Anaphylaxis Sponsored by:

2007 Dissemination

Program made possible through unrestricted educational grants provided by:

Module 8: Anaphylaxis Program

1. Anaphylaxis Program Panel..............................................................................................................................2

2. About WAO..................................................................................................................................................3-4 3. President’s Welcome and Introduction to WAO and GLORIA.........................................................................5 4. GLORIA Module 8: Anaphylaxis

a.  Abstract................................................................................................................................................6-10



b.  Slides..................................................................................................................................................11-30

5. Conclusion – Question and Answer Session

2005 – 2007 GLORIA Advisory Board Michael A. Kaliner, Chair Carlos E. Baena-Cagnani Jean Bousquet G. Walter Canonica Ronald Dahl Takeshi Fukuda Allen P. Kaplan Connie H. Katelaris Bob Q. Lanier Bee-Wah Lee Richard F. Lockey Cassim Motala Ruby Pawankar Todor Popov Noel Rodriguez Perez Lanny J. Rosenwasser Joaquin Sastre F. Estelle R. Simons Dirceu Sole Paul B. Van Cauwenberge

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WAO Secretariat 555 East Wells Street, Suite 1100 Milwaukee, WI 53202 USA Tel: +1 414 276 1791 Fax: +1 414 276 3349 [email protected] www.worldallergy.org



Anaphylaxis Program Panel Richard F. Lockey Professor of Medicine, Pediatrics and Public Health Director, Division of Allergy and Immunology Joy McCann Culverhouse Chair in Allergy and Immunology Department of Internal Medicine University of South Florida College of Medicine and James H. Haley Veterans’ Hospital Tampa, FL, USA Michael A. Kaliner Medical Director Institute for Asthma and Allergy Wheaton, MD, USA

F. Estelle R. Simons University of Manitoba Winnipeg, Manitoba, Canada

Cassim Motala Associate Professor Pediatric Medicine and Allergy Child Health Director Red Cross Children’s Hospital Cape Town, South Africa

Bob Q. Lanier North Texas Institute for Clinical Trials Fort Worth, TX, USA



About the World Allergy Organization World Allergy Organization (WAO) The World Allergy Organization (WAO) is an international umbrella organization of 74 regional and national allergy and clinical immunology societies. By collaborating with member societies, WAO provides direct educational outreach programs, symposia and lectureships to WAO individual members around the globe. The World Allergy Organization Mission WAO’s mission is to be a global resource and advocate in the field of allergy, advancing excellence in clinical care, education, research and training through a world-wide alliance of allergy and clinical immunology societies.

Programs of the World Allergy Organization World Allergy Forum (WAF) symposia

are held at major international allergy meetings. Developed by international expert advisory panels, the symposia provide up-to-the-minute presentations on scientific and clinical developments in the field of allergic disease.

The GLORIA program promotes good practice in the management of allergic diseases through programs developed by panels of world experts. GLORIA educates medical professionals worldwide through regional and national presentations and local training initiatives. GLORIA educational modules promote the World Allergy Organization’s (WAO) mission – to optimize allergy care worldwide. GLORIA Modules Module 1: Allergic Rhinitis Module 2: Allergic Conjunctivitis Module 3: Allergic Emergencies Module 4: Immunotherapy Module 5: Symptoms and Treatment of Asthma Module 6: Food Allergy

Emerging Societies Program

Module 7: Angioedema

WAO offers advice on initiating and developing allergy societies throughout the world. This proactive initiative aims to expand and improve the specialty of allergy by supporting colleagues working in the field of allergy worldwide. Through sharing practical experiences and alerting new societies to the criteria required for WAO membership, ESM creates relationships with future World Allergy Organization member societies, and educates WAO’s leadership about the challenges and opportunities faced by colleagues in developing countries.

Module 8: Anaphylaxis Module 9: Diagnosis of IgE Sensitization Module 10: Chronic Rhinosinusitis and Nasal Polyposis

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Read the latest in global allergy and asthma news and research through subscriptions to WAO’s journal partners: ACI International - Journal of the World Allergy Organization (ACII - JWAO) and International Archives of Allergy and Immunology.



WAO Member Societies National Member Societies Albanian Society of Allergology and Clinical Immunology American Academy of Allergy, Asthma and Immunology American College of Allergy, Asthma and Immunology Argentine Association of Allergy and Immunology Argentine Society of Allergy and Immunopathology Australasian Society of Clinical Immunology and Allergy Austrian Society of Allergology and Immunology Azerbaijan Society for Asthma, Allergy and Clinical Immunology Bangladesh Society of Allergy and Immunology Belgian Society of Allergology and Immunology Brazilian Society of Allergy and Immunopathology British Society for Allergy and Clinical Immunology Bulgarian National Society of Allergology Canadian Society of Allergy and Clinical Immunology Chilean Society of Allergy and Immunology China Allergology Society and Chinese Allergists (Chinese) Hong Kong Institute of Allergy Colombian Allergy, Asthma and Immunology Association Croatian Society of Allergology and Clinical Immunology Cuban Society of Allergology Danish Society of Allergology Ecuadorian Society of Allergy and Immunology Egyptian Society of Allergy and Clinical Immunology Finnish Society of Allergology and Clinical Immunology French Society of Allergology and Clinical Immunology German Society for Allergology and Clinical Immunology Georgian Association of Allergology and Clinical Immunology Hellenic Society of Allergology and Clinical Immunology Hungarian Society of Allergology and Clinical Immunology Icelandic Society of Allergy and Clinical Immunology Indian College of Allergy, Asthma and Applied Immunology Indonesian Society for Allergy and Immunology

Israel Society of Allergy and Clinical Immunology Italian Society for Allergology and Clinical Immunology Japanese Society of Allergology Korean Academy of Allergy, Asthma and Clinical Immunology Lebanese Society of Allergy and Immunology Malaysian Society of Allergy and Immunology Mexican College of Pediatricians Specialized in Allergy and Clinical Immunology Mexican College of Allergy, Asthma and Clinical Immunology Mongolian Society of Allergology Netherlands Society of Allergology Norwegian Society of Allergology and Immunopathology Paraguayan Society of Immunology and Allergy Peruvian Society of Allergy and Immunology Philippine Society of Allergy, Asthma and Immunology Polish Society of Allergology Portuguese Society of Allergology and Clinical Immunology Romanian Society of Allergology and Clinical Immunology Russian Association of Allergology and Clinical Immunology Allergy Society of South Africa Allergy and Clinical Immunology Society (Singapore) Spanish Society of Allergology and Clinical Immunology Swedish Association for Allergology Swiss Society for Allergology and Immunology Allergy and Immunology Society of Thailand Turkish National Society of Allergy and Clinical Immunology Ukrainian Association of Allergologists and Immunology Uruguayan Society of Allergology Venezuelen Society of Allergy and Immunology Vietnam Association of Allergy, Asthma and Clinical Immunology Zimbabwe Allergy Society

Associate Member Societies Czech Society of Allergology and Clinical Immunology Ecuadorian Society of Allergology and Affiliated Sciences Egyptian Society of Pediatric Allergy and Immunology Italian Association of Territorial and Hospital Allergists

Latvian Association of Allergists Panamanian Association of Allergology and Clinical Immunology Association of Allergy and Clinical Immunology of Serbia and Montenegro

Affiliate Organizations

Regional Organizations The Asian Pacific Association of Allergology and Clinical Immunology Commonwealth of Independent States Society of Immunology and Allergology European Academy of Allergology and Clinical Immunology Latin American Society of Allergy, Asthma and Immunology



International Association of Asthmology

For WAO membership information please contact the Secretariat World Allergy Orgnanization (WAO) 555 East Wells Street, Suite 1100 • Milwaukee, WI 53202-3823 USA Tel: +1 414 276 1791 • Fax: +1 414 276 3349 e-mail: [email protected] Web site: www.worldallergy.org



Dear Colleagues, As President of World Allergy Organization - WAO, I thank you for attending this presentation of the GLORIA Module on Anaphylaxis. GLORIA’s goal is to provide globally relevant teaching materials to promote the development of the specialty of allergy. WAO is grateful to our Member Societies for hosting this presentation and enabling us to bring this educational program series to you. We encourage you to visit www.worldallergy.org/gloria and download the GLORIA materials for use in your own teaching and lecturing. I am lucky to preside over WAO at this exciting time; the Organization has become very active in a wide range of activities, the leadership is dynamic, and our position in the world of allergy is firmly established., We have developed a global agenda to strengthen allergy both for patients and allergists. We are working to make WAO more visible, of greater service to our member societies, and are establishing strong and broad partnerships with our national and regional societies. WAO is helping local allergists to make the governing bodies aware of the need for allergy and to create an environment where allergy and asthma sufferers can get access to well-trained physicians. We are well advanced in our planning for the next World Allergy Congress, which will take place 2-6 December 2007 in Bangkok, Thailand. The meeting will include an innovative and interesting program designed to enlighten the world’s allergists on important advances in allergy. It will focus on new scientific achievements, new approaches to the diagnosis, and new concepts in the treatments of allergy, with a particular focus on immunotherapy and food allergy. A global organization is only as good as its ability to communicate. Our monthly email newsletter, WAO News and Notes, is keeps our members informed of clinical advances in the field and provides a ready means of rapid communications. If you are not receiving this free of charge communication, please contact us at www.worldallergy.org and share your email information. As we look to the future, we recognize that allergy is a rapidly developing and expanding field. The importance of allergy is still underappreciated, and the time when allergy is accepted as an important subspecialty of medicine and pediatrics is still on the horizon. WAO is committed to strengthening allergy through active educational and research partnerships with our 74 member societies. In the end, the many millions of patients with asthma and allergy will benefit as the importance of allergic diseases is recognized and taught more widely. Thank you again for attending this GLORIA presentation! As our activity base continues to expand, we hope you will find WAO becoming more and more relevant to your everyday practice. With my best regards,

Michael A. Kaliner President, World Allergy Organization Chair, GLORIA Advisory Board



Anaphylaxis Richard F. Lockey Professor of Medicine, Pediatrics and Public Health Director, Division of Allergy and Immunology Joy McCann Culverhouse Chair in Allergy and Immunology Department of Internal Medicine University of South Florida College of Medicine and James H. Haley Veterans’ Hospital Tampa, FL, USA Cardiovascular: Faintness, hypotension, arrhythmias, hypovolemic shock, syncope, chest pain.

Definition of Anaphylaxis Anaphylaxis is an acute hypersensitivity reaction, involving release of mediators from mast cells, basophils and recruited inflammatory cells. Anaphylaxis is defined by several signs and symptoms, which, alone or in combination, can occur within minutes or up to a few hours after exposure to a provoking agent. Anaphylaxis can be mild, moderate to severe or severe. Most cases are mild, but any anaphylaxis has the potential to become life-threatening.

Ocular: Periorbital edema, erythema, conjunctival erythema, tearing. Genito-urinary: Uterine cramps, urinary urgency or incontinence. Severe initial symptoms develop rapidly, reaching peak severity within 3-30 minutes. There may occasionally be a quiescent period of 1–8 hours before development of a second (biphasic) reaction. Protracted anaphylaxis may occur, with symptoms persisting for days. Death may occur within minutes, but only rarely has it been reported to occur days to weeks after the initial anaphylactic event.

Anaphylaxis develops rapidly, usually reaching peak severity within 5 to 30 minutes. In rare cases it can last for several days.

Classification

Causes of Anaphylaxis

The term anaphylaxis is often used to describe immunological, particularly IgE-mediated, reactions. A second term, non-allergic anaphylaxis, describes clinically identical reactions that are not immunologically mediated. Clinical diagnosis and management of both conditions are, however, identical.

1. IgE-Mediated Reactions Foods

In theory, any food protein can cause an anaphylactic reaction. Foods most frequently implicated in anaphylaxis are: • Peanuts (a legume) • Tree nuts (walnut, hazel nut/filbert, cashew, pistachio nut, Brazil nut, pine nut, almond) • Fish • Shellfish (shrimp, crab, lobster, oyster, scallops) • Milk (cow, goat) • Chicken eggs • Seeds (cottonseed, sesame, mustard) • Fruits, vegetables

Symptoms and Signs of Anaphylaxis The initial manifestation of anaphylaxis may be loss of consciousness. Patients often describe “a sense of doom.” The symptoms may be isolated to one organ system or involve several. Organ-specific symptoms include the following. Gastro-intestinal: Abdominal pain, hyperperistalsis with fecal urgency or incontinence, nausea, vomiting, diarrhea.

Food sensitivity can be so severe that a systemic reaction occurs to particle inhalation, such as from cooking fish or aerosols from opening of a package of peanuts.

Oral: Pruritus of lips, tongue and palate; edema of lips and tongue.

For example, severe allergy to pollen, ragweed, grass or tree pollen can indicate that an individual is susceptible to anaphylaxis or to the oral allergy syndrome (manifested primarily by severe oropharyngeal itching, with or without facial angioedema) caused by eating certain plant-derived foods. Such cross-reaction is due to the presence of homologous proteins in pollens and foods.

Respiratory: Upper airway obstruction from angioedema of the tongue, oropharynx or larynx; bronchospasm, chest tightness, cough, wheezing; rhinitis, sneezing, congestion, rhinorrhea. Cutaneous: Diffuse erythema, flushing, urticaria, pruritus, angioedema. 

The main allergen of all grasses is profilin, a pan-allergen found in many plants, pollens and fruits. Grasssensitive individuals can sometimes react to numerous plant-derived foods.

surgery and catheterization. Medical and dental staff may also develop occupational allergy through use of latex gloves. Foreign proteins Examples of foreign proteins that can cause anaphylaxis are insulin, seminal proteins and horse-derived antitoxins, the latter of which is used to neutralize venom in snake bites.

Typical allergen cross-reactivity associations are: • Birch pollen: apple, raw potato, carrot, celery and hazelnut • Mugwort pollen: celery, apple, peanut and kiwifruit • Ragweed pollen: melon (watermelon, cantaloupe, honeydew) and banana • Latex: banana, avocado, kiwifruit, chestnut and papaya

Elective medical procedures Allergen immunotherapy 2. Cytoxic and Immune Complex/Complement– Mediated Reactions Whole blood, serum, plasma, fractionated serum products, immunoglobulins, dextran  Anaphylactic responses have been observed after administration of whole blood or blood products, including serum, plasma, fractionated serum products and immunoglobulins. One mechanism underlying these reactions is complement activation resulting from formation of antigen-antibody reactions on the red blood cell surface or from immune complexes. Active by-products of complement activation (anaphylatoxins C3a, C4a and C5a) cause mast cell and basophil degranulation, mediator release and generation and anaphylaxis. In addition, complement products may directly induce vascular permeability and smooth muscle contraction.

Food-associated, exercise-induced anaphylaxis may occur when individuals exercise within 2-4 hours after ingesting a specific food. Affected individuals may be able to exercise without symptoms as long as the incriminated food is not consumed before exercise. Conversely, the patient can ingest the incriminated food with impunity as long as no exercise occurs for several hours after eating it. Antibiotics and other drugs Penicillin, cephalosporin, and sulphonamide antibiotics Penicillin is the most common cause of anaphylaxis. Penicillin and other antibiotics are haptens, molecules which are too small to elicit an immune response but capable of binding to serum proteins and producing IgE antibodies.

Individuals with IgA deficiency may become sensitized to IgA found in blood products. Those selective IgAdeficient subjects (1 in 500 of the general population) can develop anaphylaxis when administered blood products because of their anti-IgA antibodies (probably IgE-anti-IgA).

Serious reactions to penicillin occur about twice as frequently following intramuscular or intravenous administration compared to oral administration, although oral administration may also induce anaphylaxis. Neither atopy nor a genetic history of allergic rhinitis, asthma or eczema is a risk factor for development of penicillin allergy.

Cytotoxic reactions can also cause anaphylaxis via complement activation. Raising antibodies (IgG and IgM) against red blood cells, as occurs in a mismatched blood transfusion reaction, activates complement. This reaction causes agglutination and lysis of red blood cells and perturbation of mast cells resulting in anaphylaxis.

Muscle relaxants Muscle relaxants, such as suxamethonium, alcuronium, vecuronium, pancuronium and atracurium, are widely used in general anesthesia and account for 70-80% of all allergic reactions occurring during general anesthesia. Reactions are caused by an immediate IgE-mediated hypersensitivity reaction.

3. Non-Immunologic Mast Cell Activators Radiocontrast media, low-molecular weight chemicals Mast cells may degranulate when exposed to low-molecular-weight chemicals. Hyperosmolar iodinated contrast media may cause mast cell degranulation by activation of the complement and coagulation systems. Although less common, these reactions can also occur with newer contrast media agents.

Insects Venoms from hymenopterans (bees, wasps, yellow-jackets, hornets, fire ants) contain enzymes such as phospholipases and hyaluronidases and other proteins that can elicit an IgE antibody response.

Narcotics Narcotics are mast cell activators capable of causing elevated plasma histamine levels and non-allergic anaphylaxis. These reactions are most commonly observed by anesthesiologists.

Latex Latex is a milky sap produced by the rubber tree Hevea brasiliensis. Latex-related allergic reactions can complicate medical procedures, such as internal examinations, 

4. Modulators of Arachidonic Acid Metabolism Aspirin, ibuprofen, indomethacin and other non-steroidal anti-inflammatory agents (NSAIDs) IgE antibodies against aspirin and other NSAIDs have not been identified. Affected individuals can tolerate choline or sodium salicylates, substances structurally related to aspirin but lacking an acetyl group.

or stridor that does not respond immediately to supplemental oxygen and epinephrine. C = Circulation  Minimize or eliminate continued exposure to the causative agent by discontinuing the infusion, as with radio-contrast media, or by placing a venous tourniquet proximal to the site of injection or insect sting. Assess adequacy of perfusion by measuring pulse rate, blood pressure and capillary refill time and assessing mentation. Establish IV access with large bore (16 to 18 gauge) catheter and administer an isotonic solution such as normal saline. A second IV may be established as necessary. If a vasopressor such as dopamine becomes necessary, the patient should be immediately transferred to an intensive care setting.

5. Sulfiting Agents Sodium and potassium sulfites, bisulfites, metabisulfites and gaseous sulfur dioxides These agents are added to foods, drinks and some medications as preservatives or to prevent discoloration. In the acid environment of the stomach sulfites are converted to SO2 and H2SO3, which are then inhaled. They can then produce asthma and non-allergic hypersensitivity reactions in susceptible individuals.

The ABC mnemonic can also be used for the pharmacologic management of anaphylaxis: A = Adrenalin = epinephrine Epinephrine is the drug of choice for anaphylaxis. It stimulates both beta-and alpha-adrenergic receptors and inhibits further mediator release from mast cells and basophils. The usual dosage of epinephrine for adults is 0.3-0.5 mg of a 1:1000 w/v solution given intramuscularly every 10-20 minutes or as necessary. The dose for children is 0.01 mg/kg to a maximum of 0.3 mg intramuscularly every 5-30 minutes as necessary. Lower doses, e.g. 0.1 mg to 0.2 mg administered intramuscularly as necessary, are usually adequate to treat mild anaphylaxis associated with skin testing or immunotherapy. Epinephrine should be given early in the course of the reaction and the dose titrated to the clinical response. For a severe hypotension, 1 cc of a 1:10,000 w/v dilution of epinephrine given slowly intravenously is indicated. The patient’s response determines the rate of infusion.

6. Idiopathic Causes Exercise Like food-induced anaphylaxis, exercise alone can cause anaphylaxis. In particular exercise-induced anaphylaxis can occur during the pollinating season of plants to which the individual is allergic. Catamenial anaphylaxis Catamenial anaphylaxis is a syndrome of hypersensitivity induced by endogenous progesterone secretion. Patients affected by this condition may exhibit a cyclic pattern of attacks that occur during the premenstrual part of the cycle. Idiopathic anaphylaxis Flushing, tachycardia, angioedema, upper airway obstruction, urticaria and other signs and symptoms of anaphylaxis can occur without a recognizable cause. Diagnosis is based primarily on the patient’s history and an exhaustive search for causative factors. Serum tryptase and urinary histamine levels may be useful indicators.

B = Benadryl (diphenhydramine)  Antihistamines are not useful for the initial management of anaphylaxis but may be helpful once the patient stabilizes. Diphenhydramine may be administered intravenously, intramuscularly or orally. Cimetidine offers the theoretical benefit of reducing both histamineinduced cardiac arrhythmias, which are mediated via H2 receptors, and anaphylaxis-associated vasodilation, mediated by H1 and H2 receptors. Cimetidine, up to 300 mg every 6 to 8 hours, may be administered orally or slowly IV. Doses must be adjusted for children.

Emergency Treatment of Anaphylaxis A = Airway Ensure and establish a patient airway by repositioning the head and neck and/or performing endotracheal intubation or emergency cricothyroidotomy. Place the patient in a supine position and elevate the lower extremities. Patients in severe respiratory distress may be more comfortable in a sitting position. B = Breathing Assess adequacy of ventilation and provide the patient with sufficient oxygen to maintain adequate mentation and an oxygen saturation of at least 91%, as determined by pulse oximetry. Treat bronchospasm as necessary. Equipment for endotracheal intubation should be available for immediate use in event of respiratory failure and is indicated for poor mentation, respiratory failure

C = Corticosteroids Corticosteroids do not benefit acute anaphylaxis but may prevent relapse or protracted anaphylaxis. Hydrocortisone (100 to 200 mg) or its equivalent can be administered every 6 to 8 hours for the first 24 hours. Doses must be adjusted for children. 

Prevention of Anaphylaxis

If a reaction occurs during a medical procedure it is important to consider a possible reaction to latex or medication used during anesthesia.

Agents causing anaphylaxis should be identified when possible and avoided. Patients should be instructed in how to minimize exposure.

Epidemiology

Beta-adrenergic antagonists, including those used to treat glaucoma, may exacerbate anaphylaxis and should be avoided when possible.

Food-induced anaphylaxis The prevalence of food-induced anaphylaxis varies with dietary habits of a region. A United States survey reported an annual occurrence of 10.8 cases per 100,000 person years. Extrapolating this data to the entire population of the United States suggests approximately 29,000 food-anaphylactic episodes each year, resulting in approximately 2,000 hospitalizations and 150 deaths. Similar findings have been reported in the United Kingdom and France. Food allergy is reported to cause over one-half of all severe anaphylactic episodes in Italian children treated in emergency departments and one-third to one-half of anaphylaxis cases treated in emergency departments in North America, Europe and Australia. Food allergy is thought to be less common in non-Westernized countries. A study in Denmark reported a prevalence of 3.2 cases of food anaphylaxis per 100,000 inhabitants per year with a fatality rate of approximately 5%.

Epinephrine is the most effective treatment for anaphylaxis. Individuals at high risk for anaphylaxis should be issued epinephrine syringes for self-administration and instructed in their use. Intramuscular injection is recommended since it results in prompt elevation of plasma concentrations and has prompt physiological effects. Subcutaneous injection results in delayed epinephrine absorption. Patients must be alerted to clinical signs of impending anaphylaxis and encouraged to carry epinephrine syringes at all times and use them at the earliest onset of symptoms. Unused syringes should be replaced immediately when they reach their use-by/expiration date, as epinephrine content and bioavailability decreases in proportion to the number of months past the expiration date. Pre-treatment with glucocorticosteroids and H1 and H2 antihistamines is recommended to prevent or reduce the severity of a reaction when it is medically necessary to administer an agent known to cause anaphylaxis, e.g. radio-contrast media.

Risk factors for food anaphylaxis include asthma and previous allergic reactions to the causative food. Food-associated, exercise-induced anaphylaxis

This condition is more common in females, and over 60% of cases occur in individuals less than 30 years of age. Patients sometimes have a history of reacting to a particular food when younger and usually have positive skin tests to the food provoking anaphylaxis.

Differential Diagnosis The differential diagnosis for anaphylaxis includes: • respiratory difficulty or circulatory collapse, including vasovagal reactions • globus hystericus • status asthmaticus • foreign body aspiration • pulmonary embolism • epiglottitis • myocardial infarction • carcinoid syndrome • hereditary angioedema • pheochromocytoma • hypoglycemia • seizures • medication overdose • cold urticaria • cholinergic urticaria • sulfite or monosodium glutamate ingestion

Anaphylaxis caused by radiocontrast media Mild adverse reactions are experienced by approximately 5% of subjects receiving radiocontrast media. Estimates in the United States suggest that severe systemic reactions occur in 1 in 1,000 exposures with death in 1 in 10,000-40,000 exposures. Penicillin-induced anaphylaxis Systemic hypersensitivity reactions occur in 1-5% of courses of penicillin therapy, and 0.2% of these cases are associated with anaphylactic shock. Mortality occurs in 0.02% of the cases. If a patient has a strongly positive skin test or circulating IgE antibody to penicillin, there is a 50-60% risk of an anaphylactic reaction upon subsequent challenge. In patients with a case history suggestive of penicillin allergy and negative skin tests, the risk of anaphylaxis is very low. Atopy and mold sensitivity are not risk factors for development of penicillin allergy.

Upper airway obstruction, bronchospasm, abdominal cramps, pruritus, urticaria and angioedema are absent in vasovagal reactions. Pallor, syncope, diaphoresis and nausea usually indicate a vasovagal reaction but may occur in either condition. 

Muscle relaxants Anaphylaxis to muscle relaxants occurs in approximately 1 in 4,500 of general anesthesia cases, with fatalities occurring in 6% of these cases. Risk factors are female sex (80% of cases). Atopy is not a risk factor, but previous drug allergy may be a risk factor. In patients with a history of anaphylaxis, skin tests to different muscle relaxants may be helpful, and if the result is positive, the muscle relaxant should not be used. A negative result provides evidence that the muscle relaxant can probably be administered safely. Insect venom anaphylaxis Studies from Australia, France, Switzerland and the United States suggest incidences of systemic reactions to Hymenoptera stings ranging from 0.4% to 4% of the population. In the United States at least 40 deaths occur each year as a result of Hymenoptera stings.

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WAO Secretariat 555 East Wells Street, Suite 1100 Milwaukee, WI 53202, USA Tel: +1 414 276 1791 Fax: +1 414 276 3449 email: [email protected] Web site: www.worldallergy.org