Differential Diagnosis for Anaphylaxis: Key Considerations for Emergency Medicine

Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction with rapid onset. Characterized by generalized, multi-system manifestations, it demands immediate recognition and treatment. While the clinical presentation can be striking, several conditions can mimic anaphylaxis, necessitating a robust differential diagnosis approach to ensure accurate management and avoid misdiagnosis. This article delves into the differential diagnosis of anaphylaxis, providing a comprehensive guide for healthcare professionals to distinguish it from other conditions with overlapping symptoms.

Etiology of Anaphylaxis

Understanding the common triggers of anaphylaxis is crucial for both diagnosis and differential diagnosis. Anaphylaxis is most frequently triggered by:

• Medications: Antibiotics (penicillin, cephalosporins), nonsteroidal anti-inflammatory drugs (NSAIDs), neuromuscular blocking agents, and chemotherapy drugs are common culprits.
• Foods: Peanuts, tree nuts, milk, eggs, soy, wheat, fish, and shellfish account for the majority of food-induced anaphylaxis. Sesame and red meat (alpha-gal allergy) are also increasingly recognized.
• Insect Stings: Hymenoptera venom from bees, wasps, hornets, and fire ants are potent anaphylactic triggers.
• Latex: Natural rubber latex allergy can cause anaphylaxis, particularly in healthcare workers and individuals with spina bifida.
• Immunotherapy: Allergy shots can, paradoxically, induce anaphylaxis.
• Idiopathic Anaphylaxis: In some cases, the trigger remains unidentified, termed idiopathic anaphylaxis.

Epidemiology of Anaphylaxis

Anaphylaxis is a global health concern with a lifetime prevalence estimated between 1% and 3%, and incidence rates are rising. It affects all age groups, but is more commonly observed in younger populations and developed countries. Underdiagnosis and misdiagnosis are significant issues, contributing to increased morbidity and mortality.

Pathophysiology of Anaphylaxis

Anaphylaxis is predominantly an IgE-mediated (Type 1) hypersensitivity reaction. Upon re-exposure to an antigen, crosslinking of IgE antibodies on mast cells and basophils triggers the release of potent mediators, including histamine, tryptase, leukotrienes, prostaglandins, and platelet-activating factor. These mediators cause:

• Vasodilation and Increased Vascular Permeability: Leading to hypotension and tissue edema.
• Bronchoconstriction: Causing wheezing and respiratory distress.
• Mucus Secretion: Contributing to airway obstruction.
• Cardiac Effects: Including tachycardia and potential myocardial ischemia (Kounis syndrome).

Clinical Presentation: Recognizing Anaphylaxis

Anaphylaxis typically presents rapidly, often within minutes to an hour of exposure to the trigger. Symptoms can range from mild to life-threatening and involve multiple organ systems. Key features include:

• Cutaneous: Urticaria (hives), pruritus (itching), flushing, angioedema (swelling, particularly of the face, lips, tongue, and throat). However, cutaneous signs may be absent in up to 20% of anaphylactic reactions.
• Respiratory: Dyspnea (shortness of breath), wheezing, stridor, throat tightness, hoarseness, cough.
• Cardiovascular: Hypotension, tachycardia, dizziness, syncope (fainting).
• Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea.
• Neurological: Anxiety, confusion, sense of impending doom.

The severity of anaphylaxis is graded, with more severe reactions involving respiratory compromise, hypotension, and end-organ dysfunction. Biphasic reactions, a recurrence of symptoms hours after initial resolution, occur in up to 20% of cases, necessitating prolonged observation.

Diagnostic Evaluation of Anaphylaxis

Diagnosis of anaphylaxis is primarily clinical, based on history and physical examination. The National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria are widely used:

Clinical Criteria for Anaphylaxis (One of the following must be met):

1. Acute onset (minutes to hours) of illness with involvement of the skin or mucosal tissue (e.g., hives, pruritus, flushing, angioedema) AND at least ONE of the following:

   • Respiratory compromise (dyspnea, wheezing, stridor, hypoxemia)
   • Hypotension or symptoms of end-organ dysfunction (syncope, incontinence)

2. Two or more of the following that occur rapidly after exposure to a likely allergen (minutes to hours):

   • Skin-mucosal involvement (hives, angioedema, generalized pruritus, flushing)
   • Respiratory compromise
   • Hypotension or associated symptoms
   • Persistent gastrointestinal symptoms (cramping abdominal pain, vomiting)

3. Hypotension after exposure to a known allergen (minutes to hours):

   • Systolic blood pressure 30% decrease from baseline.

While clinical criteria are paramount, laboratory tests like serum tryptase can be supportive, particularly if drawn within a few hours of symptom onset. However, a negative tryptase does not rule out anaphylaxis.

Differential Diagnosis for Anaphylaxis

Several conditions can mimic anaphylaxis, requiring careful differentiation to ensure appropriate management. The differential diagnosis of anaphylaxis includes:

1. Angioedema

Angioedema, characterized by swelling of the deeper layers of the skin and mucosa, can present with facial, lip, tongue, and throat swelling, similar to anaphylaxis.

Distinguishing Angioedema from Anaphylaxis:

• Urticaria: Urticaria (hives) is a hallmark of anaphylaxis but is typically absent in angioedema.
• Bradykinin-mediated Angioedema: Hereditary angioedema (HAE) and acquired angioedema often lack urticaria and pruritus. They may be triggered by ACE inhibitors. HAE attacks are often slower in onset and resolution compared to anaphylaxis. Family history can be suggestive of HAE.
• Allergic Angioedema: Allergic angioedema, part of anaphylaxis, presents with urticaria and other systemic symptoms of anaphylaxis.

Key Differentiator: The presence of urticaria strongly favors anaphylaxis over bradykinin-mediated angioedema.

2. Asthma Exacerbation

Severe asthma exacerbations can cause wheezing, dyspnea, and respiratory distress, mimicking the respiratory component of anaphylaxis.

Distinguishing Asthma from Anaphylaxis:

• Trigger: Asthma exacerbations are often triggered by respiratory infections, cold air, or exercise, while anaphylaxis is triggered by allergen exposure.
• Other Systemic Symptoms: Anaphylaxis typically involves cutaneous, cardiovascular, and gastrointestinal symptoms in addition to respiratory distress. Asthma is primarily a respiratory condition.
• Response to Epinephrine: While epinephrine can be used in severe asthma, it is the first-line treatment for anaphylaxis and often provides rapid improvement. Asthma may require bronchodilators, corticosteroids, and other asthma-specific therapies.

Key Differentiator: Multisystem involvement beyond respiratory symptoms points towards anaphylaxis rather than isolated asthma exacerbation.

3. Vasovagal Syncope

Vasovagal syncope, or fainting, can occur in response to various triggers like pain, stress, or prolonged standing. It can present with pallor, diaphoresis, dizziness, and loss of consciousness, potentially mimicking the cardiovascular symptoms of anaphylaxis.

Distinguishing Vasovagal Syncope from Anaphylaxis:

• Precipitating Factors: Vasovagal syncope is often associated with triggers like emotional stress, pain, or prolonged standing. Anaphylaxis has a clear allergen exposure history.
• Skin and Mucosal Signs: Urticaria, angioedema, and flushing are typical in anaphylaxis but absent in vasovagal syncope.
• Respiratory Symptoms: Respiratory distress is not a primary feature of vasovagal syncope, unlike anaphylaxis.
• Blood Pressure and Heart Rate: Vasovagal syncope typically involves bradycardia and hypotension, while anaphylaxis may present with tachycardia and hypotension. However, both can cause hypotension.
• Response to Epinephrine: Epinephrine is not indicated for vasovagal syncope and will not improve symptoms.

Key Differentiator: Lack of skin/mucosal involvement and respiratory symptoms, along with typical vasovagal triggers, favor vasovagal syncope.

4. Anxiety and Panic Attacks

Severe anxiety or panic attacks can manifest with palpitations, shortness of breath, chest tightness, and dizziness, overlapping with some symptoms of anaphylaxis.

Distinguishing Anxiety/Panic Attacks from Anaphylaxis:

• Onset and Progression: Anaphylaxis has a rapid onset and progression following allergen exposure. Panic attacks may have a more gradual onset and are often triggered by psychological stress.
• Skin and Mucosal Signs: Urticaria and angioedema are absent in panic attacks but common in anaphylaxis.
• Wheezing and Stridor: Wheezing and stridor are indicative of bronchospasm in anaphylaxis and are not typical of panic attacks.
• Hypotension: Hypotension is a key feature of anaphylaxis and is not expected in panic attacks (though patients may feel lightheaded).
• Response to Epinephrine: Epinephrine is not indicated for panic attacks.

Key Differentiator: Absence of skin/mucosal signs, wheezing, stridor, and hypotension, along with psychological triggers, suggests a panic attack.

5. Vocal Cord Dysfunction

Vocal cord dysfunction (VCD) can cause paradoxical vocal cord adduction, leading to inspiratory stridor and dyspnea, which can be misdiagnosed as anaphylaxis, particularly laryngeal edema.

Distinguishing Vocal Cord Dysfunction from Anaphylaxis:

• Stridor Characteristics: VCD typically presents with inspiratory stridor, while anaphylaxis-related stridor can be inspiratory or expiratory.
• Wheezing: Wheezing is more common in anaphylaxis due to bronchospasm, less so in VCD.
• Other Systemic Symptoms: VCD is primarily a respiratory condition. Anaphylaxis involves multisystem symptoms.
• Response to Epinephrine: Epinephrine is not effective for VCD. VCD may respond to speech therapy techniques or anxiolytics.

Key Differentiator: Predominantly inspiratory stridor without other systemic features of anaphylaxis raises suspicion for VCD.

6. Foreign Body Airway Obstruction

Upper airway obstruction due to a foreign body can cause sudden onset respiratory distress, coughing, and stridor, mimicking anaphylaxis, especially in children.

Distinguishing Foreign Body Obstruction from Anaphylaxis:

• Sudden Choking Episode: Foreign body obstruction is often preceded by a choking episode while eating or playing with small objects. Anaphylaxis follows allergen exposure.
• Focal Findings: Physical exam for foreign body obstruction may reveal decreased breath sounds unilaterally or focal wheezing. Anaphylaxis is typically more generalized.
• Lack of Allergy History: Foreign body obstruction occurs irrespective of allergy history.
• Response to Epinephrine: Epinephrine is not effective for foreign body obstruction. The Heimlich maneuver or bronchoscopy is required for removal.

Key Differentiator: Sudden choking episode, focal respiratory findings, and lack of allergy history point toward foreign body obstruction.

7. Myocardial Ischemia/Infarction (Kounis Syndrome)

Kounis syndrome, or allergic angina, is myocardial ischemia or infarction triggered by mast cell activation and mediator release during anaphylaxis. While it is a complication of anaphylaxis, it can also present with chest pain and cardiovascular symptoms that might initially be mistaken for primary cardiac events in the absence of clear anaphylactic signs.

Distinguishing Kounis Syndrome from Primary Cardiac Events:

• Context of Allergic Reaction: Kounis syndrome occurs in the setting of anaphylaxis or allergic reaction.
• Other Anaphylactic Symptoms: Look for other signs of anaphylaxis (cutaneous, respiratory, gastrointestinal) even if subtle.
• ECG and Cardiac Markers: ECG changes and elevated cardiac enzymes may be present in both Kounis syndrome and primary cardiac events.
• History of Allergies: Patients with Kounis syndrome often have a history of allergies.

Key Differentiator: The presence of other anaphylactic symptoms or a clear allergic trigger in the context of chest pain suggests Kounis syndrome.

8. Carcinoid Syndrome

Carcinoid syndrome, caused by neuroendocrine tumors releasing vasoactive substances, can present with flushing, diarrhea, wheezing, and hypotension, superficially resembling anaphylaxis.

Distinguishing Carcinoid Syndrome from Anaphylaxis:

• Flushing Characteristics: Flushing in carcinoid syndrome is often more prolonged and may be triggered by alcohol or stress, while anaphylaxis flushing is more acute and related to allergen exposure.
• Diarrhea: Chronic diarrhea is a prominent feature of carcinoid syndrome, less so in anaphylaxis.
• Wheezing: Wheezing in carcinoid syndrome is less common and less acute than in anaphylaxis.
• Urticaria and Angioedema: Urticaria and angioedema are not typical of carcinoid syndrome.
• Urinary 5-HIAA: Elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) is diagnostic for carcinoid syndrome.

Key Differentiator: Prolonged flushing, chronic diarrhea, and absence of urticaria/angioedema, with potential for elevated urinary 5-HIAA, suggest carcinoid syndrome.

9. Gastroenteritis

Gastroenteritis, particularly viral gastroenteritis, can cause nausea, vomiting, abdominal pain, and diarrhea, mimicking the gastrointestinal symptoms of anaphylaxis.

Distinguishing Gastroenteritis from Anaphylaxis:

• Time Course: Gastroenteritis develops over hours to days, while anaphylaxis occurs rapidly after allergen exposure.
• Other Systemic Symptoms: Gastroenteritis lacks the cutaneous, respiratory, and cardiovascular symptoms characteristic of anaphylaxis.
• Fever: Fever is common in gastroenteritis, less so in anaphylaxis.
• Dehydration: Dehydration is a primary concern in gastroenteritis, while distributive shock is the cardiovascular issue in anaphylaxis.

Key Differentiator: Gradual onset, lack of cutaneous/respiratory/cardiovascular symptoms, and presence of fever favor gastroenteritis.

10. Mastocytosis

Mastocytosis is a group of disorders characterized by mast cell accumulation in various tissues. Mast cell activation in mastocytosis can cause flushing, pruritus, hypotension, and gastrointestinal symptoms, potentially resembling anaphylaxis.

Distinguishing Mastocytosis from Anaphylaxis:

• Chronic Symptoms: Mastocytosis often presents with chronic, recurrent symptoms, while anaphylaxis is an acute event.
• Skin Lesions: Cutaneous mastocytosis (urticaria pigmentosa) presents with characteristic skin lesions.
• Tryptase Levels: Baseline serum tryptase levels are often elevated in mastocytosis, and may rise further during mast cell activation episodes. Anaphylaxis tryptase elevation is transient.
• Triggers: Mastocytosis flares can be triggered by various stimuli, including temperature changes, stress, and medications, not always specific allergens.

Key Differentiator: Chronic, recurrent symptoms, characteristic skin lesions, and elevated baseline tryptase levels suggest mastocytosis.

11. Seizure

Seizures, particularly generalized tonic-clonic seizures, can cause loss of consciousness, muscle rigidity, and incontinence, which might be confused with severe anaphylaxis with hypotonia and syncope.

Distinguishing Seizure from Anaphylaxis:

• Tonic-Clonic Activity: Seizures involve characteristic tonic-clonic movements. Anaphylaxis does not.
• Postictal State: A postictal state (confusion, drowsiness) follows a seizure. This is absent in anaphylaxis once treated.
• Tongue Biting: Tongue biting may occur during seizures, not in anaphylaxis.
• Allergy History: Seizures are not directly related to allergen exposure.

Key Differentiator: Tonic-clonic activity, postictal state, and tongue biting point towards seizure.

12. Epiglottitis

Epiglottitis, inflammation of the epiglottis, can cause rapid onset sore throat, dysphagia, drooling, and stridor, particularly in children, mimicking the airway compromise of anaphylaxis.

Distinguishing Epiglottitis from Anaphylaxis:

• Predominant Sore Throat and Dysphagia: Epiglottitis is characterized by severe sore throat and difficulty swallowing, less prominent in anaphylaxis.
• “Sniffing Dog” Position: Patients with epiglottitis often assume a characteristic “sniffing dog” position to maximize airway patency.
• Lack of Urticaria and Angioedema: Cutaneous signs are not typical in epiglottitis.
• Fever: Fever is common in epiglottitis, less so in anaphylaxis.
• Lateral Neck X-ray: A lateral neck X-ray can show the “thumbprint sign,” indicative of a swollen epiglottis.

Key Differentiator: Predominant sore throat, dysphagia, “sniffing dog” position, and fever, without urticaria/angioedema, suggest epiglottitis.

Treatment and Management of Anaphylaxis

Prompt recognition and treatment of anaphylaxis are critical. The cornerstone of anaphylaxis treatment is:

1. Epinephrine: Intramuscular epinephrine is the first-line treatment. Administer 0.3-0.5 mg (0.01 mg/kg in children) of 1:1000 epinephrine into the mid-outer thigh. Repeat every 5-15 minutes as needed.
2. Airway Management: Assess and secure the airway. Intubation or cricothyroidotomy may be necessary in severe cases of airway compromise.
3. Oxygen: Administer high-flow oxygen.
4. Intravenous Fluids: Administer isotonic crystalloid solutions (1-2 liters in adults, 10-20 mL/kg in children) to address distributive shock.
5. Adjunctive Therapies:
   • Antihistamines: H1 and H2 antihistamines (diphenhydramine, ranitidine/famotidine) can help with cutaneous symptoms and pruritus.
   • Corticosteroids: Methylprednisolone or hydrocortisone may help prevent biphasic reactions and manage airway inflammation.
   • Bronchodilators: Inhaled beta-agonists (albuterol) for bronchospasm.
   • Glucagon: For patients on beta-blockers who are refractory to epinephrine.

Prognosis and Deterrence

With rapid and appropriate treatment, the prognosis for anaphylaxis is generally good. However, delayed treatment can lead to significant morbidity and mortality. Patient education is crucial for deterrence:

• Epinephrine Autoinjector: Prescribe and educate patients on the proper use of epinephrine autoinjectors.
• Allergen Avoidance: Educate patients on avoiding identified allergens.
• Medical Alert Bracelet: Recommend wearing a medical alert bracelet.
• Allergist Referral: Refer patients to an allergist for allergy testing and long-term management.

Enhancing Healthcare Team Outcomes

Effective management of anaphylaxis requires a coordinated interprofessional team approach. Education for all healthcare providers on anaphylaxis recognition and treatment, particularly epinephrine administration, is paramount. Pharmacists play a key role in patient education regarding epinephrine autoinjectors and allergen avoidance. Prompt and coordinated care is essential to improve patient outcomes in this life-threatening condition.

Conclusion

Anaphylaxis is a medical emergency requiring rapid recognition and treatment. While the clinical presentation can be distinct, a broad differential diagnosis is crucial to avoid misdiagnosis and ensure appropriate management. By carefully considering alternative conditions like angioedema, asthma, vasovagal syncope, and others, and by applying the clinical criteria for anaphylaxis, healthcare professionals can improve diagnostic accuracy and optimize patient care in these critical situations. Early epinephrine administration remains the cornerstone of anaphylaxis management and can be life-saving.

Figure: Anaphylaxis Symptoms and Systemic Effects. Infographic illustrating anaphylaxis symptoms including hives, breathing difficulty, increased heart rate, and anxiety in different body systems.

Figure: Anaphylaxis Hives. Close-up image of hives, a common skin manifestation of anaphylaxis, showing raised, red welts on the skin.

References

1.Okubo Y, Nochioka K, Testa MA. Nationwide Survey of Hospitalization Due to Pediatric Food-Induced Anaphylaxis in the United States. Pediatr Emerg Care. 2019 Nov;35(11):769-773. [PubMed: 30113437]

2.Castilano A, Sternard B, Cummings ED, Shi R, Arnold T, Bahna SL. Pitfalls in anaphylaxis diagnosis and management at a university emergency department. Allergy Asthma Proc. 2018 Jul 01;39(4):316-321. [PubMed: 30095397]

3.Akenroye AT, Ajala A, Azimi-Nekoo E, de Vos GS. Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation. Emerg Med J. 2018 Oct;35(10):623-625. [PubMed: 30093380]

4.Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy Asthma Immunol. 2018 Nov;121(5):594-597. [PubMed: 30071303]

5.Mota I, Gaspar Â, Benito-Garcia F, Correia M, Chambel M, Morais-Almeida M. Drug-induced anaphylaxis: seven-year single-center survey. Eur Ann Allergy Clin Immunol. 2018 Sep;50(5):211-216. [PubMed: 30028111]

6.Yue D, Ciccolini A, Avilla E, Waserman S. Food allergy and anaphylaxis. J Asthma Allergy. 2018;11:111-120. [PMC free article: PMC6016602] [PubMed: 29950871]

7.Parrish CP, Kim H. Food-Induced Anaphylaxis: an Update. Curr Allergy Asthma Rep. 2018 Jun 14;18(8):41. [PubMed: 29904820]

8.Protudjer JLP, Olén O, Vetander M, Kull I, Melén E, van Hage M, Wickman M, Bergström A. Milk-Related Symptoms and Immunoglobulin E Reactivity in Swedish Children from Early Life to Adolescence. Nutrients. 2018 May 21;10(5) [PMC free article: PMC5986530] [PubMed: 29883392]

9.Anagnostou K. Anaphylaxis in Children: Epidemiology, Risk Factors and Management. Curr Pediatr Rev. 2018;14(3):180-186. [PubMed: 29732976]

10.Jimenez-Rodriguez TW, Garcia-Neuer M, Alenazy LA, Castells M. Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers. J Asthma Allergy. 2018;11:121-142. [PMC free article: PMC6016596] [PubMed: 29950872]

11.Valenta R, Karaulov A, Niederberger V, Gattinger P, van Hage M, Flicker S, Linhart B, Campana R, Focke-Tejkl M, Curin M, Eckl-Dorna J, Lupinek C, Resch-Marat Y, Vrtala S, Mittermann I, Garib V, Khaitov M, Valent P, Pickl WF. Molecular Aspects of Allergens and Allergy. Adv Immunol. 2018;138:195-256. [PubMed: 29731005]

12.Graudins LV, Trubiano JA, Zubrinich CM, Elliott AS, Aung AK. Medication-related anaphylaxis treated in hospital: Agents implicated, patient outcomes, and management lessons. Pharmacoepidemiol Drug Saf. 2018 Sep;27(9):1029-1033. [PubMed: 30051944]

13.Aun MV, Kalil J, Giavina-Bianchi P. Adults and children with anaphylaxis in the emergency room: why it is not recognized? Curr Opin Allergy Clin Immunol. 2018 Oct;18(5):377-381. [PubMed: 30020259]

14.Navaradnam P, Suganthan N, Kumanan T, Sujanitha V, Mayorathan U. Kounis Syndrome and Multiorgan Failure Following Multiple Wasp Stings. Cureus. 2021 Apr 21;13(4):e14606. [PMC free article: PMC8139607] [PubMed: 34040907]

15.De Feo G, Parente R, Triggiani M. Pitfalls in anaphylaxis. Curr Opin Allergy Clin Immunol. 2018 Oct;18(5):382-386. [PubMed: 30028728]

16.Cohen N, Capua T, Pivko D, Ben-Shoshan M, Benor S, Rimon A. Trends in the diagnosis and management of anaphylaxis in a tertiary care pediatric emergency department. Ann Allergy Asthma Immunol. 2018 Sep;121(3):348-352. [PubMed: 29981442]

17.Gallagher JL, Rivera RD, Van Shepard K, Roushan T, Ahsan G, Ahamed SI, Chiu A, Jurken M, Simpson PM, Nugent M, Gobin KS, Wen CKF, Eldredge CE. Life-Threatening Allergies: Using a Patient-Engaged Approach. Telemed J E Health. 2019 Apr;25(4):319-325. [PubMed: 29969372]

18.Jang HY, Ha DH, Rah SY, Lee DH, Lee SM, Park BH. Sirtuin 6 is a negative regulator of FcεRI signaling and anaphylactic responses. J Allergy Clin Immunol. 2022 Jan;149(1):156-167.e7. [PubMed: 34051221]

19.Lindor RA, McMahon EM, Wood JP, Sadosty AT, Boie ET, Campbell RL. Anaphylaxis-related Malpractice Lawsuits. West J Emerg Med. 2018 Jul;19(4):693-700. [PMC free article: PMC6040909] [PubMed: 30013706]

20.Fineman SM. Optimal treatment of anaphylaxis: antihistamines versus epinephrine. Postgrad Med. 2014 Jul;126(4):73-81. [PubMed: 25141245]

21.Leatherman BD. Anaphylaxis in the allergy practice. Int Forum Allergy Rhinol. 2014 Sep;4 Suppl 2:S60-5. [PubMed: 25182358]

22.Rubin T, Clayton J, Adams D, Jou H, Vohra S. Systematic review of outcome measures in trials of pediatric anaphylaxis treatment. BMC Pediatr. 2014 Jun 20;14:158. [PMC free article: PMC4088301] [PubMed: 24950840]