Transcript Anaphylaxis
Anaphylaxis Objectives Definitions Pathophysiology Etiologies Signs and Symptoms Differential Diagnosis Acute Management Referrals Definitions Anaphylaxis Severe, systemic allergic reaction Involves 2 or more systems: Skin, respiratory, cardiovascular, GI tract Often life threatening IgE mediated reaction Anaphylactoid reaction (AKA Non-IgE Anaphylaxis) Identical clinical syndrome NOT IgE mediated Pathophysiology First exposure to allergen TH2 activation, IgE class switching IgE production IgE binding to mast cells Repeat exposure to allergen Activation of mast cells Pathophysiology cont. Anaphylaxis is an acute, lifethreatening systemic reaction with varied mechanisms, clinical presentations, and severity that results from the sudden systemic release of mediators from mast cells and basophils. Pathophysiology cont. Allergic Reaction: Time Course Immediate Late Phase Histamine Leukotrienes Prostaglandins Thromboxanes Bradykinins Cytokines Time Course Immediate Late phase Within seconds to minutes of exposure Similar symptoms occur 1 to 8-12 hr after onset Prolonged Protracted sx up to 32 hours May not be affected by corticosteroids Kemp SF. J Allergy Clin Immunol 2002;110:341-8. Wade JP, et al. Proc Clin Biol Res 1989;297:175-82. Brazil E, MacNamara AF. J Accid Emerg Med 1998;15:252-3. Signs and Symptoms 2 or more body systems involved Cutaneous (90%) Respiratory (40-60%) Pruritus, urticaria, angioedema, flushing Upper airway edema → Stridor, angioedema Lower airway edema → Dyspnea, wheezing Rhinitis Dizziness, syncope (30-35%) The diagnosis and Management of Anaphylaxis: An Updated Practice Parameter. J Allergy Clin Immunol 2010. Signs and Symptoms cont. Cardiovascular (30-35%) Vasodilation → Relative hypovolemia Increased capillary permeability → intravascular volume loss 50% of intravascular fluid transfers into extravascular space within 10 minutes Hypotension 2005 AHA Guidelines for CPR and ECC. The diagnosis and Management of Anaphylaxis: An Updated Practice Parameter. J Allergy Clin Immunol 2005;115:S483-523. Signs and Symptoms cont. Gastrointestinal 25-30% Abdominal pain, emesis, diarrhea Miscellaneous Headache 5-8% Substernal pain 4-6% Seizure 1-2% Sense of “impending doom” Metallic taste The diagnosis and Management of Anaphylaxis: An Updated Practice Parameter. J Allergy Clin Immunol 2005;115:S483-523. Etiologies Drugs Latex Stinging insects Foods Exercise Seminal Fluid Idiopathic Risk Factors Related to Anaphylaxis Prior hx of anaphylaxis Beta-blocker use Atopic background Latex Venom RCM - anaphylactoid Not risk factor for anaphylaxis to medications Penicillins and beta-lactam family Penicillin is most commonly reported drug allergy Up to 0.04% of PCN treated subjects Anaphylaxis - 0.001% PCN treated pt Cross-reactivity Cephalosporins – Unknown but LOW Some Carbapenems are cross-reactive* • Meropenum may be tolerated by some PCN allergic patients Aztreonam does not cross-react with other beta-lactams except ceftAzadime Idsoe O, et al. Bull World Health Organ 1968;38:159-88. Aspirin and NSAIDs Second most common cause Anaphylactic reactions Drug specific Aspirin exacerbated respiratory disease (AERD) Class specific (Due to inhibition of COX-1 and shunting to AA metabolites to produce increased amounts of Leukotrienes) Latex Prevalence < 1% general population High risk populations Health care workers (5-15%) Pts with spina bifida (24-60%) Workers with occupational latex exposure Most important factor is degree of exposure Up to 17% cases of intraoperative anaphylaxis No commercially avail skin test reagents in US Diagnosis: Hx + IgE Latex Alenius H, et al. J Lab Clin Med 1994;123:712-20. Poley G, Slater J. J Allergy Clin Immunol 2000;105:1054-62. Stinging Insects 40-50 reported deaths per year in US 3% of adults, up to1% of children Bees, yellow jackets, hornets, wasps Fire ants 25-70% chance of systemic rxn if re-stung Maintenance Venom IT reduces this risk to 1-2% if re-stung. Natural History: Systemic reaction Golden et.al. JACI 2000;105:385-90 Foods Food is the most common cause of anaphylaxis in the outpatient setting, and food allergens account for 30% of fatal cases of anaphylaxis. Most common offenders: - peanuts, tree nuts, fish, shellfish, cow’s milk, soy, and egg (Sesame Seeds) Common themes associated with fatal food anaphylaxis include the following: • • • • Reactions commonly involve peanuts and tree nuts Victims are typically teenagers and young adults; Patients have a previous history of food allergy and asthma Failure to administer epinephrine promptly Oral Allergy Syndrome (Food-Pollen Allergy) Seen in patients with seasonal allergic rhinitis Itching and swelling in mouth and oropharynx Associated with ingestion of fresh fruits, vegetables, or nuts Basically the immune system mistakenly confused certain epitopes on the fruit for a tree, grass or weed pollen (aeroallergens). Birch - apples, pears, hazelnut, carrot, potato, kiwi Ragweed – melons, banana Mugwort – celery, carrot, fennel, parsley Tolerate cooked or processed fruits, vegetables Cooking denatures the 3-D shape of the proteins such that they no longer resemble to aeroallergen. Exercise Induced Anaphylaxis Associated factors: foods and meds Within 2-4 hours after ingestion Eating the same foods without exercising does not cause symptoms Exercise changes absorption of antigen Implicated foods: celery, shrimp, apples, and wheat Avoidance of exercise 4-6 hr after eating Seminal Fluid Induced Anaphylaxis Coital anaphylaxis caused by human seminal fluid has been shown to be a result of IgE-mediated sensitization to seminal plasma proteins. Prostate-specific antigen (PSA) has been demonstrated to be a relevant allergen in some cases. It is essential to exclude other underlying causes such as allergens in natural rubber latex condoms or in drugs or foods passively transferred via seminal plasma. Patients with seminal plasma allergy may be able to conceive without undergoing desensitization, by artificial insemination with washed spermatozoa. Idiopathic Anaphylaxis The symptoms of idiopathic anaphylaxis are identical to those of episodes related to known causes. Patients with idiopathic anaphylaxis should receive an intensive evaluation, including a meticulous history to rule out a definite cause of the events. specific laboratory studies to exclude systemic disorders such as indolent systemic mastocytosis are often utilized. Differential Diagnosis Scombroid poisoning Rxn within 30 min of eating spoiled fish Tuna, mackerel, mahi-mahi Urticaria, nausea, vomiting, diarrhea, headache Histidine → Histamine Angioedema Asthma exacerbation Psychiatric conditions – panic attacks, conversion d/o Vocal cord dysfunction Vasovagal reactions Flushing syndromes Systemic mastocytosis Cardiogenic shock Other cardiovascular or respiratory events What is Red Man Syndrome? A. B. C. Anaphylactic reaction Anaphylactoid reaction Neither Red Man Syndrome Associated with rapid infusion of vancomycin Flushing, tingling, pruritus, erythema, maculopapular rash, hypotension Onset 15-45 min after start of infusion Resolves 10-60 min after d/c infusion Tx: Pretreat pt with antihistamines prior to infusion, infuse dose over 2 hr Susla G, et al. Critical Care Medicine. 2nd Ed., 2002, 335. Anaphylactoid Reactions Nonspecific mast cell release May occur with first exposure Opioids Anesthetics Vancomycin ASA, NSAIDs Radiocontrast media Individuals with a hx of anaphylactoid reactions are at increased risk of having another with future exposures. i.e. Pre-treatment protocols for RCM etc…. Anaphylactic Reaction in the operating room Incidence is 1 in 4000 to 1 in 25,000 anesthetic procedures. Mortality as high as 5% NMBA are the most common cause during anesthesia. Succinylcholine is the most common offender. Latex(23%) and Antibiotics (15%) Less common: Local anesthetics, Opioid analgesics (anaphylactoid) Presents as CV collapse, airway obstruction, flushing, and/or edema Radiocontrast Media Overall frequency of adverse rxn 5-8% Life threatening rxn < 0.1% Prevalence greatest in 20-50 yo 16-44% risk if hx of previous reaction Risk reduced to 1% if lower osmolarity agent and pretreatment used No reliable data showing a link between RCM and Iodine or shellfish. RCM Pretreatment Regimen Prednisone 50 mg po Diphenhydramine 50 mg po or IM 13, 7, and 1 hr prior to RCM administration 1 hr prior If emergency procedure Hydrocortisone 200 mg IV every 4 hr Diphenhydramine 50 IM 1 hr prior LOW OSMOLARITY CONTRAST IS BEST (and more expensive – so you will need to beg for this) Acute Management of Anaphylactic Reaction Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Epinephrine Acute Management Epinephrine IM injection in thigh (vastus lateralis) All patients with S/S of systemic reaction 0.3 – 0.5 mg (1:1000), repeat every 5 min, as necessary There is no contraindication to the use of epinephrine in a life threatening situation 2005 AHA Guidelines for CPR and ECC. Epinephrine Alpha-adrenergic effects Vasoconstriction Increase coronary and cerebral perfusion pressure Beta-adrenergic effects May increase myocardial work Reduce subendocardial perfusion Epipen in the Thigh! Acute Management cont. Antihistamines Second line treatment after administration of epi H1 antagonists H2 antagonists Diphenhydramine 25 to 50 mg slow IV or IM Ranitidine 1 mg/kg IV, cimetidine 4 mg/kg IV Inhaled beta-adrenergic agents Albuterol 2.5 – 5 mg in 3 ml saline Bronchospasm refractory to epi Ipratropium use if patient on beta-blocker 2005 AHA Guidelines for CPR and ECC. Acute Management cont. Corticosteroids High dose IV corticosteroids Methylprednisolone 1-2 mg/kg/d divided q6h Effects delayed at least 46 hours X Acute Management cont. Aggressive fluid resuscitation Isotonic crystalloid 1-2L, possibly 4L may be needed Oxygen Monitors Removal of venom sac Patients on Beta-Blockers More likely to experience more severe anaphylactic reactions. Epinephrine may be ineffective Unopposed alpha-adrenergic effects Reflex vagotonic effects Profound hypotension, bradycardia, bronchospasm Consider glucagon Activating adenyl cyclase directly and bypassing beta-adrenergic receptor Potential Therapies Glucagon Vasopressin Nonadrenergic peripheral vasoconstrictor May benefit severely hypotensive pts Dopamine If patient on beta-blocker 1 - 5 mg IV every 5 minutes Side effects – nausea, vomiting, hyperglycemia Stimulates alpha and beta adrenergic receptors Atropine Reverses cholinergic-mediated decrease in HR, BP Relative or severe bradycardia Airway Obstruction Early elective intubation recommended Hoarseness, lingual edema, stridor, oropharyngeal swelling Pts can deteriorate within ½ to 3 hours 2005 AHA Guidelines for CPR and ECC. Cardiac Arrest Cardiopulmonary resuscitation Aggressive volume expansion 2 large bore IVs with pressure bags 4-8 L of isotonic crystalloid High dose epinephrine IV 1-3 mg IV (3 min), 3-5 mg IV (3 min), 4-10ug/min infusion Antihistamine IV Corticosteroids ACLS algorithms 2005 AHA Guidelines for CPR and ECC. IV Epinephrine Risk for potentially lethal arrhythmias Not the preferred method. Administer epinephrine IV only During cardiac arrest (ACLS protocols) Profoundly hypotensive subjects unresponsive to volume replacement and several IM injections Labs in Acute Setting Serum tryptase level Peak 60-90 min after onset of sx Persist for 6 hrs Ideal measurement time 1-2 hr after onset Serum tryptase level may be normal in the setting of food allergy induced anaphylaxis Plasma histamine level Increase within 5-10 min after onset Persist 30-60 min Observation Biphasic reaction in up to 20% pts Symptoms recur within 1-8 hours Observe until asymptomatic ≥ 4 hours Longer observation if severe reaction Discharge EpiPen Corticosteroids Antihistamines Beta-agonist Buddy care Allergy consult Allergy Evaluation Detailed allergy history Labs and allergy testing Avoidance measures Therapeutic options Graded dose challenge Drug desensitization Medical warning tags/ Red Dog Tags Testing for Specific IgE Allergen-specific IgE In vivo testing Prick and ID skin tests • Venom • Foods In vitro testing RAST • Latex • Venom • Foods Clinical Scenario 25 yo AD male OIF air evac’ed from Iraq after IED explosion ICU for Acinetobacter sepsis Childhood hx rash with amoxicillin ICU team initially starts imipenem ID recommends Unasyn (amp/sulbactam) PCN Cross Reactivity Carbapenems are cross-reactive Ampicillin is a beta-lactam antibiotic Patient requires drug desensitization Drug Desensitization Conversion from highly sensitive state to a tolerant state Mast cells unresponsive to specific drug Temporary, lasting as long as therapy is uninterrupted Administration of gradually increasing doses of drug over several hours or days Sensitivity returns within 48 hr of d/c drug Fatalities Usually result from delayed administration of epinephrine Severe respiratory complications Severe cardiovascular complications There is no absolute contraindication to epinephrine administration in anaphylaxis Long Term Management Avoidance measures Pharmacologic prophylaxis to prevent recurrent anaphylactoid rxn Allergen immunotherapy Venom – 90-98% effective Patient education MedicAlert ID, red dog tags Medical record documentation What test should you order to help confirm a diagnosis of anaphylaxis? A. C-reactive protein B. Leukotriene D4 C. Serum Tryptase D. Plasma Histamine Where does the autoinjector go? A. Left Ventricle B. Deltoid C. Gluteus Maximus D. Vastus Lateralis True or False Patients with a history of seafood allergy are by definition allergy to contrast dye (because of the iodine) When to refer to A/I ? Evaluation and diagnosis, as well as long-term management, can be complex. The allergist/immunologist has the training and expertise to obtain a detailed allergy history; coordinate laboratory and allergy testing; evaluate the benefits and risks of therapeutic options; and counsel the patient on avoidance measures. For these reasons, patients with a history of anaphylaxis should be considered for referral to an allergy/immunology specialist. Link for current anaphylaxis guidelines http://www.allergyparameters.org/file_depot/0-10000000/30000-40000/30326/folder/73825/2010Anaphylaxis.pdf