bias. Alternative tests have not been performed in a blinded manner, or studies did not indicate whether or not there were blinded interpretations of the tests. (4, 5)  Some studies included patients with known allergies, and thus these highly selective populations do not represent the same population with equivocal allergy histories that would undergo testing. (5-9) In some situations, results were compared with bronchial provocation testing, considered the gold standard for inhalant allergies. However, bronchial provocation may only be performed on a subset of patients with a limited number of allergens. For example, bronchial provocation may only be performed when there are discordant results between RAST and skin prick testing. (10) While it has been suggested that LHRT may be a valuable test in those patients with discordant results of skin prick testing and RAST testing, studies focusing on this subgroup of patients were not identified in a literature search.

Conjunctival and Nasal Challenge Tests

These tests are often the tools of research protocols and are used to determine clinical sensitivity to an allergen.(3) While it has been suggested that conjunctival and nasal challenge tests may be valuable to confirm diagnosis when skin tests are negative, the studies focusing on this subgroup of patients are small, nonrandomized trials which do not permit conclusions on the clinical utility of conjunctival or nasal challenge tests. (15-20)

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy Nos. 2.04.42 and 2.01.23
2. The Allergy Report 2000. American Academy of Allergy Asthma & Immunology. Overview of Allergic Diseases: Diagnosis, Management, and Barriers to Care
3. Bernstein IL, Li JT, Bernstein DI et al. Allergy Diagnostic Testing: An Updated PracticeParameter Ann Allergy Asthma Immunol  2008;100:S1-148
4. Griese M, Kusenbach G, Reinhardt D. Histamine release test in comparison to standard tests in diagnosis of childhood allergic asthma. Ann Allergy 1990;65(1):46-51
5. Skov PS, Mosbech M, Norn S et al. Sensitive glass microfibre-based histamine analysis for allergy testing in washed blood cells. Results compared with conventional leukocyte histamine release assay. Allergy 1985;40(3):213-8
6. Ostergaard PA, Ebbensen F, Nolte H et al. Basophil histamine release in the diagnosis of house dust mite and dander allergy of asthmatic children. Comparison between prick test, RAST, basophil histamine release and bronchial provocation. Allergy 1990;45(3):231-5
7. Kleine-Tebbe J, Werfel S, Roedsgaard D et al. Comparison of fiberglass-based histamine assay with a conventional automated fluorometric histamine assay, case history, skin prick test, and specific serum IgE in patients with milk and egg allergic reactions. Allergy 1993;48(1):49-53
8. Kleine-Tebbe J, Galleani M, Jeep S et al. Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits. Allergy 1992;47(6):618-23
9. Paris-Kohler A, Demoly P, Persi L et al. In vitro diagnosis of cypress pollen allergy by using cytofluorometric analysis of basophils (Bastotest). J Allergy Clin Immunol 2000;105(2 pt 1):339-45
10. Nolte H, Storm K, Schiotz PO. Diagnostic value of a glass fibre-based histamine analysis for allergy testing in children. Allergy 1990;45(3):213-23
11. Noh G, Ahn H-S, Cho N-Y et al. The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitis. Pediatr Allergy Immunol 2007;18:63-70
12. Aberer W, Hawranek T, Reider N et al. Immunoglobulin E and G antibody profiles to grass pollen allergens during a short course of sublingual immunotherapy. J Investig Allergol Clin Immunol 2007;17(3):131-6
13. Huang S-W. Follow-up of children with rhinitis and cough associated with milk allergy. Pediatr Allergy Immunol 2007;18:81-5
14. Chapman JA, Bernstein IL, Lee RE et al. Food allergy: a practice parameter. Annals of Allergy, Asthma, & Immunol 2006;96:S1-268
15. Miadonna A, Leggieri E, Tedeschi A, et al. Clinical significance ofspecific IgE determination on nasal secretion. Clin Allergy 1983;13(2):155–164
16. Leonardi A, Battista MC, Gismondi M, et al. Antigen sensitivity evaluated by tear-specific and serum-specific IgE, skin tests, and conjunctival and nasal provocation tests in patients with ocular allergic disease. Eye 1993;7:461– 464
17. Weschta M, Rimek D, Formanek M, et al. Local production of Aspergillus fumigatus specific immunoglobulin E in nasal polyps. Laryngoscope 2003;113(10):1798 –1802
18. Small P, Barrett D, Frenkiel S, et al. Local specific IgE production in nasal polyps associated with negative skin tests and serum RAST. Ann Allergy 1985;55(5):736 –9
19. Gurgendze GV, Baraban EI, Gamkrelidze AG. Local humoral immunity in patients with pollen allergy. Allergol Immunopathol (Madr)1990;18(6):315–9
20. Tamura G, Satoh K, Chao CL, et al. Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen? Clin Exp Allergy 1991;21(4):497–502

Cross References

Xolair®, omalizumab, Regence Medical Policy Manual, Drugs, Policy No. 087

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