Histamine and tryptase levels in patients with acute allergic reactions: An emergency department–based study
Open accessAbstract
Background Emergency department visits for acute allergic reactions are common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up.Objective We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical correlates of raised beta-tryptase levels were also investigated.Methods Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and beta-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis.Results Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta-tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable beta-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable beta-tryptase levels, patients who had detectable beta-tryptase levels had a significant correlation between total tryptase and histamine levels (P <.05).Conclusions Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma histamine levels suggests basophil involvement. The clinical utility of beta-tryptase determinations in the evaluation of acute allergic reactions needs further study.
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The most specific and reliable indicator of systemic mast cell activation is a transient, event-related, substantial rise in serum tryptase above the patient's own baseline.
“the most specific and reliable marker of systemic MC activation is an acute and substantial event-related (transient) increase in the serum tryptase level over the individual’s baseline value.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [15]
The Abstract says elevated β-tryptase may be more specific for mast-cell activation than total tryptase, and the Discussion explains that β-tryptase is released when mast cells degranulate. But the Methods define elevated total tryptase using a fixed cutoff, not a rise over each patient’s baseline. The Discussion also says the clinical role of β-tryptase needs further study; it does not establish a transient baseline-relative rise as the most reliable marker. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDuring and soon after a severe anaphylactic event, serum tryptase rises substantially above the individual's baseline.
“during and shortly after a severe anaphylactic event where MC release large amounts of tryptase, the serum tryptase level increases substantially over the individual’s baseline (Fig. 1) [12–17].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [15]
The Discussion (page unavailable) says tryptase elevations are believed to begin about one hour after mast-cell stimulation, and reports elevated tryptase in some patients with acute allergic reactions. It also says many patients in this study did not have severe anaphylaxis. The paper does not establish a substantial rise over each individual's baseline during or shortly after a severe event. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTryptase has repeatedly been described as the most specific and reliable biomarker of severe systemic mast cell activation in daily practice.
“tryptase has been repeatedly described as the most specific and reliable biomarker of severe systemic MC activation in daily practice [12–18].”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [15]
The Abstract says elevated β-tryptase may be more specific for mast-cell activation than total tryptase. But the Discussion reports that histamine or total tryptase elevations were more strongly associated with signs such as hypotension and wheezing, and says β-tryptase’s clinical role needs further study. The paper therefore does not establish tryptase as the most reliable biomarker of severe systemic activation in daily practice. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAlthough prior literature and specialized-center experience made tryptase the biomarker of choice for defining anaphylaxis and MCAS, no diagnostic threshold existed.
“although it was clear that tryptase is the biomarker of choice to define anaphylaxis and thus MCAS based on previous literature data and experience in specialized centers [12–18], a diagnostic threshold was missing.”
From Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome (2019) · cites this paper as [15]
The Introduction and Discussion describe tryptase as a potential marker of mast-cell activation, but do not establish it as the biomarker of choice for anaphylaxis or MCAS; the Discussion says its clinical role needs further study. The Methods use a cutoff for elevated total tryptase, but do not establish a diagnostic threshold for either condition. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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References 28 · Cited by 277
Research works printed but not linked: 4
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- Authors
- Lin, R. Y., Schwartz, L. B., Curry, A., Pesola, G. R., Knight, R. J., Lee, H.-S., Bakalchuk, L., Tenenbaum, C., & Westfal, R. E.
- Affiliations
- New York Medical College (US)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 106
- Issue
- 1
- Pages
- 65-71
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2070765073
- Cited by
- 277
- References
- 28
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 9 · 2023: 4 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 9 · 2015: 11 · 2014: 16 · 2013: 13 · 2012: 12
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI20487)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- acute allergic reactions, plasma histamine, serum tryptase, beta-tryptase, anaphylaxis, urticaria, food allergy, emergency department patients, wheezing, erythema, heart rate, food allergy management, food allergy education
- MeSH terms
- Adult, Aged, Anaphylaxis, Blood Pressure, Emergency Medical Services, Food Hypersensitivity, Histamine, Humans, Hypersensitivity, Immediate, Middle Aged, Respiratory Sounds, Serine Endopeptidases, Tachycardia, Urticaria, Tryptases, Chymases
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