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Vinod Doreswamy, M.D. Allergy, Asthma and Clinical Immunology Northgate Office 11011 Meridian Ave. N Suite 200 Seattle, WA 98133 Ph: 206-860-4454 Fax: 206-860-4756 Madison Office 904 7th Ave 5th Floor Seattle, WA 98104 Ph: 206-860-4454 Fax: 206-860-4756 Ballard Office 1801 Market St Suite 308 Seattle, WA 98107 Ph. 206-860-4454 Fax: 206-860-4756 ANAPHYLAXIS FOR THE PRIMARY CARE PRACTITIONER September 6th 2015 CME, Raleigh NC Disclosures None Anaphylaxis - Summary • • • • • • • What is Anaphylaxis? Types, Epidemiology Mechanisms Causes Risk Factors Diagnosis Treatment Louis Pasteur, “In the fields of observation, chance favors the prepared mind.” Anaphylaxis - Discovery Anaphylaxis - Criteria Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled: 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, and swollen lipstongue-uvula) AND at least 1 of the following: A. Respiratory compromise (eg, dyspnea, wheezebronchospasm, stridor, reduced PEF, hypoxemia) B. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence) Anaphylaxis - Criteria 2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours): A. Involvement of the skin–mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) B. Respiratory compromise (eg, dyspnea, wheezebronchospasm, stridor, reduced PEF, hypoxemia) C. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) D. Persistent gastrointestinal symptoms (eg, cramping abdominal pain, vomiting) Anaphylaxis - Criteria 3. Reduced BP after exposure to a known allergen for that patient (minutes to several hours): A. Infants and children: low systolic BP (age-specific) or greater than 30% decrease in systolic BP* B. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline Anaphylaxis - Burden • • • • 0.05-2.0% lifetime prevalence 1% of ED visits for Acute Allergic reactions given Dx 40% of ED visits for food anaphylaxis given Dx 30,000 anaphylaxis, 150 deaths 2/2 Food/year Anaphylaxis - Epidemiology • • • • • • • • • • • Age Sex Atopy Route of administration Gaps in administration Time since reaction Asthma Socioeconomic Status Geography Diurnal Race Anaphylaxis – Signs/Symptoms Signs and symptoms Cutaneous Percentage of cases >90 Urticaria/angioedema 85–90 Flush 45–55 Pruritus without rash 2–5 Respiratory 40–60 Dyspnea, wheeze 45–50 Upper airway angioedema 50–60 Rhinitis 15–20 Dizziness, syncope, hypotension 30–35 Nausea, vomiting, diarrhea, pain 25–30 Headache 5–8 Substernal pain 4–6 Seizure 1–2 Anaphylaxis – Cardiovascular changes At onset of reaction Blood pressure Pulse Cardiac output Peripheral vascular resistance Intravascular volume Early stage (minutes) with no treatment Prolonged shock Anaphylaxis - Types IgG - II Anaphylaxis - Causes Immunologic mechanisms (IgE dependent) Foods - peanut, tree nut, shellfish, fish, milk, egg, sesame, food additives Food dependent Exercise induced Medications - b-lactam antibiotics and NSAIDs, biological agents Venoms - stinging insects (Hymenoptera) Natural rubber latex Occupational allergens Seminal fluid (prostate-specific antigen) Inhalants - horse, hamster, other animal dander, grass pollen (rare) Radiocontrast media Allergy shots Anaphylaxis - Causes Immunologic mechanisms (IgE independent, formerly classified as anaphylactoid reactions) Dextran, such as high-molecular-weight iron dextran Cytotoxic IgG Anti-IgA AA Metabolism disturbance – NSAIDs Kallekrein-Kinin Contact system activation – Dialysis membranes, RCM Multimediator recruitment – Complement, Clotting, lysis, Kallekreincontact Anaphylaxis - Causes Non-immunologic mechanisms Physical factors, such as exercise, cold, heat, and sunlight/UV radiation Ethanol Medications - Opioids Idiopathic anaphylaxis Hidden or previously unrecognized allergens Mastocytosis/clonal mast cell disorder FcεRI Figure 19-2 Polypeptide chain structure of the high-affinity IgE Fc receptor (FcεRI). IgE binds to the Ig-like domains of the α chain. The β chain and the γ chains mediate signal transduction. The boxes in the cytoplasmic region of the β and γ chains are ITAMs, similar to those found in the T cell receptor complex (see Fig. 6-5). A model structure of FcεRI is shown in Chapter 14, Box 14-1. © 2005 Elsevier Mast Cell Activation Mast cell activation Figure 19-3 Mast cell activation. Antigen binding to IgE cross-links FcεRI molecules on mast cells, which induces the release of mediators that cause the hypersensitivity reaction (A, B). Other stimuli, including the complement fragment C5a, can also activate mast cells. A light photomicrograph of a resting mast cell with abundant purple-staining cytoplasmic granules is shown in C. These granules are also seen in the electron micrograph of a resting mast cell shown in E. In contrast, the depleted granules of an activated mast cell are shown in the light photomicrograph (D) and electron micrograph (F). (Courtesy of Dr. Daniel Friend, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.) Downloaded from: StudentConsult (on 11 May 2010 09:13 PM) © 2005 Elsevier ANAPHYLAXIS - MEDIATORS Table 19-3. Mediators Produced by Mast Cells, Basophils, and Eosinophils Mediator Mediator category Mast cells and basophils Histamine Stored preformed in cytoplasmic granules Enzymes: neutral proteases (tryptase and/or chymase), acid hydrolases, cathepsin G, carboxypeptidase Prostaglandin D2 Major lipid mediators produced on activation Leukotrienes C4, D4, E4 Platelet-activating factor Cytokines produced on IL-3 activation TNF, MIP-1α IL-4, IL-13 IL-5 Function/pathologic effects Increases vascular permeability; stimulates smooth muscle cell contraction Degrade microbial structures; tissue damage/remodeling Vasodilation, bronchoconstriction, neutrophil chemotaxis Prolonged bronchoconstriction, mucus secretion, increased vascular permeability Chemotaxis and activation of leukocytes, bronchoconstriction, increased vascular permeability Mast cell proliferation Inflammation/late phase reaction IgE production, mucus secretion Eosinophil production and activation Effects of Mediators © 2005 Elsevier GENETIC SUSCEPTIBILITY Table 19-4. Examples of Chromosomal Locations and Genes Associated with Atopy and Asthma Chromosomal location Candidate genes Putative role of gene products in disease 5q Cytokine gene IL-4 and IL-13 promote IgE switching, IL-5 promotes cluster (IL-4, IL-5, IL- eosinophil growth and activation; CD14 is a component of 13), CD14, β2the LPS receptor which, via interaction with TLR4, may adrenergic receptor influence the balance between TH1 vs. TH2 responses to antigens; β2-adrenergic receptor regulates bronchial smooth muscle contraction 6p Class II MHC Some alleles may regulate T cell responses to allergens 11q FcεRI β chain Mediates mast cell activation 12q Stem cell factor, Stem cell factor regulates mast cell growth and interferon-γ, STAT6 differentiation; interferon-γ opposes actions of IL-4; STAT6 mediates IL-4 signal transduction 16 IL-4 receptor α chain Subunit of both IL-4 and IL-13 receptors 20p Metalloproteinase involved in airway remodeling ADAM33 2q Peptidase that may regulate chemokine and cytokine DPP10 activity 13q Transcriptional regulator involved in B cell clonal PHF11 expansion and Ig expression Risk factors for severe anaphylaxis and fatality Age •Infants •Adolescents/young adults •Pregnancy •Elderly Comorbidities •Asthma/respiratory diseases •CVDs •Mastocytosis/clonal mast cell disorders •Allergic rhinitis/eczema •Depression/psychiatric diseases •Thyroid disease Medication/chemical use •Sedatives/hypnotics/antidepressants/ ethanol/recreational drugs •B-Blockers and ACE inhibitors Anaphylaxis – Differential Diagnosis Flush Syndromes Carcinoid Medullary Ca Thyroid Perimenopause Autonomic Epilepsy Excess endogenous Histamine Mastocytosis Basophilic Leukemia Acute PML Restaurant Syndromes Scrombroidosis MSG Sulfite Miscellaneous Hereditary Angioedema Progesterone Anaphylaxis Panic attacks VCD Redman Syndrome Urticarial Vasculitis Munchausen Syndrome Shock Anaphylaxis - Diagnosis • • • • • History Histamine, Tryptase, Other mediators IgE tests – Skin, Blood Allergen challenge – food, drug Work up for DDx Schwartz DA, Immunol Allergy Clin N Am 26 (2006) 451–463 Management of Anaphylaxis 1. Immediate intervention: a. Assessment of airway, breathing, circulation, and adequacy of mentation b. Administer IM epinephrine every 5 to 15 minutes, as necessary, to control anaphylaxis signs and symptoms and prevent progression to more severe symptoms (eg, respiratory distress, hypotension, and unconsciousness) c. Place patient in recumbent position and elevate lower extremities, as tolerated The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:480, e32. Management of Anaphylaxis 2. Subsequent measures depending on response to IM epinephrine: a. Consider call for assistance and transportation to an emergency department or an intensive care facility b. Establish and maintain airway c. Administer oxygen d. Establish venous access e. Use IV (IO) crystalloid (eg, 0.9% saline or Ringer’s lactate) for fluid replacement Management of Anaphylaxis 3. Specific measures to consider after epinephrine injections, where appropriate: a. Consider dilute epinephrine infusion b. Consider H1 and H2 antihistamines c. Consider nebulized beta2-agonist (eg, albuterol) for bronchospasm resistant to epinephrine d. Consider systemic glucocorticoids e. Consider vasopressor (eg, dopamine) f. Consider glucagon for patient taking b-blocker Management of Anaphylaxis 4. Observation and subsequent outpatient follow-up: a. Observation periods after apparent resolution must be individualized b. After recovery from the acute episode, every patient should receive epinephrine autoinjectors and be instructed in proper technique c. Every patient after anaphylaxis requires a careful diagnostic evaluation in consultation with an allergistimmunologist Anaphylaxis in the Community Sponsored by ACES101210 • © Copyright 2010, AANMA • www.aanma.org ACES101210 • © Copyright 2010, AANMA • www.aanma.org QUESTIONS?