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1.
Fatal Hymenoptera Venom–triggered anaphylaxis in patients with unrecognized clonal mast cell disorder : Is mastocytosis to blame?
Matija Rijavec, Jezerka Inkret, Urška Bidovec, Tanja Carli, Nina Frelih, Andreja Kukec, Peter Korošec, Mitja Košnik, 2023, original scientific article

Abstract: Hymenoptera venom–triggered anaphylaxis (HVA) affects up to 8.9% of the general population and is the most frequent cause of anaphylaxis in adults, accounting for approximately 20% of all fatal anaphylaxis cases. Quite often, a fatal reaction is a victim’s first manifestation of HVA. Mastocytosis represents one of the most important risk factors for severe HVA. We analyzed patients with documented fatal HVA for the presence of underlying clonal mast cell disorder (cMCD). Here, we report three cases of fatal HVA, with undiagnosed underlying cMCD identified by the presence of the peripheral blood and/or bone marrow KIT p.D816V missense variant postmortem. In the first case, anaphylaxis was the initial episode and was fatal. In the other two cases, both patients were treated with specific venom immunotherapy (VIT), nevertheless, one died of HVA after VIT discontinuation, and the other during VIT; both patients had cardiovascular comorbidities and were taking beta-blockers and/or ACE inhibitors. Our results point to the importance of screening all high-risk individuals for underlying cMCD using highly sensitive molecular methods for peripheral blood KIT p.D816V variant detection, including severe HVA and possibly beekeepers, for proper management and the need for lifelong VIT to prevent unnecessary deaths. Patients at the highest risk of fatal HVA, with concomitant cardiovascular and cMCD comorbidities, might not be protected from field stings even during regular VIT. Therefore, two adrenaline autoinjectors and lifelong VIT, and possibly cotreatment with omalizumab, should be considered for high-risk patients to prevent fatal HVA episodes.
Keywords: fatal anaphylaxis, Hymenoptera venom, mastocytosis, venom immunotherapy
Published in DKUM: 16.04.2024; Views: 2; Downloads: 0
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Patch testing with the European baseline series and 10 added allergens : single centre study of 748 patients
Katja Adamič, Nisera Bajrović, Renato Eržen, Maja Jošt, Peter Kopač, Mitja Košnik, Nika Lalek, Mihaela Zidarn, Dejan Dinevski, 2022, original scientific article

Abstract: Background: The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥ 0.5% prevalence rate. Objectives: We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens. Methods: Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 hours. Readings were done on day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. Retrospective analysis was done. Results: Eight allergens not listed in the EBS had ≥ 0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II, and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings. Conclusion: We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, and Compositae mix II need to be added to the EBS.
Keywords: klinična epidemiologija, osnovna serija, kontaktna senzibilizacija, kožni testi z obliži, sočasna reaktivnost, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity
Published in DKUM: 13.07.2023; Views: 198; Downloads: 30
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FARMAKOGENOMIKA IN VREDNOTENJE INTERMITENTNEGA ZDRAVLJENJA Z ANTAGONISTI LEVKOTRIENOV PRI OTROCIH S PERSISTENTNO ASTMO
Maja Skerbinjek-Kavalar, 2013, dissertation

Abstract: V naši raziskavi smo želeli preveriti, ali je pri otrocih in mladostnikih intermitentno zdravljenje blage astme z LTRA prav tako učinkovito kot kontinuirano zdravljenje z LTRA. UDK: 616.248-053.2:615.234:577.2(043.3) V kliničnem delu raziskave smo ugotavljali urejenost astme po letu dni zdravljenja z IGK, z LTRA kontinuirano in z LTRA intermitentno. Ugotoviti smo želeli vpliv različnih načinov zdravljenja na pljučno funkcijo, ACT-vprašalnik in na biomarkerje (pH in vnetne citokine, ki so značilni za astmatsko vnetje) v kondenzatu izdihanega zraka. V raziskavi o genetiki smo želeli določiti pogostnost nekaterih alelov in genotipov v kandidatnih genih pri astmatikih in zdravih kontrolah. Ovrednotiti smo želeli njihovo povezanost s tveganjem za razvoj astme in ugotoviti, ali so posamezni SNP-ji povezani z astmo kot tako ali le z značilnimi fenotipi astme. S farmakogenetsko analizo smo želeli ugotoviti, ali so določeni polimorfizmi genov, ki so bili v prejšnjih raziskavah povezani bodisi s tveganjem za razvoj astme bodisi z odzivom na zdravljenje astme, povezani z odgovorom otrok na zdravljene z IGK, z LTR kontinuirano in z LTR intermitentno. Hipoteze, da je učinkovitost zdravljenja blage astme z LTRA intermitentno glede na klinične pokazatelje enako učinkovita kot dolgotrajno protivnetno zdravljenjenje z IGK ali z LTRA kontinuirano, nismo potrdili. Kljub temu da so bili v skupini, zdravljeni z LTRA intermitentno, vključeni bolniki z blažjo astmo, je bilo potrebno pri nekaterih bolnikih uvesti kontinuirano protivnetno zdravljenje. Z raziskavo povezanosti genotipov s fenotipi astme smo potrdili pomen nekaterih alelov oziroma genotipov SNP-jev v kandidatnih genih za astmo pri slovenskih otrocih. ORMDL3 smo potrdili kot pomembni kandidatni gen za astmo. V naši raziskavi je povezan tako s tveganjem za razvoj astme kot tudi z neatopijsko astmo in z astmo brez rinitisa. Alel C v rs4795405 je povezan s tveganjem za razvoj astme pri slovenski populaciji otrok; lahko bi vplival na pojav neatopijskega fenotipa astme in astme brez rinitisa. Potrdili smo povezavo genotipa GG rs5744247 v IL18 s simptomi zgodnje alergije, ki poveča možnost za razvoj astme. Sicer ta SNP ni povezan z atopijsko astmo, se pa je statistično značilno pogosteje pojavljal pri otrocih z astmo, ki imajo zgodnje simptome alergije, pogostnost genotipa GG pri otrocih brez zgodnjih simptomov alergije pa je bila podobna pogostnosti pri zdravih otrocih. Povezave TBXA2R z atopijsko astmo pri slovenskih otrocih nismo potrdili, našli pa smo povezavo med rs3786989 za TBXA2R in pojavom zgodnjih simptomov alergije ter povezavo med rs8113232 in astmo, ki ji je pridružen rinitis. Prav tako nismo potrdili povezave med rs833058 za VEGF in atopijsko astmo, temveč smo ugotovili, da je ta SNP povezan s pojavom zgodnjih simptomov alergije pri astmatikih, povezave med SNP rs2146323 v VEGFA in astmo ali posameznimi fenotipi nismo potrdili. SNP rs7025417 za gen IL-13 in SNP rs324011 za STAT6 nista bila povezana s tveganjem za razvoj astme ali s katerim od preučevanih fenotipov astme. SNP-ji rs3786989 in rs8113232 v TBXA2R, rs4795405 v ORMDL3 ter rs833058 v VEGFA so bili povezani s stopnjo izražanja astme, iste SNP-je smo povezali tudi bodisi s tveganjem za razvoj astme bodisi s posameznimi fenotipi astme, kar kaže na njihovo vlogo v patogenezi te bolezni. Rezultati vpliva genotipa na odziv na protivnetno zdravljenje z IGK kažejo vpliv polimorfizma rs1295686 za gen IL-13, saj imajo homozigoti za alel A boljši odgovor na zdravljenje, vpliv polimorfizma rs2139142 za gen MAPK3, kjer imajo homozigoti za alel G boljši odgovor na zdravljenje, vsi glede na porast FEV1. Boljšo urejenost astme glede izboljšanja % ACT-vprašalnika pa smo zabeležili pri polimorfizmu rs13298282 za gen TLE4 pri nosilcih vsaj enega alela C. Pri kontinuiranem zdravljenju z LTRA smo zabeležili porast pljučne funkcije oziroma FEV1 za polimorfizem rs1295686 za gen IL-13 za bolnike z vsaj enim alelom A, za polimorfizem rs2244012 za gen RAD50 pri homozigotih za alel C in z
Keywords: Astma, otrok, zdravljenje, genetika
Published in DKUM: 13.11.2013; Views: 2949; Downloads: 319
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