Basics
Description
- Anaphylaxis is a serious, life-threatening, systemic allergic reaction that is rapid in onset, and is a result of mast cell and basophil activation and degranulation.
- Skin and mucosal symptoms such as flushing, itching, urticaria, or angioedema are present in 80-90% of patients with anaphylaxis. Yet, absence of skin findings does not exclude anaphylaxis.
- In fatal anaphylaxis, initial signs and symptoms may include respiratory distress without urticaria resulting in delayed diagnosis and treatment.
Epidemiology
- 0.05-2% lifetime prevalence
- Rate of occurrence appears to be increasing.
- Estimated to be fatal in 0.7-2% of cases
Risk Factors
Genetics
There are few studies of genetic factors in human anaphylaxis; however, individuals with a previous history of anaphylaxis or a history of atopy are at increased risk for future anaphylaxis episodes.
Pathophysiology
- In anaphylaxis, mast cells and basophils are activated via an IgE-mediated (most common) or non-IgE-mediated mechanism releasing preformed and newly generated mediators of inflammation.
- Mediators include histamine, tryptase, proteoglycans, leukotrienes, prostaglandins, platelet-activating factor, and cytokines.
- Local or systemic effects can include increased vascular permeability, vasodilation, smooth muscle contraction, complement activation, and coagulation.
- IgE-mediated anaphylaxis occurs when IgE is synthesized in response to allergen exposure (sensitization) and becomes fixed to high-affinity IgE receptors located on the surface of mast cells and basophils. Subsequent allergen exposure results in receptor-bound IgE aggregation and cell activation.
- Non-IgE-mediated anaphylaxis generally results from nonimmune stimulation of mast cells or basophils. Rarely, IgG and complement can be implicated.
Etiology
- IgE-mediated:
- Foods (peanut, tree nuts, fish, shellfish, milk, egg, wheat, soy)
- Medications (antibiotics, especially, β-lactams, NSAIDs, biologic products)
- Venoms (usually from stinging insects including fire ants)
- Latex (direct exposure to natural rubber or ingestion of cross-reacting foods)
- Other (vaccines, occupational allergens, and rarely inhaled allergens)
- Non-IgE-mediated:
- Radiocontrast media (can also trigger IgE-dependent anaphylaxis)
- Medications (opiates, NSAIDs, dextrans, vancomycin, polymyxin B)
- Physical stimuli (exercise, cold, heat, sunlight/UV radiation)
- Ethanol
Diagnosis
Anaphylaxis is a clinical diagnosis that is considered highly likely when any one of the following three criteria is met:
- Acute onset of illness (minutes to hours) with involvement of skin, mucosa, or both and at least one of the following: (a) respiratory compromise or (b) reduced blood pressure or associated symptoms of organ dysfunction.
- Two or more of the following occurring acutely (minutes to hours) after exposure to a likely allergen: (a) involvement of skin-mucosal tissue (b) respiratory compromise (dyspnea, wheezing, stridor, hypoxemia), (c) reduced blood pressure or associated symptoms of organ dysfunction, (d) persistent gastrointestinal symptoms (abdominal cramping, vomiting).
- Reduced systolic blood pressure acutely (minutes to hours) after exposure to known allergen for that patient. Defined by age-specific normals or >30% decrease from patient's baseline
History
- A detailed history of exposures and events in minutes to hours prior to onset should be obtained after treatment is initiated.
- Any previous history of anaphylaxis?
- Can help direct history and patient education, especially if epinephrine was indicated but not given or if a known allergen was not recognized
- Food triggers
- Most common: peanut, tree nuts, fish, shellfish, milk, egg, wheat, soy, sesame, additives (spices, colorants, contaminants)
- Foods need to be ingested for a reaction to occur, but rarely anaphylaxis can be caused by inhalation of aerosolized vapors from cooking or processing (fish and shellfish).
- Gastrointestinal symptoms tend to be more prominent than in other etiologies.
- Medication triggers
- Specifically inquire about NSAIDs, supplements, and herbal treatments.
- β-Blockers and ACE inhibitors can increase severity and/or make treatment of anaphylaxis more difficult.
- Insect stings
- If possible, attempt to identify the insect (honeybees leave stinger at sting site).
- All patients should be referred to an allergist, as immunotherapy is effective in preventing 98% of future anaphylactic reactions.
- Natural rubber latex
- Latex-allergic patients can develop anaphylaxis after ingestion of cross-reactive foods including banana, kiwi, papaya, avocado, potato, and tomato.
Alert
For patients with anaphylaxis who are taking β-blockers or ACE inhibitors and have persistent hypotension and bradycardia despite epinephrine, consider giving glucagon.
Physical Exam
- Skin and mucosa
- Flushing, itching, conjunctival erythema, urticaria, angioedema
- Respiratory
- Upper airway: nasal itching, congestion, rhinorrhea, sneezing, dysphonia, hoarseness, stridor, drooling (can be a sign of angioedema or obstruction)
- Lower airway: tachypnea, cough, wheezing/bronchospasm, decreased peak expiratory flow
- Cyanosis, respiratory arrest
- Cardiovascular system
- Tachycardia or bradycardia (less common), hypotension, arrhythmias, shock, urinary or fecal incontinence, cardiac arrest
- Gastrointestinal
- Abdominal pain/cramping, vomiting, diarrhea, dysphagia
- Central nervous system
- Patients may appear uneasy or describe a sense of impending doom.
- Altered mental status, confusion, tunnel vision
Diagnostic Tests & Interpretation
Anaphylaxis is a clinical diagnosis; however, certain tests can aid in confirming the diagnosis. Treatment of anaphylaxis should be initiated immediately if a patient presents with a clinical picture that is consistent with anaphylaxis.
Lab
- Serum total tryptase
- Elevated 15 minutes to 3 hours after onset of anaphylaxis
- Elevated in patients with anaphylaxis due to injected medications, insect stings, and when hypotension is present
- Can be normal in anaphylaxis due to foods or in those who are normotensive
- Normal serum tryptase does not rule out anaphylaxis.
- Laboratory test that is routinely used in practice
- Plasma histamine
- Elevated if measured 15-60 minutes after onset of anaphylaxis due to its short half-life
- Blood sample requires special handling.
- Normal level does not rule out anaphylaxis.
- Urine histamine and N-methylhistamine
- 24-hour urine histamine and N-methylhistamine (metabolite) can be elevated in the context of anaphylaxis.
Imaging
Chest radiograph: may be useful to rule out foreign body aspiration, or congenital malformations of the respiratory or gastrointestinal tract
Differential Diagnosis
- Allergic/atopic
- Acute urticaria
- Acute asthma
- Pollen-food syndrome
- Cardiovascular
- Myocardial infarction
- Pulmonary embolus
- Genetic/metabolic
- Hereditary or acquired angioedema
- Infectious
- Neoplastic
- Mastocytosis/clonal mast cell disorders
- Carcinoid
- Basophilic leukemia
- Pheochromocytoma
- Neurologic
- Nonorganic disease
- Panic attack
- Vocal cord dysfunction
- Munchausen syndrome
- Other:
- Foreign body aspiration
- Scombroidosis (ingestion of fish containing high levels of histamine)
- Red Man syndrome
Treatment
Medication
First Line
- IM epinephrine 1:1,000 (1 mg/mL) solution
- 0.01 mg/kg, maximum of 0.3 mg (child) or 0.5 mg (adult), repeated q5-15min as needed (most respond to 1 or 2 doses)
- Many deaths from anaphylaxis are associated with delayed administration of epinephrine.
Second Line
- Diphenhydramine IV or PO (or equivalent H1-antihistamine)
- 1 mg/kg, maximum of 50 mg, q4-6h
- Albuterol 2.5 mg/3 mL solution
- Nebulized and inhaled via face mask
- Ranitidine IV
- Methylprednisolone IV (or equivalent glucocorticoid)
- 1-2 mg/kg, maximum of 60 mg (may be continued PO once daily for 1- to 3-day course)
- Thought to prevent biphasic or protracted anaphylaxis, but unlikely to provide benefit in initial minutes of anaphylaxis
Additional Therapies
General Measures
- Maintain airway:
- Supplemental oxygen
- Bag mask or intubation if necessary
- Maintain circulation:
- Place patient supine and elevate lower extremities if possible.
- Volume resuscitation with 0.9% saline
- IV vasopressors may be necessary in patients with refractory hypotension or shock.
Ongoing Care
Follow-up Recommendations
Most patients who are diagnosed with anaphylaxis will benefit from a referral to an allergist/immunologist for further evaluation, recommendations, and management.
Patient Monitoring
Biphasic anaphylaxis, in which symptoms recur within 1-72 hours (usually 8-10 hours) after resolution of initial symptoms, occurs in up to 23% of adults and up to 11% of children with anaphylaxis.
- A prescription for autoinjectable epinephrine should be provided on discharge in any patient diagnosed with anaphylaxis.
- A 1- to 3-day course of oral steroids may prevent or limit biphasic or protracted anaphylaxis.
- Medical monitoring after return to baseline should be individualized and depend on degree of symptoms and other risk factors.
- Patients with moderate respiratory compromise should be monitored for a minimum of 4 hours or longer if indicated (especially young patients or patients with comorbidities).
Patient Education
All patients should be instructed on allergen avoidance measures and provided with a written personalized emergency plan detailing appropriate management of future anaphylactic episodes.
Prognosis
Good with trigger identification and avoidance
Complications
- Laryngeal edema and airway obstruction
- Pulmonary edema, pulmonary hemorrhage, and pneumothorax
- Myocardial ischemia and infarction
- End-organ ischemia and damage
- Death secondary to airway obstruction (asphyxiation) and/or shock
Additional Reading
- Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Ann Allergy Asthma Immunol. 2007;98(3):252-257. [View Abstract]
- Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2)(Suppl 2):S161-S181. [View Abstract]
- Simons FE, Ardusso LR, Bil ² MB, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37. [View Abstract]
- Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006;97(1):39-43. [View Abstract]
Codes
ICD09
- 995.0 Other anaphylactic reaction
- 995.60 Anaphylactic reaction due to unspecified food
- 989.5 Toxic effect of venom
ICD10
- T78.2XXA Anaphylactic shock, unspecified, initial encounter
- T78.00XA Anaphylactic reaction due to unspecified food, init encntr
- T63.891A Toxic effect of contact with other venomous animals, accidental (unintentional), initial encounter
- T88.6XXA Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, initial encounter
SNOMED
- 39579001 Anaphylaxis (disorder)
- 91941002 Food anaphylaxis (disorder)
- 241930003 Venom-induced anaphylaxis (disorder)
- 241937000 Drug-induced anaphylaxis (disorder)
FAQ
- Q: Can a patient have an anaphylactic reaction on first exposure to an allergen?
- A: In IgE-mediated anaphylaxis, a patient must have been previously exposed to the offending allergen for sensitization to occur with a subsequent exposure potentially resulting in anaphylaxis. Remember, however, that the absence of a previous exposure on history does not exclude an allergen as causal because sensitization may have previously occurred unknowingly (through skin contact, in breast milk, in utero). Non-IgE-mediated anaphylaxis can occur on first exposure to the offending allergen.
- Q: Should patients with a history of anaphylaxis carry more than one autoinjectable epinephrine device?
- A: Yes, up to 20% of patients with anaphylaxis are reported to require a second dose of epinephrine either because of ongoing symptoms or because of biphasic anaphylaxis.
- Q: Can a patient develop anaphylaxis to an allergen that they have tolerated previously?
- A: Yes, this often occurs with medications or foods (particularly peanut, tree nuts, fish, and shellfish) especially if there is a long period of time between exposures.