Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry - 04/02/21

Doi : 10.1016/j.jaci.2020.06.008

Wojciech Francuzik, MD ^a, Franziska Ruëff, MD ^b, Andrea Bauer, MD ^c, Maria Beatrice Bilò, MD ^d,^e, Victoria Cardona, MD, PhD ^f,^g, George Christoff, MD, PhD ^h,ⁱ, Sabine Dölle-Bierke, PhD ^a, Luis Ensina, MD, PhD ^j, Montserrat Fernández Rivas, MD, PhD ^g,^k, Thomas Hawranek, MD ^l, Jonathan O'B Hourihane, MD, PhD ^m, Thilo Jakob, MD ^n,^o, Nicos G. Papadopoulos, MD, PhD ^p,^q, Claudia Pföhler, MD ^r, Iwona Poziomkowska-Gęsicka, MD, PhD ^s, Xavier Van der Brempt, MD ^t, Kathrin Scherer Hofmeier, MD ^u, Regina Treudler, MD ^v, Nicola Wagner, MD ^w, Bettina Wedi, MD ^x, Margitta Worm, MD ^a,^⁎
^a Division of Allergy and Immunology, Department of Dermatology, Venerology, and Allergology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany
^b Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany
^c University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
^d Allergy Unit, Department of Internal Medicine, University Hospital Ospedali Riuniti di Ancona, Ancona, Italy
^e Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy
^f Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron, Barcelona, Spain
^g ARADyAL Research Network
^h Faculty of Public Health, Medical University-Sofia, Sofia, Bulgaria
ⁱ Allergy Outpatient Department, Acibadem CityClinic, Tokuda Medical Centre, Sofia, Bulgaria
^j Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil
^k Department of Allergy, Hospital Clinico San Carlos, Universidad Complutense, IdISSC, Madrid, Spain
^l Department of Dermatology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
^m DM University College Cork and Cork University Hospital, Cork, Ireland
ⁿ Department of Dermatology and Allergology, University Medical Center Giessen and Marburg, Justus-Liebig University Gießen, Gießen, Germany
^o Allergy Research Group, Medical Center, University of Freiburg, Freiburg, Germany
^p Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
^q Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom
^r Department of Dermatology, Saarland University Medical Center, Homburg/Saar, Homburg, Germany
^s Clinical Allergology Department, Pomeranian Medical University in Szczecin, Szczecin, Poland
^t Allergy Vigilance Network, Nancy, France
^u Division of Allergy, Department of Dermatology, University Hospital Basel, University of Basel, Basel, Switzerland
^v Department of Dermatology, Venereology and Allergology, Leipzig Interdisciplinary Allergy Center-Comprehensive Allergy Center, University Hospital, Leipzig, Germany
^w Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
^x Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Hannover, Germany

^∗Corresponding author: Margitta Worm, MD, Klinik für Dermatologie, Venerologie und Allergologie, Charitéplatz 1, 10117, Berlin, Germany.Klinik für DermatologieVenerologie und AllergologieCharitéplatz 1Berlin10117Germany

Abstract

Background

Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach.

Objective

This study aimed to evaluate the phenotype and risk factors of VIA.

Methods

Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]).

Results

VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis.

Conclusion

Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.

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Key words : Anaphylaxis, epinephrine (adrenaline), β-blockers, insect venom allergy, Hymenoptera

Abbreviations used : ACEI, BST, ER, SIT, VIA

Mappa

Methods

Results

VIA is more frequently associated with cardiovascular symptoms

Absence of skin symptoms correlates with BST levels and increases the risk of severe anaphylaxis specifically in VIA

BST level greater than 8 ng/mL and concomitant cardiovascular conditions increase the risk of severe VIA

Other cofactors of severe reactions

One-third of patients with VIA experience repeated reactions

Patients with VIA receive epinephrine less often than do patients without VIA

Discussion

Limitations

Conclusion

Disclosure of potential conflict of interest: A. Bauer reports personal fees from ALK, Allergopharma, Allergy Therapeutics, Diater, LETI, Thermo Fisher, and Stallergens outside the submitted work. N. Wagner reports personal fees from ALK outside the submitted work. R. Treudler reports grants and personal fees from Sanofi-Genzyme, ALK-Abelló, Takeda, and Novartis and grants from Hautnetz Leipzig and Fraunhofer-IZI Leipzig outside the submitted work. V. Cardona reports personal fees from ALK, Allergopharma, Allergy Therapeutics, Diater, LET, Thermo Fisher, and Stallergens outside the submitted work. M. B. Bilò reports personal fees from ALK outside the submitted work. K. Scherer reports personal fees from Allergopharma, Sanofi-Aventis, and Shire outside submitted work. Franziska Ruëff reports personal fees outside the submitted work from ALK-Abelló, Allergopharma, Bencard, Boehringer Ingelheim, Bristol-Myers Squibb, Circassia, Dermira, DST, LEO Pharma, Lilly, Dr Gerhard Mann Chem-Pharm Fabrik GmbH, Mylan, Novartis, Pfizer, Thermo Fisher Scientific, and UCB. C. Pföhler has performed clinical studies for Allergy Therapeutics and has received speaker honoraria and travel support from Bencard, Novartis, and ALK. The rest of the authors declare that they have no relevant conflicts of interest.

Esportazione

Vol 147 - N° 2

P. 653 - Febbraio 2021 Ritorno al numero

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Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry - 04/02/21

Abstract

Background

Objective

Methods

Results

Conclusion

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