Abstract
Allergy skin prick testing—a wheal greater than 3 mm is considered positive. Eosinophils contain peroxidase, neurotoxin, cationic protein, Charcot Leyden crystal protein, and major basic protein which induces release of histamine from mast cells and damages epithelial cells.In vitro allergy testing is indicated if there is an inability to discontinue medications that would interfere with skin testing or prevent treatment of an anaphylactic response
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Pearls
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Allergy skin prick testing—a wheal greater than 3 mm is considered positive
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Eosinophils contain peroxidase, neurotoxin, cationic protein, Charcot Leyden crystal protein, and major basic protein which induces release of histamine from mast cells and damages epithelial cells
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In vitro allergy testing is indicated if there is an inability to discontinue medications that would interfere with skin testing or prevent treatment of an anaphylactic response
Epidemiology
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Increasing incidence over the past 20 years
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Increased allergen exposure
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More hygienic living conditions for general population
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~30 % of adults and ~40 % of children affected
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Seasonal allergies affect 20 % of population with perennial affecting 40 % of population
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Productivity lost approximately $639 million/year
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NHANES (National Health and Nutrition Examination Survey) study (2005): 53.9 % of study population tested positive to at least one antigen
Risk Factors
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Exposure to cigarette smoke
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Family history of atopy
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Higher socioeconomic status
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First born or only child
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Elevated total IgE
Pathophysiology
Immunology
Classification
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Innate
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Nonspecific response to foreign substances—not dependent on antigen recognition
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For example, epithelial barrier, cellular and humoral defenses, complement activation
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Adaptive
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Specific response to foreign body—requires prior exposure/sensitization
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Antigen recognition
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Naturally acquired—contact with agent
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Artificially acquired—vaccination
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For example, antibodies, cytokines, T cells
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Characteristics
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Recognition: self vs. non-self
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Surveillance
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Memory
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Specificity
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Diversity
Components
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Lymphocytes
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Derived from bone marrow progenitor cells
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T lymphocytes (cellular immunity)—all have CD2 and CD3 positivity
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Bone marrow derived → maturation in thymus
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Recognize fragments of foreign proteins via interaction with Major Histocompatibility Complex (MHC)
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Cell bound proteins responsible for presenting antigens to T cells for recognition and proliferation of clonal lines
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MHC 1: present on all nucleated cells
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MHC 2: on antigen presenting cells and B cells
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CD4 cells (T-helper cells) → primarily MHC2 interaction
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60 % of T lymphocytes—primarily located in periphery
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TH0 cells: naïve cells → activated by intracellular pathogens or allergens
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TH1 cells: mature subset which mediates defense against intracellular microbial infections
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Major products IL-2 and IFN-gamma
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TH2 cells: mature subset which down regulates TH1 and augments B-cell and Ig production
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Major products IL- 4, 5, 6, and 10
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CD8 cells (T-cytolytic cells) → primarily MHC1 interaction
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30 % of peripheral T lymphocytes
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Defense against virus infected cells → mediates cell lysis
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Response mediated by IL-2
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T regulatory cells (Treg)
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Modulate immune system, maintain tolerance to self-antigens, prevention of autoimmunity
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Exploited in the therapeutic process of allergy immunotherapy
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B lymphocytes (Humoral Immunity)
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Mature in bone marrow → migrate to lymph nodes and spleen
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T-dependent activation: B-cell processes antigen and express MHC 2 receptor allowing CD4 cell recognition → T-cell stimulates B cells via IL 2 and 4 secretion
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T-independent activation: B-cell surface receptors activated by large antigens
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Upon activation of B-cell via either pathway, cell produces plasma cells which secrete immunoglobulins
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Made of two light and two heavy chains each with variable and constant chains—allows for diversity
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Allows antigen recognition, interaction with complement, phagocytosis
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IgD: distinct function unknown, receptor on naïve B cells, minor activation of basophils and mast cells
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IgA: dimer found in secretions/mucosa, often mediates first-line immune defense for pathogens entering the body via the oral cavity
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IgM: pentamer antibody
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high avidity seen in early immune responses
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IgE: binds to allergens and triggers release of histamine and other mediators—hypersensitivity reactions
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IgG: major antibody in late immune responses
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Crosses placenta to provide neonatal immunity
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Complement fixation
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CD19 and CD21 positivity
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Natural Killer Cells
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Maturation in bone marrow
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Secrete cytokines
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Role in innate immunity → kill virus infected cells
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Activated by IL-2 → antibody-dependent cellular cytotoxicity
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CD 16 and CD 56 positivity
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Antigen Presenting Cells
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Located within skin, lymph nodes, and spleen
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Process antigens for presentation via MHC 1 and 2 to T cells
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For example, macrophages, Dendritic cells, B cells, Langerhans cells, monocytes
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Cytokines
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Proteins secreted that allow for immunomodulation, pro-inflammation, and anti-inflammatory effects → intercellular “communication”
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Modes of secretion:
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Autocrine: cellular activation produces cytokine which affects secreting cell
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Paracrine: cellular activation produces cytokine which affects nearby cells
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Endocrine: cellular activation produces distant cellular effects
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Role in inflammation
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IL-1: stimulate IL-2 secretion, phagocyte activation, pyrogen
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IL-2: stimulate T cells, B cells, and NK cells
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IL-6: acute phase response
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IL-12: proliferation of CD8, NK cells, IFN-gamma production, induce TH1 cells, suppress TH2
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IL-18: induces IFN-gamma, enhances NK cell activity
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Interferon (IFN): activates macrophages and NK cells, antiviral properties, increase MHC proteins, cytotoxic effects
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Type I: IFN-alpha, beta → potent antiviral effects
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Type II: IFN-gamma → potent immunomodulator, increases MHC expression
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TNF: acute phase response, pyrogen
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Role in allergy
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IL-4: induces B cells and mast cells to increase IgE production
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IL-5: activation and maturation of eosinophils
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IL-13: induces B cells and mast cells to increase IgE production, induction of adhesion molecules at allergic sites
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Complement
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Allows for the augmentation of immune function, mediates the interaction of antigen and antibody
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Activation via two distinct pathways:
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Classical pathway
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Primary pathway
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Activation via immune complexes, IgG and IgM of the C1 complex
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Alternative pathway
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Secondary pathway
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Activated by viruses, bacteria, parasites, IgA, IgG via C3
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Lectin pathway
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Similar to classical pathway but utilize mannose-binding lectin instead of C1
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Activation leads to opsonization “tagging,” cellular migration and activation, cellular death via lysis
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Cells important in the allergic response
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Neutrophils
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Cell margination and migration to site of inflammation
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Opsonized particles are recognized and undergo phagocytosis
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Eosinophils
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Receptors for cytokines, IgG and IgE which allow localization to inflamed endothelium
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Contains peroxidase, neurotoxin, cationic protein, Charcot Leyden crystal protein, and major basic protein
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Major basic protein → induces release of histamine from mast cells and damages epithelial cells
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Monocytes
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Immature-macrophages
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Produces IL-1 allowing vascular permeability and production of acute phase proteins
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Basophils
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Circulating granulocytes rich in histamine and heparin
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High-affinity IgE receptors → release histamine and cytokines IL-4, IL-13
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Express IL-4
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Mast cells
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Granulocyte rich in histamine and heparin
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Contained within connective tissue and mucosa—e.g., skin, mucosal lining of mouth and nose
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When activated → histamine and cytokines TNF-alpha, IL-3, -4, -6, -8, -10, -11
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Classification of Hypersensitivity Reactions: Gell and Coombs
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Type I
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Mediator: IgE hypersensitivity
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Time: Immediate
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Agents: environmental, food, medications
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Mechanism: secondary to degranulating mast cells → histamine
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Manifestations: systemic and localized anaphylaxis, sneezing, urticaria, congestion, wheals
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Type II
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Mediator: IgG cytotoxicity hypersensitivity
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Mechanism: antibody-directed against cell surface antigens → cell destruction via complement activation
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Manifestations: Hemolytic anemia, transfusion reactions, Goodpasture syndrome, Myasthenia gravis
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Type III
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Mediator: Immune complex mediated hypersensitivity (IgG)
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Agents: Bacterial antigen, medications
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Mechanism: Antigen–Antibody complex deposited on the surfaces of small vasculature, joints, and glomeruli with complement activation → massive infiltration of neutrophils
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Manifestations: Serum sickness, post-streptococcal glomerulonephritis, angioedema, GI manifestations
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Type IV
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Mediator: Cell-mediated hypersensitivity
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Time: Delayed—up to several days
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Agents: poison ivy, nickel reactions, chemicals
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Mechanism: Sensitized TH1 cells release cytokines → activate macrophages or CD8 cells → direct cellular damage and inflammation
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Manifestations: dermatitis, granulomatous disease, fungal disease
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Cellular Response of Allergic Reactions
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First exposure
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APC encounter allergen
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Uptake and process → synthesize MHC2
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Transform TH0 cells to TH2 via release of IL4
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TH2 release IL4 → stimulate antigen-specific IgE production via B cells
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Early response: within minutes of exposure to several hours
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Reexposure
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Memory B cells maintains antibody response
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Reexposure allows rapid proliferation to plasma cells → secrete high-affinity IgE
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IgE binds and sensitizes mast cell → cross linking occurs with antigen → destabilization of mast cells → degranulate and release:
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Histamine
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Main mediator of allergic reactions
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Vessel permeability, vasodilation, mucus secretion, tissue edema, broncho- constriction
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Receptors H1 and H2
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Heparin
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Anticoagulant
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Enhances migration and phagocytosis
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Leukotrienes
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Derived from the lipoxygenase pathway
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Vasodilation, mucus secretion, bronchial smooth muscle contraction, edema, increased vascular permeability
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Act upon leukotriene receptors
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Cytokines: allow cellular recruitment
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PDG2: metabolite of arachidonic acid involved in innate and adaptive immune responses
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PAF: mediator causing inflammation, platelet aggregation, and allergic response
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Late response: within several hours after exposure
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Cytokine release (primarily IL4) causes accumulation of
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TH2 cells
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Orchestrate and maintain inflammatory response → IL-3, -4, -5, -13
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Eosinophils
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Production of oxygen-free radicals → damage epithelium and promotes inflammation
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Release major basic protein
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Basophils
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B cells
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Neutrophils
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Neurogenic Response to Allergen
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Neurotransmitters play a pivotal role in pathogenesis
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Altering secretions
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Smooth muscle tone
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Vasodilation
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Cellular recruitment
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“Neurogenic inflammation”
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Activation of peripheral terminals of sensory neurons → release neurotransmitters to act on mast cells and vascular smooth muscle
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Redness and warmth due to vasodilation
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Swelling due to plasma extravasation
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Hypersensitivity due to alterations in excitability
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Allergic Rhinitis
Diagnosis
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History
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Primary symptoms, duration, frequency, alleviating/exacerbating factors, associated symptoms or conditions, recent changes in job, environment, diet
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Past medical history: History of asthma, anaphylaxis, eczema, allergen exposure, formula intolerance
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Past Surgical History: e.g., T + A, BMT, FESS
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Family history: allergic rhinitis, asthma, eczema, angioedema, food intolerance, anaphylaxis
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Chance of having atopy with:
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0 Allergic parents: 10–15 %
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1 Allergic parent: 30 %
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2 Allergic parents: 50 %
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Social history: Living accommodations, tobacco exposure, occupation
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Medication use
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Physical
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Eyes: lid edema and erythema, injection of conjunctiva and sclera, chemosis, itching, watery, photophobia, “allergic shiners,” “Dennies lines”
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Nose: supratip crease, facial grimacing, itching, nasal obstruction, inferior turbinate hypertrophy, rhinorrhea, increased mucus, sneezing
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Ears: Tympanic membrane retraction, eustachian tube dysfunction, middle ear effusion
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Oropharynx: “cobblestoning” of posterior pharyngeal wall, hypertrophy of lateral pharyngeal bands, mouth breathing, angioedema
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Laryngeal: excess secretions, vocal fold edema, laryngeal drying, erythematous arytenoids, viscous mucus
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Possible related systemic findings:
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Skin: eczema, contact dermatitis, urticaria,
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Lungs: wheezing, dyspnea, cough
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Diagnostic Testing
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In Vivo testing
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Although testing is generally safe, necessary medications and airway equipment to treat systemic anaphylaxis must be available
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Skin Testing
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Epicutaneously
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Prick test
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More specific testing than intradermal (fewer false-positive results)
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False-negative rate is 5 %
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Various antigens introduced in controlled manner—to determine reactivity and severity
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Few drops of selected antigen are placed on skin surface after small prick with needle
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Reaction >3 mm in diameter is considered positive
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Intradermal
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Typically recommended to be performed after negative prick test, but specific sensitivity is suspected.
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Not appropriate for food allergens due to high risk of false positives and risk of anaphylaxis
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Small amount of allergen injected subcutaneously
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More reproducible and sensitive testing than prick testing (fewer false negatives)
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Skin end point titration
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Intradermal injections of allergen at increasing concentrations starting with an anticipated non-reacting dose
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Wheal which initiates positive reaction is safe starting point for immunotherapy
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Technique
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Start with diluent injection (inert) typically forms 5 mm wheal measured at 10 min
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Injection of antigen at lowest reactive concentration (increasing concentration 1:5) until wheal enlarges by 2 mm → “endpoint”
“Endpoint”: concentration that produces positive wheal that continues to increase in size
Considered safe point for starting skin testing
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Injection of next stronger concentration that results in further 2 mm in growth → confirmatory concentration
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13 mm growth → major reaction, testing stopped
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Factors which affect wheal response:
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Recent exposure
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Prior immunotherapy
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Area of body tested—i.e., upper back → lower arm
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Age of patient—pediatric and geriatric tend to have less response
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Medications: steroids, leukotriene inhibitors, bronchodilators, NSAIDs
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In Vitro testing
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Serum test
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Detects specific IgE to allergens
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Suspected allergen bound to insoluble material → patient serum added
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If IgE present in serum → binding to allergen occurs
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Marker labeled anti-IgE added → washed
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Detection of marker
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Radiation: RAST (Radioallergosorbent test)
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Fluorescent: ELISA
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Indications:
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Inability to discontinue medications that would interfere with skin testing or prevent treatment of an anaphylactic response—i.e., antihistamines, H2 blockers, tricyclic anti depressants, long-term topical steroids, β-blockers
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Severe eczema or psoriasis precluding skin testing
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Extraordinarily high sensitivity to suspected allergens that may lead to potentially serious side effects (i.e., anaphylaxis)
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Poorly controlled reactive airway disease
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Scoring:
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0–6 Based on level of IgE in specimen
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More specific in determining allergen sensitivity, less sensitive than skin tests
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Management of Allergy Symptoms
Nonpharmacologic
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Avoidance
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Goals include:
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Remove sources of allergens
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Remove accumulated allergens
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Prevent allergens from returning
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Outdoor
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Pollen
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Types
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Trees—February through May
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Grass—June through August
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Weeds—August until frost
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Counts highest in morning, hot, dry windy days
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Strategies of avoidance:
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Shift outdoor activities to evening
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Keep doors and windows closed, utilize AC
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Mold (can be found both outdoor and indoor)
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Present year round
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Indoor
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Dust mites
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Keep surfaces clear
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Remove carpeting
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HEPA filters
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Wash sheets and pillow case weekly in hot water >130°
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Pet Dander
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Avoidance of pet, especially keeping pet out of bed and bedroom
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Eliminate carpeting
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Pharmacologic Therapy
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Symptomatic Relief
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Decongestants
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Reduce blood flow → agonistic action on alpha 1 and 2 adrenergic receptors
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Endothelial cells within nasal vessels
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Contraction of sphincters of the venous plexus within turbinate
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Oral agents
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Less chance for rebound congestion
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Systemic effects: irritability, insomnia, headache, tachycardia, hypertension, increased intraocular pressure, urinary retention
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Caution use in patients: hypertension, coronary disease, hyperthyroidism, glaucoma, urinary retention
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For example, pseudoephedrine and phenylephrine
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Topical nasal agents
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Rapid onset <5 min with duration of 6 h
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High local potency with fewer systemic effects
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Over use >3–5 days leads to lost effectiveness and rebound congestion. Long-term use can lead to rhinitis medicamentosa
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For example, oxymetazoline, neosynephrine, phenylephrine
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Maintenance
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Antihistamines
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Competitively bind to H1 receptors → reduced vascular permeability, smooth muscle contraction, mucus secretion, vasodilation, pruritis
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Oral
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First Generation—available over the counter, cheap
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Limited due to potential for sedative effects → high lipophilicity → crosses blood brain barrier
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Anticholinergic effects → dry mucus membranes, urinary retention, constipation, tachycardia, blurred vision: limit use in elderly
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For example, diphenhydramine, chlorpheniramine, hydroxyzine
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Second Generation
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Lower CNS penetration and thus less sedating
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Less anticholinergic effects
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Lower interaction with cytochrome P 450
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Better specificity for H1 receptor blockade
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For example, loratidine, cetirizine, fexofenadine
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Topical nasal spray
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Advantage of delivering high local concentration
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Allows higher anti-inflammatory effects, reduction of systemic exposure, reducing potential for systemic side effects
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Typically recommended for patients with seasonal allergic rhinitis
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For example, azelastaline
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-
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Anti-leukotriene
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Limited role given the lack of efficacy noted
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Combined use with antihistamines typically with additive effect
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Synthesis blockade
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Blockade of 5-lipoxygenase → prevention of LTA4 synthesis formation
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For example, Zileuton
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Receptor blockade
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Reduces number of peripheral blood eosinophils
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For example, Montelukast, zafirlukast
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Corticosteroids
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Available as oral, injection or topical intranasal delivery
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Multiple anti-inflammatory effects
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Decreased capillary permeability
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Promotes IL-10 production and IL-1 receptor antagonism
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Decreased arachidonic metabolism → decreased prostaglandins, leukotrienes, thromboxane
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Allows inhibition of cytokines and chemokines
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Decreased recruitment and migration of eosinophils
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Decreased activity of basophils and mast cells
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Decreased migration of APC, T cells, B cells
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Topical Intranasal delivery
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Recommended for persistent nasal congestion
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Systemic absorption and side effects are a theoretical concern but not well supported by the literature
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(i.e., Inhibition of growth in children, metabolic disturbances, glaucoma, cataract formation, immunosuppression, skin thinning)
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Effectiveness
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Effective for all symptoms of SAR and PAR
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Appropriate for mixed rhinitis
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Clinical response equivocal for all available steroids
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Topical side effects: Local burning, stinging, irritation, dryness
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For example, beclomethasone, budesonide, flunisolide, triamcinolone, fluticasone, mometasone
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Mast cell stabilizers
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Inhibit Ca2+-dependent mast cell degranulation
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Inhibit migration and survival of macrophages, eosinophils, monocytes
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When used prophylactically can prevent and treat symptoms, although commonly need to be used as adjunct and not first-line therapy
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Side effects: nasal burning, stinging, sneezing
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For example, Cromolyns, olpatadine (dual antihistamine/mast cell stabilizer)
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Anticholinergic agents
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Muscarinic receptor blockade → inhibits rhinorrhea, congestion, and sneezing
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Side effects: dry mouth, dizziness, blurred vision, conjunctivitis, hoarseness
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Typically suggested for treatment of rhinorrhea
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Caution in use with elderly with glaucoma and urinary retention
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For example, ipratropium
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Immunomodulation
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Allergen-specific immunotherapy
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Treats IgE-mediated allergy → regular and progressive doses of appropriate allergen → downregulation of immune response and control of symptoms
-
Benefits include:
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Improvement in quality of life
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Reduction of symptoms
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Decrease reliance on medications
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Long-term benefit after stopping treatment if they complete 3–5 years of therapy
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Decrease risk of developing asthma
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Prevent new sensitizations
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Indications for therapy
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Demonstration of IgE-mediated disease correlates with symptoms
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Insufficient response to avoidance and pharmacotherapy
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Significant side effects with medical therapy
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Unable to comply with medical therapy and avoidance of allergens
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Moderate to severe symptoms which last for majority of year or spanning across 2 or more seasons
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Effective to following antigens:
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Grass
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Tree
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Pollen
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Animal dander
-
Insect venom
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House dust mites
-
Mold
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-
Relative contraindications
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Concomitant therapy with beta-blocker
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Contraindication to administration of epinephrine
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Non-compliance of patient
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Autoimmune disease
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Pregnancy
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Uncontrolled asthma
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HIV or other immunodeficiency
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Mechanism of action
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With initial treatments → 2–3 months of increased antigen-specific IgE followed by gradual decline over 2 years
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Decline does not correlate to clinical improvement
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With decline in IgE → rise in IgG1 and IgG4
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Increase in IgG4 correlates with symptom relief
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Increase in antigen-specific suppressor T cells
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Shift TH2 cells to TH1 via increased IFN-gamma and IL12
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Decline in levels of pro-allergenic cytokines
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Reduced basophil, mast cell and lymphocyte reactivity
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Blunting of post-seasonal rise in specific IgE antibody
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Gradual decrease in symptoms with repeated exposure to same allergen level
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Schedule of treatment
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Total treatment period is 3–5 years
-
Escalation phase → first year
-
Rapid escalation versus standard schedules
-
Allows for the attainment of maintenance doses in as low as 6 days through the use of increased frequency dosing (q 3–4 h) versus 3–6 months with standard schedules
-
The most rapid of escalation schedules typically necessitate hospitalization during the escalation period
-
-
-
Maintenance phase → up to 5 years
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Every 1 week for first year, every 2 weeks for second year, every 3 weeks for third year
-
-
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Modes of Delivery
-
Subcutaneous Immunotherapy (SCIT)
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Sublingual Immunotherapy (SLIT)
-
-
Comparing SCIT and SLIT
-
Safety:
-
Fatal reactions from SCIT occur at rate of 1 in 2–2.5 million → 3.4 deaths/year
-
Between 2006 and 2009, six possible reported anaphylaxis in SLIT patients, none resulting in fatalities
-
-
Efficacy:
-
A 2007 Cochrane meta-analysis showed that immunotherapy reduced medication use, decreased clinical symptoms, and improved quality of life.
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Efficacy has been shown to last as long as 3 years post immunotherapy cessation.
-
SLIT still has minor edge over SCIT in total efficacy, although many studies showing nearing equivalence
-
-
Dosing
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Optimum SCIT maintenance dose is 5–20 μg of major allergen
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Optimum SLIT maintenance dose not elucidated, but median monthly dosing is 49× that of SCIT
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Cost
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As of 2013, SLIT is not currently covered by insurance companies and considered an out of pocket expense.
-
Cost of SCIT varies dramatically according to insurance plans, while SLIT varies between practices
-
When loss of productivity and travel expense is added into the cost of SCIT, SLIT may be comparable in cost and more convenient for the patient.
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Complications
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Typically secondary to
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Presence, severity, control status of asthma
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Dosing—inadvertent mistakes in antigen selection or concentration calculation
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Accelerated dosing schedules
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Treatment during peak pollen season
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Extensive sensitivity to allergen
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Local
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SCIT: induration, wheal
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SLIT: oral itching, irritation
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Systemic
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SCIT: coughing, wheezing, shortness of breath, urticarial, anaphylaxis
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SLIT: Gastointestinal, i.e., abdominal pain, nausea, vomiting; can also have anaphylaxis
-
-
-
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Monoclonal Antibody
-
Recombinant humanized monoclonal anti-IgE antibody → forms complexes with free IgE → blocks interaction with receptors on mast cells and basophils
-
Profound reductions
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Nasal eosinophils
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IgE receptors on dendritic cells
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T and B cells
-
-
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Onset of action: typically 7–14 days
-
Clinical benefit shown in seasonal AR and perennial AR
-
Typically recommended for patient with refractory AR
-
Well tolerated with low rate of anaphylaxis
-
Disadvantage: Costly
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Severe Manifestations of Allergic Response
Anaphylaxis
-
Definition
-
Immediate, severe, whole body, life-threatening, immunologic reaction characterized by the contraction of smooth muscle and dilatation of capillaries
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Epidemiology
-
Approximately 1,000 deaths/year in the United States
-
One of every 3,000 patients suffers an anaphylactic reaction in the US hospitals every year
-
Risk of death is twofold:
-
Airway edema—asphyxiation
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Hypotension—shock/organ failure
-
-
Causes: Food (e.g., peanuts) → idiopathic → insect stings (e.g., bees) → medications (e.g., Beta-Lactam antibiotics)
-
-
Treatment
-
Epinephrine: alpha- and beta-agonist
-
Adult dose: 0.3–0.5 cm3 (1:1,000) IM or SC
-
Pediatric dose: 0.01 mg/kg (1:1,000) IM or SC
-
May repeat dose in 10–15 min
-
10 % dose reduction with concomitant Monoamide oxidase inhibitors (MAOI) and Tricyclic Antidepressants (TCA)
-
-
Antihistamine: H1 and H2 antagonists
-
Effect on symptoms, i.e., hives, but no effect on hypotension, shock or airway obstruction
-
H1 blocker: Diphenhydramine 1 mg/kg IV or IM
-
H2 blocker: Ranitidine or Cimetidine via IV push
-
-
Steroids:
-
Typically used in asthmatic patients
-
Beneficial for late phase reactions
-
Prednisone 40 mg PO
-
Dexamethasone 20 mg IV
-
-
Bronchodilators:
-
Beta-agonist: Albuterol to break bronchospasm or overcome beta-blockade
-
Anticholinergic: Ipratropium
-
-
Dopamine: useful for maintenance of blood pressure
-
Initial dose 1 mcg/kg/min IV and titrate to 20 mcg/kg/min
-
Doses below 10 mcg typically act as beta-agonist
-
-
Angioedema
-
Hereditary angioedema
-
Classification
-
Type I: 80 %—secondary to decreased production of C1-esterase inhibitor (C1-INH)
-
Type II: 20 %—normal or elevated functionally impaired C1-INH
-
-
Importance of C1-INH
-
Complement cascade: C1-INH prevents activation of C1
-
Preventing activation of C4, C3, C5
-
Decrease capillary permeability, fluid extravasation, edema
-
-
Kallikrein/kinin system:
-
C1-INH inactivates: Factor XII, plasmin, kallikrein
-
Prevents kininogen to be converted to bradykinin
-
Decrease vasodilation, nonvascular smooth muscle contraction, edema
-
-
-
Symptoms: edema of one of following organs
-
Skin
-
GI tract
-
Respiratory tract
-
-
Clinical Presentation
-
Symptoms associated with trauma, medical procedures, emotional stress, menstruation, infections, medication use (i.e., ACE-inhibitors)
-
Typically symptoms last 2–5 days with spontaneous resolution
-
Non-pitting skin edema
-
Facial area involvement (lips, eyelids, tongue)
-
Laryngeal involvement must be ruled out
-
-
Testing:
-
C1-INH levels
-
C1q levels
-
C2 and C4 levels—typically markedly decreased/undetectable
-
Genetic screening: autosomal dominant trait
-
-
Management
-
Genetic counseling
-
Intravenous C1 esterase inhibitor concentrate
-
Attenuated androgens, i.e., danazol, stanozolol
-
Trial of antihistamines, glucocorticoids, epinephrine
-
Although some reports suggest no response
-
-
Intubation if airway involved
-
Cessation of any offending agents, i.e., ACE-Inhibitors
-
-
-
Acquired Angioedema
-
Secondary to increased destruction or metabolism of C1-INH
-
Typically noted in patients with rheumatologic disorders, B-cell lymphoproliferative disease, IgG autoantibodies against C1-INH
-
-
ACE-Inhibitor therapy Induced
-
Associated with 0.1–0.5 % of patients
-
No sex predominance
-
Onset may occur during first week to as far as several years post initiation
-
Symptom resolution with 24–48 h
-
Typically with normal C1-INH levels and function
-
Treatment: discontinue ACE-I, start antihistamines, anticholinergics, corticosteroids
-
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Del Signore, A.G., Patel, Z.M. (2014). Allergy and Immunology. In: Lin, F., Patel, Z. (eds) ENT Board Prep. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8354-0_7
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