Anaphylaxis, meaning "without protection," is a systemic, potentially life-threatening hypersensitivity reaction. It occurs abruptly and variably, as a result of an IgE-mediated release of histamine and other mediators from mast cells and basophils in previously sensitized individuals. The severe allergic response is a medical emergency and is estimated to be responsible for more than 500 deaths annually. Anaphylactoid reactions (sometimes called pseudoanaphylaxis) present clinically like anaphylaxis, but their mechanism is not IgE-mediated. Also, unlike a hypersensitivity reaction, they tend to occur following initial exposure to an offending agent by direct toxic effect to cell mediators or indirect activation of the complement cascade.

The number of substances that cause anaphylactic reactions is staggering and continues to expand as new diagnostic and therapeutic agents are developed. Some substances are listed below.

Anaphylactic Reactions

• Antibiotics, particularly penicillin (74% of fatalities; 1 fatality per 7.5 million injections) and cephalosporins (5% to 16% cross-reactivity in penicillin-allergic individuals); much more common when administered parenterally
• Hymenoptera venom (e.g., bees, wasps) and other insect (e.g., fire ants) stings or bites (approximately 40 deaths reported annually in the United States)
• Foods (e.g., nuts, shellfish, egg whites, chamomile tea, berries). Chamomile may have cross-reactivity with ragweed pollen
• Allergen extracts for skin testing and immunotherapy
• Egg-embryo–grown vaccines (MMR, yellow fever, and influenza)
• Blood transfusions, especially in IgA-deficient persons when exposed to multiple transfusions
• Equine antisera (historically used in rabies and tetanus antitoxins, but human sera now used for these immunizations without negative response; equine antisera still used for treatment of botulism, gangrene, and for snake bites); affects 0.4% to 4% of the population
• Topical or inhaled latex particles; includes anaphylaxis secondary to condoms; healthcare workers, children, and rubber-industry workers at particular risk; may have cross-sensitivity with bananas, avocados, and chestnuts as well as dandelion root
• Glycoprotein in seminal fluid—extremely rare reaction reported in sexual partners
• Insulin—now extremely rare given the use of human insulin
• Chymopapain injections for disk herniation; anaphylaxis may occur in individuals sensitized from exposure to papain (Carica papaya, a crude fraction of papaya found in meat tenderizer and used to clarify beer as well as sterilize soft contact lenses)
• Echinacea purpurea pollen—case report of anaphylaxis from high dose echinacea (two times the recommended amount) in a woman with a history of allergy to raw fruits and vegetables; she had had previous exposure to echinacea, but anaphylactoid reactions have also been reported following initial exposure; it is theorized that the immunomodulatory properties of echinaea may exacerbate IgE-mediated reactions
• Thiamine (vitamin B₁)—anaphylaxis reported with parenteral administration for ethanol intoxication; vitamins, like other medicines, can cause either anaphylaxis or anaphylactoid reactions

Anaphylactoid Reactions

• Radiopaque contrast media (some clinical reaction in 4% to 13% of the population; true anaphylactoid reaction 0.25% with hyperosmolar agents; rates with low osmolar agents are 1% to 3% for some clinical reaction and <0.04% for anaphylactoid reaction)
• Aspirin or NSAID use, especially in asthma patients (15% to 20% of asthmatics have some intolerance to aspirin or NSAIDs; those with nasal polyps more likely to have an anaphylactoid reaction)
• Opiate analgesics—most commonly from direct stimulation of histamine release; very rarely IgE mediated, which would be classified as anaphylaxis
• Food coloring (e.g., tartrazine [FD&C yellow dye No. 5])—5% to 30% of those with aspirin or NSAID allergy have cross-sensitivity to tartrazine although clinical significance not entirely clear
• Food preservatives, especially sulfites, bisulfites, and metabisulfites found in beer, wine, shellfish, fresh fruits, and vegetables
• Exercise induced anaphylaxis follows ingestion of certain foods to which a subclinical sensitivity may be present (e.g. celery, shrimp, apples, squid, wheat, hazelnuts, and chicken); tends to occur in athletes; mechanism unclear but may be related to endogenous opioids; atopic personal or family history commonly but not universally associated
• Intravenous induction agents and neuromuscular blockers used during anesthesia (may cause either anaphylactic or anaphylactoid reactions)
• Elevated progesterone levels during menstrual cycle
• Munchausen's anaphylaxis: purposeful self-induction of anaphylactoid reaction (very difficult to diagnose and manage)
• Idiopathic

• Route of administration of the agent (intravenous much more provocative than oral or topical) 
• Frequency and speed of administration (e.g., if immunotherapy is administered too frequently; however, frequent exposure to an allergen followed by a long delay and reexposure can also precipitate anaphylaxis) 
• Atopy—particularly increased risk for anaphylactic reaction from latex, exercise, or radiopaque contrast media
• Asthma—particularly if undertreated and receiving immunotherapy 
• Occupational exposure (e.g., rubber industry) 
• Therapy with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) (see section entitled Complications/Sequelae) 

Symptoms, which may range from very mild to fatal, may appear alone or in combination seconds to minutes after exposure, although a delay of 1 to 24 hours is not unusual. The sooner that symptoms begin following antigen exposure, the more severe they tend to be. Most deaths from anaphylaxis occur within 30 minutes. Skin and respiratory symptoms are the most common, while cardiac and respiratory are the most dangerous.

• Skin: erythema, flushing, pruritus (often the first symptom), urticaria, angioedema, diaphoresis 
• Respiratory system: rhinitis, laryngeal edema, hoarseness, dysphonia, stridor, dyspnea, bronchospasm, chest tightness, wheezing, asphyxia (from edematous obstruction) 
• Cardiovascular system: tachycardia, hypotension, dysrhythmia (PVCs, PACs, atrial fibrillation), hypovolemia, vascular collapse (shock), myocardial infarction 
• Gastrointestinal tract: cramping abdominal pain, nausea, vomiting, diarrhea, incontinence, tenesmus 
• Neurologic system: tingling of face, mouth, palms, and soles; headache, feelings of oppression or impending doom, light headedness, disorientation, syncope, seizures 

A history of exposure to an antigen or an agent that is an identifiable trigger, in the presence of signs and symptoms of anaphylaxis, typically makes the diagnosis obvious. In the absence of such conditions, the following should be considered in the differential diagnosis:

• Acute myocardial infarction 
• Pulmonary embolism 
• Acute asthma attack; sometimes accompanied by idiopathic urticaria
• Epiglottitis
• Tracheal foreign body
• Other causes of shock (hemorrhagic, cardiogenic, septic)
• Hereditary angioedema, particularly if laryngeal edema and abdominal pain are present
• Leukemia or mastocytosis; both cause increased production of histamines; anaphylactic-like reaction can be induced in the presence of opiates
• Seizure disorder; autonomic epilepsy
• Transfusion reaction
• Vasovagal reaction
• Cold urticaria
• Functional disorders (e.g., panic attacks)
• Pheochromocytoma
• Scombroid poisoning from spoiled fish
• "Chinese Restaurant Syndrome" (MSG ingestion)
• Cardiac arrhythmia
• Hyperventilation
• Other causes of flush: carcinoid syndrome, medullary carcinoma of the thyroid, menopause

Physicians must be alert to the most common as well as the most potentially life-threatening organ systems affected by or involved with anaphylaxis. The history of an antigenic exposure is helpful for the diagnosis. The skin is often affected initially, but the progression from urticaria to shock can be rapid (within minutes). Stridor, hypersalivation, hoarseness, and angioedema generally coincide with upper respiratory obstruction, while tachycardia and low blood pressure indicate possible impending shock.

• Complete blood count with differential, looking for signs of hemoconcentration as well as eosinophilia 
• Urinary histamines
• Serum histamine level if less than or equal to 1 hour from the time of exposure 
• Measurement of serum tryptase levels (peaks 1 to 1˝ hours following exposure and remains elevated for 5 hours), allergen-specific IgE, or anaphylatoxins (C3a and C5a) 
• CPK, LDH, AST may be elevated in the case of damage to the myocardium and exercise-induced anaphylaxis
• ECG 

Anaphylaxis

• Allergen binds to IgE antibody on surface membrane of mast cells and basophils
• IgE-allergen interaction leads to release of inflammatory mediators including histamine and bradykinins from granules of mast cells and basophils
• Histamine acts at H₁ and H₂ receptors causing vasodilation, increased vascular permeability, bronchial constriction, and enhanced mucus secretion 
• Prostaglandins and leukotrienes are synthesized by mast cells, further exacerbating bronchial constriction, mucus secretion, and increased vascular permeability 

Anaphylactoid Reaction

• Non-IgE mediated release of bioactive mediators from mast cells and basophils; occurs from direct action of the substance on those cells and via induction of the complement cascade 

Chest X ray may show hyperinflation, atelectasis, and/or pulmonary edema; also, necessary to check endotracheal tube placement if intubation takes place.

• Intradermal skin testing—to detect IgE-mediated reactions 
• Radioallergosorbent test (RAST)—to detect IgE antibodies by measuring serum IgE bound to antigen; not as sensitive as skin testing 
• Additional tests may be required to distinguish from conditions in the differential diagnosis 

The most important principle for treatment of anaphylaxis is to initiate appropriate therapy and supportive care as quickly as possible. Basic life support and advanced cardiac life support should be initiated by trained individuals. The keys to caring for the victim of an anaphylactic reaction include:

• Maintaining adequate oxygenation and normal blood pressure with fluid expanders
• Treating any cardiac arrhythmias
• Preventing sequelae

Epinephrine is the drug of choice, but high doses may have serious, life-threatening cardiac effects (particularly in the elderly and those with a history of heart disease), inducing hypertension and increased myocardial oxygen demand, and potentially causing cardiac arrhythmias, ischemia, or infarction.

The goal of drug therapy in the case of anaphylaxis is to inhibit release of chemical mediators or reverse their effects on target tissues.

• Epinephrine—generally administered IM by emergency personnel but can be given SL, IV, or via endotracheal tube if necessary. Self-administration of preloaded syringe [0.3 cc of 1:1,000 SC in adults and 0.3 cc of 1:2,000 in children] or aerosolized metered dose inhaler may occur prior to presentation to EMTs or emergency room staff. 
• Diphenhydramine (25 to 100 mg) or chlorpheniramine—(4 to 10 mg) administered every 4 to 6 hours IM for mild to moderate reactions or IV for severe reactions; pediatric dose is 5 mg/kg/day in 4 to 6 divided doses—blocks histamine release, prevents laryngeal edema, and prevents recurrences 
• Corticosteroids, while not necessary for the acute treatment, are important for preventing later-onset sequelae. Either hydrocortisone (200 mg) or methylprednisolone (125 to 250 mg) administered IV, followed by a course of oral prednisone for 7 to 10 days tends to minimize late relapse; oral steroids may also be used prophylactically, as in the case of known reaction to radiocontrast material 
• Albuterol sulfate—nebulizers for persistent bronchospasm; anticholinergic agents (e.g., ipratropium bromide) may be considered as well and aminophylline IV (5 mg/kg over 10 to 30 minutes) followed by oral maintenance—for asthmatic reactions that do not respond to epinephrine 
• An H₂ blocker, namely cimetidine (300 mg IV upon initial presentation and every 6 hours PO or IV for 2 days); helps to prevent delayed relapse 
• Dopamine (5 mcg/kg/min) may be considered if severe hypotension or shock persist despite epinephrine and large volumes of crystalloid fluid; other vasopressors may be tried pending evaluation and progress by trained professionals in the medical intensive care unit 
• Positive pressure 100% oxygen with assisted ventilation—to treat cyanosis, dyspnea, or wheezing 
• Glucagon IV (1 to 5 mg bolus followed by continuous drip); for patients on beta-blockers or resistant to the usual approaches discussed 

Endotrachael intubation or tracheostomy with or without mechanical ventilation maintains the airway in cases of severe laryngeal edema or loss of consciousness, and assists with progressive hypoxia or status asthmaticus. Intubation may be difficult due to distortion from laryngeal edema. If an airway cannot be secured quickly enough by this method, cricothyrotomy may be necessary.

Because of the need for immediate emergency care, complementary and alternative therapies are not considered appropriate for first line treatment of an anaphylactic reaction. CAM therapies may be useful, though, in the prevention of an allergic response in general and recurrent episodes of anaphylaxis specifically. Some CAM approaches may also lessen the severity of any allergic reaction and may improve non–life-threatening symptoms, such as gastrointestinal dysfunction, that can occur with anaphylaxis. Substances and approaches that show some promise for possible adjunctive treatment of anaphylaxis include:

• Flavonoids, such as quercetin—prophylaxis suggested by traditional use and animal studies; vitamin C potentiates quercetin 
• Omega-3 fatty acids (such as alpha-linolenic acid)—lower mortality rate in animal studies 
• Zinc—animal study suggests reduced GI disturbance under anaphylactic conditions 
• Certain single and combination herbal remedies (see section entitled Herbs) 
• Acupuncture—small animal study showed lower mortality rate when used immediately for treatment 

(See sections that follow for more details on each of these topics.)

It is important to remember that nutraceuticals and botanicals, like medications, can cause allergic reactions, including anaphylaxis. In addition to a few herbs and supplements mentioned in the Etiology section, see a list of other herbs associated with rare reports of allergic reactions at the end of the section entitled Herbs.

Omega-3 Fatty Acids

Omega-3 fatty acids have anti-inflammatory properties that, theoretically, may be protective from the extreme reaction of anaphylaxis. Animal studies, however, of IgE antibody response to egg albumin in mice fed alpha-linolenic acid (an omega-3 fatty acid) versus mice fed linoleic acid (an omega-6 fatty acid) are somewhat conflicting. Some studies show increased IgE-meditated reactions in the omega-6 fed animals (as would be expected) and others show increased IgE-mediated reactions in the omega-3 fed animals. What is consistent, though, is a lower mortality rate from anaphylactic shock in the mice on a high omega-3 fatty acid diet compared to those on a high omega-6 diet (Oh-hashi et al. 1997).

Quercetin & Other Flavonoids

Naturopathic doctors have recommended that people with known allergies take quercetin (a naturally occurring flavonoid) prior to allergen exposure; quercetin and other flavonoids stabilize mast cell degranulation, possibly lessening the severity of a response to an antigen (Pizzorno and Murray 1999). Allergy-susceptible individuals can take quercetin supplements or eat foods high in flavonoids on a regular basis.

Animal studies appear to validate this traditional use of quercetin as well as its mechanism of action. In two separate guinea pig studies, quercetin:

• Exhibited membrane-stabilizing effects (Wang et al. 1991)
• Inhibited histamine release (Wang et al. 1991)
• Inhibited the anaphylaxis response in smooth muscle cells of guinea pigs (Nemoto and Okamura 1992)

Vitamin C

Vitamin C is thought to enhance the activity of quercetin (Pizzorno and Murray 1999).

Zinc

Zinc may be protective against development of gastrointestinal symptoms from anaphylaxis. As discussed in the section entitled Pathology/Pathophysiology, anaphylaxis is generally characterized by contraction of smooth muscle and dilation of capillaries due to release of active substances such as histamine and bradykinin; in the GI tract these effects contribute to gastrointestinal disturbances. A small animal study suggests that zinc has anti-inflammatory and antioxidant properties in the GI tract under extreme conditions such as malnutrition; similarly, zinc appeared to protect the malnourished guinea pigs in this trial from anaphylactic intestinal dysfunction (Darmon et al. 1997).

Several animal studies of medicinal plants used traditionally in South Korea and other parts of Asia for prevention or treatment of allergic reactions suggest that the following botanicals, among others, may have merit for prevention of anaphylaxis and other allergic responses in susceptible individuals (Kim et al. 1999c; Kim et al. 1999d; Kim and Yang 1999; Lee et al. 1999; Wu et al. 1991):

• Castanea crenata (Sweet chestnut tree) is an herb that has been used in Asian countries to treat whooping-cough. According to results of an animal study, this herbal extract (100 or 200 mg/kg) inhibited percutaneous anaphylaxis and significantly reduced histamine and serotonin induced vascular permeability. A bioassay revealed that quercetin was the active component in C. crenata extract (Lee et al. 1999). (See subsection Quercetin and Other Flavonoids within the section entitled Nutrition.) 
• Centipeda minima (Spreading sneezeweed) has been used historically in traditional Chinese medicine for anti-inflammatory and anti-allergy purposes; contains flavonoids and sesquiterpene lactones. These active constituents appear to inhibit histamine release from mast cells (Wu et al. 1991).
• Salviae miltiorrhizae (Danshen root) is an herb traditionally used for the treatment of allergies. An aqueous extract of salviae radix root (SRRAE) (0.001 to 1 mg/g) inhibited skin related allergic reactions but not systemic anaphylaxis in rats (Kim et al. 1999c).
• Rosa davurica (Asian rose spp.) traditionally used to regulate immune response was tested in rats. Pretreatment with RdF extract (0.0001 to 1 g/kg) inhibited experimentally induced systemic anaphylaxis by reducing histamine levels in serum and preventing IgE-mediated TNF-alpha production in mast cells (Kim et al. 1999d).
• Aqueous extracts of Poncirus trifoliata (Hardy orange) have been traditionally used for the treatment of allergic diseases. Pretreatment of mice with P. trifoliata fruit extract (PTFE) (200 mg/kg) inhibited systemic anaphylaxis by arresting IgE production (Kim et al. 1999a). 

Some combination herbs have also been tested in animal studies including Sosiho-Tang (SS-Tang), a Korean medicine traditionally used for allergies, that contains:

• Bupleurum falcatum (Bupleurum) 
• Scutellaria baicalensis George (Skullcap root)
• Panax ginseng (Asian ginseng) 
• Pinelliae tenata (Pinelliae tuber) 
• Glycyrrhiza uralensis (Glycyrrhiza glabra; Licorice root) 
• Zingiber officinale (Ginger root) 
• Zizyphus jujuba (Jujube) 

When administered prior to antigen challenge, doses of 1g/kg reduced plasma histamine levels and inhibited anaphylaxis. However, the large doses of SS-Tang required to achieve beneficial effects may limit the application of this herbal remedy for treatment of anaphylaxis (Kim et al. 1999d).

Kumhwang-San, another combination remedy, is traditionally used to treat allergic skin conditions; in one study, this herbal formula reduced serum histamine levels in rats in a dose-dependent manner (0.01 to 10 mg/kg). Ingredients in this formula include:

• Citrus aurantium (Orange peel, bitter) 
• Trichosanthis rhosthornii (Snakeground root) 
• Atractylodes macrocephalae (Largehead atractylodis) 
• Curcumae longa (Turmeric root) 
• Machili cortex
• Arisaema erubescens (Jack-in-the-pulpit tuber) 
• Glycyrrhizae glabra (Licorice root) 
• Angelicae archangelica (Angelica root)
• Phellodendron amurense (Amur cork-tree) 
• Rheum palmatum (Rhubarb) 

Other herbs with anti-allergic activity that may also be beneficial when used alone to prevent reactions include (Tsumura and Kampo 1991):

• Scutellaria baicalensis (Skullcap root)
• Glycyrrhiza glabra or G. uralensis (Licorice root)
• Ganoderma lucidum (Reishi mushroom) 

Consultation with an herbalist can help decide what single or combination of agents is best for an individual patient.

On the other hand, certain herbal remedies may induce allergic reactions, although this happens much less frequently with herbs than it does with pharmaceutical preparations. Herbs for which there have been rare reports of hypersensitivity include (Blumenthal et al. 2000):

• Arnica Montana (frequently used as a homeopathic remedy) 
• Cynara scolymus (Artichoke leaf)—should not be used in case of an allergy to artichokes; Cnicus benedictus (Blessed Thistle herb)
• Capsicum spp. (Cayenne pepper)
• Cinnamomum verum (Cinnamon bark)
• Taraxacum officinale (Dandelion root)—rare cross-reactivity with latex allergy due to sesquiterpene lactone present in the both the latex and dandelion
• Echinacea purpurea (Echinacea)
• Foeniculum vulgare (Fennel oil and fennel seed)
• Tanacetum parthenium/Chrysanthemum parthenium (Feverfew) 
• Ginkgo biloba (Ginkgo biloba leaf extract)
• Populus spp.(Poplar bud)—may cross-react with salicylate sensitivity
• Plantago spp. (Psyllium seed)—reaction more common with powder or liquid
• Achillea millefolium (Yarrow)

While standard medical care should not be delayed in the case of anaphylaxis, there are several homeopathic remedies that have been used for allergic reactions including symptoms of anaphylaxis; these may, therefore, prove of value for adjunctive care (Morrison 1993):

• Aconite napellus—helps in the setting of tremendous anxiety and fear of dying that may accompany or follow an anaphylactic reaction.
• Arnica montana—may be used for adjunctive treatment of anaphylactic shock
• Apis—for skin related symptoms

Mice randomized to control (n = 15) or electroacupuncture (EA; n = 25) were sensitized to and subsequently challenged with bovine serum. The animals in the treatment group were immediately treated with EA applied to renzhong (GV 26) and chengjiang (CV 24) points for 20 minutes. The control group had a 60% mortality rate and the EA group had a significantly reduced mortality rate of 20% (Jian 1985). Again, while treatment of anaphylaxis should never be delayed, this study raises the question as to whether acupuncture may be a useful adjunct to conventional treatment for anaphylaxis. More research is needed, including in humans.

Continuous cardiac monitoring should be started as soon as possible; admission to an intensive care unit may be necessary and in some cases, Swan-Ganz catheterization may be required.

On occasion, persistent or delayed-onset reactions occur 4 to 12 hours after the initial event (known as a biphasic response). Patients who have experienced anaphylaxis should be observed for at least 24 hours following recovery. They should also be given steroids, H₁ and H₂ blockers, and metered-dose inhalers, if used in initial treatment, to prevent delayed reactions.

• Avoidance of any known or suspected etiologic agents including avoidance of new medications unless absolutely necessary, particularly in susceptible individuals
• Avoidance of cephalosporins with history of anaphylaxis from penicillin
• Administration of antibiotics and other medications orally whenever possible
• Pretreatment with antihistamines and systemic corticosteroids before studies using radiocontrast material
• Avoidance of products made with echinacea flowers in allergy-prone individuals may be warranted (see section on Etiology)
• Referral to an allergist for skin and other testing
• Appropriate individuals should carry preloaded epinephrine-containing syringes with 0.3 ml of 1:1,000 solution for adults and 0.3 ml of 1:2,000 solution for children for self-treatment in case of exposure to antigen; especially for insect stings and food allergies
• Medic-Alert bracelet for patients who have had previous anaphylactic reactions
• Skin testing before antiserum or allergenic extracts are administered
• Desensitization and immunotherapy when appropriate with observation for at least 30 minutes following treatments; in such settings of controlled administration of antigens, emergency equipment must be readily available; consider checking FEV1 in asthmatics prior to immunotherapy and avoid this treatment when FEV1 is <70%.

• Beta-blockers may worsen an anaphylactic reaction and inhibit the effects of epinephrine
• Monoamine oxidase inhibitors interfere with the degradation of epinephrine, increasing its half-life and therefore its risks
• ACE inhibitors and ARBs can cause life-threatening pharyngeal edema and inhibit angiotensin II, an endogenous compensatory mechanism for hypotension; levels of angiotensin I and II are inversely related to severity of an anaphylactic reaction

Most patients treated aggressively and appropriately for anaphylaxis do quite well. Airway obstruction and irreversible vascular collapse result in approximately 400 to 800 deaths annually from anaphylaxis. Not everyone who is re-exposed to an inciting agent develops anaphylaxis again; however, a high percentage do, and the risk is too great to warrant the chance of repeat exposure.

Several of the medications used to treat anaphylaxis may pose a risk to the fetus; however, this life-threatening circumstance requires immediate response and administration for the ultimate protection of both the mother and the fetus.

Atkinson TP, Kaliner MA. Anaphylaxis. Med Clin North Am. 1992;76(4):841-855.

Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000:7-9, 10-12, 27-29, 52-55, 65-71, 78-83, 88-102, 124-129, 160-169, 314-321, 419-423.

Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med. 1991;324(25):1785-1790.

Briner WW Jr, Sheffer AL. Exercise-induced anaphylaxis. Med Sci Sports Exerc. 1992;24(8):849-850.

Brown AF. Anaphylactic shock: mechanisms and treatment. J Accid Emerg Med. 1995;12(2):89-100.

Burks AW, Sampson HA. Anaphylaxis and food allergy. Clin Rev Allergy Immunol. 1999;17(3):339-360.

Darmon N, Pelissier MA, Candalh C, et al. Zinc and intestinal anaphylaxis to cow's milk proteins in malnourished guinea pigs. Pediatr Res. 1997;42(2):208-213.

Dykewicz MS. Anaphylaxis and stinging insect reactions. Compr Ther. 1996;22(9):579-585.

Ewan PW. ABC of allergies: anaphylaxis. BMJ. 1998;316(7142):1442-1445.

Friday GA Jr, Fireman P. Anaphylaxis. Ear Nose Throat J. 1996;75(1):21-24.

Goldman L, Bennett JC. Cecil Textbook of Medicine. Vol. 2. 21st ed. Philadelphia, Pa: W.B. Saunders Company; 2000:1450-1452.

James JM. Anaphylaxis: multiple etiologies-focused therapy. J Ark Med Soc. 1996;93(6):281-287.

Jian M. Influence of adrenergic antagonist and naloxone on the anti-allergic shock effect of electro-acupuncture in mice. Acupunct Electrother Res. 1985;10(3):163-167.

Kagy L, Blaiss MS. Anaphylaxis in children. Pediatr Ann. 1998;27(11):727-734.

Kim HM, Kim HJ, Park ST. Inhibition of immunoglobulin E production by Poncirus trifoliata fruit extract. J Ethnopharmacol. 1999;66(3):283-288.

Kim HM, Kim YY, Jang HY, Moon SJ, An NH. Action of Sosiho-Tang on systemic and local anaphylaxis by anal administration. Immunopharmacol Immunotoxicol. 1999;21(3):635-643.

Kim HM, Lee EH, Lee JH, Jung JA, Kim JJ. Salviae radix root extract inhibits immunoglobulin E-mediated allergic reaction. Gen Pharmacol. 1999;32(5):603-608.

Kim HM, Park YA, Lee EJ, Shin TY. Inhibition of immediate-type allergic reaction by Rosa davurica Pall. in a murine model. J Ethnopharmacol. 1999;67(1):53-60.

Kim HM, Yang DJ. Effect of Kumhwang-San on anaphylactic reaction in a murine model. Immunopharmacol Immunotoxicol. 1999;21(1):163-174.

Lee E, Choi EJ, Cheong H, Kim YR, Ryu SY, Kim KM. Anti-allergic actions of the leaves of Castanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation. Arch Pharm Res. 1999;22(3):320-323.

Middleton E Jr, et al. Allergy: Principles and Practice. Vol. 2. 5th ed. St. Louis, Mo: Mosby; 1998:1079-1089.

Morrison R. Desktop Guide to Keynotes and Confirmatory Symptoms. Albany, Calif: Hahnemann Clinic Publishing; 1993:3-7, 27-30, 58-62, 104.

Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust. 1998;168(4):170-171.

Nemoto K, Okamura T. Intracellular signals in IgG-mediated anaphylactic contraction of single smooth muscle cells. Jpn J Allergol. 1992;41(2):125-134.

Oh-hashi K, Watanabe S, Kobayashi T, Okuyama H. Reevaluation of the effect of a high alpha-linolenate and a high linoleate diet on antigen-induced antibody and anaphylactic responses in mice. Biol Pharm Bull. 1997;20(3):217-223.

Okazaki M, Kitani H, Mifune T, et al. Food-dependent exercise-induced anaphylaxis. Intern Med. 1992;31(8):1052-1055.

Patterson R, et al. Allergic Diseases: Diagnosis and Management. 5th ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1997:439-454.

Patterson R, Harris KE. Idiopathic anaphylaxis. Allergy Asthma Proc. 1999;20(5):311-315.

Pizzorno JE Jr, Murray MT. Textbook of Natural Medicine. Vol. 1. 2nd ed. New York, NY: Churchill Livingstone; 1999:456-459, 746-749, 751-759.

Rosen P, et al. Emergency Medicine: Concepts and Clinical Practice. Vol. 3. 4th ed. St. Louis, Mo: Mosby; 1998:2759-2774.

Stephen JM, Grant R, Yeh CS. Anaphylaxis from administration of intravenous thiamine. Am J Emerg Med. 1992;10(1):61-63.

Tsumura A, Kampo A. How the Japanese Updated Traditional Herbal Medicine. Tokyo: Japan Publications; 1991:191-192.

Wang YZ, Palmer JM, Cooke HJ. Neuroimmune regulation of colonic secretion in guinea pigs. Am J Physiol. 1991;260:(2 pt 1):G307-G314.

Wu JB, Chun YT, Ebizuka Y, Sankawa U. Biologically active constituents of Centipeda minima: sesquiterpenes of potential anti-allergy activity. Chem Pharm Bull (Tokyo). 1991;39(12):3272-3275.

Wyatt R. Anaphylaxis. How to recognize, treat, and prevent potentially fatal attacks. Postgrad Med. 1996;100(2):87-90, 96-99.