Notification

In Vitro Allergy Testing


Notification Issue Date: 02/22/2019

This version of the policy will become effective 03/25/2019. Policy has been updated to communicate the continued coverage of ELISA, ImmunoCAP, and MAST, and the removal of RAST and FAST for in vitro allergy testing, due to review of most current clinical guidelines. Policy has been updated to establish lymphocyte stimulation tests (to include lymphocyte mitogen response assays, lymphocyte transformation tests, and others as detailed in the policy) as a category of testing considered experimental/investigational for in vitro allergy testing, based upon most current clinical guidelines. CPT code 86353 was added to the policy to represent lymphocyte stimulation tests, which are considered experimental/investigational.



Medical Policy Bulletin


Title:In Vitro Allergy Testing

Policy #:06.02.26d

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

In vitro allergy testing (e.g., enzyme-linked immunosorbent assay [ELISA], ImmunoCAP, and multiple antigen simultaneous test [MAST]) for the measurement of serum immune globulin E (IgE) is considered medically necessary and, therefore, covered for a maximum of 30 tests per calendar year per individual to determine if an individual's serum contains IgE antibodies against specific allergens.

NOT MEDICALLY NECESSARY

Multiallergen screening is a qualitative test that does not quantify specific antigens; therefore, it is considered not medically necessary and not covered. Qualitative multiallergen screening is considered not medically necessary and, therefore, not covered because the available published peer-reviewed literature does not support its use in the treatment of illness.

EXPERIMENTAL/INVESTIGATIONAL

The following tests are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature:
  • Leukocyte histamine release test
  • Cytotoxic food testing
  • Lymphocyte stimulation test
  • Immune globulin G (IgG) ELISA, indirect method

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, in vitro allergy testing is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met. However, services that are identified in this policy as experimental/investigational or not medically necessary are not eligible for coverage or reimbursement by the Company.

Services that are experimental/investigational are a benefit contract exclusion for all products of the Company. Therefore, they are not eligible for reimbursement consideration.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA has approved the Allergen ImmunoCAP® devices under the 510(k) process.

There are numerous ImmunoCAP® models approved by the FDA for measurement of specific serum IgE antibodies to the respective allergens bound to the ImmunoCAP®.

Description

An allergy is defined as an acquired hypersensitivity to a substance (allergen) that does not normally cause a reaction. It is essentially a disorder of the immune system that results in an antibody-antigen reaction. The most common manifestations of allergy involve the respiratory tract or the skin.

In vitro allergy testing detects antigen-specific immune globulin E (IgE) antibodies in serum. This type of testing may be required when direct skin testing is not possible for inhalant allergens (e.g., pollens, molds, dust, mites, animal danders), foods, insect stings, or other allergens such as drugs. In vitro allergy testing is appropriate for individuals who have skin reactions/conditions such as severe dermatographism, ichthyosis, or generalized eczema. It is also appropriate for uncooperative individuals (young children or individuals with mental and/or physical handicaps), individuals with a high risk of anaphylaxis from skin testing, or individuals for whom direct skin testing has been inconclusive.

The tools that are used for in vitro allergy testing are all variations of one biomedical technology known as an immunoassay. Immunoassays, used in both research and clinical settings, are used to quantify biological molecules of interest, capitalizing on their properties as antigens or antibodies. This assay can measure the concentration of a particular biomolecule via the antigen-antibody reaction, a naturally occurring event in the human immune response. In this reaction, a part of a pathogen known as an antigen is detected by immune effector cells and eventually bound by an antibody to be neutralized. The antibody involved in allergic response is known as IgE; the antibody-antigen complex is labeled by an anti-IgE molecule that is tagged with a chemical agent for visualization. The quality of an immunoassay depends upon the specificity and selectivity of antibody reagents used, as well as the method of visualization employed (e.g., radioisotopes, enzyme-catalyzed colored products, fluorescence).

In vitro allergy tests must be interpreted in the context of each individual's specific clinical history; the diagnosis of an allergic disorder cannot be based solely on a laboratory result. Allergy is a dynamic physiologic response with multiple contributing variables, including, but not limited to, presence of allergen-specific IgE. While most patients who experience symptoms of hypersensitivity upon allergen exposure show measurable levels of allergen-specific IgE, rarely some patients may not have any allergen-specific IgE detectable with routine testing. Specific IgE tests are important and recommended in the identification of allergy, but it should be noted that alone they are not sufficient to diagnose allergy.

The following blood tests may be used to aid in the diagnosis, evaluation, and treatment of allergy:

Multiple allergen simultaneous test (MAST), along with radioallergosorbent test (RAST®) and fluoroallergosorbent test (FAST™) are in vitro techniques for determining whether an individiual’s serum contains IgE antibodies against specific allergens of clinical importance. RAST® was developed in 1974 by Pharmacia Diagnostics AB (Uppsala, Sweden) as a tool to measure allergen-specific IgE. In this methodology, the allergen is coupled to a paper disc. The patient’s serum is added to the disc, whereby an antigen-antibody complex forms in the case of allergy. Radioactive IgE is added and complexes, and a gamma counter scores the level of binding to inform on intensity of the allergy. RAST® is a brand name, but over time has become a catch-all term to (erroneously) refer to any in vitro assay for allergen-specific IgE. Though RAST® was initially the in vitro allergy test of choice, it is an older technology that has largely been replaced by the use of other immunoassays such as ImmunoCAP® and ELISA testing. FAST™, developed in 1987, has a similar mechanism of action as RAST®, but instead of radiolabeling, uses fluorescence labeling and detects antigen-antibody activity using a spectroflurometer. MASTs are also similar to RAST® in that the specific allergen of interest is coupled to a solid phase (typically nitrocellulose instead of paper), antibodies from the added serum complex to the antigen if allergy exists, and a tagged anti-IgE is added to visualize the binding. Unlike RAST® and FAST™, MAST is not a registered brand name, but rather a category of immunoassays. Some MASTs use chemiluminescence visualization, others use colored products resulting from the oxidation of various organic substrates.

Enzyme-linked immunosorbent assay (ELISA), also known as enzyme immunoassay, is a plate-based assay technique designed for detecting and quantifying substances such as peptides, antibodies, and hormones. In allergy testing, the antigen is immobilized on a solid surface, then complexed with an antibody, which is linked to an enzyme (such as horseradish peroxidase). The enzyme reacts with a substrate that produces a colorimetric product, which can be quantified.

Created in 1989 by the developer of RAST®, ImmunoCAP is described as the next generation of laboratory allergy testing. These assays can be performed singly for just one allergen (ImmunoCAP®), or in multiplex format (ImmunoCAP® Immuno Solid-phase Allergen Chip [ISAC]). While the singleplex assay determines IgE levels against one chosen allergen, the multiplex assay uses a fixed array of 112 native allergen components (classifying it as a MAST). The ImmunoCAP technology uses a three-dimensional, activated cellulose polymer encased in a capsule that increases the surface area and can bind to more antibodies. ImmunoCAP is lauded for its ability to obtain quantified allergen-specific IgE antibody levels, in addition to the lack of interference from allergen-specific IgG antibodies.

The leukocyte histamine release test is an in vitro method of allergy testing that measures the amount of histamine secreted from basophils, a type of white blood cell, upon exposure to an allergen extract added to the serum sample.

Cytotoxic food testing involves mixing a suspected offending substance with a sample of the individual's blood. The sample is then observed under a microscope for changes in the white blood cells.

Lymphocyte stimulation tests, otherwise known as lymphocyte response assays, lymphocyte proliferation assays, and lymphocyte transformation tests, measure the ability of lymphocytes to respond in vitro to an activation stimulus. This method requires the isolation of peripheral blood mononuclear cells, which are then put in tissue culture with a foreign antigen of interest. Subsequent measurement of the number of dividing cells indicates immune stimulation.

Immune globulin G (IgG) ELISA, indirect method, tests IgG immune reaction (rather than IgE immune reaction) in serum. At the present time, there is insufficient data to support the reliability of allergen-specific IgG assays for routine diagnostic testing.

There is insufficient evidence to support the efficacy of the following in vitro tests for the diagnosis and treatment of allergy: the leukocyte histamine release test, cytotoxic food testing, the lymphocyte proliferation test, and IgG ELISA, indirect method.
References


Abbas AK, Lichtman AH, Pillai S. Introduction to the immune system. In: Abbas AK, Lichtman AH, Pillai S. Basic Immunology: Functions and Disorders of the Immune System. 4th edition. Philadelphia PA: Elsevier Saunders, 2009: p1-22.

Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy, Asthma, Immunol. 2008;100(3): s1-s22.

Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States. J Allergy Clin Immunol. 2010;126(6 0):S1–S58.

Cox KL, Devanarayan V, Kriauciunas A, et al. Immunoassay methods. In: Sittampalam GS, Coussens NP, Brimacombe K, et al., eds. Assay Guidance Manual. Bethesda, MD: Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2012: 1-44.

ELISA/ACT Biotechnologies LLC. Our unique testing method. [ELISA/ACT Web site]. 01/2019. Available at: https://www.elisaact.com/why-eab/our-unique-testing-method/. Accessed January 10, 2019.

ELISA/ACT Biotechnologies LLC. A technical overview of the LRA by ELISA/ACT® Procedure. [ELISA/ACT Web site]. 01/2019. Available at: https://www.elisaact.com/wp-content/uploads/2015/03/EABTechnicalOverview.pdf. Accessed January 10, 2019.

Galbiati V, Papale A, Kummer E, Corsini E. In vitro models to evaluate drug-induced hypersensitivity: potential test based on activation of dendritic cells. Frontiers in Pharmacology. 2016;7(204): 1-10.

Giavi S, Megremis S, Papadopoulos NG. Lymphocyte stimulation test for the diagnosis of non-IgE-mediated cow’s milk allergy: a step closer to a noninvasive diagnostic tool? Int Arch Allergy Immunol. 2012;157:1-2.

Golbert T. A review of controversial diagnostic and therapeutic techniques employed in allergy. J Allergy Clin Immunol. 1975;56(3):17-190.

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.

Gueant JL, Moneret-Vautrin DA, Dejardin G, et al. Comparative evaluation of RAST and FAST for 11 allergens in 288 patients. Allergy.1989;44(3):204-8.

Han M, Shin S, Park H, et al. Comparison of three multiple allergen simultaneous tests: RIDA Allergy Screen, MAST Optigen, and Polycheck Allergy. BioMed Research International. 2012;2013:340513.

Kimura M, Oh S, Narabayashi S, Taguchi T. Usefulness of lymphocyte stimulation test for the diagnosis of intestinal cow’s milk allergy in infants. Int Arch Allergy Immunol. 2012;157:58-64.

Kowal K, DuBuske L. Overview of in vitro allergy tests. [UpToDate Web site]. 08/02/2017. Available at: https://www.uptodate.com/contents/overview-of-in-vitro-allergy-tests?search=immunocap&source=search_result&selectedTitle=1~25&usage_type=default&display_rank=1. [via subscription only]. Accessed January 3, 2019.

Makhija M, O’Gorman MRG. Chapter 31: Common in vitro tests for allergy and immunology. In: Allergy and Asthma Proceedings. OceanSide Publications; 2012:S108-S111.

Novitas Solutions, Inc. Local Coverage Determination (LCD). L36241: Allergy Testing. [Novitas Solutions Web site]. Original: 10/01/2015. (Revised: 01/01/2018.) Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=36241&ver=57&Keyword=in+vitro+allergy+test&KeywordSearchType=Or&Date=&PolicyType=Both&ArticleType=SAD%7cEd&Cntrctr=323*1&KeyWordLookUp=Doc&SearchType=Advanced&CoverageSelection=Both&kq=true&bc=IAAAACAAAAAA& . Accessed January 3, 2019.

Thermo Fisher Scientific. ImmunoCAP lab tests. [Phadia Web site]. 01/2012. Available at: http://www.phadia.com/da/Products/Allergy-testing-products/ImmunoCAP-Lab-Tests/. Accessed January 3, 2019.

Thermo Fisher Scientific. Overview of ELISA. [Thermo Fisher Web site]. Available at: https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-elisa.html. Accessed January 7, 2019.

Quest Diagnostics. ImmunoCAP® Specific IgE Blood Test. [Quest Diagnostics Web site]. 01/2019. Available at: https://www.questdiagnostics.com/home/physicians/testing-services/by-test-name/immunocap.html?utm_medium=print&utm_campaign=allergy&utm_source=aafp. Accessed January 4, 2019.

Rodriguez GE. A new IgE fluorescent allergosorbent test (FAST). Clinical Immunology Newsletter. 1988;9(5):81-84.

Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update - 2014. J Allergy Clin Immunol. 2014;134(5):1016-1025.

Seltzer JM, Halpern GM, Tsay YG. Correlation of allergy test results obtained by IgE FAST, RAST, and prick-puncture methods. Ann Allergy. 1985;54(1):25-30.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. ImmunoCAP™ Specific IgE 510(k) submission. Substantial equivalence determination decision memorandum. 510(k) Premarket approval letter. [FDA Web site]. 05/10/17. Available at:https://www.accessdata.fda.gov/cdrh_docs/reviews/k163370.pdf . Accessed October 10, 2017.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. UniCAP Specific IgE 510(k) submission. Summary of safety and effectiveness. 510(k) Premarket approval letter. [FDA Web site]. 06/09/05. Available at:https://www.accessdata.fda.gov/cdrh_docs/pdf5/k051218.pdf . Accessed October 10, 2017.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. ImmunoCAP® Rapid Inhalant Profile 1. 510(k) summary. [FDA Web site]. 03/13/09. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf8/K081830.pdf. Accessed October 10, 2017.

Van Hage M, Hamsten C, Valenta R. ImmunoCAP assays: pros and cons in allergology. J Allergy Clin Immunol. 2017;140:974-977.

Wuthrich B. Unproven techniques in allergy diagnosis. J Invest Allergol Clin Immunol. 1995;15(2):86-90.

Yoshimura T, Kurita C, Hayata M, Nagai H. Diagnosis of drug allergy by the lymphocyte stimulation tests with the MTT [3-{4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Biol Pharm Bull. 1993;16(7):686-689.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

MEDICALLY NECESSARY


82785

THE FOLLOWING CODES ARE USED TO REPRESENT MULTIPLE ANTIGEN SIMULTANEOUS TEST (MAST), AND ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) FOR ALLERGEN-SPECIFIC IgE

86003, 86008


NOT MEDICALLY NECESSARY

86005


EXPERIMENTAL/INVESTIGATIONAL

86001, 86343, 86353

THE FOLLOWING CODE IS USED TO REPRESENT CYTOTOXIC FOOD TESTING

95199



Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)

N/A


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

06.02.26d:
03/25/2019This version of the policy will become effective 03/25/2019. Policy has been updated to communicate the continued coverage of ELISA, ImmunoCAP, and MAST, and the removal of RAST and FAST for in vitro allergy testing, due to review of most current clinical guidelines. Policy has been updated to establish lymphocyte stimulation tests (to include lymphocyte mitogen response assays, lymphocyte transformation tests, and others as detailed in the policy) as a category of testing considered experimental/investigational for in vitro allergy testing, based upon most current clinical guidelines. CPT code 86353 was added to the policy to represent lymphocyte stimulation tests, which are considered experimental/investigational.

06.02.26c:
01/01/2018This policy has been identified for the annual code update, effective 01/01/2018.
The update is due to the annual code review.

The following CPT codes have undergone narrative change: 86003, 86005
The following CPT code 86008 was added to the policy.

06.02.26b:
11/22/2017The policy has undergone a routine review, and no revisions have been made.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 03/25/2019
Version Issued Date: 03/25/2019
Version Reissued Date: N/A

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