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Slide 1 - Anaphylaxis Jay Prochnau, MD Indiana University Health Arnett Allergy/Asthma Lafayette, IN
Slide 2 - Disclosures Conduct research in COPD and asthma for GSK and Genentech/Roche No conflicts of interest
Slide 3 - Anaphylaxis Definition Symptoms Mechanisms Causes Treatment Workup/prevention
Slide 4 - Definitions “Ana” = against, “phylaxis” = protection Coin termed in 1902 by Portier and Richet Attempts to vaccinate dogs against the toxin of sea anemones led to death at much lower doses
Slide 5 - Definitions “I know it when I see it” Potter Stewart World Allergy Organization: “A severe, life threatening, generalized or systemic hypersensitivity reaction” NIAID/FAAN: “A serious allergic reaction that is rapid in onset and may cause death”
Slide 6 - Criteria Criterion 1 – acute onset (minutes to hours) of an illness involving the skin, mucosal tissue or both (eg hives, pruritus, flushing, swollen tongue/lips/uvula) and at least one of the following: Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia, reduced peak flow) Reduced blood pressure or associated signs/symptoms (hypotonia, syncope) Criterion 2 – 2 or more of the following that occur rapidly (minutes to hours) after exposure to a likely allergen: Skin involvement Respiratory compromise Reduced BP Persistent GI symptoms (abdominal cramping, vomiting) Criterion 3 – reduced BP after known allergen (minutes to hours) Systolic <90mmHg (<70 in children), or 30% decrease is SBP
Slide 7 - Working definition An potentially fatal reaction that involves more than one organ system
Slide 8 - Definitions Anaphylaxis can be immunologic or non-immunologic, IgE mediated or non-IgE mediated Non-IgE mediated anaphylaxis used to be called “anaphylactoid”
Slide 9 - Signs and symptoms Cutaneous >90% Urticaria and angioedema 85-90% Flushing 50% Pruritus, no rash 2-5% Respiratory 40-60% Dyspnea, wheeze 45-50% Upper airway swelling 50-60% Rhinitis 15-20%
Slide 10 - Signs and symptoms Circulatory Dizziness, syncope, hypotension, tachycardia 30-35% GI Nausea, vomiting, diarrhea, cramping 25-30% Miscellaneous Headache 5-8% Chest pain 4-6% Seizures 1-2%
Slide 11 - Signs and symptoms
Slide 12 - ppt slide no 12 content not found
Slide 13 - Mechanisms of anaphylaxis Main mediator of anaphylaxis is histamine Histamine released from mast cells Mast cell degranulation triggered by cross linking of IgE antibodies bound to IgE receptors
Slide 14 - Mechanisms of anaphylaxis
Slide 15 - Effects of histamine Activation of itch receptors Pruritus, urticaria Vasodilation Urticaria, edema Smooth muscle contraction Wheezing Increased vascular permeability edema, ↓ BP
Slide 16 - Other mast cell mediators Neutral proteases Tryptase, chymase, carboxypeptidase Proteoglycans Heparin, chondroitin sulfate Leukotrienes Prostoglandins Platelet activating factor
Slide 17 - Causes of anaphylaxis Medications Most common cause of anaphylaxis (inpatient) Drug reactions responsible for 230,000 hospital admissions in the US annually Foods Food allergy affects 6-8% of children, 3-4% of adults Most common cause of anaphylaxis at home Insect stings 40 deaths/year estimated due to Hymenoptera stings Blood products Anti-IgA antibodies in an IgA deficient patient
Slide 18 - Causes of anaphylaxis Exercise May be food dependent Vaccines Gelatin, ovalbumin Human seminal plasma anaphylaxis Aeroallergens uncommon cause of anaphylaxis (horse)
Slide 19 - Anaphylaxis to medications Antibiotics Most common medication class associated with anaphylaxis Penicillin, sulfonamides Vancomycin – usually non IgE mediated/direct mast cell activation NSAIDs Second most common Most probably not IgE mediated Radiocontrast media Usually not IgE mediated Incidence appears to be diminishing
Slide 20 - Anaphylaxis to medications Perioperative anaphylaxis Most common neuromuscular blocking agents (62%) Natural rubber latex (16%) Intraoperative antibiotics Protamine use to reverse heparin Opioid analgesics Non IgE mediated Directly activate mast cells
Slide 21 - Anaphylaxis to foods
Slide 22 - Anaphylaxis to foods Any food can cause anaphylaxis Most common peanut and tree nuts “Big 6” foods Peanut/tree nuts Shellfish/fish Cow’s milk Egg Soy Wheat
Slide 23 - Anaphylaxis to insect stings Hymenoptera venoms most common Hymenoptera = “membrane winged” insects Yellow jacket, yellow hornet, white faced hornet, paper wasp, honeybee, imported fire ant (in the south) Anaphylaxis reported to multicolored asian lady beetles
Slide 24 - Causes of anaphylaxis Up to 60% of cases of anaphylaxis referred to allergy specialty clinics have no apparent trigger = “idiopathic anaphylaxis”
Slide 25 - Differential diagnosis of anaphylaxis ACE inhibitor mediated angioedema Mediated by bradykinin, not histamine May affect up to 2.2% of patients on ACE inhibitors Restaurant syndromes Scombroid fish poisoning Anisakiasis MSG Sulfites Mastocytosis Systemic mastocytosis, mast cell activation syndrome
Slide 26 - Differential diagnosis of anaphylaxis Nonorganic disease Vocal cord dysfunction, globus hystericus, panic attack Vasovagal syncope Pallor as opposed to flushing Bradycardia as opposed to tachycardia Myocardial infarction or stroke Flushing disorders Menopause Medications that cause flushing (niacin) Alcohol
Slide 27 - Differential diagnosis of anaphylaxis Tumors Carcinoid Pheochromocytoma GI tumors: VIPoma Medullary carinoma of the thyroid Idiopathic capillary leak syndrome Rare, can be fatal Undifferentiated somatoform anaphylaxis
Slide 28 - Diagnosis of anaphylaxis Diagnosis of anaphylaxis is primarily clinical Laboratory workup may be helpful Histamine Stays elevated for 30-60 minutes Urinary metabolites may stay elevated for 24 hours Tryptase Stays elevated for 4-6 hours May not be elevated in anaphylaxis due to food allergy Platelet activating factor (PAF) “BNP” of anaphylaxis Increasing levels of PAF may indicate greater severity
Slide 29 - Tryptase in anaphylaxis
Slide 30 - PAF in anaphylaxis N Engl J Med 2008 Jan 3;358(1):28-35N
Slide 31 - Treatment of anaphylaxis ABCs Protection of airway crucial, early intubation if necessary Laryngeal edema most common cause of death from anaphylaxis Supplemental oxygen Pressure support Place patient in recumbent position, elevate lower extremities IV fluids, pressors if necessary
Slide 32 - Treatment of anaphylaxis “EASI” Epinephrine 1:1000 First line therapy for anaphylaxis Should be given IM (as opposed to SC or IV), lateral thigh (vastus lateralis muscle) for optimal absorption Dose 0.3 to 0.5ml for adults, 0.01ml/kg for children Can be repeated every 5-15 minutes as needed Antihistamines Diphenhydramine or hydroxyzine 50mg every 6 hours Steroids Methylprednisolone or prednisone to prevent biphasic reaction Inhaled beta-agonists (e.g., albuterol)
Slide 33 - Absorption by administration site
Slide 34 - Prevention of anaphylaxis Allergy referral Careful history and directed testing to identify trigger of anaphylaxis Skin testing vs RAST testing Skin testing to medications is of limited utility with the exception of penicillin Patients should have access to an epinephrine autoinjector
Slide 35 - Prevention of anaphylaxis
Slide 36 - Prevention of anaphylaxis
Slide 37 - Prevention of anaphylaxis Medication allergy Avoidance Desensitization if necessary Food allergy Avoidance Trials with oral immunotherapy look promising Hymenoptera allergy Venom immunotherapy 98% curative, 100% effective
Slide 38 - Prevention of anaphylaxis Radiocontrast media allergy Use of lower osmolar or nonionic contrast media Pretreatment with steroids and antihistamines Prednisone 50mg 12h, 6h and 1h and diphenhydramine 50mg 1h prior to RCM administration Hydrocortisone 200mg and diphenhydramine 50mg pre-procedure Risk of reaction 60% if high osmolar contrast is used again, 6% with either low osmolar contrast media or with pretreatment, 0.6% with low osmolar contrast media and pretreatment
Slide 39 - Mast cell activation disorders Primary mast cell disorders Mastocytosis Monoconal mast cell activation disorder (MMAD) Secondary mast cell disorders Allergic disorders (IgE mediated urticaria/anaphylaxis) Chronic autoimmune urticaria/angioedema Idiopathic mast cell disorders Idiopathic anaphylaxis Idiopathic urticaria/angioedema Idiopathic mast cell activation syndrome (MCAS)
Slide 40 - Questions