Allergy immunotherapy is a treatment designed to prevent allergic reaction from occurring, thus treating the basic cause of the disease process.  Immunotherapy involves giving gradually increasing doses of the substance, or allergen, to which the person is allergic.  This causes the immune system to become less sensitive to the substance thereby reducing the symptoms of allergy when the substance in encountered in the future.

Medically Necessary:

Allergy immunotherapy is considered medically necessary in individuals with a demonstrated hypersensitivity that cannot be managed by medications or avoidance and the specific type of immunotherapy is not identified below as investigational/not medically necessary.

Investigational/Not Medically Necessary:

Allergy immunotherapy is considered investigational/not medically necessary in all other cases where the hypersensitivity can be managed by medication or avoidance, and also for the specific types of immunotherapy listed below:

• Provocative and neutralization therapy for food allergies using sublingual, intradermal, and subcutaneous routes
• High dose (at least 20-375 times the cumulative subcutaneous dose) or low dose sublingual immunotherapy
• Oral immunotherapy (antigens in capsules that are swallowed immediately)
• Repository emulsion therapy
• Urine autoinjections and autogenous immunization therapy
• Rotational diets and multiple food elimination diets
• Enzyme potentiated desensitization (EPD)
• Acupuncture for allergies
• Allergoids (modification of allergens to reduce allergenicity)
• Ecology units/environmental chemical avoidance for multiple chemical sensitivity syndrome
• Homeopathy for allergies
• Idiopathic environmental intolerance (also know as multiple chemical sensitivity syndrome, clinical ecology, chemical AIDS, environmental/chemical hypersensitivity disease, total allergy syndrome, cerebral allergy, 20^th-century disease)
• Photoinactivated extracts
• Polymerized extracts
• Poison ivy/poison oak extracts for immunotherapy in the prevention of toxicodendron (Rhus) dermatitis

Based on available peer-reviewed medical literature, allergy immunotherapy has been demonstrated to be an effective therapy for the treatment of allergies when the conventional treatments of medication and avoidance have failed.  In individuals with hypersensitivity, the goal of allergy immunotherapy is to prevent allergic reactions from occurring.

Subcutaneous immunotherapy (SCIT) is the current standard of care.  It is established as effective for patients with allergic rhinitis and/or asthma, especially for allergies to grass pollen, ragweed pollen, birch pollen, mountain cedar pollen, house dust mite, cladosporium, alternaria, and cats. It is also effective for anaphylaxis to hymenoptera venom. Alternative routes of administration such as oral (OIT) and sublingual (SLIT) have been studied.

Since 1986, there have been at least 22 double blinded, placebo-controlled studies published in peer-reviewed journals assessing the effectiveness of sublingual immunotherapy (SLIT).  The vast majority of these studies were conducted outside of the United States and with small sample sizes. In a review study published by Canonica and Passalacqua in 2003, analysis revealed that all but three of the studies confirmed the clinical efficacy of SLIT in rhinitis induced by common allergens (when compared to placebo).  There have been no head-to-head studies comparing the effectiveness of SLIT to SCIT (the gold standard). Additionally, the allergen extracts that have been FDA approved for use in SCIT do not have a similar approval for use in SLIT and are used as an off-labeled indication.  Additionally, it is uncertain exactly what dose of allergen extract is required when administered via the sublingual route. There is inadequate data to document the efficacy of immunotherapy for allergies to food, fungi, molds, yeasts, and other undefined allergens, or for the treatment of atopic dermatitis or eczema, angioedema, and urticaria.

Although the Allergic Rhinitis and its Impact on Asthma (ARIA) Workshop Report concluded, in collaboration with the World Health Organization (WHO), that high dose SLIT therapy was efficacious for treating allergies to pollen and dust mites, the fact that there have been no direct comparisons to the gold standard of SCIT and that there are no FDA approved allergen extracts for sublingual delivery make this form of immunotherapy investigational/not medically necessary at this time.

Lastly, there is no published data to support the clinical efficacy of oral immunotherapy.

An allergy is an abnormal reaction or increased sensitivity to certain substances in the environment.  The substances that cause this sensitivity or reaction are called allergens and can vary from naturally occurring materials, such as pollen and grass, to man-made materials including soaps or chemicals.  According to the National Institute of Allergy and Infectious Diseases, about 20% of the general population experience allergic reactions triggered by harmless agents such as pollens, molds, and dust mites.  First line treatment includes avoidance and minimization of exposure when possible.  Medication, including antihistamines, bronchodilators, leucotriene inhibitors, and steroids (cortisone), may be used to reverse some of the symptoms of these allergic reactions.

Allergy immunotherapy is a form of treatment designed to prevent the allergic reaction from ever occurring, thus treating the basic cause of the disease process.  Its mechanism of action is based upon the fact that the body produces different antibodies to the same antigen depending on how the antigen is introduced into the body. Allergy immunotherapy is typically used in patients where the use of conservative treatments, such as avoidance and medications, has been found to be inadequate.  Allergy immunotherapy begins with exposing the patient to very low doses to prevent serious reactions, and progresses gradually to increased doses injected once or twice a week.  This allows the body to slowly develop immunity to the antigen without the development of symptoms.  After a period of time, a maximum dose of antigen is reached and injections are maintained at this dosage with the interval between injections changed to between two and six weeks.  Immunotherapy may need to be administered continuously for several years.  Immunotherapy does not cure allergies but rather makes the patient less sensitive to them.  In some cases, allergic symptoms may be controlled to the point of disappearance, allowing a person to avoid allergen reactions.

Immunotherapy has been demonstrated to be effective in patients with allergic runny nose (rhinitis), allergic watery and red eyes (conjunctivitis), or extreme skin irritation to wasp stings.  In some individuals, allergy immunotherapy may be effective in allergic asthma as well.  Subcutaneous immunotherapy (SCIT) is the current standard of care and is the most common and effective route for administration of allergy immunotherapy. Sublingual immunotherapy (SLIT), generally performed as sublingual-swallow, has been suggested as an alternative route for administration of immunotherapy.  Sublingual immunotherapy involves administration of antigen drops under the tongue.  The antigen drops are administered in gradually increasing doses in an effort to build up individual tolerance to the allergy-causing substance.

A reaction to allergy immunotherapy treatment can occur within the first 30 minutes following an injection, or it may be delayed for up to 12-24 hours.  Most reactions are local, such as itching, pain and swelling when therapy is administered via injection.  Occasionally, more severe reactions (such as hives or shock) may occur.  The most severe reactions usually occur within the first 30 minutes after an injection; any reactions occurring after that time are generally mild.  To monitor for these effects, treatment is given in a medical office.  Environmental interventions, such as avoidance of allergens, and medications may be used in conjunction with allergy immunotherapy.

Autogenous immunization therapy: a medical technique that involves the injection of a person's own sterilized urine for the purpose of treating allergies

Ecology units: a special section of a hospital or medical facility that is designed for the treatment of chemical sensitivity; these units are designed to minimize the presence of various chemicals in the environment

Enzyme potentiated desensitization (EPD): the combination of injections with an enzyme to improve the response to medical treatment for allergies

Multiple chemical avoidance: a treatment method that involves avoiding substances that cause allergic reactions

Photoinactivated extracts: a man-made form of any substance that causes allergic reactions, where the substance has been altered using strong light;  the purpose of this light exposure is to decrease the substance's ability to cause an allergic reaction while maintaining its ability to build an immune resistance to it

Polymerized extracts: a man-made form of any substance that causes allergic reactions, where the individual molecules of the substance have been linked into a long chain; the purpose of this linking is to decrease the substance's ability to cause an allergic reaction while maintaining its ability to build an immune resistance to it

Provocative and neutralization therapy: a medical therapy that involves the injection under the skin of substances suspected of triggering an allergic reaction in sufficient quantity to cause symptoms similar to the patient's complaints; this is then followed by an immediate injection of a weaker or stronger dilution of the same antigen to relieve the symptoms

Repository emulsion therapy: a form of therapy where certain materials are placed inside the body to improve allergies

Rotational diets: a type of diet that involves eating only limited foods or types of foods for a certain period of time on a cyclical basis to help identify foods that may cause allergic responses

Toxicodendron (Rhus) dermatitis: a form of allergic reaction caused by contact with a specific irritant from a plant, most commonly poison ivy, poison sumac, or poison oak

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the members contract benefits in effect at the time of service to determine coverage or non-coverage or these services as it applies to an individual member.

When services are Medically Necessary:

CPT

ICD-9 Diagnosis

When services are also Medically Necessary:

CPT

ICD-9 Procedure

ICD-9 Diagnosis

When Services are Investigational/Not Medically Necessary:

For the procedure codes listed above with the following diagnosis codes, or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary

ICD-9 Diagnosis

When services are also Investigational/Not Medically Necessary:

CPT

ICD-9 Procedure

ICD-9 Diagnosis

Peer Reviewed Publications:

1. Akdis CA, Blaser K. Immunologic mechanisms of allergen-specific immunotherapy. Adv Exp Med Biol. 2001; 495:247-259.
2. ARIA Workshop Group. Allergic rhinitis and its impact on asthma. J Allergy and Clin Immunol. 2001; 108(5 Suppl): S147-334.
3. Bousquet J, Scheinmann P, Guinnepain MT, et al. Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study. Allergy. 1999; 54(3): 249-260.
4. Broide D, Malling HJ. Immunologic treatment of allergic diseases. Curr Opin Allergy Clin Immunol. 2001; 1(6):541-543.
5. Canonica GW, Passalacqua G. Non-injection routes for immunotherapy. J Allergy Clin Immunol. 2003; 111(3):437-448.
6. Casale TB. Status of immunotherapy: current and future. J Allergy Clin Immunol. 2004; 113(6):1036-1039.
7. Esch RE, Portnoy J. Allergen immunotherapy. Curr Allergy Asthma Rep. 2001; 1(6):491-497.
8. Frew AJ, Smith HE. Sublingual immunotherapy. J Allergy Clin Immunol. 2001; 107(3): 441-444. 
9. Frew AJ. Assessment and modulation of the immune response: Immunotherapy of allergic disease. J Allergy Clin Immunol. 2003; 111(2):712-719.
10. Kagi MK, Wuthrich B. Different methods of local allergen-specific immunotherapy. Allergy. 2002; 57(5):379-388.
11. Li JT, Lockley RF, Bernstein IL, et al. Allergen immunotherapy: a practice parameter. American Academy of Allergy, Asthma and Immunotherapy. American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 2003; 90(Suppl 1):1-40.
12. Li XM, Sampson HA. Novel approaches for the treatment of food allergy. Curr Opin Allergy Clin Immunol. 2002; 2(3):273-278. 
13. Lima MT, Wilson D, Pitkin L, et al. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Clin Exp Allergy. 2002; 32(4):507-514.
14. Lockey RF. ARIA: Global guidelines and new forms of allergen immunotherapy. J Allergy Clini Immunol. 2001; 108(4):497-499.
15. Lombardi C, Gargioni S, Melchiorre A, et al. Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study. Allergy. 2001; 56(10):989-992.
16. Malling HJ. Allergen-specific immunotherapy in allergic rhinitis. Curr Opin Allergy Clin Immunol. 2001 1(1):43-46.
17. Mungan D, Misirligil Z, and Gurbuz L. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma - a placebo controlled study. Ann Allergy, Asthma Immunol. 1999; 82(5):485-490.
18. Nelson HS, Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2004; 113(4):635-642. 
19. Passalacqua G, Lombardi C, Canonica GW. Sublingual immunotherapy: an update. Curr Opin Allergy Clin Immunol. 2004; 4(1):31-36.
20. Patriarca G, Nucera E, Pollastrini E, et al. Sublingual desensitization: a new approach to latex allergy problem. Anesth Analg. 2002; 95(4):956-960.
21. Pawankar R, Fokkens W. Evidence-based treatment of allergic rhinitis. Curr Allergy Asthma Rep. 2001; 1(3):218-226.
22. Rakoski J, Wessner D. A short assessment of sublingual immunotherapy. Int Arch Allergy Immunol. 2001; 126(3):185-187.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Physicians. Clinical Ecology. Ann Intern Med 1989; 111(2):168-78.
2. Blue Cross Blue Shield Assoc. Sublingual immunotherapy for allergies. Technology Evaluation Center. Volume 18, No 4 June 2003. 
3. Diagnosis and management of rhinitis. Ann Allergy Asthma Immunol. 1998; 81(5 Pt 2):478-518.

1. American Academy of Allergy, Asthma, and Immunology (AAAAI) Board of Directors. Idiopathic Environmental Intolerances Position Statement. Available at:
   http://www.aaaai.org/media/resources/academy_statements/position_statements/ps35.asp. Accessed on January 21, 2007.
2. American Academy of Allergy, Asthma, and Immunology (AAAAI). Available at http://www.aaaai.org/patients/publicedmat/tips/whatareallergyshots.stm  Accessed on January 21, 2007.
3. American College of Occupational and Environmental Medicine. (ACOEM) Position Statement on Multiple chemical sensitivities: idiopathic environmental intolerance. Available at: http://www.acoem.org/guidelines.aspx?id=862  http://www.acoem.org/policys/article.asp?ID=46J.  Accessed on January 22, 2007.
4. National Institute of Allergy and Infectious Diseases. Available at: www.niaid.nih.gov.  Accessed on January 21, 2007.

Allergy Immunotherapy
Desensitization
Neutralization Therapy
Provocative Therapy
Repository Emulsion Therapy
Rinkel Method of Allergy Immunotherapy
Sublingual
Urine, Autoinjection

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