120 Anaphylaxis
• E nvironmental exposures: Bee or wasp sting,
BASIC INFORMATION
DEFINITION
Anaphylaxis is a severe allergic reaction that is
rapid in onset and life-threatening. In anaphy-
laxis, immunoglobulin E (IgE)-mediated systemic
degranulation of mast cells causes respiratory,
cardiovascular, gastrointestinal, and mucocuta-
neous signs or symptoms. Anaphylactoid reaction
is an entity closely related to anaphylaxis and
is caused by release of mast cells and baso-
phil mediators triggered by non–IgE-mediated
events.
SYNONYM
Anaphylactoid reaction
ICD-10CM CODES
T78.2 Anaphylactic shock, unspecified,
initial encounter
T78.00XA Anaphylactic reaction due to
unspecified food, initial encounter
T80.52XA Anaphylactic reaction due to
vaccination, initial encounter
T63.94XA Toxic effect of contact with
unspecified venomous animal,
undetermined, initial encounter
EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE: The incidence of anaphylaxis in
the U.S. is 50 to 2000 episodes per 100,000
persons. Lifetime prevalence is 0.05% to 2%,
with a mortality rate of 1%. Anaphylaxis rates
are 0.0004% for food, 0.7% to 10% for penicil-
lin, 0.22% to 1% for contrast media, and 0.5%
to 5% after insect stings. Mortality rates are
0.65% to 2% of patients presenting with ana-
phylaxis. Annual mortality is nearly 500 to 1000
persons/yr in the U.S.
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
• Mucocutaneous: Urticaria, pruritus, skin
flushing, angioedema (Table E1)
• Respiratory: Dyspnea, cough, wheezing,
hypoxia, stridor, rhinitis
• Gastrointestinal: Nausea, vomiting, diarrhea,
dysphagia, abdominal pain
• Cardiovascular: Hypotension, tachycardia,
weakness, dizziness, syncope, malaise, vas-
cular collapse (Table E2)
ETIOLOGY
• Anaphylaxis results from a sudden system-
atic release of histamine and other inflam-
matory mediators from basophils and mast
cells. Virtually any substance may induce
anaphylaxis. In an acute setting, the cause of
anaphylaxis is often unidentifiable:
• Foods and food additives: Peanuts, tree
nuts, eggs, shellfish, fish, cow’s milk, fruits,
soy
• Medications: Antibiotics (especially penicil-
lins and sulfa-based agents), insulin, allergen
extracts, opiates, vaccines, NSAIDs, contrast
media, streptokinase
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• R apidly establish intravenous (IV) access and
snake venom, fire ant venom
• Blood products: Plasma, immunoglobulin,
cryoprecipitate, whole blood
• Latex
• Exercise
• Box 1 summarizes agents frequently associ-
ated with immune and nonimmune types of
anaphylaxis
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Allergic reaction
• Other causes of shock such as sepsis or
pulmonary embolism
• Endocrine disorders (carcinoid, adrenal crisis,
paradoxical pheochromocytoma)
• Systemic mastocytosis
• Serum sickness
• Severe asthma (the key clinical difference is
the abrupt onset of symptoms in anaphylaxis
versus a history of progressive worsening of
symptoms)
• Scombroid poisoning
• Localized angioedema
• Acute urticaria
• Presyncopal syndromes including vasovagal
reactions
• Airway foreign body
• Globus hystericus, anxiety disorder
WORKUP
Workup is aimed at ruling out other conditions
that may mimic anaphylaxis. Given the poten-
tially life-threatening nature of anaphylaxis,
treatment should not be delayed. Clinical criteria
for diagnosing anaphylaxis are summarized in
Box 2.
LABORATORY TESTS
• Laboratory evaluation is generally not helpful
because anaphylaxis is typically a clinical
diagnosis.
• Elevated serum and urine histamine levels
and serum tryptase levels can be useful for
diagnosis of anaphylaxis, but these tests are
not commonly available in the emergency
setting.
IMAGING STUDIES
• Generally not helpful.
• Chest radiography for evaluation of foreign
body aspiration or pulmonary pathology is
indicated in patients with acute respiratory
compromise.
• Consider ECG in all patients with sudden
loss of consciousness or reports of chest
pain or dyspnea and in any elderly patient.
ECG in anaphylaxis usually reveals sinus
tachycardia.
TREATMENT
NONPHARMACOLOGIC THERAPY
• Establish and protect airway. Provide supple-
mental O2 if indicated.
administer IV fluids (i.e., normal saline).
• Cardiac monitoring is recommended.
ACUTE GENERAL Rx
• 0.3 to 0.5 mg intramuscular epinephrine
(1:1000 concentration) should be rapidly
administered for adults and children >30
kg in the lateral thigh. 0.01 mg/kg intra-
muscular epinephrine (1:1000 concentration)
should be administered for children <30
kg. Intramuscular administration is preferred
because it provides more reliable and quicker
rise to effective plasma levels. The dose may
be repeated after approximately 5 to 15
min if symptoms persist. Patients with mild
episodes should be observed for 1 hour after
resolution of symptoms. Patients with severe
symptoms should be observed for at least 6
hours.
• Adjunct therapies include H1 and H2 receptor
antagonists such as diphenhydramine 25 to
50 mg IV or intramuscular (or by mouth [PO]
in mild cases) and famotidine 20 to 40 mg
IV (or PO in mild cases). Although useful to
improve cutaneous erythema and pruritus,
H1 antagonists are not as effective as epi-
nephrine, since onset of action is 1 to 2 hr,
and they are not effective in reversing upper
airway obstruction or improving hypotension.
• Corticosteroids are not useful in the acute
episode because of their slow onset of
action; however, they should be administered
in most cases to prevent prolonged or recur-
rent anaphylaxis. Commonly used agents are
prednisone, methylprednisolone 40 to 250
mg IV in adults (1 to 2 mg/kg in children), or
dexamethasone.
• Aerosolized β-agonists (e.g., albuterol, 2.5
to 5.0 mg, repeat prn 20 min) are useful to
control bronchospasm.
• Vasopressor therapy with IV epinephrine
(1:10,000 concentration) indicated in patients
with refractory hypotension/cardiovascular
collapse after crystalloid resuscitation.
• Patients taking beta-blocking medications
may be refractory to initial treatment; con-
sider administration of IV glucagon.
• Table 3 summarizes drugs and other agents
used in anaphylaxis therapy.
• Fig. E1 illustrates an algorithm for the man-
agement of a patient with severe anaphylaxis.
PEARLS &
CONSIDERATIONS
COMMENTS
• Patient education regarding the nature of the
illness and preventive measures is recom-
mended. A documented history of previous
anaphylactic episodes or known triggers is
the most reliable method of identifying indi-
viduals at risk.
• Prescription for a prefilled epinephrine
syringe (EpiPen or EpiPen Jr.) should be
given, and the patient should be instructed on
the use of this emergency kit, and to carry it
with them at all times. School-aged children
Anaphylaxis 120.e1

TABLE E1 Dynamics of Cardiovascular Abnormalities in Anaphylactic Shock

At Onset of Reaction Early Stage (Minutes) with No Treatment Prolonged Shock
Blood pressure ↓ ↓↓ ↓↓↓
Pulse ↑ ↑ ↑↑
Cardiac output ↑ ↓ ↓↓
PVR ↓ →↓* →↑↓*
Intravascular volume →↓ ↓ ↓↓↓

*Peripheral vascular resistance (PVR) can vary, likely depending on internal compensation response.
From LoVerde D, Iweala OI, Eginli A, Krishnaswamy G. Anaphylaxis. Chest. 2018;153(2):528-543. https://doi.org/10.1016/j.chest.2017.07.033

TABLE E2 Signs and Symptoms of Anaphylaxis: Frequency

of Occurrence
Sign or Symptom Percentage of Cases (%)
Cutaneous >90
Urticaria and angioedema 85-90
Flush 45-55
Pruritus without rash 2-5
Respiratory 40-60
Dyspnea, wheeze 45-50
Upper airway angioedema 50-60
Rhinitis 15-20
Dizziness, syncope, hypotension 30-35
Abdominal
Nausea, vomiting, diarrhea, cramping 25-30
pain
Miscellaneous
Headache 5-8
Substernal pain 4-6
Seizure 1-2

Anaphylaxis

1st line

Epinephrine 0.3−0.5 mg repeated as needed

Fluid boluses if hemoconcentration or hypotensive
Avoidance/elimination of causal agent
O2 for SpO2 93%−95%
Airway protection (difficult airway procedures)
Methylprednisolone 1 mg/kg/day for 72 hr max
(+ antihistaminics)

2nd line
(persisting shock)

Methylene blue
Vasopressin
Angiotensin ?
Glucagon

FIG. E1 Management of a patient with severe anaphylaxis. O2, Oxygen; SpO2, oxygen saturation mea-
sured by pulse oximetry. (From Parrillo JE, Dellinger RP: Critical care medicine, principles of diagnosis and
management in the adult, ed 5, Philadelphia, 2019, Elsevier.)

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 Anaphylaxis 121

BOX 1  Agents Frequently Associated With Immune and Nonimmune Types of Anaphylaxis
A
Immunologic Mechanisms
Immunoglobulin E (IgE)-mediated:
Food (nuts, shellfish, fruits, etc.)
Venoms (stinging insects)
Medications (β-lactam antibiotics, NSAIDs, neuromuscular blocking agents, etc.)
Natural rubber latex
Seminal fluid
Radiocontrast media (in some cases)
IgE-Independent
Radiocontrast media (in most cases)
Dextrans

and Disorders
Diseases
Monoclonal antibodies (Rituximab)
Medications (β-lactam antibiotics, NSAIDs, etc.)
Natural rubber latex
Seminal fluid
Nonimmunologic Mechanisms
Medications (opioids, protamine, etc.)
From Parrillo JE, Dellinger RP. Critical care medicine, principles of diagnosis and management in the adult, ed 5, Philadelphia, 2019, Elsevier.
I
BOX 2  Clinical Criteria for Diagnosing Anaphylaxis
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled:
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized urticaria,
itching or flushing, swollen lips/tongue/uvula) and at least one of the following:
a. Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia collapse, syncope, incontinence)
OR
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):
a. Involvement of the skin-mucosal tissue (e.g., generalized urticaria, itch/flush, swollen lips/tongue/uvula)
b. Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced blood pressure or associated symptoms (e.g., hypotonia collapse, syncope, incontinence)
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)
OR
3. Reduced blood pressure after exposure to known allergen for that patient (minutes to several hours)
a. Infants and children: Low systolic blood pressure (age-specific) or >30% decrease in systolic blood pressure
b. Adults: Systolic blood pressure of <90 mm Hg or >30% decrease from that person’s baseline
From Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium, J Allergy Clin Immunol 117(2):391-397, 2006. https://doi.org/10.1016/j.jaci.2005.12.1303.

TABLE 3 Management of a Patient With Anaphylaxis

Treatment Mechanism(s) of Effect Dosage(s) Comments; Adverse Reactions
PATIENT EMERGENCY MANAGEMENT (DEPENDENT ON SEVERITY OF SYMPTOMS)
Epinephrine (adrenaline) α1-, β1-, β2-Adrenergic effects 0.01 mg/kg, up to 0.5 mg IM in lateral thigh Tachycardia, hypertension, nervousness,
Adrenaclick, Auvi-Q, EpiPen Jr./EpiPen: headache, nausea, irritability, tremor
0.15 mg IM for 8-25 kg
0.3 mg IM for 25 kg or more
Epinephrine autoinjector:
0.1 mg for 7.5-15 kg
0.15 mg for 15-25 kg
0.3 mg for 25 kg or more
Cetirizine (liquid) Antihistamine (competitive of Cetirizine liquid: 5 mg/5 ml0.25 mg/kg, up to 10 mg Hypotension, tachycardia, somnolence
H1 receptor) PO
Alternative: Diphenhydramine Antihistamine (competitive of 1.25 mg/kg up to 50 mg PO or IM Hypotension, tachycardia, somnolence,
H1 receptor) paradoxical excitement
Transport to an emergency facility
EMERGENCY PERSONNEL MANAGEMENT (DEPENDENT ON SEVERITY OF SYMPTOMS)
Epinephrine (adrenaline) α1-, β1-, β2-Adrenergic effects 0.01 mg/kg, up to 0.5 mg IM in lateral thigh Tachycardia, hypertension, nervousness,
Epinephrine autoinjector: headache, nausea, irritability, tremor
0.1 mg for 7.5-15 kg
0.15 mg for 15-25 kg
0.3 mg for 25 kg or more
0.01 ml/kg/dose of 1:1,000 (vial) solution, up to 0.5
ml IM
May repeat every 10-15 min
For severe hypotension: 0.01 ml/kg/dose of 1:10,000
slow IV push
Continued
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122 Anaphylaxis

TABLE 3 Management of a Patient With Anaphylaxis—cont’d

Treatment Mechanism(s) of Effect Dosage(s) Comments; Adverse Reactions
SUPPLEMENTAL OXYGEN AND AIRWAY MANAGEMENT
Volume Expanders
Crystalloids (normal saline or 30 ml/kg in 1st hr Rate titrated against BP response
Ringer lactate) If tolerated, place patient supine with
legs raised
Colloids (hydroxyethyl starch) 10 ml/kg rapidly followed by slow infusion Rate titrated against BP response
If tolerated, place patient supine with
legs raised
Antihistamines
Cetirizine (liquid) Antihistamine (competitive of Cetirizine liquid: 5 mg/5 ml Hypotension, tachycardia, somnolence
H1 receptor) 0.25 mg/kg, up to 10 mg PO
Alternative: Diphenhydramine Antihistamine (competitive of 1.25 mg/kg, up to 50 mg PO, IM, or IV Hypotension, tachycardia, somnolence,
H1 receptor) paradoxic excitement
Ranitidine Antihistamine (competitive of 1 mg/kg, up to 50 mg IV Headache, mental confusion
H2 receptor) Should be administered slowly
Alternative: Cimetidine Antihistamine (competitive of 4 mg/kg, up to 200 mg IV Headache, mental confusion
H2 receptor) Should be administered slowly
Corticosteroids
Methylprednisolone Antiinflammatory Solu-Medrol (IV): 1-2 mg/kg, up to 125 mg IV Hypertension, edema, nervousness,
Depo-Medrol (IM): 1 mg/kg, up to 80 mg IM agitation
Prednisone Antiinflammatory 1 mg/kg up, to 75 mg PO Hypertension, edema, nervousness,
agitation
Nebulized albuterol β-Agonist 0.83 mg/ml (3 ml) via mask with O2 Palpitations, nervousness, CNS
stimulation, tachycardia; use to
supplement epinephrine when
bronchospasm appears unresponsive;
may repeat
POSTEMERGENCY MANAGEMENT
Antihistamine Cetirizine (5-10 mg qd) or
loratadine (5-10 mg qd) for
3 days
Corticosteroids Optional: Oral prednisone (1
mg/kg up to 75 mg) daily
for 3 days
Preventive Treatment
Prescription for epinephrine autoinjector and antihistamine
Provide written plan outlining patient emergency management (may download form from http://www.aap.org or http://www.foodallergy.org)
Follow-up evaluation to determine/confirm etiology
Immunotherapy for insect sting allergy
Patient Education
Instruction on avoidance of causative agent
Information on recognizing early signs of anaphylaxis
Stress early treatment of allergic symptoms to avoid systemic anaphylaxis
Encourage wearing medical identification jewelry

BP, Blood pressure; CNS, central nervous system; IM, intramuscularly; IV, intravenously; PO, orally; qd, every day.
From Kliegman RM, Geme JS. Nelson Textbook of Pediatrics, Philadelphia, 2019, Elsevier.

should keep an additional EpiPen at school
with the appropriate staff.
• Patients should also be advised to carry or
wear a MedicAlert ID describing substances
that have caused anaphylaxis.
• Avoidance of radiologic contrast is also rec-
ommended in those who have had a prior
reaction. However, pretreatment regimens SUGGESTED READINGS
with methylprednisolone or diphenhydr- Available on the eBook. See ad in front of
amine, exist for those who have had contrast book for details.
reactions in the past.
• Venom immunotherapy immediately after a AUTHORS: Rory Merritt, MD, MEHP, and
sting is effective and recommended for up to Rachel Smith Shain, MD
5 yr after the anaphylactic incident.

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on January 13, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
Anaphylaxis 122.e1

SUGGESTED READINGS
Lieberman PL: Recognition and first-line treatment of anaphylaxis, Am J Med
127(1 Suppl):S6-S11, 2014. https://doi.org/10.1016/j.amjmed.2013.09.008.
Lieberman P et al: Anaphylaxis--a practice parameter update 2015, Ann
Allergy Asthma Immunol 115(5):341-384, 2015. https://doi.org/10.1016/j.
anai.2015.07.019.
LoVerde D et al: Anaphylaxis, Chest 153(2):528-543, 2018. https://doi.
org/10.1016/j.chest.2017.07.033.
Mustafa SS: Anaphylaxis. Medscape website. Published May 16, 2018. Available at
http://emedicine.medscape.com/article/135065-overview#a0101. Accessed
August, 21 2021.
Nowak RM, Macias CG: Anaphylaxis on the other front line: perspectives from the
emergency department, Am J Med 127(1 Suppl):S34-S44, 2014. https://doi.
org/10.1016/j.amjmed.2013.09.012.
Pflipsen MC, Vega Colon KM: Anaphylaxis: recognition and management, Am Fam
Physician 102(6):355-362, 2020.
Sampson HA et al: Second symposium on the definition and management of ana-
phylaxis: summary report--Second National Institute of Allergy and Infectious
Disease/Food Allergy and Anaphylaxis Network symposium, J Allergy Clin
Immunol 117(2):391-397, 2006. https://doi.org/10.1016/j.jaci.2005.12.1303.
Sclar DA, Lieberman PL: Anaphylaxis: underdiagnosed, underreported, and
undertreated, Am J Med 127(1 Suppl):S1-S5, 2014. https://doi.org/10.1016/j.
amjmed.2013.09.007.

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on January 13, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.