Anaphylaxis Emergencies for the general physician Shuaib Nasser Consultant in Allergy and Asthma Cambridge University Hospitals NHS Foundation Trust
Definition- Anaphylaxis A potentially life-threatening hypersensitivity reaction, usually rapid in onset and progression, with airway obstruction or hypotension, often with cutaneous features A severe, life-threatening, generalised or systemic hypersensitivity reaction This is characterised by rapidly developing life-threatening airway and/or breathing and/or circulation problems usually associated with skin and mucosal changes 2008 RCUK A serious, generalized or systemic, allergic or hypersensitivity reaction that can be life-threatening or fatal WAO 2014
Definitions Biphasic anaphylaxis - recurrence of symptoms within 1 72 hours with no further exposure to the allergen Up to 20% and typically occurs within 8 hours Non-immune anaphylaxis is the current term used by the World Allergy Organization to replace pseudoanaphylaxis or anaphylactoid reactions - does not involve an allergic mechanism but due to direct mast cell degranulation
Epidemiology Incidence is 4 100 per 100,000 persons per year Lee JK 2011 Tejedor-Alonso M 2015 Lifetime risk of 0.05 2% and ~30% > one attack Rates likely increasing esp foodinduced anaphylaxis in young people and females 1980s - 20 per 100,000 /yr 1990s - 50 per 100,000 /yr 500 1,000 deaths per year (2.4 per million in the US) 20 deaths per year (0.33 per million in the UK) 15 deaths per year (0.64 per million in Australia) Mortality rates reduced / stable between the 1970s and 2000s Death from anaphylaxis most commonly triggered by medications
Fig 1 Journal of Allergy and Clinical Immunology 2015 135, 956-963.e1DOI: (10.1016/j.jaci.2014.10.021) Copyright 2014 The Authors
Fig 3 Time trend for anaphylaxis hospital admissions and fatalities Journal of Allergy and Clinical Immunology 2015 135, 956-963.e1DOI: (10.1016/j.jaci.2014.10.021) Copyright 2014 The Authors
Fig 4 Cause of fatal food-induced anaphylaxis cases by trigger in children (A) and adults (B) and by 5-year groups (C) Journal of Allergy and Clinical Immunology 2015 135, 956-963.e1DOI: (10.1016/j.jaci.2014.10.021) Copyright 2014 The Authors
Common Causes of Anaphylaxis Drugs causing anaphylaxis or anaphylactoid reactions Antibiotics- especially penicillins Neuromuscular blockers Aspirin Non-steroidal anti-inflammatory drugs Intravenous contrast media Opioid analgesics Foods commonly causing anaphylaxis Peanuts Tree nuts (eg, brazil nut, almond, hazelnut) Fruit Fish Shellfish Egg Milk wheat Sesame Pulses (other than peanuts) Others Bee and wasp stings Chlorhexidine Exercise Latex Immunotherapy Seminal fluid Idiopathic
Gadolinium Anaphylaxis 65 year old man underwent MRI angiography IV Gadovist (gadobutrol) Tongue and facial angioedema BP unrecordable 4 doses of IV adrenaline (0.1mg) 2 doses of IM adrenaline, Hydrocortisone, gelofusin, n.saline Tryptase at 1 hr 69.1 +ve ST Gadovist -ve ST Magnovist
58 M office worker FDEIA Standard weekend breakfast -sausages, bacon, toast and butter 30 min later, started work on his car 60min later - Urticaria over neck and shoulders, arms and trunk ED - Treated with antihistamines and oral steroids 6 wks later bacon sandwich for lunch and then packed suitcases for his holiday Took a shower Light-headedness, loss of vision, unable to stand Paramedics - BP 70/40 & Rx IM adrenaline and IV Piriton, steroids 5 reactions all at weekends and never occurred at work +ve ST to Wheat +ve sp IgE omega-5 gliadin Confirming wheat/food dependent exercise induced anaphylaxis Described with other foods Celery, shellfish, cabbage, peaches, grapes, chicken, hazelnuts, apples
NY Times Pulitzer Prize-winning Journalist Anthony Shadid 43 d.16 th feb 2012 Covering Syrian uprising and walking along Syrian- Turkey border behind horses before suddenonset asthma symptoms and death Father said son had lifelong asthma More allergic to horses than anything else
Suspected anaphylaxis during anaesthesia Causes in 111 patients Not investigated 4% Physiological/ Pharmacological (3) 3% NSAID 10% Ondansetron 1% NMBA 35% 103 patients: with confirmed allergy 3 patients : not allergy; pharmac/physiol 5 patients: not investigated. Chlorhexidine (3) 3% Patent blue 10% Gelofusine 10% Antibiotic 23% IV anaesthetics 1% Dua and Ewan
Multiple mechanisms for mast cell activation
Differential diagnosis Vasovagal Excess histamine Non organic disease production Flush Syndromes panic attacks Mastocytosis Carcinoid VCD Basophillic leukaemia Pheochromyctoma Globus Hydatid cyst Peri-menopausal Other APML Oral hypoglycaemia HAE Shock Medullary carcinoma thyroid Red man syndrome Hypovolaemic (vancomycin) Idiopathic Cardiogenic Serum sickness Restaurant syndromes Septic Urticarial vasculitis Scrombroidosi Acute respiratory syndromes Sulphites Asthma Foreign body aspiration PE Epiglottitis
Serum tryptase Indicates mast cell degranulation b-tryptase release From mast cell secretory granules IgE or non-ige-mediated anaphylactic or non-ige reactions blood sample at onset of reaction, 1-4 hr & at 24 hr for baseline Must record timing of sample Cheap and easy test Invaluable when elevated Post-mortem levels useful within 72h of death
Time course of fatal anaphylaxis Food Resp arrest 30-35min Stings Shock 10-15min Intravenous injection Death 5min Pumphrey R 2004
Fatal and near fatal food reactions Risk factors 13 children/adolescents Age 2-17y (PN 4, nut 6, egg 2, milk 1) Asthma in 12/13, known food allergy, multiple allergies 7 near-fatal 6/7 received adrenaline in first 30mins 6 fatal 3 had AAI; none had it available adrenaline given late, time from onset of Sx: 22-160m only 2/6 had adrenaline in first hour (most>1h) Sampson NEJM 1992
Failure to administer adrenaline Fatal anaphylaxis: only 13% received adrenaline before arrest Total (%) 124 (100) 48 (34) 17(13) 60 (48) Pumphrey, CEA 2000
Effect of adrenaline Stimulates alpha-1 receptors SM contraction Stimulates alpha-2 receptors Stabilises mast cells SM contraction Stimulates beta-1 receptors Increase HR & contractility Increase cardiac output Stimulates beta-2 receptors Bronchodilation
Acute Rx in ED NICE Guidance 2011 CG134 Document trigger, timing Tryptase after Rx,1-2h & observe for biphasic response Provide adrenaline AI Refer to allergy clinic Identify cause, cross-reacting allergies, assess severity Avoidance advice, induce tolerance Control by early self-treatment, written Rx plan
diagnosis and management Clinical Backed up by appropriate tests ST, sp IgE, challenge sensitisation v. allergy Understanding of natural history Risk assessment Rx co-morbidities Asthma, eczema, rhinitis Personalised Rx plan
Assessing risk for future severity No asthma Non-severe asthma x 2.1 Severe asthma x 3.3 Gonzalez-Perez et al JACI 2010 Previous severity Amount of allergen Which allergen Components resolved Co-factors Asthma Viral infections Alcohol NSAIDs Tryptase baseline Beta-blockers, ACEI Other Age Travel Psychological factors
BSACI guideline: prescribing an adrenaline auto injector Clin Exp Allergy Oct 2016 Clinical & Experimental Allergy Volume 46, Issue 10, pages 1258-1280, 29 SEP 2016 DOI: 10.1111/cea.12788 http://onlinelibrary.wiley.com/doi/10.1111/cea.12788/full#cea12788-fig-0001
Resuscitation Council UK
Resuscitation Council UK
Management approach in allergy clinic