{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:51:17Z","timestamp":1792875077128,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual\u2019s baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.<\/jats:p>","DOI":"10.3390\/ijms21239030","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T03:51:16Z","timestamp":1606535476000},"page":"9030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5095","authenticated-orcid":false,"given":"Peter","family":"Valent","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Division of Hematology and Hemostaseology and Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Akin","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, MI 48106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-0693","authenticated-orcid":false,"given":"Boguslaw","family":"Nedoszytko","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Bonadonna","sequence":"additional","affiliation":[{"name":"Allergy Unit, Verona University Hospital, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-8226","authenticated-orcid":false,"given":"Karin","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Division of Allergy, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Niedoszytko","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Brockow","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Biederstein, Technical University of Munich, D-80802 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Siebenhaar","sequence":"additional","affiliation":[{"name":"Dermatological Allergology, Department of Dermatology and Allergy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7318-2093","authenticated-orcid":false,"given":"Massimo","family":"Triggiani","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology, University of Salerno, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-4408","authenticated-orcid":false,"given":"Michel","family":"Arock","sequence":"additional","affiliation":[{"name":"Department of Hematological Biology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Pierre et Marie Curie University (UPMC), 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0487-0957","authenticated-orcid":false,"given":"Jan","family":"Romantowski","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Allergy &amp; Immunology, Virginia Commonwealth University, Richmond, VA 23284, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-8260","authenticated-orcid":false,"given":"Dean","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Mast cells and basophils","volume":"16","author":"Schwartz","year":"2002","journal-title":"Clin. Allergy Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1182\/blood-2007-11-078097","article-title":"Mast cells and mastocytosis","volume":"112","author":"Metcalfe","year":"2008","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and mast cells in allergic disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1056\/NEJMra1409760","article-title":"Mast cells, mastocytosis, and related disorders","volume":"373","author":"Theoharides","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10743","DOI":"10.7150\/thno.46719","article-title":"Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich\u2019s visions to precision medicine concepts","volume":"10","author":"Valent","year":"2020","journal-title":"Theranostics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10238-005-0064-5","article-title":"Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity","volume":"5","author":"Gibbs","year":"2005","journal-title":"Clin. Exp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/0091-6749(94)90345-X","article-title":"The clinical relevance of basophil releasability","volume":"94","author":"Marone","year":"1994","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5913","DOI":"10.4049\/jimmunol.165.10.5913","article-title":"Multiple defects in Fc epsilon RI signaling in Syk-deficient nonreleaser basophils and IL-3-induced recovery of Syk expression and secretion","volume":"165","author":"Kepley","year":"2000","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0161-5890(02)00082-2","article-title":"Association of the Src homology 2 domain-containing inositol 5\u2032 phosphatase (SHIP) to releasability in human basophils","volume":"38","author":"Macdonald","year":"2002","journal-title":"Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1111\/j.1398-9995.2012.02879.x.","article-title":"The interaction between Lyn and Fc\u03b5RI\u03b2 is indispensable for Fc\u03b5RI-mediated human mast cell activation","volume":"67","author":"Okayama","year":"2012","journal-title":"Allergy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1365-2222.2010.03667.x","article-title":"Characterization of syk expression in human lung mast cells: Relationship with function","volume":"41","author":"Havard","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/ACI.0b013e3283036a90","article-title":"Understanding the mechanisms of anaphylaxis","volume":"8","author":"Peavy","year":"2008","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jaci.2009.08.035","article-title":"Mechanisms of mast cell signaling in anaphylaxis","volume":"124","author":"Metcalfe","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1159\/000315937","article-title":"Anaphylaxis: Mechanisms of mast cell activation","volume":"95","author":"Kalesnikoff","year":"2010","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1111\/cea.12318","article-title":"Risk factors and management of severe life-threatening anaphylaxis in patients with clonal mast cell disorders","volume":"44","author":"Valent","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_16","first-page":"288","article-title":"Mastocytosis and allergic diseases","volume":"24","author":"Bonadonna","year":"2014","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.iac.2014.02.004","article-title":"Epidemiology, diagnosis, and treatment of hymenoptera venom allergy in mastocytosis patients","volume":"34","author":"Niedoszytko","year":"2014","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1182\/blood-2006-06-028100","article-title":"Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with \u201cidiopathic\u201d anaphylaxis","volume":"110","author":"Akin","year":"2007","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000096442","article-title":"Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: Monoclonal mast cell activation syndrome","volume":"142","author":"Sonneck","year":"2007","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.jaci.2010.08.035","article-title":"Mast cell activation syndrome: Proposed diagnostic criteria","volume":"126","author":"Akin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000328760","article-title":"Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal","volume":"157","author":"Valent","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/all.12126","article-title":"Mast cell activation syndromes: Definition and classification","volume":"68","author":"Valent","year":"2013","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.jaip.2019.01.006","article-title":"Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome","volume":"7","author":"Valent","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.jaci.2015.09.001","article-title":"Tryptase levels in children presenting with anaphylaxis: Temporal trends and associated factors","volume":"137","author":"Halbrich","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1111\/all.13226","article-title":"Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective","volume":"72","author":"Baretto","year":"2017","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s12016-020-08777-7","article-title":"Using baseline and peak serum tryptase levels to diagnose anaphylaxis: A review","volume":"58","author":"Passia","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5472","DOI":"10.4049\/jimmunol.154.10.5472","article-title":"Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNAs in human mast cells and basophils by competitive reverse transcription-polymerase chain reaction","volume":"154","author":"Xia","year":"1995","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.4049\/jimmunol.138.7.2184","article-title":"Evaluation of human peripheral blood leukocytes for mast cell tryptase","volume":"138","author":"Castells","year":"1987","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jaci.2004.02.032","article-title":"Expression of alpha-tryptase and beta-tryptase by human basophils","volume":"113","author":"Min","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1182\/blood.V98.8.2580","article-title":"Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms","volume":"98","author":"Samorapoompichit","year":"2001","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1056\/NEJM198706253162603","article-title":"Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis","volume":"316","author":"Schwartz","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1172\/JCI118337","article-title":"The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis","volume":"96","author":"Schwartz","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1056\/NEJM198707023170106","article-title":"Mediators of immediate hypersensitivity reactions","volume":"317","author":"Serafin","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0750-7658(05)81026-3","article-title":"Improved diagnosis of anaphylactoid reactions by measurement of serum tryptase and urinary methylhistamine","volume":"12","author":"Watkins","year":"1993","journal-title":"Ann. Fr. Anesth. Reanim."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.jaip.2014.06.011","article-title":"Mast cell activation syndrome: Improved identification by combined determinations of serum tryptase and 24-hour urine 11\u03b2-prostaglandin2\u03b1","volume":"2","author":"Ravi","year":"2014","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.advms.2017.12.003","article-title":"Markers of anaphylaxis\u2014A systematic review","volume":"63","author":"Klimek","year":"2018","journal-title":"Adv. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1016\/j.jaip.2020.02.021","article-title":"The utility of measuring urinary metabolites of mast cell mediators in systemic mastocytosis and mast cell activation syndrome","volume":"8","author":"Butterfield","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/all.13663","article-title":"Massive release of the histamine-degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients","volume":"74","author":"Boehm","year":"2019","journal-title":"Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.jaip.2019.10.048","article-title":"Idiopathic anaphylaxis: A form of mast cell activation syndrome","volume":"8","author":"Giannetti","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jaci.2009.02.003","article-title":"Assessing anaphylactic risk? Consider mast cell clonality","volume":"123","author":"Metcalfe","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1111\/j.1398-9995.2009.02108.x","article-title":"How much specific is the association between hymenoptera venom allergy and mastocytosis?","volume":"64","author":"Bonadonna","year":"2009","journal-title":"Allergy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/cea.12369","article-title":"The presence of mast cell clonality in patients with unexplained anaphylaxis","volume":"44","author":"Sander","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jaci.2014.11.035","article-title":"Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels","volume":"136","author":"Zanotti","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bonadonna, P., Bonifacio, M., Lombardo, C., and Zanotti, R. (2016). Hymenoptera allergy and mast cell activation syndromes. Curr. Allergy Asthma Rep., 16.","DOI":"10.1007\/s11882-015-0582-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1016\/j.jaip.2019.05.027","article-title":"Frequency of clonal mast cell diseases among patients presenting with anaphylaxis: A prospective study in 178 patients from 5 tertiary centers in Spain","volume":"7","author":"Fiandor","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s11882-019-0887-x","article-title":"Mast cell activation in the context of elevated basal serum tryptase: Genetics and presentations","volume":"19","author":"Khoury","year":"2019","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_47","first-page":"31029","article-title":"Heritable risk for severe anaphylaxis associated with increased \u03b1-tryptase-encoding germline copy number at TPSAB1","volume":"S0091\u20136749","author":"Lyons","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Greiner, G., Sprinzl, B., G\u00f3>rska, A., Ratzinger, F., Gurbisz, M., Witzeneder, N., Schmetterer, K.G., Gisslinger, B., Uyanik, G., and Hadzijusufovic, E. (2020). Hereditary alpha tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood, in press.","DOI":"10.1182\/blood.2020006157"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1182\/blood-2013-10-534685","article-title":"A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection","volume":"124","author":"Saleh","year":"2014","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Valent, P., Akin, C., Gleixner, K.V., Sperr, W.R., Reiter, A., Arock, M., and Triggiani, M. (2019). Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122976"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Smiljkovic, D., Kiss, R., Lupinek, C., Hoermann, G., Greiner, G., Witzeneder, N., Krajnik, G., Trautinger, F., Vrtala, S., and Mittermann, I. (2020). Microarray-based detection of allergen-reactive IgE in patients with mastocytosis. J. Allergy Clin. Immunol. Pract., 8.","DOI":"10.1016\/j.jaip.2020.04.030"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.17219\/acem\/65691","article-title":"Genetic polymorphisms and their involvement in the regulation of the inflammatory response in asthma and COPD","volume":"27","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-981-15-3449-2_4","article-title":"The role of genetics, the environment, and epigenetics in atopic dermatitis","volume":"1253","author":"Mu","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"adv00163","DOI":"10.2340\/00015555-3513","article-title":"Genetics in atopic dermatitis: Historical perspective and future prospects","volume":"100","author":"Brown","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nedoszytko, B., Reszka, E., Gutowska-Owsiak, D., Trzeciak, M., Lange, M., Jarczak, J., Niedoszytko, M., Jablonska, E., Romantowski, J., and Strapagiel, D. (2020). Genetic and epigenetic aspects of atopic dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186484"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lee, E., Kim, J.H., Lee, S.Y., Kang, M.J., Park, Y.M., Park, M.J., Rhee, E.-S., Ahn, K., Kim, K.W., and Shin, Y.H. (2020). Association of IL13 genetic polymorphisms with atopic dermatitis. Ann. Allergy Asthma Immunol., 125.","DOI":"10.1016\/j.anai.2020.04.023"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.jaci.2013.11.039","article-title":"Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities","volume":"133","author":"Lyons","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/ng.3696","article-title":"Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number","volume":"48","author":"Lyons","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/gim.2017.136","article-title":"A common haplotype containing functional CACNA1H variants is frequently coinherited with increased TPSAB1 copy number","volume":"20","author":"Lyons","year":"2018","journal-title":"Genet. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1016\/j.jaip.2020.01.012","article-title":"Usefulness of testing for hereditary alpha tryptasemia in symptomatic patients with elevated tryptase","volume":"8","author":"Carrigan","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/ACI.0000000000000678","article-title":"Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia","volume":"20","author":"Lyons","year":"2020","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1093\/annonc\/mdx290","article-title":"Midostaurin: A magic bullet that blocks mast cell expansion and activation","volume":"28","author":"Valent","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Reiter, A., George, T.I., and Gotlib, J. (2020). New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis. Blood, 135.","DOI":"10.1182\/blood.2019000932"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1111\/j.1365-2222.2009.03353.x","article-title":"Midostaurin (PKC412) inhibits immunoglobulin E-dependent activation and mediator release in human blood basophils and mast cells","volume":"39","author":"Krauth","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.jaci.2020.03.044","article-title":"Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis","volume":"146","author":"Hartmann","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/all.13237","article-title":"Omalizumab prevents anaphylaxis and improves symptoms in systemic mastocytosis: Efficacy and safety observations","volume":"73","author":"Vestergaard","year":"2018","journal-title":"Allergy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1016\/j.jaip.2019.03.039","article-title":"Omalizumab therapy for mast cell-mediator symptoms in patients with ISM, CM, MMAS, and MCAS","volume":"7","author":"Lemal","year":"2019","journal-title":"J. Allergy Clin. Immunol. 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