A. Direct skin test
• Percutaneous (scratch, prick, or puncture)
• Intracutaneous (intradermal)
  
  (NOTE: The number of tests required may vary widely from patient to patient, depending on the patient’s history. Rarely are more than 40 percutaneous or 20 intracutaneous tests required.
  
The utilization of intracutaneous tests is limited to the assessment of hymenoptera venom allergy (stinging insects) and allergies to specific drugs.)

(NOTE: This testing modality identifies allergens causing contact dermatitis. The suspected allergens are applied to the patient’s back under dressings and allowed to remain in contact with the skin for 48 hours. The area is then examined for evidence of delayed hypersensitivity reactions.)

D. Specific IgE in vitro tests such as Enzyme-linked immunosorbent assay (ELISA), ImmunoCAP, Radioallergosorbent test (RAST), Multiple radioallergosorbent tests (MAST) detect antigen-specific IgE antibodies in the member’s serum.
(NOTE: Serologic specific IgE tests and percutaneous skin tests are considered interchangeable as confirmatory tests in terms of their sensitivity and specificity. The number of tests required may vary widely from patient to patient, depending on the patient’s history. Rarely are more than 40 serologic specific IgE tests required. As with percutaneous testing, the need for serologic specific IgE testing should be based on the findings during a complete history and physical examination of the patient consistent with IgE mediated allergic disease.
The NIH’s National Asthma Education Program asthma management guidelines recommend that those patients with persistent asthma on daily medications be evaluated for environmental allergen sensitivity using either skin or blood allergy testing.

The guidelines also state in vitro tests may have an advantage over skin tests in certain situations which include some of those listed below:
• When direct skin testing is not possible due to marked dermatographia;
• When direct skin testing is not possible due to widespread eczema or dermatitis which may be secondary to physical contact with various substances or agents and/or substances taken internally;
• When the patient has a history of allergy, other than to medical agents, which presents hazard to one's health (i.e., due to history of severe allergy where performing skin tests could potentially result in a dangerous reaction);
• When the patient is taking a long-acting antihistamine or other medications (e.g., long-term tricyclic agents such as doxepin and amitriptyline) that interfere with the reaction of the allergy skin test, and the member cannot discontinue the medication long enough to perform the skin test;
• When the patient is on medications (e.g., beta-blockers and MAO inhibitors) that augment the risk of testing (e.g., anaphylaxis, severe bronchospasm);
• When direct skin testing would be difficult or impossible to administer such as in young children or in patients with mental or physical impairments;
• When direct skin testing has not been conclusive and further diagnostic testing is necessary (i.e., skin testing results are negative in a patient with a history strongly suggestive of atopy).
• When there is an inappropriate response to the saline (negative) and/or histamine (positive) control, making skin testing impossible; or
• When the allergen in question is uncommon and/or does not have a readily available commercial extract.)
E. Total serum IgE concentration

(NOTE: This testing modality may be indicated for those patients suspected of having allergic bronchopulmonary aspergillosis, immune deficiency disease characterized by increased IgE levels (e.g., Wiskott-Aldrich syndrome, hyper-IgE staphylococcal abscess syndrome), IgE myeloma, or pemphigoid.)

F. Certain bronchial challenge tests

(NOTE: Histamine or methacholine is used to perform this test when it is necessary to determine if the patient has hyper-responsive airways. Volatile chemicals are used to perform the test when the allergy is encountered in an occupational setting. If dust, ragweed, or other common allergens are the suspected cause of the problem, this test is not medically necessary, since skin tests can be used in these situations.)

G. Double-blind food challenge test

(NOTE: With this test, the patient ingests the food to which sensitivity is suspected. Both the patient and the physician are “blinded.” This is usually done at home, but in some instances of extreme suspected hypersensitivity, it may be performed in the office setting.)

H. Serial Endpoint Testing (SET)
• It is considered medically necessary for the determination of a safe starting dose for testing or immunotherapy when there is potential for the specific allergen in question to produce a severe systemic allergic reaction or anaphylaxis.

(NOTE: Serial endpoint testing involves a subcutaneous injection of increasing doses of an allergen to detrmine the lowest concentration that produces a positive reaction.)

A. Provocative tests for food or food additive allergies
B. Nasal challenge test
C. Conjunctival challenge test (ophthalmic mucous membrane test)
D. Leukocyte histamine release test (LHRT)
E. Rebuck skin window test
F. Passive transfer or P-X (Prausnitz-Küstner) test (obsolete - replaced by Radioallergosorbent Tests)
G. IgG and IgG4 RAST/ELISA testing

(NOTE: Please refer to a separate policy on 'Antigen Leukocyte Antibody Test - ALCAT' Policy #099 in the Pathology Section.

Measurement of allergen-specific IgG or IgG4 antibodies in the evaluation of food allergy is considered a test of unproven or no value by the American Academy of Allergy, Asthma & Immunology - AAAI, American College of Allergy, Asthma & Immunology - ACAAI, the Joint Council of Allergy, Asthma and Immunology - JCAAI, and the American Gastroenterological Association - AGA.

A position statement from the European Academy of Allergy and Clinical Immunology (EAACI) concludes "food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints". This position paper was endorsed by the American Academy of Allergy, Asthma and Immunology. A similar position statement from the Canadian Society of Allergy and Clinical Immunology (CSACI) also concludes that "the presence of specific IgG to food is a marker of exposure and tolerance to food… expected in normal, healthy adults and children" and "the inappropriate use of this test only increases the likelihood of false diagnoses being made, resulting in unnecessary dietary restrictions".

Currently, there is insufficient evidence in the published, peer-reviewed scientific literature to support the use of cytotoxic tests, e.g., ALCAT in the diagnosis or management of chemical or food allergies.)

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[INFORMATIONAL NOTE: The policy on leukocyte histamine release test (LHRT), listed as an investigational allergy test, is based on a 2003 focused review on LHRT. A review of the literature from 1995 to 2003 did not identify published peer-reviewed articles that would prompt reconsideration of this interpretation, and thus the policy statement is unchanged. LHRH is a technique to evaluate the in vitro release of histamine from leukocytes (i.e., basophils) in response to exposure to an allergen, and thus is designed to provide an in vitro correlate to an in vivo allergic response (i.e., skin prick testing). In contrast, the RAST test attempts to correlate the presence of allergy to serum levels of antigen-specific IgE as an index of allergic reactivity. Initially, measurements of histamine release required isolation of leukocytes from whole blood followed by the isolation of the released histamine; the laboratory techniques were difficult and time consuming and thus LHRT was generally only used as a research tool. Recently, a special type of glass fiber has been developed that binds histamine with high affinity and selectivity. These glass fibers can be used as a “solid phase” to absorb the histamine that is released directly into the blood. The recent commercial availability of simplified and automated methods of laboratory analysis (i.e., both ELISA and radioimmunoassays) have renewed interest in the clinical applications of LHRT in the evaluation of food, inhalant, and drug allergies. Technologies related to histamine release assays include assays for the release of sulphidoleukotriene or the flow cytometric detection of CD36 expression on the stimulated basophils. Both of these tests are similar to LHRT in that they detect the activation of basophils as a direct reflection of the immune response.

The published literature regarding LHRT was reviewed using the same criteria as used in the TEC Assessment of SET. For example, quality indicators for studies of diagnostic trials included:

• Prospective enrollment
• Representative patient population enrolled
  • Appropriate spectrum of patients
  • Unbiased enrollment (no referral bias)
  • Few patients not enrolled that are eligible
  • Appropriate accounting for all eligible patients
• All eligible patients received both tests
• LHRT was interpreted independently of alternative test (i.e., skin prick, RAST, or bronchial provocation test)
• Alternative tests were interpreted independently of LHRT

86001
86003
86005
86343
95004
95017
95018
95024
95027
95028
95044
95052
95056
95060
95065
95070
95071
95076
95079