LCD L36241: Allergy Testing

Compliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits.

History/Background and/or General Information

Allergy is a form of exaggerated sensitivity or hypersensitivity to a substance that is either inhaled, ingested, injected, or comes in contact with the skin or eye. The term allergy is used to describe situations where hypersensitivity results from heightened or altered reactivity of the immune system in response to external substances. Allergic or hypersensitivity disorders may be manifested by generalized systemic reactions as well as localized reactions in any part of the body. The reactions may be acute, subacute, or chronic, immediate or delayed, and may be caused by a variety of offending agents; pollen, molds, mites, dust, feathers, animal fur or dander, stinging insect venoms, foods, drugs, etc.

Allergy testing is performed to determine a patient's immunologic sensitivity or reaction to particular allergens for the purpose of identifying the cause of the allergic state, and is based on findings during a complete medical and immunologic history and appropriate physical exam. There are several different types of diagnostic modalities available for allergy testing. Positive and negative controls should be performed with all tests and tests used should have proven efficacy as demonstrated through scientifically valid medical studies published in peer review journals. 1,2,3,4

This policy addresses immediate (IgE-mediated) hypersensitivity and delayed (cell mediated) hypersensitivity and includes in vivo testing (skin tests), organ challenge tests, in vitro testing, limitations, and provider qualifications. The specific allergy testing described below is considered medically reasonable and necessary in accordance with the criteria noted in accordance with evidence-based guidelines.

Covered Indications

A. In Vivo Testing (skin tests):

In vivo testing (skin tests) include the performance and evaluation of selective cutaneous and mucous membrane tests in correlation with history, physician examination, and other observations of the patient. The tests are performed to determine body sensitivity and reaction to the antigen for the purpose of diagnosing the presence of allergic reaction to antigenic stimuli. Prick/puncture tests or intracutaneous tests are the preferred techniques for immunoglobulin E (IgE)-mediated hypersensitivity. 1

• Percutaneous testing (scratch, puncture, prick), immediate type reaction, will be considered medically reasonable and necessary when used to evaluate IgE mediated hypersensitivity to inhalants, foods, Hymenoptera (stinging insects), chemicals, and specific drugs (e.g., penicillins and macromolecular agents). 1

• Intracutaneous (intradermal) testing, immediate type reaction, will be considered medically reasonable and necessary when used to evaluate IgE mediated hypersensitivity to inhalants, Hymenoptera venoms (e.g., bee venom), drugs (e.g., penicillin, insulin, heparin, muscle relaxants) and/or chemicals. 1,2

• Patch testing is used to differentiate allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). Patch testing is the gold standard method of identifying the cause of allergic contact dermatitis. This testing is indicated to evaluate a nonspecific dermatitis, allergic contact dermatitis, pruritus, and other dermatitis to determine the causative antigen. It is a diagnostic test reserved for patients with skin eruptions for which a contact allergy source is likely. 1,2

The patch test procedure can induce an eczematous reaction in miniature by applying suspect allergens to normal skin, allowing the physician to determine a specific patient allergy. Patch tests are applied to the skin on the patient's back and left in place for 48 hours. The test is interpreted after 48 hours, and typically once again at 72 hours or 96 hours, and the reactions are systemically scored and recorded. The patient is then informed and educated regarding specific allergies and avoidance of exposure. Avoidance of the identified allergen(s) is critical to patient improvement and resolution of the dermatitis. 1

Allergy patch testing will be considered medically reasonable and necessary when used to diagnose allergic contact dermatitis for patients with a clear-cut clinical suspicion of contact allergy, and they are tested with the chemicals relevant to the problem, which may include the following:

• Dermatitis due to detergents, oils and greases, solvents, drugs and medicines in contact with skin, other chemical products, food in contact with skin, plants (except food), cosmetics, and metals, such as nickel and rubber additives (this is not an all-inclusive list). 1,2,3

• Photo patch testing will be considered medically reasonable and necessary to evaluate unique allergies resulting from photosensitization (e.g., photo-allergic contact dermatitis). 1

• Photo testing will be considered medically reasonable and necessary to evaluate skin abnormalities (e.g., itching, blisters, hives) resulting from exposure to sunlight. 1

• Intracutaneous (intradermal) Dilutional Testing (IDT) (also known as Skin Endpoint Titration [SET]), immediate type reaction is intradermal testing of sequential and incremental dilutions of a single antigen. The endpoint is determined by intradermal testing with the use of approximately 0.1 ml of serial five-fold dilution extract. The endpoint is the weakest dilution that produces a positive skin reaction and initiates progressive increase in the diameter of the wheals with each stronger dilution. For example, if Hymenoptera venom sensitivity is suspected, initial prick/puncture tests followed by serial endpoint titration with intracutaneous tests may be required. 1,5

• Intracutaneous (intradermal) dilutional testing will be considered medically reasonable and necessary when used for determining the starting dose for immunotherapy for individuals with Hymenoptera venom sensitivity and significant aeroallergen sensitivity.

• Intracutaneous (intradermal) testing, delayed reaction

• Intracutaneous (intradermal) testing will be considered medically reasonable and necessary when used in epidemiologic testing of susceptible populations exposed to bacterial and fungal pathogens (e.g., tuberculin skin test). The tuberculin skin test is elicited by the intracutaneous injection of 0.1 mL of standardized purified protein derivative (PPD) starting with the intermediate strength of 5 tuberculin units. The size of the delayed skin test response is measured 48 hours after antigen challenge, and the largest diameter of the palpable firm area that outlines the induration reaction should be measured to the nearest millimeter. 1

B. Organ Challenge Tests:

Controlled challenges or supervised exposure are considered the gold standard for assessing whether clinical sensitivity is present. When tests for IgE-mediated immunity are ambiguous, organ challenge testing is used to determine if clinical sensitivity exists. Organ challenge test material may be applied to the mucosae of the conjunctivae, nares, GI tract, or bronchi. All organ challenge tests should be preceded by a control test with diluent and, if possible, the procedure should be performed on a double blind or at least single, blind basis. Considerable experience with these methods is required for proper interpretation and analysis. Specific organ challenge tests will be considered medically reasonable and necessary under the following conditions 1,4,6 :

Ophthalmic mucous membrane challenge tests and direct nasal mucous membrane challenge tests provided that levels of allergic mediators (such as histamine and tryptase) are measured.

Inhalation bronchial challenge tests to evaluate new allergens and to substantiate the role of allergens in patients with significant symptoms. Results of these tests are ordinarily evaluated by objective measures of pulmonary function and occasionally by characterization of bronchoalveolar lavage samples.

• Inhalation bronchial challenge tests should be performed as dose-response assays wherein provocation concentration thresholds can be determined on the basis of allergen concentration required to cause a significant decrease in pulmonary function measurements.

• Oral food challenge (OFC) testing is a physician-supervised oral provocation procedure where a patient ingests gradually increasing amounts of a food under medical supervision until an age-appropriate serving is reached or the feeding is terminated because of symptoms. Prior to conducting an OFC, the patient’s medical history, age, past adverse food reactions, skin prick testing (SPT), and serum food allergen-specific IgE results must be considered.

• Oral food challenge testing will be considered medically reasonable and necessary when the diagnosis is uncertain for:

• Food allergy dermatitis

• Anaphylactic shock due to an adverse food reaction

• Allergy to medicinal agents

• Allergy to foods

C. In Vitro Testing:

Specific IgE In Vitro Tests

• Examples include 1,7 :

• ELISA (Enzyme linked immunosorbent assay)

• MAST (Multiple thread allergosorbent test)

• IP (Immuno-peroxidase test)

• PRIST (Paper radioimmunosorbent test)

• CAP (ImmunoCap assay)

Specific IgE immunoassays detect antigen-specific IgE antibodies in the patient's serum. Testing must be based on a careful history/physical examination which suggests IgE- mediated disease. The choice of specific allergen specificities for testing should be guided by a comprehensive physical exam that includes objective symptoms to select appropriate testing. In situations in which a high pretest probability has been determined, confirmation of sensitization is frequently conducted by IgE antibody testing due to the possible risk of life-threatening anaphylaxis and/or the possibility of starting a course of immunotherapy. Specific IgE in vitro tests are useful when testing for inhalant allergens (pollens, molds, dust mites, animal dander), specific foods, insect stings, and other allergens such as drugs or latex, when direct skin testing is impossible due to extensive dermatitis, or in marked dermatographism. 1,5,7

In-vitro allergen specific IgE testing will be considered medically reasonable and necessary under the following conditions 1,5,7 :

• Direct skin testing is not possible due to extensive dermatitis, dermographism, ichthyosis, or generalized eczema.

• For patients who cannot be safely withdrawn from medications that interfere with skin testing (such as long-acting antihistamines, tricyclic antidepressants).

• Testing of uncooperative patients with mental or physical impairments.

• As adjunctive laboratory testing for disease activity of allergic bronchopulmonary Aspergillosis (ABPA) and certain parasitic diseases.

• The evaluation of cross-reactivity between insect venoms (e.g., fire ant, bee, wasp, yellow jacket, hornet).

• When the pretest probability of Hymenoptera venom allergy is strong and the skin test result is negative, serological detection of IgE antibodies is recommended for vespid, wasp, honeybee, bumblebee, and fire ant venoms.

• When clinical history suggests an unusually greater risk of anaphylaxis from skin testing than usual (e.g., when a patient has a history of a previous systemic reaction to skin testing or when an unusual allergen is not available as a licensed skin test extract).

• Measurements of total IgE serum levels are not appropriate in most general allergy testing which is performed to determine a patient’s immunologic sensitivity or reaction to particular allergens for the purpose of identifying the cause of the allergic state. Total serum IgE levels will only be considered medically reasonable and necessary for the following 1 :

• Follow up of bronchopulmonary Aspergillosis (ABPA),

• Select immunodeficiency such as the syndrome of hyper-IgE,

• Eczematous dermatitis,

• Recurrent pyogenic infections, or

• Evaluation for omalizumab therapy.

Limitations

• The number of allergy tests performed should be judicious and dependent upon the patient’s history, physical findings and provider’s clinical judgment. All patients should not necessarily receive the same tests or the same number of sensitivity tests. Rather, testing should be patient specific based on the history and physical examination. 1

• Per evidence-based guidelines, the number of skin tests (e.g., 70 prick/puncture and 40 intracutaneous tests) for inhalant allergens is justified as an initial diagnostic evaluation. Also, up to 80 patch tests may be required for ACD diagnosis. 1,8-10

• In-vitro testing performed in addition to skin testing for the same antigen is not usually necessary, except in the case of suspected latex sensitivity, Hymenoptera, or nut/peanut sensitivity where both the skin test and the in-vitro test may be performed. 1

• Intracutaneous (intradermal) tests for food sensitivity are not recommended because of numerous false-positive test findings and possible risks. 1

• Food allergy tests are inappropriate for investigation of chronic idiopathic urticaria (CIU) or angioedema. 1

• Routine utilization of a large number of skin tests or routine annual tests without a discernable indication is not acceptable. 1

• Please refer to the CMS IOM Publication 100-03, Medicare National Coverage Determinations (NCD) Manual , Chapter 1, Part 2, Section 110.11 Food Allergy Testing and Treatment, Section 110.12 Challenge Ingestion Food Testing, and Section 110.13 Cytotoxic Food Tests for additional limitations.

• Please refer to the CMS IOM Publication 100-03, Medicare National Coverage Determinations (NCD) Manual , Chapter 1, Part 4, Section 230.10 Incontinence Control Devices for additional limitations.

The following tests are considered not medically reasonable and necessary:

• Allergen specific IgE; qualitative, multiallergen screen and multiplex microarray chip for IgE antibody detection are non-specific screening tests that do not identify a specific antigen. 1,5 These tests are screening tools and therefore are not covered by Medicare.

• Provocation-neutralization 1,11

• Electrodermal testing 1,6,11

• Applied kinesiology 1,6,11

• Iridology 1

• Hair analysis 1,6,11

• Lymphocyte proliferation test 1,11

• Basophil activation tests (BAT) to diagnose food or drug allergies 1,6,11,12

• T-cell proliferation assay 6

• Facial thermography 6

• Breath condensate analysis 1

• In vitro tests for delayed hypersensitivity to contact allergens (e.g., metals and bone cement) 3

• Immunoglobulin G (IgG) allergy testing 13

• Tests to diagnose Food Allergy:

• Food specific IgG, IgG4, and IgG/IgG4 antibody tests 1,6,11

• Atopy patch tests to diagnose non-contact food allergy 1,11

• Intradermal testing to diagnose food allergy 6

• Component-resolved diagnostics (CRD) to diagnose food allergy 6

• Epitope binding testing to diagnose food allergy 6

• T-cell responses to food allergens 6

• Platelet activating factor (PAF) to diagnose food allergy 6

• Gastric juice analysis 6,11

• Mediator release assay (LEAP diet) 11

• Cytotoxic food testing 1,11

• Please refer to the CMS IOM Publication 100-03, Medicare National Coverage Determinations (NCD) Manual , Chapter 1, Part 2, Section 110.11 Food Allergy Testing and Treatment, Section 110.12 Challenge Ingestion Food Testing, and Section 110.13 Cytotoxic Food Tests for additional coverage restrictions.

Provider Qualifications

Multiple guidelines and appropriate use criteria are available for allergy testing.

Pretest probability is used to determine if allergy testing is appropriate and is based on the patient’s clinical history.

A literature search was conducted using the following key words: allergy; allergen; allergy testing; guideline; practice parameters; meta-analysis; systematic review; diagnosis; IgE; pretest probability; clinical history; skin testing; skin prick tests; food allergy; drug allergy; venom allergy; insect hypersensitivity; Hymenoptera venom; anaphylaxis; urticaria; in vitro allergy tests; in vivo allergy tests; specific IgE antibodies; allergic contact dermatitis; patch testing; oral food challenge; immediate IgE-mediated hypersensitivity; delayed (cell mediated) hypersensitivity; atopic dermatitis; multiallergen screen; photoallergy; allergic rhinitis; asthma; cockroach; house dust mites; and inhalant allergy.

Evidence-based guidelines