Mast cell activation syndrome: Current understanding and research needs

Mariana Castells¹, Matthew P Giannetti², Matthew J Hamilton³, Peter Novak⁴, Olga Pozdnyakova⁵, Jennifer Nicoloro-SantaBarbara⁶, Susan V Jennings⁷, Clair Francomano⁸, Brian Kim⁹, Sarah C Glover¹⁰, Stephen J Galli¹¹, Anne Maitland¹², Andrew White¹³, J Pablo Abonia¹⁴, Valerie Slee⁷, Peter Valent¹⁵, Joseph H Butterfield¹⁶, Melody Carter¹⁷, Dean D Metcalfe¹⁷, Cem Akin¹⁸, Jonathan J Lyons¹⁹, Alkis Togias¹⁷, Lisa Wheatley¹⁷, Joshua D Milner²⁰

Affiliations

¹ Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: mcastells@bwh.harvard.edu.
² Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
³ Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁴ Department of Neurology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁵ department of Pathology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁶ department of Psychiatry, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁷ The Mast Cell Disease Society Inc, Sterling, Mass.
⁸ Medical and Molecular Genetics, Riley Children's Health, Indianapolis, Ind.
⁹ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁰ Gastroenterology & Hepatology, Tulane University School of Medicine, New Orleans, La.
¹¹ Departments of Pathology and Immunology and Microbiology, and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
¹² Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Allergy and Immunology Services, Metrodora Institute, Salt Lake City, Utah.
¹³ Division of Allergy and Immunology, Scripps Clinic, San Diego, Calif.
¹⁴ Departent of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
¹⁵ Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
¹⁶ Division of Allergic Diseases and the Mayo Clinic Program for Mast Cell and Eosinophilic Disorders, Mayo Clinic, Rochester, Minn.
¹⁷ Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁸ Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Mich.
¹⁹ Division of Allergy and Immunology, Department of Medicine, University of California-San Diego, La Jolla, Calif; Veterans Affairs San Diego Healthcare System, La Jolla, Calif.
²⁰ Division of Pediatric Allergy, Immunology and Rheumatology, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY.

PMID: 38851398
PMCID: PMC11881543
DOI: 10.1016/j.jaci.2024.05.025

Review

Mast cell activation syndrome: Current understanding and research needs

Mariana Castells et al. J Allergy Clin Immunol. 2024 Aug.

. 2024 Aug;154(2):255-263.

doi: 10.1016/j.jaci.2024.05.025. Epub 2024 Jun 6.

Authors

Affiliations

¹ Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: mcastells@bwh.harvard.edu.
² Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
³ Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁴ Department of Neurology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁵ department of Pathology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁶ department of Psychiatry, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
⁷ The Mast Cell Disease Society Inc, Sterling, Mass.
⁸ Medical and Molecular Genetics, Riley Children's Health, Indianapolis, Ind.
⁹ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
¹⁰ Gastroenterology & Hepatology, Tulane University School of Medicine, New Orleans, La.
¹¹ Departments of Pathology and Immunology and Microbiology, and the Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
¹² Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Allergy and Immunology Services, Metrodora Institute, Salt Lake City, Utah.
¹³ Division of Allergy and Immunology, Scripps Clinic, San Diego, Calif.
¹⁴ Departent of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
¹⁵ Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
¹⁶ Division of Allergic Diseases and the Mayo Clinic Program for Mast Cell and Eosinophilic Disorders, Mayo Clinic, Rochester, Minn.
¹⁷ Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁸ Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Mich.
¹⁹ Division of Allergy and Immunology, Department of Medicine, University of California-San Diego, La Jolla, Calif; Veterans Affairs San Diego Healthcare System, La Jolla, Calif.
²⁰ Division of Pediatric Allergy, Immunology and Rheumatology, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY.

PMID: 38851398
PMCID: PMC11881543
DOI: 10.1016/j.jaci.2024.05.025

Abstract

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients remain to be elucidated. Here we summarize the known literature, identify gaps in knowledge, and highlight research needs. Covered topics include contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; mechanistic research; management of typical and refractory symptoms; and MCAS-specific education for patients and health care providers.

Keywords: Mast cell; Mast cell activation syndrome; hereditary alpha-tryptasemia; mast cell activation–related disorders; mastocytosis; tryptase.

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Conflict of interest statement

Disclosure statement M.C.C. and D.D.M. were supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not represent the official views of the NIH. Disclosure of potential conflict of interest: M. Castells has received research funding and consulting fees from Blueprint Medicines and consulting fees from Cogent Biosciences. M. P. Giannetti has received research funding and consulting fees from Blueprint Medicines and consulting fees from Cogent Biosciences. M. J. Hamilton has received consulting fees from Blueprint Medicines. P. Novak has received funding from Mona Taliaferro/Bay Shore Recycling, the National Heart, Lung, and Blood Institute (NHLNI; 1OT2HL156812-01), and FBRI (2022A018462); is current or previous shareholder of Moderna, Edidas Medicine, Novavax, and Pfizer; and has received royalties from Oxford University Press. J. Nicoloro-SantaBarbara has received consulting fees from Cogent Biosciences and Blueprint Medicines. S. C. Glover received consulting fees from Blueprint Medicine, Janssen, BMS, AbbVie, and Takeda. S. J. Galli has received research funding from and is scientific advisor to Evommune; and is on the scientific advisory board of Jasper Therapeutics. A. White is on the speakers bureau at Blueprint Medicines; and received consulting fees from Cogent Biosciences and Blueprint Medicines. P. Valent received funding from BMS/Celgene and AOP Orphan; and consultancy fees from Novartis, BMS/Celgene, Blueprint, Pfizer, Cogent, and Stemline. J. H. Butterfield has received a fee for the licensing of HMC-1 cell lines. D. D. Metcalfe has received consulting fees from Visterra. J. D. Milner has received consulting fees from Blueprint Medicines. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

**FIG 1.**
MC mediators induce symptoms across organ systems.

**FIG 2.**
Differential MCA and mediator release.

**FIG 3.**
Diagnostic algorithm for evaluation of MCA symptoms.

See this image and copyright information in PMC

References

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1. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 2012;157:215–25. - PMC - PubMed
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Mast cell activation syndrome: Current understanding and research needs

Affiliations

Mast cell activation syndrome: Current understanding and research needs

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

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Full Text Sources