Introduction

Allergy desensitization, allergen immunotherapy (AIT), or hypo-sensitization was first introduced by Leonard Noon in 1911, who proposed that people with hay fever were sensitive to grass pollen toxins.[1] Desensitization is "a method, to develop a temporary state of tolerance to an agent responsible for an allergic or hypersensitivity reaction."[2] It is a disease-modifying treatment and lasts longer even after stopping the treatment, which then provides prophylactic effects.[3][4][5][6][7][8]

Immunotherapy is the treatment of allergic disease by promoting or suppressing immunity. Allergen immunotherapy is a group of therapies that seek to promote immune tolerance to allergens.[2] Hyposensitization is a term formerly used as synonymous with allergen immunotherapy because complete desensitization is rare with immunotherapy.

Types of Allergic or Hypersensitivity Disorders

Respiratory tract disorders include allergic rhinitis, allergic aspergillus rhinosinusitis, allergic bronchopulmonary aspergillosis (ABPA), or allergic asthma.[2] Ocular disorders include allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. [2] Skin and mucous membranes disorders include allergic contact urticaria, oral allergy syndrome, acute urticaria due to IgE-mediated allergy, and atopic eczema.[2] Drug hypersensitivity includes exanthematous drug eruption, drug-induced urticaria, angioedema and anaphylaxis, and Samter's syndrome.[2] Food hypersensitivity includes food-induced urticaria, angioedema anaphylaxis, IgE-mediated food-induced gastrointestinal hypersensitivity, and oral allergy syndrome.[2] Insect hypersensitivity or allergies include anaphylaxis, cutaneous reactions or local reaction to Hymenoptera venom.

Anatomy and Physiology

Several cellular and molecular mechanisms explain the beneficial effects of immunotherapy including allergic specific suppression of inducible CD4(+), CD 25+, forkhead box p3+ T-regulatory cells, and IL-10 secreting T-regulatory cells; preventing their increase in peripheral blood. Other mechanisms include suppression of eosinophils, mast cells, and basophils, and antibody switch from IgE to IgG4.[9]

Indications

 Indications for Desensitization[1][2]

• Moderate-to-severe symptoms of allergic rhinitis
• Allergic asthma
• Allergic conjunctivitis
• Allergic rhino-conjunctivitis
• Atopic dermatitis
• Immune-mediated and IgE-mediated food allergy
• Insect allergy that causes significant local reaction and anaphylaxis

Other Immunotherapies[2]

• Vaccination and biological agents in infectious disease and primary immunodeficiencies.
• Immunosuppressive agents in autoimmune disease and organ transplant
• Biological and monoclonal agents
• Food hypersensitivity

Contraindications

• No evidence of the effectiveness of immunotherapy if specific IgE antibodies test results are negative[2]
• When suspected clinical symptoms and exposure do not correlate with positive IgE test results[2]

Equipment

Required Equipment and Procedures[3]

• All extracts require storage in a refrigerator at 4 C
• Administration is via subcutaneous injection
• Seventy percent isopropanol for sanitization
• Sterile syringes and vials
• Mixing log
• Policy and procedure manual

Personnel

Because the allergy desensitization process can cause severe reactions including anaphylaxis, a physician should supervise trained personnel.[3] The required training is[3]:

• Preparation of allergenic products
• Successful completion of a written test on aseptic technique and extract preparation and media-fill testing
• Knowledge of antiseptic hand cleaning and disinfection of mixing surfaces
• Ability to identify, measure, and mix ingredients

Preparation

The prescribing physician should select allergen extracts. The physician should consider several important factors including the quality of allergen extracts, cross-reactivity, and degradation of allergens and immunotherapy doses, for example, the starting dose will be lower than the maintenance dose.[3]

Technique

Allergenic proteins from pollen, dander, dust mites, insects, mold, among others are the main ingredient of allergen extract. However, the final product is a mixture of diluents or solvents and preservatives. Different extracts including aqueous, glycerinated, lyophilized, acetone precipitated, alum-precipitated are available. Diluents will keep the allergen in liquid form; commonly used agents are glycerin, phenol saline, and HSA. The staff should use measures that include good personal hygiene, hand washing, and antiseptics to clean working areas. These include a water-based disinfectant followed by the application of alcohol on working surfaces for preparing allergen extracts. Alcohol kills organisms by dehydration. Sanitization will prevent bacterial contamination.[3]

Clinical Significance

Asthma

Allergen immunotherapy can reduce short-term symptoms in allergic asthma; however, there is a moderate increase in the risk of systemic and local reactions based on meta-analysis.[6] A 3-year course of either sublingual or subcutaneous immunotherapy prevents asthma for up to 2 years in children and adolescents with grass/birch pollen that triggers moderate to severe allergic rhinitis; However, this still requires further research.[4]

Allergic Rhinitis

• Allergen immunotherapy is clinically effective, cost-effective, and disease-modifying in allergic rhinitis compared to standard drugs.[10][11]
• Sublingual immunotherapy for pediatric allergic rhinitis has shown improvement in symptomatic management and a decreased medication need based on a meta-analysis of the randomized controlled trials. More trials with a larger sample size are underway to assess safety in the pediatric population.[12]

Allergic Rhino-Conjunctivitis

Allergen immunotherapy has been found to be beneficial in improving rhino-conjunctivitis symptoms[13]. Some evidence suggests that there is a maintenance effect on reducing symptoms after discontinuation of immunotherapy.[14]

Enhancing Healthcare Team Outcomes

Current and Future Trends in Allergen Immunotherapy

There are different approaches to providing safety and overcoming the risk of severe adverse allergic reactions during immunotherapy. The data from the meta-analysis suggest new allergen preparations available are allergoids, recombinant allergens (recA) and modified-recombinant allergens (recA). Studies on virus-like-particles and CpG-motifs, adjuvants like MPL and aluminum hydroxide have been shown to increase immunological response and can improve safety and efficacy.[8] The latest approaches to allergen immunotherapy include the application of extract patches on the skin and/or inguinal lymph node injection. Recombinant technology or chemicals may alter allergen molecules that make them less reactive; this may be due to suppression of Th2 responses or stimulation of toll-like receptor (approval is pending).[15] The new advances in allergy immunotherapy not only provide disease-modifying treatments but are also cost-effective and improve the quality of life.[16] The major allergen Bet v 1 involved in birch pollen allergy may be the future of allergen immunotherapy for rhino conjunctivitis.[17]

Doses, Delivery, and Application of Immunotherapy 

• Comparison of pediatric and adult systemic reaction to subcutaneous immunotherapy shows significant grade 1 and Grade 2 systemic reactions that are higher in a pediatric population than adults. However, further studies are needed to evaluate the dosing strategy in children.[18]
• Subcutaneous allergen immunotherapy has shown that SCIT rarely causes any major clinical problems; there is a risk of less than 1.5% in patients who are HIV positive without AIDS, cancer (in remission), severe asthma, transplantation,  and during pregnancy, based on web-based survey.[19]
• Subcutaneous immunotherapy has the lowest risk of an allergic reaction ranking compared with 3 different methods of delivering immunotherapy; sublingual liquid (SLIT), sublingual tablets (AIT) and oral mucosal therapy (OMIT) using toothpaste. However, there are no significant differences between any of these delivery options. The most convenient factor for most patients is home immunotherapy administration.[20]