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Anaphylaxis, Pediatric

Basics

Description

- 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.

- 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

- Allergic/atopic - Acute urticaria - Acute asthma - Pollen-food syndrome

- Genetic/metabolic - Hereditary or acquired angioedema

- Neurologic - Nonorganic disease - Panic attack - Vocal cord dysfunction - Munchausen syndrome

- Albuterol 2.5 mg/3 mL solution - Nebulized and inhaled via face mask

  • 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 triggersMost 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 triggersSpecifically inquire about NSAIDs, supplements, and herbal treatments.β-Blockers and ACE inhibitors can increase severity and/or make treatment of anaphylaxis more difficult.
  • Insect stingsIf 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 latexLatex-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 mucosaFlushing, itching, conjunctival erythema, urticaria, angioedema
  • RespiratoryUpper 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 flowCyanosis, respiratory arrest
  • Cardiovascular systemTachycardia or bradycardia (less common), hypotension, arrhythmias, shock, urinary or fecal incontinence, cardiac arrest
  • GastrointestinalAbdominal pain/cramping, vomiting, diarrhea, dysphagia
  • Central nervous systemPatients 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 tryptaseElevated 15 minutes to 3 hours after onset of anaphylaxisElevated in patients with anaphylaxis due to injected medications, insect stings, and when hypotension is presentCan be normal in anaphylaxis due to foods or in those who are normotensiveNormal serum tryptase does not rule out anaphylaxis.Laboratory test that is routinely used in practice
  • Plasma histamineElevated if measured 15-60 minutes after onset of anaphylaxis due to its short half-lifeBlood sample requires special handling.Normal level does not rule out anaphylaxis.
  • Urine histamine and N-methylhistamine24-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/atopicAcute urticariaAcute asthmaPollen-food syndrome
  • CardiovascularMyocardial infarctionPulmonary embolus
  • Genetic/metabolicHereditary or acquired angioedema
  • Infectious
  • NeoplasticMastocytosis/clonal mast cell disordersCarcinoidBasophilic leukemiaPheochromocytoma
  • Neurologic
  • Nonorganic diseasePanic attackVocal cord dysfunctionMunchausen syndrome
  • Other:Foreign body aspirationScombroidosis (ingestion of fish containing high levels of histamine)Red Man syndrome

Treatment

Medication

First Line

  • IM epinephrine 1:1,000 (1 mg/mL) solution0.01 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 solutionNebulized 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 oxygenBag mask or intubation if necessary
  • Maintain circulation:Place patient supine and elevate lower extremities if possible.Volume resuscitation with 0.9% salineIV 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.