FIRST QATAR ALLERGY CONFERENCE Adrenaline autoinjector is underprescribed in typical cold urticaria patients living in tropical climate countries y y y Mojca Bizjak1,2 , Mitja Košnik1,3 , Dejan Dinevski2, Simony Francis Thomsen4 ,y Daria Fomina5,6, Elena Borzova7,8, Kanokvalai Kulthanan9 , Raisa Meshkova10 , Fernando M Aarestrup11, Dalia Melina Ahsan12,13, Mona Al-Ahmad14, Sabine Altrichter12,13, 15 , Andrea Bauer16, Maxi Brockstädt12,13, Célia Costa17, Semra Demir18, Roberta Fachini Criado19, Luis Felipe Ensina20, Asli Gelincik18, Ana Maria Giménez-Arnau21, Margarida Gonçalo22, Maia Gotua23, Jesper Grønlund Holm4, Naoko Inomata24, Alicja Kasperska-Zajac25, Maryam Khoshkhui26, Aliya Klyucharova27,28, Emek Kocatürk29, Rongbiao Lu30, Michael Makris31, Natalya Maltseva5, Maria Pasali31, Marisa Paulino17, David Pesqué21, Jonny Peter32,33, German Dario Ramón34, Carla Ritchie35, Solange Oliveira Rodrigues Valle36, Michael Rudenko37, Agnieszka Sikora25, Nicola Wagner38, 39 40 41 12,13y * Paraskevi Xepapadaki y , Xiaoyang Xue , Zuotao Zhao , Dorothea Terhorst-Molawi , Marcus Maurer12,13 * 9Department of Dermatology, Urticaria Center of Reference Address for Correspondence: y Mojca Bizjak1,2 and Excellence (UCARE), Faculty of Medicine Siriraj Hospital, y Mahidol University, Bangkok, Thailand COLD-CE steering committee member, *both authors 10 have contributed equally Department of Clinical Immunology and Allergology, 1 Division of Allergy, Urticaria Center of Reference and Urticaria Center of Reference and Excellence (UCARE), Excellence (UCARE), University Clinic of Respiratory and Smolensk State Medical University, Smolensk, Russian Allergic Diseases Golnik, Golnik, Slovenia Federation 11 2 Faculty of Medicine, University of Maribor, Maribor, Faculdade de Ciências, Médicas e da Saúde de Juiz de Fora Slovenia (SUPREMA), Urticaria Center of Reference and Excellence 3 Faculty of Medicine, University of Ljubljana, Ljubljana, (UCARE), Hospital Maternidade Therezinha de Jesus, Minas Slovenia Gerais, Brazil 12 4 Department of Dermatology, Urticaria Center of Reference Urticaria Center of Reference and Excellence (UCARE), and Excellence (UCARE), Bispebjerg Hospital, University of Institute of Allergology, Charité –Universitätsmedizin Berlin, Copenhagen, Copenhagen, Denmark corporate member of Freie Universität Berlin and Humboldt- 5 Center of Allergy and Immunology, Urticaria Center of Universität zu Berlin, Berlin, Germany 13 Reference and Excellence (UCARE), Clinical State Hospital Fraunhofer Institute for Translational Medicine and 52, Moscow Ministry of Healthcare, Moscow, Russian Pharmacology ITMP, Allergology and Immunology, Berlin, Federation Germany 14 6 Department of Clinical Immunology and Allergology, I.M. Microbiology Department, Faculty of Medicine, Urticaria Sechenov First Moscow State Medical University, Moscow, Center of Reference and Excellence (UCARE), Kuwait Russian Federation University, Safat, Kuwait 15 7 Department of Dermatology and Venereology, I.M. Department of Dermatology and Venerology, Urticaria Sechenov First Moscow State Medical University, Moscow, Center of Reference and Excellence (UCARE), Russian Federation Comprehensive Allergy Center, Kepler University Hospital, 8 Department of Clinical Genetics, Veltischev Research and Linz, Austria 16 Clinical Institute for Pediatrics of the Pirogov Russian Department of Dermatology, Urticaria Center of National Research Medical University, Moscow, Russian Reference and Excellence (UCARE), University Allergy Federation Center, University Hospital Carl Gustav Carus, Technical QATAR MEDICAL JOURNAL 1 VOL. 2022 / FQAC / ART. 19 Adrenaline autoinjector is underprescribed in typical cold urticaria patients living in tropical climate countries Bizjak et al. University, Dresden, Germany 35Adults and Pediatrics Allergy Unit, Urticaria Center of 17 Immunoallergology Department, Urticaria Center of Reference and Excellence (UCARE), Hospital Italiano de Reference and Excellence (UCARE), Hospital de Santa Maria, Buenos Aires, Buenos Aires, Argentina CHULN, Lisbon, Portugal 36 Department of Internal Medicine, Immunology Service, 18 Division of Allergy, Department of Internal Medicine, Urticaria Center of Reference and Excellence (UCARE), Istanbul Faculty of Medicine, Urticaria Center of Reference Federal University of Rio de Janeiro, Rio de Janeiro, Brazil and Excellence (UCARE), Istanbul University, Istanbul, Turkey 37 London Allergy and Immunology Centre, Urticaria Center 19 Faculdade de Medicina do ABC (FMABC), Urticaria Center of Reference and Excellence (UCARE), London, UK of Reference and Excellence (UCARE), Santo André, Brazil 38 Department of Dermatology, Urticaria Center of 20 Division of Allergy, Clinical Immunology and Reference and Excellence (UCARE), University Hospital of Rheumatology, Department of Pediatrics, Urticaria Center Erlangen, University of Erlangen-Nuremberg (FAU), of Reference and Excellence (UCARE), Federal University of Germany São Paulo, São Paulo, Brazil 39 Allergy Unit, 2nd Pediatric Clinic, Urticaria Center of 21 Department of Dermatology, Urticaria Center of Reference and Excellence (UCARE), National and Reference and Excellence (UCARE), Hospital del Mar, IMIM, Kapodistrian University of Athens, Greece Universitat Autònoma, Barcelona, Spain 40 Department of General Practice, Urticaria Center of 22 Clinic of Dermatology, Urticaria Center of Reference and Reference and Excellence (UCARE), Community Health Excellence (UCARE), University Hospital and Faculty of Service Center, Guangzhou City, China Medicine, University of Coimbra, Coimbra, Portugal 41 Department of Dermatology and Venerology, Urticaria 23 Center of Allergy and Immunology, Urticaria Center of Center of Reference and Excellence (UCARE), Beijing Key Reference and Excellence (UCARE), Tbilsi, Georgia Laboratory of Molecular Diagnosis on Dermatoses and 24 Department of Environmental Immuno-Dermatology, National Clinical Research Center for Skin and Immune Urticaria Center of Reference and Excellence (UCARE), Diseases, Peking University First Hospital, Beijing, China Yokohama City University Graduate School of Medicine, Email: mojca.bizjak@klinika-golnik.si Yokohama, Japan 25 European Center for Diagnosis and Treatment of http://doi.org/10.5339/qmj.2022.fqac.19 Urticaria/Angioedema (GA2LEN UCARE /ACARE Network) © 2022 Bizjak, Košnik, Dinevski, Thomsen, Fomina, Borzova, & Department of Clinical Allergology and Urticaria of Medical Kulthanan, Meshkova, Aarestrup, Ahsan, Al-Ahmad, Altrichter,, University of Silesia, Poland Bauer, Brockstädt, Costa, Demir, Criado, Ensina, Gelincik, 26 Allergy Research Center, Mashhad University of Medical Giménez-Arnau, Gonçalo, Gotua, Holm, Inomata, Kasperska- Sciences, Mashhad, Iran Zajac, Khoshkhui, Klyucharova, Kocatürk, Lu, Makris, Maltseva, 27 Pasali, Paulino, Pesqué, Peter, Ramón, Ritchie, Valle, Rudenko, Department of Clinical Immunology and Allergology, Sikora, Wagner, Xepapadaki, Xue, Zhao, Terhorst-Molawi, Maurer, Republican Center of Clinical Immunology and Allergology, licensee HBKU Press. Urticaria Center of Reference and Excellence (UCARE), Republican Clinical Hospital, Kazan State Medical University, Kazan, Russian Federation Cite this article as: Bizjak M, Košnik M, 28 Dinevski D, Thomsen SF, Fomina D, Borzova E, Department of Internal Diseases, Institute of Fundamental Kulthanan K, Meshkova R, Aarestrup FM, Medicine and Biology (IFMB) of Kazan Federal University, Ahsan DM, Al-Ahmad M, Altrichter S, Bauer A, Kazan, Russian Federation Brockstädt M, Costa C, Demir S, Criado RF, 29 Department of Dermatology, Urticaria Center of Ensina LF, Gelincik A, Giménez-Arnau AM, Reference and Excellence (UCARE), Koç University School of Gonçalo M, Gotua M, Holm JG, Inomata N, Kasperska-Zajac A, Khoshkhui M, Klyucharova A, Medicine, Istanbul, Turkey Kocatürk E, Lu R, Makris M, Maltseva N, Pasali M, 30 Department of Dermatology, Urticaria Center of Paulino M, Pesqué D, Peter J, Ramón GD, Reference and Excellence (UCARE), The Third Affiliated Ritchie C, Rodrigues Valle SO, Rudenko M, Hospital of Sun Yat-sen University, Guangzhou, China Sikora A, Wagner N, Xepapadaki P, Xue X, Zhao Z, 31 Allergy Unit, Second Department of Dermatology and Terhorst-Molawi D, Maurer M. Adrenaline auto- injector is underprescribed in typical cold urti- Venereology, Urticaria Center of Reference and Excellence caria patients living in tropical climate countries, (UCARE), National and Kapodistrian University of Athens, Qatar Medical Journal 2022(2):19 http://doi. University General Hospital "Attikon", Athens, Greece org/10.5339/qmj.2022.fqac.19 32 Division of Allergy and Clinical Immunology, Department of Medicine, Urticaria Center of Reference and Excellence (UCARE), University of Cape Town, Cape Town, South Africa 33 Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa 34 Instituto de Alergia e Inmunologia del Sur, Urticaria Center of Reference and Excellence (UCARE), Buenos Aires, Argentina 2 QATAR MEDICAL JOURNAL VOL. 2022 / FQAC / ART. 19 Adrenaline autoinjector is underprescribed in typical cold urticaria patients living in tropical climate countries Bizjak et al. ABSTRACT Background: The diagnosis of typical cold urticaria significantly differ between these countries (44% vs. (ColdU) relies on whealing in response to local cold 42%, p ¼ 1.000; R29C2). Residents of tropical stimulation testing (CST). It can also manifest with countries had a higher frequency of ColdA induced by cold-induced anaphylaxis (ColdA). To date, it is largely cold air than residents of temperate (36% vs. 12%, unclear how often patients with ColdU receive p ¼ .001; R29C4) or cold (36% vs. 12%, p ¼ .007; adrenaline treatment and are provided with an R25C4) countries. Cardiovascular manifestations adrenaline autoinjector (AAI). induced by cold air were diagnosed in 33% (n ¼ 11) Methods: An international, cross-sectional study, of residents of tropical countries, but only 18% COLD-CE (i.e., comprehensive evaluation of ColdU (n ¼ 2) and 36% (n ¼ 4) of them had received and other cold-induced reactions), was carried out at adrenaline and AAI, respectively (R13 2 15C7). 32 UCAREs. Detailed patient history was taken and Furthermore, hypotension and/or loss of conscious- CST with an ice cube and/or TempTestw performed. ness induced by cold air occurred in 18% (n ¼ 6) of ColdA was defined as an acute cold-induced (ie, by patients, but only 17% (n ¼ 1) received adrenaline cold water, air or surfaces) involvement of the skin (R13 2 14C10). ColdA was induced by complete cold and/or visible mucosal tissue and at least one of the water immersion in 9% (n ¼ 3) of patients, and none following clinical signs/symptoms: cardiovascular of them received adrenaline treatment nor AAI manifestations, difficulty breathing, or gastrointestinal (R13 2 15C3). symptoms. Conclusion: Our findings suggest that ColdA is Results: Of the 551 ColdU patients, 75% (n ¼ 412) undertreated and call for changes in ColdU had a positive CST. Of them, concomitant chronic management. spontaneous urticaria was diagnosed in 10%. Of 372 Acknowledgement: This work benefited from the patients with stand-alone ColdU, 69% were women support of the GA2LEN UCARE network (www. and 91% adults. Their median age was 36 (IQR ga2len-ucare.com), and the results reported here 26 2 48) years. Patients were also categorized into were presented at the First Qatar Allergy Conference residents of countries with a tropical (n ¼ 33), and published in Allergy, the European Journal of temperate (n ¼ 264), or cold (n ¼ 75) climate Allergy and Clinical Immunology. (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than Keywords: adrenaline autoinjector, cold urticaria, tropical countries (30% vs. 12%, p ¼ .038; Table 1: COLD-CE, cold-induced anaphylaxis R31C1), although the frequency of ColdA did not REFERENCES 1. Bizjak M, Košnik M, Dinevski D, Thomsen SF, Fomina D, implementation of GA(2) LEN Urticaria Centers et al. Risk factors for systemic reactions in typical cold of Reference and Excellence. Allergy. 2016;71 urticaria: Results from the COLD-CE study. Allergy. (8):1210 –8. 2021 Dec 4. 3. Maltseva N, Borzova E, Fomina D, et al. Cold urticaria – 2. Maurer M, Metz M, Bindslev-Jensen C, Bousquet J, what we know and what we do notknow. Allergy. Canonica GW, Church MK, et al. Definition, aims, and 2021;76(4):1077 –94. QATAR MEDICAL JOURNAL 3 VOL. 2022 / FQAC / ART. 19 Table 1. Previous adrenaline treatment, AAI prescription or both stratified by systemic reactions in typical ColdU patients. VOL. 2022 / FQAC / ART. 19 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 4 QATAR MEDICAL JOURNAL Hypotension and/or loss of ColdU ColdA – broad definition Cardiovascular manifestations consciousness a Anya CWI Air Anya CWI Air Any CWI Air R1 Mixed adult/ N ¼ 372 145 (39%) 107 (29%) 53 (14%) 116 (31%) 88 (24%) 31 (8%) 48 (13%) 41 (11%) 10 (3%) pediatric R2 Adrenaline receivedb 12 (3%) 12 (8%) 8 (8%) 4 (8%) 11 (10%) 7 (8%) 4 (13%) 8 (17%) 5 (12%) 3 (30%) R3 AAI prescribedb 93 (25%) 54 (37%) 44 (41%) 15 (28%) 49 (42%) 41 (47%) 9 (29%) 24 (50%) 21 (51%) 4 (40%) R4 Bothc 8 (2%) 8 (6%) 5 (5%) 3 (6%) 7 (6%) 4 (5%) 3 (10%) 5 (10%) 3 (7%) 2 (20%) R5 Adult ( $ 18 years) N ¼ 338 135 (40%) 98 (29%) 51 (15%) 106 (31%) 79 (23%) 29 (9%) 41 (12%) 35 (10%) 9 (3%) R6 Adrenaline receivedb 10 (3%) 10 (7%) 7 (7%) 3 (6%) 9 (9%) 6 (8%) 3 (10%) 6 (15%) 4 (11%) 2 (22%) R7 AAI prescribedb 85 (25%) 51 (38%) 42 (43%) 14 (28%) 46 (43%) 39 (49%) 8 (28%) 22 (54%) 20 (57%) 3 (33%) R8 Bothc 7 (2%) 7 (5%) 5 (5%) 2 (4%) 6 (6%) 4 (5%) 2 (7%) 4 (10%) 3 (9%) 1 (11%) R9 Pediatric N ¼ 34 10 (29%) 9 (27%) 2 (6%) 10 (29%) 9 (27%) 2 (6%) 7 (21%) 6 (18%) 1 (3%) R10 Adrenaline receivedb 2 (6%) 2 (20%) 1 (11%) 1 (50%) 2 (20%) 1 (11%) 1 (50%) 2 (29%) 1 (17%) 1 (100%) R11 AAI prescribedb 8 (24%) 3 (30%) 2 (22%) 1 (50%) 3 (30%) 2 (22%) 1 (50%) 2 (29%) 1 (17%) 1 (100%) R12 Bothc 1 (3%) 1 (10%) 0 1 (50%) 1 (10%) 0 1 (50%) 1 (14%) 0 1 (100%) R13 Tropical climate N ¼ 33 14 (42%) 3 (9%) 12 (36%) 12 (36%) 1 (3%) 11 (33%) 7 (21%) 3 (9%) 6 (18%) R14 Adrenaline receivedb 2 (6%) 2 (14%) 0 2 (17%) 2 (17%) 0 2 (18%) 1 (14%) 0 1 (17%) R15 AAI prescribedb 4 (12%) 4 (29%) 0 4 (33%) 4 (33%) 0 4 (36%) 3 (43%) 1 (33%) 3 (50%) R16 Bothc 2 (6%) 2 (14%) 0 2 (17%) 2 (17%) 0 2 (18%) 1 (14%) 0 1 (17%) R17 Temperate climate N ¼ 264 115 (44%) 94 (36%) 32 (12%) 95 (36%) 80 (30%) 18 (7%) 38 (14%) 35 (13%) 3 (1%) R18 Adrenaline receivedb 10 (4%) 10 (9%) 8 (9%) 2 (6%) 9 (10%) 7 (9%) 2 (11%) 7 (18%) 5 (14%) 2 (67%) R19 AAI prescribedb 78 (30%) 46 (40%) 41 (44%) 10 (31%) 42 (44%) 38 (48%) 5 (28%) 20 (53%) 19 (54%) 1 (33%) R20 Bothc 6 (2%) 6 (5%) 5 (5%) 1 (3%) 5 (5%) 4 (5%) 1 (6%) 4 (11%) 3 (9%) 1 (33%) R21 Cold climate N ¼ 75 16 (21%) 10 (13%) 9 (12%) 9 (12%) 7 (9%) 2 (3%) 3 (4%) 3 (4%) 1 (1%) Adrenaline autoinjector is underprescribed in typical cold urticaria patients living in tropical climate countries R22 Adrenaline receivedb 0 0 0 0 0 0 0 0 0 0 R23 AAI prescribedb 11 (15%) 4 (25%) 3 (30%) 1 (11%) 3 (33%) 3 (43%) 0 1 (33%) 1 (33%) 0 R24 Bothc 0 0 0 0 0 0 0 0 0 0 Bizjak et al. Table 1 – continued R25 Tropical vs. cold (p-value) .035 .750 .007 .007 .430 < .001 .009 .367 .003 R26 Adrenaline receivedb .091 .209 NA .486 .486 NA 1.000 1.000 NA 1.000 R27 AAI prescribedb 1.000 1.000 .528 .338 1.000 1.000 1.000 1.000 1.000 1.000 R28 Bothc .091 .209 NA .486 .486 NA 1.000 1.000 NA 1.000 R29 Tropical vs. temperate 1.000 .001 .001 1.000 < .001 < .001 .306 .781 < .001 (p-value) R30 Adrenaline receivedb .630 .619 1.000 .297 .357 1.000 .622 1.000 1.000 .226 R31 AAI prescribedb .038 .564 .260 1.000 .549 1.000 .694 .699 .595 1.000 R32 Bothc .219 .210 1.000 .176 .176 1.000 .539 1.000 1.000 1.000 R33 Temperate vs. cold (p-value) < .001 < .001 1.000 < .001 < .001 .267 .015 .023 1.000 R34 Adrenaline receivedb .125 .610 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 R35 AAI prescribedb .011 .286 .512 .401 .729 1.000 1.000 .606 .595 1.000 R36 Bothc .345 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 Note: Data are given as no. (%). Statistical significance of differences between patient groups was calculated using Fisher’s exact test. Statistically significant p-values ( p <.05) are in bold. Abbreviations: AAI, adrenaline autoinjector; C, column; ColdA, cold-induced anaphylaxis; CWI, complete cold water immersion; N, number of patients; NA, not applicable (ie, no statistics are computed because at least one of the variables is a constant); R, row. a Any cold trigger (i.e., complete cold water immersion, cold ambient air exposure, transition from cold outdoors to warm indoors, localized contact with cold liquids without immersion or ice, and contact with cold surfaces). b Unknown indication(s). c Adrenaline received & AAI prescribed. Adrenaline autoinjector is underprescribed in typical cold urticaria patients living in tropical climate countries VOL. 2022 / FQAC / ART. 19 QATAR MEDICAL JOURNAL Bizjak et al. 5