Anaphylaxis

By admin On Dec 17, 2023

Ovid: 5-Minute Sports Medicine Consult, The

Anaphylaxis

Kristina M. Wilson

Basics

The causative agent in anaphylaxis remains unknown in up to 1/3 of cases.
Food is the most common causative agent (about 1/3 of known cases) in children.
Pharmacotherapeutic agents are the most common cause in adults.
Other common causes include Hymenoptera stings and latex.
Key to management and treatment is early recognition and immediate initiation of appropriate medical therapy.
Epinephrine is the undisputed initial therapy for anaphylaxis, and its administration never should be delayed.
Failure to inject epinephrine promptly has been identified as the most important factor contributing to death in patients experiencing anaphylaxis.

Description

Serious allergic reaction that is rapid in onset and may cause death
A systemic condition caused by an IgE-mediated reaction that is often life-threatening and almost always unanticipated:
- Involves the respiratory and/or cardiovascular systems
- Patients may have a history of less severe reaction previously on exposure to relevant allergen.
Exercise-induced anaphylaxis (EIAn):
- Occurs in response to physical exertion
- Subset of patients must have associated food trigger—food-dependent exercise-induced anaphylaxis (FDEIAn).
Cold urticaria:
- Reproducible, rapid onset of erythema, pruritus, and edema after exposure to cold
- Most idiopathic
- Occasionally involves abnormal circulating proteins (ie, cryoglobulins or cryofibrinogens); agglutinate or precipitate at lower temperatures

Epidemiology

Death rates from the most common causes of anaphylaxis have varied:
- Food-induced has remained stable.
- Insect sting has declined.
- Drug-induced has increased significantly—300% over past decade.
Exercise-induced anaphylaxis:
- Female-to-male ratio 2:2.5
- Most reported cases in young adults and adolescents
- Most patients have a reduction in the number of attacks over time (2)[B].

Incidence

8–50/100,000 person-years in Western countries
Incidence rates vary widely owing to differences in sample populations, data-collection methods, and varying definitions of anaphylaxis.

Prevalence

Lifetime prevalence of 0.05–2.0% in Western countries, rising especially in children
Exercise-induced anaphylaxis and food-dependent, exercise-induced anaphylaxis:
- Difficult: Few systematic attempts to determine
- Best estimates are from a cross-sectional survey of school nurses in Japan (3)[B]:
  - EIAn 0.03%
  - FDEIAn 0.017%

Risk Factors

Prior anaphylaxis event can predict subsequent anaphylaxis:
- As the only risk factor, prior anaphylaxis has a poor ability to identify patients who might develop anaphylaxis.
- 14% of anaphylaxis admissions for peanut sensitivity have a prior history of anaphylaxis.
Often occurs following a previous mild allergic reaction to the same allergen.
Most proposed risk factors have limited value owing to a low specificity.
- Coexisting atopic disease; particularly poorly controlled asthma
- Older age at 1st reaction to food allergy
Clinical risk factors for fatality in anaphylactic reactions (1)[B]:
- Food-induced:
  - Coexisting asthma (90–100%)
  - Age >10 yrs at the time of anaphylactic episode (54–65%)
  - Absence of or delayed access to an adrenaline autoinjector (80–87%)
  - Peanut or tree-nut allergy (38–81%)
- Drug-induced:
  - Elderly age group (75% were 55–85 yrs old)
  - Presence of cardiovascular (33%) or respiratory (17%) comorbidity
- Insect sting: Male predominance (95% male)

General Prevention

Avoidance of known allergen
No available tests exist to predict the likelihood of a person developing anaphylaxis.
Neither size of skin prick test wheal nor the level of serum-specific IgE correlates with reaction severity.
Immunotherapy:
- Hymenoptera venom and penicillin: Currently available
- Food allergens: Being investigated
Exercise-induced anaphylaxis:
- Daily administration of an H₁ antihistamine
- Food restriction 2–6 hrs prior to athletic activity
Cold-induced anaphylaxis:
- Avoidance of:
  - Cold water and air
  - Cold food and beverages
Promising outlooks: Characterization of β-cell epitope responses:
- Specific allergenic epitopes may correlate with severity of reaction.
- Individuals have a unique fingerprint of IgE-specific allergenic epitopes, and characterization of this profile may help to determine risk of anaphylaxis.

P.21

Etiology

Allergic: IgE-mediated:
- Drugs
- Venom
- Latex
- Vaccines
- Food
Nonallergic: Direct basophil/mast cell mediated
- Radio-contrast dye
- Opioid drugs

Diagnosis

Diagnosis is made based on clinical symptoms:
- Do not underestimate the potential severity of an allergic reaction in its early stages.
- Symptoms may progress rapidly.
Suspicion of anaphylaxis requires immediate medical intervention and should not be delayed by diagnostic tests.
Clinical criteria for diagnosing anaphylaxis (1)[C]:
- Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives; pruritus or flushing; swollen lips, tongue, and/or uvula) and at least one of the following:
  - Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow (PEF), hypoxemia)
  - Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia/collapse, syncope, incontinence)
- 2 or more of the following that occur rapidly after exposure to a likely allergen for that patient:
  - Involvement of the skin–mucosal tissue (eg, generalized hives; itch or flush; swollen lips, tongue, and/or uvula)
  - Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduce PEF, hypoxemia)
  - Reduced BP or associated symptoms (eg, hypotonia/collapse, syncope, incontinence)
  - Persistent GI symptoms (eg, crampy abdominal pain, vomiting)
- Reduced BP after exposure to known allergen for that patient:
  - Infants and children: Low systolic BP (age-specific) or >30% decrease in systolic BP
  - Adults: Systolic BP of <90 mm Hg or >30% decrease from that person's baseline

History

Previous history of anaphylaxis
Symptoms
- Fatigue
- Pruritus
- Urticaria
- Angioedema
- Wheezing
- Rhinitis
- GI distress
- Cardiovascular collapse
Time between exposure or suspected exposure and event, may happen within seconds
Recent changes in baseline health
Contributing environmental factors:
- Extremes of temperature
- Elevated humidity
- Increased pollen count
Contributing personal factors:
- Physical exertion
- Ethanol consumption
- Insect sting
- Food consumption
- Stress
- Menses
Medications:
- NSAIDs
- Aspirin
- Antibiotics
- ACE inhibitors
Comorbid medical conditions:
- Asthma
- COPD
- Cardiovascular disease
- Mastocytosis
If patient has a history of anaphylaxis: Previous treatments and their effects

Physical Exam

Respiratory: Bronchospasm, laryngeal edema
Cardiovascular: Hypotension, dysrhythmias, myocardial ischemia
GI: Nausea, vomiting, diarrhea
Cutaneous: Urticaria, angioedema
Hematologic: Activation of intrinsic coagulation pathway sometimes leading to disseminated intravascular coagulation (DIC), thrombocytopenia
Neurologic: Seizures
Death can occur from airway obstruction or circulatory collapse.

Diagnostic Tests & Interpretation

Lab

There are no specific tests to make the diagnosis of anaphylaxis, and evaluation should not delay diagnosis and treatment.
For respiratory distress after administration of epinephrine, an arterial blood gas analysis may be helpful in evaluating ventilatory status.
These changes can be noted during anaphylaxis:
- Elevation of plasma histamine level
- Increase in hematocrit secondary to fluid extravasation
May obtain tryptase levels:
- Must be drawn within 3 hrs of symptom onset
- Must be placed on ice
- Rarely elevated in food-induced anaphylaxis

Diagnostic Procedures/Surgery

ECG: Abnormalities including dysrhythmias, ischemic changes, infarction

P.22

Differential Diagnosis

Pulmonary embolism
Acute myocardial infarction
Airway obstruction
Asthma
Tension pneumothorax
NSAID reaction
Vasovagal collapse
Septic shock
Hereditary angioedema
Serum sickness
Systemic mastocytosis
Pheochromocytoma
Carcinoid syndrome

Treatment

Pre-Hospital

ABCs
Remove trigger (ie, stinger from insect).
Early administration of epinephrine IM in the anterolateral thigh positively affects outcome (4)[B].
- If preloaded epinephrine is available, it is prudent to administer prior to emergency personnel arriving if anaphylaxis is suspected.
- May be administered every 5–15 min as needed based on patient's condition.
- Call 911 for emergent transfer to hospital.
Recumbent position with legs elevated (5)[B]: Maintenance of central vascular compartment volume
Albuterol: Metered-dose inhaler (MDI) or nebulized solution if bronchospasm not relieved by administration of epinephrine: Every 20 min or continuously
Diphenhydramine: Cochrane Review 2007 of H₁ antihistamines in anaphylaxis revealed no studies that provided evidence for the use of H₁ antihistamines in anaphylaxis (6)[B].
- Onset of action takes 1–2 hrs.
- Relieves pruritus, urticaria, and angioedema
- Works synergistically with epinephrine
- Does not relieve upper or lower respiratory tract obstruction or circulatory collapse
- Does not prevent fatality

ED Treatment

Continuous cardiac and vital sign monitoring until stable.
Persistent bronchospasm can be treated with β-agonist bronchodilators.
Hypotension should be treated with isotonic volume. Vasopressors and Trendelenburg positioning are useful adjuncts.
Antihistamines (both H₁ and H₂ blockers) have been shown to be helpful in preventing histamine interactions with target tissues.
- Not a 1st-line treatment
- Does not treat life-threatening symptoms of anaphylaxis (6)[B]
- Most helpful treating cutaneous symptoms
Corticosteroids have never been shown in placebo-controlled trials to affect the course of anaphylaxis but are used to treat associated conditions (eg, asthma, allergic rhinitis):
- Onset 4–6 hrs
- May decrease the chance of having a biphasic reaction:
  - 2nd episode of anaphylaxis after treatment for 1st episode
  - Occurs 2–72 hrs after onset of 1st episode
  - 80% occur within the 1st 4 hrs of initial episode.
Glucagon is useful in epinephrine-resistant anaphylaxis from β-adrenergic blocking agents.

Medication

First Line

Epinephrine (EpiPen):

Adult: 0.3–0.5 mg (use 1:1,000 dilution for SC route)
Children: 0.01 mg/kg SC (maximum dose 0.3 mg)
Preloaded syringe: 0.15 mg per injector (EpiPen Jr) and 0.30 mg per injector (EpiPen)
Refractory hypotension:
- Epinephrine drip 0.1–1 mcg/kg/min (maximum 10 mcg/min)
- Titrated based on clinical effect; must be on cardiac monitor owing to risk of lethal cardiac arrhythmias

Second Line

β-agonist: Albuterol:
- MDI
- Continuous nebulizer treatment
H₁ antagonist: Diphenhydramine:
- Adult: 50 mg IV
- Children: 1–2 mg/kg slow IV pump (IVP)
Steroids:
- Methylprednisolone: Severe reactions:
  - Adult: 125 mg IV
  - Children: 1–2 mg/kg IV (maximum single dose 60–80 mg)
- Prednisone: Mild reactions:
  - Adult: 60 mg PO
  - Children: 1–2 mg/kg PO (maximum single dose 60–80 mg)
- Hydrocortisone:
  - Adults: 500 mg IV
  - Children: 4–8 mg/kg per dose IV
Oxygen: Respiratory distress/hypoxia
H₂ antagonist:
- Ranitidine: Adult: 50 mg IV or
- Cimetidine: 300 mg IV; children: 1–2 mg/kg (maximum dose 75–150 mg)
Glucagon: For refractory hypotension, especially if patient is on a beta blocker:
- Adult: 1 mg IV
- Children: 20–30 mcg/kg (maximum dose 1 mg) given over 5 min; followed by an infusion of 5–15 mcg/min titrated to effect

In-Patient Considerations

Initial Stabilization

ABCs:
- Ensure adequate ventilation.
- Endotracheal intubation may be required but is difficult because of laryngeal edema or spasm.
- Transtracheal jet insufflation or cricothyrotomy may be necessary to control the airway.
Epinephrine IM
Aggressive volume resuscitation with crystalloids to maintain BP; transfer of as much as 50% of the intravascular fluid into the extravascular space may occur within 10 min.
In volume-refractory hypotension, may need continuous IV epinephrine or other vasopressors (eg, vasopressin or dopamine)
Monitor for biphasic reaction

P.23

Admission Criteria

Intubated patients, patients in respiratory distress, and patients with refractory hypotension should be admitted to an ICU setting.
A monitored bed may be necessary for the patient who has not had substantial response to initial therapy.
Patients with significant generalized reactions and persistent symptoms should be admitted for observation for 24 hr.

Discharge Criteria

Individualized based on the following criteria (7)[C]:
- Initial presentation
- Response to therapy
- Availability of close observation at home
- Accessibility of a medical facility from home
Patients with complete resolution of symptoms may be discharged after 4–6 hr of ED observation.
- Epinephrine duration—1 hr
- Majority of biphasic reactions occur within the 1st 4 hr of initial episode.
Continuation of H₁ antagonist, H₂ antagonist, and corticosteroids for minimum 48 hr after discharge
Patients with allergic reactions should have follow-up within 48 hr of discharge to evaluate effectiveness of outpatient therapy.
Severity of the reaction should be emphasized to each patient and family.
Anaphylaxis action plans:
- Education about prevention and prehospital management
- Prescription for self-administered epinephrine and instructions on its use
- Patients with a known trigger should be counseled on strict avoidance of that trigger.
- Limited evidence on their impact on recurrence of anaphylaxis or reduction in fatal events (8)[B]
A follow-up visit with an allergist is also recommended for consideration of allergy testing exercise ± food provocation test.

References

1. Shadick NA, Liang MH, Partridge AJ, et al. The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study. J Allergy Clin Immunol. 1999;104:123–127.

2. Aihara Y, Takahashi Y, Kotoyori T, et al. Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students. J Allergy Clin Immunol. 2001;108:1035–1039.

3. Tang ML, Osborne N, Allen K. Epidemiology of anaphylaxis. Curr Opin Allergy Clin Immunol. 2009;9:351–356.

4. Sheikh A, Shehata YA, Brown SG, et al. Adrenaline for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2009;64:204–212.

5. Oswalt ML, Kemp SF. Anaphylaxis: office management and prevention. Immunol Allergy Clin North Am. 2007;27:177–191.

6. Sheikh A, ten Broek VM, Brown SGA, et al. H₁ antihistamines for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2007;1:CD006160.

7. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions—guidelines for healthcare providers. Resuscitation. 2008;77:157–169.

8. Nurmatov U, Worth A, Sheikh A. Anaphylaxis management plans for the acute and long-term management of anaphylaxis: a systematic review. J Allergy Clin Immunol. 2008;122:353–61, 361.e1–361.e3.

Additional Reading

Liberman DB, Teach SJ. Management of anaphylaxis in children. Pediatr Emerg Care. 2008;24:861–866.

Lieberman P. Epidemiology of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:316–320.

Pumphrey RSH. When should self-injectible epinephrine be prescribed for food allergy and when should it be used? Curr Opin Allergy Clin Immunol. 2008;8:254–260.

Soar J, Guideline Development Group. Emergency treatment of anaphylaxis in adults: concise guidance. Clin Med. 2009;9:181–185.