Response to Comments: Allergy Diagnostic Testing

The commenters requested that the final LCD should describe in vitro allergen-specific IgE testing and skin testing as complementary diagnostic modalities and should avoid language that could be interpreted as establishing a default preference for one modality over the other. The commenters stated that such an approach would be more consistent with cited clinical literature and practice guidelines, would preserve clinician judgment based on individual patient circumstances, and would help maintain access to medically appropriate testing, including for beneficiaries in primary care, rural, underserved, and other settings in which skin testing may be less feasible.

Thank you for your comments. Medical literature and major professional society guidelines generally identify skin prick testing (SPT) as the preferred initial diagnostic modality for many IgE-mediated allergic conditions, particularly due to its higher sensitivity, especially for inhalants and certain food allergens. Accordingly, when skin testing is available, feasible, and clinically appropriate, it is generally expected to be considered as the initial diagnostic approach. Serum specific IgE (sIgE) testing is an established complementary modality and may be used as an alternative initial test when skin testing is not possible, would be unreliable, or is not reasonably available due to patient specific clinical factors, access limitations, or resource constraints inherent to the practice setting. Selection of sIgE testing in lieu of skin testing—particularly outside of known contraindications—should be supported by documentation describing the clinical circumstances that render skin testing impractical or inappropriate. In select cases, additional testing with an alternate approach may be medically necessary when initial results are equivocal or inconclusive; however, routine duplicate testing of the same allergen(s) with both skin and serum modalities is usually not indicated. Regardless of modality, test results must be interpreted in the context of the patient’s clinical history, as evidence of IgE sensitization alone does not establish a diagnosis of clinical allergy. Documentation to support the diagnostic approach and any clinical and non-clinical factors that affect the clinician’s choice of testing is strongly recommended when addressing exceptional circumstances.

Commenters requested that CMS broaden the stated indications for total serum IgE testing beyond those currently listed in the policy. Specifically, commenters requested recognition of total serum IgE as an indicator of atopic disease, as a tool for serial monitoring of treatment response, and as an aid in interpreting specific IgE test results. Commenters also requested that CMS recognize total serum IgE testing as reasonable and necessary in the evaluation of asthma and chronic spontaneous urticaria, including to support disease characterization and therapeutic decision-making, as well as in evaluating eligibility for omalizumab therapy in food allergy treatment.

Thank you for your comments. We acknowledge the broader clinical utility of total serum IgE testing, including its role in the diagnostic evaluation of conditions that extend beyond traditional IgE‑mediated allergy testing (i.e. IgE-mediated and delayed hypersensitivities to external allergens upon exposure) and for the additional conditions in which omalizumab therapy has been granted through FDA approval. We also recognize that, although total serum IgE is not routinely indicated for diagnosing classic atopic disorders, it may provide complementary information when an atopic condition is part of the differential diagnosis, particularly when interpreted alongside serum specific IgE levels and in consideration of the age‑dependent variability of IgE. However, we maintain that routine serial measurements of total serum IgE for assessing adequacy of treatment in IgE‑mediated allergic conditions are not supported by current specialty society guidelines. Repeat testing is generally not indicated unless there is a change in clinical status—such as new or worsening symptoms—that warrants further diagnostic evaluation. Accordingly, this LCD has been updated to reflect this acknowledgment. Uses of total serum IgE testing that fall outside the traditional allergy‑related indications addressed in this policy are outside the defined scope of the LCD; however, their omission should not be interpreted as a non‑coverage determination. Coverage for such services may still be considered when supported by appropriate clinical documentation and consistent with Medicare regulations.

Commenters requested that the Billing and Coding article be revised to include the following ICD-10-CM diagnosis codes for allergy diagnostic testing: bronchiectasis, uncomplicated (J47.9); nonfamilial hypogammaglobulinemia (D80.1); allergic rhinitis, unspecified (J30.9); other adverse food reactions, not elsewhere classified, initial encounter (T78.1XXA); and chronic cough (R05.3).

Thank you for your comments. With respect to the request for additional ICD‑10‑CM diagnosis codes, several additional diagnoses will be added to the Billing and Coding Article as they relate to traditional allergy diagnostic testing (i.e. IgE‑mediated and delayed hypersensitivity reactions to external allergens following exposure). Certain nonspecific diagnoses, however, will not be included, as ICD-10-CM coding conventions require reporting to the highest level of specificity. In addition, we will be clarifying in the LCD and Billing and Coding article that total serum IgE testing when used for purposes outside traditional IgE‑mediated allergy evaluation is outside the scope of this LCD; however, omission of such diagnoses should not be interpreted as a non‑coverage determination. Coverage for these services may still be considered when supported by appropriate clinical documentation and consistent with applicable Medicare requirements. Accordingly, the ICD‑10 diagnosis codes referenced for non‑allergy‑related indications will not be added. Please refer to the updated Billing and Coding Article for additional details.

A commenter requested that Pregnancy should be explicitly recognized as an indication for allergen-specific serum IgE testing, as skin testing may be avoided due to safety considerations.

Thank you for your comment. While pregnancy is not considered an absolute contraindication to skin testing, it may be regarded as a relative contraindication. The decision to perform any allergy diagnostic testing during a patient’s pregnancy, including the choice of skin testing versus serum specific IgE testing rests with the treating clinician who must determine whether any potential risk—however small—is justified in the clinical context. Serum IgE testing should only be accomplished in the pregnant female when there is concern for a life-threatening allergic issue related to the pregnancy and a delay in treatment would confer undue risk to the mother or fetus.

In response to this comment, the LCD has been revised to clarify that allergen specific serum IgE testing may be used as an alternative initial test when the potential benefit of skin testing does not outweigh the associated anaphylactic risk. In addition, we acknowledge that there are instances in which skin testing is not possible, would be unreliable, or is not reasonably available due to patient specific clinical factors, access limitations, or resource constraints inherent to the practice setting. The responsibility lies with the physician to evaluate the clinical scenario, consider all appropriate testing options, and select the most suitable method for assessing Type I IgE-mediated hypersensitivity. In all cases, the medical record must include clear documentation of the clinical indications, relevant history, rationale for test selection, and consideration of applicable specialty guidelines. This documentation, while an added responsibility for providers, enables individualized assessment of medical necessity and supports appropriate oversight if a MAC determines that further evaluation of potential inappropriate use is warranted.

Commenters requested that the article be revised to better align with current clinical standards for patch testing by recognizing that comprehensive testing may require up to 80–90 allergens when medically necessary, clarifying that monitoring and reading of patch tests may extend up to 10 days in clinically appropriate cases, clarifying that patch testing for allergic contact dermatitis due to formaldehyde or formaldehyde-releasing preservatives is covered, explicitly applying generally accepted professional testing standards to skin patch testing, and adding appropriate ICD-10-CM diagnosis codes to the Billing and Coding Article to support medical necessity for CPT^® code 95044.

Thank you for your comments. After further review, we agree that, in limited circumstances, monitoring of skin reactions during patch testing may extend up to 10 days and that current specialty society guidelines support testing up to 80–90 allergens to optimize diagnostic accuracy, consistent with the approach endorsed by the American Contact Dermatitis Society and the North American Contact Dermatitis Group. Accordingly, the LCD will be revised to reflect this. We also recognize that specialty societies identify formaldehyde as a validated contact allergen appropriate for inclusion in standard patch-testing panels for delayed-type hypersensitivity, and the statement at issue will be clarified to specify that it applies solely to IgE-mediated hypersensitivity. With respect to the request for additional ICD-10 diagnosis codes, we agree that several additional diagnoses should be added to the Billing and Coding Article. However, certain nonspecific diagnoses will not be included, consistent with coding conventions requiring the highest level of diagnostic specificity. Please refer to the revised Billing and Coding Article for additional details.

Commenters requested that the article reflect the full range of accepted clinical practice for challenge testing, including recognition that organ challenge testing may be performed using open, single-blind, or double-blind methods as clinically appropriate; that inhalation/bronchial challenge testing language be expanded to include commonly used non-allergenic agents such as methacholine and mannitol and clarify how the standard of three measurements applies to spirometry for billing purposes; that oral food challenges be described as the gold standard for diagnosing food allergy and as appropriate for assessing threshold, tolerance, or resolution of allergy without implying they are indicated only after inconclusive skin prick or serum specific IgE testing; and that drug challenge testing be recognized as an essential tool for diagnosing or removing inaccurate drug allergy labels, including when alternative diagnostic methods are not validated or substitute medications may be less effective, more costly, or carry greater risk.

Thank you for your comments. After review, we agree the LCD should better reflect accepted clinical practice for organ challenge testing. While double‑blind, placebo‑controlled challenges have historically been considered the gold standard, open and single‑blind challenges are appropriate and commonly used in many clinical contexts.

We also agree that discussion of spirometry parameters and the number of measurements used to define a unit of service is more appropriately addressed in the associated Billing and Coding Article rather than the LCD, and such language has been removed accordingly. The LCD has been updated to include additional background on non‑allergenic bronchoprovocation agents, such as methacholine and mannitol, and other commonly used methods to provide a more complete description of the evaluation of airway hyperresponsiveness.

In addition, the LCD has been revised to clarify that oral food challenges are not limited to situations in which skin prick or serum specific IgE testing is inconclusive but may be indicated when such testing is unavailable or when confirmation of clinical relevance is necessary to avoid unwarranted dietary restriction. With respect to assessing tolerance or resolution, routine repeat testing performed solely for surveillance is not considered reasonable and necessary. Documentation must support the medical necessity of the oral food challenge as part of the diagnostic evaluation of suspected IgE‑mediated food allergy, whether in the initial diagnosis or if persistent concern upon follow up.

Finally, we agree that evaluation of suspected drug hypersensitivity must be individualized based on the specific medication, the patient’s clinical history, and the availability and reliability of diagnostic testing. In situations where validated skin or serum specific IgE testing is unavailable or limited, drug challenge testing may represent the most appropriate diagnostic approach. The LCD also recognizes the importance of drug allergy de-labeling, as inaccurate allergy labels may restrict access to first line therapies and lead to less effective, more costly, or higher‑risk treatment alternatives.

Commenters requested that the article be revised to provide clearer, more clinically precise terminology, including what is meant by “unrelated” in terms of multiallergen panels, and to better define the scope of services addressed in the proposed LCD, including whether the policy applies only to traditional allergy testing or more broadly to immunologic diagnostic testing. Commenters also requested more complete and current descriptions of key diagnostic modalities, including oral food challenges, bronchial challenges, component-resolved diagnostics, drug allergy assessment, and total IgE testing, so that the article more accurately reflects current evidence, professional guidelines, and clinical practice.

Thank you for your comments. This policy addresses both immediate IgE-mediated hypersensitivity reactions and delayed cell-mediated hypersensitivity. It includes guidance for in vivo testing, such as skin prick testing, patch testing, and organ challenge testing, as well as serum specific IgE in vitro testing, including applicable limitations and provider qualifications. Diagnostic immunology testing performed for the evaluation of immune system function is outside the scope of this policy, and this distinction will be clarified in the LCD. As this is a broad Local Coverage Determination, the policy is intended to use terminology that is widely recognized and reflects the most commonly used verbiage across multiple specialties, while also referencing alternative terminology where appropriate for specific testing modalities. In response to these comments, we conducted an additional comprehensive literature review and carefully evaluated the materials submitted by commenters. Based on this review, we expanded the descriptions of several diagnostic modalities to better reflect current evidence and practice patterns, while maintaining a concise and generalizable presentation appropriate to the LCD format.

In addition, we are clarifying that Qualitative multiallergen screening tests that provide only a single positive/negative result without identifying or quantifying individual allergens remain non covered, as they do not provide clinically actionable information for diagnosing allergen specific hypersensitivities.

Multiplex microarray testing that evaluates multiple allergen categories simultaneously (e.g., aeroallergens, food allergens, venoms, latex) on one single platform is considered screening and is not covered 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 specific suspected allergens may be considered reasonable and necessary when ordered based on the patient’s clinical history, symptoms, relevant exposures, and/or differential diagnosis.

Commenters requested that the policy clarify that serum specific IgE testing may be performed in appropriate practice settings, including primary care, when ordered and furnished by qualified practitioners acting within their scope of practice and licensure; address utilization and frequency expectations; recognize economic considerations associated with access to in vitro testing; and explicitly acknowledge coverage considerations for certain patient populations and clinical scenarios including pediatric outgrowth of allergies, delayed hypersensitivity reactions, patients with reactions to chemotherapy, and other high‑risk medication or biologic reactions.

Thank you for your comments. We recognize that allergy diagnostic testing may be furnished by physicians or other qualified healthcare providers whose training, clinical experience, and state’s scope of practice support the performance and interpretation of such testing. In addition, this MAC does not limit coverage of medically necessary allergy testing to a specific specialty. However, because in vivo allergy testing may result in local or systemic allergic reactions, including anaphylaxis, such testing should be conducted in an appropriate clinical setting under the direct supervision of a physician trained in the recognition and management of allergic reactions and capable of initiating appropriate emergency intervention when necessary. As such, providers are expected to possess the appropriate knowledge, competency, and clinical judgment to select, perform, and interpret skin testing, serum specific IgE testing, and/or organ specific challenge procedures when applicable. The determination of which diagnostic modality to use must be consistent with accepted standards of medical practice, the provider’s training and experience, and the resources available within the clinical setting. Providers must act within their state-defined scope of practice and ensure that all services meet Medicare’s reasonable and necessary requirements, as outlined in this LCD and the Medicare Program Integrity Manual Chapter 13, section 3.6.2.2.

Regarding economic considerations associated with serum specific IgE (sIgE) testing. While such data may inform population‑level utilization analyses, coverage determinations under this LCD are based on whether services are reasonable and necessary for the individual beneficiary. Economic considerations alone do not establish medical necessity and do not supersede clinical indications or guideline‑supported testing expectations.

Recommendations regarding the inclusion of language addressing scope of practice and licensure, as well as observations on the appropriate number of tests performed are acknowledged, and clarifications will be made. This aligns with Medicare’s definition of “reasonable and necessary” services in the Medicare Program Integrity Manual, Chapter 3, Section 3.6.2.2.

This LCD is intended to provide a comprehensive framework for coverage of allergy diagnostic testing across the range of in vivo and in vitro modalities used to evaluate IgE‑mediated and delayed hypersensitivity reactions. The policy is written to apply broadly to the Medicare population. Although pediatric beneficiaries represent a smaller proportion of the Medicare population, we recognize their distinct clinical considerations. However, additional pediatric‑specific operational detail is beyond the scope of this coverage policy; their omission should not be interpreted as a non‑coverage determination.

Regarding chemotherapeutic agents, biologics, and other high‑risk medications, the LCD outlines the general principles of drug allergy evaluation without restricting coverage to specific agents or therapeutic classes. The policy clarifies that drug allergy testing is not limited by the medication involved, ensuring that beneficiaries retain access to medically necessary diagnostic services across a broad range of drug‑related reactions.

Commenters requested that CMS recognize the clinical utility of component resolved diagnostics (CRD), including singleplex allergen component testing, and revise the article accordingly. Commenters stated that these tests are supported by international and specialty society guidelines in selected clinical scenarios, particularly when extract-based testing and clinical history are insufficient or when risk stratification is needed. Commenters also noted that certain component tests, such as Ara h 2 for peanut allergy, Cor a 14 for hazelnut, Ano o 3 for cashew, and alpha-gal specific IgE testing, are used to support diagnosis and inform clinical decision-making.

Thank you for your comment. We agree that component resolved diagnostic (CRD) testing has recognized limited indications within standard allergy diagnostic practice. Current evidence based guidelines supports use of singleplex allergen component testing, whether recombinant or extracted from raw whole allergen, in selected clinical scenarios where clinical history and whole‑allergen testing alone may not provide sufficient diagnostic clarity, such as for certain food allergies (e.g., Ana o 3 (cashew), Ara h 2 (peanut), and Cor a 14 (hazelnut)) or conditions like alpha‑gal syndrome. CRD may also assist in more precise identification of clinically relevant allergen components when developing an allergen immunotherapy treatment strategy.

We acknowledge that additional allergen component tests continue to be explored in the literature. However, it remains essential to emphasize that molecular allergy diagnostics do not replace a thorough clinical history, physical examination, and in vitro or vivo testing using whole allergen specific IgE assays.

Furthermore, the use of CRD within precision or personalized medicine frameworks—particularly broad multiplex panels performed without supporting clinical signs, symptoms, or a defined clinical suspicion—does not meet Medicare’s reasonable and necessary criteria. Testing performed in the absence of a relevant clinical context constitutes screening, and screening services are not covered by Medicare unless explicitly authorized by statute or regulation. In addition, broad identification of an array of sensitizations in the absence of clinical correlation may introduce unnecessary confusion into the diagnostic workup and may increase the risk of misinterpretation or false diagnosis.

In summary, while CRD may offer value in select, clinically indicated scenarios—including limited use in refining allergen specific immunotherapy planning—its use must be grounded in documented clinical relevance. Testing undertaken solely to identify potential sensitizations without corresponding clinical correlation does not meet Medicare coverage requirements and may adversely affect diagnostic clarity.