Anaphylaxis Johannes Ring Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein Technische Universität München Munich, Bavaria, Germany GA2LEN Center of Excellence EU frame program Christine Kühne Center for Allergy Research and Education (CK-CARE) XXII World Allergy Congress WAC 4 – 4 december 2011, Cancun Mexico

Anaphylaxis: definition by the World Allergy Organization „Anaphylaxis is an (acute) severe, life-threatening generalized or systemic hypersensitivity reaction“ (regardless of mechanism) there is no universal agreement on its definition or criteria for diagnosis. Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. In MC it is unknown what may cause death. Johansson SGO et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, J Allergy Clin Immunol. 2004;113:832-6. 3

Increase in Incidence of Anaphylaxis Liew WK. Anaphylaxis fatalities and admissions in Australia. J Allergy Clin Immunol 2009;123:434-42

Anaphylactic Reaction after Infusion of Dextran 60

Day 1, Unit 2a

Severity grading of anaphylactic reactions according to Ring and Meßmer (Lancet, 1977) Grade Symptoms observed Skin Gastro-intestinal Respiratory Cardio-vascular I Itch Flush Urticaria Angioedema - II „ (not obligatory) Nausea Cramps Rhinorrhoea Hoarseness Dyspnoea Tachycardia (>20/min) RR changes (>20mmHg syst) Arrhythmia III Vomitus Defecation Laryngeal edema Bronchospasm Cyanosis Shock IV Respiratory arrest Cardiac arrest

Mast Cells Activators Mediators Allergen Histamine Auto-Ab (IgE,FcRI) Anaphylatoxin Tryptase Basic agents (Neuropeptides, 48/80,MBP) Adenosin Chemokines Stem cell factor (c-kit-Ligand) Microbial Peptides Mast Cells Mediators Histamine Proteoglykanes Proteases Other Enzymes Cytokines Lipid mediators I. Weichenmeier, H. Behrendt

33 jährige Patientin mit Mastozytose (ISM) seit 4 Jahren Bronchialasthma Keine frühere Allergie oder Anaphylaxie Basale Tryptase 57µg/l Patientin wurde von Wespe in den Nacken gestochen Patientin hatte kein Notfall-Set dabei Tachykardie, Kollaps, Bewußtseinsverlust innerhalb weniger Minuten Reanimation anfangs erfolgreich, aber später auf Intensivstation Tod durch hypoxischen Hirnschaden Frage einer evtl. „prophylaktischen“ ASIT (Immuntherapie)

Mechanisms of anaphylaxis nettle rash dyspnoea diarrhea, vomiting mast cell shock mediator substances eg histamine Day 1, Unit 2a

Triggers of Anaphylaxis Modif. After Hompes S et al 2009 Trigger Adults Children Foods 16 54 Insects 55 Drugs 21 8

Elicitors or letal anaphylaxis Drugs Insect venoms Auch idiopathische Ax Foods Pumphrey. Clin Exp Allergy 2000; 30:1144

Circumstances of fatal food anaphylaxis Most of patients are aware of food allergy Mostly young asthmatics Several mild reactions in previous history Difficulties in complete avoidance Reactions occur mostly not at home, but in school, kindergarden , bars, restaurants, „Take-Away“, Caterer Kaum eine andere Gruppe von Erkrankungen hat in den letzten Jahrzehnten eine ähnliche Zunahme erlebt wie die Allergien. ¼ aller Menschen sind bereits davon betroffen

Summation anaphylaxis Sport Nahrungsmittel Klima NM-Allergie Arzneimittel Streß Infekte Alkohol

Guidelines in Anaphylaxis 1994 Konsensuskonferenz DGAI Tryba et al Allergo-J 2005 Update parameter AAAAI Lieberman et al JACI 2006 2nd symposium NIH / FAN Sampson et al JACI 2007 Leitlinie Akutmaßnahmen bei Anaphylaxie Ring et al (DGAKI) Allergo-J 2007 Anaphylaxis in childhood (EAACI) Muraro et al Allergy 2008 Epinephrine – drug of choice (WAO) Kemp et al WAO Journal 2011 Development of Global Guidelines (WAO) Simons et al JACI

Development of „Anaphylaxis School“ by working group AGATE (AG Anaphylaxis Training and Education) Johannes Ring, Knut Brockow, Claudia Kugler, Martine Grosber Verena Thiebes (München TUM) Kirsten Beyer, Norbert Gebert (Berlin) Margitta Worm (Berlin) Tilo Biedermann, A Fischer (Tübingen) Alexander Dorsch (Hohenkammer) Ricarda Eben, B Przybilla (München LMU) Frank Friedrichs (Aachen) Uwe Gieler, S Schallmayer (Gießen) Thilo Jakob (Freiburg) Lars Lange (Bonn) Oliver Pfaar, Ludger Klimek (Wiesbaden) Imke Reese (München) Ernst Rietschel (Köln) Sabine Schnadt (daab) Rüdiger Szczepanski (Osnabrück)

Symptoms of anaphylaxis Skin: Itch, reddening, swelling, nettle rash Gastrointestinal tract: Itchy palate, nausea, vomiting, abdominal cramps, diarrhea Respiratory tract: Cold, narrow throat, stridor, cough, dyspnoea Cardiovascular: Vertigo, disorientation, tachycardia hypotension, collapse, unconsciousness shock Day 1, Unit 2a

AGATE Interdisciplinary Group: Dermatologist Emergency Physician ENT Pneumologist Nutritionist Pediatrician Psychologist Patient organisation

Struktured educational programs („Schools“) in allergy Asthma Arbeitsgemeinschaft Asthma-Schulung (AGAS) Neurodermitis Arbeitsgemeinschaft Neurodermitis-Schulung (AGNES) Anaphylaxie Arbeitsgemeinschaft Anaphylaxie – Training und Edukation (AGATE)

Basics of Treatment of Anaphylaxis General measures Volume Adrenaline Antihistamine Glucocorticoids

„Emergency Set“ for self-medication Adrenaline, Antihistamine, Cortisone Application galenics for easy swallowing Adrenaline as Autoinjector + +

Objectives of AGATE Basic knowledge anaphylaxis (symptoms, medication) Coping with anaphylactic reactions Practical training in use of self medication Avoiding triggers Coping with fear Exchange of experiences with other patients

Who is educated? Patients and relatives Patients to whom an epinephrine autoinjector was prescribed (anaphylaxis, adults with mastocytosis) Train the Trainer Seminars: Physicians (Allergists), Psychologists, Nutritionists

Structure of Programmme Outpatient education 2 Meetings with 4 units of 45 minutes Interdisciplinary approach Standardised programme with manual Groups of 6 adults or 12 parents of 6 children

TU =teaching unit á 45 minutes Qualification for „Anaphylaxis Trainer“ according to the AGATE curriculum: Contents Opportunities and limits of educational programs (1 TU) Basics of organization and management of patient education schools (3 TU) Psychosocial aspects (6 TU) Pedagogic basics (8 TU) Medical aspects of anaphylaxis (10 TU) TU =teaching unit á 45 minutes

Qualification for „Anaphylaxis Trainer“ according to the AGATE curriculum: Pedagogic content Methodic/didactic opportunities for all age groups Adequate didactic tools and gadgets for working with children, parents and adults or kindergarden personel Group dynamics Group structuring, processes, intervention methods Relaxation and body perception Role performance games illustrating initiation and solution of problems under everyday conditions

Anaphylaxis School: Contents 1st Day Basics of anaphylaxis Symptoms, early warning signs Triggers Diagnosis and differential diagnoses Individual risk and influencing factors Survey of treatment options Trigger avoidance Allergen-specific immunotherapy (ASIT) Outlook to future approaches Practical management in case of emergency Emergency set: medications Application of emergency medication Adrenaline autoinjector training Day 1, Unit 1 b

Anaphylaxis School: Contents 2nd Day What to do in case of emergency? (repetition) Anaphylaxis Recognition Remembering Counteracting Taking serious Elicitor-specific modules for: Foods - Drugs Insect venoms - Latex Everyday survival strategies Anaphylaxis and social environment Day 2, Unit 1b

Qualification for „Anaphylaxis Trainer“ according to the AGATE curriculum Medical: Allergist or equivalent experience Psychological: Psychology, Psychosomatic medicine, Psychotherapy, pedagogics plus > 1 year experience in behavioural therapy with chronic diseases Nutrition: ecotrophology, dietary assistance with special experience in food allergy (membership in WG) Nurse/children‘s nurse: optional

Qualification for „Anaphylaxis Trainer“ according to the AGATE curriculum: Program Hospitation (observer) in anaphylaxis school Train-the-Trainer seminar Supervision Certificate

inform social environment take emergency drugs always along avoid triggers train application of emergency drugs know alternatives Prevention inform social environment immunotherapy for Insect venom allergy individual emergency plan know symptoms remember Day 1, Unit 3

Conclusions Anaphylaxis is not rare Main elicitors are drugs, insects and foods Adrenaline is the main drug in acute treatment It is important to find causal elicitor by allergy diagnostics If possible, allergen-specific immunotherapy Research regarding „summation“ factors is necessary Strict avoidance of elicitor is best prevention The „anaphylaxis school“ program is helpful in acute management and avoidance of elicitors thus facilitating patient‘s life

Thanks to: K. Brockow C. Kugler U. Darsow M. Grosber V. Thiebes