LCD L40341: Allergy Diagnostic Testing

Overview

Allergy is a hyper-immunologic response to environmental substances, known as allergens, that commonly affect organs such as the skin, eyes, ears, nose, throat, and respiratory and gastrointestinal (GI) tracts. 1-4 An allergen is an antigenic substance that triggers this immune response. 5

A Type I Hypersensitivity reaction is the primary mechanism driven by immunoglobulin E (IgE) antibodies. These antibodies activate mast cells and basophils which release histamine and other pro-inflammatory mediators upon encountering the allergen. 1,3,4,6,7 Symptoms can include itchy, watery eyes, sneezing, coughing, skin redness, local or wide-spread hives (urticaria), asthma, angioedema, vomiting, diarrhea, and in severe cases, anaphylaxis. 1,8,9

In some cases, allergens can also cause a Type IV Hypersensitivity reaction, which is delayed and mediated by chemical messengers (cytokines) released by sensitized helper T cells. 4,10,11

Allergic reactions vary from person to person, and not everyone reacts to allergens in the same way. Therefore, when symptoms are significant, diagnostic testing may be necessary to identify the specific allergen(s) and guide treatment.

This policy addresses both immediate IgE-mediated hypersensitivity reactions and delayed cell-mediated hypersensitivity. It includes guidelines for in vivo testing (such as skin tests), organ challenge tests, serum specific IgE in vitro testing, and details on limitations and provider qualifications. Notably, other diagnostic immunology testing for the evaluation of immune system function is outside the scope of this policy.

Coverage Indications

Indications for Allergy Testing

Allergic diagnostic testing is generally divided into 2 main types: in vivo and in vitro testing.

Allergy testing is covered when it has proven efficacy as demonstrated through scientifically valid peer reviewed published medical studies.

A comprehensive medical and immunologic history and physical examination with testing based on reasonable exposure to the suspected allergen(s) should be demonstrated in the documentation to support reasonable and necessary coverage requirements.

Due to the possibility of unforeseen severe allergic reactions, medical supervision and resuscitative equipment must be available during in vivo testing.

In Vivo Testing

In vivo testing includes various skin tests and other organ specific testing to diagnose allergic reactions. Findings must be correlated with clinical symptoms. The use of positive and negative controls is required.

• Percutaneous Testing - commonly used for suspected IgE-mediated allergic reactions to inhalants, Hymenoptera venoms (wasps, honeybees, yellow jackets, hornets, imported fire ants, and others), foods, and certain drugs and occupational exposures.

• Intracutaneous/Intradermal Testing (IDT) - used when percutaneous tests are negative, yet suspicion remains high. Not recommended for food or latex allergy due to risk of systemic reactions.

• Skin Endpoint Titration (SET) Testing (also known as Intradermal Dilutional Testing) - used to determine immunotherapy starting doses for primarily Hymenoptera venom or aeroallergen sensitivities.

• Skin Patch Testing - used for diagnosis of allergic contact dermatitis (ACD) caused by various substances (e.g., detergents, oils, metals, drugs, chemicals, food products). Custom patch testing may be needed based on clinical history.

• Photo Patch Testing - used if exposure to allergens is suspected to be worsened with ultraviolet (UV) light.

• Photo Testing - involves skin irradiation with UV light to evaluate photosensitivity.

• Delayed Hypersensitivity Skin Testing - commonly used for testing contact allergens (see skin patch testing) and infections with intracellular pathogens (such as tuberculin), or anergy tests.

Organ Challenge Testing/Allergen Provocation Testing - In vivo testing via organ challenge is reserved for cases where clinical history suggests allergy, but initial skin or serum specific IgE testing is inconclusive and/or when objective confirmation of a clinically relevant allergic response is required. Testing should be performed in a clinical setting in which immediate emergent response by the physician and/or clinical staff is readily available. Testing may be performed in an open, single-blinded or double-blinded fashion.

• Nasal Mucous Membrane Challenge Test - Confirms the cause of allergic rhinitis.

• Ophthalmic Mucous Membrane (Conjunctival) Challenge Test- Assesses localized eye symptoms in the diagnosis of allergic conjunctivitis and may assist in the diagnosis of allergic rhinitis.

• Inhalation/Bronchial Challenge Test - Measures airway hyperresponsiveness, often used in asthma cases and in identifying hypersensitivity reactions to environmental or occupational exposures.

• Must be measured objectively, compared with a placebo control, usually involving some form of pulmonary function testing (e.g., measurement of FEV 1 before and after introduction of suspected allergen or other direct/indirect stimuli).

• Oral Challenge Test - Administers food or drug allergens in increasing doses to monitor reactions. The service is allowed once per patient encounter, regardless of the number of items tested, and includes evaluation of the patient’s response to the test items.

• Food Challenge Test: Considered reasonable and necessary for the following indications: suspected IgE- mediated food allergy, anaphylactic shock due to an adverse food reaction, and suspected food-related dermatitis.

• The need for oral food challenge (OFC) would stem from non-confirmatory results after having performed more commonly utilized first line in vivo testing such as skin prick testing (SPT) or patch testing, or in vitro testing such as serum specific IgE testing; unless testing for suspected allergen is not readily available or unless there is further need to confirm the clinical relevance of the allergen hypersensitivity identified on skin and/or serum testing in order to avoid unnecessary food restriction.

• OFC testing is discontinued if objective reactions are identified, or the last dose of food tested does not elicit any reactive systems.

• Testing performed by the patient in the home, and not in the office setting under medical supervision, will not be covered.

• Challenge ingestion food testing is not payable when used to diagnose rheumatoid arthritis, depression, or respiratory disorder. Please refer to CMS Pub. 100-03, Medicare National Coverage Determinations (NCD) Manual, Chapter 1, Part 2, Section 110.12 for additional coverage details.

• Sublingual, intracutaneous and subcutaneous provocative and neutralization testing and neutralization therapy for food allergies are excluded from Medicare coverage. Please refer to CMS Pub. 100-03, Medicare National Coverage Determinations (NCD) Manual, Chapter 1, Part 2, Section 110.11 for additional details.

• Drug Challenge Testing: Gradual administration of suspected drug allergens under close medical supervision. Used in the diagnosis of suspected IgE-mediated drug allergy, especially drugs such as nonsteroid anti-inflammatory drugs (NSAIDs), local anesthetics, non-beta lactam antibiotics, and other medications.

• The need for oral drug challenge would stem from non-confirmatory results after having performed more commonly utilized first line in vivo testing such as SPT or patch testing, or in vitro testing such as serum specific IgE testing; unless testing for suspected allergen is not readily available or unless there is further need to confirm the clinical relevance of the allergen hypersensitivity identified on skin and/or serum testing in order to avoid unnecessary drug restriction.

• Oral drug challenge may be appropriate for the evaluation of previously avoided drugs when there is a remote and/or questionable history of suspected drug allergy to determine whether the allergy labeling is accurate or whether there is need to resolve a drug allergy label (de-label), especially of essential medications (e.g. antibiotics, chemotherapeutics). In these instances, documentation to support medical necessity is warranted.

In Vitro Testing

Immunoassays measuring serum IgE levels are an alternative diagnostic approach.

• Total Serum IgE*: Covered for indications including:

• Follow up of Allergic bronchopulmonary aspergillosis (ABPA)

• Select immunodeficiency such as Hyper-IgE syndromes *

• Eczematous dermatitis

• Recurrent Pyogenic infections *

• Evaluation for omalizumab therapy

* Note: The indications for Total Serum IgE testing are not confined to traditional allergy testing (i.e. IgE-mediated and delayed hypersensitivities to external allergens upon exposure), where its use is limited. It is also recognized that Total Serum IgE may have additional roles in the diagnostic evaluation of other immunologic disorders, malignancies, and parasitic infections. These uses fall outside the defined scope of this LCD and are therefore not all specifically addressed. Any omission in this case should not be interpreted as a non‑coverage determination.

• Allergen Specific Serum IgE: Covered for indications including:

• Contraindications to skin testing secondary to widespread skin disease (e.g., dermatographism, ichthyosis, extensive dermatitis, generalized eczema)

• Medication use impacting skin testing results that cannot be safely discontinued (e.g., long-acting antihistamines, tricyclic antidepressants)

• Uncooperative patients secondary to age and/or mental and/or physical impairment

• Patients for whom the potential benefits of skin testing do not outweigh the associated anaphylactic risk

• Uncontrolled asthma

• Inconclusive skin testing results to rule out cross-reactivity and/or in setting of persistent clinical suspicion for allergy

Limitations

• Inhalant allergy evaluation may require up to 70 percutaneous tests and up to 40 intracutaneous tests if percutaneous tests are negative; therefore, greater than 70 percutaneous and 40 intracutaneous tests would not be reasonable and necessary.

• Patch tests may require up to 80-90 tests; therefore, greater than 90 tests would not be reasonable and necessary.

• Routine repeat testing is not considered reasonable and necessary unless documentation supports the need (e.g., changes in environmental exposure, new clinical signs/symptoms, lack of efficacy of current immunotherapy).

• The total number of tests performed (e.g. skin prick, intracutaneous, patch testing, or serum testing) should not exceed generally accepted standards of testing set forth by professional associations.

• Routine in vitro testing performed in addition to skin testing for the same antigen is not reasonable and 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 when indicated.

• IgE-mediated allergy testing for substances such as newsprint, sugar, cornstarch, orris root, tobacco smoke, cotton, formaldehyde, and smog is not supported by evidence and hence is not reasonable and necessary.

• Allergen‑specific IgE:

• Qualitative multiallergen screening tests (single result reported as positive or negative without identification or quantification of individual allergens) are not considered reasonable and necessary as the information they provide does not offer clinical utility in diagnosing allergen‑specific hypersensitivities.

• Multiplex microarray test utilizing a single platform or chip to simultaneously assess multiple categories of allergens (e.g. aeroallergens, food allergens, venoms, latex) is considered screening and is therefore not reasonable and necessary when not clearly supported by the patient’s documented clinical history, presenting signs and symptoms, relevant exposures and/or differential diagnosis.

• Singleplex testing directed at suspected allergen(s) is considered reasonable and necessary when ordered based on the patient’s documented clinical history, presenting signs and symptoms, relevant exposures and/or differential diagnosis.

• Coverage for all serum lab testing requires performance in CLIA (Clinical Laboratory Improvement Amendments of 1988) certified laboratories. (42 CFR §493.3)

Background

In Vivo Testing

Skin testing is the first line diagnostic method for assessing type I IgE mediated hypersensitivity related to allergic conjunctivitis, rhinitis, asthma, dermatitis, food, drug, venom, and some occupational related allergies. 1,2,4,12-15 Skin testing can be performed using various methods, including percutaneous testing, intracutaneous or intradermal testing, intradermal dilutional or SET testing, and/or patch testing. Type IV cell-mediated (delayed) hypersensitivity reactions may also be evaluated using certain types of skin testing. The diagnosis of IgE or cell-mediated (delayed) hypersensitivity conditions does not rely on diagnostic testing alone. Results must be correlated with the patient’s clinical history and physical examination. 2,99

Percutaneous Testing (by scratch, puncture, or prick): SPT describes the most common, and preferred method, for diagnosing immediate hypersensitivity to allergens. 1,2,13,14 A small amount of allergen is introduced to the skin through a small prick or puncture, causing an allergic reaction that results in raised, red, and itchy areas (wheal and flare) which indicates sensitivity. 4,7,13 This method is quick, safe, and cost-effective. Medical supervision is required due to the risk of anaphylaxis. 1,12-14,16,100 It is most sensitive for aeroallergens but may be less reliable for venoms, foods, and drugs. Intradermal testing is often performed when percutaneous results are negative, particularly for venom allergies. 13,14,17,18