ANAPHYLAXIS

ANAPHYLAXIS - BobbyPeters, MD, FAAEM
BASICS
DESCRIPTION
• An IgE mediated acute, systemic reaction following antigen exposure in a sensitized person
• A non-IgE mediated idiopathic anaphylactoid reaction also may occur. Anaphylactoid reactions are clinically indistinguishable from anaphylaxis and are treated in the same manner.
• System(s) Affected: Cardiovascular; Endocrine/Metabolic; Gastrointestinal; Hematologic/Lymphatic/Immunologic; Pulmonary; and Skin/Exocrine
• Synonym(s): Anaphylactoid reactions
GENERAL PREVENTION
• Avoid inducing drugs and foods.
• Carry a prefilled epinephrine syringe.
• Avoid areas where insect exposure likely. Avoid wearing insect attractants (e.g., perfumes, colored clothing); avoid bare feet outdoors.
• Carry or wear a medical alert ID about the anaphylaxis-causing substance or event.
• When radiologic contrast is unavoidable, use of low osmolar contrast agents (e.g., iothalamate) reduces the risk of contrast reactions to 3.1%.
- Only 0.22% were considered severe.
- Stop beta-blockers before administering contrast materials.
- Pretreat with diphenhydramine (50 mg IV) and a steroid (e.g., methylprednisolone 60 mg IV q6h until procedure). Start methylprednisolone the day before the procedure is scheduled.
• Those with frequent (>6 per year) episodes of idiopathic anaphylaxis should be treated prophylactically with prednisone (40-60 mg/d in a single morning dose), hydroxyzine (25 mg t.i.d.), and albuterol (2 mg PO t.i.d.). The prednisone should be rapidly tapered to a every other day regimen.
ALERT
• Have a latex-free kit (gloves, etc) available for the treatment of latex-allergic patients. Some latex-allergic patients will react to tropical fruits, such as kiwi, bananas, avocados, and chestnuts.
• Avoid beta-blockers.
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• Up to 40,000 cases of idiopathic anaphylaxis occur per year with no identifiable cause.
• Drug-induced anaphylaxis in 1/2,700 hospitalized patients
• Anaphylaxis deaths: 0.3-0.7/100,000 per year
RISK FACTORS
• Previous anaphylaxis
• History of atopy or asthma
Genetics
Genetic predisposition for sensitization to antigens.
ETIOLOGY
• IgE-mediated mast cell degranulation
• Complement activation (C3a, C4a, C5a) by antigen-antibody complexes that contain complement-fixing antibodies.
• Other non-IgE-dependent anaphylaxis-like syndromes may be caused by modulators of arachidonic acid metabolism, sulfiting agents, exercise-induced anaphylaxis, and idiopathic recurrent anaphylaxis.
• Some important causes of anaphylaxis are:
- Antimicrobials (e.g., penicillin)
- Blood products (especially in IgA deficiency)
- Iodinated contrast media
- Ethylene oxide gas (dialysis tubing, other sterilized products)
- Exercise
- Foods (Common: Peanuts, nuts, fish, crustaceans, mollusks, cow milk, eggs, and soy)
- Immunotherapy
- Insect stings (e.g., honeybees, wasps, kissing bugs, and deer flies)
- Latex rubber (gloves, catheters)
- Macromolecules (e.g., chymopapain, insulin, dextran, glucocorticoid, and protamine)
- Vaccines
ASSOCIATED CONDITIONS
• Asthma
• Atopy


DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
• Pruritus, flushing, urticaria, angioedema
• Dyspnea, cough, rhonchi
• Rhinorrhea, bronchorrhea, wheezing
• Difficulty swallowing
• Nausea, vomiting, diarrhea, cramps, bloating
• Tachycardia, hypotension, shock, syncope
• Malaise, shivering
• Mydriasis
TESTS
Lab
• Hypoxemia, hypercarbia, acidosis
• Acidosis may cause apparent hyperkalemia by moving potassium extracellularly.
• Elevated serum tryptase, a mast cell enzyme for allergic and anaphylactic reactions. (11)[B]
• Drugs that may alter lab results: Epinephrine and albuterol may cause apparent hypokalemia by shifting K+ intracellularly.
DIFFERENTIAL DIAGNOSIS
• Anaphylactoid reactions
- May occur after the 1st contact with substance, such as polymyxin, pentamidine, radiographic contrast media, and aspirin.
• Carcinoid syndrome
• Globus hystericus
- May mimic pharyngeal edema
• Hereditary angioedema
- C1q esterase deficiency with painless, pruritus-free angioedema without urticaria, flushing, or wheezing
• Pheochromocytoma
- Paradoxically, because of beta-2 stimulation, some patients have hypotensive attacks accompanied by tachycardia.
- Urticaria, angioedema, and wheezing are absent
• Pseudoanaphylactic reaction
- After injection of procaine penicillin
- Is a drug effect of procaine and not a penicillin allergy
• Scombroid poisoning
- From ingestion of dark meat fish (e.g., tuna, mackerel, and mahi-mahi)
- Histamine-like mediator: Symptoms include flushing, sweating, nausea, vomiting, diarrhea, headache, palpitations, dizziness, rash, swelling of face and tongue, respiratory distress, and vasodilatory shock.
• Serum sickness
- Occurs several days after exposure
• Systemic mastocytosis
- Benign or malignant overgrowth of mast cells
- Urticaria pigmentosa seen in the benign form and the presence of reddish brown macular-papular cutaneous lesions, which urticate after trauma: Darier's sign.
• Vasovagal reactions
- Bradycardia and hypotension without tachycardia, flushing, urticaria, angioedema, pruritus, and wheezing
• Pulmonary embolism, foreign body aspiration, and arrhythmia
TREATMENT
GENERAL MEASURES
• Treatment depends on severity
• Maintain a patent airway
- Endotracheal intubation and assisted ventilation may be necessary.
- Possibly tracheostomy or needle cricothyrotomy in children 12 years
• Oxygen
• IV fluids (normal saline/lactated ringers)
Diet
Nothing until acute symptoms are controlled.
Activity
Bedrest until anaphylaxis clears and patient hemodynamically stable.
MEDICATION (DRUGS)
First Line
• Epinephrine
- Less severe reaction: 0.3-0.5 mg (0.01 mg/kg in children) = (0.3-0.5 mL of a 1:1,000 solution, 0.01 mL/kg in children), SQ q20-30min as needed up to 3 doses
- Life-threatening reactions: 0.5 mg (5 mL of a 1:10,000 solution) (for children: 0.05-0.1 mL/kg per dose) given IV slowly q5-10min as needed. If IV access is not possible, endotracheal or intraosseous may be effective.
• Diphenhydramine, an H1 blocker: 25-50 mg intravenously (IM or PO:) q6h for 72 hours (children 1.25 mg/kg to 25 mg)
• Cimetidine, an H2 blocker: 300 mg IV over 3-5 minutes (children 5-10 mg/kg per dose) and then 400 mg PO. b.i.d. is helpful and may be more effective than diphenhydramine.
• Corticosteroids: No immediate effect and unclear if they prevent recurrence.
- Hydrocortisone sodium succinate: 250-500 mg IV q4-6h (4-8 mg/kg for children) or
- Prednisone: 1 mg/kg in children, up to 60 mg
- Methylprednisolone: 60-125 mg IV in adults (1-2 mg/kg in children)
• Bronchodilator, if persistent bronchospasm
- Inhaled beta-2 agonists. Continuous nebulized albuterol of 10 mg per hour or 2.5 mg q15-20 min is safe, effective, and preferable to aminophylline as a first line.
• Laryngeal edema:
- Epinephrine: 5 mL 1:1,000 by nebulizer is more effective than racemic epinephrine and usually available.
• Persistent hypotension
- Dopamine: 200 mg in 500 mL of dextrose in water given by infusion pump; titrate to BP (3-20 mcg/ kg per minute)
- Glucagon: May be beneficial for resistant hypotension caused by concurrent beta-blockade therapy; 50 mcg/kg IV bolus over 1 minute, or alternatively, give as continuous infusion at 5-15 mcg/min
• Normal saline or Ringer's lactate: As necessary to maintain tissue perfusion
• Oral antihistamines and steroids for 72 hours
ALERT
Geriatric Considerations
Epinephrine may induce myocardial ischemia in those with cardiac disease, but is the drug of choice. Be alert for anticholinergic and CNS side effects after giving diphenhydramine or cimetidine.
Pediatric Considerations
Epinephrine could reduce the placental blood flow, but may save the life of the mother and fetus. It also increases risk of congenital malformation.
Second Line
• Several reports of tranexamic acid: 1,000 mg IV or sigma-aminocaproic acid for refractory anaphylaxis
• These drugs are not standard care; use only in patients who do not respond to other therapy.
• Aminophylline: 5-6 mg/kg IV in 100 cc D5W over 20 minutes, then maintenance at 1 mg/kg/h drip
• Anti-IgE monoclonal antibody may have a role in long-term management of food-induced anaphylaxis. (12)[B]
• Venom immunotherapy has been effective in the prevention of sting anaphylaxis, but with a high side-effect risk. (13)[A]
FOLLOW-UP
DISPOSITION
Admission Criteria
Moderate-severe anaphylaxis, admit for observation
Discharge Criteria
Outpatient: Patients with cutaneous angioedema, urticaria, and minimal bronchospasm may be released when symptoms and signs have cleared.
Issues for Referral
• Allergist referral, if anaphylaxis cause unclear
• Patients with anaphylaxis from insect stings benefit from desensitization immunotherapy.
PROGNOSIS
• Good prognosis if treated immediately; worse outcome with a delay of >30 minutes in administration of epinephrine
• Of those with idiopathic anaphylaxis, 60% are free of anaphylactic episodes at 2.5 years; most others were steroid-free
COMPLICATIONS
• Hypoxemia
• Cardiac arrest
• Death
REFERENCES
1. Anne S, et al. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol.1995;74:167.
2. The Diagnosis and Management of Anaphylaxis. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy. Asthma and Immunology. Allergy 1998;6.
3. Freeman TM. Allergy and Immunology. Anaphylaxis: Diagnosis and treatment. Prim Care. 1998;25:809.
4. Hoste S, Van Aken, Stevens E. Tranexamic acid in the treatment of anaphylactic shock. Acta Anaesthesiologica Belgica. 1991;42:113-116.
5. Patterson R, Hogan B, Yarnold PR, Harris KE. Idiopathic anaphylaxis: An attempt to estimate the incidence in the United States. Arch Int ed. 1995;155:869-871.
6. Sandler SG, Mallory, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev. 1995;9:1-8.
7. Sloop GD, Friedberg C. Complications of blood transfusion: how to recognize and respond to noninfectious reactions. Postgrad Med. 1995;98:159-162,166,169-172.
8. Tanus T, Mines D, Atkins PC, Levinson AL. Serum tryptase in idiopathic anaphylaxis: A case report and review of the literature. Ann Emerg Med. 1994;24:104-107.
9. Tintinalli JE, et al. Emergency Medicine, A Comprehensive Study Guide. 4th ed. New York, NY: McGraw-Hill; 1995.
10. Wittbrodt ET, Spinler A. Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media. Ann Pharmacother. 994;28:236-241.
11. Brown SG, Blackman KE, Heddle RJ. Can serum mast cell tryptase help diagnose anaphylaxis? EMA. 16;2:120-124.
12. Leung DY, Shanahan WR, Li XM, Sampson HA. New approaches for the treatment of anaphylaxis. Novartis Foundation Symposium. 257:248-260.
13. Brown SG, Wiese MD, Blackman KE, Heddle RJ. Ant venom immunotherapy: A double-blind, placebo-controlled, crossover trial. Lancet. 361;9362:1001-1006.