Personalized Management Strategies in Mast Cell Disorders: ECNM-AIM User’s Guide for Daily Clinical Practice
2022; Elsevier BV; Volume: 10; Issue: 8 Linguagem: Inglês
10.1016/j.jaip.2022.03.007
ISSN2213-2201
AutoresPeter Valent, Karin Hartmann, Juliana Schwaab, Iván Álvarez‐Twöse, Knut Brockow, Patrizia Bonadonna, Olivier Hermine, Marek Niedoszytko, Melody C. Carter, Gregor Hoermann, Wolfgang R. Sperr, Joseph H. Butterfield, Celalettin Üstün, Roberta Zanotti, Deepti Radia, Mariana Castells, Massimo Triggiani, Lawrence B. Schwartz, Alberto Órfão, Tracy I. George, Karl Sotlar, Jason Gotlib, Andreas Reiter, Hans‐Peter Horny, Michel Arock, Cem Akin, Dean D. Metcalfe,
Tópico(s)Food Allergy and Anaphylaxis Research
ResumoMastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user’s guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice. Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user’s guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice. INFORMATION FOR CATEGORY 1 CME CREDITCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaci-inpractice.org/. Fax or other copies will not be accepted.Date of Original Release: August 1, 2022. Credit may be obtained for these courses until July 31, 2023.Copyright Statement: Copyright © 2022-2024. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Peter Valent, MD, Karin Hartmann, MD, Juliana Schwaab, MD, Ivan Alvarez-Twose, MD, PhD, Knut Brockow, MD, Patrizia Bonadonna, MD, Olivier Hermine, MD, PhD, Marek Niedoszytko, MD, PhD, Melody C. Carter, MD, Gregor Hoermann, MD, PhD, Wolfgang R. Sperr, MD, Joseph H. Butterfield, MD, Celalettin Ustun, MD, Roberta Zanotti, MD, Deepti H. Radia, MD, Mariana Castells, MD, PhD, Massimo Triggiani, MD, PhD, Lawrence B. Schwartz, MD, PhD, Alberto Orfao, MD, PhD, Tracy I. George, MD, Karl Sotlar, MD, Jason Gotlib, MD, MS, Andreas Reiter, MD, Hans-Peter Horny, MD, Michel Arock, PharmD, PhD, Cem Akin, MD, PhD, and Dean D. Metcalfe, MD, MS (authors); David A. Khan, MD (editor)Learning objectives: 1.To promote the ability to diagnose, classify, and manage mast cell disorders including mastocytosis and mast cell activation syndromes (MCAS) and relevant comorbidities using diagnostic criteria, algorithms, and guidelines.2.To develop the skills to identify prognostic variables and apply scoring systems to individual patients to predict hematologic stability and disease progression.3.To recognize predisposing and triggering factors of MCAS events in patients with known MCAS and/or mastocytosis and learn avoidance measures and prophylactic therapies.Recognition of Commercial Support: This CME has not received external commercial support.Disclosure of Relevant Financial Relationships with Commercial Interests: P. Valent reports advisory board and honoraria from Novartis. K. Hartmann reports consultancy and honoraria from Novartis. I. Alvarez-Twose reports consultancy (honoraria) for Novartis. P. Bonadonna reports consultancy (honoraria) for Novartis. O. Hermine reports research grants from Novartis. M. Niedoszytko reports honoraria and support in clinical trials from Novartis. G. Hoermann reports honoraria from Novartis. W. R. Sperr reports consultancy (honoraria) for Novartis. R. Zanotti reports consultancy (honoraria) for Novartis. D. Radia reports advisory board and honoraria for/from Novartis. M. Triggiani reports consultancy (honoraria) for Novartis. L. B. Schwartz reports grants as site PI from Novartis for their midostaurin study. A. Orfao reports consultancy (honoraria) for Novartis. K. Sotlar reports advisory board and honoraria for Novartis. J. Gotlib reports research grants (funds for administration of clinical trials) from Novartis; reports advisory board, honoraria and reimbursement of travel expenses from Novartis. A. Reiter reports consultancy (honoraria) and research support for/from Novartis. H.-P. Horny reports advisory board and honoraria for/from Novartis. M. Arock reports honoraria from Novartis. C. Akin reports consultancy (honoraria) from Novartis. All other authors and reviewers reported no relevant financial relationships.IntroductionMast cells (MCs) are tissue-resident immune cells involved in a diversity of physiologic and pathologic reactions in health and disease.1Schwartz L.B. Mast cells and basophils.Clin Allergy Immunol. 2002; 16: 3-42PubMed Google Scholar, 2Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (404) Google Scholar, 3Galli S.J. Tsai M. IgE and mast cells in allergic disease.Nat Med. 2012; 18: 693-704Crossref PubMed Scopus (1071) Google Scholar, 4Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (273) Google Scholar, 5Galli S.J. Gaudenzio N. Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns.Annu Rev Immunol. 2020; 38: 49-77Crossref PubMed Scopus (78) Google Scholar, 6Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts.Theranostics. 2020; 10: 10743-10768Crossref PubMed Scopus (41) Google Scholar MCs exhibit a number of activation-linked surface antigens, including high-affinity receptors for IgE.1Schwartz L.B. Mast cells and basophils.Clin Allergy Immunol. 2002; 16: 3-42PubMed Google Scholar, 2Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (404) Google Scholar, 3Galli S.J. Tsai M. IgE and mast cells in allergic disease.Nat Med. 2012; 18: 693-704Crossref PubMed Scopus (1071) Google Scholar, 4Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (273) Google Scholar, 5Galli S.J. Gaudenzio N. Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns.Annu Rev Immunol. 2020; 38: 49-77Crossref PubMed Scopus (78) Google Scholar, 6Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts.Theranostics. 2020; 10: 10743-10768Crossref PubMed Scopus (41) Google Scholar MCs also produce proinflammatory and vasoactive mediators, several of which are stored within cytoplasmic metachromatic granules.1Schwartz L.B. Mast cells and basophils.Clin Allergy Immunol. 2002; 16: 3-42PubMed Google Scholar, 2Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (404) Google Scholar, 3Galli S.J. Tsai M. IgE and mast cells in allergic disease.Nat Med. 2012; 18: 693-704Crossref PubMed Scopus (1071) Google Scholar, 4Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (273) Google Scholar, 5Galli S.J. Gaudenzio N. Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns.Annu Rev Immunol. 2020; 38: 49-77Crossref PubMed Scopus (78) Google Scholar, 6Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts.Theranostics. 2020; 10: 10743-10768Crossref PubMed Scopus (41) Google Scholar During an anaphylactic reaction, MC activation is associated with both the rapid generation of arachidonic metabolites and immediate release of preformed, granule-derived mediators.1Schwartz L.B. Mast cells and basophils.Clin Allergy Immunol. 2002; 16: 3-42PubMed Google Scholar, 2Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (404) Google Scholar, 3Galli S.J. Tsai M. IgE and mast cells in allergic disease.Nat Med. 2012; 18: 693-704Crossref PubMed Scopus (1071) Google Scholar, 4Theoharides T.C. Valent P. Akin C. Mast cells, mastocytosis, and related disorders.N Engl J Med. 2015; 373: 163-172Crossref PubMed Scopus (273) Google Scholar, 5Galli S.J. Gaudenzio N. Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns.Annu Rev Immunol. 2020; 38: 49-77Crossref PubMed Scopus (78) Google Scholar, 6Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts.Theranostics. 2020; 10: 10743-10768Crossref PubMed Scopus (41) Google ScholarMC disorders include (1) MC hyperplasia, defined by expansion of nonclonal MCs; (2) mastocytosis (clonal disease of MCs), (3) myelomastocytic leukemia, an extremely rare malignancy; and (4) MC activation disorders, including MC activation syndromes (MCASs) (see Table E1 in this article’s Online Repository at www.jaci-inpractice.org).2Metcalfe D.D. Mast cells and mastocytosis.Blood. 2008; 112: 946-956Crossref PubMed Scopus (404) Google Scholar,6Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts.Theranostics. 2020; 10: 10743-10768Crossref PubMed Scopus (41) Google Scholar, 7Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (923) Google Scholar, 8Escribano L. Akin C. Castells M. Orfao A. Metcalfe D.D. Mastocytosis: current concepts in diagnosis and treatment.Ann Hematol. 2002; 81: 677-690Crossref PubMed Scopus (179) Google Scholar, 9Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 10Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (616) Google Scholar, 11Arock M. Valent P. Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives.Expert Rev Hematol. 2010; 3: 497-516Crossref PubMed Scopus (104) Google Scholar, 12Akin C. Valent P. Metcalfe D.D. Mast cell activation syndrome: proposed diagnostic criteria.J Allergy Clin Immunol. 2010; 126: 1099-1104Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar, 13Valent P. Akin C. Arock M. Brockow K. Butterfield J.H. Carter M.C. 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: 215-225Crossref PubMed Scopus (415) Google Scholar, 14Valent P. Sotlar K. Sperr W.R. Escribano L. Yavuz S. Reiter A. et al.Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.Ann Oncol. 2014; 25: 1691-1700Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 15Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (337) Google Scholar Based on World Health Organization (WHO) criteria, mastocytosis is classified into cutaneous mastocytosis (CM), systemic mastocytosis (SM), and MC sarcoma (MCS).7Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (923) Google Scholar, 8Escribano L. Akin C. Castells M. Orfao A. Metcalfe D.D. Mastocytosis: current concepts in diagnosis and treatment.Ann Hematol. 2002; 81: 677-690Crossref PubMed Scopus (179) Google Scholar, 9Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 10Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (616) Google Scholar, 11Arock M. Valent P. Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives.Expert Rev Hematol. 2010; 3: 497-516Crossref PubMed Scopus (104) Google Scholar,14Valent P. Sotlar K. Sperr W.R. Escribano L. Yavuz S. Reiter A. et al.Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.Ann Oncol. 2014; 25: 1691-1700Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 15Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (337) Google Scholar, 16Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Advances in the classification and treatment of mastocytosis: current status and outlook toward the future.Cancer Res. 2017; 77: 1261-1270Crossref PubMed Scopus (155) Google Scholar Although diagnostic criteria for each of these conditions have been established and recommendations for diagnosis and management are available,7Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (923) Google Scholar, 8Escribano L. Akin C. Castells M. Orfao A. Metcalfe D.D. Mastocytosis: current concepts in diagnosis and treatment.Ann Hematol. 2002; 81: 677-690Crossref PubMed Scopus (179) Google Scholar, 9Valent P. Sperr W.R. Schwartz L.B. Horny H.P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms.J Allergy Clin Immunol. 2004; 114: 3-11Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 10Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (616) Google Scholar, 11Arock M. Valent P. Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives.Expert Rev Hematol. 2010; 3: 497-516Crossref PubMed Scopus (104) Google Scholar, 12Akin C. Valent P. Metcalfe D.D. Mast cell activation syndrome: proposed diagnostic criteria.J Allergy Clin Immunol. 2010; 126: 1099-1104Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar, 13Valent P. Akin C. Arock M. Brockow K. Butterfield J.H. Carter M.C. 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: 215-225Crossref PubMed Scopus (415) Google Scholar, 14Valent P. Sotlar K. Sperr W.R. Escribano L. Yavuz S. Reiter A. et al.Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.Ann Oncol. 2014; 25: 1691-1700Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar, 15Valent P. Akin C. Metcalfe D.D. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts.Blood. 2017; 129: 1420-1427Crossref PubMed Scopus (337) Google Scholar, 16Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Advances in the classification and treatment of mastocytosis: current status and outlook toward the future.Cancer Res. 2017; 77: 1261-1270Crossref PubMed Scopus (155) Google Scholar, 17Reiter A. George T.I. Gotlib J. New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis.Blood. 2020; 135: 1365-1376Crossref PubMed Google Scholar there remain ongoing discussions about diagnostic algorithms, prognostication, and optimal management. In fact, over recent years, a number of novel disease-related and patient-related prognostic factors have been identified.16Valent P. Akin C. Hartmann K. Nilsson G. Reiter A. Hermine O. et al.Advances in the classification and treatment of mastocytosis: current status and outlook toward the future.Cancer Res. 2017; 77: 1261-1270Crossref PubMed Scopus (155) Google Scholar, 17Reiter A. George T.I. Gotlib J. New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis.Blood. 2020; 135: 1365-1376Crossref PubMed Google Scholar, 18Schwaab J. Schnittger S. Sotlar K. Walz C. Fabarius A. Pfirrmann M. et al.Comprehensive mutational profiling in advanced systemic mastocytosis.Blood. 2013; 122: 2460-2466Crossref PubMed Scopus (167) Google Scholar, 19Jawhar M. Schwaab J. Schnittger S. Meggendorfer M. Pfirrmann M. Sotlar K. et al.Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis.Leukemia. 2016; 30: 136-143Crossref PubMed Scopus (128) Google Scholar, 20Jawhar M. Schwaab J. Hausmann D. Clemens J. Naumann N. Henzler T. et al.Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis.Leukemia. 2016; 30: 2342-2350Crossref PubMed Scopus (53) Google Scholar, 21Naumann N. Jawhar M. Schwaab J. Kluger S. Lübke J. Metzgeroth G. et al.Incidence and prognostic impact of cytogenetic aberrations in patients with systemic mastocytosis.Genes Chromosomes Cancer. 2018; 57: 252-259Crossref PubMed Scopus (32) Google Scholar, 22Muñoz-González J.I. Jara-Acevedo M. Alvarez-Twose I. Merker J.D. Teodosio C. Hou Y. et al.Impact of somatic and germline mutations on the outcome of systemic mastocytosis.Blood Adv. 2018; 2: 2814-2828Crossref PubMed Scopus (31) Google Scholar, 23Muñoz-González J.I. Álvarez-Twose I. Jara-Acevedo M. Henriques A. Viñas E. Prieto C. et al.Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis.Blood. 2019; 134: 456-468Crossref PubMed Scopus (27) Google Scholar, 24Trizuljak J. Sperr W.R. Nekvindová L. Elberink H.O. Gleixner K.V. Gorska A. et al.Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification.Allergy. 2020; 75: 1927-1938Crossref PubMed Scopus (19) Google Scholar, 25Kluin-Nelemans H.C. Jawhar M. Reiter A. van Anrooij B. Gotlib J. Hartmann K. et al.Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis.Theranostics. 2021; 11: 292-303Crossref PubMed Google Scholar, 26Kluin-Nelemans H.C. Reiter A. Illerhaus A. van Anrooij B. Hartmann K. Span L.F.R. et al.Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry.Leukemia. 2020; 34: 1090-1101Crossref PubMed Scopus (12) Google Scholar In addition, predisposing factors and critical comorbidities have been defined and several prognostic scoring systems established.18Schwaab J. Schnittger S. Sotlar K. Walz C. Fabarius A. Pfirrmann M. et al.Comprehensive mutational profiling in advanced systemic mastocytosis.Blood. 2013; 122: 2460-2466Crossref PubMed Scopus (167) Google Scholar, 19Jawhar M. Schwaab J. Schnittger S. Meggendorfer M. Pfirrmann M. Sotlar K. et al.Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis.Leukemia. 2016; 30: 136-143Crossref PubMed Scopus (128) Google Scholar, 20Jawhar M. Schwaab J. Hausmann D. Clemens J. Naumann N. Henzler T. et al.Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis.Leukemia. 2016; 30: 2342-2350Crossref PubMed Scopus (53) Google Scholar, 21Naumann N. Jawhar M. Schwaab J. Kluger S. Lübke J. Metzgeroth G. et al.Incidence and prognostic impact of cytogenetic aberrations in patients with systemic mastocytosis.Genes Chromosomes Cancer. 2018; 57: 252-259Crossref PubMed Scopus (32) Google Scholar, 22Muñoz-González J.I. Jara-Acevedo M. Alvarez-Twose I. Merker J.D. Teodosio C. Hou Y. et al.Impact of somatic and germline mutations on the outcome of systemic mastocytosis.Blood Adv. 2018; 2: 2814-2828Crossref PubMed Scopus (31) Google Scholar, 23Muñoz-González J.I. Álvarez-Twose I. Jara-Acevedo M. Henriques A. Viñas E. Prieto C. et al.Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis.Blood. 2019; 134: 456-468Crossref PubMed Scopus (27) Google Scholar, 24Trizuljak J. Sperr W.R. Nekvindová L. Elberink H.O. Gleixner K.V. Gorska A. et al.Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification.Allergy. 2020; 75: 1927-1938Crossref PubMed Scopus (19) Google Scholar, 25Kluin-Nelemans H.C. Jawhar M. Reiter A. van Anrooij B. Gotlib J. Hartmann K. et al.Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis.Theranostics. 2021; 11: 292-303Crossref PubMed Google Scholar, 26Kluin-Nelemans H.C. Reiter A. Illerhaus A. van Anrooij B. Hartmann K. Span L.F.R. et al.Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry.Leukemia. 2020; 34: 1090-1101Crossref PubMed Scopus (12) Google Scholar, 27Sperr W.R. Kundi M. Alvarez-Twose I. van Anrooij B. Oude Elberink J.N.G. Gorska A. et al.International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study.Lancet Haematol. 2019; 6: e638-e649Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 28Jawhar M. Schwaab J. Álvarez-Twose I. Shoumariyeh K. Naumann N. Lübke J. et al.MARS: Mutation-Adjusted Risk Score for advanced systemic mastocytosis.J Clin Oncol. 2019; 37: 2846-2856Crossref PubMed Scopus (45) Google Scholar, 29Muñoz-González J.I. Álvarez-Twose I. Jara-Acevedo M. Zanotti R. Perkins C. Jawhar M. et al.Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study.Lancet Haematol. 2021; 8: e194-e204Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar A critical point is that in a number of patients, 2 or even 3 MC-involving pathologies may be detected, which potentially act together to initiate or aggravate symptoms in these patients.30Castells M.C. Mastocytosis: moving the field to precision and personalized medicine.Immunol Allergy Clin North Am. 2018; 38 (xv-xvii)Google Scholar, 31Valent P. Akin C. Gleixner K.V. Sperr W.R. Reiter A. Arock M. et al.Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches.Int J Mol Sci. 2019; 20: 2976Crossref Scopus (39) Google Scholar, 32Castells M.C. Mast cell disorders: a framework of allergy and hematology symptoms leading to personalized treatments.Ann Allergy Asthma Immunol. 2021; 127: 403-404Abstract Full Text Full Text PDF PubMed Google Scholar, 33Zanotti R. Tanasi I. Crosera L. Bonifacio M. Schena D. Orsolini G. et al.Systemic mastocytosis: multidisciplinary approach.Mediterr J Hematol Infect Dis. 2021; 13e2021068Crossref PubMed Scopus (3) Google ScholarIn this article, we include an overview of new diagnostic markers and therapeutic concepts in MC disorders, with special emphasis on multidisciplinary aspects and challenges. In addition, we provide a user’s guide for application of biomarkers, diagnostic algorithms, and disease management strategies in routine medical practice. Our proposed recommendations focus on adult patients and were developed by a consortium of experts from the European Competence Network on Mastocytosis (ECNM) and the American Initiative in Mast Cell Diseases (AIM).Approach to Patients with Suspected SM and/or MCAS: Initial ScreenInitial clinical assessment includes a detailed case history and precise physical examination, including an inspection of the skin.7Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (923) Google Scholar,10Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Brockow K. et al.Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria.Eur J Clin Invest. 2007; 37: 435-453Crossref PubMed Scopus (616) Google Scholar,31Valent P. Akin C. Gleixner K.V. Sperr W.R. Reiter A. Arock M. et al.Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches.Int J Mol Sci. 2019; 20: 2976Crossref Scopus (39) Google Scholar,34Hartmann K. Escribano L. Grattan C. Brockow K. Carter M.C. Alvarez-Twose I. et al.Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.J Allergy Clin Immunol. 2016; 137: 35-45Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar Typical maculopapular skin lesions with a positive Darier’s sign are a strong indication for the presence of mastocytosis, which is usually confirmed by histology.34Hartmann K. Escribano L. Grattan C. Brockow K. Carter M.C. Alvarez-Twose I. et al.Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology.J Allergy Clin Immunol. 2016; 137: 35-45Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar Unlike in children, in whom the diagnosis is usually CM, most adult patients are diagnosed with SM.7Valent P. Horny H.P. Escribano L. Longley B.J. Li C.Y. Schwartz L.B. et al.Diagnostic criteria and classification of mastocytosis: a consensus proposal.Leuk Res. 2001; 25: 603-625Crossref PubMed Scopus (923) Google Scholar,10Valent P. Akin C. Escribano L. Födinger M. Hartmann K. Br
Referência(s)