Anaphylaxis

para>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 β-blockers.

COMMONLY ASSOCIATED CONDITIONS

Asthma
Atopy

DIAGNOSIS

HISTORY

Rapid progression within minutes to hours of the signs and symptoms of anaphylaxis, with or without an obvious trigger, including but not limited to cutaneous symptoms (>90% of cases), respiratory symptoms (40-60%), GI symptoms (25-30%), and cardiovascular symptoms (30-35%)

PHYSICAL EXAM

Pruritus, flushing, urticaria, angioedema
Dyspnea, cough, rhonchi
Rhinorrhea, bronchorrhea, wheezing, stridor
Difficulty swallowing
Nausea, vomiting, diarrhea, cramps, bloating
Tachycardia, hypotension, shock, syncope
Malaise, shivering
Mydriasis

DIFFERENTIAL DIAGNOSIS

Vasodepressor reactions: most commonly mimics anaphylaxis (i.e., Bezhold-Jarisch reflex, vasodilatation, bradycardia, hypotension, resulting in pallor, nausea, vomiting, and weakness)
Flushing syndromes: carcinoid, alcohol ingestion, spicy foods, drug-ingestion (i.e., disulfiram, griseofulvin, and cephalosporins), medullar carcinoma of thyroid, and pheochromocytoma
- Wet versus dry flushing
  - Wet: sweating mediated by sympathetic cholinergic nerves
  - Dry: direct vasodilation (i.e., carcinoid also releases histamine, kallikrein, and prostaglandins)
Restaurant syndromes
- MSG ingestion (Chinese restaurant syndrome)
- Sulfites
- Scombroisosis: histamine poisoning secondary to ingestion of histamine in spoiled fish (i.e., tuna, mackerel)
Excess endogenous production of histamine syndromes
- Systemic mastocytosis
- Urticaria pigmentosa
- Basophilic leukemia
Nonorganic disease
- Panic attack
- Vocal cord dysfunction syndrome
- Globus hystericus
- Munchausen stridor
Hereditary angioedema: rare autosomal dominant condition caused by low levels of plasma C1 inhibitor (inhibits the kinin pathway)
Tracheal foreign body
Pseudoanaphylaxis: syncope and neurologic symptoms after administration of procaine penicillin. Reaction is caused by procaine, not penicillin.
Red man syndrome (i.e., vancomycin)

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Little data to support extensive testing; targeted IgE antibodies of little value due to low sensitivity and specificity
Elevated serum tryptase, a mast cell enzyme for allergic and anaphylactic reactions (1)[B], plasma histamine, and 24-hour urinary histamine metabolites (i.e., N-methylhistamine)
Tryptase: sensitivity of 89% and specificity of 88% (2)[B]
Plasma histamine levels begin to rise within 5 to 10 minutes and remain elevated for 30 to 60 minutes and are little help if patient is seen after 1 hour of event onset.
Tryptase peaks 60 to 90 minutes after onset of anaphylaxis and persist longer than histamine, up to 5 hours after onset (must be drawn within 90 minutes).
Other markers include CD63, CD203c, prostaglandin D2, and carboxypeptidase.

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
Supine position, legs elevated (if in shock)
IV fluids (normal saline/lactated Ringer)

MEDICATION

First Line

Epinephrine
- Less severe reaction: 0.3 to 0.5 mg (0.01 mg/kg in children) = (0.3 to 0.5 mL of a 1:1,000 solution, 0.01 mL/kg in children), IM lateral thigh q20-30min PRN, up to 3 doses
- Life-threatening reactions: 0.5 mg (5 mL of a 1:10,000 solution) (for children: 0.05 to 0.1 mL/kg per dose) IV, slowly: q5-10min as needed. If IV access is not possible, endotracheal or intraosseous may be effective.
Antihistamines: not life-saving, but alleviate itching and urticarial. Vasodilatory effect and can trigger hypotension, thus, must be given with epinephrine
- Diphenhydramine: an H1 blocker: 25 to 50 mg IV (IM or PO) q6h for 72 hours (children 1.25 mg/kg to 25 mg)
- Cimetidine: an H2 blocker: 300 mg IV over 3 to 5 minutes (children 5 to 10 mg/kg per dose) and then 400 mg PO BID is helpful and may be more effective than diphenhydramine.
Corticosteroids: although routinely used, no immediate effect and no evidence for their use in the emergency department (3)[B]
- Hydrocortisone sodium succinate: 250 to 500 mg IV q4-6h (4 to 8 mg/kg for children)
Prednisone: 1 mg/kg in children, up to 60 mg
Methylprednisolone: 60 to 125 mg IV in adults (1 to 2 mg/kg in children)
Bronchodilator, if persistent bronchospasm
- Inhaled β2 agonists. Continuous nebulized albuterol of 10 mg/hr or 2.5 mg q15-20min is safe, effective, and preferable to aminophylline as a first line.
Laryngeal edema
- Epinephrine: 5 mL of 1:1,000 by nebulizer is more effective than racemic epinephrine and is usually available.
Persistent hypotension
- Dopamine: 400 mg in 500 mL of dextrose in water given by infusion pump; titrate to BP (2 to 20 Î¼g/kg/min).
- Atropine: adult (0.3 to 0.5 mg IV q10min PRN, max dose 2 mg) in case of bradycardia
- Glucagon: may be beneficial for resistant hypotension caused by concurrent β-blockade therapy; 50 Î¼g/kg IV bolus over 1 minute, or alternatively, give as continuous infusion at 5 to 15 Î¼g/min
Normal saline or Ringer lactate: adult (1 to 2 L rapidly), child (30 mL/kg in the 1st hour)
Oral antihistamines for 72 hours

Geriatric Considerations

Epinephrine may induce myocardial ischemia in those with cardiac disease, but it 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 the 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; used only in patients who do not respond to other therapy
Aminophylline: 5 to 6 mg/kg IV in 100 mL D5W over 20 minutes, then maintenance at 1 mg/kg/hr drip
Anti-IgE monoclonal antibody may have a role in long-term management of food-induced anaphylaxis.
Venom immunotherapy has been effective in the prevention of sting anaphylaxis but with a high side-effect risk (4)[A].

ISSUES FOR REFERRAL

Allergist referral if anaphylaxis cause unclear
Patients with anaphylaxis from insect stings benefit from desensitization immunotherapy.

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization
Moderate to severe anaphylaxis, admit for observation for 8 to 24 hours.

DISCHARGE CRITERIA

Outpatient: Patients with cutaneous angioedema, urticaria, without bronchospasm may be released when symptoms and signs have cleared.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Bed rest until anaphylaxis clears and patient is hemodynamically stable

DIET

NPO until acute symptoms are controlled

PATIENT EDUCATION

Asthma and Allergy Foundation of America, 1717 Massachusetts Avenue, Suite 305, Washington, DC 20036; (800)-7-ASTHMA or American Allergy Association, P.O. Box 7273, Menlo Park, CA 94026, (415) 322-1663
Medic-Alert-type tags (Medic-Alert Foundation, Turlock, CA 95381-1009)
Avoid β-blockers, if possible.
Instruct patient in the use of the epinephrine auto-injector (Epipen) usage.

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.

COMPLICATIONS

Hypoxemia
Cardiac arrest
Death

REFERENCES

11 Brown SG, Blackman KE, Heddle RJ. Can serum mast cell tryptase help diagnose anaphylaxis? Emerg Med Australas. 2004;16(2):120-124.22 Narita M, Nomura I, Aota A, et al. Usefulness of serum tryptase in the diagnosis of anaphylaxis by food allergy in childhood. J Allergy Clin Immunol. 2006;7(2):s307.33 Choo KJ, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2010;65(10):1205-1211.44 Brown SG, Wiese MD, Blackman KE, et al. Ant venom immunotherapy: a double-blind, placebo-controlled, crossover trial. Lancet. 2003;361(9362):1001-1006.

ADDITIONAL READING

Gonz ¡lez-P ©rez A, Aponte Z, Vidaurre CF, et al. Anaphylaxis epidemiology in patients with and patients without asthma: a United Kingdom database review. J Allergy Clin Immunol. 2010;125(5):1098.e1-1104.e1.
Lieberman P, Kemp S, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3)(Suppl 2):S483-S523.
Pitsios C, Dimitriou A, Stefanaki EC, et al. Anaphylaxis during skin testing with food allergens in children. Eur J Pediatr. 2010;169(5):613-615.
Sheikh A, Shehata YA, Brown SG, et al. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2008;(4):CD006312.
Sheikh A, ten Broek V, Brown SG, et al. H1-antihistamines for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2007;(1):CD006160.
Tanus T, Mines D, Atkins PC, et al. Serum tryptase in idiopathic anaphylaxis: a case report and review of the literature. Ann Emerg Med. 1994;24(1):104-107.
Wittbrodt ET, Spinler SA. Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media. Ann Pharmacother. 1994;28(2):236-241.

CODES

ICD10

T78.00XA Anaphylactic reaction due to unspecified food, init encntr
T88.6XXA Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, initial encounter
T78.2XXA Anaphylactic shock, unspecified, initial encounter
T63.91XA Toxic effect of contact w unsp venomous animal, acc, init
T78.00XD Anaphylactic reaction due to unspecified food, subs encntr
T88.6XXD Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, sunsequent encounter
T88.6XXS Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, sequela
T63.91XD Toxic effect of contact w unsp venomous animal, acc, subs
T63.91XS Toxic effect of contact w unsp venom animal, acc, sequela
T78.2XXD Anaphylactic shock, unspecified, subsequent encounter
T78.2XXS Anaphylactic shock, unspecified, sequela
T78.00XS Anaphylactic reaction due to unspecified food, sequela

ICD9

995.0 Other anaphylactic reaction
995.60 Anaphylactic reaction due to unspecified food
989.5 Toxic effect of venom

SNOMED

Anaphylaxis (disorder)
Drug-induced anaphylaxis (disorder)
Food anaphylaxis (disorder)
Anaphylaxis secondary to bite and/or sting (disorder)

CLINICAL PEARLS

Allergy to one species of legume (e.g., peanuts) or one type of seafood (e.g., shrimp) does not mean allergy to all products in that category. Skin testing is useful.
Measles, mumps, rubella (MMR) and influenza vaccines can be safely administered to those with a history of egg allergy.
Penicillin-allergic patients can generally tolerate 2nd- and 3rd-generation cephalosporins as well as monobactams (e.g., aztreonam). Generally, they will be allergic to carbapenems (e.g., imipenem) and 1st-generation cephalosporins.
IgA-deficient patients should have washed RBCs for transfusion.
Those allergic to seafood are not allergic to iodine-based radiocontrast. Shellfish allergy is protein-related.

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