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Three Part Question

In [children with anaphylactic reactions] do [steroids] prevent [biphasic reactions]?

Clinical Scenario

A 6 year old boy has been brought into the paediatric emergency department after an anaphylactic reaction to granary bread. After appropriate treatment the child's symptoms resolve. You wonder whether discharging with steroids will prevent a biphasic reaction?

Search Strategy

Original search

Medline 1946 to June, week 1 2013. EMBASE 1980–2013, week 26. Cochrane Library ‘((exp hypersensitivity/) OR (exp anaphylaxis/) OR (anaphyla$.mp) OR (aller$.mp) OR (acute ADJ allergic ADJ reaction)) AND ((biphasic.mp) OR (exp recurrence/) OR (early ADJ phase ADJ reaction) OR (late ADJ phase ADJ reaction) OR (delayed ADJ reaction)) AND ((exp steroids/) OR (exp adrenal cortex hormones/) OR (exp prednisolone/) OR (exp dexamethasone/) OR (exp hydrocortisone/) OR (exp glucocorticoids/) OR (steroi$.mp)). Limits: English language, humans, children 0–18 years. Cochrane Library: title, abstract, keywords (steroids) and title, abstract, keywords (allergy) and title, abstract, keywords (biphasic).

Second search

Medline 1946–March, week 1 2014 {exp Anaphylaxis/or anaphylaxis.mp. OR anaphyla$.mp. OR (acute adj allergic adj reaction).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier] OR aller$.mp.} AND {biphasic.mp.}. Limits: English language and humans and “all child (0 to 18 years)”.

Search Outcome

Original search

A total of 490 papers were discovered but only three papers, one of which was a Cochrane review, were found to be relevant.

Second search

Fifty-one papers were found, which included two systematic reviews and an additional three studies, and one guideline. Only the most recent of the reviews is included. The relevant papers are summarised in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Choo, KJL et al 2012 Scotland	All eligible papers including patients experiencing anaphylactic reaction caused by food, insect venoms, medication, anaesthetics, diagnostic agents, vaccinations, latex or exercise	Systematic Review	Mortality rate	There were no high quality randomised or quasi-randomised controlled trials comparing glucocorticoids with any control treatment	Only considers glucocorticoids effect on anaphylaxis and not mild allergic reactions
			Prevention of biphasic or prolonged anaphylaxis	There were no high quality randomised or quasi-randomised controlled trials comparing glucocorticoids with any control treatment
Lee and Greenes 2000 USA	All children admitted to a children’s hospital over a 14 year period with ICD9 codes for allergy and anaphylaxis. 108 episodes were documented. 105 episodes resolved after initial treatment	Retrospective analysis of medical records.	Biphasic reactions	6 (6%)	Only considers children admitted to hospital and not those cared for exclusively in PED. Steroid dose not specified. Limited statistical power. Retrospective nature could have missed cases.
			Steroid used initially	Uniphasic 84.4% vs biphasic 83.3%, ns
Poachanukoon and Paopairochanakorn 2006 Thailand	All patients attending ED of a tertiary hospital in Thailand over a 12 month period using IDC9 and 10 codes for allergy and anaphylaxis. 65 anaphylactic reactions identified.	Retrospective case note study.	Biphasic reaction	8 (13%)	Retrospective study. No p values provided in paper.
			Use of steroids in biphasic reactions	No significant difference in steroid usage between biphasic and monophasic groups (79.5% vs. 87.5%)
Mehr et al. 2009 Australia	Children presenting to the ED of a tertiary Paediatric Hospital (Royal Children's Hospital, Melbourne), 1998-2003. 109 episodes in 104 children.	Retrospective case note study.	Biphasic reactions	12 (11%)	Only those admitted for more than 6 hours were included. Steroid dose not specified.
			Corticosteroids	Uniphasic 79% vs biphasic 83%, p=1.0
Ellis and Day 2007 Canada	Prospective evaluation of patients attending or admitted from 2 EDs over a three year period 1999-2001. Patients discharged from the ED were contacted within 72 hours to check whether they had had a biphasic reaction. 134 patients were identified but follow-up data was only available for 103.	Prospective cohort study.	Biphasic reaction	20 (19.4%)	There were only 10 cases of patients under the age of 13 years. Steroids did not seem to be widely used.
			Corticosteroid	Uniphasic (55.4%) vs biphasic (35.0%), p=0.07
			Prednisone equivalent/average dose	113/63 mg vs 101/31 mg, p=0.06
Lertnawapan and Maek-a-nantawat 2011 Thailand	Patients presenting to the ED of a University Hospital with anaphylaxis. 208 cases over the study period 2004-2008.	Cohort study	Biphasic reaction	13 (6.3%)	Unclear whether it was prospective or retrospective or a combination of both. Median age was 21 years, but the number of children was not specified.
			Steroid use	Uniphasic 86.7% vs biphasic 76.9%, ns
Tole and Lieberman 2007 USA	9 studies and case series identified.	Systematic review	Use of steroids	2 studies specifically stated that steroids had no effect on the incidence of biphasic reactions. 2 studies suggested that steroids did have an effect.	These were not trials, nor were they prospective studies. Only small numbers were involved (for a total of 72 biphasic reactions). The studies were not specifically paediatric. The studies by Ellis and Day and Lee and Greenes are tabulated because of their size and paediatric population.

Comment(s)

Steroids are recommended in the management of anaphylactic reactions (Soar et al, 2008). The rationale is that they, “may help prevent or shorten protracted reactions” and, “in asthma, early corticosteroid treatment is beneficial in adults and children”. The guideline also recommends giving patients being discharged antihistamines and steroids as these, “may decrease the chance of further reaction”. Little evidence is presented to justify these recommendations. Indeed, the authors of the 2007 position paper of the European Academy of Allergology and Immunology on the management of anaphylaxis in childhood acknowledge that the efficacy of steroids in reducing the risk of late phase reactions “has not been fully proven”. Their recommendation on the use of steroids is graded only D. The literature identified relates to 590 anaphylactic reactions only 59 of which were biphasic (Tole and Lieberman identified a further 46 biphasic reactions). Statistically equal proportions of patients with uniphasic and biphasic reactions had received steroid treatment on presentation. As there are no randomised controlled trials of the use of steroids in anaphylaxis it is difficult to know whether they might have an effect on the incidence of biphasic reactions. Given the benefits of steroids in the management of asthma, wheeze and cutaneous reactions, there are still good reasons for continuing to use them in anaphylaxis.

Editor Comment

ED, emergency department; NS, not significant; PED, paediatric emergency department.

Clinical Bottom Line

There is a lack of randomised controlled trial evidence to suggest that steroids reduce the incidence of biphasic anaphylactic reactions.

References

1. Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis Cochrane systematic review Allergy 2010;65(10):1205-11.
2. Lee JM, Greenes DS. Biphasic Anaphylactic Reactions in Pediatrics Pediatrics. 2000;106(4):762-6.
3. Poachanukoon O, Paopairochanakorn C. Incidence of anaphylaxis in the emergency department: a 1-year study in a university hospital Asian Pac J Allergy Immunol 2006;24(2-3):111-6.
4. Mehr S, Liew WK, Tey D, et al. Clinical predictors for biphasic reactions in children presenting with anaphylaxis. Clinical & Experimental Allergy 2009:39:1390-1396.
5. Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol. 2007;98:64-69.
6. Lertnawapan R, Maek-a-nantawat W. Anaphylaxis and biphasic phase in Thailand: 4-year observation. Allergology International 2011;60:283-289.
7. Tole JW, Lieberman P. Biphasic anaphylaxis: Review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin N Am 2007;27:309-326.
8. Muraro A, Roberts G, Clark A, et al. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology. Allergy 2007;62:857-871.
9. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions - guidelines for healthcare providers. Resuscitation 2008;77:157-169.