Mast cell activation syndrome: Current understanding and research needs - 05/08/24

Doi : 10.1016/j.jaci.2024.05.025

Mariana Castells, MD, PhD ^a,^f,^⁎ , Matthew P. Giannetti, MD ^a,^f, Matthew J. Hamilton, MD ^b,^f, Peter Novak, MD, PhD ^c,^f, Olga Pozdnyakova, MD, PhD ^d,^f, Jennifer Nicoloro-SantaBarbara, PhD ^e,^f, Susan V. Jennings, PhD ^g, Clair Francomano, MD ^h, Brian Kim, MD ⁱ, Sarah C. Glover, DO ^j, Stephen J. Galli, MD ^k, Anne Maitland, MD, PhD ^l,^w, Andrew White, MD ^m, J. Pablo Abonia, MD ⁿ, Valerie Slee, RN, BSN ^g, Peter Valent, MD ^o,^p, Joseph H. Butterfield, MD ^q, Melody Carter, MD ^r, Dean D. Metcalfe, MD ^r, Cem Akin, MD, PhD ^s, Jonathan J. Lyons, MD ^t,^u, Alkis Togias, MD ^r, Lisa Wheatley, MD ^r, Joshua D. Milner, MD ^v
^a Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, Mass
^b Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women’s Hospital, Boston, Mass
^c Department of Neurology, Brigham and Women’s Hospital, Boston, Mass
^d department of Pathology, Brigham and Women’s Hospital, Boston, Mass
^e department of Psychiatry, Brigham and Women’s Hospital, Boston, Mass
^f Harvard Medical School, Boston, Mass
^g The Mast Cell Disease Society Inc, Sterling, Mass
^h Medical and Molecular Genetics, Riley Children’s Health, Indianapolis, Ind
ⁱ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
^j Gastroenterology & Hepatology, Tulane University School of Medicine, New Orleans, La
^k 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
^l Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
^m Division of Allergy and Immunology, Scripps Clinic, San Diego, Calif
ⁿ Departent of Pediatrics, Cincinnati Children’s Hospital, Cincinnati, Ohio
^o Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
^p Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria
^q Division of Allergic Diseases and the Mayo Clinic Program for Mast Cell and Eosinophilic Disorders, Mayo Clinic, Rochester, Minn
^r Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^s Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Mich
^t Division of Allergy and Immunology, Department of Medicine, University of California–San Diego, La Jolla, Calif
^u Veterans Affairs San Diego Healthcare System, La Jolla, Calif
^v Division of Pediatric Allergy, Immunology and Rheumatology, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY
^w Allergy and Immunology Services, Metrodora Institute, Salt Lake City, Utah

^∗Corresponding author: Mariana Castells, MD, PhD, Mastocytosis Center, Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, 60 Fenwood Rd, Hale Building for Transformational Medicine, 5th Fl 5002N, Boston, MA 02132.Mastocytosis CenterDivision of Allergy and Clinical ImmunologyBrigham and Women’s Hospital60 Fenwood RdHale Building for Transformational Medicine5th Fl 5002NBostonMA02132

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.

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Key words : Mast cell activation syndrome, Mast cell, mastocytosis, hereditary alpha-tryptasemia, tryptase, mast cell activation–related disorders

Abbreviations used : BST, EDS, GI, HαT, MC, MCA, MCAD, MCAS, PGD2, PGF2α, POTS, SM