Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine), 4th Ed.

CHAPTER 68. Anaphylaxis

Jessica Barber

E. Bradshaw Bunney

HIGH-YIELD FACTS

• More than 50% of anaphylaxis cases are idiopathic; therefore, a high index of suspicion is needed to make the diagnosis in children.

• Airway compromise can occur rapidly.

• Epinephrine is the first-line medication for the treatment of moderate-to-severe anaphylaxis.

• In severe anaphylaxis if 2 to 3 fluid boluses (20 cc/kg) are given, as well as epinephrine; if hypotension persists, an epinephrine drip is indicated.

Anaphylaxis is a severe, potentially life-threatening hypersensitivity reaction characterized by skin or mucosal manifestations that include a pruritic rash, urticaria, or angioedema, respiratory compromise associated with airway edema and bronchospasm, and/or cardiovascular compromise that can result in distributive shock. It occurs within minutes to hours after exposure to an offending allergen. The estimated risk of anaphylaxis per person in the United States is 0.05% to 2%; this likely is an underestimate of the true severity of the problem due to underdiagnosis and underreporting.1 Food allergy is the most common cause of anaphylaxis and is increasing in prevalence.2Anaphylaxis from food allergy leads to approximately 150 fatalities in the United States each year, and the more rapid the onset of symptoms, the more likely the reaction will be life threatening.3,4 In over 50% of anaphylaxis cases no precipitating cause is identified, therefore the emergency physician must have a high level of suspicion for the disorder to recognize the symptoms and initiate proper treatment.5 Asthma is known to have a strong association with anaphylaxis which may aid in more rapid diagnosis.2,6,7

PATHOPHYSIOLOGY

Anaphylaxis is an immunologic reaction. An initial exposure to an allergen results in the development of a specific IgE antibody to the antigen. The IgE antibody resides on the cell membrane of basophils and mast cells. When a subsequent exposure to the allergen occurs, the allergen binds to the IgE on the basophil and mast cells, and stimulates the release of multiple mediators, including histamine, leukotriene C4, prostaglandin D2, and tryptase. These mediators lead to increased production and release of respiratory secretions, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability. An anaphylactoid reaction involves the release of similar mediators without involvement of the immune system. Intravenous (IV) contrast allergy is an example of an anaphylactoid reaction.

ALLERGENS

Food is the number one cause of anaphylaxis. More than 90% of food-related anaphylaxis is caused by exposure to nuts and shellfish.8,9 In infants, cow’s milk and eggs are the most common causes of anaphylaxis.10 Once the food that caused the anaphylaxis is identified, thorough education of the parents and child is necessary to avoid reexposure. Although there has been an increase in hospital admissions due to food-related anaphylaxis, fatalities have remained stable.2,6

Insect stings are a common cause of a localized allergic reaction and can also cause anaphylaxis. According to the CDC there are 90 to 100 deaths per year in the United States from insect stings.11

Drug-related allergies are quite common. The most common medications causing anaphylaxis are aspirin, NSAIDs, and α-lactam antibiotics. IV administration of medication has a higher incidence of anaphylaxis and more rapid onset of the anaphylactic symptoms. Rates of death due to drug allergies have increased 300% over the last decade.6

Latex allergy is becoming an increasingly common cause of allergic reaction in children; it can occur following exposure to gloves, tourniquets, or a Foley catheter. Chui3 found that in pediatric patients, risk factors for developing a latex allergy included spina bifida, surgery in the first year of life, multiple surgeries, urogenital malformations, and atopy. Atopy is the genetic predisposition to produce IgE to common proteins, and can lead to hay fever, allergies to dust and grass pollen, and asthma.

Parents often worry about the risk of childhood immunizations causing an allergic reaction or anaphylaxis: Lajeunesse recently published that the risk of anaphylaxis after vaccination continues to be rare, without any fatalities.12

PRESENTATION

In general, anaphylaxis is categorized as mild, moderate, and severe. Mild anaphylaxis consists primarily of skin and mucosal manifestations. These include redness, flushing, urticaria (hives), itching, and angioedema. In addition, mild anaphylaxis can produce some wheezing or throat irritation and mild tachycardia, without respiratory or cardiovascular compromise. Moderate anaphylaxis has the same cutaneous manifestations, with the addition of difficulty breathing, barky cough, stridor, light-headedness, and tachycardia. Severe anaphylaxis can cause severe respiratory distress and cardiovascular manifestations that range from hypotension and tachycardia to fulminant shock. Gastrointestinal symptoms such as vomiting, diarrhea, and crampy abdominal pain frequently accompany moderate-to-severe anaphylaxis.

In an anaphylactic reaction, the onset of symptoms ranges from minutes to a few hours after contact with an allergen, thus a history of such exposure is helpful in those patients with known severe allergies. However, as 50% of anaphylactic reactions are idiopathic, the diagnosis often needs to be made based on the constellation of symptoms at presentation, and not on information about an allergen exposure. Therefore, it is critical that the clinician considers anaphylaxis in a hypotensive child with respiratory distress.

The diagnosis is made easier when the characteristic urticarial rash is present. However, if the clinician fails to look at the skin because he or she is focusing on the critical nature of the patient the rash can be missed. In addition, up to 20% of children with anaphylaxis will present without a rash.13

Although most patients with anaphylaxis who are hypotensive will be tachycardic, insect stings have been associated with hypotension and a relative bradycardia. The cause of the bradycardia is unknown.4,14

ANCILLARY TESTS

In general, laboratory tests or radiographic tests will not help to diagnose anaphylaxis. Some advocate the use of serial measurement of tryptase when the diagnosis is uncertain, as studies have shown an association between increased tryptase concentration and anaphylaxis.7,15 This is more useful to confirm the diagnosis because the levels take approximately 1 to 2 hours to peak.2

TREATMENT

As with all critically ill children, treatment begins with establishing an airway. The airway may be difficult to secure in the child with severe mucosal edema. Immediate endotracheal intubation is done in any child at risk of respiratory arrest. The clinician must always consider rescue airway techniques they may need to employ, such as cricothyrotomy and jet insufflation, should endotracheal intubation not be possible. Oxygen (100%) is indicated in all anaphylactic children with respiratory symptoms who are hypoxic. The medications used to treat anaphylaxis are listed in Table 68-1.

TABLE 68-1

Medications used for the Treatment of Anaphylaxis

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Epinephrine is the primary drug of choice for treating moderate-to-severe forms of anaphylaxis.16 The dose is 0.01 mL/kg of 1:1000 IM or SC every 15 minutes, or 0.01 mL/kg of 1:10,000 IV. Recent studies have shown that IM is preferred over SC because of more efficient absorption.13,16,17 Inhaled epinephrine has been shown not to achieve the serum epinephrine levels needed to treat anaphylaxis and should not be used either in the emergency department or in the prehospital setting.16 It is important to remember in children with moderate-to-severe anaphylaxis that there is no contraindication to the use of epinephrine.8,9,13 Recent reviews of pediatric anaphylaxis estimate that only 24% to 57% of children in moderate-to-severe anaphylaxis got epinephrine despite it being the first-line treatment.2,18 Failure to inject epinephrine quickly has been identified as the main factor in contributing to death from anaphylaxis.13 Bronchospasm may respond to inhaled α-agonists, but there is little to no evidence supporting this.

IV fluids are a mainstay for treating anaphylaxis in patients who are hypotensive. The relaxation of the vascular smooth muscle combined with the increased capillary permeability leads to considerable third-space accumulation of fluids, which can result in distributive shock. IV crystalloids are given as a 20 cc/kg bolus over 10 to 20 minutes; multiple boluses may be necessary. If hypotension persists, then an epinephrine or dopamine continuous IV drip should be considered.13

H1 antihistamines such as diphenhydramine are often used in treating anaphylaxis, particularly the histamine-related rash and pruritus, but do not replace epinephrine as the first-line agent in moderate-to-severe anaphylaxis. Some authors have advocated not using diphenhydramine except in truly mild cases because of the sedative effect which may cause decreased recognition of symptoms and complicate signs of anaphylaxis in infants and children.8,19

H2 antihistamines, such as cimetidine, have been used in the treatment of anaphylaxis based on theoretical efficacy, but have not been proven to be of benefit. Some studies have shown that the combination of H1 and H2 antihistamines may be superior than to either alone.13

Steroids, such as methylprednisolone, have been used to prevent recurrence of symptoms or a delayed reaction, based on their anti-inflammatory properties; the evidence for this is weak, and they are not a first-line medication in the treatment of anaphylaxis.13,17,19

Removal of the allergen, if possible, is always done. The child should remain lying or in the Trendelenburg position until symptoms have completely resolved. There is evidence that abrupt changes in position, from lying to sitting or standing, has been associated with fatalities in pediatric anaphylactic patients.7

SPECIAL CONDITIONS

Exercise-induced anaphylaxis is initially characterized by mild fleeting, pinpoint wheals that are brought on by an increase in body temperature; symptoms can then progress toward respiratory and vascular compromise. Food-dependent exercise-induced anaphylaxis (FDEIA) is characterized by anaphylaxis during or soon after exercise which was preceded by the ingestion of a causal food. Neither the exercise alone nor the food alone will trigger the allergic response. The exercise can consist of mild or aggressive aerobic activity. Five to fifteen percent of exercise-related anaphylaxis can be caused by FDEIA. The most common food associated with FDEIA is wheat, but soy, peaches, and shellfish have also been implicated.6,20

On rare occasion, anaphylaxis has been associated with the use of anesthetic agents. In one study, the most frequent cause of anesthetic-induced anaphylaxis was from the paralytic agents, succinylcholine, and rocuronium.21

DISPOSITION

In general, any child with severe anaphylaxis involving vascular collapse should be admitted to the ICU. Any child with respiratory symptoms that have completely resolved should be observed for a minimum of 4 to 6 hours before discharge to ensure that a delayed-phase reaction does not occur.13 Patients being discharged are given strict instructions to return if symptoms recur. Patients with first-time anaphylaxis should be referred to an allergist.

Autoinjectable epinephrine is used by patients for immediate treatment of anaphylaxis symptoms outside the hospital. They are of single use and come in two doses, 0.3 mg and 0.15 mg. Many have advocated that additional, smaller doses, be produced to better serve the pediatric population. A general guideline proposed by Sicherer is that the 0.15-mg dose is used in children weighing 10 to 25 kg, and the 0.3-mg dose be used in children weighing 25 kg and over. Although the 0.3-mg dose in a 25-kg child is 1.2 times the recommended dose, some authors recommend this dose because the benefit of aggressively treating anaphylaxis outweighs the small potential risk of overdosing with epinephrine in otherwise healthy children.22,23 Those that should go home with autoinjectable epinephrine are those with cardiovascular or respiratory reaction, exercise-induced anaphylaxis, idiopathic anaphylaxis, generalized urticaria from insect sting, and food allergy.2,8,16

REFERENCES

1. Peavy RD, Metcalfe DD. Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:310–315.

2. Jarvinen KM. Food-induced anaphylaxis. Curr Opin Allergy Clin Immunol. 2011;11:255–261.

3. Chiu AM, Kelly KJ. Anaphylaxis: drug allergy, insect stings, and latex. Immunol Allergy Clin North Am. 2005;5:389.

4. Khan BQ, Kemp SF. Pathophysiology of anaphylaxis. Curr Opin Allergy Clin Immunol. 2011;11:319–325.

5. Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006;97:39.

6. Koplin JJ, Martin PE, Allen KJ. An update on epidemiology of anaphylaxis in children and adults. Curr Opin Allergy Clin Immunol. 2011;11:492–496.

7. Simons FE, Ardusso LR, Bilo MB, et al. 2012 Update: World Allergy Organiation Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol. 2012;12:389–399.

8. Muraro A, Roberts G, Clark A, et al. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology. Allergy. 2007;62:857.

9. National Guidelines Clearinghouse. http://www.guideline.gov/content.aspx?id=38449. Accessed May 15, 2014.

10. Simons FE. Anaphylaxis in infants: can recognition and management be improved? J Allergy Clin Immunol. 2007;120:537.

11. Tracy JM, Khan FS, Demain, JG. Insect anaphylaxis: where are we? The stinging facts 2012. Curr Opin Allergy Clin Immunol. 2012;12:400–405.

12. Lajeunesse, ME, Hunt LP, Heath PT, Finn A. Anaphylaxis as an adverse event following immunization in the UK and Ireland. Arch Dis Child. 2012;97:487–490.

13. Liberman DB, Teach SJ. Management of anaphylaxis in children. Pediatr Emerg Care. 2008;24:861–869.

14. Brown SG. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol. 2005;5:359.

15. Tewari A, Du TG, Lack G. The difficulties of diagnosing food-dependent exercise-induced anaphylaxis in childhood—a case study and review. Pediatr Allergy Immunol. 2006;17:157.

16. Walker DM. Update on epinephrine (adrenaline) for pediatric emergencies. Current Opin Pediatr. 2009;21:313–319.

17. Russel S, Monroe K, Losek JD. Anaphylaxis Management in the Pediatric Emergency Department. Pediatr Emerg Care. 2010;26:71–76.

18. Stone KD. Advances in pediatric allergy. Curr Opin Pediatr. 2004;16: 571.

19. Simons FE. Pharmacologic treatment of anaphylaxis: can the evidence base be strengthened? Curr Opin Allergy Clin Immunol. 2010; 10:384–393.

20. Inomata N. Wheat allergy. Curr Opin Allergy Clin Immunol. 2009;9: 238–243.

21. Laxenaire MC, Mertes PM. Anaphylaxis during anaesthesia. Results of a two-year survey in France. Br J Anaesth. 2001;87:549.

22. Sicherer SH, Simons FE. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics. 2007;119:638.

23. Simons FE, Gu X, Silver NA, Simons KJ. EpiPen Jr versus EpiPen in young children weighing 15 to 30 kg at risk for anaphylaxis. J Allergy Clin Immunol. 2002;109:171.