11/4/2013 The Other Deadly AAA: Allergy, Angioedema, and Anaphylaxis � Disclosure – No relevant financial interests H. Gene Hern, MD, MS, FACEP, FAAEM Assoc. Clinical Professor, UCSF Residency Director, Alameda County - Highland General Oakland, California A code is called in room 2 � As you run down the hall pulling on your gloves, you see a visitor unravel as she watches a 42 year old woman with two kids become unresponsive while she is talking to her 1
11/4/2013 � The patient recently rec’d some IM PCN � What is the best line to get on this for her Strep Throat. obese woman? � She is 240 lbs. Currently has no IV � Do I need a line first? access on she is flushed and warm. � What dose of epi do I use? � As you push the curtains away and � How can I give it? begin to roll her into the code room you begin to ask yourself the following questions… Objectives Perspectives � What to do on a Cruise… � After this lecture you will: � 1902 Portier and Richet – Appreciate the spectrum of Allergic reactions – Extract of jellyfish tentacles injected into a dog – Recognize systemic and non-systemic � Anaphylaxis from Greek “ against � 1st time tolerated reactions protection ” � 2nd time death (several weeks later.) – Formulate your own strategy for dealing with them – Become a greater advocate for the � (ana, against; phylax, guard or protect) distribution of the Epi-Pen 2
11/4/2013 What does this tell us… Spectrum of Allergic reactions � Early researchers had too much time on � Non-Systemic their hands � Systemic � It takes more than three weeks to cruise the Mediterranean Non-Systemic Allergic Spectrum of Allergic reactions Reactions � Non-Systemic � Urticaria � Systemic � Angioedema 3
11/4/2013 Non-Systemic Allergic Reactions � Urticaria � Case: 65 year old man calls 911 for lip and tongue swelling � Angioedema � He is anxious and meets the ambulance at the curb � He has a HTN and takes a BP med he can’t remember Urticaria and Angioedema � Effects up to 20% of population at some point � Acute and Self-Limited – (some chronic forms exist) � Similar pathological reaction in different locations 4
11/4/2013 � Angioedema – Reaction deep in dermis and Sub Q tissue. – Non-Pruritic – Skin may appear normal – Face, Eyelids, Tongue 5
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11/4/2013 Coexisting?? Pathogenesis � Urticaria and Angioedema co-exist in � Multiple mediators and Pathways many patients. – Allergen stimulation of IgE -> mast cell � For unknown reasons: – Complement Cascade (C3a,4a,5a) -> mast cells directly � Some patients manifest urticaria (40%), – Hageman factor, via coagulation cascade, � Some angioedema (20%), induces formation of other mediators � Some both (40%) bradykinin and kallikrein Etiology of Angioedema � Allergic � Hereditary � ACE Inhibitor related � Unknown Data from: Zingale LC, Beltrami L, Zanichelli A, et al. Angioedema without urticaria: a large clinical survey. CMAJ 2006; 175:1065. 7
11/4/2013 Etiology - Hereditary HAE - Hereditary Angioedema � Associations with autoimmuine � 1:10000 pts. disorders � All races � SLE (7% of SLE pts. will develop hives/allergic � All sexes reactions) � Recurrent attacks � Rheumatoid Arthritis � Truly Hereditary – 2-5 days in duration – Unresponsive to standard allergic therapy – HAE - Hereditary Angioedema – First described in 1876 (J.L. Milton) Angioedema and ACE Angioedema and Inhibitors ACE Inhibitors � Review of 108 cases of Angioedema � The ACE Inhibitor issue � 69% caused by ACE Inhibitor � Bradykinin response � 30 min to 3 days of symptoms � ACE (the actual enzyme) works on two � Single dose to 5 years substrates � Airway mgmt (intub. or cric) 13% – Angiotensin I and Bradykinin – 50% of these were Diabetic • Chiu A.G., et al, Ann Otol Rhinol Laryngol 110(9):834, � By inhibiting ACE, Bradykinin levels September 2001 accumulate and cause Angioedema 8
11/4/2013 Urticaria and Angioedema - Urticaria and Angioedema - Treatment Treatment First line � Steroids?? Anti-Histamines (H1 blockers) � Probably… - Diphenhydramine � 43 pts. acute urticaria. H2 blockers – Much improved pruritis and rash at both 2 - Ranitidine, etc. and 5 days. P<.0001 - Studies for efficacy are small but do show • Pollack, C.V., et al, Ann Emerg Med 26(5):547, difference Urticaria and Angioedema - Urticaria and Angioedema - Treatment Treatment � And gosh darn it… � What if it isn’t allergic???? – Stop the ACE Inhibitor � Hered. Angio. With C1-Inh. Def. – Vanderbilt Study with 82 ACE I related – Give C1 esterase inhibitor concentrate cases 1.8 in pts, who didn ’ t stop taking meds � 69% resolution in 30 min � Recurrence rate 18.7 per 100 person-yrs vs. � 95% resolution in 4 hours • Waytes AT, Rosen FS, Frank MM. N Engl J Med. • Brown, NJ, et al, JAMA 278(3):232, July 16, 1996 Jun 20;334(25):1630-4. 1997 – FFP 9
11/4/2013 Urticaria and Angioedema - Urticaria and Angioedema - Treatment Treatment � Newer Treatments � Obviously advanced airway plans etc. should treatment fail or should the – Ecallantide - Blocks the pathway (Kallikrein Inhibitor) patient decompensate… – Icatibant - Blocks the pathway (Bradykinin B2 receptor antagonist) � Recent case from last month… � J Am Acad Derm, Nov 2010 � Ann Emerg Med, Sep 2010 – 8 patients. Mean time to sx improvement 51 min. Complete relief 4.4 hrs vs. 47 hx controls relief at 33 hrs Urticaria and Angioedema - Treatment � Last Week… 10
11/4/2013 An add’l tip for oxygenation � Can Achieve � 20-30 LPM � Temporizing 11
11/4/2013 Spectrum of Allergic reactions Spectrum of Allergic reactions � Non-Systemic � Non-Systemic � Systemic � Systemic Systemic Allergic reactions - Systemic Allergic reactions - Anaphylaxis Anaphylaxis – Historic Iatros � First fatal anaphylaxis 4000 years ago - � Horse serum for DT(early) Hymenoptera sting � PCN - First fatality 1949 – Currently, iatros more common than Hymenoptera – Today -- 500 fatalities annually � Hymenoptera venom (yellow jackets, hornets, � radiocontrast dyes honeybees, bumblebees, wasps) � beta-lactam antibiotics � 50 deaths per year in the United States – 1-5 per 10,000 administrations -far outnumbering deaths from snake bites – 10% of these are life-threatening – 1% are fatal. � Only 9-25% of fatal stings report previous hymenoptera – Majority from IV or IM administrations rather than oral allergy therapy – Anaphylactic reactions to foods � shellfish, nuts (esp. peanuts), and eggs 12
11/4/2013 Anaphylaxis - Anaphylaxis - Onset of Pathophysiology Symptoms � IgE mediated hypersensitivity reaction � Most occur within seconds to minutes � Similar to allergic rhinitis but more profound – Histamine and other pre-formed mediators � Few are asymptomatic for an hour and – Overwhelming vascular permeability THEN develop symptoms � Anaphylactoid reactions (non IgE-mediated) – clinically indistinguishable from true anaphylaxis Anaphylaxis - Anaphylaxis - Duration of Duration of Symptoms Symptoms � Most patients � NO particular test or spectrum of clinical – Predictable - uniphasic course which resolves symptoms predicts who will have with treatment biphasic or protracted responses � 20% of patients - have BIPHASIC reactions – A second episode up to eight hours following apparent recovery from the initial event � Rarely, symptoms may persist >1 day 13
11/4/2013 Anaphylaxis - Symptoms Anaphylaxis – “New” definitions � Multi-System Spectrum � 1 – Acute onset of skin, mucosal tissue and either – CV - HypoTN, Shock, CP, MI, Arrhythmias – Respiratory Compromise – RESP - Wheezing, Bronchospasm – Or – Neuro - Anxiety, Confusion, Dizziness, SZ – Reduced BP with end organ evidence – Derm - Pruritis, Angioedema, Urticaria – GI - N/V, Diarrhea � 2 nd Criteria � 3 rd Criteria � Two or more of the following after � Reduced BP after exposure to a exposure to likely allergen KNOWN allergen for that patient – Skin/mucosal inflammation – <90 mm HG or a drop of 30% from baseline – Resp. compromise – Reduced BP – To detect reaction in patients with only 1 – Persistent GI symptoms (Vomiting, pain) organ system affected but clearly known to be allergic (peanuts, bee stings) 14
11/4/2013 Anaphylaxis - Causes of Anaphylaxis - Treatment Death � Airway Obstruction � Consider Anaphylaxis as one end of an Allergic spectrum � Cardiovascular Collapse � While it may share characteristics with Angioedema, it is wise to think of them � Target Therapies Accordingly as the same identity (at least initially) � The initial treatment is the same Anaphylaxis - Treatment Anaphylaxis - Treatment � Preparation � Universal Initial Therapy � Make sure you know where your difficult � Critical Care Room airway tools are � Get ALL the relevant Data – Nasal vasoconstrictors � ABC’s – Cricothyrotomy kit � Vital Signs – Fiberoptic Intubating Bronchoscope 15
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