Biphasic allergic reactions in children – observation period
Date First Published:
May 21, 2010
Last Updated:
October 13, 2014
Report by:
Nalayini Jeyavel, Clinical Fellow (Luton and Dunstable University HOSPITAL)
Search checked by:
Hemavathi Muniswamy, Luton and Dunstable University HOSPITAL
Three-Part Question:
[In patients under 16 years old with an acute allergic reaction] is [4 hours observation] sufficient to [exclude biphasic reaction?]
Clinical Scenario:
29 month old boy had a representation with severe hives and vomiting 14 hrs from initial presentation with severe anaphylactic reaction to the Emergency department, you just wonder this child should be observed longer.
Search Strategy:
Medline 1984 – 2014
(Exp allergy.ti,ab or anaphylaxis.ti.ab AND biphasic) (Limit to English Language and Humans and (Age Groups All Child 0 to 18 years))
(Exp allergy.ti,ab or anaphylaxis.ti.ab AND biphasic) (Limit to English Language and Humans and (Age Groups All Child 0 to 18 years))
Outcome:
20 papers were identified using Medline. Five papers provided evidence that was relevant to the three-part question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Biphasic reactions in children undergoing oral food challenges Juhee Lee, M.D., Jackie P.-D. Garrett, M.D., Terri Brown-Whitehorn, M.D., and Jonathan M.Spergel, M.D., Ph.D 2013 USA | 1688 oral food challenges (OFCs) were analyzed | A retrospective chart review (July 2007 - March 2011) | Biphasic reactions were rare. | 614 challenges (36.4%) were positive, and nine resulted in biphasic reactions (1.5% of positive chanllenges) 310 met anaphylaxis criteria, six resulted in biphasic reactions (1.9%). | Retrospective chart review Study relied on parental calls on biphasic reactions, Possible missed cases who received care outside the study net work |
| The interval from resolution of initial reaction to onset of second reaction | Ranged from 2 to 24 hrs | ||||
| Anaphylaxis and Biphasic Phase in Thailand: 4-year Observation. Ratchaya Lertnawapan and Wirach Maek-a-nantawat 2011 Thailand | 208 cases of anaphylaxis were identified | Observational study (2004 – 2008) | The prevalence of anaphylaxis is increasing. | Among 6.3 of the patients who developed biphasic reaction. | Study setting Recall bias |
| The occurrence of biphasic reactions might be affected by early management and early recognitionof cases. | The median times from onset to hospital arrival and the arrival to administration of epinephrine were also significantly longer in the biphasic group than the non-biphasic patients (p = 0.002 and p = 0.001, respectively). | ||||
| Clinical predictors for biphasic reactions in children presenting with anaphylaxis S.Mehr, W.K.Liew, D.Tey, M.L.K.Tang 2009 Australia | 109 cases were included | Retrospective study over a 5 year duration | Uniphasic;Biphasic | There were 95 uniphasic (87%), 12 (11%) biphasic and two protracted reactions (2%). | Its respective design Inability to measure biphasic reactions in non-hospitalized individuals. Potential inadequate or incomplete documentation |
| Children who received >1 dose of adrenaline and/or a fluid bolus for treatment of their primary anaphylactic reaction were at increased risk of developing a biphasic reaction. | For the management of the primary anaphylactic reaction, children developing biphasic reactions were more likely to have received >1 dose of adrenaline (58% vs. 22%, P=0.01) and/or a fluid bolus (42% vs. 8%, P=0.01) than those experiencing uniphasic reactions | ||||
| Incidence and characteristics of biphasic anaphylaxis Anne K. Ellis, MD, FRCPC, and James H. Day, MD, FRCPC 2006 Ontario | Prospective evaluation of 103 patients | Prospective study | The second-phase onset was 10 hours on average, but it occurred as late as 38 hours. | Twenty patients (19.4%) experienced confirmed biphasic reactivity. | Lacking evidence to determine course for Biphasic allergic reactions (5/20 - unknown cause) |
| Second phase reactivity has significant implications for clinical management of patients. | Average time to onset of the second phase was 10 hours (range, 2-38 hours); 8 patients (40.0%) had their second phase occur more than 10 hours after the initial reaction. | ||||
| Biphasic reactors in this study took significantly longer to achieve resolution of their initial symptoms | Time to resolution of initial symptoms was significantly longer for biphasic reactors (112 vs 133 minutes; P = .03). | ||||
| Biphasic Anaphylactic Reactions in Pediatrics Joyce M.Lee and David S. Greenes 2000 America | 108 anaphylactic episodes were included | Retrospective study (1985 - 1999) | Retrospective study Study was performed in hospitalized children and many patients with anaphylaxis were likely discharged directly from the Emergency Department, and others may have been treated solely by their primary physicians. |
Author Commentary:
Anaphylaxis is the clinical syndrome representing a life threatening systemic allergic reaction. According to Stark BJ, Sullivan TJ. Arch Intern Med. 2001: Variants of the usual monophasic anaphylaxis syndrome include late onset anaphylaxis, biphasic anaphylaxis and protracted anaphylaxis.
According to Sampson HA, Mendelson L, Rosen JP. N Engl J Med 1992, and Stark BJ, Sullivan TJ. Allergy Clin Immunol 1986: The biphasic reaction of anaphylaxis is a recurrence of anaphylactic symptoms after intial remission has occurred. Case series of these biphasic reactions reveal that recurrence can be severe enough to necessitate intubation and treatment with vasopressor agents.
According to Mertes PM, Malinovsky JM, Mouton-Faivre C et al. And Weiler HA: Many contributing factors masking the actual incidence of anaphylaxis includes unawareness, nonidentification, especially in some circumstances such as the perioperative period: emergencies, and life saving or unconditional management and death with unidentified cause: and missed diagnosis of a case presenting mild symptoms.
Mehr S,Liew WK,Tey D,Tang ML et al 2009 found for management of primary anaphylactic reaction, children developing biphasic reactions were more likely to have received > 1 dose of adrenaline (58% vs 22%, P = 0.01) and/or fluid bolus (42% vs 8%, P= 0.01) than those experiencing uniphasic reactions. The absence of either factor was strongly predictive of the absence of biphasic reaction (negative predictive value 99%), but the presence of either factor was poorly predictive of biphasic reaction (positive predictive value of 32%).
Lertnawapan R,Maek-a-nantawat W et al 2011 reported the median time interval (minutes) from onset to administration of epinephrine was significantly longer in biphasic group than non- biphasic patients, 240 (IQR 122.5-380) vs 70v(IQR 40-135) minutes, p=0.002. Also the median time interval (minutes) from onset to hospital arrival was longer in the biphasic group than the non-biphasic group, p = 0.002.
A variety of antigens led to biphasic reactions, the most common being foods (35.0%) and Hyemenoptera venom (25.0%).The occurrence rates of inciting antigens were not significantly different between uniphasic and biphasic reactions (P > .25); Ellis AK,Day JH et al 2006.
According to Sampson HA, Mendelson L, Rosen JP. N Engl J Med 1992, and Stark BJ, Sullivan TJ. Allergy Clin Immunol 1986: The biphasic reaction of anaphylaxis is a recurrence of anaphylactic symptoms after intial remission has occurred. Case series of these biphasic reactions reveal that recurrence can be severe enough to necessitate intubation and treatment with vasopressor agents.
According to Mertes PM, Malinovsky JM, Mouton-Faivre C et al. And Weiler HA: Many contributing factors masking the actual incidence of anaphylaxis includes unawareness, nonidentification, especially in some circumstances such as the perioperative period: emergencies, and life saving or unconditional management and death with unidentified cause: and missed diagnosis of a case presenting mild symptoms.
Mehr S,Liew WK,Tey D,Tang ML et al 2009 found for management of primary anaphylactic reaction, children developing biphasic reactions were more likely to have received > 1 dose of adrenaline (58% vs 22%, P = 0.01) and/or fluid bolus (42% vs 8%, P= 0.01) than those experiencing uniphasic reactions. The absence of either factor was strongly predictive of the absence of biphasic reaction (negative predictive value 99%), but the presence of either factor was poorly predictive of biphasic reaction (positive predictive value of 32%).
Lertnawapan R,Maek-a-nantawat W et al 2011 reported the median time interval (minutes) from onset to administration of epinephrine was significantly longer in biphasic group than non- biphasic patients, 240 (IQR 122.5-380) vs 70v(IQR 40-135) minutes, p=0.002. Also the median time interval (minutes) from onset to hospital arrival was longer in the biphasic group than the non-biphasic group, p = 0.002.
A variety of antigens led to biphasic reactions, the most common being foods (35.0%) and Hyemenoptera venom (25.0%).The occurrence rates of inciting antigens were not significantly different between uniphasic and biphasic reactions (P > .25); Ellis AK,Day JH et al 2006.
Bottom Line:
The wide range of reported asymptomatic intervals make it difficult to determine appropriate clinical guidelines for duration of clinical observation. Patients with an episode of anaphylaxis to be observed for 8-24hrs to monitor for biphasic reactions and reactions may even occur later up to 72hours after resolution of primary event.
All patients at risk of a biphasic reaction, clinicians must ensure any patients discharge from hospital following anaphylaxis has an emergency plan in place and injectable adrenaline available to ensure adequate management of any subsequent biphasic reaction.
All patients at risk of a biphasic reaction, clinicians must ensure any patients discharge from hospital following anaphylaxis has an emergency plan in place and injectable adrenaline available to ensure adequate management of any subsequent biphasic reaction.
References:
- Juhee Lee, M.D., Jackie P.-D. Garrett, M.D., Terri Brown-Whitehorn, M.D., and Jonathan M.Spergel, M.D., Ph.D. Biphasic reactions in children undergoing oral food challenges
- Ratchaya Lertnawapan and Wirach Maek-a-nantawat. Anaphylaxis and Biphasic Phase in Thailand: 4-year Observation.
- S.Mehr, W.K.Liew, D.Tey, M.L.K.Tang. Clinical predictors for biphasic reactions in children presenting with anaphylaxis
- Anne K. Ellis, MD, FRCPC, and James H. Day, MD, FRCPC. Incidence and characteristics of biphasic anaphylaxis
- Joyce M.Lee and David S. Greenes . Biphasic Anaphylactic Reactions in Pediatrics