Allergen Immunotherapy Information Session

Transcript:
Welcome to the AllergiEnd® Allergen Immunotherapy information session. 
Let me begin by saying that allergen-specific immunotherapy is the only treatment that leads to prolonged tolerance against offending allergens that cause allergic symptoms and disease. Desensitization or hyposensitization is prescribed therapeutically to reduce environmental allergen-specific IgE-mediated sensitivity in hypersensitive (or atopic) individuals. Desensitization has also been proven to reduce demands on constrained health services, as allergen immunotherapy has shown impressive direct and indirect cost savings compared to symptomatic allergy and asthma management alone. 

At a basic level, low doses of the offending allergens are slowly introduced to the patient's immune system via subcutaneous or sublingual delivery modes. Patients who tolerate the allergen exposure have these doses progressively increased, initially by volume and subsequently by the concentration of the specific mixtures referred to as the "build-up" phase. Doses are delivered weekly in the case of injections or daily with oral drops under the tongue. These regimes are becoming more standardized and generally agreed upon by national and international allergy and immunology societies. 

So how does "desensitization" work? 

IgE sensitizes mast cells and basophils by binding to the receptor for the antibody on their surfaces. When exposed to the natural allergen, the mast cells and basophils release histamines, prostaglandins, cytokines, and chemokines, producing the immediate type I allergic reaction seen in patients with allergic rhinitis. Further inflammation occurs after the initial allergic phase, leading to other clinical symptoms such as rhinoconjunctivitis, eczema, asthma, and possibly systemic reactions, such as anaphylaxis, in highly susceptible individuals. One such evolved theory for allergen immunotherapy's mechanism of action is that at around 6-8 weeks after commencing treatment, interleukin-10 (IL-10) is produced and promotes the production of allergen-specific IgG4 from B cells and reduces proinflammatory cytokine release from mast cells, and turns down eosinophil activity. 

Thus, when natural exposure to the allergen occurs, IgG antibodies compete with or block the IgE effector mechanisms, including basophil histamine release, preventing the excessive chemical reactions that cause allergy symptoms. Biopsies taken from patients' skin and nasal mucosa on allergen immunotherapy reveal reductions in inflammatory cell numbers, including mast cells, basophils, and eosinophils. More recent studies have found T cells that regulate IgE production to specific allergens may be stimulated by the low doses of the allergens during immunotherapy hence the name desensitization, generating immune tolerance to the allergen. Another possible reason for allergen immunotherapy's role in producing immune tolerance may be the induction of allergen-specific IgA, which has been observed; these antibodies can induce monocytic cells to produce IL-10, the immunoregulatory cytokine just mentioned. Allergen-specific Treg cells (or regulatory T cells) and their subsequent suppression of cytokine production are essential in producing tolerance to environmental allergens. 

Let's discuss the current National Clinical practice parameters or guidelines. 

For reference, you can download the Allergen Immunotherapy flowchart protocol. Allergen immunotherapy is indicated if the allergy is IgE-mediated as documented by skin testing or specific IgE laboratory testing. Additionally, if the patient's symptoms are not easily controlled with medication or encompass more than one season and are likely to comply with the treatment program, they are a good candidate for allergen immunotherapy. Also notable, allergen immunotherapy is recommended for patients with allergic asthma unresponsive to allergen avoidance, even when patients can achieve symptomatic relief with drug therapy.

Examples of potential allergens for which immunotherapy is proven effective include:

• Animal dander such as cat hair and dog skin

• Cockroach and dust mites

• Mold

• Outdoor allergens such as trees, grasses, and weeds

  
  

The Practice of Allergen Immunotherapy

Target therapeutic or maintenance dose ranges for the most prevalent allergens known to induce allergic sensitization and observed to respond to immunotherapy treatment are well established and available to review in published texts and medical journals. Allergists worldwide, particularly in the US, have arrived at 4 or 5 stage tenfold dilutions from the therapeutic dose to begin treatment. It is typical to begin a patient with a 4 stage treatment set, equating to a 1 to 1,000 concentration of the target therapeutic dose when using this dilution method and progressively increasing the concentration to 1 to 100, 1 to 10, and eventually arriving at the 1 to 1 target dose. These treatment sets are compounded or mixed and labeled as the patient-specific build-up phase for safety and tolerance. Initial concentrations of the target allergens are mixed or compounded and recommended doses are small and will not make the patient ill. As the immune system becomes accustomed to the allergen, the concentration and doses increase; this allows the patient to be exposed to the allergen in the environment without the immune system overreacting.

There are generally two methods:

1. Sublingual Immunotherapy (SLIT) involves under-the-tongue drops once or twice daily.

2. Subcutaneous Immunotherapy (SCIT), which are injections given weekly, bi-weekly or monthly at the physician's office, or at times at home by the patient.

Allergen immunotherapy or allergy shots are indicated in patients whose triggering allergens are not readily avoidable. Treatment plans vary, but in general, they follow these guidelines:

Subcutaneous Immunotherapy 

• Follows initial dosing of short intervals (every seven days). Dosing volume is increased by 0.05 to 0.1 milliliter with each injection if no reaction occurs, usually up until 0.5 milliliters per injection. Food allergens are not treated by injection.

• The initial build-up dosing to the intended "therapeutic dose concentration" is followed by a maintenance dosage regimen at monthly intervals determined by the patient's tolerance and relief of symptoms.

• The length of therapy varies from 2 to 5 years upon reaching the maintenance dose.

• The physician should review the patient's progress at regular intervals, approximately once every 2-3 months. The treatment discontinuation of therapy may be considered after 2 to 3 years of treatment compliance, and the patient's symptoms have been controlled with less use of rescue or symptomatic relief medications. The risk of relapse must be weighed against the patient's preference for discontinuation of therapy.

Subcutaneous (Not Intramuscular) Administration 

• Physicians should give the allergy injection subcutaneously in the lateral or posterior portion of the arm. Immunotherapy should be given subcutaneously.

• Subcutaneous injections result in forming a reservoir of allergen immunotherapy extract that is slowly absorbed. Absorption that is too rapid after an intramuscular injection could lead to a systemic reaction. The skin should be pinched and lifted off the muscles to avoid intramuscular or intravenous injection and increase access to the subcutaneous tissues.

• Physicians should administer each immunotherapy injection in the posterior portion of the middle third of the arm at the junction of the deltoid and triceps muscles. This location tends to have a greater amount of subcutaneous tissue than other areas of the upper arm.

Management of Local Reactions

Local reactions to SCIT at the injection site are common and usually reported as redness, pruritus, and swelling. In many patients, these mildly uncomfortable reactions are self-resolving, rarely require dose adjustments, and are not necessarily predictive of future reactions or potential systemic reactions. Local reactions can be managed with cool compresses, topical corticosteroids, and/or oral antihistamines. In addition, treating patients with 10 milligrams of daily Cetirizine (Zyrtec) during the build-up phase of allergen immunotherapy can reduce local reactions. Thank you for taking some time out of your busy schedule; let me end with what I said at the beginning, allergen-specific immunotherapy is the only treatment that leads to prolonged tolerance against offending allergens that cause allergic symptoms and disease. Desensitization has also been proven to reduce demands on constrained health services, as allergen immunotherapy has shown impressive direct and indirect cost savings compared to symptomatic allergy and asthma management alone. Your patients are looking for real disease correction treatment and not simply masking their symptoms; they are often miserable and suffering from productivity losses from either lost work or school days. AllergiEnd® Allergen Immunotherapy is your solution.