1. Heritable risk for severe anaphylaxis associated with increased [alpha]-tryptase-encoding germline copy number at TPSAB1Jonathan J. Lyons, Jack Chovanec, Michael P. O'Connell, Yihui Liu, Julij Šelb, Roberta Zanotti, Yun Bai, Jiwon Kim, Quang T. Le, Tom DiMaggio, Matija Rijavec, Peter Korošec, 2020 Povzetek: Background: An elevated basal serum tryptase level is associated with severe systemic anaphylaxis, most notably caused by Hymenoptera envenomation. Although clonal mast cell disease is the culprit in some individuals, it does not fully explain this clinical association. Objective: Our aim was to determine the prevalence and associated impact of tryptase genotypes on anaphylaxis in humans. Methods: Cohorts with systemic mastocytosis (SM) and venom as well as idiopathic anaphylaxis from referral centers in Italy, Slovenia, and the United States, underwent tryptase genotyping by droplet digital PCR. Associated anaphylaxis severity (Mueller scale) was subsequently examined. Healthy volunteers and controls with nonatopic disease were recruited and tryptase was genotyped by droplet digital PCR and in silico analysis of genome sequence, respectively. The effects of pooled and recombinant human tryptases, protease activated receptor 2 agonist and antagonist peptides, and a tryptase-neutralizing mAb on human umbilical vein endothelial cell permeability were assayed using a Transwell system. Results: Hereditary [alpha]-tryptasemia (H[alpha]T)--a genetic trait caused by increased [alpha]-tryptase-encoding Tryptase-[alpha]/[beta]1 (TPSAB1) copy number resulting in elevated BST level--was common in healthy individuals (5.6% [n = 7 of 125]) and controls with nonatopic disease (5.3% [n = 21 of 398]). H[alpha]T was associated with grade IV venom anaphylaxis (relative risk = 2.0; P < .05) and more prevalent in both idiopathic anaphylaxis (n = 8 of 47; [17%; P = .006]) and SM (n = 10 of 82 [12.2%; P = .03]) relative to the controls. Among patients with SM, concomitant H[alpha]T was associated with increased risk for systemic anaphylaxis (relative risk = 9.5; P = .007). In vitro, protease-activated receptor-2-dependent vascular permeability was induced by pooled mature tryptases but not [alpha]- or [beta]-tryptase homotetramers. Conclusions: Risk for severe anaphylaxis in humans is associated with inherited differences in [alpha]-tryptase-encoding copies at TPSAB1.
Ključne besede: mastocytosis, venoms, hypersensitivity, anaphylaxis - diagnosis, mast cells, idiopathic anaphylaxis, mast cell activation, hereditary alpha-tryptasemia
DiRROS - Objavljeno: 11.09.2020; Ogledov: 481; Prenosov: 66 |
2. Management of suspected immediate perioperative allergic reactions : an international overview and consensus recommendationsLene Heise Garvey, Pascale Dewachter, David L. Hepner, Paul Michel Mertes, Susanna Voltolini, Russel C. Clarke, Peter J. Cooke, Tomaz Garcez, Anne Berit Guttormsen, Didier G. Ebo, Philip M. Hopkins, Peter Kopač, 2019 Povzetek: Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.
Ključne besede: allergy and immunology, drug hypersensitivity, anesthesia, drug-related side effects and adverse reactions, anaphylaxis, epinephrine, Delphi technique, perioperative period, allergic reactions, hypersensitivity reaction, adrenaline, perioperative anaphylaxis, allergy testing, guideline
DiRROS - Objavljeno: 09.10.2020; Ogledov: 328; Prenosov: 112 |
3. The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions : current statusPeter Kopač, Philip M. Hopkins, Anne Berit Guttormsen, Tomaz Garcez, Pascale Dewachter, Peter J. Cooke, Russel C. Clarke, Sinisa Savic, Mogens Krøigaard, Didier G. Ebo, Lene Heise Garvey, 2019 Povzetek: Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.
Ključne besede: allergy and immunology, drug hypersensitivity, anesthesia, drug-related side effects and adverse reactions, anaphylaxis, perioperative period, allergic reactions, hypersensitivity reaction, perioperative anaphylaxis, allergy testing, challenge testing, drug provocation test
DiRROS - Objavljeno: 09.10.2020; Ogledov: 295; Prenosov: 231 |
4. Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactionsPhilip M. Hopkins, Peter J. Cooke, Russel C. Clarke, Anne Berit Guttormsen, Peter R. Platt, Pascale Dewachter, Didier G. Ebo, Tomaz Garcez, Lene Heise Garvey, David L. Hepner, Peter Kopač, 2019 Povzetek: Background: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. Methods: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. Results: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. Conclusion: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.
Ključne besede: alergy and immunology, anesthesia, anaphylaxis, drug hypersensitivity, drug-related side effects and adverse reactions, perioperative period, surgery, operative surgical procedures
DiRROS - Objavljeno: 09.10.2020; Ogledov: 254; Prenosov: 100 |
5. Anaesthetic management of patients with pre-existing allergic conditions : a narrative reviewPascale Dewachter, Peter Kopač, Jose Julio Laguna, Paul Michel Mertes, Vito Sabato, Gerald W. Volcheck, Peter J. Cooke, 2019 Povzetek: This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in agal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgEmediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.
Ključne besede: allergy and immunology, drug hypersensitivity, food hypersensitivity, immediate hypersensitivity, anaphylaxis, anesthesia, drug-related side effects and adverse reactions, perioperative period, adverse effects
DiRROS - Objavljeno: 16.10.2020; Ogledov: 326; Prenosov: 71 |
6. Comparative epidemiology of suspected perioperative hypersensitivity reactionsPaul Michel Mertes, Didier G. Ebo, Tomaz Garcez, Michael Rose, Vito Sabato, Tomonori Takazawa, Peter J. Cooke, Russel C. Clarke, Pascale Dewachter, Lene Heise Garvey, Anne Berit Guttormsen, David L. Hepner, Philip M. Hopkins, David A. Khan, Peter Kopač, Peter R. Platt, Louise C. Savic, 2019 Povzetek: Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.
Ključne besede: anaphylaxis, anti-bacterial agents, blood, chlorhexidine, latex, neuromuscular blocking agents, hypersensitivity, drug hypersensitivity, sugammadex, antibiotics, blood products, perioperative anaphylaxis, perioperative hypersensitivity
DiRROS - Objavljeno: 16.10.2020; Ogledov: 406; Prenosov: 76 |
7. An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactionsLene Heise Garvey, Didier G. Ebo, Paul Michel Mertes, Pascale Dewachter, Tomaz Garcez, Peter Kopač, Jose Julio Laguna, Anca Chiriac, Ingrid Terreehorst, Susanna Voltolini, K Scherer, 2019 Povzetek: Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper are to provide recommendations for the investigation of immediate type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.
Ključne besede: allergy and immunology -- diagnosis, drug hypersensitivity -- diagnosis, anaphylaxis, anesthesia, anesthetics, opioid analgesics, anti-bacterial agents, anti-inflammatory agents, non-steroidal opioids, antibiotics
DiRROS - Objavljeno: 16.10.2020; Ogledov: 353; Prenosov: 91 |
8. Mast cell activation test in the diagnosis of allergic disease and anaphylaxisRajia Bahri, Adnan Custovic, Peter Korošec, Marina Tsoumani, Martin Barron, Jiakai Wu, Rebekah Sayers, Alf Weimann, Monica Ruiz-Garcia, Nandinee Patel, Mira Šilar, 2018 Povzetek: Background. Food allergy is an increasing public health issue and the commonest cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy resulting in over-diagnosis and adverse impact on health-related quality of life. Objective. To undertake initial validation and assessment of a novel diagnostic tool, the mast cell activation test (MAT). Methods. Primary human mast cells (hMCs) were generated from peripheral blood precursors, and sensitized using patient sera and then incubated with allergen. Mast cell degranulation was assessed by flow cytometry and mediator release. We compared the diagnostic performance of MAT to existing diagnostic tools to assess in a cohort of peanut-sensitized individuals undergoing double-blind, placebo-controlled challenge. Results. hMCs sensitized with sera from peanut, grass pollen and hymenoptera- (wasp venom) allergic patients demonstrated allergen-specific and dose-dependent degranulation by both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandins D2 and ß-hexosaminidase release). In this cohort of peanut-sensitized individuals, MAT was found to have superior discrimination performance compared to other testing modalities including component-resolved diagnostics and basophil activation test. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge. Conclusion. MAT is a robust tool which may confer superior diagnostic performance compared to existing allergy diagnostics, and may be useful to explore differences in effector cell function between basophils and mast cells during allergic reactions.
Ključne besede: allergy and immunology -- diagnosis, anaphylaxis, immunologic tests, mast cells, food hypersensitivity, basophil activation test, BAT, mast cell activation test
DiRROS - Objavljeno: 30.11.2020; Ogledov: 329; Prenosov: 150
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9. Important and specific role for basophils in acute allergic reactionsPeter Korošec, Bernhard F. Gibbs, Matija Rijavec, Adnan Custovic, Paul J. Turner, 2018 Povzetek: IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FceRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis, and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.
Ključne besede: allergy and immunology, basophils, anaphylaxis
DiRROS - Objavljeno: 14.12.2020; Ogledov: 230; Prenosov: 111
Celotno besedilo (511,01 KB) |
10. Routine KIT p.D816V screening identifies clonal mast cell disease in Hymenoptera allergic patients regularly missed using baseline tryptase levels alonePeter Korošec, Jonathan J. Lyons, Mitja Košnik, Samo Zver, Vladka Čurin-Šerbec, Yihui Liu, Young Hwan Park, Ajda Demšar, Nisera Bajrović, Matevž Škerget, Peter Kopač, Mihaela Zidarn, Renato Eržen, Matija Rijavec, Julij Šelb, 2021 Povzetek: Background. Clonal mast cell disorders and elevated BST of unknown cause(s) are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have normal BST (<11.4 ng/mL). Objective. To evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. Methods. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis referred to our center in the years 2018-19. KIT p.D816V was determined in the peripheral blood with qPCR and tryptase genotyping was performed by droplet-digital PCR. Results. 351 patients (93.9%) had normal levels of BST and KIT p.D816V was detected in 8% of patients (28/351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2%[24/132] vs 1.8%[4/88 in grade III; 0/131 in other grades] in lower grades; P<0.001). In grade IV patients with normal BST, KIT p.D816V was associated with more severe symptoms including a significantly higher frequency of loss of consciousness (58.3%[14/24] vs 34.3%[37/108]; P=0.03) and absence of skin symptoms (41.7%[10/24] vs 15.7%[17/108]; P=0.004). Among patients with normal BST, KIT p.D816V (OR [95%CI]: 10.25[3.75-36.14]; P<0.0001) was the major risk factor associated with severe HVA. Hereditary [alpha]-tryptasemia (H[alpha]T), due to increased germline copies of TPSAB1 encoding [alpha]-tryptase was the most common cause (65.2%; 15/23) of elevated BST in patients with HVA and together with KIT p.D816V accounted for 90% (20/23) of BST elevations in HVA patients. Conclusion. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk HVA patients regularly missed using BST alone.
Ključne besede: anaphylaxis, venoms, hypersensitivity, hereditary alpha-tryptasemia
DiRROS - Objavljeno: 31.03.2021; Ogledov: 89; Prenosov: 41 |
