IMMUNOLOGY

Skin Test Wheal and Flare Mechanism: 

• Introduction of antigen into the skin causes local mast cell activation via cross-linking of preformed, antigen-specific, membrane-bound IgE.

• The release of preformed histamine from mast cells causes increased vascular permeability via smooth muscle contraction and development of wheal; inflammatory mediators initiate neural reflex vasodilation, leading to development of flare.

CLINICAL PEARLS 

• Skin testing is a practical, reliable, and well-tolerated method of establishing IgE-mediated disease. • Interpretation of skin testing should be done by an experienced practitioner, in the presence of positive and negative controls, and may be confounded by dermatographism or antihistamine use.

• The presence of a positive skin test documents the presence of allergen-specific IgE antibody. Diagnosis of allergy can be made only by correlating skin testing results with the presence of clinical symptoms.

Allergen immunotherapy: Definition, indication, and reactions

Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity. Specific IgE antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures, (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma or reduce the risk of anaphylaxis from a future insect sting, (3) when the patient experiences undesirable side effects from pharmacotherapy, and (4) when avoidance is not possible. Furthermore, patients may seek to benefit from economic savings of allergen immunotherapy compared with pharmacotherapy over time. Several studies have reported that immunotherapy in children with allergic rhinitis appears to prevent the development of new allergic sensitizations and/or new-onset asthma. Humoral, cellular, and tissue level changes occur with allergen immunotherapy including large increases in antiallergen IgG4 antibodies, a decrease in the postseasonal rise of antiallergen IgE antibodies, reduced numbers of nasal mucosal mast cells and eosinophils, induction of Treg cells, and suppression of Th2 more than Th1 lymphocytes. There is a corresponding increase in IL-10 and transforming growth factor beta. In the United States, allergen immunotherapy is administered by the subcutaneous route in the physician’s office, whereas primarily in some countries in Europe, it is administered for allergic rhinitis and asthma by the sublingual route by the patient at home.

Specific allergen immunotherapy, often called “allergy shots,” has been defined as the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. The purpose of allergen immunotherapy is to provide protection against the allergic symptoms and inflammatory reactions associated with natural exposure to these allergens. Although the single best marker that explains immunotherapy’s efficacy is unknown, there are many immunologic changes that occur with immunotherapy

INDICATION AND DURATION

 Immunotherapy is indicated for patients who have clinically significant IgE-mediated allergic rhinitis,asthma,4 and hymenoptera sensitivity.5 Specific IgE for appropriate allergens must be documented and symptoms should correlate with exposure to those specific allergens selected for immunotherapy.6–8 Other indications for allergen immunotherapy include inadequate symptom control despite pharmacotherapy and avoidance measures, undesirable side effects from pharmacotherapy, and when avoidance is not possible.In addition, immunotherapy may prevent the development of new sensitizations and/or new-onset asthma. The relative contraindications to allergen immunotherapy include severe or uncontrolled asthma, significant cardiovascular disease, and
-blocker use.Immunotherapy is not currently approved for food allergy or chronic urticaria and/or angioedema. However, the most recent immunotherapy practice parameter suggests an expanded indication, atopic dermatitis in subjects with aeroallergen sensitization. Multiple controlled studies have shown that immunotherapy is effective treatment for allergic rhinitis due grass, ragweed, and birch pollen.Immunotherapy with house-dust mite vaccines is an effective treatment for both allergic asthma and allergic rhinitis. Studies favoring allergen immunotherapy in patients with asthma have been published for grasses, trees (birch),ragweed, cat, and fungi (Alternaria and Cladosporium).Patients with mild asthma are more likely to benefit from immunotherapy than patients with moderate or severe asthma who may be at increased risk for adverse reactions to immunotherapy. To appropriately choose allergens for cutaneous testing and immunotherapy, it is important to be familiar with the significant aeroallergens in a patient’s geographic location

Immunologic changes with immunotherapy

Antibody changes 

Increase in allergen-specific IgG (specifically IgG4) 

Early increase and late decrease in serum-specific IgE 

Decrease in seasonal rise of specific IgE 

Cellular changes 

Decreased mediator release from mast cells, 

basophils, and eosinophils 

Reduction of tissue mast cells and eosinophils 

Induction of regulatory T cells and suppression of Th2 Th1 cells 

Increased secretion of IL-10 and TGF-
 

Decrease in histamine-releasing factors