1. Remission of chronic urticaria in patients treated with omalizumabKlara Cvenkel, Mojca Bizjak, Julij Šelb, Mitja Košnik, 2024, original scientific article Abstract: Introduction: This study examined the remission probability and duration in chronic spontaneous urticaria (CSU) patients resistant to second-generation H1-antihistamines (sgAHs) undergoing omalizumab treatment.
Methods: This is a retrospective observational study of 176 adult CSU patients exhibiting a significant pruritus component (≥ 8) of the weekly urticaria activity score (UAS7) despite four daily sgAH tablets and starting omalizumab treatment with 300 mg every 4 weeks. After excluding 13 nonresponders, we analyzed 163 omalizumab responders (mean age 51.8 years, 74.4% female). The intervals between applications were increased. Discontinuation was considered for patients that remained asymptomatic on a gradually reduced dosage (to 150 mg every 12 weeks) without sgAHs.
Results: Omalizumab discontinuation was possible in 25.8% (42/163). The duration of omalizumab treatment before remission ranged from 7 to 6 months. Twenty-one patients (50.0%) maintained complete remission until the end of the observation period (September 2021) for 8 to 68 months. Of the relapsed patients, 71.4% (15/21) effectively controlled CSU with sgAHs. Six patients (28.6%; 6/21) required omalizumab reintroduction after 6 to 40 months of remission, responding favorably.
Conclusions: The study shows that a quarter of severe CSU patients achieve long-term remission. In addition, sgAHs effectively
manage symptoms in a majority of relapsed cases, and those requiring omalizumab reintroduction respond favorably.
Keywords: urticaria, antihistamines, omalizumab, urticaria, remission, urticaria relapse
Published in DiRROS: 16.06.2025; Views: 14; Downloads: 8
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2. Risk of anaphylaxis associated with cold urticariaMojca Bizjak, Krzysztof Rutkowski, Ricardo Assero, 2024, review article Abstract: Purpose of review
Cold-induced anaphylaxis (ColdA) is a poorly understood form of anaphylaxis that occurs in patients with cold urticaria (ColdU). This comprehensive review aims to deepen the understanding of ColdA. It emphasizes the identification of high-risk ColdU patients susceptible to ColdA and provides recommendations for their effective management.
Recent findings
Recent studies, including the large international COLD-CE study, have identified clinical features of ColdU patients associated with increased ColdA risk. These individuals can now be recognized through routine clinical assessments. Key diagnostic indicators for assessing ColdU and the risk of ColdA include oropharyngeal/laryngeal symptoms and positive standard local cold provocation tests. ColdA has been defined as acute cold-induced involvement of the skin and/or visible mucosal tissue accompanied by cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms, but a universally accepted definition is lacking. Additionally, ColdA has recently been recognized as an indication for prescribing adrenaline (epinephrine) autoinjectors, marking a significant advancement in disease management.
Summary
ColdA is a major and potentially life-threatening concern for a subset of ColdU patients. Early recognition of high-risk patients, coupled with education and preparedness of both patients and healthcare providers, is crucial for effectively managing this challenging condition. Further research is needed to expand understanding of the underlying pathophysiological mechanisms of ColdA, identify potential cofactors influencing ColdA, and improve disease-management strategies.
Keywords: adrenaline (epinephrine), autoinjector, cold-induced anaphylaxis, cold urticaria, management, risk factors
Published in DiRROS: 28.05.2025; Views: 123; Downloads: 78
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3. Cold-induced anaphylaxis : new insights into clinical and genetic characteristicsMojca Bizjak, Peter Korošec, Mitja Košnik, Julij Šelb, Urška Bidovec, Manca Svetina, Samo Zver, Dejan Dinevski, Matija Rijavec, 2025, original scientific article Abstract: The pathogenesis of cold urticaria (ColdU) and cold-induced anaphylaxis (ColdA) remains poorly understood, and ColdA is underrepresented in anaphylaxis literature. Laboratory features to guide management are largely unknown. This study evaluated basal serum tryptase (BST) and total immunoglobulin E (IgE) levels in ColdU and ColdA, their associations with clinical features, and the utility of testing for the KIT p.D816V variant in blood leukocytes and hereditary a-tryptasemia (HaT).
Keywords: anaphylaxis, cold urticaria, hereditary α-tryptasemia, KIT p.D816V, mast cell, total IgE, tryptase
Published in DiRROS: 21.05.2025; Views: 208; Downloads: 89
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4. Dietary habits of shooting athletes : a comparative study of Slovenian and foreign athletesTadeja Jakus, Nika Černe, Mojca Stubelj, 2024, original scientific article Abstract: Purpose: Shooting is a sport in which dietary habits and the timing of meals is not often represented. The aim of this paper is to compare the dietary habits, timing of meals and training frequency of Slovenian and foreign athletes. Methods: The sample included 88 shooter athletes (35 Slovenian and 53 foreign athletes), aged 14 to 60, who participate in competitions. Data by dietary habits, diet, training and BMI were collected via a questionnaire. Results: Athletes train and compete most frequently using an air rifle. Foreign athletes train more often and spend more time training than Slovenian athletes (p < 0.001). The average BMI was 24.9 ± 4.9 kg/m2 and was higher in athletes who competed at national level (26.8 ± 5.6 kg/m2) compared to international level (23.0 ± 3.1 kg/ m2) (p = 0.022). We found a difference between the groups in lunch (p = 0.041), morning (p = 0.020) and evening (p = 0.008) snacks. Slovenian athletes reached for food during training less frequently than foreign athletes (p = 0.007). More than half of the athletes (p < 0.001). Conclusions -athletes tend to train more frequently, have better nutritional planning and eat more meals after training than their Slovenian counterparts.
Keywords: shooting, nutrition, eating behaviour
Published in DiRROS: 13.03.2025; Views: 255; Downloads: 175
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5. Autoimmune mast cell activation test as a diagnostic tool in chronic spontaneous urticariaAna Koren, Luka Dejanović, Matija Rijavec, Peter Kopač, Mojca Bizjak, Mihaela Zidarn, Mitja Košnik, Peter Korošec, 2024, original scientific article Abstract: first_pagesettingsOrder Article Reprints
Open AccessArticle
Autoimmune Mast Cell Activation Test as a Diagnostic Tool in Chronic Spontaneous Urticaria
by Ana Koren 1,*ORCID,Luka Dejanović 1ORCID,Matija Rijavec 1,2ORCID,Peter Kopač 1,3ORCID,Mojca Bizjak 1ORCID,Mihaela Zidarn 1,3,Mitja Košnik 1,3ORCID andPeter Korošec 1,4
1
University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia
2
Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
3
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
4
Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(17), 9281; https://doi.org/10.3390/ijms25179281
Submission received: 25 July 2024 / Revised: 23 August 2024 / Accepted: 25 August 2024 / Published: 27 August 2024
(This article belongs to the Special Issue Progression of Allergy and Immune Response)
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Abstract
Chronic spontaneous urticaria (CSU) is associated with skin mast cell activation, and its triggering mechanisms are not completely elucidated. Evidence suggests an autoimmune component of CSU. Our aim was to assess the usefulness of an autoimmune mast cell activation test (aiMAT) for diagnosing and differentiating CSU into different subtypes. We enrolled 43 patients with active, uncontrolled CSU before starting treatment with omalizumab and 15 controls. Patients were evaluated based on omalizumab response. aiMATs were performed using non-IgE-sensitized (NS) or myeloma IgE-sensitized (S) LAD2 cells, which were then stimulated with CSU/control sera (25 µL and 10 µL). The expression of CD63 was assessed with flow cytometry. CD63 response on NS-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.0007) and with 10 µL CSU/control sera (p = 0.0001). The ROC curve analysis demonstrated an area under the curve (AUC) of 0.82. The cutoff for autoimmune-non-IgE-sensitized-MAT was 40.3% CD63+ LAD2, which resulted in 73.3% sensitivity and 81.4% specificity. CD63 response on S-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.03). The ROC curve analysis demonstrated an AUC of 0.66. The cutoff for the autoimmune-myeloma IgE-sensitized-MAT was 58.4% CD63+ cells, which resulted in 62.8% sensitivity and 66.7% specificity. Overall, 36 out of 43 (84%) patients responded to omalizumab, and 7 (16%) were nonresponders. We found no differences between LAD2 CD63 response and response to omalizumab. In conclusion, aiMAT could represent a new diagnostic tool in CSU. Additional studies are needed to evaluate the potential benefits during omalizumab therapy.
Keywords: mast cell activation test, LAD2, chronic spontaneous urticaria, omalizumab, CD63 expression
Published in DiRROS: 06.03.2025; Views: 217; Downloads: 128
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6. Key differences between chronic inducible and spontaneous urticariaMojca Bizjak, Mitja Košnik, 2024, original scientific article Abstract: Introduction: The latest international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends limited laboratory testing for chronic spontaneous urticaria (CSU) and selective testing for only certain chronic inducible urticaria (CIndU) subtypes, though the rationale for these recommendations is poorly explained. This study aimed to improve the understanding of CIndU subtypes by comprehensively comparing their demographic, clinical, and laboratory characteristics with those of the better-characterized CSU.
Methods: We conducted a retrospective analysis of 567 patients (median age 41 years, 67% female) diagnosed with CSU, symptomatic dermographism (SD), cold urticaria (ColdU), cholinergic urticaria (CholU), and delayed pressure urticaria (DPU).
Results: Our findings revealed that patients with SD, ColdU, and CholU had lower levels of C-reactive protein (CRP), higher total serum immunoglobulin E (IgE) levels, and higher basophil counts compared to CSU patients. These subtypes also had distinct demographic and clinical features, such as a younger age of onset and a longer disease duration. In contrast, patients with DPU had significantly higher CRP levels and neutrophil counts compared to those with CSU.
Discussion: These findings highlight the heterogeneity among chronic urticaria subtypes, suggesting that a tailored approach to laboratory testing may be more effective. The distinct immunological and clinical features observed in CIndU subtypes suggest a need for subtype-specific diagnostic and therapeutic guidelines.
Keywords: blood cell count, C-reactive protein, chronic inducible urticaria, chronic spontaneous urticaria, immunoglobulin E
Published in DiRROS: 21.02.2025; Views: 256; Downloads: 158
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7. Risk factors for systemic reactions in typical cold urticaria : results from the COLD-CE studyMojca 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, original scientific article Abstract: 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.
Keywords: urticaria, risk factors, epinephrine - therapeutic use, self administration, intramuscular injections - methods, cold urticaria, systemic reactions, adrenaline autoinjector
Published in DiRROS: 31.08.2022; Views: 1229; Downloads: 463
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8. Patch testing with the European baseline series and 10 added allergens : single centre study of 748 patientsMojca Bizjak, 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: allergy and immunology -- diagnosis, hypersensitivity -- diagnosis, skin tests, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity
Published in DiRROS: 24.06.2022; Views: 1234; Downloads: 442
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9. Cryoglobulins, cryofibrinogens, and cold agglutinins in cold urticaria : literature review, retrospective patient analysis, and observational study in 49 patientsKatharina Ginter, Dalia Melina Ahsan, Mojca Bizjak, Karoline Krause, Marcus Maurer, Sabine Altrichter, Dorothea Terhorst, 2021, original scientific article Abstract: Introduction: Cryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU. Methods: We conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Johanna Briggs Institute's critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations. Results: Our systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens, and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of nine ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder). Conclusion: Our investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail.
Keywords: urticaria, review, observational study, retrospective studies, cold urticaria, cryoglobulins, cryofibrinogens, cold agglutinins, retrospective analysis
Published in DiRROS: 28.05.2021; Views: 1887; Downloads: 1454
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10. Cold agglutinins and cryoglobulins associate with clinical and laboratory parameters of cold urticariaMojca Bizjak, Mitja Košnik, Dorothea Terhorst, Dejan Dinevski, Marcus Maurer, 2021, original scientific article Abstract: 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.
Keywords: urticaria, mast cells, cold-induced urticaria, cold urticaria, cryoglobulins, cold agglutinin, degranulation, clinical parameters, laboratory parameters
Published in DiRROS: 10.05.2021; Views: 2099; Downloads: 1562
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