{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:43:54Z","timestamp":1790876634670,"version":"4.1.0"},"reference-count":111,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The association between Hymenoptera venom\u2010triggered anaphylaxis (HVA) and clonal mast cell\u2010related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for <jats:italic>KIT<\/jats:italic> p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of <jats:italic>KIT<\/jats:italic> p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom\u2010triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from \u2018how many patients with cMCD have anaphylaxis?\u2019 to \u2018how many patients with anaphylaxis have cMCD?\u2019. The discovery of hereditary \u03b1\u2010tryptasemia (H\u03b1T)\u2014a genetic trait caused by an increased copy number of the Tryptase Alpha\/Beta 1 (<jats:italic>TPSAB1)<\/jats:italic> gene\u2010, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. H\u03b1T is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk\u00a0=\u00a02.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of \u03b1\/\u03b2 \u2010tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and H\u03b1T, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell\u2010related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and\/or H\u03b1T in cases of severe anaphylaxis triggered by food or drugs.<\/jats:p>","DOI":"10.1111\/cea.14264","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:35:29Z","timestamp":1674110129000},"page":"392-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Clonal mast cell disorders and hereditary \u03b1\u2010tryptasemia as risk factors for anaphylaxis"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2035-6998","authenticated-orcid":false,"given":"Mark","family":"Ka\u010dar","sequence":"first","affiliation":[{"name":"University Hospital of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-4952","authenticated-orcid":false,"given":"Matija","family":"Rijavec","sequence":"additional","affiliation":[{"name":"University Hospital of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Biotechnical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julij","family":"\u0160elb","sequence":"additional","affiliation":[{"name":"University Hospital of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-1599","authenticated-orcid":false,"given":"Peter","family":"Koro\u0161ec","sequence":"additional","affiliation":[{"name":"University Hospital of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00130832-200208000-00008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2009.03324.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32830638c5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2005.00963.x"},{"key":"e_1_2_9_6_1","volume-title":"Insect Sting Allergy Stuttgart Gustav Fischer","author":"Mueller UR","year":"1990"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022952"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80940-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(84)90384-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12948-015-0030-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.046"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)61367-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)61784-X"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13262"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.03.017"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.10.049"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.1.15"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01569.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.12.1578"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70270-7"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1993.tb00984.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(83)90630-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.12.12"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-731893"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13246380"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.05.003"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2015.03.015"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40629-020-00120-y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000646"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000048188"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329218"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000328760"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122976"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2007.02804.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12225"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.11.018"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32833b280c"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2018.04.010"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.02.043"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.06.035"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.07.037"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.035"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329856"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.11.025"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.11.44"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12617"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12132"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.10.004"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.05.044"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.9.2237.2237"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.72"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.24"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2010.10.004"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.277897"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2014.11.029"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.08.023"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.01.006"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-453183"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000096442"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.02.019"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25371"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.227"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1159\/000524532"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2013.06.014"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21239030"},{"key":"e_1_2_9_67_1","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01406-y"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.034553"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.06.020"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259085"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2018.04.003"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3696"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.06.017"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190701"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/829068"},{"issue":"5","key":"e_1_2_9_77_1","first-page":"1","article-title":"Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss\u2010of\u2010function mutations","volume":"124","author":"Trivedi NN","year":"2009","journal-title":"J Allergy Clin Immunol [Internet]"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114944"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006157"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.05.057"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.01.016"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.04.004"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.5.2310"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119290"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501079"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14040"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13969"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13982"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007936"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02108.x"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3527"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2008.01780.x"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X0603400618"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01345.x"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000097168.32472.0D"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199211000-00016"},{"issue":"6","key":"e_1_2_9_97_1","first-page":"442","article-title":"Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice","volume":"21","author":"Mertes PM","year":"2011","journal-title":"J Investig Allergol Clin Immunol"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.07.022"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000031"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2018.02.024"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.10.063"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X0903700415"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2009.09.019"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-014-0450-8"},{"key":"e_1_2_9_105_1","first-page":"1","article-title":"Case report: mastocytosis: the long road to diagnosis","volume":"12","author":"Rama TA","year":"2021","journal-title":"Front Immunol"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12317"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14844"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.039"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.02.008"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12916"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2021.06.019"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13801"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.14264","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.14264","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.14264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T01:36:03Z","timestamp":1692668163000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.14264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":111,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/cea.14264"],"URL":"https:\/\/doi.org\/10.1111\/cea.14264","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]},"assertion":[{"value":"2022-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}