Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels
Open accessAbstract
Background Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels.Objective We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels.Methods Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis.Results In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004).Conclusions The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.
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Systemic mastocytosis patients with basal tryptase below 30 ng/mL can develop severe life-threatening anaphylaxis and MCAS at apparently similar frequency to those with higher tryptase.
“SM patients with a low basal tryptase level (below 30 ng/mL) can develop severe life-threatening anaphylaxis and thus MCAS in apparently a similar manner and frequency when compared to patients with SM with higher serum tryptase levels [43–47].”
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 [45]
The Abstract reports severe Hymenoptera sting-induced anaphylaxis in patients with basal tryptase below 11.4 ng/mL, 16 of whom were diagnosed with indolent systemic mastocytosis. That supports the possibility of severe anaphylaxis below 30 ng/mL, but the study does not compare its frequency with that in higher-tryptase SM patients. It reports one monoclonal mast cell activation syndrome diagnosis separately and does not establish the claim that these SM patients consequently developed MCAS. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPatients with systemic mastocytosis and anaphylaxis seem to have a lower baseline serum tryptase in contrast to patients with systemic mastocytosis without anaphylaxis.
“One should be cautious that patients with SM and anaphylaxis seem to have a lower bST in contrast to patients with SM without anaphylaxis [61,62,63,64,65].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [65]
The Abstract reports indolent systemic mastocytosis in 16 patients with Hymenoptera sting-induced anaphylaxis and normal baseline serum tryptase. But the study did not compare them with patients who had systemic mastocytosis without anaphylaxis, so it does not establish the claimed lower tryptase level between those groups. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe risk of MCAS does not appear to rise with higher serum tryptase levels.
“the risk of MCAS does not appear to increase with higher serum tryptase levels [43–46].”
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 [45]
The Results report higher baseline tryptase in patients with clonal mast cell disorders, and the Discussion associates levels of at least 7.95 ng/mL with risk of systemic mastocytosis. These are not findings about MCAS risk: the paper identifies only one patient with monoclonal mast cell activation syndrome and does not assess whether MCAS risk changes as tryptase rises. (LLM, conf=0.75)
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“One should be cautious that patients with SM and anaphylaxis seem to have a lower bST in contrast to patients with SM without anaphylaxis [61–65].”
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- Authors
- Zanotti, R., Lombardo, C., Passalacqua, G., Caimmi, C., Bonifacio, M., De Matteis, G., Perbellini, O., Rossini, M., Schena, D., Busa, M., Marcotulli, M. C., Bilò, M. B., Franchini, M., Marchi, G., Simioni, L., & Bonadonna, P.
- Affiliations
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Ospedale Policlinico San Martino (IT)
- Azienda Ospedaliero-Universitaria delle Marche (IT)
- Corresponding author
- Passalacqua, Giovanni
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 136
- Issue
- 1
- Pages
- 135-139
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2039688853
- Cited by
- 123
- References
- 19
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 16 · 2020: 11 · 2019: 12 · 2018: 12 · 2017: 15 · 2016: 11 · 2015: 8
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- 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 › Rheumatology › Eosinophilic Disorders and Syndromes
- Keywords
- systemic mastocytosis, hymenoptera venom allergy, anaphylaxis, serum tryptase, bone marrow examination, hypotension, angioedema, urticaria, bone mineral density
- MeSH terms
- Adult, Aged, Allergens, Anaphylaxis, Animals, Bone Marrow Cells, Female, Humans, Hymenoptera, Hypersensitivity, Insect Bites and Stings, Male, Mast Cells, Mastocytosis, Middle Aged, Venoms, Tryptases
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