Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Anaphylaxis Jay Prochnau, MD Indiana University Health Arnett Allergy/Asthma Lafayette, IN Disclosures • Conduct research in COPD and asthma for GSK and Genentech/Roche • No conflicts of interest Anaphylaxis • • • • • • Definition Symptoms Mechanisms Causes Treatment Workup/prevention 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 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” 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 Working definition • An potentially fatal reaction that involves more than one organ system Definitions • Anaphylaxis can be immunologic or non-immunologic, IgE mediated or non-IgE mediated • Non-IgE mediated anaphylaxis used to be called “anaphylactoid” Signs and symptoms • Cutaneous – Urticaria and angioedema – Flushing – Pruritus, no rash • Respiratory – Dyspnea, wheeze – Upper airway swelling – Rhinitis >90% 85-90% 50% 2-5% 40-60% 45-50% 50-60% 15-20% Signs and symptoms • Circulatory – Dizziness, syncope, hypotension, tachycardia 30-35% • GI – Nausea, vomiting, diarrhea, cramping 25-30% • Miscellaneous – Headache – Chest pain – Seizures 5-8% 4-6% 1-2% Signs and symptoms 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 Mechanisms of anaphylaxis Effects of histamine • Activation of itch receptors Pruritus, urticaria • Vasodilation Urticaria, edema • Smooth muscle contraction Wheezing • Increased vascular permeability edema, ↓ BP Other mast cell mediators • Neutral proteases – Tryptase, chymase, carboxypeptidase • Proteoglycans – Heparin, chondroitin sulfate • Leukotrienes • Prostoglandins • Platelet activating factor 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 Causes of anaphylaxis • Exercise – May be food dependent • Vaccines – Gelatin, ovalbumin • Human seminal plasma anaphylaxis • Aeroallergens – uncommon cause of anaphylaxis (horse) 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 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 Anaphylaxis to foods 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 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 Causes of anaphylaxis • Up to 60% of cases of anaphylaxis referred to allergy specialty clinics have no apparent trigger = “idiopathic anaphylaxis” 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 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 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 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 Tryptase in anaphylaxis PAF in anaphylaxis • N N Engl J Med 2008 Jan 3;358(1):28-35 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 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) Absorption by administration site 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 Prevention of anaphylaxis Prevention of anaphylaxis 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 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 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) Questions