Anaphylaxis is a frequently unexpected and potentially life-threatening clinical syndrome. The term anaphylaxis means the opposite of phylaxis or protection. Symptoms may vary from mild generalized pruritus to airway obstruction, hypotension, and death brought on by the release of potent chemical mediators from mast cells and basophils through either allergic or nonallergic mechanisms. Rapid recognition, diagnosis, and early treatment of even mild symptoms is crucial in avoiding deaths and in lessening morbidity.
The term anaphylaxis was coined by Portier and Richet in 1902. ' They observed unexpected fatal acute reactions in dogs previously immunized with sea anemone toxin after a second injection of a tiny amount of the same toxin a few weeks later. The first recognized human cases of fatal anaphylaxis occurred as a result of horse serum therapy used in a variety of illnesses in the preantibiotic era. Heterologous serum was replaced by penicillin as the principal cause of anaphylaxis after World War II. With the growing array of new pharmaceutical agents has come a longer list of potential causes of anaphylaxis.
Anaphylactic reactions often occur within seconds or minutes after exposure to an antigen. The most severe reactions usually begin 5 to 10 minutes after exposure although Stark and Sullivan noted that many severe reactions did not occur until several hours after exposure.2 Although ingestion and injection are the most common routes of exposure, highly sensitive patients may react through skin contact or inhalation. Reactions tend to be more severe when antigen exposure is parenteral. Generally, two or more organ systems are involved including the skin, respiratory tract, gastrointestinal tract, and cardiovascular system.
Cutaneous symptoms include a feeling of warmth, itching, flushing, urticaria, and angioedema. Nausea, vomiting, diarrhea (occasionally bloody), and abdominal cramps may occur as a result of gastrointestinal tract involvement in anaphylaxis. The respiratory tract is often the site of severe or fatal anaphylactic symptoms. Throat constriction may be mild but may progress to hoarseness and stridor secondary to laryngeal edema causing life-threatening upper airway obstruction. Chest tightness, wheezing, and dyspnea may occur as a result of bronchospasm. Nasal and ocular symptoms such as rhinorrhea, nasal congestion, itchy and watery eyes, and sneezing often occur in anaphylaxis secondary to allergen extract overdosage.
Cardiovascular symptoms are often severe and refractory and include hypotension, arrhythmias, and shock. Whether the heart itself is a target organ remains a matter of controversy.3 Some patients describe a feeling of impending doom. Deaths tend to occur more frequently in older patients with underlying cardiovascular disease because of their reduced capacity to withstand the profound physiologic changes induced by anaphylaxis. Women may experience uterine cramps as a result of anaphylaxis.
Mast Cell Mediators Involved in Anaphylaxis
Anaphylaxis may occur through both immunologie and nonimmunologic mechanisms. In classic anaphy!axis, foreign antigen interacts with antigen-specific IgE molecules attached to receptors on the surface of mast cells and basophils in a previously sensitized individual. The bridging of adjacent IgE molecules by antigen triggers a sequence of intracellular events culminating in degranutation and the release of preformed chemical mediators including histamine and chemotactic factors (Table 1 ).
Histamine is a potent substance causing vasodilation, increased vascular permeability, and bronchial smooth muscle constriction. Degranulation of mast cells stimulates the production of lipid mediators such as leukotrienes, prostaglandins, and platelet activating factor. These substances are capable of exerting the profound biochemical and physiological effects of anaphylaxis although their individual roles are not yet clearly defined. A biphasic and protracted pattern of anaphylaxis with symptoms lasting up to 32 hours was described in some patients experiencing severe anaphylaxis.2 Evidence of inflammatory processes is apparent in these more severe cases.
Examples of non-IgE immunologie anaphylaxis include complement activation by immune complexes that generate the potent anaphylatoxins C3a and C5a, which directly trigger mast cell and basophil degranulation. Human gamma globulin and other IgA-containing blood products given to IgA-deficient individuals, who have anti-IgA antibodies, may trigger complement-mediated anaphylaxis.
Nonimmunologic anaphylaxis, often referred to as "anaphylactoid," is simply anaphylaxis where an IgE-dependent or other immunologie mechanism cannot be shown. Radio contrast media allergy is a prime example of this type of reaction. Direct activation of the mast cell occurs in these instances in an unpredictable fashion.
Foods Causing Anaphylaxis
ETIOLOGY AND EPIDEMIOLOGY
Proteins, polysaccharides, and haptens are all implicated in the etiology of anaphylaxis. Anaphylaxis occurs in both atopies and nonatopics. Most studies have generally found an equal or slightly higher incidence of anaphylaxis in atopic versus nonatopic individuals. The true overall incidence remains unknown. Orange and Donsky reported the incidence of fetal anaphylaxis to be 0.4 per 1 million persons per year in Ontario based on seven reported cases in 3 years.4 This is likely to be an underestimate because the disease is not reportable. The incidence in children is not known, and no age group is spared.
Infants less than 1 year old can experience lifethreatening anaphylaxis often as a result of hypersensitivity to basic foods such as milk, eggs, and soybean. These same infants often outgrow their sensitivity by the age of 3.5 Food-induced anaphylaxis is responsible for many severe reactions and some deaths in older children and adolescents and appears to be more severe in asthmatics.6 The most important cause of deaths in this report was peanut. Other foods causing anaphylaxis include fish, shellfish, other legumes, seeds, eggs, milk, and nuts. Candy containing cottonseed as an unlisted ingrethent may cause severe anaphylaxis.7 Cottonseed may also be found in foods such as cakes, breads, and doughnuts. Vegetables, fruits, and grains are much less common causes of anaphylaxis. A more complete listing of foods responsible for anaphylaxis can be found in Table 2, Measles-mumps-rubella (MMR) vaccine containing minute quantities of egg protein may induce anaphylaxis in a highly egg-allergic individual.
Prick skin testing or in vitro tests for serum-specific IgE, such as RAST radioallergosorbent test), can identify sensitive individuals with a high degree of accuracy. Intradermal testing with foods not only causes nonspecific irritant reactions but has also been associated with serious and fetal anaphylactic reactions.8 Prick and intradermal skin testing with MMR or measles vaccine to determine the presence of hypersensitivity followed by a modified desensitization protocol in children with positive reactions allowed successful administration of vaccine to eggallergic children in one report.9
Reactions to stinging insects including wasps, honey bees, yellow jackets, hornets, and fire ants are an important cause of systemic allergic reactions in children. The frequency of stinging insect allergy ranges from .8% in children to 3.3% in adults.10,11 The risk of such reactions is increased in children as a result of increased exposure to stings. The severity of reactions and the death rate are much greater in adults. Children under 16 years of age experiencing cutaneous reactions such as urticaria and angioedema alone do not have an increased risk of developing more severe life-threatening type reactions in the future.12 The likelihood of subsequent systemic reactions in these children is approximately 10% to 20% versus 50% to 60% in comparable groups of adults.13 Children and young adults also are more likely to outgrow their sensitivity than adults.14 Deaths from stinging insects are more likely in older adults with underlying cardiovascular disease than in children and healthy young adults. Venom skin testing and RAST are invaluable in determining the presence of venom-specific IgE and the degree of sensitivity. Skin testing is considered to be more sensitive.
Many different drugs are capable of causing anaphylaxis. Since its introduction in the 1940s, penicillin and its derivatives have been responsible for more deaths due to anaphylaxis than any other single cause. Several hundred deaths have been estimated to occur each year in the United States from penicillin and its semisynthetic derivatives.
Deaths are more common when the medication is given parenterally rather than orally. Penicillin G skin testing by a trained allergist using freshly diluted penicillin G, penicilloyl polytysine (Pre-pen, Kremers Urban, Milwaukee, Wisconsin), and minor determinant mixture (degradation products of penicillin) by both prick and intradermal methods can be used to predict serious potential reactions in patients giving a history of penicillin allergy.15 THhte latter is not yet commercially available. Penicillin desensitization can be undertaken in allergic individuals. This will allow successful administration of the drug in serious infections. An estimate of 3% to 7% of patients with a documented history of penicillin allergy and positive skin tests will react to cephalosporins.16 Patients allergic to penicillin should therefore not routinely be given cephalosporins.
Many other drugs and therapeutic agents have been shown to cause anaphylaxis, usually through an IgE-dependent mechanism. They include sulfonamides, tetracycline, nitrofurantoin, cytarabine, cyclosporin, aspirin (non-IgE), insulin, horse serum, chymopapain, psyllium, methylprednisolone, dextran, vancomycin, and many others (Table 3).
Other causes of anaphylaxis include skin testing and immunotherapy with allergen extracts in individuals with allergic disorders such as rhinitis and asthma. Anaphylaxis is rare in properly performed skin testing. Prick, puncture, or scratch testing should precede intracutaneous testing to avoid systemic reactions. In inhalant allergen immunotherapy (eg, pollen, mold, mite, dust, and animal dander), accidental overdose, inadvertent intravascular injection, administration of extract to actively wheezing asthmatics, and prolonged interruption of the schedule without adequate reduction in dose are all potential causes of iatrogenic anaphylaxis.
Exercise-induced anaphylaxis is a distinct form of anaphylaxis often seen in well-trained athletes. These patients may experience a sensation of warmth, flushing, urticaria, angioedema, wheezing, dyspnea, and even vascular collapse during exercise.17 Some patients with this disorder have noted these symptoms only when certain foods such as shellfish, celery, and peaches are ingested before exercise.18
Ethylene oxide used extensively in plastic tubing sterilization may act as a hapten and cause anaphylaxis in sensitized individuals.19 Rubber products such as latex gloves and condoms have recently been demonstrated to cause anaphylaxis.20
The reason for the marked increase in reported cases of latex-induced anaphylaxis is not clear, although a change in the manufacturing methods may be responsible for the increased antigenicity of the product. Latex-cuffed enema tips used in barium enemas as well as bladder catheters have also been reported to trigger anaphylaxis. Reactions may occur during surgical procedures and have been associated with fatalities. Patients who are at increased risk include individuals with a history of myelomeningocele, those who have had recurrent bladder catheterizations, medical personnel and individuals who have had urticarial reactions or pruritus from rubber gloves, blowing up balloons or exposure to other latex products.
Sulfiting agents used to preserve foods and alcoholic beverages infrequently have been shown to be a cause of anaphylaxis.21 Anaphylaxis to environmental allergens such as pollen and mold has been described in individuals exposed to these allergens through minor abrasions in the skin occurring while riding an alpine slide or through inhalation.22·23 Other infrequent causes of anaphytaxis include human seminal plasma, hormones (eg, progesterone and ACTH), and enzymes (eg, chymopapain and streptokinase).
A large number of patients have no satisfactory explanation for the etiology of their bouts of anaphylaxis and are labeled as having idiopathic anaphylaxis.24 This is far more common in adults than in children.
The diagnosis of anaphylaxis generally does not require laboratory support. In instances where the patient has not developed the more typical symptoms and there is doubt as to whether the patient has experienced anaphylaxis, serum can be assayed for tryptase (available from the Medical College of Virginia, Richmond, Virginia) within the first 4 hours after clinical symptoms have begun. An elevated level of tryptase confirms that anaphylaxis has occurred.
The signs and symptoms as well as the clinical setting are usually sufficient to distinguish anaphylaxis from other acute syndromes. Vasovagal reactions may result in syncope and hypotension. The presence of bradycardia, pallor, diaphoresis, and lack of cutaneous or respiratory symptoms usually suffices to distinguish this from anaphylaxis. Scombroid poisoning of tuna, bluefish, and mackerel can give rise to acute allergic symptoms indistinguishable from anaphylaxis because oif the presence of very high levels of histamine due to improper handling. Aged cheeses can result in a similar clinical picture.
Hyperventilation, cardiac or septic shock, adult respiratory distress syndrome, cold'induced urticaria, and hereditary angioneurotic edema may occasionally be confused with the diagnosis of anaphylaxis.
TREATMENT OF ANAPHYLAXIS
The treatment of anaphylaxis depends on the early recognition of symptoms and signs described earlier and prompt reversal of respiratory and cardiovascular compii' cations that often accompany anaphylaxis. It is imperative to establish the cause and severity of the reaction (eg, medication, insect sting, food, and exercise). If a medication is suspected as the cause, its use should be terminated immediately. Possible preexisting medical problems such as cardiac or pulmonary disease should be ascertained from relatives or the patient, if possible.
Table 4 lists guidelines for managing acute anaphylaxis. Epinephrine is the drug of choice in all cases. The proper dose administered quickly is effective in preventing or reversing cardiovascular and upper and lower airway respiratory tract complications. Epinephrine relaxes bronchial smooth muscle and supports blood pressure. Usually .30 to .40 mL of aqueous epinephrine 1:1000 injected subcutaneously in the older child or adult or .01 mL/kg to a maximum of .30 mL in younger children is effective. The signs and symptoms of anaphylaxis will generally abate within a few minutes after a single injection. A second epinephrine injection should be given into the site of an insect sting, drug injection, or allergen injection to retard systemic absorption of the antigen. A lightly placed tourniquet proximal to the site of the offending injection or sting will also slow down absorption of the antigen. Epinephrine may be administered every 10 to 15 minutes as needed up to a total of three doses until symptoms resolve. In severe anaphylaxis when vascular access has not yet been obtained, .10 mL/kg of 1:10 000 epinephrine (children) diluted in 5 mL of saline can be given via a long catheter into an endotracheal tube.25 Hyperventilation will assist in rapid absorption.
Causes of Anaphylaxis
In severe cases of hypotension, volume expansion with albumin or normal saline should be instituted through a large bore catheter. Central venous pressure should be monitored to ensure adequacy of therapy and to guard against fluid overload. Children should receive up to 30 mL/kg of fluid replacement in the first hour. If hypotension is profound and unresponsive, epinephrine can be diluted 1:10 and given intravenously over 5 minutes. Vasopressors such as dopamine, which spares renal blood flow, or norepinephrine may be necessary in refractory hypotension even with adequate volume replacement. Norepinephrine bitanrate 2 mg in 500 mL of saline or glucose solution can be administered intravenously and titrated to maintain systolic blood pressure at the desired level. Dopamine 200 mg in 250 mL can also be titrated to maintain adequate systolic pressure (2 to 25 µ/kgminute).
Management of Acute Anaphylaxls
Although not used as commonly in children and adolescents, beta-blockers may counteract the effectiveness of epinephrine.26 Patients may not respond or even worsen as a result of unopposed alpha adrenergic stimulation. The addition of nebulized beta-2 selective adrenergic drugs, glucagon 1 to 5 mg intravenously, or nebulized atropine (.05 to .075 mg/kg every 4 hours) should be considered in such instances.27
If bronchospasm persists, aminophylline can be added with a loading dose of 5 to 6 mg/kg over 30 minutes followed by an infusion of .5 to 1 mg/kg/hour in children. Late reactions can occur in severe anaphy!axis from any cause. To treat or prevent this complication, hydrocortisone sodium succinate or equivalent 4 to 8 mg/kg intravenously every 6 hours may be given. Antihistamine therapy with diphenhydramine 1 to 2 mg/kg intramuscularly or intravenously every 4 to 6 hours to a maximum of 75 mg may help pruritus, flushing, and urticaria but must not be used as a primary therapeutic agent. H2 blocking agents such as ranitidine 12.5 to 50 mg intravenously every 6 to 8 hours may be effective in more severe cases. Supportive measures should also include oxygen by mask or nasal cannula at 4 L per minute.
It is important to maintain a patent airway by extending the neck to keep the airway open and to use the Trendelenburg position if blood pressure fells. Vital signs should be monitored frequently and heart and lung sounds carefully evaluated for resolution of signs. Should hypotension occur, urinary output should be measured to evaluate possible renal failure.
Equipment should be available to intubate if necessary or even perform cricothyrotomy. Patients who experience severe anaphylaxis should be observed for at least 4 to 8 hours or sometimes longer. Those with milder episodes that resolve promptly can be discharged sooner.
PREVENTION OF ANAPHYLAXIS
It is important that the cause of an anaphylactic reaction be determined in order to plan for the prevention of future episodes. Patients with known sensitivity should avoid exposure and ingestion, if possible, of substances known to cause anaphylaxis. Immediate hypersensitivity skin testing for foods, stinging insect venoms, vaccines, heterologous serum, and a few therapeutic agents (penicillin, insulin, chymopapain, and streptokinase) has proven to be very effective in identifying allergic individuals. Although generally quite safe when properly performed, skin testing has on rare occasions caused serious reactions and fatalities and should therefore only be performed by a trained allergist with the necessary equipment to treat anaphylaxis. Testing for penicillin or venom hypersensitivity should be delayed for 4 weeks because of the possibility of false-negative results during the refractory period following anaphylaxis. Venom-sensitive patients should avoid insectinfested areas, and if skin tests are positive, venom immunotherapy should be instituted. Desensitization for Hymenoptera sensitivity is successful in preventing anaphylaxis in 98% or more of patients.28
Medical identification bracelets should be worn at all times to warn others of known allergies in the wearer (Medic-Alert, Turlock, California). Patients and families should be taught to recognize the symptoms and signs of an allergic reaction and how to administer epinephrine in the form of an EpiPen (Center Labs, Port Washington, New York) or the Ana-Kit/Ana-Guard (Hollister Stier, Spokane, Washington). The EpiPen (.3 mg of aqueous epinephrine) is an easy-to-use automatic preloaded syringe for use in adults and children weighing 25 kg or more. In children 15 to 25 kg, the EpiPen Jr (.15 mg epinephrine) is recommended, and in smaller children, a 26or 27-gauge TB syringe and individual vials of 1:1000 aqueous epinephrine should be provided to parents with careful instructions on subcutaneous administration. The EpiPen has the advantage of ease of administration, but the Ana-Kit contains two doses of epinephrine. Parents of children with a history of food and stinging insect allergy should provide epinephrine kits to schools and camps with instructions on when and how to administer them. Because beta-blocking drugs antagonize the effect of epinephrine, patients with either a history of anaphylaxis or those receiving allergen or venom immunotherapy should avoid this class of medications.
Physicians should carefully inquire about the history of drug allergy before medication is given and if possible, an oral rather than the parenteral form of the medication should be given. Previous allergic reactions should be prominently displayed on the patient's medical record, and alternative medication should be given if there is doubt about a drug allergy. The physician should be aware of potential cross reactions between drugs such as between penicillins and cephalosporins. Aspirin-sensitive patients should avoid all nonsteroidal anti- inflammatory agents. Telling patients what drug is being given may remind them of a past allergic reaction.
In patients who are at increased risk for having latex allergy or in those who have had allergic reactions to latex in the past, measures should be taken to avoid anaphylaxis. Vinyl rather than latex gloves should be used for medical, dental, and surgical procedures. Avoidance of latex catheters, balloons, and dental dams is also recommended. Patients with suspected latex allergy should be evaluated by an allergy specialist prior to any surgical or dental procedures and should wear a medical identification bracelet.
After any injection of medication or allergen extract, a patient should wait at least 20 to 30 minutes in the office or hospital under observation. The physician should always have appropriate medication and equipment available in the office to treat anaphylaxis.
Patients and parents of young children with known allergies to food should be extremely careful. All labels should be scrutinized on prepared foods for possible allergens. Patients and parents should inquire from waiters and cooks in restaurants about the potential presence of allergens in meals. Legumes such as peanuts, peas, and soybeans, to which some patients are extremely sensitive, can be hidden in food preparations with or without obvious identification of these substances. This has become an increasing concern with the growing use of peanut products in prepared and restaurant foods. Occasional reactions may occur when foods are contaminated during preparation or cooking with other potentially allergenic foods. In extreme cases of peanut sensitivity, the mere presence of peanuts or peanut butter in the same school classroom may lead to instances of antigen contact or inhalation and possibly result in anaphylaxis. Special arrangements with schools and daycare centers may need to be made to avoid problems.
Treatment Schedule for Prevention of Radio Contrast Media Reactions
Patients with exercise-induced anaphylaxis should not exercise within at least 4 to 6 hours after eating. At the first sign of itching, exercise should be terminated. These individuals should never exercise alone and should be prepared to immediately administer epinephrine if anaphylaxis occurs. Aspirin and nonsteroidal anti- inflammatory drugs also should be avoided in these patients.
Patients with anaphylactic reactions to contrast media may require further studies with similar agents. The risk of repeat reactions ranges from 17% to 60%.z9 Pretreatment with corticosteroids, antihistamines, and ephedrine reduces the possibility of reactions to approximately 4% in high-risk patients undergoing intravenously administered radio contrast media.30 Suggested pretreatment medications are outlined in Table 5.
Patients must be informed of the medical necessity of the procedure and the possibility of reactions. The H2 receptor antagonist cimetidine given intravenously before use of radio contrast media may increase the risk of anaphylaxis.31 The recent introduction of nonionic contrast media should greatly lessen the risk of reactions in the future.
Prevention of anaphylaxis in children requires diligence by both the patients and their parents as well as their physician. Identification of the etiology of the reaction by both a careful history and, in some instances, allergy testing is essential. A favorable outcome depends on the success of subsequent avoidance measures. Prompt recognition and treatment of anaphylaxis will help reduce both morbidity and mortality.
The authors thank Mary Prendergast and Janet Couturier for their secretarial assistance in preparing this manuscript.
1. Portier P, Richet C. De l'action anaphylactique de certain venins. CR Soc Bid (Para). 190Z;54:170.
2. Start: BJ, Sullivan Tj, Biphasic and protracted anaphylaxis. 1 Allergy Clin Jmmunol. 1986:78:76-83.
3. Wasserman Sl. The heart in anaphylaxis. J Allergy Clin Immune!. 1 986; 7 7:663-665.
4. Orange RP, Donsky GJ. Anaphylaxis. in: Middleton E, Reed CE, Ellis EF, eds. Allergy: Principles and Procace. St Louis, Mo: CV Mosby Co; 1978:564.
5. Bock SA. The natural history of food sensitivity. J Allergy Clin Immunol. 1982; 69:173-177.
6. Yunginger JW, Sweeney KG, Stumer WQ, et al. Fatal food-induced anaphylaxis. MMA. 1988;260: 1450- 1452.
7. Atkins FM, Wilson M, Bock SA. Cottonseed hypersensitivity. New concerns over an ol;d problem. J Aliergy Clin Immunol. 1988;82: 242-250.
8. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotrierapy (IT) and skin testing (ST). ] Allergy CIm Immunol. 1987:79:660-677.
9. Herman Jj, Radin R, Schneiderman R. Allergie reactions to measles (rubeola) vaccine in patients hypersensitive tu egg protein. J Rediatr. 1983; 102: 196:; 199.
10. Settipane GA, Goyd GK. Prevalence of bee sting allergy in 4.992 boy scouts. Acta Allergologi. 1970:25:286-291.
11. Golden DBK. Epidemiology of allergy to insect venoms and stings. Allergy Prue. 1989;10;103-107.
12. Schubetth KC, Lichtenstein LM, Kagey-Sobotka A, SMo M, Kwiterovich RA, Valentine MD. Epidemiologie study of insect alletgy in children. II. Effect of accidental stings in allergic children. J Pediatr, 1983; 102:361 -365.
13. Valentine MD, Golden DBK. Diagnosis of insect allergy. In: Levine Ml. Lockey Vf, eds. Monograph on insect Allergj. 2nd ed. Pittsburgh, Pa: American Academy of Allergy and Immunology; 1986:39.
14.; Savliwala MN, Reisman RE. Studies of the natural history of stinging insect allergy: long-term follow-up of patients without immunotherapy. J Allergy Clin Immunol. 1987:80:741-745.
15. Mendelson LM, Ressler C, Rosen JP, Selcow JE. Routine elective penicillin allergy skin testing in children and adolescents: study of sensiruatlon. J Allergy Clin Immunol. 1984:73:76-81.
16. Saxon A. Immediate hypersensitivity reactions to beta-laciam antibiotics. Ann Interm Med. 1987; 107:204-2 15.
17. Sheffer AL, Soter NA, McFadden ER Jr, Austen KF. Exercise- induced anaphylaxis: a distinct form of physical allergy. J Allergy Clin Imtnunol. 1983;71:311-316.
18. Kidd JM HI, Cohen SH, Soeman AJ, Fink JN. rood-dependent exercise-induced anaphylaxis, J Allergy Clin Immunol. 1983;71:407-411.
19. Leitman SF, Boltansky H, Alter HJ, Pearson FC, Kaliner MA. Allergic reactions in healthy plateletphereeis donors caused by sensitiration to ethylene oxide gas. N Engl JMed. 1986;3 15:1192-1196.
20. Slater J. Rubber anaphylaxis. N Engl; Med. 1989;320:1126-1130.
21. Sokol WN, Hydick IB. Nasal congestion, urticaria and angioedema caused by an IgE-mediated reaction to sodium metabisulfite. Ann Allergy. 1990;65:233-238.
22. Spitalny KC, Famham JE, Witherell LE, et al. Alpine slide anaphylaxis. N Engl J Med, 1984:310:1034-1037.
23. Broom BC, Fitiriarris R Life-threatening inhalant allergy: typical anaphylaxis induced by inhalational allergen challenge in patients with idiopathic recurrent anaphylaxis. Clin Allergy. 1983; 13: 169-179.
24. Wiggin CA, Dykewici MS, Ffctterson R. ldiopalhic anaphylaxis; a review. Ann Allergy. 1989;62:1-3.
25. Powers KD, Domwitz LG. EndoDacheal administration of emergency medications, South Med J. 1984:77:340-341,346.
26. Toogood J. Beta blocker therapy and the risk of anaphylaxis. Con Med Assoc 1987;136:929-933.
27. Kniker WT. Anaphylaxis in children and adults. In: Blerman CW, Fearlman DS, eds. Allergic Diseases From infancy to Adulthood. Philadelphia, Pa: WB Saunders; 1987:667-677.
28. Hunt KJ, Valentine MD, Sobotka AK, Benton AW, Amodio FJ, Lichtenstein LM. A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med. 197 8;299:157-161.
29. Shehadi WH. Adverse reactions to intravascularly administered contrast media. AJR Am J Roentgenol. 1975;124:145.
30. Greenberger PA, Palteraon R, Radin RC. Two pretreatment regimens for high-risk patients receiving radiographie contrast media. J Allergy Clin Immunol. 1984:74:540543.
31. Greenberger PA. Prophylaxis against repeat contrast media reactions in 857 cases. Arch intern Med. 1985; 1 45: 197 -2 20.
Mast Cell Mediators Involved in Anaphylaxis
Foods Causing Anaphylaxis
Causes of Anaphylaxis
Management of Acute Anaphylaxls
Treatment Schedule for Prevention of Radio Contrast Media Reactions