Type I hypersensitivity reactions Notes

NOTES NOTES TYPE I HYPERSENSITIVITY REACTIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Exaggerated immune reaction mediated by IgE antibodies (atopy) triggered by harmless antigen (allergens) Sensitization phase ▪ Allergen → antigen presenting cells (APCs) → B-cell, Th2 cells assist in IgE production → bind via Fc region to mast cells → mast cells sensitized Re-exposure/effector phase ▪ Cytotropic/IgE receptor binding; allergens bind to Fab region of IgE on sensitized cells → activates mediator release ▪ Early phase reactions (within minutes) ▫ Primarily mast cell-release of preformed mediators (e.g. histamine, proteases, chemotactants); causes vasodilation, capillary leak, increased secretions, bronchial smooth muscle contraction ▪ Late phase reactions (8–12 hours) ▫ Mediators require synthesis (e.g. interleukins 4, 5, 10; leukotrienes); increases early downstream effects, prolongs inflammatory response Common Type I hypersensitivity reactions ▪ Ingested allergens ▫ Foods, dander, bee stings, mold, drugs/ medications, pollen ▪ Other allergens ▫ Latex, lotions, soaps, penicillin ▪ Atopic eczema ▪ Allergic urticaria ▪ Allergic rhinitis (Hay fever) ▪ Allergic asthma ▪ Anaphylaxis ▪ Eosinophilic esophagitis CAUSES ▪ Causes of hyper/overactive re-exposure/ effector phase unclear; environmental exposure (esp. in early childhood), genetic factors ▪ “Atopic march”: multiple atopic (IgEmediated) diseases occur over lifetime SIGNS & SYMPTOMS ▪ Range from mild, local (e.g. urticaria, rhinorrhea, itching) to life-threatening anaphylactic reaction (e.g. cardiac arrhythmia, shock, bronchospasm, laryngeal obstruction) DIAGNOSIS LAB RESULTS ▪ Skin allergen testing, variable sensitivities ▪ Eosinophilia OTHER DIAGNOSTICS ▪ History of symptoms, frequency, triggers TREATMENT MEDICATIONS ▪ Symptom-based ▫ Antihistamines (e.g. H1 blockers), corticosteroids, epinephrine OTHER INTERVENTIONS ▪ Hypo/de-sensitization ▫ Escalating doses of allergen subcutaneously injected over course of years; variable effectiveness, more severe reactions less responsive OSMOSIS.ORG 219

ACUTE RHINITIS osms.it/acute-rhinitis PATHOLOGY & CAUSES ▪ IgE-mediated immune response upon re-exposure of airborne allergens to eyes, nose ▪ AKA hay fever ▪ Local mast cells of eye, nose mucosa degranulate, release immediate mediators (e.g. histamine) CAUSES ▪ Hay, pollen (seasonal due to flowering plants), dust, animal hair, mold spores SIGNS & SYMPTOMS ▪ Due to increased fluid in eyes, nasal cavity ▫ Conjunctival injection, eyelid edema; sneezing; rhinorrhea, nasal obstruction; edematous bluish-red nasal turbinates DIAGNOSIS LAB RESULTS ▪ Skin allergen tests ▫ Subdermal introduction of defined amount of allergen to volar surface of forearm; observe for “wheal-and-flare” reaction at specific site OTHER DIAGNOSTICS ▪ Clinical presentation ▫ History of symptoms, frequency, triggering events TREATMENT MEDICATIONS ▪ Oral antihistamine (e.g. H1 blockers) ▪ Nasal corticosteroids OTHER INTERVENTIONS ▪ Nasal irrigation ▪ Environmental control (to avoid antigen) ▪ When severe, hypo/desensitization to allergen 220 OSMOSIS.ORG

Chapter 36 Type I Hypersensitivity Reactions ANAPHYLAXIS osms.it/anaphylaxis PATHOLOGY & CAUSES ▪ Generalized, life-threatening allergic response ▪ Systemic release of large quantities of immune mediators; symptoms most severe at site of greatest mediator concentration Immune mediators ▪ Histamine (ubiquitous systemic concentration) ▫ Vasodilator, immune system modulator ▫ H1 receptor → tachycardia, pruritus, rhinorrhea, bronchospasm ▫ H2 receptor → flushing, hypotension ▪ Tryptase (high skin concentration) ▫ Activate complement, coagulation pathways, kallikrein–kinin systems ▫ Angioedema, hypotension, disseminated intravascular coagulation (DIC) ▪ Leukotriene C4, prostaglandin D2 (in high lung concentration) ▫ Bronchoconstriction, increased mucus secretion CAUSES ▪ Drugs (e.g. beta-lactam antibiotics, insulin) ▪ Foods (e.g. nuts, eggs, seafood) ▪ Proteins (e.g. blood transfusions, tetanus antitoxin) ▪ Latex SIGNS & SYMPTOMS ▪ Generalized, mild-moderate ▫ Flushing, feeling of doom, tachycardia, urticaria, incontinence ▪ Generalized, severe ▫ Syncope, shock, hypoxia, cardiorespiratory collapse DIAGNOSIS OTHER DIAGNOSTICS ▪ Clinical presentation ▫ Symptoms indicate allergic reaction TREATMENT MEDICATIONS ▪ Immediate, necessary ▫ Epinephrine intravenously (IV) (1:10,000)/intramuscularly (IM) (1:1,000), repeat every 30 minutes with potential epinephrine infusion after bolus(es) ▪ Adjunct therapy ▫ H1, H2 receptor blockers, IV corticosteroids ▪ IV fluids, O2 supplementation ▪ Critical care ▫ Intubation, vasopressors if necessary OSMOSIS.ORG 221

FOOD ALLERGY osms.it/food-allergy PATHOLOGY & CAUSES ▪ Adverse food reaction; immune response to ingested antigens ▪ Distinct from non-immunologic adverse food reactions ▫ Enzyme deficiency (e.g. lactase), toxin ingestions (e.g. staphylococcal toxin), intolerance (e.g. caffeine) TYPES IgE-mediated ▪ Rapid onset (minutes to couple hours after ingestion); immune mediator release from tissue mast cells, circulating basophils; common allergens include peanuts, soy, milk, wheat, fish Non-IgE mediated ▪ Symptoms subacute to chronic in nature; leukocytosis; local, lymphocytic destruction of gastrointestinal (GI) tissue; celiac disease, food protein-induced enterocolitis syndrome (FPIES) Mixed IgE/non-IgE-mediated ▪ Variable immune response, acute responses involving IgE-mediation, others favoring leukocytes (e.g. eosinophils, lymphocytes); atopic dermatitis, eosinophilic esophagitis, eosinophilic gastroenteritis 222 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Dermatologic (e.g. pruritus, erythema, urticaria), GI (e.g. nausea, vomiting, abdominal pain, diarrhea), anaphylactic (e.g.cardiac/respiratory reactions) ▪ Non-IgE-mediated food allergies ▫ Nonspecific, subacute/chronic GI symptoms; distinct dermatologic vesicular, papular eruptions; dermatitis herpetiformis in celiac disease DIAGNOSIS LAB RESULTS ▪ Skin allergen testing OTHER DIAGNOSTICS ▪ Food elimination trials TREATMENT MEDICATIONS ▪ Antihistamines ▫ May be of little value unless urticaria, angioedema present OTHER INTERVENTIONS ▪ Elimination of offending food from diet; mild disease may remit with time