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Cited by 146Mast cells and histamineFood Allergy and Anaphylaxis ResearchAsthma and respiratory diseases

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

Open access
Valent, Peter, Bonadonna, Patrizia, Hartmann, Karin, Broesby-Olsen, Sigurd, Brockow, Knut, Butterfield, Joseph H., Triggiani, Massimo, Lyons, Jonathan J. +4 more·2019·International Archives of Allergy and Immunology
DOI 10.1159/000501079PMC PMC7115850
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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.

Integrity signals

Registry

Crossref · 10.1159/000501079

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

47 of 106 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Tryptases make up more than 20% of the total protein in tissue mast cells.

    “tryptases account for >20% of the total protein content in tissue MC [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] source

      The Abstract (page unavailable) describes human β-tryptase as abundant in mast cells. It does not state that tryptases exceed 20% of total protein in tissue mast cells, so the numerical claim is unsupported by our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    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.”
    Quote in the paperSubstantial claim4 of 7 sources checked
    • cites [12] source

      The Introduction reports that serum or plasma tryptase rises during insect-sting anaphylaxis and correlates with reaction severity; the Results also note preliminary evidence of increases during mast-cell-mediator attacks. But the paper does not establish that a transient rise over an individual’s own baseline is the most specific and reliable marker of systemic mast-cell activation. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [13] source
    • cites [14] source
    • cites [15] source

      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 measured
    • cites [16] source

      The Introduction says tryptase selectively indicates mast-cell activation, and the Results show an event-related rise followed by a decline after venom challenge. But the paper does not establish that a substantial rise in serum tryptase over an individual’s own baseline is the most specific and reliable marker; its before-and-after challenge measurements used plasma, and its Methods describe fixed ranges for elevated levels. No page numbers are available in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] source

      In the proposed diagnostic criteria section (page unavailable), the paper says tryptase rises transiently during mast cell activation and recommends comparing levels measured during symptoms with the patient’s baseline. It does not establish that a substantial rise in tryptase is the most specific and reliable indicator compared with other mast-cell mediators, which it also recommends measuring. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [18] source
  • Premisecitation

    Serum tryptase baseline concentrations differ according to the underlying disease and the person's genetic makeup.

    “the baseline level of tryptase varies depending on the underlying disease and the genetic background.”
    Quote in the paperSubstantial claim3 of 9 sources checked
    • cites [25] source
    • cites [26] source
    • cites [27] source

      In “Cellular origin, historical overview and development of the test” (page unavailable), the paper reports that basal tryptase is usually elevated in systemic mastocytosis but normal in most cases of cutaneous mastocytosis, supporting variation by underlying disease. The searched passages do not establish that a person’s genetic background independently determines baseline tryptase; the mention of elevated levels in familial mast-cell activation syndromes does not make that broader point. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [28] source

      In “To the Editor” (page not provided), the authors report elevated basal tryptase segregating in nine families with an autosomal dominant inheritance pattern, supporting the genetic-background part of the claim. They associate elevated tryptase with clinical features but do not establish that baseline concentrations vary according to the underlying disease; they say whether the elevation is primary or secondary remains under investigation. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [29] source
    • cites [30] source

      The Introduction (page unavailable) links increased TPSAB1 copy number to elevated basal serum tryptase and describes a gene-dose effect in hereditary α-tryptasemia. This supports variation with genetic makeup, but the paper does not establish that baseline levels vary across underlying diseases generally. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [31] source
    • cites [32] source
    • cites [33] source
  • Premisecitation

    More than 30% of patients with myeloid neoplasms, including mastocytosis, have raised basal tryptase.

    “over 30% of all patients with myeloid neoplasms, including mastocytosis, have elevated basal tryptase levels.”
    Quote in the paperSubstantial claim3 of 7 sources checked
    • cites [25] source
    • cites [26] source
    • cites [27] source

      The section “Elevated basal serum tryptase levels are frequently detected in patient with myeloid neoplasms” (page not provided) reports elevated levels in more than 90% of patients with systemic mastocytosis, about 30–40% with AML, and about 30–35% with CML. It says the incidence is lower in MPN and MDS and gives no rate for all myeloid neoplasms combined, so it does not establish the claimed overall figure of over 30%. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [28] source

      The 'To the Editor' section reports elevated basal tryptase in families with inherited tryptasemia and says that the patients assessed did not meet criteria for systemic mastocytosis. Searches for myeloid neoplasms and a prevalence above 30% found no passage in our copy addressing that claim; no page number is provided for the section. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [29] source
    • cites [30] source

      The Introduction links increased TPSAB1 copy number to elevated basal serum tryptase, and the Subjects section mentions mastocytosis study protocols. Neither passage reports the proportion of patients with myeloid neoplasms who have elevated basal tryptase. Searches for myeloid neoplasms, mastocytosis, and the claimed 30% prevalence found no supporting passage in our copy; page numbers were not provided. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [31] source
  • Premisecitation

    The 20% + 2 formula was put forward by a consensus group in 2012.

    “the 20% + 2 formula was proposed by the consensus group in 2012.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
  • Classified as probably not a substantial claim. 7
  • May combine two claims. 13

  • Classified as probably not a substantial claim.

    Premisecitation

    MCAS is diagnosed when there is documented recurrent episodic occurrence of typical systemic symptoms produced by mast cell mediators and involving at least two organ systems.

    “documented recurrent episodic occurrence of typical systemic symptoms that are produced by MC mediators and involve at least 2 organ systems”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [19] source

      The Clinical Symptoms section (p. 3) says recurrent symptoms involving two or more organ systems increase the likelihood of systemic mast cell activation. It also says symptoms alone are not diagnostic; the Definition and Proposed MCA Criteria section (p. 3) requires evidence of increased mast-cell mediators and generally a response to mediator-targeting treatment. The claim therefore describes a clinical criterion but overstates it as sufficient for an MCAS diagnosis. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [21] source

      The paper’s diagnostic-criteria passage identifies episodic mast-cell-related symptoms affecting two or more organ systems as the first criterion. It also requires a specified rise in serum tryptase and improvement with mast-cell-targeting treatment, so the symptoms alone do not establish an MCAS diagnosis. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [22] source

      The “Symptoms Produced by Systemic MCA” section describes severe, recurrent symptoms affecting more than one organ or tissue, supporting the symptom pattern in the claim. But “Consensus Criteria and Classification of MCAS” says diagnosis also requires biochemical evidence of mast-cell involvement and a response to mediator-targeting treatment; the symptoms alone do not establish MCAS. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    After deliberations and shared practical experience, the faculty produced a consensus proposal and introduced the 20% + 2 formula at the Working Conference.

    “After in-depth deliberations and based on shared practical experience, the faculty did come up with a consensus proposal and put forth the 20% + 2 formula during the Working Conference [21].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] source

      The paper’s main text says an international consensus group met and introduced MCAS diagnostic criteria, including a serum tryptase increase of 20% over baseline plus 2 ng/mL. It does not say the formula was put forth at a Working Conference or describe the group’s deliberations and shared practical experience. No page numbers are provided in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    These conditions include tryptase gene replications such as hereditary alpha tryptasemia, chronic infections such as helminth infections, renal insufficiency especially in hemodialysis patients, and myeloid neoplasms including myelodysplastic syndromes, systemic mastocytosis, acute myeloid leukemia, chronic myeloid leukemia, and chronic eosinophilic leukemia.

    “These include tryptase gene replications such as hereditary alpha tryptasemia; chronic infections, such as helminth infections; renal insufficiency – especially hemodialysis patients; and myeloid neoplasms, including myelodysplastic syndromes, SM, acute myeloid leukemia, chronic myeloid leukemia (CML), and chronic eosinophilic leukemia [25–33].”
    Quote in the paperNot a substantial claim3 of 9 sources checked
    • cites [25] source
    • cites [26] source
    • cites [27] source

      The sections on healthy individuals and myeloid neoplasms report elevated tryptase with chronic active helminth infection, renal failure, and each listed neoplasm. The References section names a study of raised baseline tryptase in hemodialysis patients. Our copy does not identify tryptase gene replication or hereditary alpha tryptasemia as a cause. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [28] source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [29] source
    • cites [30] source
    • cites [31] source
    • cites [32] source
    • cites [33] source

  • May combine two claims.

    Premisecitation

    Although 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.”
    Quote in the paperSubstantial claim4 of 7 sources checked
    • cites [12] source

      The Introduction (page unavailable) describes tryptase measurements during insect-sting anaphylaxis that correlate with reaction severity, supporting its use as an anaphylaxis marker. The paper does not establish it as the biomarker of choice for defining anaphylaxis or MCAS, or address whether a diagnostic threshold for those conditions was missing. Its threshold discussion concerns baseline tryptase in mastocytosis, not diagnosis of anaphylaxis or MCAS. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [13] source
    • cites [14] source
    • cites [15] source

      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
    • cites [16] source

      The Introduction and Discussion describe circulating tryptase as a useful, relatively selective indicator of mast-cell activation and report its clinical use in suspected anaphylaxis. The paper does not discuss MCAS or establish tryptase as its biomarker of choice. Its Methods give ranges for normal and elevated tryptase, so it does not support an unqualified claim that no threshold existed, although it does not set out a diagnostic threshold for MCAS. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] source

      In “Proposed Criteria for the diagnosis of idiopathic mast cell activation syndrome” (page unavailable), the paper identifies serum tryptase as a test for mast-cell activation, calls for comparison with baseline, and says objective diagnostic guidelines lacked consensus. It does not call tryptase the biomarker of choice over other mediators, and it gives a conditional >15 ng/ml criterion rather than saying no diagnostic threshold of any kind existed. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [18] source

  • Classified as probably not a substantial claim.

    Premisecitation

    At the 2010 Working Conference, one issue discussed was the smallest rise in serum tryptase above baseline that would count as significant systemic mast cell activation and as a diagnostic marker of MCAS.

    “one of the deliberation points was the minimal increase in serum tryptase over the individual’s baseline that would meet the criterion of a significant systemic MC activation and would thus count as a diagnostic marker of MCAS [21].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] source

      The main text (page unavailable) says a consensus group met to establish MCAS diagnostic criteria and identifies a serum tryptase rise of 20% above baseline plus 2 ng/mL as one criterion. It does not identify a 2010 Working Conference or say that determining the minimum rise was a specific deliberation point. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Using the 11.4 ng/mL threshold, raised basal tryptase is frequent in otherwise healthy people (about 5-10% of the general population), in various reactive states, and in hematologic disorders, especially myeloid malignancies (about 20-30%).

    “when taking the 11.4 threshold as denominator, an increased basal tryptase level is found frequently in otherwise healthy individuals (roughly 5–10% of the general population), in diverse reactive states, and in hematologic disorders, especially in myeloid malignancies (roughly 20–30%; Table 2) [25–31].”
    Quote in the paperSubstantial claim3 of 7 sources checked
    • cites [25] source
    • cites [26] source
    • cites [27] source

      In “Total serum tryptase levels in healthy individuals” (page unavailable), the paper recognizes 11.4 ng/mL as a cutoff used by many centers and says many healthy people have levels between 10 and 15 ng/mL, but it does not give a 5–10% prevalence above 11.4 ng/mL. In “Elevated basal serum tryptase levels are frequently detected in patient with myeloid neoplasms” (page unavailable), it reports elevations in several myeloid disorders, but gives disease-specific figures measured against >15 ng/mL rather than an overall 20–30% figure at 11.4 ng/mL. It mentions some nonmalignant causes of increases, while saying infections and other inflammatory processes generally leave levels stable. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [28] source

      The To the Editor section reports elevated basal tryptase in nine families referred for allergic disease or suspected mastocytosis; it does not establish how frequently elevated levels occur in otherwise healthy people. Searches for the 11.4 ng/mL threshold, the 5–10% and 20–30% estimates, reactive states, and myeloid malignancies found no passage supporting those claims in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [29] source
    • cites [30] source

      The Introduction links increased TPSAB1 copy number to elevated basal serum tryptase, and the ClinSeq methods describe measuring tryptase in healthy adults. Neither those passages nor searches for the 11.4 ng/mL threshold, population prevalence, reactive states, or myeloid malignancies establish the frequencies claimed; the paper’s reported screening threshold is >8 ng/mL. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [31] source

  • Classified as probably not a substantial claim.

    Premisecitation

    MCAS is diagnosed when there is a documented clinically meaningful response to drugs that target mast cell mediators and/or suppress mast cell activation.

    “a documented clinically meaningful response to drugs that either target MC-derived mediators (e.g., H1 antihistamines or antileukotrienes) and/or suppress MC activation (e.g., cromoglycate, ketotifen, or omalizumab) [19, 21, 22].”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [19] source

      The Definition and Proposed MCA Criteria (p. 3) includes an objective major response to drugs affecting mast-cell mediators as one diagnostic criterion, and Response to Therapy (p. 4) names histamine receptor blockers, leukotriene receptor blockers and cromolyn. The paper requires clinical symptoms and a mediator increase as well; it does not establish a drug response alone as sufficient for diagnosis or name ketotifen or omalizumab among the examples. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [21] source
    • cites [22] source

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    The 20% + 2 formula was later further validated in independent case series.

    “Later, the 20% + 2 formula was further validated in independent case series – see below.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The 20% + 2 formula was validated against the available literature and all published retrospective cases and found applicable and robust in both allergy and mastocytosis.

    “The 20% + 2 formula was subsequently validated against the available literature and all retrospective cases published, and the formula was found to be applicable and robust both in the context of allergy and in the context of mastocytosis (K.B., L.B., and P.V., unpublished observation)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Mature tryptases are stored mainly in heparin-containing metachromatic granules of human mast cells, whereas pro-tryptases are released spontaneously and continuously from resting mast cells.

    “Whereas mature tryptases are mostly stored in the heparin-containing metachromatic granules of human MC, the precursor forms (pro-tryptases) are released spontaneously and constantly from resting MC [10, 11].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] source
    • cites [11] source

  • May combine two claims.

    Interpretationcitation

    Independent groups have validated the 20% + 2 approach in clinical practice and judged it sound.

    “Since then, this approach has been validated in clinical practice by independent groups and found to be sound.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] source

  • May combine two claims.

    Interpretationreasoning

    Because tryptases are released at a steady rate and are chemically and biologically stable, the basal serum tryptase level is very consistent in healthy people.

    “Based on a constant release rate in the steady state and the chemical and biological stability of tryptases, the resulting basal serum tryptase level is remarkably consistent in healthy individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    In other cases, continuous basal release or extra alpha-tryptase gene copies can cause persistently elevated basal tryptase, which also does not indicate systemic mast cell activation or MCAS.

    “In other cases, a constantly increased basal release or an extra amount of alpha tryptase gene copies can lead to a persistently elevated basal tryptase – again, however, such persistently elevated tryptase is not an indication of systemic MC activation or MCAS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    After the event, tryptase returns to baseline over several hours (up to 24 h), giving a reliable diagnostic window of about 2-4 h.

    “Thereafter, the tryptase level returns to baseline, which may take several hours (up to 24 h), providing a reliable diagnostic window of about 2–4 h for laboratory investigations [18].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] source

  • May combine two claims.

    Interpretationreasoning

    Using only an absolute extra amount of tryptase as the criterion would fail in people with very low basal tryptase and in systemic mastocytosis patients with tryptase above 100 or 200 ng/mL.

    “Employing only an absolute amount of extra tryptase as criterion (e.g., plus extra 20 ng/mL) would fail in those who have very low basal tryptase levels (1–5 ng/mL) and in those with systemic mastocytosis (SM) with a tryptase level exceeding 100 or 200 ng/mL.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These alternative markers may serve as criteria for less severe mast cell activation or as indicators of therapeutic targets (PGD2), but not as a robust criterion for MCAS.

    “Therefore, these markers may qualify as criteria for less severe forms of MC activation or as indicators of targets of therapeutic intervention (PGD2), but not as a robust criterion for MCAS.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    The 20% + 2 consensus equation is a sound tool for measuring a clinically relevant tryptase rise independent of baseline, including in people with normal/low tryptase (<10 ng/mL), slightly elevated tryptase (<50 ng/mL), and clearly or massively elevated tryptase.

    “The 20% + 2 consensus equation is a sound tool to measure a clinically relevant increase in tryptase independent of the baseline level, including individuals with normal/low tryptase (<10 ng/mL), those with slightly elevated tryptase (<50 ng/mL) and those with clearly or even massively elevated tryptase.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Diamino-oxidase has been described as a marker that increases in MCAS patients and has specificity and time course similar to serum tryptase.

    “More recently, diamino-oxidase, a histamine-degrading enzyme, has been described as a marker that increases in MCAS patients and has a similar specificity and time course compared to serum tryptase levels [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] source
18 of 18

  • The paper relies on this without support.

    Many users are unfamiliar with the 20% + 2 formula and ask questions about it and why it was proposed in the MCAS context.

    “many users are not familiar with this approach and ask questions related to this formula and why it has been proposed in the MCAS context.”

  • The paper relies on this without support.

    There is ongoing discussion about the use and usefulness of the MCAS criteria in daily practice.

    “there remains an ongoing discussion on their use and usefulness in daily practice.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tryptase is a useful and specific marker to demonstrate mast cell activation and degranulation when an acute value (within 4 h after the event) and a baseline value (at least 24 h after the event) are compared and meet the consensus formula (increase of 20% + 2).

    “Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2).”

    From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]

    The Introduction (page unavailable) describes tryptase as a specific marker of severe systemic mast-cell activation, gives a 2–4-hour diagnostic window, and specifies an event-related rise of at least 20% over baseline plus 2 ng/mL. It says tryptase may take up to 24 hours to return to baseline, but does not explicitly prescribe collecting the baseline sample at least 24 hours after the event. The Summary and Future Perspectives also cautions that the formula usually does not capture mild or local activation, a limitation absent from the claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The approach of using sAT greater than sBT -1.2 + 2 ng/mL has been validated and is broadly accepted.

    “This approach has been validated and is broadly accepted.”

    From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [44]

    The Validation of the 20% + 2 Formula in Clinical Practice section says the formula has been validated, and the Introduction says the MCAS criteria are generally accepted. But the paper specifies a threshold of 20% over baseline plus 2 ng/mL—equivalent to 1.2 × sBT + 2—not the stated sBT − 1.2 + 2 ng/mL. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • According to the consensus formula, an acute serum tryptase (aST) ≥ [(1.2 × baseline serum tryptase (bST)) + 2] depicts mast cell activation (MCA).

    “According to the consensus formula, an aST ≥ [(1.2 × bST) + 2], depicts MCA [10,11].”

    From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]

  • An increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome.

    “A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome.”

    From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]

  • Overall, the most used and validated approach is the consensus formula.

    “Overall, the most used and validated approach is the consensus formula.”

    From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [10]

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Authors
Valent, P., Bonadonna, P., Hartmann, K., Broesby-Olsen, S., Brockow, K., Butterfield, J. H., Triggiani, M., Lyons, J. J., Oude Elberink, J. N. G., Arock, M., Metcalfe, D. D., & Akin, C.
Affiliations
  • Ludwig Boltzmann Institute for Hematology and Oncology (AT)
  • Azienda Ospedaliera Universitaria Integrata Verona (IT)
  • University of Basel (CH)
  • Technical University of Munich (DE)
  • Mayo Clinic (US)
  • University of Salerno (IT)
  • National Institutes of Health (US)
  • Pitié-Salpêtrière Hospital (FR)
  • University of Michigan (US)
ORCID
Venue
International Archives of Allergy and Immunology
Publisher
S. Karger AG
Published
2019
Volume
180
Issue
1
Pages
44-51
ISSN
  • 1018-2438 (ISSN-L)
  • 1423-0097
DOI
10.1159/000501079
PMC
PMC7115850
OpenAlex
W2953893361
Cited by
146
References
58
Citations by year
2026: 21 · 2025: 12 · 2024: 20 · 2023: 17 · 2022: 29 · 2021: 23 · 2020: 18 · 2019: 3 · 2018: 1 · 2014: 1
FWCI
1.58
Type
journal article
Language
en
Open access
Licence
Locations
  • International Archives of Allergy and Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
  • edoc (University of Basel) (submittedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
  • Pfizer
  • Universität Basel
  • Austrian Science Fund (#F4704-B20, F4701, F4701-B20)
  • National Institute of Allergy and Infectious Diseases
  • NHLBI Division of Intramural Research
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
mast cell activation syndrome, tryptase, serum tryptase, mast cell activation, anaphylaxis, mastocytosis, diagnostic criteria
MeSH terms
Anaphylaxis, Humans, Mast Cells, Mastocytosis, Reference Values, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Tryptases

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Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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