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Risk factors for systemic reactions in typical cold urticaria : results from the COLD-CE study
Mojca Bizjak, Mitja Košnik, Dejan Dinevski, Simon Francis Thomsen, Daria Fomina, Elena Borzova, Kanokvalai Kulthanan, Raisa Meshkova, Dalia Melina Ahsan, Mona Al-Ahmad, Jovan Miljković, Dorothea Terhorst, Marcus Maurer, 2022, izvirni znanstveni članek

Povzetek: Background. Cold urticaria (ColdU), i.e. the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. Methods. An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. Results. Of 551 ColdU patients, 75% (n=412) had a positive CST and ColdA occurred in 37% (n=151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n=40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs 39%, p=0.003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. Conclusion. ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.
Ključne besede: urticaria, risk factors, epinephrine - therapeutic use, self administration, intramuscular injections - methods, cold urticaria, systemic reactions, adrenaline autoinjector
Objavljeno v DiRROS: 31.08.2022; Ogledov: 64; Prenosov: 18
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Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide : a protocol for a systematic review of observational studies
Tanja Carli, Igor Locatelli, Mitja Košnik, Andreja Kukec, 2022, pregledni znanstveni članek

Povzetek: Introduction Systemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide. Methods and analysis Searching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review. Ethics and dissemination No ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals.
Ključne besede: systemic allergic reaction (SAR), Hymenoptera venom, systematic literature review
Objavljeno v DiRROS: 31.08.2022; Ogledov: 69; Prenosov: 29
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Patch testing with the European baseline series and 10 added allergens : single centre study of 748 patients
Mojca Bizjak, Katja Adamič, Nisera Bajrović, Renato Eržen, Maja Jošt, Peter Kopač, Mitja Košnik, Nika Lalek, Mihaela Zidarn, Dejan Dinevski, 2022, izvirni znanstveni članek

Povzetek: 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.
Ključne besede: allergy and immunology -- diagnosis, hypersensitivity -- diagnosis, skin tests, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity
Objavljeno v DiRROS: 24.06.2022; Ogledov: 121; Prenosov: 38
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Natural history of the hymenoptera venom sensitivity reactions in adults : study design
Simona Perčič, Lidija Bojanić, Mitja Košnik, Andreja Kukec, 2022, izvirni znanstveni članek

Povzetek: Background: Allergic reactions to Hymenoptera stings can have varying levels of severity, according to the Müller grading system. Methods: By an epidemiological concept, this is a retrospective cohort study. The observed cohort was represented by patients referred to the University Clinic Golnik due to Hymenoptera allergic reaction in the period from 1997 to 2015. From the immunological database of the University Clinic Golnik, we obtained laboratory data (sIgE, skin tests and basophil activation test). The clinical characteristics of patients were obtained from BIRPIS. With the help of a questionnaire, which was sent to each patient in the period from May 2019 to April 2021, we obtained epidemiological data. For the assessment of the association between the severity of allergic reaction for the observed outcome, the severity of the first allergic reaction after Hymenoptera sting was used. Other variables were grouped according to risk factors. Discussion: We will identify the risk factors that could play an important role in a severe systemic reaction: the aetiology of the Hymenoptera sting, sex, age, history and severity of previous systemic reactions, being re-stung in an interval of two months, the frequency of re-stings, atopy, genetic predisposition, preventive medication use, other medication use, beekeeping or living next to beehives and why immunotherapy was not taken. Laboratory data will also be analysed to determine if there is any association with laboratory tests and the severity of the allergic reactions after Hymenoptera stings. Conclusions: Several new approaches are introduced in the study design. The most important is that the protocol covers epidemiological data gained from the questionnaire, as well as clinical data gained from the Immunological database and BIRPIS database. We expect to obtain significant results that will explain the risk factors for the natural history of Hymenoptera sting allergic reactions and will help allergologists, as well as general doctors, when facing those patients allergic to Hymenoptera venom without immunotherapy.
Ključne besede: hymenoptera venom allergy, risk factors, epidemiological association
Objavljeno v DiRROS: 06.04.2022; Ogledov: 222; Prenosov: 131
.pdf Celotno besedilo (786,63 KB)

Allergies and COVID-19 vaccines : an ENDA/EAACI position paper
Annick Barbaud, Lene Heise Garvey, Alessandra Arcolaci, Knut Brockow, Francesca Mori, Cristobalina Mayorga, Maja Jošt, Mitja Košnik, Mihaela Zidarn, Maria J Torres, 2022, izvirni znanstveni članek

Povzetek: Anaphylaxis, which is rare, has been reported after COVID 19 vaccination, but its management is not standardized. Method. Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. Results. No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine, are excipients. The authors propose allergy evaluation of persons with the following histories: 1- anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2- anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine, 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions. These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.
Ključne besede: SARS-CoV-2, COVID-19, COVID-19 vaccines, allergens, anapylaxis, drug hypersensitivity
Objavljeno v DiRROS: 07.02.2022; Ogledov: 276; Prenosov: 87
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Mnenje za spremljanje bolnikov po preboleli covidni pljučnici
Matjaž Turel, Natalija Edelbaher, Matjaž Fležar, Matevž Harlander, Peter Kecelj, Izidor Kern, Majda Kočar, Peter Kopač, Mitja Košnik, Robert Marčun, Igor Požek, Mirjana Rajer, Irena Šarc, Jurij Šorli, Dušanka Vidovič, Katarina Osolnik, 2021, izvirni znanstveni članek

Povzetek: Pljučnica je najpogostejši vzrok za težji potek okužbe z virusom SARS-CoV-2 in s hospitalizacijo. Potek covidne pljučnice je lahko različen; infiltrati, vidni na rentgenski sliki, se lahko resorbirajo spontano, včasih pa je potrebno zdravljenje s sistem-skimi glukokortikoidi. Ob odpustu iz bolnišnice zdravljenje običajno še ni končano, zato je Združenje pulmologov Slovenije v želji po enotnem obravnavanju bolnikov s covidno pljučnico izdelalo mnenje za obravnavo in sledenje bolnikov po od-pustu iz bolnišnice. Zavedamo se, da ob novi bolezni ne gre za dokončno priporočilo, saj bodo nova spoznanja o covidni pljučnici zanesljivo zahtevala obnavljanje priporočil.
Ključne besede: covid-19, mnenja, pljučnica, pulmologija, sistemski glukokortikoidi, covidna pljučnica
Objavljeno v DiRROS: 15.12.2021; Ogledov: 549; Prenosov: 62
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Hymenoptera venom immunotherapy : immune mechanisms of induced protection and tolerance
Ajda Demšar, Peter Korošec, Mitja Košnik, Mihaela Zidarn, Matija Rijavec, 2021, pregledni znanstveni članek

Povzetek: Hymenoptera venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after Hymenoptera venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure longterm tolerance post-therapy.
Ključne besede: allergy and immunology, hypersensitivity, immunotherapy, immune tolerance, venoms, Hymenoptera, Hymenoptera venom, short-term protection, long-term tolerance
Objavljeno v DiRROS: 16.08.2021; Ogledov: 397; Prenosov: 120
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Cold agglutinins and cryoglobulins associate with clinical and laboratory parameters of cold urticaria
Mojca Bizjak, Mitja Košnik, Dorothea Terhorst, Dejan Dinevski, Marcus Maurer, 2021, izvirni znanstveni članek

Povzetek: Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (n = 16) of 35 tested patients had a positive cold agglutinin test and 27% (n = 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (P = 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (P = 0.009) or immersion in cold water (P = 0.041), and aggravated by increased summer humidity (P = 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (P = 0.043), and lower disease control based on Urticaria Control Test (P = 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = -0.372, P = 0.028) and monocyte counts (r = -0.425, P = 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733, P = 0.025) and cold urticaria duration (r = 0.683, P = 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.
Ključne besede: urticaria, mast cells, cold-induced urticaria, cold urticaria, cryoglobulins, cold agglutinin, degranulation, clinical parameters, laboratory parameters
Objavljeno v DiRROS: 10.05.2021; Ogledov: 763; Prenosov: 628
.pdf Celotno besedilo (1,61 MB)
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Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies
Jean Bousquet, Jean-Paul Cristol, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Adrian Martineau, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alessandro Fiocchi, Nisera Bajrović, Natalija Edelbaher, Maja Jošt, Peter Kopač, Anja Koren, Mitja Košnik, Karmen Kramer Vrščaj, Samo Kreft, Nika Lalek, Bojan Madjar, Tonka Poplas-Susič, Irma Rozman Sinur, Tanja Soklič, Katja Triller Vadnal, Nadja Triller, Jure Urbančič, Mihaela Zidarn, 2020, pregledni znanstveni članek

Povzetek: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR[gamma]:Peroxisome proliferator-activated receptor, NF[kappa]B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2[alpha]:Elongation initiation factor 2[alpha]). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Ključne besede: Covid-19, SARS-CoV-2, food, insulin resistance, obesity, Nrf2, nutrients, TRPA1
Objavljeno v DiRROS: 25.01.2021; Ogledov: 977; Prenosov: 358
.pdf Celotno besedilo (1,61 MB)

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