Do Corticosteroids Prevent Biphasic Anaphylaxis?

doi:10.1016/j.jaip.2017.05.022

The Journal of Allergy and Clinical Immunology: In Practice

Volume 5, Issue 5, September–October 2017, Pages 1194-1205

https://doi.org/10.1016/j.jaip.2017.05.022 Get rights and content

Anaphylaxis is a severe hypersensitivity reaction that is rapid in onset and can result in death. The pattern of an anaphylactic reaction can be uniphasic (or monophasic), biphasic (also called delayed or late phase), or refractory in nature. The most widely cited definition of biphasic anaphylaxis is a recurrence of anaphylactic symptoms after initial resolution despite no further exposure to the trigger. Corticosteroids are thought by some to prevent the development of biphasic symptoms and, therefore, commonly used in the emergency treatment of anaphylaxis but this has not been systemtically analyzed. In this review, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus were searched for articles using “anaphylaxis” combined with the key terms “biphasic” and/or “corticosteroids” and/or “epinephrine.” A total of 31 appropriate studies were identified. Biphasic anaphylactic reactions are more likely to occur in moderate to severe anaphylaxis or when anaphylaxis is not treated with timely epinephrine. Because of the potential detrimental adverse effects of corticosteroids and lack of compelling evidence demonstrating an effective role in reducing anaphylaxis severity or preventing biphasic anaphylaxis, we do not advocate for their routine use in anaphylaxis.

Section snippets

Methods

We defined a biphasic anaphylactic reaction as the recurrence or new symptoms of anaphylaxis after an anaphylactic event without reexposure to the trigger, following an asymptomatic interval of at least 1 hour. Studies that clearly documented reactions meeting this definition were included. We included relevant case series, prospective and retrospective cohort studies, and clinical trials. Studies that did not describe biphasic reactions and isolated case reports were excluded. We followed the

Conclusions

Biphasic anaphylactic reactions are more likely to occur in moderate to severe anaphylaxis or when anaphylaxis is not treated with timely epinephrine. Because of the potential detrimental adverse effects of corticosteroids and lack of compelling evidence demonstrating an effective role in reducing anaphylaxis severity or preventing biphasic anaphylaxis, we do not advocate for their routine use in anaphylaxis.

References (87)

F.E.R. Simons et al.
World allergy organization guidelines for the assessment and management of anaphylaxis
World Allergy Organ J
(2011)
R.A. Wood et al.
Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States
J Allergy Clin Immunol
(2014)
D.M. Douglas et al.
Biphasic systemic anaphylaxis: an inpatient and outpatient study
J Allergy Clin Immunol
(1994)
P. Lieberman
Biphasic anaphylactic reactions
Ann Allergy Asthma Immunol
(2005)
J.W. Tole et al.
Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations
Immunol Allergy Clin North Am
(2007)
B.J. Stark et al.
Biphasic and protracted anaphylaxis
J Allergy Clin Immunol
(1986)
S.E. Scranton et al.
Incidence and characteristics of biphasic reactions after allergen immunotherapy
J Allergy Clin Immunol
(2009)
R. Lertnawapan et al.
Anaphylaxis and biphasic phase in Thailand: 4-year observation
Allergol Int
(2011)
S.G. Brown et al.
Anaphylaxis: clinical patterns, mediator release, and severity
J Allergy Clin Immunol
(2013)
B.E. Grunau et al.
Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis
Ann Emerg Med
(2014)

W. Alqurashi et al.

Epidemiology and clinical predictors of biphasic reactions in children with anaphylaxis

Ann Allergy Asthma Immunol

(2015)

S. Lee et al.

Predictors of biphasic reactions in the emergency department for patients with anaphylaxis

J Allergy Clin Immunol Pract

(2014)

D.V. Smit et al.

Anaphylaxis presentations to an emergency department in Hong Kong: incidence and predictors of biphasic reactions

J Emerg Med

(2005)

O. Jirapongsananuruk et al.

Features of patients with anaphylaxis admitted to a university hospital

Ann Allergy Asthma Immunol

(2007)

R. Confino-Cohen et al.

Allergen immunotherapy-induced biphasic systemic reactions: incidence, characteristics, and outcome: a prospective study

Ann Allergy Asthma Immunol

(2010)

B.S. Ko et al.

Biphasic reactions in patients with anaphylaxis treated with corticosteroids

Ann Allergy Asthma Immunol

(2015)

A. Sugiura et al.

Combined use of ECMO and hemodialysis in the case of contrast-induced biphasic anaphylactic shock

Am J Emerg Med

(2016)

L.B. Grabenhenrich et al.

Anaphylaxis in children and adolescents: the European Anaphylaxis Registry

J Allergy Clin Immunol

(2016)

A.M. Altman et al.

Anaphylaxis in America: a national physician survey

J Allergy Clin Immunol

(2015)

A.K. Ellis et al.

Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients

Ann Allergy Asthma Immunol

(2007)

S.A. Bock et al.

Further fatalities caused by anaphylactic reactions to food, 2001-2006

J Allergy Clin Immunol

(2007)

R.S. Pumphrey et al.

Further fatal allergic reactions to food in the United Kingdom, 1999-2006

J Allergy Clin Immunol

(2007)

F.E. Simons et al.

Anaphylaxis in the community: learning from the survivors

J Allergy Clin Immunol

(2009)

E. Hochstadter et al.

Increasing visits for anaphylaxis and the benefits of early epinephrine administration: a 4-year study at a pediatric emergency department in Montreal, Canada

J Allergy Clin Immunol

(2016)

J.T. Fleming et al.

Early treatment of food-induced anaphylaxis with epinephrine is associated with a lower risk of hospitalization

J Allergy Clin Immunol Pract

(2015)

A.K. Ellis

Priority role of epinephrine in anaphylaxis further underscored–the impact on biphasic anaphylaxis

Ann Allergy Asthma Immunol

(2015)

P. Vadas

The platelet-activating factor pathway in food allergy and anaphylaxis

Ann Allergy Asthma Immunol

(2016)

P. Vadas et al.

Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis

J Allergy Clin Immunol

(2013)

P. Vadas et al.

Effect of epinephrine on platelet-activating factor-stimulated human vascular smooth muscle cells

J Allergy Clin Immunol

(2012)

P. Lieberman et al.

Anaphylaxis—a practice parameter update 2015

Ann Allergy Asthma Immunol

(2015)

E.C. Matsui et al.

Weighing the evidence: bias and confounding in epidemiologic studies in allergy/immunology

J Allergy Clin Immunol

(2017)

H.A. Sampson 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

Ann Emerg Med

(2006)

S.A.M. Kularatne et al.

Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: an open labelled randomized controlled trial

Toxicon

(2016)

M.S. Davenport et al.

The evidence for and against corticosteroid prophylaxis in at-risk patients

Radiol Clin North Am

(2017)

D. Liu et al.

A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy

Allergy Asthma Clin Immunol

(2013)

S. Kayani et al.

Adverse behavioral effects of treatment for acute exacerbation of asthma in children: a comparison of two doses of oral steroids

Chest

(2002)

A. Patel et al.

Immediate hypersensitivity reactions to corticosteroids

Ann Allergy Asthma Immunol

(2015)

F.E. Simons et al.

International consensus on (ICON) anaphylaxis

World Allergy Organ J

(2014)

J.P. Ioannidis et al.

Increasing value and reducing waste in research design, conduct, and analysis

Lancet

(2014)

P.K. Smith et al.

Risk multipliers for severe food anaphylaxis

World Allergy Organ J

(2015)

P. Lieberman et al.

The diagnosis and management of anaphylaxis practice parameter: 2010 update

J Allergy Clin Immunol

(2010)

CIHI

Anaphylaxis and allergy in the emergency department. 2015

A. Sheikh et al.

Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England

J R Soc Med

(2008)

Cited by (87)

Anaphylaxis: A 2023 practice parameter update
2024, Annals of Allergy, Asthma and Immunology
This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.
Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data
2023, Annals of Allergy, Asthma and Immunology
Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse.
To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management.
Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form.
Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes.
Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions.
Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]).
Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.
Anaphylactic reaction as an etiology of ischemic stroke: A case report
2023, Radiology Case Reports
A 28-year-old man was brought to the emergency room (ER) with a history of decrease of consciousness 30 minutes before admission. In the previous 1 hour, the patient felt bitten or stabbed in the left temple area. Physical examination showed signs of N VII paresis, upper extremity motoric 3/2 (right/left) and lower extremity 3/2 (right/left), positive left extremity hypesthesia. Noncontrast MRI brain examination showed increased DWI signal intensity, suggesting diffusion restriction in bilateral centrum semiovale, bilateral posterior crus internal capsule, and bilateral corpus callosum leading to suspicion of acute-hyperacute ischemia. The therapy given while in the emergency room was IVFD asering, IV dexamethasone 5 mg, IV diphenhydramine 10 mg, oral paracetamol 500 mg, oral aspirin 80 mg, oral clopidogrel 75 mg, and oral atorvastatin 40 mg. We report a case of stroke due to an anaphylactic reaction in an effort to add to the point of view if the same case occurs.
Allergic Acute Coronary Syndrome—Kounis Syndrome
2023, Immunology and Allergy Clinics of North America
Drug Hypersensitivity Reactions
2023, Immunology and Allergy Clinics of North America
Anaphylaxis: Emergency Department Treatment
2023, Immunology and Allergy Clinics of North America

View all citing articles on Scopus

: Conflicts of interest: A. K. Ellis has received research support and consultancy/speaker fees from Pfizer; has received consultancy fees from ALK Abello, Merck, and Novartis; has received research support from Circassia Ltd, Green Cross, GlaxoSmithKline, Merck, Novartis, Sanofi, and SunPharma Advance Research Corporation; and has received lecture fees from Aralez, AstraZeneca, Merck, Novartis, Pfizer, and Takeda. W. Alqurashi declares no relevant conflicts of interest.

View full text

Review and Feature ArticleDo Corticosteroids Prevent Biphasic Anaphylaxis?

Section snippets

Methods

Conclusions

World Allergy Organ J

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Immunol Allergy Clin North Am

J Allergy Clin Immunol

J Allergy Clin Immunol

Allergol Int

J Allergy Clin Immunol

Ann Emerg Med

Ann Allergy Asthma Immunol

J Allergy Clin Immunol Pract

J Emerg Med

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

Am J Emerg Med

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol Pract

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

Ann Emerg Med

Toxicon

Radiol Clin North Am

Allergy Asthma Clin Immunol

Chest

Ann Allergy Asthma Immunol

World Allergy Organ J

Lancet

World Allergy Organ J

The diagnosis and management of anaphylaxis practice parameter: 2010 update

J Allergy Clin Immunol

Anaphylaxis and allergy in the emergency department. 2015

Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England

J R Soc Med

Review and Feature Article
Do Corticosteroids Prevent Biphasic Anaphylaxis?