Evidence map›Paper›PMID 31256161›Full record

ReviewInternational archives of allergy and immunology2019

Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome.

Peter Valent, Patrizia Bonadonna, Karin Hartmann, Sigurd Broesby-Olsen, Knut Brockow, Joseph H Butterfield, Massimo Triggiani, Jonathan J Lyons, Joanna N G Oude Elberink, Michel Arock and 2 more

Open access · bronzeAbstract readReview
In one paragraph

Review in International archives of allergy and immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 132 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Hereditary Alpha-Tryptasemia (HαT) as a Risk Modifier for Severe Anaphylaxis.Immunology and allergy clinics of North America · 2026
    Review
  6. Markedly Increased Diamine Oxidase During Acute Anaphylaxis Is Associated With an Underlying Clonal Mast Cell Disorder.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026
    Article
  7. Characteristics and outcomes of patients with pediatric-onset non-mastocytosis mast cell activation disorders: A CEREMAST study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026
    Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Diagnosis and management of mast cell activation syndrome (MCAS) in Canada: a practical approach.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2025
    Review
  13. Role of Mast Cells and Their Mediators in Chronic Kidney Diseases.International journal of molecular sciences · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 11 institutions in 8 countries.

Peter ValentDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria, peter.valent@meduniwien.ac.at.
Patrizia BonadonnaAllergy Unit, Verona University Hospital, Verona, Italy.
Karin HartmannDivision of Allergy, Department of Dermatology, University of Basel, Basel, Switzerland.
Sigurd Broesby-OlsenDepartment of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
Knut BrockowDepartment of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany.
Joseph H ButterfieldDivision of Allergic Diseases, Mayo Clinic, Rochester, Minnesota, USA.
Massimo TriggianiDivision of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
Jonathan J LyonsLaboratory of Allergic Diseases, NIAID, NIH, Bethesda, Maryland, USA.
Joanna N G Oude ElberinkDepartment of Allergology, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands.
Michel ArockDepartment of Hematological Biology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University (UPMC), Paris, France.
Dean D MetcalfeLaboratory of Allergic Diseases, NIAID, NIH, Bethesda, Maryland, USA.
Cem AkinDivision of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Michigan, USA.
National Institutes of Health · USMayo Clinic · USMedical University of Vienna · ATOdense University Hospital · DKSorbonne Université · FRTechnical University of Munich · DEUniversity Medical Center Groningen · NLUniversity of Basel · CHUniversity of Michigan · USUniversity of Salerno · ITUniversity of Verona · IT

Funding

The Pathogenesis, Diagnosis, And Treatment Of Systemic Mast Cell DisordersZIAAI000249 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KOMAROW, HIRSH D · 2009 to 2025
$16.5M
Translational studies in allergic reactions and inflammationZIAAI001192 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LYONS, JONATHAN · 2014 to 2023
$12.7M
Austrian Science Fund FWF F 4701Austrian Science Fund FWF F 4704
6 · The paper itself

Abstract

Mast cell activation syndrome (MCAS) is a condition characterized by recurrent episodes of clinically relevant, systemic, severe reactions to mast cell (MC)-derived mediators released in the context of anaphylaxis or another acute MC-related event. It is important to document MC involvement in these reactions in order to establish the diagnosis MCAS. 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. However, the baseline level of tryptase varies depending on the underlying disease and the genetic background. For example, an estimated 3-5% of healthy individuals exhibit duplications or multiple copies of the TPSAB1 gene encoding for alpha-tryptase, and over 30% of all patients with myeloid neoplasms, including mastocytosis, have elevated basal tryptase levels. Therefore, it is of utmost importance to adjust the event-related diagnostic (MCAS-confirming) increase in tryptase over the individual baseline in a robust approach. To address this challenge, the 20% + 2 formula was proposed by the consensus group in 2012. Since then, this approach has been validated in clinical practice by independent groups and found to be sound. In the current article, we discuss the emerging importance and value of the 20% + 2 formula in clinical practice and its role as a criterion of severe systemic MC activation and MCAS.

Indexed as

BiomarkersAnaphylaxisHumansMast CellsMastocytosisReference ValuesReproducibility of ResultsSensitivity and SpecificityTryptasesBiomarkersTryptasesAllergyAnaphylaxisIgEMast cell activationMast cellsTryptase

Identifiers

PMID31256161
PMCPMC7115850
OpenAlexW2953893361

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.