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. Author manuscript; available in PMC: 2023 Dec 5.
Published in final edited form as: Ann Allergy Asthma Immunol. 2023 May 19;131(2):170–175. doi: 10.1016/j.anai.2023.05.009

How to define severity

A review of allergic reaction severity scoring systems

Ami Shah *, Timothy E Dribin †,‡, Julie Wang *
PMCID: PMC10696494  NIHMSID: NIHMS1945979  PMID: 37209834

Abstract

Numerous scoring systems have been developed to improve and standardize the diagnosis and management of acute allergic reactions and anaphylaxis; however, considerable variability exists among these systems. This review article discusses existing severity scoring systems and identifies specific knowledge gaps that remain. Future research is needed to resolve the limitations of existing grading systems, including attempting to link reaction severity with treatment advice and conducting validation studies in different clinical settings, patient populations, and geographies to promote grading system application and dissemination in both clinical care and research.

Introduction

Allergic reactions can be due to a variety of triggers including foods, medications, and insect stings, but sometimes, the cause may not be known. Symptoms can range from mild, self-limiting local cutaneous reactions to life-threatening cardiopulmonary arrest. Although providers can usually and reliably identify reactions at both ends of the severity spectrum, controversy exists on ways to classify reactions positioned between the 2 severity extremes. Different allergic reaction scoring systems have been developed to support diagnostic and management decisions and to standardize research outcomes. In this review, we compare different allergic reaction grading systems, including related knowledge gaps and future research needs.

Defining Anaphylaxis

There is no reference standard to diagnose anaphylaxis; however, definitions have been proposed to reduce diagnostic uncertainty and standardize management decisions.1 As stated by the practice parameters from the American Academy of Allergy, Asthma, and Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force, anaphylaxis is an “acute, life-threatening systemic reaction with varied mechanisms, clinical presentations, and severity.”2 This vague definition encompasses a broad range of clinical scenarios and may contribute to uncertainty as to whether reactions constitute anaphylaxis because the perception of severity may vary depending on who is making the assessment (eg, patients and caregivers, primary care physicians, allergists, emergency care physicians, public health officials) and their ability to recognize symptoms, previous training, and the clinical setting and related resource availability.3,4

However, despite these differences, it is important to harmonize the terminology used to assess reaction severity given that it may affect management strategies, including whether to give epinephrine.4 For example, the underutilization of epinephrine in community and emergency department (ED) settings has been partially attributed to the challenge of diagnosing anaphylaxis, especially when the trigger is not known, when signs are only subjective (eg, “I’m having trouble breathing”), and when the diagnosis overlaps with other conditions.5 The challenge of diagnosing anaphylaxis has also been observed among allergists6 and pediatricians.7 Universal anaphylaxis diagnostic criteria can improve communication among patients, caregivers, and providers from different specialties and can help standardize reaction management.4 Consensus diagnostic criteria are also vital in public health for disease surveillance and in research to evaluate outcomes in clinical and interventional studies.4

In 2005, the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network (NIAID/FAAN) developed clinical criteria to define anaphylaxis (Table 1).8 The criteria outline 3 different clinical scenarios that would qualify as anaphylaxis. The NIAID/FAAN criteria have been retrospectively and prospectively validated in the ED.9,10 In the prospective study, they had a sensitivity and specificity of 95.1% and 70.8%, respectively, in diagnosing anaphylaxis.10 However, these studies are limited because there is no reference standard for diagnosing anaphylaxis, and instead, the expert opinion of 2 board-certified allergists was used as the reference for defining anaphylaxis.10 Since the initial publication of the NIAID/FAAN criteria, international allergy organizations have identified a need to refine the criteria. For instance, the World Allergy Organization (WAO) noted that the NIAID/FAAN criteria included vague terminology such as “persistent gastrointestinal symptoms” and failed to categorize a patient who has isolated upper (eg, stridor) or lower respiratory involvement (eg, wheezing) after a known allergen exposure as having anaphylaxis and for whom epinephrine should be administered.1 For these reasons, the WAO submitted a revision to the NIAID/FAAN criteria (Table 1) in 2019.1 In addition to addressing the previously mentioned points, the revised WAO criteria do not classify food-induced reactions with nonsevere gastrointestinal and dermatologic/mucosal findings as anaphylaxis,1 whereas the NIAID/FAAN criteria do8 (Table 1).

Table 1.

Criteria to Diagnose Anaphylaxis per NIAID/FAAN in 2006 and WAO in 20191,8

NIAID/FAAN Criteria WAO Revised Criteria
1. Acute onset of an illness (min to several h) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips/tongue/uvula) AND AT LEAST 1 OF THE FOLLOWING:
 a. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
 b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)		  1. Acute onset ofan illness (min to several h) with involvement ofthe skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips/tongue/uvula) AND AT LEAST 1 OF THE FOLLOWING:
 a. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
 b. Reduced BP or associated symptoms ofend-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)
 c. Severe gastrointestinal symptoms (eg, severe crampy abdominal pain, repetitive vomiting), especially after exposure to non-food allergens
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (min to several h):
 a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula)
 b. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia)
 c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
 d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)		 2. Acute onset ofhypotension or bronchospasm or laryngeal involvement after exposure to a known or highly probable allergen for that patient (min to several h), even in the absence of typical skin involvement:
 a. Infants and children: low systolic BP (age specific) or >30% decrease in systolic BP
 b. Adults: systolic BP of <90 mm Hg or >30% decrease from that person's baseline
3. Reduced BP after exposure to known allergen for that patient (min to several h):
 a. Infants and children: low systolic BP (age specific) or >30% decrease in systolic BP
 b. Adults: systolic BP of <90 mm Hg or >30% decrease from that person's baseline
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It is also important to recognize that anaphylaxis occurs along a severity spectrum. For example, although a child with hives and persistent abdominal pain and a child with shock after food allergen exposure would both constitute anaphylaxis cases per the NIAID/FAAN criteria, the management and potential outcomes of these reactions are distinct. Although the first reaction almost always responds to a single dose of epinephrine, the latter may require aggressive fluid resuscitation and a continuous infusion of epinephrine in the intensive care unit. In addition, differentiating reaction severity can affect decision making for long-term management, including immunotherapy. Furthermore, the severity of a single reaction may change over time with delayed, persistent, or refractory symptoms, which is not addressed by existing scoring systems. For these reasons, there has been an impetus to develop scoring systems to standardize the assessment, and potentially the management, of both anaphylaxis and nonanaphylactic reactions.

Scoring Systems

Numerous scoring systems have been developed to characterize the severity of anaphylaxis and nonanaphylactic reactions11–23 (Table 2). Most systems were developed based on the expertise of a few individuals11–14,16–18 whereas more recent scales have been developed with input from multidisciplinary and/or international expert panels.20–23 The ideal grading system, as noted by the European Academy of Allergy and Clinical Immunology (EAACI), would be developed on the basis of a statistical analysis of objective data collected from a large patient population with a broad range of clinical symptom severity.4 Although this is well intentioned, in the US, for example, there is no national registry to accurately capture signs/symptoms, clinical courses, and other clinically relevant outcomes.4 A widely used 3-tier grading system was retrospectively derived by Brown in 2004, using logistic regression to analyze associations between individual reaction characteristics and either hypotension or hypoxia for patients who presented to the ED with systemic hypersensitivity reactions. Mild reactions were limited to skin involvement whereas hypotension or hypoxia characterized severe reactions, and the severity grades were correlated with epinephrine usage.15

Table 2.

Comparison of existing allergic reaction scoring systems

Category Gold et al,23 2023 Chinthrajah et al,22 2022 Dribin et al,21 2021 Cox et al,20 2017 Niggeman and Beyer,19 2015 Astier et al,182006 Hourihane et al,17 2005 Ewan and Clark,16 2005 Brown,15 2004 Sampson,14 2003 Lockey et al,13 1988 Ring and Messmer,12 1977 Mueller,11 1959
Stakeholders involved in development Allergists, public health safety officials—International Allergists, industry partners—United States Allergists, general and pediatric ED physicians—United States Allergists, industry partners, health regulatory authorities—International Allergists—Germany Allergists—United States, France Allergists—United Kingdom Allergists—United Kingdom Emergency medicine physician—Australia Allergists—United States Allergists—United States Allergists— Germany Allergists—United States
Methods Expert opinion Expert opinion Delphi Expert opinion Expert opinion Expert opinion Expert opinion Expert opinion Recursive Partitioning Expert opinion Expert opinion Expert opinion Expert opinion
Scale 1–3 1–5 1–5 1–5 1–3 1–5 5 levels 1–5 1–3 1–5 3 levels 1–4 4 levels
Is anaphylaxis defined at a particular grade? All 3 levels describe anaphylaxis No No Yes, grade 4 and 5 Yes, grade 3 No Severe reaction is defined at a score of ≥ 14 Severe reaction is defined as grade 5 Moderate and severe reactions (grade 2 and 3) are categorized as anaphylaxis Bolded symptoms are identified as absolute indications for epinephrine Severe reaction is defined No Severe allergic reaction and shock are identified
Allergen Specific? Vaccine Food No Initially designed for aeroallergen IT, but later modified to be used with any allergenic trigger No Food Food, specifically designed to grade reactions during peanut OFC Food No Food Venom IT Colloid volume substance Venom from insect stings
Age Specific? All ages All ages All ages All ages All ages Some criteria not applicable to infants, and alternative criteria not provided (eg, abdominal pain) All ages Some criteria not applicable to infants (eg, “mild asthma”) Some criteria not applicable for young children/ infants (eg, hypotension criteria only listed for adults) All ages All ages Children and infant specific criteria not available for certain criteria (eg, tachy-cardia, hypotension) Some criteria not applicable to infants, and alternative criteria not provided (eg, dizziness, confusion, feeling of impending disaster)
Organ Systems Skin Skin Skin Skin Skin Skin Skin Skin Skin Skin Skin General (eg, fever) Skin
Involved  GI  GI  GI  GI  GI  GI  GI  GI  GI  GI  GI  Skin  GI
 CV  CV  CV  CV  CV  CV  CV  CV  CV  CV  CV  GI  CV
 Upp Resp  Upp Resp  Lwr Resp  Upp Resp  Lwr Resp  Lwr Resp  Lwr Resp  Lwr Resp  Lwr Resp  Upp Resp  Lwr Resp  CV  Lwr Resp
 Lwr Resp  Lwr Resp  Neuro  Lwr Resp  Neuro  Neuro  Lwr Resp Neuro  Lwr Resp  Neuro
Subjective Criteria? None None None None None None Yes; eg, “severe respiratory symptoms” Yes; eg, “pronounced dyspnea” Yes; eg, “dyspnea” Yes; eg, mild lip swelling is listed as Grade I GI symptoms whereas angioe- dema is listed as Grade II cutaneous symptom. The same symptom can be classified differently depending on the observer Yes; eg, “GI symptoms” is listed as criterion for a moderate systemic reaction, but does not detail what specific symptoms qualify Yes; eg, “mild but not life-threatening respiratory disturbance” Yes; eg, “dyspnea”
Nonspecific scale elements? None None None None Yes; eg, specific criteria for hypotension and tachycardia notoutlined Yes; eg, specific criteria for hypotension is not outlined Yes; eg, “severe respiratory symptoms” is not outlined further Yes; eg, “GI symptoms” is not outlined further None Yes; eg, mild hypotension is a criterion but not defined Yes; eg, there is an “other” criterion without details Yes; eg, “measurable but not life- threatening GI disturbance or respiratory disturbance” not outlined further Yes; eg, “fall in blood pressure” is listed but not defined (continued)
Treatment of symptoms affect grading? No Yes, cough responding to short broncho- dilator treatment is classified at a lower severity than are lower respiratory symptoms that are refractory to treatment No Does not mention specific medications, but does consider response to “treatment” in establishing grade No Does not mention specific medications but does consider response to “treatment” in establishing grade No No No No No No No
Non-sign or symptom criteria Laboratory values are part of determining level Final score depends on amount of peanut consumed
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Abbreviations: CV, cardiovascular; GI, gastrointestinal; IT, immunotherapy; Lwr Resp, lower respiratory; Neuro, neurologic; OFC, oral food challenge; Upp Resp, upper respiratory

Although some scoring systems are allergen specific, including for foods,14,16–18,22 drugs,12 vaccines,23 venom from insect stings,11 and immunotherapy,13,20 others apply to any allergens.15,19,21 In addition, grading systems like the Brighton criteria apply to only severe or anaphylactic reactions23 whereas others (eg, WAO, Niggeman, and Brown) include nonanaphylactic and anaphylactic reactions.14,15,19,20 Scoring systems generally assign a numerical score ranging from 1 to 3, 4, or 5, with lower numbers representing less severe reactions and high numbers indicating severe reactions, based on the presence of signs, symptoms and sometimes therapies. Although the 3-tier systems may be easier to remember and use clinically, they lack the granularity of the 4- or 5-tier systems, which may be advantageous for research purposes. Furthermore, grading scales incorporate different signs and symptoms to assess reaction severity, and the same signs and symptoms may result in different severity labels depending on the grading system. For instance, some systems do not account for upper airway or neurologic involvement whereas others do (Table 2) (eg, Consortium for Food Allergy Research, WAO, Brighton criteria), and in both the WAO and Brighton criteria, any gastrointestinal symptoms are scored at least at moderate severity because they were both initially designed for non–food allergenic triggers.20,23

Per the EAACI, the ideal scoring system “works across the range of allergenic triggers and addresses the needs of different stakeholder groups.”4 Dribin et al21 identified optimal scoring system criteria, including the ability of the grading scale to be widely applicable across multiple clinical scenarios, allergens, and ages. A limitation of some systems is the inclusion of variables that cannot be easily obtained in all clinical environments, such as changes in peak expiratory flow, to help categorize reactions.18 In addition, owing to the heterogeneity of existing scoring systems, different grades would be assigned to a reaction depending on which scoring system was used. For example, when using the Brighton criteria, localized hives away from the site of vaccine injection are considered major criteria, whereas localized hives would be considered less severe reactions when using non–vaccine grading scales. Another limitation of most grading scales is that they do not apply to infants and young children who cannot verbalize subjective symptoms (eg, abdominal pain, dizziness, confusion, the feeling of impending doom), and for whom signs such as hypotension may represent more severe reactions than in older individuals.11,15,16,18

Dribin et al emphasized that the optimal grading system should contain objective, measurable, and easily recognizable signs and symptoms.21 Many of the earlier scoring systems used subjective and nonspecific terminology (eg, dyspnea, “severe respiratory symptoms,” decrease in blood pressure). In addition, some grading scales incorporate therapies and treatment responses,18,20,22 and although therapies such as epinephrine are a valuable proxy of reaction severity and have face validity, there is well-documented variation in using therapies that may result in over- or undergrading. Similarly, if symptoms resolve after medication administration, it is challenging to determine whether the response was secondary to the treatment or instead would have occurred irrespective of the medication. For this reason, Dribin et al noted that the optimal grading system should not include treatments.

Finally, the grading system should be user-friendly for all stakeholders.4 This can be difficult to accomplish given the needs of stakeholders, and the settings in which they practice differ considerably. Patients and caregivers, along with ED and primary care physicians, need a simple, easy-to-use guide that links symptom severity with treatment recommendations (give epinephrine or not give epinephrine). In contrast, a detailed scoring system would be advantageous for researchers to report adverse events during clinical trials. Although an overly simplistic system may omit important reaction details, an overly complicated scale may not be adopted by patients, caregivers, or clinicians. To overcome the need for simplicity and nuance, the EAACI recommends developing both a pocket guide and a detailed version of the grading system (an approach taken by Dribin et al21) to meet the needs of different end users.4

Knowledge Gaps and Future Directions

Arguably, the most important criteria to assess the quality of a scoring system are whether it can provide an accurate assessment of severity across a range of clinical settings, link severity with treatment recommendations, and be easily translated into real-world scenarios in different clinical settings. Later, we outline 3 overarching knowledge gaps specific to grading scales and propose potential strategies and solutions to address these gaps.

Gap 1: Need for a Scoring System That Accurately Captures Severity Across a Range of Clinical Settings, Allergic Triggers, and Patient Ages

The heterogeneity of existing scoring systems limits their generalizability. Eller et al24 applied multiple different scoring systems to more than 2000 allergic reactions during food or drug challenges and found that there was poor agreement of severity among the grading systems. Concerns have also been recognized about the ability of the scoring systems to correctly identify milder reactions. Stafford et al presented an international group of multidisciplinary healthcare professionals with various clinical scenarios of food-induced allergic reactions and asked them to identify the most and least severe. These vignettes were also scored using published scoring systems. The study found that most of the scoring systems tend to overestimate the severity of mild reactions, especially those that were designed for non–food triggers.3 Similarly, Hourihane et al determined that up to 71% of vaccine-related anaphylaxis diagnosed by the Brighton criteria did not meet NIAID or WAO criteria for anaphylaxis.25 Overestimating severity may negatively affect public health by fueling vaccine hesitancy or resistance.26 Finally, factors used to determine severity by stakeholders may not be appropriately captured in these grading systems. For example, Stafford’s group recognized that inadequate treatment response was important for healthcare professionals to determine severity,3 but most of the published scoring systems do not incorporate this information (Table 2). In addition, Stafford’s group noted that clinicians found a scenario more severe if there was persistence of symptoms over time3; however, most scoring systems do not incorporate a reaction’s evolution with time into the evaluation. Dribin et al note 1 way to address delayed, persistent, and biphasic reactions would be to grade the reaction severity longitudinally at various snapshots of the reaction duration21; nonetheless, external validation is necessary to determine whether this approach is practical. Of the scoring systems that exist in the literature, we believe that the grading system developed by Dribin et al21 is most easily applicable to different patient ages, allergens, and clinical settings, and should be the basis for further refinement and validation studies to ensure accuracy and reliability.

Gap 2: Need to Link Severity With Treatment Recommendations

In addition to accurately determining severity, scoring systems must meet the needs of different stakeholders (eg, patients, caregivers, ED, and primary care physicians), including guidance on whether to administer epinephrine. Considerable variation in using epinephrine has been noted in the ED, with significant underuse in treating anaphylaxis and overuse in treating nonanaphylactic reactions (eg, isolated angioedema).27 Although the threshold to treat an allergic reaction with epinephrine may vary between patients on the basis of their ability to recognize symptoms and access emergency care, it is important for a decision-making tool to quickly provide immediate treatment advice based on the severity of signs and symptoms.28 Some scoring systems (eg, WAO, Niggeman et al19) do indicate which grades constitute anaphylaxis and thus specify when to use epinephrine; 20 however, scoring systems must be validated in different clinical settings to provide data-driven treatment recommendations. Future investigations are needed to develop consensus guidelines on when to administer epinephrine to manage acute allergic reactions, which would be beneficial for patients and their families, primary care providers, ED and emergency medical service providers, and allergists, and could also help standardize clinical trial protocols. Consensus methods (eg, Delphi) are 1 option to address this gap because randomized controlled trials are not feasible.

Gap 3: Need to Externally Validate and Determine Strategies for Effective Implementation

Grading systems should be externally validated4,27,28; however, this is challenging to accomplish when using retrospectively captured data that are unlikely to capture all clinical variables included in different scoring systems. Despite the benefit of international registries, registries may capture different data elements, making it challenging to apply different grading systems and link reaction severity with clinically important outcomes. Thus, prospective validation studies in different clinical settings are needed to evaluate the usability and functionality of different scoring systems. An ED study found that only 9% of ED providers used the NIAID/FAAN criteria, reinforcing that unless scoring systems are readily accessible (eg, integrated into electronic medical records) and are viewed as helpful, they will not be used.29 Furthermore, no grading systems that we know of have been developed on the basis of input from patients and caregivers from diverse backgrounds and socioeconomic statuses. Although patients and caregivers may lack the medical knowledge to differentiate between mild and severe symptoms, they are essential to ensuring grading systems are patient centered. We propose that the severity grading system for allergic reactions developed by Dribin et al should be the basis for future studies to validate and refine the grading system, with input from international experts and patient and family advisors.

Conclusion

Allergic reaction grading systems are essential tools to standardize clinical care practices and harmonize research outcomes. Despite the development of numerous grading systems over the past decade, there is no widely adopted or validated grading system, thus limiting their application and generalizability. To resolve the limitations of existing grading systems, future research is needed that includes linking severity to treatment recommendations, conducting validation studies in different clinical settings, and incorporating the perspectives of patients and caregivers from diverse backgrounds and socioeconomic statuses.

Key Messages.

  • A universal allergic reaction scoring system is essential to standardize clinical care and harmonize research outcomes.

  • There is considerable heterogeneity between existing scoring systems, which affects their generalizability.

  • Existing knowledge gaps include the need to link reaction severity with treatment recommendations.

  • Prospective validation and refinement of scoring systems in different clinical settings and patient populations are necessary to promote their implementation and dissemination.

Funding:

The project was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, under Award Number 2UL1TR001425-05A1.

Disclosures:

Dr Wang reports research support paid to institution from the National Institute of Allergy and Infectious Diseases, Aimmune, DBV Technologies, and Siolta; consultancy fees from ALK Abello and Jubilant HollisterStier; and royalty payments from UpToDate. The remaining authors have no conflicts of interest to report.

Footnotes

Disclaimers: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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