BlueCross and BlueShield of Montana Medical Policy/Codes
Allergy Management
Chapter: Medicine: Tests
Current Effective Date: December 27, 2013
Original Effective Date: August 05, 1999
Publish Date: December 27, 2013
Revised Dates: August 21, 2002, October 9, 2002, March 5, 2003, August 20, 2003, January 11, 2006, January 15, 2008, November 7, 2011; December 6, 2013
Description

An allergy is an abnormal reaction to an ordinarily harmless substance called an allergen. When an allergen (such as pollen) is absorbed into the body of an allergic individual that individual's immune system views the allergen as an invader and a chain reaction is initiated. White blood cells of the immune system produce IgE antibodies. These antibodies attach themselves to special mast cells causing a release of potent chemicals such as histamine. These chemicals cause generalized symptoms as well as localized reactions in any organ system of the body. The reactions may be acute, subacute, chronic, immediate or delayed, and may be caused by numerous offending agents, such as pollen, molds, dust, mites, animal dander, stinging insect venoms, foods, and drugs. 

Allergy Testing:  The optimum management of the allergic patient should include a careful history and physical examination and confirmation of the cause of the allergic reaction obtained from some of the testing methods. 

Direct Skin Testing is used to identify offending allergens. These tests include, but are not limited to:

  • Percutaneous (scratch, prick, or puncture): This test consists of placing a drop of allergen on the skin making a needle scratch, prick, or puncture through the drop and into the underlying epidermis. The number of tests required may vary widely dependent on the patient's age and degree of hypersensitivity. Rarely are more than 40 percutaneous tests required.
  • Intracutaneous (intradermal): This test involves the injection of a small amount of one or more allergic substances (within a solution) between the epidermal and dermal layers of the skin. Intradermal testing is considered to be more sensitive but less specific than percutaneous testing for the detection of IgE antibodies. Testing for drug and insect sting sensitivity should always be done using intradermal testing. The number of intracutaneous tests may also vary from patient to patient. Rarely are more than 20 intracutaneous tests required. Intradermal testing from delayed hypersensitivity of the tuberculin type should not exceed six to eight tests.
  • Patch (Application) Testing: This test involves application of the suspected allergen(s) to the patient's back, which are covered with dressings and allowed to remain in contact with the skin for 48 hours. The area is then examined for evidence of delayed hypersensitivity reactions. Patch testing with 20 to 30 allergens using a screening patch test will detect as many as 70% of all cases of allergies causing contact dermatitis.
  • Photo Patch Test: This test uses ultraviolet light the suspected allergen is applied to a patch of skin and left on for 48 hours. If no reaction occurs, the area is exposed to a dose of ultraviolet light sufficient to produce inflammatory redness of the skin. If the test is positive, a more severe reaction develops at the patch site than on the surrounding skin.

Serum Allergy Testing (IgE) (RAST, MAST, FAST, ELISA, PRIST):  These tests are essential alternatives for patients in whom skin testing is contraindicated or unacceptable. This includes, but is not limited to those individuals in whom direct skin testing:

1.         May be impossible due to extensive dermatitis or marked dermatographism,

2.         May be impossible as the patient may be unable to cooperate or stop using antihistamines,

3.         May be impossible in children less than four years of age,

4.         Has not been conclusive, and further diagnostic testing is necessary, or

5.         Has been refused by the patient.                                                            

Specific IgE In Vitro Testing / IgE  Concentration Food-specific Testing:

This test detects antigen-specific IgE antibodies in the patient’s serum. These tests are considered equivalent to percutaneous skin testing for inhalant allergens (pollens, molds, dust, mites, and animal danders), foods and other allergens.

Total Serum IgE Concentration:  This testing modality is not indicated in most allergic patients, but may be indicated for those patients suspected of having allergic bronchopulmonary aspergillosis, immune deficiency disease characterized by increased IgE levels (e.g., Wiskott-Aldrich syndrome, hyper-IgE staphylococcal abscess syndrome), IgE myeloma, or pemphigoid. In addition, a total IgE level is indicated in the evaluation of asthmatic patients being considered for therapy with monoclonal antibody to IgE.

Serial dilution end point titration (SDET), Serial endpoint testing (SET), sequential incremental testing also known as Rinkel/Rinkel method:  This test is a form of intradermal skin testing that uses increasing doses of antigen to determine the concentration at which the reaction changes from negative to positive (the “endpoint”). The test has been used for diagnosing allergic disorders, and is a potential alternative to other diagnostic tests such as skin prick testing or in vitro testing for this purpose.  In addition, SET has been used to guide the initiation of immunotherapy, by using the endpoint dilution as the starting antigen dose.

Nasal cytogram is the microscopic study of nasal secretions used to determine whether a patient has an allergy to inhalants or food, or if an acute or chronic viral infection is present, resulting in rhinitis or otitis.

Bronchial Challenge Test:  Histamine or methacholine is used to perform this test when it is necessary to determine if the patient has hyper-responsive airways. Volatile chemicals are used to perform this test when the allergy is encountered in an occupational setting.

Double Blind Food Challenge Test:  With this test, the patient ingests the food to which sensitivity is suspected. Both the patient and the physician are "blinded." This is usually done at home, but in some instances of suspected extreme hypersensitivity, it may be performed in the office setting.

Sublingual provocation food testing dates back to 1944. The test consists of placing three drops of an allergenic extract under a patient's tongue and waiting 10 minutes for any symptoms to appear. When the physician is satisfied he has determined the cause of the symptoms, he administers a "neutralizing" dose, which is usually three drops of a diluted solution of the same allergenic extract. The symptoms are then expected to disappear in the same sequence in which they appeared. Advocates claim that if the neutralizing dose is given before a challenge test (for instance, eating a meal containing the offending food), the person will not have symptoms.

Nasal Challenge Test (Also called nasal mucous membrane test; nasal challenge/provocation test):  This test has been proposed as a tool in the diagnosis of allergic rhinitis. It is performed to duplicate the patient’s main symptoms or signs by controlled exposure to a suspected antigen and is delivered by direct application to the nasal mucous membranes. Evaluation of the patient’s response to the allergen is recorded.

Conjunctival Challenge Testing (ophthalmic mucous membrane test):  Allergenic extract is placed into the conjunctival sac of the eye, followed by observation for redness, itchiness, tearing of the eye, and other similar symptoms.

Cytotoxic Food Testing (Leukocytotoxic Test):  This test involves the response of specially collected white blood cells to the presence of food extracts to which the patient is allergic. 

Leukocyte Histamine Release Test (LHRT):  Measures the amount of histamine released from the white blood cells in response to exposure to an allergen.

Rebuck Skin Window Test:  A test of the inflammatory process in which the skin is abraded and a cover slip is applied to the abraded area. The cover slips are removed and replaced at intervals and examined for the presence of cells involved in the immune response.

Passive Transfer of P-X (Prausnitz-Kustner Test):  Performed by injecting serum intradermally from a suspect allergic patient into a nonallergic patient and later challenging the injection site with antigens.

Antigen leukocyte cellular antibody test (ALCAT): A test that is purported to measure a patient’s food intolerances, e.g., through proprietary technology, an evaluation of the patient’s white blood cells response when exposed to a variety of different foods.  

IgG Food and Environmental Testing IgG4 Antigen Levels:  These tests are a subclass of immunoglobulin G. Selective deficiencies in one or more of the four IgG subclasses are seen in some patients with repeated infections. Measurements of IgG4 antibodies have been used in research settings to determine response to allergy treatments.

Mediator Release Test® (MRT®) involves the measurement of the aggregate release of inflammatory mediators from an individual's immunocytes after exposure to various food extracts and chemicals (e.g., food additives). A determination is made of the difference in volume of circulating immunocytes and plasma before and after an in vitro antigen challenge. For the Mediator Release Test®, portions of an individual's blood sample is incubated with various food extracts and food additives (typically 150 different substances). The degree of reactivity is determined by the degree of mediator release from the cells. A response, change in cellular and plasma volume, is thought to indicate a hypersensitivity reaction and results are used as a basis for modifying an individuals diet. The MRT® is one component of the Lifestyle Eating and Performance (LEAP®) Program of oligoantigenic dieting. This type of testing has been promoted for individuals with, among other conditions, irritable bowel syndrome, chronic fatigue syndrome, migraine headaches, and dermatologic conditions (e.g., eczema, dermatitis).

Allergy Therapy:  Once the offending agent has been identified, treatment is managed by avoidance, medication, or immunotherapy.

Avoidance is the preferred treatment to eliminate the allergen, requiring a change of diet, occupation, or residence; discontinuance of a drug; or removal of a household pet. However, complete avoidance may be impossible.

Medication may provide symptomatic relief for the patient but, does not address the cause of the problem. Medications may include steroids, antihistamines, or decongestants.

Immunity has been defined as freedom from or protection against certain diseases. Conventional or traditional immunotherapy, desensitization, or allergy shots, are recommended for patients with moderate to severe symptoms throughout most of the year who do not respond adequately to medications, and whose symptoms are triggered by an allergen that is not easily avoided (such as pollens or house dust mites). Immunotherapy involves the repeated injections of allergenic extracts (tiny amounts of allergen) that are given over a period of three to five years. By gradually increasing the amount of extract, tolerance to the offending allergen will increase, and the patient's symptoms will be relieved. Gradual injections may begin once or twice weekly over a period of four to six months. After the maintenance dose is achieved, the interval between injections may range between two and six weeks. Immunotherapy may be administered continuously for several years. Suspensions for injection of airborne or insect venom allergens should be prepared for the patient individually and under physician supervision.

Rapid Immunotherapy:  Drug, pollen, or venom Rush or Rapid Immunotherapy (RIT) is done if sensitivity has been established by history, anaphylactic shock, positive challenge testing, and/or positive skin testing. In cases where drug administration for treatment is essential and no alternative exists, RIT desensitization is done by increasing dosages of allergen through intravenous access or injections. In some situations, the patient is hospitalized to provide oxygen, epinephrine, and resuscitation equipment to promptly treat the patient for any life-threatening reaction; and, the allergen doses are increased over a one to three day period. RIT can be done in the office setting for a period of less than 8 (eight) hours, which includes an observation period following the last injection. Premedication of antihistamines and steroids are given the day before and the morning of RIT. Baseline spirometry may be performed in asthmatic patients. An example of RIT is when penicillin desensitization is used as an emergent need to prepare an allergic patient for treatment of bacterial endocarditis.

Provocative and Neutralization Therapy: This method has been purported as a test for allergies, foods, and environmental chemicals. Patients are exposed to test doses of substances, and observed for the presence of symptoms. Then a diluted version of the offending substance is given to relieve symptoms.

Sublingual immunotherapy (SLIT) targets absorption to the sublingual and buccal mucosa. Allergen preparations used for SLIT are held under the tongue for one to several minutes and then swallowed or spit out.

Regulatory Status

No allergy extracts for sublingual immunotherapy are currently cleared or approved by the U.S. Food and Drug Administration (FDA).

Topical: localized application of an allergen directly to the organ creating the allergy response, such as the nose for allergic rhinitis.

Urine auto-injections (autogenous urine immunization): In this treatment, a patient’s urine is collected and sterilized. It is injected into the donating patient and presumed to provide relief from allergy symptoms. 

Repository emulsion therapy: This technique uses mineral oil and antigenic material. The water in oil emulsion provides a slower release of these materials providing protection for a prolonged period of time.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there is any exclusion or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

The following methods of allergy testing and allergy therapy may be considered medically necessary in those individuals with a history of allergic disease:

Allergy Testing

Direct Skin Testing

  1. Percutaneous (scratch, prick, or puncture);
  2. Intracutaneous (intradermal);
  3. Skin patch testing (application);
  4. Photo Patch.

Serum Allergy Testing (IgE)

  1. Radioallergosorbent (RAST);
  2. Multiple Radioallergosorbent (MAST);
  3. Florescent Allergosorbent (FAST);
  4. Enzyme-linked Immunosorbent Assay (ELISA);
  5. Paper Radioimmunosorbent Test (PRIST).

Total Serum IgE Concentration may be considered medically necessary in those individuals suspected of having:

  1. Allergic bronchopulmonary aspergillosis;
  2. Immune deficiency disease (i.e., Wiskott-Aldrich syndrome, hyper-IgE staphylococcal abscess syndrome);
  3. IgE myeloma;
  4. Pemphigoid.

Serial endpoint testing (SET) may be considered medically necessary for the determination of a safe starting dose for testing or immunotherapy when there is potential for the specific allergen in question to produce a severe systemic allergic reaction or anaphylaxis.

Nasal cytograms may be considered medically necessary when performed for the purpose of identifying exudative evidence of nasal allergy or infection.    

Bronchial challenge testing may be considered medically necessary for those individuals with hyper-responsive airways.

Double blind food challenge testing may be considered medically necessary for those individuals suspected of sensitivity to food products.

The following methods of allergy testing are considered experimental, investigational and unproven for the following tests:

  1. Provocative tests for food or food additive allergies;
  2. Neutralization Testing;
  3. Nasal Challenge tests;
  4. Conjunctival challenge test (ophthalmic mucous membrane test);
  5. Cytotoxic food tests (Bryan’s Test);
  6. Leukocyte histamine release test (LHRT);
  7. Rebuck skin window test;
  8. Passive transfer or P-X (Prausnitz-Kustner test);
  9. Antigen leukocyte cellular antibody test (ALCAT);
  10. Sublingual provocation food testing;
  11. Specific IgE In Vitro Testing / IgE Concentration food-specific allergy testing;
  12. IgG Food and Environmental Testing;
  13. Any aspect of the Lifestyle Eating and Performance (LEAP) program, including the Mediator Release Test (MRT) used to identify “delayed food allergies” and treatments, which include dietary manipulation and/or supplements or herbs. 

Allergy Therapy

Allergy Immunotherapy may be considered medically necessary in individuals with demonstrated hypersensitivity that cannot be managed by medications and avoidance.

Rush or Rapid Immunotherapy (RIT) may be considered medically necessary for the rapid or hyper-accelerated rate desensitization by increasing doses of allergen injections.

The following methods of allergy immunotherapy are considered experimental, investigational and unproven for the treatment of food, molds, chemicals, pollens, and other allergies including the preparation of and administration of immunotherapy:

  1. Provocative and neutralization therapy; using intradermal and subcutaneous routes; AND
  2. Sublingual immunotherapy (SLIT); oral application of natural or enzymatically altered antigens; AND
  3. Topical; localized application of an allergen directly to the organ creating the allergy response, such as the nose for allergic rhinitis; AND
  4. Urine auto-injections (autogenous urine immunization); freshly collected urine, having been sterilized and filtrated, injected to the donating patient; AND
  5. Repository emulsion therapy; solutions of vegetable and mineral oils containing additional allergens, to produce slow releases of the allergens at the injection site.

Allergen-proof supplies (mattresses, mattress casings, pillows, or pillow casings) are considered not medically necessary as they are considered personal convenience items.

Policy Guidelines

When 83516 and/or 86160 are billed to represent ALCAT testing, it is considered experimental, investigational and unproven per the coverage section.

Rationale

Current allergy management uses specific tests to identify and confirm the causative agent (the "allergen"), and skin tests are the most convenient. These tests should be selected and based on the information provided by the patient's history. It is common practice to do prick skin testing first. This is usually sufficient for detecting sensitivity to most allergens. More sensitive intradermal testing can be used to test suspected inhaled allergens that have previously produced negative or equivocal prick tests. For foods, prick tests alone are diagnostic. Food intradermal tests are likely to produce positive reactions of no clinical significance, as determined by double-blind oral symptom provoking challenge tests. On the other hand, insect sting and drug testing are accurate only when performed by intradermal testing.

There is sufficient peer-reviewed clinical evidence to support the use of in vitro IgE antibody tests (ELISA, FAST, MAST, PRIST, RAST) in terms of clinical effectiveness and safety, for specific subgroups of individuals. These include patients who cannot be withdrawn from medications that interfere with skin testing, who have had a previous systemic reaction from skin testing, for patients with extensive dermatitis, and occasionally, for patients in who skin testing would be difficult, such as young children. Furthermore, total serum IgE concentration has effectively been used in individuals suspected of having an immune deficiency characterized by increasing IgE levels (a person who has allergies usually has elevated blood levels of IgE). Proper diagnosis of the condition can result in effective treatment.

Avoidance/Environmental controls are the most important component of therapy. In many cases, if a patient can eliminate their exposure to an allergen their symptoms will decrease markedly and there is no need for further forms of treatment.

The second mode of therapy is medication. Medication is an important form of therapy and in some patients such as asthmatics, it is essential. In recent years, newer and better medications (e.g., antihistamines, corticosteroids, bronchodilators) make complete control of the allergic patient possible. In most situations, medication relieves or alleviates the symptoms but does not address the cause. In many patients, medication and avoidance are enough to relieve the patient adequately so that no further treatment is necessary.

Immunotherapy (e.g., desensitization, hyposensitization, allergy injection therapy or “allergy shots”) is used to treat patients who are sensitive to inhaled allergens, such as pollens, molds, dander, and house dust. Studies have found immunotherapy to be extremely effective of stinging insect allergy. Immunotherapy for food allergies is not recommended because of the chance of a severe allergic reaction to the injection and because avoidance can often be achieved. Conventional/Traditional Immunotherapy or rapid immunotherapy (RIT) is not a cure, only a treatment modality. Ideally, immunotherapy should provide the allergic patient with maximal clinical benefit with minimal risk. The concerns with RIT as compared to traditional immunotherapy, has been the higher rate of systemic reactions. Premedication with corticosteroids and antihistamines have been shown to lower the incidence of systemic reactions with RIT significantly. The major risk factor of allergy immunotherapy is anaphylaxis. Immunotherapy should be administered under the supervision of an appropriately trained physician who can recognize early signs and symptoms of anaphylaxis and administer emergency medications if needed.

After careful study of existing data, The American Academy of Allergy and Immunology says no controlled clinical studies demonstrate either diagnostic or therapeutic effects of sublingual provocation food testing. The academy concludes that use of the tests should be reserved for experiments in well-designed trials.

A MEDLINE search of the literature through October 2007 reveals no new published clinical trials on any of the allergy tests listed as investigational in this medical policy. Specifically, there are no randomized, controlled clinical trials documenting outcomes and impact on treatment decision for provocation food tests, neutralization testing, nasal challenge tests, conjunctival challenge tests, cytotoxic food tests, LHRT, IgG4, MRT and dermatome testing.

2010 Update

A structured evidence-based assessment of sublingual immunotherapy for adults conducted by the Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) concluded “[w]hether [sublingual immunotherapy] improves health outcomes when compared with injection [allergen-specific immunotherapy] has not yet been demonstrated in the investigational setting. It is uncertain whether FDA-licensed allergen preparations manufactured for allergy testing and injection [allergen-specific immunotherapy] are suitable for sublingual administration. Based on the above, use of sublingual immunotherapy for patients with allergies does not meet the TEC criteria.”

Cox et al. stated that sublingual immunotherapy (SLIT) has been utilized with frequency in Europe and is viewed with increasing interest by allergists in the United States. A Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees evaluated the evidence on the effectiveness of SLIT. The task force concluded that despite clear evidence that SLIT is an effective treatment, there are still many unanswered questions, including effective dosage, treatment schedules, and overall duration of treatment. Until these questions have been answered, an assessment of the cost/benefit ratio of the treatment cannot be made.  Sublingual immunotherapy does seem to be associated with few severe side effects, but it has not been used in high-risk asthmatic patients, nor in the studies reviewed has it been used as a mixture of non-cross-reacting allergens. There is currently no allergy extract approved for this use in the United States.

Hoeks et al. examined the evidence of the safety and effectiveness of SLIT as a curative therapy for allergies in children. All randomized, double blind and placebo-controlled studies on SLIT in asthma or rhinoconjunctivitis in children were selected from Medline, Embase and Cochrane Central Register of Controlled Trials. Thirteen controlled trials on SLIT in children were selected, five studies on children with house dust mite allergy and eight studies on children with grass pollen allergy. After treatment with SLIT, reported symptoms decreased without improvement of objective parameters. These investigators concluded that it was impossible to substantiate the claim of authors of the studies regarding the favorable effects of SLIT in children with asthma or rhinoconjunctivitis, since all studies had serious methodological flaws. However, the studies showed that SLIT seems to be safe in children in the doses applied. This is in agreement with the findings of Röder et al. who reported that there is currently insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with allergic rhinoconjunctivitis.

2012 Update

Much of the available literature on the accuracy of intradermal dilutional testing (IDT) and serial endpoint testing (SET) was derived during the 1970s and 1980s. None of these studies showed improvement in allergy-related symptoms and/or quality of life based on the testing and, therefore, systematic review is difficult for this type of allergy testing. Nevertheless, IDT has become an established approach to allergy testing by the American Association of Otolaryngology, as reported by Krouse and Mabry. SET, in particular, is generally considered the method of choice for life-threatening and antibiotic-related allergies in which other testing techniques may not be available or may be dangerous.

The advantages to IDT over other allergy testing are:

  • Determination of a safe starting dose;
  • Reliability of testing greater in many drug-related allergies;
  • Higher sensitivity than skin prick testing for allergies.

The disadvantage to IDT over other allergy testing is:

  • Less specific than skin prick testing or serum IgE;
  • More extensive procedure that can require up to six rounds of intradermal injections before the diagnosis is established.

Although there is little primary literature on SET and health outcomes, recent guidelines and publications have discussed the need for this more intensive type of testing for certain drug allergies in particular. For example, the Centers for Disease Control and Prevention (CDC) recommend the use of SET testing in the management of patients with secondary syphilis or neurosyphillis and a history of penicillin allergy. 

Summary

Based on the literature cited above, use of serial endpoint testing is considered medically necessary in specific situations, i.e., when there is a high likelihood for a severe allergic reaction to specific agents such as antibiotics or other high-risk allergens.

Practice Guidelines and Position Statements

American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology: a 2008 guideline on allergy diagnostic testing includes the following recommendations on intracutaneous tests:

“…When compared with specific nasal challenge, skin endpoint titration (SET) is equivalent to prick/puncture skin tests.”

“Intracutaneous tests should be performed with small volumes (approximately 0.02 to 0.05 mL) of allergens injected intracutaneously with a disposable 0.5- or 1.0-mL syringe.”

“As a general rule, the starting dose of an intracutaneous allergen test ranges from 100- to 1,000-fold more dilute than the allergen concentration used for prick/puncture tests.”

2013 Update

A search of peer reviewed literature through July 2013 was performed. The following is a summary of the key literature to date.

SLIT compared to placebo

At the time of the 2003 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment, (1) there were 21 published randomized controlled trials (RCTs) comparing SLIT to placebo suggesting that sublingual immunotherapy (SLIT) decreased one or more symptoms for patients with pollen or dust mite allergies. Systemic adverse effects occurred in only one study, and these were not life-threatening. However, whether SLIT improved health outcomes when compared with injection allergen-specific immunotherapy (SCIT), the gold standard comparison, could not be determined from the available evidence. Due to the paucity of studies comparing SCIT to SLIT and the lack of FDA-approved agents for use in SLIT, the use of SLIT for allergen immunotherapy was considered experimental, investigational and unproven.

Since the TEC Assessment, numerous placebo-controlled RCTs and meta-analyses of RCTs have been published. In 2013, Lin and colleagues conducted a comparative effectiveness review for the Agency for Healthcare Research and Quality (AHRQ) on allergen-specific therapy for treating allergic rhinoconjunctivitis and/or asthma. (2) The authors identified 60 studies comparing SLIT to placebo or another intervention. (Studies using SCIT as the comparison intervention were evaluated separately; see section below on SLIT compared to SCIT). Over two-thirds of the studies (71%) compared SLIT to placebo, 14% compared SLIT to pharmacotherapy or rescue medication, and 15% compared SLIT to another intervention. Most of the studies (66%) evaluated seasonal allergens, 31% evaluated perennial allergens and the remainder addressed both types of allergens. About half of the studies used only one allergen and the other half used multiple allergens. Only 22% of the studies were rated as having a low risk of bias. Most (68%) were considered to have a moderate risk of bias and 14% to have a high risk of bias. The authors did not pool study findings because of heterogeneity among studies, i.e., in types of allergen extracts, sources of allergen extracts, doses, treatment duration, and outcome scoring systems. The review concluded that there is high-grade evidence that SLIT improves asthma symptoms compared to placebo or another intervention (13 RCTs) and moderate-grade evidence that SLIT improves rhinitis/rhinoconjunctivitis symptoms compared to placebo or another intervention (35 RCTs). There was moderate-grade evidence that SLIT improves other outcomes in this population, e.g., decreased medication use and increased quality of life. Lin and colleagues also published the findings of the systematic review in a peer-reviewed journal in 2013. (3) The review focused on studies comparing SLIT to placebo, pharmacotherapy or another SLIT regimen and did not address SCIT. Like the AHRQ review, study findings were not pooled. The authors noted that high-quality studies are needed to determine optimal dosing strategies.

In addition, several reviews of systematic reviews have been published. In 2011, de Bot and colleagues evaluated the quality of systematic reviews and meta-analyses on SLIT for treating allergic rhinitis in children. (4) The investigators used the Assessment of Multiple Systematic Reviews (AMSTAR) quality evaluation tool to rate the reviews. The maximum score on the AMSTAR is 11; a score of 0-4=low quality, 5-8= moderate quality, and 9-11=high quality. The authors identified 10 systematic reviews. None of these were rated as high quality; 6 were rated as moderate quality, and 4 as low quality. This analysis indicates that while there are numerous systematic reviews on SLIT, the methodologic quality remains suboptimal. This research suggests that SLIT for children could be promising, but methodologic flaws preclude definitive conclusions.

In 2009, Compalati and colleagues evaluated meta-analyses of RCTs on specific immunotherapy for respiratory allergy. (5) They identified 7 meta-analyses of placebo-controlled RCTs using well-defined inclusion criteria, allergens, doses, and outcome measurement; 5 were on SLIT and 2 were on SCIT. Regarding evidence on SLIT, this analysis corroborated that there is evidence of efficacy compared to placebo but that questions remain, in particular regarding the optimal dose. This review highlighted the lack of consistent relationships between treatment dose, duration, and clinical efficacy.

Representative meta-analyses are summarized briefly below.

A 2012 meta-analysis by Di Bona and colleagues focused on studies of immunotherapy in adults and children with seasonal allergic rhinitis. (6) To be included in the meta-analysis, trials needed to be double-blind, placebo-controlled and evaluate natural grass pollen extracts for treating individuals with a history of grass pollen allergy. The authors identified 22 trials on SLIT versus placebo; 10 used sublingual drops and 12 used tablets. The authors also identified 14 studies on SCIT versus placebo. The investigators conducted an indirect meta-analysis, evaluating the impact of SLIT and SCIT, compared to placebo, on outcomes. The primary outcomes of the meta-analysis were reduction in symptoms and reduction in medication use. Because studies used different scoring symptoms, effect size was calculated as a standard mean difference (SMD). Compared to placebo, both SCIT and SLIT (drops and tablets) resulted in significantly greater reductions in symptom and medication scores. The effect size of SCIT versus placebo for the symptom score was -0.92 (95% confidence interval [CI]: -1.26 to -0.58). The effect size for SLIT administered via drops was SMD: -0.25, 95% CI: -0.45 to -0.05 and for SLIT administered by tablets was SMD: -0.40, 95% CI: -0.54 to -0.27. Results were similar for medication use. The investigators noted the larger effect sizes in their pooled analysis of studies comparing SCIT to placebo.

A 2011 Cochrane review addressed SLIT for treating allergic conjunctivitis in adults and/or children. (7) A total of 57 trials met inclusion criteria, and 42 of these had data available for meta-analysis. All of the trials were conducted in countries other than the United States. The primary outcome of the meta-analysis was the total ocular symptom score. In a pooled analysis of data from 36 trials with a total of 3,399 participants, there was a significantly greater reduction in total ocular symptom scores in the SLIT group compared to placebo (SMD: -0.41, 95% CI: -0.53 to -0.28, p<0.0001). This review supports the conclusion that SLIT is moderately effective in reducing ocular symptom scores compared to placebo but that concerns about the overall quality of the evidence base remain.

In 2011, Radulovic and colleagues published a meta-analysis of double-blind, placebo-controlled RCTs on SLIT for allergic rhinitis in adults and/or children. (8) Sixty studies met inclusion criteria, and 49 (total n=4,589) of these had efficacy data available suitable for meta-analysis. Most of the studies (n=23) used grass pollen; other allergens used included ragweed, house dust mites, and trees. In a pooled analysis of study findings, there was a significantly greater reduction in symptom scores with active SLIT treatment compared to placebo (SMD: -0.49, 95% CI: -0.64 to -0.34, p<0.0001). In addition, a pooled analysis found a significantly greater reduction in medication use scores with SLIT versus placebo (SMD: -0.32, 95% CI: -0.43 to -0.21, p<0.0001).

SLIT compared to SCIT

Few published randomized trials have compared SLIT and SCIT head-to-head. A 2012 review by Bahceciler and Galip listed 8 RCTs comparing SLIT and SCIT. (9) Sample sizes in individual studies ranged from 20 to 58 participants. Three of the studies were published in the 1990s and the other 5 were published between 2004 and 2012. Pipet and colleagues reported that none of the studies from the 1990s found a statistically significant difference in efficacy between the 2 routes of administration. (10) Three of the newer RCTs compared the efficacy of dust-mite specific SLIT and SCIT and were published by investigators in Turkey. (11-13) Similar to the older studies, none of these RCTs found statistically significant differences between treatment with SLIT and SCIT in overall reduction of symptoms or medication use. For example, Eifan and colleagues published findings on 48 children with asthma or rhinitis who had been sensitized to house dust mites. (11) Participants were randomized to receive treatment with SLIT (n=16), SCIT (n=16), or usual pharmacotherapy alone (n=16). There was no significant difference in efficacy between the SLIT and SCIT groups. Compared to pharmacotherapy alone, both immunotherapy groups demonstrated significant reduction in rhinitis and asthma symptom scores and medication use scores.

The 2013 AHRQ comparative effectiveness review, discussed above, identified 8 RCTs comparing sublingual and subcutaneous immunotherapy. (2) The report stated that only 1 study was considered to be at low risk of bias and most of the studies had biases related to improper concealment of allocation to the interventions, unblinded interventions and incomplete reporting of missing data. The authors were unable to pool study findings because of heterogeneity. Regarding the question of comparative effectiveness of SLIT and SCIT, the report concluded that there was low-grade evidence that SCIT is more effective than SLIT at controlling allergy symptoms and dust mite allergy symptoms. Moreover, the report concluded that there was moderate-grade evidence that SCIT provides better symptom control for allergic nasal and/or eye symptoms than SLIT.

Also in 2013, Dretzke and colleagues published a systematic review that included an indirect comparison of SCIT and SLIT using data from placebo-controlled trials. (14) Several outcomes were examined. For symptom score, the overall standardized score difference (SSD) was 0.35 (95% CI: 0.13 to 0.59), a statistically significant result that favored SCIT. The overall SSD for medication score was 0.27 (95% CI: 0.03 to 0.53) which was statistically significant in favor of SCIT. The authors noted that there was substantial heterogeneity among trials and that it is difficult to draw conclusions about the clinical significance of the difference in outcomes between SCIT and SLIT.

In 2011, Sieber and colleagues published a meta-analysis of individual patient data from 4 observational studies on treatment of allergic rhinitis. (15) A total of 665 patients were treated with SLIT and 182 with SCIT. The median rhinitis symptom score decreased from 3.00 to 2.00 (range 1.00 to 4.00) in both treatment groups; p<0.001 for changes within-group. The median conjunctivitis symptom score decreased from 2.00 to 1.00 (range 0.00-3.00) in each group; p<0.001 for changes within-group. In addition, the median asthma symptom score decreased from 3.00 to 2.00 (range 1.00-4.00) in each group; p<0.001 for changes within-group. There were no significant differences in symptom scores when the SLIT group was compared to the SCIT group.

In terms of the relative safety of SCIT and SLIT, the 2009 Pipet review (10) cites reports of fatalities after SCIT, although subsequent examination of 13 deaths occurring between 1992 and 1996 suggested that unstable asthma was a major risk factor. It is generally believed that SCIT is safe when performed with proper patient selection and established security principles. A 2012 review of sublingual immunotherapy for allergic rhinitis stated that no SLIT-related fatalities have been reported. (16) There may be a larger number of mild-to-moderate adverse effects with SLIT than SCIT. The 2012 meta-analysis by Di Bona and colleagues (6) included 22 placebo-controlled studies on SLIT and 14 on SCIT The investigators identified a total of 960 adverse events (AEs) in patients who received SCIT (0.86 AE per patient) and 4,046 AEs in patients who received SLIT (2.13 AEs per patient). Most of the AEs were modest in severity. The authors did not report the total number of serious AEs. However, they stated that there were 12 episodes of anaphylaxis requiring epinephrine treatment in patients treated with SCIT and only 1 in patients treated with SLIT. There were also 2 reported episodes of anaphylaxis in patients treated with placebo in the SCIT studies.

Ongoing Clinical Trials

Long-Term Effects of Sublingual Grass Therapy (NCT01335139): (17) This double-blind trial is randomizing adults with seasonal allergic rhinitis to treatment with SCIT and placebo SLIT or SLIT and placebo SCIT. The primary outcome is nasal response to an allergen challenge and secondary outcomes include use of rescue medication, quality of life and hay fever severity. The estimated completion date is September 2014.

Practice Guidelines and Position Statements

In 2013, the American Academy of Allergy, Asthma and Immunology and the European Academy of Allergy and Clinical Immunology published a consensus report on allergy immunotherapy. (18) The report summarized the literature and current practices in the U.S. and Europe; it did not include clinical recommendations. The authors concluded, “AIT (allergy immunotherapy) is effective in reducing symptoms of allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition, AIT modifies the underlying course of disease. However, AIT remains a niche treatment secondary to symptomatic drugs because of its cost, long duration of treatment and concerns regarding safety and effectiveness…”

In 2011, a joint task force of the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology issued updated practice parameters for allergen immunotherapy. (19) The document stated that RCTs of SLIT for individuals with allergic rhinitis and asthma have demonstrated significant improvement in symptoms. The authors note that there are no FDA approved extract formulations for a non-injection route of immunotherapy.

Summary

Sublingual immunotherapy (SLIT) is a potential alternative to subcutaneous immunotherapy (SCIT) for providing allergen-specific therapy. Despite multiple placebo-controlled studies evaluating SLIT, questions remain about the optimal dosing, duration of treatment, and the use of multiple allergens. Moreover, there are few head-to-head studies comparing SLIT to SCIT. The limited number of comparative trial tended to have small sample sizes and were likely underpowered. Several 2013 systematic reviews tended to find better outcomes with SCIT than with SLIT, but findings are not conclusive due to the limited number of trials and variability in study design. There are also insufficient data to draw firm conclusions about the relative safety of SLIT versus SCIT. A recent meta-analysis of placebo-controlled trials suggests there may be more mild-to-moderate adverse events with SLIT than SCIT, but there are only data on a small number of serious adverse events. Because of the above limitations in the evidence and the absence of any FDA-approved allergy extracts for sublingual immunotherapy, this treatment is considered experimental, investigational and unproven.

A MEDLINE search of the literature through July 2013 revealed no new published clinical trials on the allergy tests or allergy therapy listed as experimental, investigational and unproven in this medical policy. Specifically, there are no randomized, controlled clinical trials documenting outcomes and impact on treatment decision for Rebuck skin window test, passive transfer of P-X (Prausnitz-Kustner test), antigen leukocyte cellular antibody test (ALCAT), provocation and neutralization therapy, cytotoxic food tests, leukocyte histamine release test (LHRT), topical localized application of an allergen, urine auto-injections, or repository emulsion therapy.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

99.12, V15.09, V72.7, 477.0-477.9

ICD-10 Codes

J30.1-J30.9, Z01.82, Z91.010-Z91.048, 3E0D7GC

Procedural Codes: 82785, 83516, 86001, 86003, 86005, 86160, 86343, 86486, 89190, 95004, 95017, 95018, 95024, 95027, 95028, 95044, 95052, 95056, 95060, 95065, 95070, 95071, 95076, 95079, 95117, 95120, 95125, 95130, 95131, 95132, 95133, 95134, 95144, 95145, 95146, 95147, 95148, 95149, 95165, 95170, 95180, 95199, J7665, J7674
References
  1. Blue Cross Blue Shield Association Technology Evaluation Center (TEC). Sublingual immunotherapy for allergies. TEC Assessment 2003; Volume 18, Tab 4.
  2. Lin SY, Erekosima N, Suarez-Cuervo C et al. Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma: Comparative Effectiveness Review No. 111. (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2007-10061-I.) AHRQ Publication No. 13-EHC061-EF. 2013. Available online at: www.effectivehealthcare.ahrq.gov . Last accessed 2013 April.
  3. Lin SY, Erekosima N, Kim JM et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA 2013; 309(12):1278-88.
  4. De Bot C. M., Moed H, Berger MY et al. Sublingual immunotherapy in children with allergic rhinitis: quality of systematic reviews. Pediatr Allergy Immunol 2011; 22(6):548-58.
  5. Compalati E, Penagos M, Tarantini F et al. Specific immunotherapy for respiratory allergy: state of the art according to current meta-analyses. Ann Allergy Asthma Immunol 2009; 102(1-Jan):22-8.
  6. Di Bona D, Plaia A, Leto-Barone MS et al. Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a meta-analysis-based comparison. J Allergy Clin Immunol 2012; 130(5):1097-107 e2.
  7. Calderon MA, Penagos M, Sheikh A et al. Sublingual immunotherapy for treating allergic conjunctivitis. Cochrane Database Syst Rev 2011; (7):CD007685.
  8. Radulovic S, Wilson D, Calderon M et al. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66(6):740-52.
  9. Bahceciler NN, Galip N. Comparing subcutaneous and sublingual immunotherapy: what do we know? Curr Opin Allergy Clin Immunol 2012; 12(6):640-7.
  10. Pipet A, Botturi K, Pinot D et al. Allergen-specific immunotherapy in allergic rhinitis and asthma: Mechanisms and proof of efficacy. Respir Med 2009; 103(6):800-12.
  11. Eifan AO, Akkoc T, Yildiz A et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 2010; 40(6):922-32.
  12. Yukselen A, Kendirli SG, Yilmaz MEoo-ys et al. Int Arch Allergy Immunol 2011; 157(3-Jan):288-98.
  13. Keles S, Karokov-Aydiner E, Ozen A et al. A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. J Allergy Clin Immunol 2011; 128(4):808-15.
  14. Dretzke J, Meadows A, Novielli N et al. Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: A systematic review and indirect comparison. J Allergy Clin Immunol 2013 [Epub ahead of print].
  15. Sieber J, Shah-Hosseini K, Mosges R. Specific immunotherapy for allergic rhinitis to grass and tree pollens in daily medical practice- symptom load with sublingual immunotherapy compared to subcutaneous immunotherapy. Ann Med 2011; 43(6):418-24.
  16. Wise SK, Schlosser RJ. Evidence-based practice: sublingual immunotherapy for allergic rhinitis. Otolaryngol Clin North Am 2012; 45(5):1045-54.
  17. Sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Long-Term Effects of Sublingual Grass Therapy (NCT01335139). Available online at: www.clinicaltrials.gov. Last accessed April, 2013.
  18. Burks AW, Calderon MA, Casale T et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol 2013 [Epub ahead of print].
  19. American Academy of Allergy Asthma Immunology, American College of Allergy Asthma Immunology, Joint Council of Allergy Asthma Immunology. Allergen immunotherapy: a practice parameter third update. 2011. Available online at: www.guideline.gov. Last accessed April, 2013.
  20. Sublingual Immunotherapy as a Technique of Allergen Specific Therapy. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Manual (2013 May) Medicine 2.01.17.
  21. Reisman, R.E.American Academy of Allergy: Position statements - controversial techniques" The Journal of Allergy and Clinical Immunology (1981 May) 57(5):333-8.
  22. Stark, B.J., Earl, H.S., et al. Acute and chronic desensitization of penicillin-allergic patients using oral antibiotics. Journal of Allergy and Clinical Immunology (1987 March) 79(3):523-32.
  23. Allergy Immunotherapy, Provocation/Neutralization. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (1987 May): 2-10.
  24. Allergy Immunotherapy, Serial Dilution Endpoint Titration (Rinkel Method. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (1987 May):11-9.
  25. Allergy Testing, Provocation Testing for Food Allergies. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (1987 July):185-92.
  26. Allergy Testing, Serial Dilution Endpoint Titration. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (1987 July):193-6.
  27. Borish, L., Tamir, R., et al. Intravenous desensitization to beta-lactam antibiotics. Journal of Allergy and Clinical Immunology (1987 September) 80 (3 Part 1):314-9.
  28. In Vitro Allergy Tests for Specific IgE. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (1990 May): 56-84.
  29. Berkow, Robert M.D., and Andrew J. Fletcher, M.B., B.Chir. eds. 1992. The Merck Manual, 17th edition. New Jersey: Merck & Company., Inc.:319-25.
  30. The Use of In Vitro Tests for IgE Antibody in the Specific Diagnosis of IgE-Mediated Disorders and in the Formulation of Allergen Immunotherapy. American Academy of Allergy, Asthma and Immunology, Physician Reference Materials: Position Statement 21 (1992 August) 90(2):263-7.
  31. Bernstein, J.A., Kagen, S.L., et al. Rapid venom immunotherapy is safe for routine use in the treatment of patients with Hymenoptera anaphylaxis. Annals of Allergy (1994 November) 73(5):423-8.
  32. Feliziani, V., Lattuada, G., et al. Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. Allergologia Et Immunopathologia (1995 September-October) 23(5):224-30.
  33. American Academy of Allergy, Asthma, and Immunology Physician Reference Materials: Position Statement 8 - Controversial Techniques. Journal of Allergy and Clinical Immunology (1981 May) 67(5): 333-8. Prepared by AAAAI - (Copyright: 1996):1-13.  http://www.aaaaai.org.
  34. Sharkey P. and J. Portnoy. Rush immunotherapy: experience with a one-day schedule. Annals of Allergy, Asthma, and Immunology (1996 February) 76(2):175-80.
  35. Greinder, D.K. Risk management in allergen immunotherapy. Journal of Allergy and Clinical Immunology (1996 December) 98(6 Part 3): S330-4.
  36. Use of Immunotherapy in a Primary Care Office. American Family Physician, American Academy of Family Physicians. Prepared by Craig, R., et.al. (1998 April 15):1-13
  37. Poon, A.W., Goodman, C.S., et al. In vitro and skin testing for allergy: comparable clinical utility and costs. American Journal of Managed Care (1998 July) 4(7):969-85.
  38. American College of Allergy, Asthma & Immunology. Fact Sheet: Efficacy and Safety of Immunotherapy. Prepared by ACAAI - (Copyright: 1998 October 7):1-4.
  39. National Institutes of Health Immunologic Mechanism of Allergy Immunotherapy - Protocol # 99-I-0146. (1999): 1-6. Prepared by Warren grant Magnuson Clinical Center http://clinicalstudies.info.nih.gov.
  40. Joint Task Force on Practice Parameters for Immunology. The Joint Council of Allergy, Asthma, and Immunology (1999 November 22) http://www.jcaai.org.
  41. Joint Task Force on Practice Parameters for Allergy Testing. The Joint Council of Allergy, Asthma, and Immunology (2000 March 21) (Web site) : http://www.jcaai.org.
  42. Antico, A., Lima, G., et al. Assay of prick test inoculum volume. II. “Average values and individual variability. Annals of Allergy, Asthma, and Immunology (2000 August) 85:145-9.
  43. Disorders with Type IV Hypersensitivity Reactions. (2001) Merck Osteoporosis Education System - 1995-2001 Merck & Co., Inc. http://www.merck.com.
  44. Medscape Practical Issues in the Management of Hypersensitivity Reactions 2001. Prepared by Stephen A. Tilles, M.D. (2001 Southern Medical Association: Southern Medicine Journal 94(8): 810-2) http://www.medscape.com.
  45. Moverare, R., Vesterinen, E., et al. Pollen-specific rush immunotherapy: Clinical efficacy and effects on antibody concentrations. Annals of Allergy, Asthma, and Immunology (2001 March) 86(3):337-42.
  46. Li, J.T., Lockey, R.F., et al. Allergen immunotherapy: a practice parameter. Annals of Allergy, Asthma, and Immunology (2003 January) 90(1):1-40.
  47. Krouse, J.H., and R.L. Mabry. Skin testing for inhalant allergy 2003: current strategies. Otolaryngol Head Neck Surg (2003) 129(4 suppl):S33-S49.
  48. Histamine levels and nasal cytology in children with chronic otitis media and rhinitis.  Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Reference Manual (2003 March) Medicine 2.04.01.
  49. Sublingual Immunotherapy for Adults. Chicago, Illinois: Blue Cross Blue Shield Association Technical Evaluation Center (2003 June):1-46.
  50. Harvey, S.M., Laurie, S., et al. Safety of rush immunotherapy to multiple aeroallergens in an adult population. Annals of Allergy, Asthma, & Immunology (2004 April) 92:414-9.
  51. Casale, T.B. Status of immunotherapy: current and future. Journal of Allergy and Clinical Immunology (2004 June) 113(6):1036-9.
  52. Smith, H. et al. Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis. Journal of Allergy and Clinical Immunotherapy (2004) 114(4):831-7.
  53. Messaad. D., Sahla, H., et al. Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction (2004 June 15) 140 (12):1001-6.
  54. Schwindt, C.D., Hutcheson, P.S., et al. Role of intradermal skin tests in the evaluation of clinically relevant respiratory allergy assessed using patient history and nasal challenges. Annals of Allergy and Asthma Immunology (2005 June) 94(6):627-33.
  55. Cox, L.S., Linnemann, D.L., et al. Sublingual immunotherapy:  a comprehensive review. Journal of Allergy and Clinical Immunology (2006) 117(5):1021-35.
  56. Ridout, S., Matthews, S., et al. The diagnosis of Brazil nut allergy using history, skin prick tests, serum-specific immunoglobulin E and food challenges. Clinical and Experimental Allergy (2006 February) 36(2):226-32.
  57. Astier, C., Morisset, M., et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. Journal of Allergy and Clinical Immunology (2006 July): 118(1):250-6.
  58. Bahceciler, N.N., Ozdemir, C., et al. Immunologic aspects of sublingual immunotherapy in the treatment of allergy and asthma. Current Medicine and Chemistry (2007) 14(3):265-9.
  59. Rondón, C., Romero, J.J., et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. The Journal of Allergy and Clinical Immunology (2007 April) 119 (4):899-905.
  60. Klunker, S., Saggar, L.R., et al. Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis:  Inhibition of IgE-facilitated allergen binding. Journal of Allergy and Clinical Immunology (2007 September) 120(3):688-95.
  61. Sublingual immunotherapy as a technique of allergen specific therapy. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Manual (2009 February) Medicine 2.01.17.
  62. Serial Endpoint Testing for the Diagnosis and Treatment of Allergic Disorders. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Manual (2009 May) Medicine 2.01.23.
  63. Bernstein, I.L., Li, J.T., et al. American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology. Allergy diagnostic testing: an updated practice parameter. Part 1. Ann Allergy Asthma Immunol (2008)100(Suppl 3): S15-S66. Summary available online at: http://www.guideline.gov . accessed  November 2011.
  64. Serial Endpoint Testing for the Diagnosis and Treatment of Allergic Disorders. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Manual (2011 June) Medicine 2.01.23.
History
November 2011  Removed Serial End Point Testing (SET). SET will be seperate policy.
December 2013 Policy formatting and language revised.  Title changed from "Allergy Testing and Treatment" to "Allergy Management".  Combined "Sublingual Immunotherapy as a Technique of Allergen Specific Therapy" and "Serial Endpoint Testing for the Diagnosis and Treatment of Allergic Disorders" into this policy.
BCBSMT Home
®Registered marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. ®LIVE SMART. LIVE HEALTHY. is a registered mark of BCBSMT, an independent licensee of the Blue Cross and Blue Shield Association, serving the residents and businesses of Montana.
CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
Allergy Management