Modified guidelines identify anaphylaxis in more infants, young children
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Key takeaways:
- Current guidelines have not been validated in infants and toddlers.
- Overlooked symptoms include flushing, drooling and regurgitation.
- The modified criteria identified anaphylaxis in all the infants.
Modified criteria that incorporated symptoms specific to infants and young children increased identification of anaphylaxis in these age groups, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Health care professionals also would benefit from improved training in identifying and managing anaphylaxis, Michael Pistiner, MD, MMSc, director of food allergy advocacy, education and prevention, Mass General for Children, and colleagues wrote.
Need for guidelines
“Among many reasons, anaphylaxis is particularly challenging to diagnose in young patients given their nonverbal or minimally verbal status,” Pistiner told Healio.
For example, he said, infants and toddlers may be unable to articulate that their mouth or ears are becoming itchy or that they are beginning to have an upset stomach.
“This emphasizes the importance that clinicians be educated of, look for or ask about objective signs that function as surrogates for subjective experiences that infants and young children may not be able to communicate,” Pistiner said.
Another consideration is that infants, toddlers and young children appear to be able to remain in a state of compensated shock with stable blood pressures for longer periods of time than one may expect in older patients, he added.
“If clinicians rely upon hypotension as the predominant cardiovascular sign as in the current criterion, they may be missing the early presentation of anaphylactic shock pathophysiology in this specific patient population,” Pistiner said.
The criteria for identifying anaphylaxis published by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN) in 2006 have not been validated in infants and toddlers aged 2 years and younger.
An evidence-based practice parameter for diagnosing and treating anaphylaxis developed by a joint task force and published in 2023 recommended additional research into these knowledge gaps in recognizing anaphylaxis among infants and toddlers.
Pistiner noted the dangers of misdiagnosis in children among these age groups.
“Anaphylaxis is a life-threatening systemic reaction that can be triggered by many things, such as certain food proteins, insect venom or medications,” he said.
Delays in recognizing anaphylaxis or missing the diagnosis completely can set back appropriate treatment with prompt administration of intramuscular epinephrine.
“Delays in identification and treatment can therefore result in increased morbidity, probability of biphasic reactions, admission rates and, in rare instances, increased mortality,” he said.
Consequently, the researchers aimed to identify anaphylaxis symptoms specific to infants and toddlers, develop clinical criteria that incorporated these findings, and compare these criteria against the NIAID/FAAN guidelines.
For example, flushing or pruritis, drooling, regurgitation, increased fussiness or irritability, and drowsiness and/or somnolence often are overlooked or underrecognized in infant anaphylaxis, the researchers said.
The researchers also included signs of laryngeal involvement such as a hoarse voice or cry, swollen tongue or uvula, and earlier markers of cardiovascular compromise, among other symptoms, in their modifications.
“Compared to the NIAID/FAAN guidelines, our modified criteria account for age-specific differences, including the addition of surrogate signs to replace subjective symptoms as well as the incorporation of signs of compensated shock and cardiovascular compromise, such as tachycardia, cyanosis and mental status change, to supplement signs and symptoms of decompensated shock currently incorporated within the NIAID/FAAN criteria, such as hypotension,” Pistiner said.
Modifications in action
The retrospective chart review included 175 children aged 6 years and younger (mean age, 25.5 months; 58.3% boys; 52% white; 89.1% with no previous anaphylaxis) who presented with a suspected allergic or anaphylactic reaction to a single urban tertiary care pediatric ED between April 2016 and September 2019.
The cohort included 57 infants (33%) aged younger than 12 months; 68 toddlers (39%) aged 12 months to younger than 36 months; and 50 children (29%) aged 36 months and older.
There were 148 cases of anaphylaxis that met NIAID/FAAN criteria in the full cohort, and attendings diagnosed anaphylaxis in 74% of the children, 71% of the toddlers and 59% of the infants.
The NIAID/FAAN criteria captured 85% of the 175 encounters, including 77% of infants, 85% of toddlers and 92% of children. However, the modified criteria captured 98% of the encounters, including 100% of infants, 96% of toddlers and 98% of children.
The researchers called the differences between the criteria in overall captures and in the infant groups statistically significant (P < .001 for both). The difference between the criteria in the toddler groups was notable but not statistically significant.
The modified criteria also found 43% more patients with cardiovascular impairment, compared with the NIAID/FAAN criteria (P < .001), with statistical significance across all three age groups.
Altered mental status (29.2%) and tachycardia (26.9%) were the most common cardiovascular or end organ dysfunction signs or symptoms in the full cohort, with 38.6% of infants, 27.7% of toddlers and 20.4% of children experiencing altered mental status and 24.6% of infants, 33.8% of toddlers and 20.4% of children experiencing tachycardia.
There was a 32% increase in the number of patients with respiratory symptoms across all the age groups, according to the modified criteria, compared with the NIAID/FAAN criteria as well (P < .001). These differences also were statistically significant in each individual age group, the researchers added.
Cough was the most common respiratory symptom, including 24% of the full cohort, 12.3% of infants, 26.2% of toddlers and 34.7% of children. The NIAID/FAAN criteria do not directly mention cough, the researchers said, but their modified criteria include it.
Also, tachypnea was seen in 19.3% of infants, 9.2% of toddlers and 6.1% of children.
None of the age groups had any significant differences in gastrointestinal or mucocutaneous symptoms based on the NIAID/FAAN and modified criteria. Vomiting was the most common gastrointestinal symptom (46.8%).
The most common mucocutaneous symptoms included hives/urticaria (71.9%), swollen ears/eyes/face (39.8%), swollen lips (36.8%), flushing (33.9%) and pruritis (32.2%). There was a predominance of toddlers and children in lip swelling.
Angioedema of the eyes, ears and face impacted 29.8% of infants, 52.3% of toddlers and 34.7% of children overall. But throat symptoms, which may be difficult to detect among infants because of their inability to communicate, were observed in 1.8% of infants, 4.6% of toddlers and 30.6% of children.
Abdominal pain, which the researchers said is similarly difficult to observe in children who cannot communicate, was observed in 1.8% of infants, 3.1% of toddlers and 26.5% of children.
Conclusions, next steps
The use of the modified criteria enhanced the identification of anaphylaxis among infants and potentially in toddlers, the researchers concluded, although they called for improved training in recognizing and managing anaphylaxis among health care professionals.
“From our team’s clinical experience and looking at the results of our study, we think it’s important to look at the higher rates of cardiovascular involvement reported in this age group after the addition of signs of compensated shock within our modified criteria,” Pistiner said.
“Included in the NIAID/FAAN criteria, syncope, hypotension, hypotonia and incontinence were rarely seen in our cohort. However, our additions of altered mental status and tachycardia were present in 39% and 25% of presentations in infants, respectively,” he continued.
Further, Pistiner said, these findings highlight the importance of thinking about and looking for signs of compensated shock and cardiovascular compromise when anaphylaxis is on the differential when evaluating young patients.
“We hope that our findings will help providers improve recognition of anaphylaxis in general, but importantly to also identify cardiovascular and respiratory symptoms that may necessitate urgent treatment and further care,” he said.
The researchers called for multicenter prospective studies that would use a structured flowsheet for reporting these symptoms and signs to reduce the variability in the degree of documentation in evaluating how effective these modified criteria may be while validating the use of these modified criteria for identifying anaphylaxis in infants and toddlers.
Reference:
- Mass General for Children investigators propose modified criteria for identifying anaphylaxis in infants and young children. https://www.massgeneral.org/news/press-release/identifying-signs-anaphylaxis-infants-toddlers. Published June 28, 2024. Accessed July 8, 2024.
Perspective
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Physiologic patterns and manifestations of anaphylaxis differ in infants and toddlers, and they are not included in the current criteria. Also, these children cannot communicate their symptoms like older children or adults, so they cannot meet some of the criteria set for adults.
Previous studies by these investigators and others have identified a range of observed symptoms and signs in infants and toddlers during allergic reactions. Using the objective criteria developed for adults will miss cases that do not have the typical signs and symptoms, such as hypotension and dyspnea, even though they show subtle signs including behavioral changes, tachycardia, floppy posture, drooling, hoarse cry, cough and increased work of breathing.
By building on previous studies that catalog manifestations in infants and toddlers and identifying objective signs and surrogate markers that can be included in modified criteria, we can improve the diagnosis of anaphylaxis in infants and toddlers.
Clearly, the modifications suggested in this study are beneficial, as shown by the much-improved sensitivity of the modified criteria. The increased accuracy will lead to better guidance for affected patients and families and will hopefully reduce the risk for future severe reactions by steering those patients to expert care, counselling and treatment.
As for further modifications to the guidelines for these age groups, it would be difficult to improve upon the work of these investigators, who are renowned for their expertise and research on anaphylaxis in young children.
However, as mentioned in the article, there is work to be done on validating these criteria in larger cohorts and different populations, as this was a single-center study. There is a need to create a kind of checklist, described by the authors as a “structured flowsheet,” to help clinicians and researchers identify patients with anaphylaxis more quickly, efficiently and accurately. Additionally, there will be a need to validate that instrument prospectively in clinical studies. Using these modified criteria will also lead to better characterization of young children with severe anaphylaxis and to targeting treatment and prevention more efficiently to those patients.
Perspective
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In an attempt to acknowledge age-specific signs and symptoms that more accurately identify anaphylaxis in young children, the authors developed and compared a modified criteria for “likely anaphylaxis” against the widely used 2006 NIAID/FAAN criteria by performing a retrospective chart review of 337 clinical encounters presenting with suspected allergic or anaphylactic reactions to a urban tertiary care pediatric ED.
The authors found that the modified anaphylaxis clinical criteria had significantly improved sensitivity for diagnosing anaphylaxis in young children, particularly infants, compared with the NIAID/FAAN criteria.
The authors stress that subtle findings and differences in age need to be considered when assessing potential anaphylaxis. This includes the fact that while hypotension and syncope were not observed in infants and toddlers, pediatric-specific signs of cardiac impairment and/or compensated shock were instead observed more frequently.
These symptoms, such as tachycardia and cyanosis, and laryngeal symptoms are not mentioned in NIAID/FAAN criteria but have been added to the World Allergy Organization modifications, as drooling and hoarse voice/cry are symptoms of laryngeal involvement seen in young children.
As mentioned earlier, one of the greatest changes is seen in the toddler age, where subtle findings may need to be noted. As an example, throat symptoms and abdominal pain may be difficult to identify in a nonverbal child.
The authors suggest that future multicenter prospective studies using a structured flowsheet for the reporting of symptoms/signs may reduce variability in the degree of documentation and may be powered to elucidate more nuanced differences while evaluating the effectiveness of this modified criteria.
Overall, this is important new information that highlights the need for suspicion and considering subtle symptoms when faced with a young child or infant with anaphylaxis.
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