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ABC of allergies: Anaphylaxis -- Ewan 316 (7142): 1442 -- BMJ
@import url(/css/common.css); @import url(/css/layout.css); @import url(/css/header.footer.style2.css); @import url(/css/services.css); @import url(/css/section.article.css); Jump to: Page Content, Site Navigation, Site Search, You are seeing this message because your web browser does not support basic web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better. Search the BMJ
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 Search this site: Advanced search Register for free services | Subscribe | Sign In Research Methods and Reporting Education Clinical reviewPractice ShortcutsEndgames News Comment Editor's choiceEditorialsLettersRapid ResponsesFeaturesObservationsHead to headAnalysisViews & reviewsObituariesMinervaFillersBlogsPodcast Topics Clinical topicsNon-clinical topicsSeriesTheme issues Print Issues Last seven daysPast weeks (Monday-Sunday)Print issue archiveRapid responsesPolls archiveDebates archiveBlogsAudioAcademic medicineUS highlights 2006BMJ USA 2001-5 About BMJ Home > Education > BMJ 1998;316(7142):1442 (9 May), doi: BMJ 1998;316:1442-1445 ( 9 May )Clinical reviewABC of allergiesAnaphylaxis Pamela W Ewan. Anaphylaxis and anaphylactic deathare becoming more common and particularly affect children and youngs. Anaphylaxis can be frightening to deal with because of itsrapid onset and severity. Doctors in many fields, but particularlythose working in general practice and in accident and emergencydepartments, need to know how to treat it. Features of anaphylaxis Erythema Pruritus (generalised) Urticaria Angio-oedema Laryngeal oedema Asthma Rhinitis Conjunctivitis Itching of palate or external auditory meatus Nausea, vomiting, abdominal pain Palpitations Sense of impending doom Fainting, lightheadedness Collapse Loss of consciousness  Definition Anaphylaxis means a severe systemic allergic reaction. Nouniversally accepted definition exists because anaphylaxis comprises aconstellation of features, and the argument arises over which featuresare essential features. A good working definition is that it involvesone or both of two severe features: respiratory difficulty (which maybe due to laryngeal oedema or asthma) and hypotension (which canpresent as fainting, collapse, or loss of consciousness). Otherfeatures are usually present. The confusion arises because systemicallergic reactions can be mild, moderate, or severe. For example,generalised urticaria, angio-oedema, and rhinitis would not bedescribed as anaphylaxis, as neither respiratory difficulty norhypotension the potentially life threatening featuresis present.  View larger version (23K):[in this window][in a new window] Activation of mast cells by allergen crosslinking of adjacentIgE on cell surface in a type I allergic reaction Mechanism An allergic reaction results from the interaction of anallergen with specific IgE antibodies, bound to Fc receptors for IgE onmast cells and basophils. This leads to activation of the mast cell andrelease of preformed mediators stored in granules (including histamine), as well as of newly formed mediators, which are synthesised rapidly. These mediators are responsible for the clinical features. Rapid systemic release of large quantities of mediators will cause capillary leakage and mucosal oedema, resulting in shock andasphyxia. Effects of mast cell mediators Physiological effect Clinical expression Danger Capillaryleakage Urticaria Angio-oedema Laryngealoedema Asphyxia Hypotension Shock Mucosal oedema Laryngealoedema Asphyxia Rhinitis Asthma Respiratoryarrest Smooth musclecontraction Asthma Respiratory arrest Abdominal pain Anaphylactoid reactions are caused by activation of mast cellsand release of the same mediators, but without the involvement of IgEantibodies. For example, certain drugs act directly on mast cells. Forpractical purposes (management) it is not necessary to distinguish ananaphylactic from an anaphylactoid reaction. This difference isrelevant only when investigations are being considered. Incidence Hardly any data exist on the overall incidence of anaphylaxis.One recent study examining cases of anaphylaxis presenting to anaccident and emergency department in Cambridge (to which all cases froma defined area would be brought) found that 1 in 1500 patientsattending the department had anaphylaxis with loss of consciousness orcollapse (equivalent to 1 in 10 000 a year in the population) and thatthe rate almost trebled when systemic allergic reactions withrespiratory difficulty were included. Most other data relate tospecific causesfor example, anaphylaxis due to allergy to penicillinor to anaesthetic drugsand are quite variable. Aetiology Foods are the commonest cause ofanaphylaxis, and evidence suggests that this is an increasing problem,now documented for allergies to peanuts and other nuts. Insect venom isthe next most common cause of anaphylaxis. A rapidly increasing problem is allergy to latex rubber. This is probably related to the enormous increase in the use of latex rubber gloves by medical and paramedical staff, as well as to the increase in atopy. Rare causes include exercise, vaccines, and semen. Allergen immunotherapy (desensitisation) may induce anaphylaxis. Common causes of anaphylaxis Foods Bee and wasp stings Drugs Latex rubber Foods commonly causing anaphylaxis Peanuts Tree nuts (eg, brazil nut, almond, hazelnut) Fish Shellfish Egg Milk Sesame Pulses (other thanpeanuts) Drugs causing anaphylaxis or anaphylactoid reactions Antibiotics (especially penicillin) Intravenous anaesthetic drugs Aspirin Non-steroidal anti-inflammatory drugs Intravenous contrast media Opioid analgesics Clinical features It is important to recognise that the picture will vary withthe cause. When an allergen is injected systemically (insect stings,intravenous drugs) cardiovascular problems, especially hypotension andshock, predominate. This is especially true when large boluses aregiven intravenously, as at induction of anaesthesia. Foods that areabsorbed transmucosally (from the oral mucosa down) seem especially tocause lip, facial, and laryngeal oedema. Respiratory difficultytherefore predominates. With severe reactions onset occurs soon afterexposure (within minutes), and progression is rapid. Four brief case histories Case 1Woman aged 20, six months pregnant Trigger: Chinese meal Symptoms and treatment: one hour after start of meal felt faint; mildasthma; sever dyspnoea and laryngeal oedema; loss of consciousness; takento acccident and emergency department after 10 minutes; on arrival cyanosed, respiratory arrest; periorbital oedema; salbutamol infusion;cardiac arrest four minutes later; adrenaline given; intubated withdifficulty and ventilated Recovered (see figure next page) Cause: allergy to green pepperCase 2Woman aged 30 Trigger: one teasponful muesli Symptoms and treatment: immediate itching of mouth; throat swollenand uncomfortable inside; vomited; dyspnoea (could not breathe, differentfrom her asthma); laryngeal oedema (obstruction in throat); lightheaded;no loss of consciousness; used her own salbutamol inhaler (no effect);taken to accident and emergency department; respiratory distress; intenseerythema and generalised urticaria; given intramuscular adrenaline and chlorpheniramine Rapid recovery Cause: allergy to brazil nuts and hazelnutsCase 3Boy aged 8 months Trigger: Tiny quantity of peanut butter Symptoms: blisters around mouth; distressed; vomiting; dyspnoea; urticaria Cause: allergy to peanutsCase 4Woman aged 26 Trigger: vaginal examinations during labour Symptoms: itching of vulva; oedema of labia; generalised urticaria and pruritus; mild dyspnoea; felt woozy, lightheaded, odd, shaking Cause: allergy to latex rubber Latex rubber anaphylaxisunusuallydevelops more slowly (30 minutes or longer from the time of exposure), as the allergen has to beabsorbed through the skin or mucosa (for example, during abdominal orgynaecological surgery, vaginal examination, dental work, or simplycontact with, or wearing, rubber gloves). Healthcare workers areespecially at risk.  View larger version (97K):[in this window][in a new window] Allergy to latex rubber is common in healthcare workers Investigations The only immediate test that is useful at the time of reactionis mast cell tryptase. Tryptase is released from mast cells in bothanaphylactic and anaphylactoid reactions. It is an indicator of mastcell activation but does not distinguish mechanisms or throw light oncauses. It is usually but not always raised in severe reactions but maynot be in less severe systemic reactions. As mast cell tryptase is onlyraised transiently, blood should be taken when it peaks at about anhour after the onset of the reaction. This test remains to be fullyevaluated. Management Adrenaline (epinephrine) is the mostimportant drug for anaphylaxis and should be given intramuscularly. Itis almost always effective. Do notgive adrenaline intravenously except in special circumstances (seetext) Drug treatment of anaphylaxis in s Intramuscular adrenaline0.5 ml (500 µg), 1 in 1000 solution (1 mg/ml) Intramuscular or slow intravenous chlorpheniramine 10 mg Intramuscular or slow intravenous hydrocortisone 200 mg This should be followed by chlorpheniramine and hydrocortisone(intramuscular or slow intravenous). This is usually all that isrequired, provided that treatment is started early. Treatment failureis more likely if administration of adrenaline is delayed. Biphasicreactions have been described but are probably rare; administration ofhydrocortisone should minimise the risk of late relapse. Difficulties may arise if the clinical picture is evolvingwhen the patient is first assessed. Adrenaline should be given to allpatients with respiratory difficulty or hypotension. If these featuresare absent but there are other features of a systemic allergicreaction, it is appropriate to give chlorpheniramine and hydrocortisoneand reassess. If in doubt, give 500 µg adrenaline intramuscularly inan or the appropriate dose in a child. Doses of intramuscular adrenaline in children Age (years) Volume of 1 in 1000 Dose (µg) strength (1 mg/ml) 1 0.1 ml 100 2-3 0.2 ml* 200 4-7 0.3 ml* 300 8-11 0.4 ml* 400 >11 0.5 ml* 500 This is a guide based on average weight for differentage bands. No evidence exists for particular doses for different agebands, and published schedules therefore differ. *Reduce dose in children of below averageheight. There can be risks associated with intravenous adrenaline.Adrenaline should not be given intravenously except under special circumstances: profound shock (which is immediately life threatening) or during anaesthesia. Even then, if intravenous adrenaline is given, adilute solution (1 in 10 000) must be administered very slowly inaliquots (with a maximum initial dose of 100 µg (that is, 1 ml))with cardiac monitoring. Such treatment therefore is rarely indicatedoutside hospital. Although myocardial infarction has been reported in theliterature as being associated with the use of adrenaline, thisreflects a bias in reporting, as the effective and safe use ofadrenaline is not considered worth reporting. Those with wideexperience of its use find adrenaline extremely safe.  Blockers may increase the severity of an anaphylacticreaction and may antagonise some of the beneficial actions ofadrenaline. However, if a patient with anaphylaxis is taking blockers this should not prevent the use of adrenaline. Supporting treatments If the patient has hypotension then he or she should lie flatwith the legs raised, but if respiratory difficulty is the dominant problem it may be better for the patient to sit up. Oxygen should beadministered. Key to management of anaphylaxis Awareness Recognise it (consider in differential diagnosis) Treat quickly Deaths in otherwise healthy young people could thenbe avoided Anaphylaxisis easily treatable, and patients can make a complete recovery An inhaled 2 agonist should be given if there is asthma.Inhaled adrenaline is effective for mild to moderate laryngeal oedema but would not be given if intramuscular adrenaline had already beengiven as first line treatment, and it is not a substitute forintramuscular adrenaline. If drugs are not rapidly effective for shock,intravenous fluids should be given rapidly.  View larger version (13K):[in this window][in a new window] Entry in patient's hospital notes (case 1, box previouspage) 9 hours after anaphylaxis with cardiorespiratory arrest, showingeffectiveness of prompt treatment Long term management Patients are commonly sent home from accident and emergencydepartments without further advice. Patients are not infrequently givenan ampoule of adrenaline or a preloaded adrenaline syringe withoutinstruction. This is of little or no value and frightens patients. What to do after an anaphylactic reaction Action Aim Take blood at 1-5 hours for measurement of mast celltryptase To confirm anaphylaxis or anaphylactoid reaction Refer to an allergy clinic to determine cause To prevent further attacks Organise self treatment of future reactions (best done by anallergist) To prevent morbidity (early treatment is thekey) It is important to refer patients to an allergist ideally,one with expertise in anaphylaxis. The cause should be determined, andadvice given on avoidance to prevent further attacks. The cause isdetermined by taking a detailed and structured allergy history, then,in the case of IgE mediated reactions, confirmed (for most allergens)by skin prick tests. The cause is sometimes obvious from the history(as in case 3, previous page, where a typical reaction immediatelyfollowed ingestion of peanut butter). In case 1 the cause was alsoindicated by the history as there had been two allergic reactions, thefirst milder one after a "ploughman's lunch" with few ingredientsand the second after a large Chinese meal containing at least sixsuspected allergens. Green pepper was the common factor. Skin tests(directly through the flesh of green pepper and also with an aqueoutract of green pepper that we prepared) were strongly positive,confirming the diagnosis.  View larger version (23K):[in this window][in a new window] Preloaded adrenaline syringes are available for self treatmentof anaphylaxis Early self treatment is highly effective, and reactions canusually be stopped easily. Syringes preloaded with adrenaline are easyfor patients to use and readily available. They deliver fixedintramuscular doses and are available in two strengths: for s(containing 0.3 ml of 1 in 1000 strength (that is, 300 µg)) and forchildren (0.3 ml of 1 in 2000 (150 µg)). The appropriate selftreatment varies and may include other drugs. This should be determinedby a specialist as, once a cause is determined and avoidance measuresare in place, further reactions after inadvertent exposure are usuallyless severe. A written treatment plan should be provided by theallergist, and the patient (and relatives) should be taught how andwhen to use the treatments providedfor example, trainer syringes areavailable. Somepatients who have had an anaphylactic reaction wear a Medic Alertbracelet or necklacewith an inscription endorsed by a doctor thatalerts other doctors to the possible cause of any futurereaction To be of help to children, schools and nurseries needtraining. Some allergists have developed links with communitypaediatricians, whose teams are best placed to deliver training. Thisrequires expertise, which is now developed in only a few centres. Theteam in Cambridge is therefore coordinating the production of national guidelines. Further reading Stewart AG, Ewan PW. The incidence, aetiologyand management of anaphylaxis presenting to an accident and emergencydepartment. Q J Med 1996;89:859-64 Fisher MMcD, Baldo BA. The incidence and clinicalfeatures of anaphylactic reactions during anaesthesia in Australia.Ann Fr Anesth Reanim 1993;12:97-104 Ewan PW. Clinical study of peanut and nut allergy in62 consecutive patients: new features and associations.BMJ 1996;312:1074-8 Turjanmaa K, Alenius H, Makinen-Kiljunen S, ReunalaT, Palosuo T. Natural rubber latex allergy. Allergy1996;51:593-602 Vickers DW, Maynard L, Ewan PW. Management ofchildren with potential anaphylactic reactions in the community: atraining package and proposal for good practice. Clin ExpAllergy 1997;27:898-903 If there is no local allergist the general practitioner or thedoctor in the accident and emergency department should provide thedrugs for self treatment, but it is essential that these are given withadvice and training. Practice nurses should have trainer syringes forthis purpose. AcknowledgmentsPamela W Ewan is a Medical Research Council clinical scientist andhonorary consultant in allergy and clinical immunology atAddenbrooke's Hospital, Cambridge. The ABC of allergies is edited by Stephen Durham, honoraryconsultant physician in respiratory medicine at the Royal Brompton Hospital, London. It will be published as a book later in the year.© BMJ 1998   CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this? This article has been cited by other articles: Gilbar, P. J, Ridge, A. M (2004). Inappropriate labelling of patients as opioid allergic. J Oncol Pharm Pract 10: 177-182 [Abstract] Gompels, L L, Bethune, C, Johnston, S L, Gompels, M M (2002). Proposed use of adrenaline (epinephrine) in anaphylaxis and related conditions: a study of senior house officers starting accident and emergency posts. Postgrad. Med. J. 78: 416-418 [Abstract] [Full text] Brown, V., Brandner, B., Brook, J., Adiseshiah, M. (2002). Cardiac arrest after administration of Omnipaque radiocontrast medium during endoluminal repair of abdominal aortic aneurysm. Br J Anaesth 88: 133-135 [Abstract] [Full text] Neugut, A. I., Ghatak, A. T., Miller, R. L. (2001). Anaphylaxis in the United States: An Investigation Into Its Epidemiology. Arch Intern Med 161: 15-21 [Abstract] [Full text] Jowett, N. I (2000). Speed of treatment affects outcome in anaphylaxis. BMJ 321: 571-571 [Full text] Sheikh, A., Alves, B. (2000). Hospital admissions for acute anaphylaxis: time trend study. BMJ 320: 1441-1441 [Full text] Rapid Responses:Read all Rapid ResponsesCorrect dose of adrenalineLuis F Sacabmj.com, 26 May 1998[Full text]UntitledAnthony A F T Brownbmj.com, 7 Jul 1998[Full text] This Article Extract  PDF Correction (v316,p1584) Respond to this article Read responses to this article Alert me when this article is cited Alert me when responses are posted Alert me when a correction is posted View citation map Services Email this article to a friend Find similar articles in BMJ Find similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Read articles citing this article Citing Articles via Google Scholar Google Scholar Articles by Ewan, P. W Search for Related Content PubMed PubMed Citation Articles by Ewan, P. W Related Content Immunology (including allergy) Drugs: CNS (not psychiatric) Pain (neurology) Ophthalmology Child health Find this article in its weekly table of contents Bookmark with What's this? 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