Unit
- Type I hypersensitivity: Allergic reactions involve IgE antibodies binding to mast cells and basophils. Upon re-exposure to an allergen, cross-linking triggers degranulation, releasing histamine, leukotrienes, and prostaglandins, leading to immediate symptoms like sneezing, hives, or wheezing.
- Th2 cell polarization: In atopic individuals, naive T cells differentiate into Th2 cells, producing cytokines IL-4, IL-5, and IL-13. These cytokines promote IgE class switching, eosinophil recruitment, and mucus production, amplifying the allergic response.
- Mast cell activation: Mast cells reside in tissues near blood vessels and nerves. When activated, they release preformed mediators rapidly (histamine, tryptase) and synthesize lipid mediators (prostaglandins, leukotrienes) that cause vasodilation, bronchoconstriction, and increased vascular permeability.
- Eosinophil involvement: Eosinophils migrate to tissues under IL-5 influence and release cytotoxic granules that damage epithelium, contributing to chronic inflammation in conditions like atopic dermatitis and eosinophilic esophagitis.
- Late-phase reaction: The immediate response subsides within hours, but a late-phase reaction emerges 4-8 hours later. It is driven by recruited inflammatory cells (eosinophils, neutrophils) and leads to prolonged swelling, redness, and tissue damage.
- Genetic predisposition: Multiple genes, including those encoding HLA molecules, IL-4 receptor, and filaggrin, are associated with allergic disease. Filaggrin mutations impair skin barrier function, increasing percutaneous allergen exposure and sensitization risk.
- Barrier dysfunction hypothesis: An impaired epithelial barrier (skin, respiratory, gut) allows allergens to penetrate and interact with immune cells. This early exposure, particularly in the skin, can lead to sensitization and progression to allergic disease (atopic march).
- Oral tolerance mechanisms: The gut immune system normally induces tolerance to dietary antigens via regulatory T cells (Tregs). When oral tolerance fails, food allergens trigger IgE-mediated reactions. Factors like timing of introduction and microbiome composition influence tolerance development.
- Dendritic cell sampling: Dendritic cells in mucosal tissues capture allergens and migrate to lymph nodes, where they process and present antigen fragments to naive T cells. Depending on the cytokine milieu, dendritic cells promote Th2 polarization in atopic individuals, initiating the adaptive allergic response.
- Regulatory T cell imbalance: Regulatory T cells (Tregs) normally suppress Th2 responses and maintain immune tolerance. In allergic children, a relative deficiency or functional impairment of Tregs allows unchecked Th2 expansion, leading to higher IgE levels and more severe clinical symptoms.
- Anaphylaxis pathophysiology: Anaphylaxis results from widespread mast cell and basophil degranulation, releasing massive amounts of histamine and other mediators into the circulation. This causes systemic effects including laryngeal edema, bronchospasm, hypotension, and urticaria, requiring prompt intramuscular epinephrine administration.
- Allergen immunotherapy mechanism: Subcutaneous or sublingual immunotherapy gradually shifts the immune response from Th2 toward Th1 and Treg dominance. Over time, it induces allergen-specific IgG4 blocking antibodies and reduces IgE binding, leading to decreased mast cell activation and improved clinical tolerance to the allergen.
Scope of Practice
Role: Pediatric Allergy Specialist
Within scope:
- Ordering and interpreting allergen-specific IgE tests and skin prick tests
- Diagnosing allergic conditions based on history and test results
- Developing individualized management plans including medication and immunotherapy
- Educating families on allergen avoidance and emergency treatment
- Coordinating care with primary care providers and subspecialists
Outside scope:
- Performing procedures outside allergy specialty (e.g., surgery, general pediatrics)
- Prescribing medications for conditions unrelated to allergy (e.g., antibiotics for infection)
- Providing definitive treatment without appropriate diagnostic confirmation
- Managing acute anaphylaxis in the field without proper emergency equipment
- Offering cure claims or unsupported alternative treatments
Quick Revision
- Pediatric allergic reactions are type I hypersensitivity responses mediated by IgE and Th2 cells.
- Mast cell degranulation and eosinophil recruitment drive both immediate and late-phase symptoms.
- Genetic factors like filaggrin mutations and environmental influences shape an individual's atopic risk.
- Barrier integrity and oral tolerance are critical for preventing sensitization.