Medscape: Pediatric Anaphylaxis

Pediatric Anaphylaxis
Author: Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP; Chief Editor: Kirsten A Bechtel, MD more…
Updated: Nov 7, 2014
Overview
Anaphylaxis is an acute, potentially life­threatening syndrome — with multisystemic manifestations due to the rapid
release of inflammatory mediators. In children, foods can be a significant trigger for immunoglobulin E (IgE)­
mediated anaphylaxis. Milk, eggs, wheat, and soy (MEWS) as a group are the most common food allergens;
however, peanuts and fish are among the most potent. In fact, children can develop anaphylaxis from the fumes of
cooking fish or residual peanut in a candy bar.
Other common triggers include preservatives (in food and drugs), medications (antibiotics), insect venom (bee sting),
and bioactive substances (eg, blood, blood products). Environmental allergens such as pollens, molds, and dust
mites are a less common and infrequent cause of anaphylaxis. Non­IgE triggers include infection, opiates,
radiocontrast dye, and exercise.
To see complete information on Anaphylaxis, please go to the main article by clicking here.
Anaphylaxis vs anaphylaxis syndrome
Although the clinical presentation and management are the same, the term anaphylaxis generally refers to IgEmediated
reactions, whereas the term anaphylactoid generally refers to non–IgE­mediated reactions. The term
anaphylaxis syndrome is best used to describe clinical symptoms and signs.
Pathophysiology
IgE­ and Non–IgE­Mediated Reactions
Both IgE and non­IgE activation of mast cells and basophils ignites a cascade that results in the release and
production of several inflammatory and vasoactive substances. These bioactive materials include histamine,
tryptase, heparin, prostaglandins (PGD2
, PGF2
), leukotrienes (LTC4
, LTD4
, and LTE4
), cytokines (TNF‑α), and
platelet­activating factor (PAF). In anaphylaxis, these substances most commonly involve the skin, respiratory,
cardiovascular, and gastrointestinal systems. As a result, urticaria, angioedema, bronchospasm, bronchorrhea,
laryngospasm, increased vascular permeability and decreased vascular tone, and bloody diarrhea can develop.
The most common cause of mediator release is due to an IgE­mediated reaction. A previously sensitized B
lymphocyte produces IgE against a specific antigen. The IgE resides on the mast cells and basophils. When the
specific antigen, or one similar to it, binds to the high affinity FcεRI­α receptor of the immunoglobulin, mast cell and
basophil degranulation occurs.
Non­IgE mediator release can be triggered by several different mechanisms including stimulation of the complement
cascade to produce C3a, C4a, and C5a anaphylatoxin, neuropeptide and cytokine activity, and direct stimulation of
the kallikrein­kinin system by certain agents (eg, opiates, radiocontrast media).
Activation of Histamine Receptors
Many of the clinical presentations seen in anaphylaxis are due to activation of multiple histamine receptors.
[1] For
example, acute bronchospasm (wheezing, dyspnea) is a result of the interaction between H1 and H2
receptor
activity; bronchial smooth muscle constriction and increased mucus viscosity from H1
receptor activity and H2 activity
causes increased mucus production. The combination of H1 and H2
receptor stimulation results in increased
vascular permeability, flushing, hypotension, tachycardia, and headache. H1 and H3 activity results in cutaneous itch
and nasal congestion.
Other Precipitating Agents in Anaphylaxis
Histamine, however, is not the only agent to cause symptoms in anaphylaxis.
[2] Prostaglandins, leukotrienes, and
PAF all contribute to the bronchoconstriction, vascular changes, and changes in vascular capacitance (increased
vascular permeability and vasodilatation). One study showed an inverse correlation between PAF acetylhydrolase
activity and the severity of anaphylaxis.
[3] Compared with a placebo group, patients with anaphylaxis due to peanuts
who had low PAF acetylhydrolase activity were more likely to have a fatal outcome.
Common Triggers of Pediatric Anaphylaxis
Foods are the most common trigger of anaphylaxis in children, with peanuts being the most frequent primary cause.
[4] The following list is only meant to be illustrative of the more common anaphylactic triggers and therefore should
not be considered an exhaustive listing. These triggering agents may cause an IgE­ or non–IgE­mediated
anaphylaxis:
Foods (most common cause in children) – Milk, eggs, wheat, soy, fish, shellfish, legumes (peanuts), tree
nuts
[5] Medicinals – Antibiotics (penicillins, cephalosporins), local anesthetics (lidocaine), analgesics (aspirin,
nonsteroidal anti­inflammatory drugs [NSAIDS] [ibuprofen], opiates [codeine, morphine]), dextran,
radiocontrast media
Biologics – Venoms (bee sting, ant or snake bite), blood and blood products, vaccines, allergen extractsPreservatives and additives – Metabisulfite, monosodium glutamate
Other – Latex
Unknown, idiopathic causes
Epidemiology of Anaphylaxis in Children
Although Bohlke and colleagues estimated the rate of anaphylaxis in children at 10.5 per 100,000 person­years,
[6] the Rochester Epidemiology Project showed a rate of 75.1 per 100,000 person­years in children aged 9 years and
65.2 per 100,000 person­years in children aged 10­19­years old.
[7] Furthermore, anaphylaxis appears to be more
common in boys until the age of 15 years; a female preponderance then continues through adulthood.
[8, 9] Infants
younger than 12 months of age with anaphylaxis will more often have a history of atopic dermatitis.
[10] While asthma is more prevalent and has a higher mortality rate in black children, race does not appear to affect the
likelihood of developing anaphylaxis.
[11] Evaluation of Pediatric Anaphylaxis
Signs and Symptoms
Anaphylaxis involves a range of signs and symptoms from hives, wheezing and angioedema to cardiovascular
collapse and death.
[12, 13] More than 80% of the patients will present with cutaneous symptoms (eg, hives, pruritus,
facial swelling). Generally, at least 2 organ systems (skin, respiratory, cardiovascular, gastrointestinal systems) are
involved; however, anaphylaxis can present with a low systolic blood pressure for age or decrease in systolic blood
pressure by more than 30% after known allergen exposure alone.
[14] The Second National Institute of Allergy and Infectious Disease (NIAID) / FAAN symposium proposed diagnostic
criteria that would identify at least 95% of the patients with anaphylaxis.
[14] The primary clinical diagnostic criteria
include the acute onset of skin and/or mucosal symptoms along with either respiratory compromise (eg,
bronchospasm, stridor, shortness of breath) and/or persistent gastrointestinal symptoms (crampy abdominal pain,
vomiting) and/or reduced blood pressure or associated symptoms of end­organ dysfunction (eg, hypotonia, syncope,
incontinence).
Usually, cutaneous symptoms present first. Often, a history of exposure to a known trigger is given, (eg, bee sting,
peanut ingestion, antibiotic administration). At times, the inciting agent may be unknown or unclear. Symptoms may
develop slowly and insidiously over several hours or may rapidly progress over several minutes. Parenteral agents
generally have a faster onset of symptoms than ingested ones.
Anaphylaxis may result in respiratory failure, shock, multiorgan system failure, and disseminated intravascular
coagulation. Between 5% and 20% of patients may experience a recurrence of anaphylaxis 8­12 hours after the
initial presentation.
[15] Prolonged symptoms can last up to 32 hours despite treatment.
[12] To see complete information on Anaphylaxis, please go to the main article by clicking here.
Special challenges
Initial symptoms may include an awareness that “something isn’t right”; a tingling sensation in the mouth; itchy,
watery nose and eyes; and/or the feeling of being warm and flushed. However, children and especially infants may
not be able to verbally express the initial subjective symptoms of anaphylaxis. Infants may be more likely to have
crying, persistent vomiting and irritability than older children.
[10] Additionally, the verbal child may not be able to
identify the triggering agent (eg, food) even when known to the parent or caretaker.
Differential Diagnosis
Angioedema
Asthma
Bee and Hymenoptera Stings
Carcinoid Tumor
Exercise­Induced Anaphylaxis
Serum Sickness
Shock
Shock, Cardiogenic
Shock, Hypovolemic
Status Asthmaticus
Syncope
Toxicity, Seafood
Anaphylaxis is essentially a clinical diagnosis. The primary clinical diagnostic criteria include the acute onset of skin
and/or mucosal symptoms along with either respiratory compromise (eg, bronchospasm, stridor, shortness of breath)
and/or persistent gastrointestinal symptoms (crampy abdominal pain, vomiting) and/or reduced blood pressure or
associated symptoms of end­organ dysfunction (eg, hypotonia, syncope, incontinence).
Other problems to be considered include mastocytosis, physical urticaria, “red man syndrome” (related to the
intravenous administration of vancomycin), and vocal cord dysfunction.
Diagnosis of Pediatric AnaphylaxisLaboratory tests generally are not useful for the acute diagnosis of this condition, although serum histamine and
tryptase may be of limited help in confirming the diagnosis retrospectively; other tests (eg, specific antigen testing
following recovery) may provide some clues to triggering agents.
[16] Serum Histamine and Tryptase levels
Serum histamine level rises quickly with the onset of symptoms but does not remain elevated after 30­60 minutes.
Serum tryptase level peaks 60­90 minutes after the onset of symptoms and remains elevated for up to 5 hours. β­
tryptase is released with degranulation of mast cells, whereas α­tryptase is secreted constitutively by the mast cells.
The ratio of total tryptase to β­tryptase can help distinguish systemic mastocytosis from anaphylaxis. A ratio ≤10
implies anaphylaxis, whereas a ratio ≥20 is consistent with systemic mastocytosis.
[17] C1INH, VMA, RAST, and Cutaneous Antigen Testing
Other tests that may be useful in distinguishing anaphylaxis from the differential diagnosis include C1 inhibitor
functional assay (C1INH) (hereditary angioedema) and urine vanillylmandelic acid (VMA) and serum serotonin levels
(carcinoid syndrome).
Radioallergosorbent test (RAST) or cutaneous antigen testing (preferably by a specialist) can be used after recovery
to try to identify the inciting antigen.
Treatment of Children With Anaphylaxis
Overview
The early use of epinephrine is the most important step in managing anaphylaxis. Administration in the anterolateral
thigh appears to provide superior absorption compared with deltoid and subcutaneous injections.
Prehospital care should be directed at stabilization of the airway, breathing, and circulation (the “ABCs”). In
addition, intravenous (IV) access should be obtained; intraosseous (IO) access should be considered when IV
access cannot be quickly obtained in unstable patients.
Patients with signs of poor profusion should be placed in a modified Trendelenburg position with the legs elevated.
Crystalloid fluids should be given rapidly if the patient is hypotensive or has other signs of shock.
Emergency department consultation with a pediatric critical care specialist should be obtained in unstable patients
and those unresponsive to treatment. Outpatient consultation with an allergist is appropriate for most patients with
anaphylaxis, especially those with the following factors:
Significant clinical presentation or those requiring prolonged treatment
History of atopic disease
Unclear trigger or inciting agent
Recurrent episodes of anaphylaxis
Not all patients will present in shock. Most patients present with skin complaints (eg, urticaria, angioedema) along
with respiratory, gastrointestinal, or cardiovascular symptoms. Primary attention is directed at the stabilization of the
patient’s airway, breathing, and circulation. If not already given, epinephrine (which acts as a physiologic antagonist)
should be administered as soon as the diagnosis is suspected.
It cannot be stressed enough that the early use of epinephrine is the most important step in managing anaphylaxis.
[12, 18, 19] Antihistamines (H1 and H2 blockers), corticosteroids, crystalloid fluids, and other adrenergic agonists can
also be beneficial in the management of this condition.
To see complete information on Anaphylaxis, please go to the main article by clicking here.
Observation Versus Inpatient Monitoring
Even patients with mild symptoms should be observed for a minimum period of time. Although the time of
observation should be individualized to the patient, a minimum of 4­8 hours appears appropriate.
Children who require fluid resuscitation, multiple doses of epinephrine, or repeated doses of a bronchodilator should
be hospitalized. At a minimum, children who require vasopressors or glucagon should be admitted to a tertiary
pediatric intensive care center (PICU).
Airway Management
If the patient is hypoxic or has respiratory complaints, high­flow oxygen (warm, humidified air is preferred) by
nonrebreather mask should be given. In the awake child who is having some difficulty maintaining their airway, a
nasopharyngeal (NP) airway is better tolerated than an oropharyngeal (OP) airway.
Continuous positive airway pressure (CPAP) may be considered before using an advanced airway (eg, noninvasive
pharyngeal airway, endotracheal intubation) if the child is unable to maintain his or her airway, has decreased
oxygen saturation, and/or has a decreasing level of consciousness. The use of noninvasive positive pressure (eg,
CPAP) may help avoid the need for an advanced airway. In patients with signs of significant hypoxia, an advanced
airway (eg, supraglottic airway device, endotracheal intubation) should be considered. The airway should be secured
with an endotracheal tube early in cases of upper airway obstruction.
Nebulized albuterol (2.5­5 mg/dose) may be used for bronchospasm not responding to epinephrine. Although the
addition of ipratropium to albuterol has been shown to be beneficial in severe asthma exacerbations in children, this
combination in anaphylaxis has not been studied. Nebulized epinephrine has been used for stridor secondary to
laryngeal edema but has not been studied in anaphylaxis.
Epinephrine Administration
Epinephrine is the first drug of choice. The 1:1000 strength should preferentially be administered intramuscularly(IM) in to the thigh. Subcutaneous (SC) administration is no longer recommended.
[14, 18, 20] Because of the risk of
potentially lethal dysrhythmias, IV/IO epinephrine (1:10,000) should be reserved for the patient with uncompensated
shock.
The epinephrine dose may be repeated every 5­15 minutes. Administration in the anterolateral thigh appears to
provide superior absorption compared with deltoid and SC injections.
[21, 22] Subcutaneous injection is not
recommended. For mild symptoms, diphenhydramine may be given orally via IM/IV administration.
Nebulized albuterol (2.5­5 mg/dose) may be used for bronchospasm not responding to epinephrine. Although the
addition of ipratropium to albuterol has been shown to be beneficial in severe asthma exacerbations in children, this
combination in anaphylaxis has not been studied. Nebulized epinephrine has been used for stridor secondary to
laryngeal edema but has not been studied in anaphylaxis.
Blood Pressure Management
Patients with hypotension unresponsive to positioning and epinephrine should receive a 20 mL/kg rapid crystalloid
fluid bolus (eg, lactated Ringer or isotonic sodium chloride). Repeat boluses up to 60­80 mL/kg may be necessary
for correcting the hypovolemia.
Recall that children are more likely to have compensated shock in which tachycardia and signs of hypoperfusion (eg,
decreased peripheral pulses, cool extremities) are present, but the blood pressure is normal.
[23] A systolic pressure
of less than the 5
th percentile for age would indicate uncompensated shock, which correlates to the following:
< 70 mm Hg in children aged 1­12 months
< 70 mm Hg + (2× age in years) in children aged 1­10 years
< 90 mm Hg in children aged ≥10 years
Glucagon may help with refractory symptoms in the patient taking a beta­blocker. In children, administer 20­30
mcg/kg (not to exceed a cumulative dose of 1 mg) IV over 5 minutes, followed by an IV maintenance infusion and
titrated to clinical effect at 5­15 mcg/min.
Treatment for Patients Unresponsive to Fluid Resuscitation
Patients unresponsive to fluid resuscitation should receive vasopressors as follows:
Epinephrine (0.1­1 mcg/kg/min IV) should be considered as the initial vasopressor in children. Doses at < 0.3
mcg/kg/min will tend to have more β­activity, whereas α­action becomes more pronounced at higher doses.
Dopamine (2­20 mcg/kg/min IV) may be used in addition to epinephrine. Greater α­activity is seen at higher
doses.
Norepinephrine (0.1­2 mcg/kg/min IV) is a potent vasopressor. It is usually considered in children
unresponsive to epinephrine.
Treatment of Cutaneous Symptoms
The combination of H1 and H2 antihistamines appears to be more effective, especially for cutaneous symptoms.
[14,
24] The onset of activity of these agents is slower than epinephrine and are considered next­in­line treatment.
Second­generation H1 antihistamines (eg, cetirizine, loratadine) have not been studied in anaphylaxis.
Diphenhydramine 1 mg/kg (not to exceed 50 mg/dose) may be given IV/IM/PO or ranitidine, which has a beneficial
side effect profile in children, 1 mg/kg (not to exceed 50 mg/dose IV or 150 mg/dose PO) may be given. The oral
use of these agents should be restricted to mild cases.
Treatment of Late Phase Reaction
Corticosteroids do not have an immediate effect on the symptoms of anaphylaxis but may help reduce or prevent a
biphasic “late phase” reaction. The choice of methylprednisolone (IV), prednisone, or prednisolone (PO) 1­2 mg/kg
should be based on the patient’s presentation and condition. The effect and time of onset are similar among these
agents. The dose may be repeated at 6­hour intervals as indicated.
No published studies compare dexamethasone with other corticosteroids in the treatment of anaphylaxis. However,
based on its use in other allergic conditions, a dose of dexamethasone 0.15­0.6 mg/kg IV would be appropriate.
Outcomes in Pediatric Anaphylaxis
The prognosis is good if anaphylaxis is treated early. The development of shock, however, is a poor prognostic
indicator. In fact, the risk of death due to respiratory and cardiovascular complications is significant in anaphylaxis.
Estimates of mortality from anaphylaxis vary from 100 to more than 500 cases per year in the United States; the
estimated death rate is 0.002%.
[25] Delayed/biphasic anaphylactic response
A delayed or biphasic anaphylactic response may occur in 1­20% of patients.
[26] The literature is unclear as to which
patients are at greatest risk from having this condition. The secondary response may be milder, the same, or more
severe than the initial presentation. Patients with greater risk of biphasic response should be observed a minimum
of 12­24 hours. Severity of symptoms, delay in receiving epinephrine, and ingested antigen have been implicated as
risk factors.
All patients who had more than mild symptoms and/or required more than 4 hours of observation should be given a
prescription for an auto­injector of epinephrine. Patients and families should be advised to call 911 or seek
immediate medical attention after epinephrine self­administration.
Patients should be continued on H1 and H2 blockers for 3 days after resolution of symptoms. A second generation
H1 may be used as part of discharge care. A 3­day course of oral steroids may be warranted.Patient Follow­up for Pediatric Anaphylaxis
Patients with anaphylaxis should follow up with their pediatrician and be given a referral for allergy evaluation and
counseling. Moreover, patients and their caregivers should be educated about exposure risk, early management,
and access to medical care.
Consider discharging patients with an action plan (such as those from the American Academy of Asthma, Allergy
and Immunology [AAAAI] or Food Allergy and Anaphylaxis Network [FAAN]). Exposure to inciting agent, if known,
should be avoided.
For excellent patient education resources, visit eMedicineHealth’s Allergies Center. Also, see eMedicineHealth’s
patient education articles Severe Allergic Reaction (Anaphylactic Shock), Food Allergy, and Allergy: Insect Sting.
Contributor Information and Disclosures
Author
Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP Associate Professor of Pediatrics and Emergency Medicine,
Associate Medical Director for Compliance and Business Affairs and EMS/Pre­Hospital Care Coordinator,
Department of Pediatrics, Division of Pediatric Emergency Medicine/Emergency Pediatric Group, Emory
University School of Medicine; Consulting Staff, Children’s Sedation Service, Children’s Healthcare of Atlanta
Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP is a member of the following medical societies: American
Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and American College of
Emergency Physicians
Disclosure: Nothing to disclose.
Chief Editor
Kirsten A Bechtel, MD Associate Professor of Pediatrics, Section of Pediatric Emergency Medicine, Yale
University School of Medicine; Attending Physician, Department of Pediatric Emergency Medicine, Yale­New
Haven Children’s Hospital
Kirsten A Bechtel, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Additional Contributors
Kirsten A Bechtel, MD Associate Professor, Department of Pediatrics, Yale University School of Medicine;
Attending Physician, Department of Pediatric Emergency Medicine, Yale­New Haven Children’s Hospital
Kirsten A Bechtel, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor­in­Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Wayne Wolfram, MD, MPH Associate Professor, Department of Emergency Medicine, Mercy St Vincent
Medical Center
Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency
Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
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