Extrinsic and Intrinsic Modulators of Anaphylaxis
Abstract
The severity of anaphylaxis is determined by many factors. The allergenic source as well as the age of the affected individual and the route of allergen exposure encompass the major contributors of the clinical outcome. Moreover, the severity can be modulated further by intrinsic and extrinsic factors. Among these, the genetic predisposition, certain comorbidities such as uncontrolled asthma, and hormonal fluctuations have been proposed as intrinsic and antihypertensive medications or physical activity as extrinsic factors. Recent advances have highlighted immunologic pathways that may exacerbate the response to allergens through receptors on mast cells, basophils, platelets, and other granulocytes. Atopy, platelet-activating factor acetylhydrolase deficiency, hereditary alpha tryptasemia, and clonal mast cell disorders are examples associated with genetic alterations that may predispose to severe anaphylaxis. Identifying risk factors that lower the threshold of reactivity or increase the severity of multisystem reactions is important in the management of this patient population.
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HαT seems to be a disease-modifying trait in anaphylaxis and PMCD.
“However, it seems to be a disease-modifying trait in anaphylaxis and PMCD [19,20,21].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [21]
There is a consensus that HαT is a risk modifier of severe anaphylaxis.
“There is a consensus that HαT is a risk modifier of severe anaphylaxis [21,48,49,50,51,52,53].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [21]
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Matito, A., & Carter, M. (2015) · Current Allergy and Asthma Reports · doi:10.1007/s11882-015-0525-1 · Cited by 39 · see citing works
Self-citationPromising option in the prevention of idiopathic anaphylaxis: Omalizumab
Demirtürk, M., Gelincik, A. A., Çolakoğlu, B., Murat, D. A. L., & Büyüköztürk, S. (2012) · The Journal of Dermatology · doi:10.1111/j.1346-8138.2012.01520.x · Cited by 39 · see citing works
Evaluation of vaccination safety in children with mastocytosis
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PAF, rather than Histamine, Participates in Mouse Anaphylactic Hypotension
Shibamoto, T., Liu, W., Cui, S., Zhang, W., Takano, H., & Kurata, Y. (2008) · Pharmacology · doi:10.1159/000141516 · Cited by 35 · see citing works
Update in Pediatric Anaphylaxis
Chipps, B. E. (2013) · Clinical Pediatrics · doi:10.1177/0009922812474683 · Cited by 33 · see citing works
Clinical response to omalizumab in patients with hereditary α-tryptasemia
Alvarez, L. B. M., Barker, R., Nelson, C. G., DiMaggio, T., Stone, K. D., Milner, J. D., Rosenthal, J. A., Petroni, D., Glover, S. C., & Lyons, J. J. (2019) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2019.09.026 · Cited by 29 · see citing works
Tacquard, C. A., Oulehri, W., Collange, O., Garvey, L. H., Nicoll, S., Tuzin, N., Gény, B., & Mertès, P. (2019) · Clinical & Experimental Allergy · doi:10.1111/cea.13540 · Cited by 27 · see citing works
Wang, M., Shibamoto, T., Tanida, M., Kuda, Y., & Kurata, Y. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.09.010 · Cited by 25 · see citing works
Liu, L., Fahy, K. E., Awoyemi, A. A., Thapa, P., Kelly, L. E., Chen, J., Bihl, J. C., Cool, D. R., Chen, Y., Rapp, C. M., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901393 · Cited by 25 · see citing works
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Twelve-year follow-up of omalizumab therapy for anaphylaxis in 2 patients with systemic mastocytosis
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Self-citationInfant anaphylaxis: the importance of early recognition
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Risk factors in Hymenoptera venom allergy
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Flagged first, then by citations
Cited by
Sorted by citations
Pouessel, G., Tacquard, C. A., Tanno, L. K., Mertès, P., & Lezmi, G. (2024) · Clinical & Experimental Allergy · doi:10.1111/cea.14434 · Cited by 25 · see citing works
Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
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“However, it seems to be a disease-modifying trait in anaphylaxis and PMCD [19–21].”
BackgroundAbrams, E. M., Alqurashi, W., Fischer, D. A. V., Leek, T. K. V., & Ellis, A. K. (2024) · Allergy Asthma and Clinical Immunology · doi:10.1186/s13223-024-00926-3 · Cited by 10 · see citing works
Pouessel, G., Egea, C., Divaret‐Chauveau, A., Beaumont, P., Bradatan, E., Dumond, P., Diesnis, R., Tscheiller, S., van der Brempt, X., Braun, C., et al. (2025) · Clinical & Experimental Allergy · doi:10.1111/cea.70089 · Cited by 5 · see citing works
Pediatric idiopathic anaphylaxis: practical management from infants to adolescents
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Tryptase in drug-induced anaphylaxis: the need for acute and baseline values
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Novelties in the pragmatic management of anaphylaxis in pediatric age
Marseglia, G. L., Tosca, M. A., del Giudice, M. M., Manti, S., Ciprandi, G., & Licari, A. (2026) · European Journal of Pediatrics · doi:10.1007/s00431-026-07147-3 · Cited by 1 · see citing works
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Evaluation of Mast Cell Disease in Women: A Case Study of Delayed Diagnosis of Systemic Mastocytosis
Hatcher, V. R., Alix, V. C., Hellu, T. S., Schuldt, M. M., & Adams, K. E. (2025) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2025.01.019 · Cited by 1 · see citing works
Self‐reported accidental allergic reactions among patients with challenge‐verified food allergy
Svendsen, S. V., Senders, A. S., Oropeza, A. R., Lassen, A. T., Bindslev‐Jensen, C., & Mortz, C. G. (2025) · Clinical and Translational Allergy · doi:10.1002/clt2.70067 · Cited by 1 · see citing works
Golden, D. B. K., & Carter, M. C. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.05.020
Self-citationWiederholte Anaphylaxie nach pflanzlichen Nahrungsmitteln bei regelmäßigem Alkoholkonsum
Bergmann, A., Wolters, P., Balakirski, G., & Hofmann, S. C. (2024) · Aktuelle Dermatologie · doi:10.1055/a-2194-1525
Managing anaphylaxis in patients on β-blockers
Miyashiro, D., Abud, E. M., Cook, K. A., & White, A. A. (2025) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2025.06.031
Zhou, Z., Zhang, J., Dai, N., & Li, Z. (2025) · Frontiers in Allergy · doi:10.3389/falgy.2025.1658895
Reply to “Fatal reactions to alpha-gal might be due to comorbid mast cell diseases”
Platts‐Mills, T. A. E., Workman, L., Richards, N. E., Wilson, J. M., & McFeely, E. M. (2026) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2026.01.019
Cofactors in Anaphylaxis: Insights From the European Anaphylaxis Registry
Worm, M., Dölle-Bierke, S., Pouessel, G., Ruëff, F., Hartmann, K., Pföhler, C., Bilò, M. B., Wagner, N., Papadopoulos, N. G., Lange, L., et al. (2026) · Clinical & Experimental Allergy · doi:10.1111/cea.70457
Self-citation
- Authors
- Carter, M. C., Park, J., Vadas, P., & Worm, M.
- Affiliations
- National Institutes of Health (US)
- St. Michael's Hospital (CA)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Carter, Melody C.
- Venue
- The Journal of Allergy and Clinical Immunology In Practice
- Publisher
- Elsevier BV
- Published
- 2023-07
- Volume
- 11
- Issue
- 7
- Pages
- 1998-2006
- ISSN
- 2213-2198 (ISSN-L)
- OpenAlex
- W4377696084
- Cited by
- 17
- References
- 107
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 3
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Allergy and Clinical Immunology In Practice (publishedVersion)
- PubMed (publishedVersion)
- 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
- anaphylaxis, anaphylaxis severity, risk factors, genetic susceptibility, asthma, hormonal fluctuations, antihypertensive drugs, physical activity, mast cells, basophils, platelets, granulocytes, atopy, hereditary alpha-tryptasemia, clonal mast cell disorders
- MeSH terms
- Allergens, Anaphylaxis, Basophils, Humans, Mast Cells, Mastocytosis, Risk Factors, Tryptases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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