Response to Comments: Allergy Testing

Three comments were received requesting to revise the language in the proposed LCD regarding the number of patch tests that may be required for allergic contact dermatitis (ACD) diagnosis from 65 to 80-90 in order to ensure comprehensive patch testing which involves a much higher probability of producing a diagnosis of a specific allergy. Two commenters indicated that 80 patch tests is the number of allergens indicated in the North American Contact Dermatitis Group standard tray and one commenter indicated that 90 patches is the number in the American Contact Dermatitis Society standard tray. One commenter also requested that occupational dermatitis be added as an indication for patch testing in the proposed LCD and requested the addition of the following ICD-10 codes to the associated billing and coding article to support this indication: L24.9, L25.0, L25.1, L25.2, L25.3, L25.4, L25.5, L25.8, L25.9, L30.9, H01.119, H01.131, H01.132, H01.133, H01.134, H01.135, H01.136, H01.139. The second commenter requested the addition of the following ICD-10 codes to the associated billing and coding article for patch testing to use in reporting an unknown cause of contact dermatitis: L23.9, L24.9, L25.0, L25.1, L25.2, L25.3, L25.4, L25.5, L25.8, L25.9, L28.0, L29.8, L29.9, L30.8, L30.9, H01.111, H01.112, H01.113, H01.114, H01.115, H01.116, H01.131, H01.132, H01.133, H01.134, H01.135, H01.36. Three full-text, peer reviewed articles were included with one comment and access to three abstracts were provided with the second comment; however, full-text articles were unavailable for these abstracts.

We appreciate this comment. After review of the submitted literature, the language in the finalized LCD will be revised to indicate that up to 80 patch tests may be required for ACD diagnosis. Regarding the request for occupational dermatitis to be added as an indication, the language in the ‘Summary of Evidence’ section will be revised in the finalized LCD to include the following language: When clinical evaluations imply that exposure to a specific contactant has occurred either in an occupational or nonoccupational setting, patch testing may be used to confirm the diagnosis. The associated billing and coding article related to patch testing for allergic contact dermatitis and irritant contact dermatitis is not specific for particular region(s) of the body, but rather focuses on the specific cause of the allergic contact dermatitis or irritant contact dermatitis. Therefore, concerning the ICD-10 codes requested for addition to the associated billing and coding article, the following ICD-10 codes will be added to the finalized article: L23.9, L24.9, L25.0, L25.1, L25.2, L25.3, L25.4, L25.5, L25.8, L25.9*, and L30.8. (*this ICD-10 code should be used to report contact dermatitis or contact eczema [occupational] NOS).

A comment was received regarding the ‘Covered Indications’ section for ‘A. In Vivo Testing (skin tests)’, bullet #6. Intracutaneous (intradermal) Dilutional Testing (IDT) in the proposed LCD. The commenter requested removal of ‘significant aeroallergen sensitivity’ from the last sentence of this section. The commenter noted that IDT has been found to be an unproven technique in the field of allergy; except for stinging insect-Hymenoptera and imported fire ant skin testing. In this regard, the commenter requested the following addition to ‘The following tests are considered not medically reasonable and necessary‘ section: Serial/skin end point titration testing other than for testing for stinging insect allergy and drug allergy. The commenter also provided recommended language for the ‘Summary of Evidence’ section for intracutaneous (intradermal) dilutional testing (skin endpoint titration). Six references were cited with this comment. However, no full-text articles were included with this comment.

We appreciate this comment. The evidence reviewed during the revision of this LCD indicated that intracutaneous (intradermal) dilutional testing is beneficial for determining the starting dose for immunotherapy for individuals with Hymenoptera venom sensitivity and significant aeroallergen sensitivity. Therefore, in the absence of any new full-text evidence submitted with the request, the LCD will not be revised as requested. The LCD Reconsideration Process may be followed to request a revision to the LCD once the LCD becomes effective.

A comment was received regarding the ‘The following tests are considered not medically reasonable and necessary’ section of the proposed LCD, under ‘Tests to diagnose Food Allergy’. The commenter requested that the 4th bullet be revised to read: Component-resolved diagnostics (CRD) to diagnose food allergy (except for diagnosis of peanut allergy). In this regard, the commenter provided recommended language for the ‘Summary of Evidence’ section for CRD. Four references were cited with this comment. However, no full-text articles were included with this comment.

We appreciate this comment. However, the evidence reviewed during the revision of this LCD did not support component-resolved diagnostics (CRD) to diagnose food allergy. In the absence of any new full-text evidence submitted with the request, the LCD will not be revised as requested. The LCD Reconsideration Process may be followed to request a revision to the LCD once the LCD becomes effective.

A comment was received regarding the ‘Provider Qualifications’ section of the proposed LCD. The commenter stated: “I do not believe that NPPs should be prescribing immunotherapy until such a time as there are recognized NPP fellowships with certifications, and currently there are not.” No references were cited with this comment.

Thank you for the comment. The language in the ‘Provider Qualifications’ section of the final LCD has been revised. We believe the revised language will eliminate any confusion and/or concerns.

A comment was received indicating: “Limitations on number of allergy tests for in vitro specific IgE tests should be specified. The proposed LCD limit of <70 prick/puncture and 40 intracutaneous tests appears to be based on Summary Statement 43 found in Bernstein et al, 2008 (Page S29). However, the proposed LCD does not specify limits for in vitro specific IgE tests. We suggest that the LCD also specify that the limits on the number of skin prick tests also apply to in vitro sIgE tests based on the recommendations in the same evidence-based guidelines. This is supported by Summary Statement 129: Recommendations concerning the number of specific IgE tein telests for confirmation of suspected clinical sensitivity correspond to those discussed for prick/puncture tests in Summary Statement 43 (Page S29).” The commenter also requests the proposed LCD be revised to indicate in vitro specific IgE tests are considered medically reasonable and necessary for telemedicine consults during the COVID-19 pandemic.

Thank you for the comment. In response to the request for a specific number of in vitro specific IgE testing allowed, we defer to the language in the ‘Limitations’ section of the proposed LCD: 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. Therefore, the finalized LCD will not be revised in this regard.

In regard to the request for revision of the proposed LCD for coverage of in vitro specific IgE tests for telemedicine consults during the COVID-19 pandemic, the CMS website provides a list of services payable under the Medicare Physician Fee Schedule when furnished via telehealth specifically for PHE for the COVID-19 pandemic (https://www.cms.gov/Medicare/Medicare-General-Information/Telehealth/Telehealth-Codes). Therefore, the finalized LCD will not be revised.

A comment was received that “the restrictions on coverage/medical necessity for in vitro sIgE testing in the proposed LCD are problematic barriers and disproportionately impact BIPOC communities and those living in low income areas. Skin tests are almost exclusively performed by allergy specialists, and with rare exceptions not accessible in primary care settings. It is not clinically appropriate, economically efficient, or even logistically feasible for primary care providers to refer all of their asthma and allergy patients to a specialist for skin testing, as there is a significant short-fall in the supply of allergy specialists in the U.S. According to Sun and Heimall, 2020, there are fewer than 5500 allergy specialists in the U.S. Compounding the short-fall in supply of allergy specialists is an uneven distribution of where allergy specialists are accessible. Sun and Heimall, 2020 found that 81.5% of all counties in the U.S. have no allergy specialist providers. They also found that the presence of allergy specialist providers is closely associated in areas with high-median incomes. Kanaley et al., 2020 also found significant inequities in access to allergy specialists that fell along socioeconomic and racial lines, which most heavily impacted BIPOC communities. Restrictions on coverage/medical necessity for in vitro sIgE testing as described in the proposed LCD, continue to exacerbate systemic racial and economic inequities in patient care for allergic diseases. Removing these restrictions is the only way for BIPOC communities and those living in low income areas to access allergy testing benefits." Two references were included with this comment.

Thank you for the comment and references. It was certainly not our intent to restrict access to care. Multiple guidelines and appropriate use criteria are available for allergy testing and were used in the revision of this LCD with the Medicare population in mind and coverage criteria to help ensure quality of care. Therefore, the final LCD will not be revised.

A comment was received that stated “The limitations on medical necessity for specific IgE testing in the proposed LCD appear to be based on Summary Statements 122 (Page S45) & 129 (Page S49) in Bernstein et al., 2008. Summary Statements 122 & 129 describe relative contraindications for skin testing, and where specific IgE tests are preferred. It is not accurate to characterize the clinical scenarios in these summary statements as absolute indications for specific IgE tests. In fact, Summary Statement 129 (Page S49) states just the opposite: There are no clinical scenarios in which immunoassays for allergen specific IgE can be considered either absolutely indicated or contraindicated. In other words, specific IgE tests are medically appropriate and indicated in both patients with the conditions that interfere with skin testing, as well as for patients who do not suffer from conditions that interfere with skin testing."

Thank you for the comment. The evidence-based guidelines provided by Bernstein et al also state: In general, skin prick/puncture testing is more sensitive for detecting sensitization to inhalant allergens and confirming clinical allergy. However, specific IgE assays with defined quantifiable threshold levels can also predict positive respiratory responses following allergen exposure. These guidelines also indicate that under specific circumstances, IgE immunoassays may be preferable to skin testing, such as widespread skin disease, patients receiving skin test suppressive therapy, uncooperative patients, or when the patient’s history proposes an extraordinarily greater risk of anaphylaxis from skin testing. Also, antihistamines and drugs such as tricyclic antidepressants decrease or block skin test reactivity. Therefore, when a patient cannot be safely withdrawn from a medication that would interfere with skin testing, an immunoassay may be appropriate. The sensitivity of these immunoassays compared with prick/puncture skin tests range from less than 50% to greater than 90%, with the mean at about 70% to 75% for most studies. Consequently, skin tests are highly beneficial for the diagnosis of IgE-mediated sensitivity. Therefore, the final LCD will not be revised.

A comment was received that indicated “Support for limiting medical necessity of specific IgE testing as described in the proposed LCD does not appear in this paper (i.e., Hamilton and Oppenheimer, 2015) does not represent the opinions of the authors, and should therefore be removed as a supporting reference.”

Thank you for the comment. Hamilton et al provided a clinical management review to examine the role that IgE antibody measurements play in the diagnostic algorithm when considering the pretest likelihood of disease on the basis of the patient’s clinical history. This review supports the importance of a comprehensive physical exam that includes objective symptoms to provide guidance in choosing specific allergen specificities. As noted in the ‘Summary of Evidence’ section of the proposed LCD, Hamilton et al also indicated: A quantitative singleplex IgE antibody assay assessment can be beneficial in situations in which there is a moderate pretest likelihood of aeroallergen-related allergic disease and the suspected allergen can be distinguished from the patient’s history. The age of the individual is considered in selecting the specific IgE antibody assay used to determine sensitization (skin test or serology). Serological assays are typically used for children possibly because pediatricians seldom conduct skin testing and serology can decrease the fear of potential risk of adverse events after allergen administration; while skin tests are performed more frequently for adults. Therefore, this reference will not be removed from the finalized LCD.

A comment was received that indicated “Support for limiting medical necessity of specific IgE testing as described in the proposed LCD does not appear in this paper (i.e. Griffiths et al., 2017), and should therefore be removed as a supporting reference. The authors actually recommend that in vitro specific IgE tests should be the single preferred test for possible allergy to nuts, wheat, other specific foods, and anaphylaxis of any cause (Page 215). Furthermore, the authors also suggest preferential use of specific IgE tests citing ‘continuing variability’ in commercially available allergen extracts for skin testing. They specifically mention that up to 10-fold variability has been observed in birch pollen extracts (Page 222).”

Thank you for the comment. Griffiths et al provided a comparison of the performance of skin prick, ImmunoCAP, and ISAC tests in the diagnosis of patients with allergy. The language in the proposed LCD, which has cited Griffiths et al, has been reviewed and verified to be accurate. The information in this reference was used in revising this LCD; therefore, the reference will not be removed from the finalized LCD.

A comment was received that indicated “Literature Supporting Equivalent coverage/medical necessity for Specific IgE Testing Not Cited by Proposed LCD: Hamilton RG. Clinical laboratory assessment of immediate-type hypersensitivity. J Allergy Clin Immunol 2010;125:S284-96. For food and respiratory allergy, IgE antibody as detected in the serum by using current autoanalyzer technology and in the skin by using the epicutaneous test are considered equivalent as confirmatory tests in terms of their sensitivity and accuracy (Page S291). NIAID-Sponsored Expert Panel, Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Am Acad Dermatol. 2011;64:175-192. doi:10.1016/j.jaad.2010.11.020. The EP recommends sIgE tests for identifying foods that potentially provoke IgE-mediated food-induced allergic reactions, but alone these tests are not diagnostic of FA (Page S4). sIgE tests are useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions, and specified ‘cutoff’ levels, defined as 95% predictive values, may be more predictive than SPTs (SPT=skin prick test) of clinical reactivity in certain populations, but when used alone they are not diagnostic of FA (Page S4). Fluorescence-labeled antibody assays have comparable sensitivity to that of SPTs, and the absolute levels of sIgE antibodies may directly correlate with the likelihood of clinical reactivity when compared with oral food challenges for the identification of foods provoking IgE-mediated FA (Page S4). These guidelines have been included in the proposed LCD. However, the above bullets from the guidelines not mentioned or addressed in the proposed LCD. Adkinson NF, Hamilton RG. Clinical History-Driving Diagnosis of Allergic Diseases: Utilizing in vitro IgE Testing. J Allergy Clin Immunol Pract 2015;3:871-6. Figure 1 (Page 873) displays a diagnostic algorithm indicating that either specific IgE tests or skin prick tests are acceptable without preference for one over another. Table II (Page 873) details relative sensitivity and specificity performance characteristics of Specific IgE Tests(Serum IgE Assay) vs Skin Prick Tests (Puncture skin test) vs Intradermal skin tests broken down by allergen group: Inhalants, Foods, Venoms, Drugs. Specific IgE tests and skin prick tests are considered to be equivalent overall in their sensitivity and specificity. NHLBI/NAEPP EPR-3 (2007) and EPR-4 (2020) Asthma Guidelines Both the EPR-3 and EPR-4 Asthma guideline from the National Institutes of Health give equal consideration to skin prick tests and in vitro sIgE testing for aiding in the diagnosis of allergic triggers for asthmatics. The EPR-3 guidelines also state that skin prick tests and in vitro sIgE tests are equal in sensitivity. Comments on language regarding Sensitivity and Specificity of Allergy Tests - Throughout the proposed LCD, skin testing is mentioned as being more sensitive than in vitro sIgE tests. However, the proposed LCD has not considered the most recent and authoritative literature. In a Grand Rounds Review on in vitro sIgE testing, Adkinson and Hamilton, 2015 (Table II, Page 873) summarize the relative sensitivity and specificity performance characteristics of skin tests vs in vitro sIgE tests. The current consensus is that overall, skin prick tests and in vitro sIgE tests have equivalent/comparable sensitivity and specificity for inhalant allergens, food allergens, hymenoptera, and certain drugs. We suggest that the proposed LCD be revised to reflect the equivalent/comparable sensitivity and specificity of skin prick test and in vitro sIgE tests as described by Adkinson and Hamilton, 2015. Suggested coverage/medical necessity for in vitro specific IgE tests- In vitro specific IgE tests should be considered medically reasonable and necessary when used to evaluate IgE mediated hypersensitivity to inhalants, foods, Hymenoptera (stinging insects), and specific drugs. We suggest that the limitations on coverage/medical necessity for in vitro specific IgE tests in the proposed LCD should be revised/re-incorporated into the LCD solely as contraindications for skin testing. Whole Allergens and Allergen Component tests not available through Skin Testing - While there is significant overlap in the selection of FDA cleared allergen extracts for skin testing and in vitro sIgE allergens, there are many allergens that are only available as in vitro test and not available as skin tests. This includes all allergen component tests (e.g. Ara h 2, Alpha-Gal, ovomucoid) as well as many whole allergen in vitro tests. The restrictions on in vitro sIgE testing in the proposed LCD would deny medically appropriate coverage for these allergens where a skin testing alternative does not exist.” Furthermore, the commenter stated that “While there is significant overlap in the selection of FDA cleared allergen extracts for skin testing and in vitro sIgE allergens, there are many allergens that are only available as in vitro test and not available as skin tests. This includes all allergen component tests (e.g. Ara h 2, Alpha-Gal, ovomucoid) as well as many whole allergen in vitro tests. The restrictions on in vitro sIgE testing in the proposed LCD would deny medically appropriate coverage for these allergens where a skin testing alternative does not exist.” Four references were included.

Thank you for the comment. Two guidelines for asthma were submitted and reviewed. They both indicate that skin testing and in vitro testing are appropriate for inhalant allergens and are equal in sensitivity. The third reference was an article for a case study for a pediatric patient (Adkinson and Hamilton article referred to in the comment). This case report concerned a single, pediatric patient with a yellow-jacket sting-not included in the Medicare aged population. The fourth reference (Hamilton, 2010) was a technical article regarding the clinical laboratory assessment of immediate-type hypersensitivity in relation to skin and autoanalyzer technology.

The evidence reviewed during the revision of this LCD indicates skin prick/puncture tests generally have better overall predictability and are the preferred initial diagnostic approach for IgE-mediated hypersensitivity. Although the advantages for both are acknowledged in the evidence submitted with the comment. Regardless, the chosen method of testing must be based on a careful history/physical examination which suggests IgE- mediated disease. The finalized LCD will not be revised in this regard.