The management of the allergy following a diagnosis can be a complex process
depending upon the number of allergens causing an immunological response and
the severity of the associated symptoms. There are three courses of treatments
for allergy, which may be used individually, or in a combination with one
another:

  1. Avoidance and environmental control - the goal of this treatment is to minimize exposure to allergy triggers.
  2. Pharmacotherapy - this treatment can include one or more types of oral antihistamines, oral steroids, nasal sprays including corticosteroids, eye drops, leukotriene modifiers, and/or nasal sinus rinse with saline. Many take these medications without identifying the allergens that are causing the symptoms. This is an on-going therapy and the long-term health effects are unknown.
  3. Immunotherapy - this treatment involves injection of a patient with an allergen solution in an effort to develop an immune system tolerance. It treats the cause of the disease rather than managing the symptoms.

The management plan must be individualized, with careful consideration given
to the patient's preference, disease severity, and response (or lack of
response) to previous treatment.  
  
 **Overview:**  
Allergy Immunotherapy (AIT) is defined as the repeated administration of
specific allergens to patients with IgE-mediated conditions, for the purpose
of providing protection against the allergic symptoms and inflammatory
reactions associated with natural exposure to these allergens. Immunotherapy
(hyposensitization) may extend over a period of years, usually on an
increasing dosage scale. This is followed by a build-up of tolerance to the
antigen (as evidenced by the markedly higher doses that can be administered)
and a decline in the symptoms and medication requirements of the patient.
Indications for immunotherapy are determined by diagnostic testing appropriate
to the individual needs of each patient and his/her clinical history of
allergic diseases. It is an effective treatment for allergic asthma and
rhinitis/conjunctivitis, as well as stinging insect hypersensitivity. In
addition to reducing symptoms, AIT can change the course of allergic disease
and induce allergen-specific immune tolerance. It appears to have duration of
efficacy of up to 12 years and can prevent the development of asthma and new
allergen sensitivities.  
  
The presence of IgE antibodies alone does not infer the need for
immunotherapy. For example, the presence of IgE antibodies to an allergen not
locally found, with no history of exposure or expectation of exposure would
not be considered clinically relevant, and therefore, is non-covered.  
  
Allergen immunotherapy should be differentiated from the process of
desensitization, which usually applies to the rapid progressive administration
of an allergenic substance to render effector cells less reactive. This is
commonly referred to as "Rush" or "Cluster" immunotherapy.  
  
The major risk of allergen immunotherapy is anaphylaxis. An assessment of the
patient's current health status should be made before administration of the
allergy immunotherapy injection to determine whether there were any health
changes that might require modifying or withholding the patient's
immunotherapy treatment. Poorly controlled asthma has been identified as a
risk factor for a severe immunotherapy-induced reaction. Allergen
immunotherapy should, therefore, be administered under the supervision of an
appropriately trained physician who can recognize early symptoms and signs of
anaphylaxis and administer emergency medications where necessary. In addition,
immunotherapy should be administered only in facilities equipped to treat
anaphylaxis. It would be rare to see the patient receive allergy immunotherapy
in the home by a properly trained individual due to the risk of anaphylaxis
and death.  
  
The physician prescribing immunotherapy should be trained and experienced in
prescribing and administering immunotherapy. The prescribing physician must
select the appropriate allergen extracts based on the patient's clinical
history, allergen exposure history, and the test results for specific IgE
antibodies. The quality of the allergen extracts available is an important
consideration. When preparing mixtures of allergen extracts, the prescribing
physician must consider the cross-reactivity of allergen extracts and the
potential for allergen degradation caused by proteolytic enzymes. The
prescribing physician must specify the starting immunotherapy dose, the target
maintenance dose, and the immunotherapy schedule.  
  
Immunotherapy should be administered in a setting that permits the prompt
recognition and management of adverse reactions. The preferred location for
such administration is the prescribing physician's office. However, patients
can receive immunotherapy injections at another health care facility if the
physician and staff at that location are trained and equipped to recognize and
manage immunotherapy reactions, particularly anaphylaxis. Patients should wait
at the physician's office/medical clinic for at least 30 minutes after the
immunotherapy injection(s) so that reactions can be recognized and treated
promptly if they occur.

Injections of allergen immunotherapy extract can cause local or systemic
reactions. Most serious systemic reactions develop within 30 minutes after the
immunotherapy injection. However, immunotherapy induced systemic reactions can
occur after 30 minutes. The immunotherapy dose and schedule, as well as the
benefits and risks of continuing immunotherapy, should be evaluated by the
prescribing physician after any immunotherapy-induced systemic reaction.  
  
Immunotherapy has two phases: A **build-up phase** and a **maintenance
phase**.  
  
The **build-up phase** (also called updosing, induction, or the dose-increase
phase) includes the initiation and subsequent rise of applicable antigen
concentrations. The starting dose of an allergenic extract and the progression
of the dose must be individualized for each patient. Documentation of this
phase should include the initial concentration, any changes/delay of progress
and the reasoning for such delays, and the target concentration.  
  
Injections usually occur 1-3 times per week and can take anywhere from 8-28
weeks to achieve a maintenance dose. Since it should be rare that injections
would be administered less frequent than the dosing intervals above, providers
should expect denials when reporting these services less frequently. Various
techniques such as cluster immunotherapy and rush immunotherapy are also
included in the build-up phase and should be documented as such in the medical
records. Accelerated schedules entail administration of several injections at
increasing doses on a single visit. Accelerated schedules offer the advantage
of achieving the therapeutic dose earlier but might be associated with
increased risk of systemic reaction in some patients.  
  
The **maintenance phase** occurs when the effective therapeutic dose is
reached. This dose is defined as the dose that provides therapeutic efficacy
without significant adverse local or systemic reactions. This dose may not be
the initial target concentration, but documentation should clearly show why
the target concentration is not being used. All references to the therapeutic
effective dose should be referenced to the maintenance concentrate and should
be noted as a volume-to-volume dilution (eg.1:100 vol/vol dilution of
maintenance concentrate). Although all treatment regimens must be
individualized for a given patient, acceptable maintenance dose concentrations
are generally as the following:

  1. For standard allergen extracts: 500 to 2000 allergy units (AU; e.g. for dust mite): or  
1000-4000 bioequivalent allergy units (BAU; e.g. for grass or cat).

  2. For non-standardized extracts: a suggested maintenance dose is 3000-5000 protein nitrogen units (PNU) or 0.5ml of a 1:100 or 1:200 wt/vol dilution of manufacturer's extract.
  3. For major known allergen concentration of the extract: a range between 5 and 20 micrograms of major allergen is the recommended maintenance dose for inhalant allergens and 100 micrograms for Hymenoptra venom.

Documentation of the extracts being used should include concentrations. The
maintenance concentrate should be formulated to deliver a full projected
therapeutic dose of each of its constituent components. However, some patients
might not tolerate the targeted therapeutic dose because of local reactions,
systemic reactions, or both, and their maintenance dose would be lower to the
highest tolerated effective therapeutic dose. The maintenance dose of
immunotherapy for a particular patient must be individualized. Significant
subtherapeutic dosing in a maintenance manner will be considered not
reasonable and not necessary.  
  
The duration of all forms of immunotherapy must be individualized. A
presumption of failure can be made when, after 12-24 months of therapy, a
person does not experience:

  1. a noticeable decrease of symptoms,
  2. an increase in tolerance to the offending allergen, and
  3. a reduction in medication usage.

Treatment will not be reimbursed after a 2-year period when there is no
apparent clinical benefit as noted above.  
  
The American Academy of Allergy, Asthma, and Immunology (AAAAI), the American
College of Allergy, Asthma, and Immunology (ACAAI), and Joint Council of
Allergy, Asthma, and Immunology for Allergen Immunotherapy issued guidelines
in 2011 regarding immunotherapy frequency and duration:

  1. Cluster immunotherapy is an accelerated build-up schedule that entails administering several injections at increasing dose (generally 2-3 per visit) sequentially in a single day of treatment on nonconsecutive days. The maintenance dose is generally achieved more rapidly than with a conventional (single injection per visit) build-up schedule (generally 4-8 weeks).
  2. Rush immunotherapy is an accelerated immunotherapy buildup schedule that entails administrating incremental doses of the rapid administration of incremental doses of allergens at intervals varying between 15 and 60 minutes over 1 to 3 days until the target schedules for inhalant allergens can be associated with a greater risk of systemic reactions, particularly in high risk patients, and premedication primarily with antihistamines and corticosteroids appears to reduce the risk associated with rush immunotherapy. When maintenance dose is achieved, intervals between injections can be progressively increased as tolerated to 4 - 6 weeks.
  3. Venom immunotherapy (VIT) injections generally are given at weekly intervals. The maintenance dose and clinical protection can routinely be achieved with 8 weekly treatments, and even 2-day rush schedules can be used in most patients without an increased risk of systemic reactions. VIT intervals between maintenance dose injections can increase to 4 weeks the first year of VIT and eventually to every 6 - 8 weeks during subsequent years.
  4. Patients receiving maintenance immunotherapy should have follow-up visits at least every 6 to 12 months. Periodic visits should include a reassessment of symptoms and medication use, the medical history since the previous visit, and an evaluation of the clinical response to immunotherapy. The immunotherapy schedule and dose, reaction history, and patient compliance should also be evaluated.
  5. The patient's response to immunotherapy should be evaluated on a regular basis. A decision about continuation of effective immunotherapy should generally be made after the initial period of 3 to 5 years of treatment. Some patients might experience sustained clinical remission of their allergic disease after discontinuing immunotherapy, but others might relapse. The severity of disease, benefits sustained from treatment, and convenience of treatment are all factors that should be considered in determining whether to continue or stop immunotherapy for any individual patient. Currently, there are inadequate diagnostic tools available to identify which patients will experience a sustained clinical remission after discontinuing inhalant immunotherapy. Therefore, the duration of treatment should be determined by the physician and patient after considering the benefits and risks associated with discontinuing or continuing inhalant immunotherapy.
  6. Although there are no specific tests to distinguish which patients will relapse after discontinuing VIT, there are clinical features that are associated with a higher chance of relapse, notably a history of a very severe reaction to a sting, an increased baseline serum tryptase level, a systemic reaction during VIT (to a sting or a venom injection), honeybee venom allergy, and treatment duration of less than 5 years.

**Allergen Supply:**  
Payment may be made for a reasonable supply of antigens that have been
prepared for a particular patient when certain criteria are met. See: CMS Pub
100-02 _Medicare Benefit Policy Manual_ , Chapter 15 - Covered Medical and
Other Health Services, Section - 50.4.4.1 - Antigens (Rev. 186, Issued:
04-16-14, Effective: 01-01 01, Implementation: 05-12-14)

**Providers of Immunotherapy:**  
The physician prescribing immunotherapy should be trained and experienced in
prescribing and administering immunotherapy. For those providers without
formal training moving into an allergy type practice, ongoing yearly training
specifically for allergy testing and treatment should be evident in CMEs. If
any Medicare entity requests documentation of training, formal training, or
ongoing CME updates, this information must be made available.

Antigens need to be prepared by a physician who is a doctor of medicine or
osteopathy who has examined the patient and has determined a plan of treatment
and a dosage regimen. (CMS Pub 100-02 _Medicare Benefit Policy Manual_ ,
Chapter 15, Section 50.4.4.1)

WPS GHA would continue to expect compliance with CMS Pub 100-02 _Medicare
Benefit Policy Manual_ , Chapter 15 - Covered Medical and Other Health
Services Sections, Section 60.2 - Services of Nonphysician Personnel Furnished
Incident to Physician's Services.  
  
**Indications:**  
Indications for immunotherapy are determined by appropriate diagnostic
procedures coordinated with clinical judgment and knowledge of the natural
history of allergic diseases. The following indications are considered
medically reasonable and necessary for allergy immunotherapy:

1\. Controlled studies have shown that allergen immunotherapy is effective for
patients with:

a. Allergic rhinitis,  
b. Allergic conjunctivitis,  
c. Allergic asthma, and  
d. Stinging insect hypersensitivity.

Allergen-induced asthma is an indication for immunotherapy along the
guidelines for allergic rhinitis when there is a poor response to
environmental control or pharmacologic treatment. Allergen immunotherapy in
asthmatic patients should not be initiated unless the patient's asthma is
stable. Patients with severe or uncontrolled asthma are at increased risk for
systemic reactions to immunotherapy injections.

2\. The necessity of allergen immunotherapy depends on the:

a. Degree to which symptoms can be reduced by medications,  
b. Ability of the patient to tolerate possible side effects of the medication,  
c. Amount, type, and cost of the medications required to control symptoms,  
d. Significant exposure to an allergen in which there is a significant level
of sensitivity, and the pattern of symptoms conform to the pattern of
exposure, and  
e. Whether conservative therapies (including avoidance) have failed to control
the symptoms, or avoidance of the relevant antigen (e.g., dust mites, pollen,
and mold) is impractical.

3. Animal dander sensitivity (epidermal) may respond to immunotherapy. While removal of the offending allergen is recommended, this is often not possible or there may be occupational or other sources of exposure. Antihistamines are used first before immunotherapy, but a trial of immunotherapy may be warranted if the antihistamines do not relieve symptoms. 

 4.   Aeroallergen immunotherapy is indicated for patients with allergic rhinitis due to:

a.   Seasonal pollinosis caused by trees, grasses, and weeds.  
b. The treatment of mold-induced rhinitis.  
c. Perennials such as cat and dog dander, dust mite and cockroach.

5\. Standardized dust mite extracts appear effective for immunotherapy. Other
environmental allergens (e.g., kapok, jute, feathers, and unstandardized house
dust extracts) are of questionable value in immunotherapy, however, and
generally should not be used.

6\. Venom immunotherapy is indicated for patients who have a severe systemic
anaphylactic reaction after an insect sting and a positive skin test or other
documented IgE sensitivity to specific insect venom.

7\. Patients with delayed systemic reactions, with symptoms of anaphylaxis or
serum sickness and with a positive skin test or presence of venom specific IgE
by in vitro testing are also recommended for treatment.

 8.  Rapid desensitization is indicated in cases of allergy to insulin, penicillin and horse serum, as well as sulfonamides, cephalosporins and other commonly used drugs (e.g. aspirin). Rush desensitization can also be used in select patients with stinging insect allergies. In patients with a positive history of reaction and with documented skin test reactivity, every effort should be made to avoid the use of these substances. When circumstances require the use of one of these substances, the patient will have to be desensitized. Desensitization may need to be repeated if future circumstances require an additional course of the offending allergen. Full-dose therapy should be initiated immediately after reactions (treated and controlled), requiring strict physician monitoring in a setting with continuous monitoring of vital signs and cardio-respiratory status. In most cases, this can be performed in a physician's office if a physician trained to treat anaphylaxis is physically present for the entire duration. In cases where the initial reaction was severe, desensitization should be performed in the ambulatory care department of a hospital.

**Limitations:**  
The following allergy immunotherapy services are considered investigational
and experimental, therefore, are not medically necessary. The effectiveness
also has not been established; therefore, these indications will not be
covered;

  1. Angioedema. 
  2. Food hypersensitivity/allergy. 
  3. Intrinsic (non-allergic) asthma. 
  4. Migraine headaches. 
  5. Non-allergic vasomotor rhinitis.

The following allergy immunotherapy services are considered investigational
and experimental, and are therefore not medically necessary. The effectiveness
also has not been established; therefore, these indications will not be
covered:

  1. Therapy with allergoids or adjuvants. 
  2. Therapy via other administration:  

    1. Oral or sublingual food immunotherapy*,
    2. Epicutaneous immunotherapy,
    3. Intralymphatic immunotherapy,
    4. Intranasal immunotherapy, or
    5. Sublingual immunotherapy. 
  3. Desensitization with commercially available extracts of poison ivy, poison oak, or poison sumac. 
  4. Desensitization for hymenoptera sensitivity using whole body extracts, with the exception of fire ant extracts**. 
  5. Desensitization with bacterial vaccine (BAC: bacterial, antigen complex, streptococcus vaccine, staphylo-strepto vaccine, serobacterin, staphylococcus phage lysate). 
  6. Food allergenic extracts immunotherapy. 
  7. Intracutaneous desensitization (Rinkel Injection Therapy, RIT). 
  8. Intracutaneous titration. 
  9. Neutralization therapy (intradermal and subcutaneous). 
  10. Repository emulsion therapy. 
  11. Sublingual desensitization***. 
  12. Sublingual provocative therapy***. 
  13. Urine auto-injection (autogenous urine immunotherapy). 
  14. Allergen immunotherapy for the management of skin and mucous membrane diseases such as atopic dermatitis, chronic urticaria, and Candida vulvovaginitis. 
  15. Postmortem examination for IgE antibodies to identify allergens responsible for lethal anaphylaxis (postmortem work is not-covered by Medicare).

Patients who are mentally or physically unable to communicate clearly with the
allergist and those with a history of noncompliance are not good candidates
for allergy immunotherapy. If a patient cannot communicate clearly with the
physician; it will be difficult for the patient to report signs and symptoms,
especially early symptoms, suggestive of systemic reactions.  
  
*Several clinical trials with oral and sublingual immunotherapy demonstrate an increased tolerance to oral food challenge in subjects with food hypersensitivity while receiving therapy. Oral and sublingual food immunotherapy is investigational. At present, the only treatment for food hypersensitivity is avoidance.   
  
**Immunotherapy with whole-body extracts of biting insects or other arthropod
is covered only for fire ant extracts.  
  
***Sublingual immunotherapy (SLIT) involves the use of FDA approved allergenic
extracts administered orally. In early 2014, the FDA approved oral
administration of 3 allergenic extracts, two for grasses and one for ragweed.
These extracts are not approved by the FDA for anyone over the age of 65
years. Medicare does not cover sublingual immunotherapy. Effective October 31,
1988, sublingual intracutaneous and subcutaneous provocative and
neutralization testing and neutralization therapy for food allergies are
excluded from Medicare coverage because available evidence does not show that
these tests and therapies are effective. (CMS Pub 100-03 Medicare National
Coverage Determinations Manual, Chapter 1- Coverage Determinations, Part 2,
Section 110.11 - Food Allergy Testing and Treatment).