The importance of the fresh water outflow on a station situated in front of the Po river (Po di Goro)

The fractions of dissolved organic and inorganic nitrogen and phosphorus in sea water samples were monitored at the station S1, placed in front of the Po River mouth (44?44\u2770"N, 12?27\u2741"E). The aim was to extent our knowledge about the biochemical situation in an area that is highly influenced by fresh water loads by the .. 288 largest Italian river, and to estimate the portions of organic and inorganic nitrogen and phosphorus that were lost from the System due to physical and biochemical interactions. For this purpose, we chose to examine a sampling period with scarce river outflow (April 1995) and one with greater outflow (July 1995). Despite great nutrient loads in both sampling periods, our estimates revealed that almost the whole fraction of inorganic phosphorus (up to 92 % at April) and a part of the inorganic nitrogen (30 % at April and 42 % at July) was readily consumed at the station. Surprisingly the dissolved organic fraction of nitrogen (DON) was much greater at the station (up to 3120 % in April) than in the river water, and it constituted a conspicuous part of the total dissolved nitrogen in the study area. On the contrary, the dissolved organic fraction of phosphorus (DOP) did not accumulate in the coastal area, compared to the river water

Nirmatrelvir/ritonavir (Paxlovid®): French pharmacovigilance survey 2022

International audienceINTRODUCTION: Nirmatrelvir/ritonavir (Paxlovid®) is currently one of the few therapeutic options for coronavirus disease 2019 (COVID-19) curative treatment in non-oxygen-requiring adult patients at-high risk of progressing to severe disease. This recently approved boosted antiviral therapy presents a significant risk of drug-drug interactions (DDI). As part of the enhanced surveillance program in France for COVID-19 drugs and vaccines, the French national pharmacovigilance database (BNPV [base nationale de pharmacovigilance]) was queried in order to better characterize the drug safety profile, with a special focus on DDI. The aim of the study was to describe the adverse drug reactions reported through the BNPV. METHOD: All nirmatrelvir/ritonavir reports validated in the BNPV from the first authorization in France (January, 20th 2022) to December, 3rd 2022 (date of the query) were considered. An analysis of the scientific literature (PubMed®) and from the WHO pharmacovigilance database (Vigibase) was also performed. RESULTS: Over this period (11 months), 228 reports (40% of serious reports) were registered with a sex ratio of 1.9 female/1 male and a mean age of 66 years old. DDI reports account for more than 13% of reports (n=30) and were mainly related to immunosuppressive drugs overexposure (n=16). A total of 10/228 reports with fatal outcomes were reported in complex clinical settings. The main reported unexpected adverse drug reaction (ADRs) were high blood pressure (n=7), confusion (n=5), acute kidney injuries (AKI, n=7) and various skin reactions (n=22). Apart from situations of disease recurrence (not found in this analysis), data from Pubmed® and Vigibase also reported the above-mentioned events of interest. CONCLUSION: Overall, this analysis shows that nirmatrelvir/ritonavir safety profile was conform to current summary of product characteristics (SmPC). The main concern was the risk of DDI. Therefore, SmPC and expert recommendations should be systematically consulted before initiation of this antiviral, which is particularly indicated in polypharmacy patients. A case-by-case multidisciplinary approach including a clinical pharmacologist is required in these complex situations. Blood pressure elevation, confusion, cutaneous reactions and AKIs were the main unexpected ADRs of interest to follow, but need to be confirmed with a qualitative approach over time and new reports

Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis

International audienceObjective: Based on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.Methods: We investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.Results: We show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = -0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).Conclusions: Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS

Cytochromes P450 and P-Glycoprotein Phenotypic Assessment to Optimize Psychotropic Pharmacotherapy: A Retrospective Analysis of Four Years of Practice in Psychiatry

Altered cytochromes P450 enzymes (CYP) and P-glycoprotein transporter (P-gp) activity may explain variabilities in drug response. In this study, we analyzed four years of phenotypic assessments of CYP/P-gp activities to optimize pharmacotherapy in psychiatry. A low-dose probe cocktail was administered to evaluate CYP1A2, 2B6, 2D6, 2C9, 2C19, 3A4, and P-gp activities using the probe/metabolite concentration ratio in blood or the AUC. A therapeutic adjustment was suggested depending on the phenotyping results. From January 2017 to June 2021, we performed 32 phenotypings, 10 for adverse drug reaction, 6 for non-response, and 16 for both reasons. Depending on the CYP/P-gp evaluated, only 23% to 56% of patients had normal activity. Activity was decreased in up to 57% and increased in up to 60% of cases, depending on the CYP/P-gp evaluated. In 11/32 cases (34%), the therapeutic problem was attributable to the patient&rsquo;s metabolic profile. In 10/32 cases (31%), phenotyping excluded the metabolic profile as the cause of the therapeutic problem. For all ten individuals for which we had follow-up information, phenotyping allowed us to clearly state or clearly exclude the metabolic profile as a possible cause of therapeutic failure. Among them, seven showed a clinical improvement after dosage adaptation, or drug or pharmacological class switching. Our study confirmed the interest of CYP and P-gp phenotyping for therapeutic optimization in psychiatry

Risk Management Framework for Nano-Biomaterials Used in Medical Devices and Advanced Therapy Medicinal Products

The convergence of nanotechnology and biotechnology has led to substantial advancements in nano-biomaterials (NBMs) used in medical devices (MD) and advanced therapy medicinal products (ATMP). However, there are concerns that applications of NBMs for medical diagnostics, therapeutics and regenerative medicine could also pose health and/or environmental risks since the current understanding of their safety is incomplete. A scientific strategy is therefore needed to assess all risks emerging along the life cycles of these products. To address this need, an overarching risk management framework (RMF) for NBMs used in MD and ATMP is presented in this paper, as a result of a collaborative effort of a team of experts within the EU Project BIORIMA and with relevant inputs from external stakeholders. The framework, in line with current regulatory requirements, is designed according to state-of-the-art approaches to risk assessment and management of both nanomaterials and biomaterials. The collection/generation of data for NBMs safety assessment is based on innovative integrated approaches to testing and assessment (IATA). The framework can support stakeholders (e.g., manufacturers, regulators, consultants) in systematically assessing not only patient safety but also occupational (including healthcare workers) and environmental risks along the life cycle of MD and ATMP. The outputs of the framework enable the user to identify suitable safe(r)-by-design alternatives and/or risk management measures and to compare the risks of NBMs to their (clinical) benefits, based on efficacy, quality and cost criteria, in order to inform robust risk management decision-making.</p

7th drug hypersensitivity meeting: part one

Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics of HLA alleles associated with nevirapine hypersensitivity Rebecca Pavlos, Elizabeth Mckinnin, David Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Jing Yuan, Silvana Gaudieri, Mary Carrington, David Haas, Simon Mallal, Elizabeth Phillips O4 Do we need to measure total ige for the interpretation of analytical results of ImmunoCAP dnd 3gAllergy specific IgE? Douwe De Boer, Paul Menheere, Chris Nieuwhof, Judith Bons O5 Neutrophil activation in systemic anaphylaxis: results from the multicentric NASA study Friederike Jonsson, Luc De Chaisemartin, Vanessa Granger, Caitlin Gillis, Aurelie Gouel, Catherine Neukirch, Fadia Dib, Pascale Roland Nicaise, Dan Longrois, Florence Tubach, Sylvie Martin, Pierre Bruhns, NASA Study Group O6 Purpuric drug eruptions due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small-cell lung cancer (NSCLC): a clinic-pathological study of 32 cases Kai-Lung Chen, Shu-Ling Liao, Yi-Shuan Sheen, Yung-Tsu Cho, Che-Wen Yang, Jau-Yu Liau, Chia-Yu Chu Poster presentations: Poster Walk 1—Anaphylaxis (P01–P09) P1 Anaphylactic reactions during anaesthesia and the perioperative period Rita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas, M. A. Pereira-Barbosa P2 Anaphylaxis to chlorhexidine: is there a cross-reactivity to alexidine? Antonia Bünter, Nisha Gupta, Tatjana Pecaric Petkovic, Nicole Wirth, Werner J. Pichler, Oliver Hausmann P3 Cefotaxime-induced severe anaphylaxis in a neonate Mehtap Yazicioglu, Pinar G. Ozdemir, Gokce Ciplak, Ozkan Kaya P4 Clinical features and diagnosis of anaphylaxis resulting from exposure to chlorhexidine Peter John Cooke P5 Drug-induced anaphylaxis: five-year single-center survey Inês Mota, Ângela Gaspar, Filipe Benito-Garcia, Marta Chambel, Mário Morais-Almeida P6 Intraoperative severe anaphylactic reaction due to patent blue v dye Luis Marques, Eva Alcoceba, Silvia Lara P7 Kounis syndrome in the setting of anaphylaxis to diclofenac Leonor Carneiro-Leão, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P8 Perioperative anaphylaxis audit: Royal Melbourne Hospital Katherine Nicholls, William Lay, Olivia Smith, Christine Collins, Gary Unglik, Kymble Spriggs, Priscilla Auyeung, Jeremy McComish, Jo A. Douglass P9 Recurrent peri-operative anaphylaxis: a perfect storm Jonny G. Peter, Paul Potter Poster Walk 2: DH regions and patient groups (P10–P19) P10 A rare presentation of amoxicillin allergy in a young child Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas P11 Adverse drug reactions in children: antibiotics or virus? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P12 Allergic reactions in invasive medical procedures Bárbara Kong Cardoso, Elza Tomaz, Sara Correia, Filipe Inácio P13 Antibiotic allergy in children: room for improvement Annabelle Arnold, Natasha Bear, Kristina Rueter, Grace Gong, Michael O’Sullivan, Saravanan Muthusamy, Valerie Noble, Michaela Lucas P14 Drug hypersensitivity reactions in children and results of diagnostic evaluation Neringa Buterleviciute, Odilija Rudzeviciene P15 Nonimmediate cutaneous drug reactions in children: are skin tests required? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P16 Pediatric patients with a history of penicillin allergy and a positive penicillin skin test may not be at an increased risk for multiple drug allergies Sara May, Thanai Pongdee, Miguel Park P17 Proved hypersensitivity to drugs according data of Vilnius University Hospital Santariskiu Klinikos Linas Griguola, Arturas Vinikovas, Simona Kašinskaite, Violeta Kvedariene P18 Self-reported prevalence of drug hypersensitivity reactions among students in Celal Bayar University, Turkey Ayse Aktas, Suheyla Rahman, Huseyin Elbi, Beyhan Cengiz Ozyurt P19 Severe drug hypersensitivity reactions in pediatric age Ozlem Cavkaytar, Betul Karaatmaca, Pinar Gur Cetinkaya, Saliha Esenboga, Umit M. Sahiner, Bulent E. Sekerel, Ozge Soyer Poster Walk 3: Desensitisation (P20–P28) P20 A protocol for desensitisation to valaciclovir Celia Zubrinich, Bianca Tong, Mittal Patel, Michelle Giles, Robyn O’Hehir, Robert Puy P21 A rare case of desensitization to modafinil Josefina Cernadas, Luís Amaral, Fabrícia Carolino P22 A sixteen-day desensitization protocol in delayed type hypersensitivity reactions to oral drugs Semra Demir, Asli Gelincik, Muge Olgac, Raif Caskun, Derya Unal, Bahauddin Colakoglu, Suna Buyukozturk P23 Desensitization to intravenous etoposide using a 12 and a 13-step protocol. Two cases report Olga Vega Matute, Amalia Bernad, Gabriel Gastaminza, Roselle Madamba, Carlos Lacasa, M. J. Goikoetxea, Carmen D’Amelio, Jose Rifón, Nicolas Martínez, Marta Ferrer P24 Drug desensitisation in oncology: the experience of an immunoallergology department for 5 years Carmelita Ribeiro, Emília Faria, Cristina Frutuoso, Anabela Barros, Rosário Lebre, Alice Pego, Ana Todo Bom P25 Filgrastim anaphylaxis: a successful desensitization protocol Luis Amaral, Josefina Cernadas P26 Galsulfase hypersensitivity and desensitization of a mucopolysaccharidosis VI patient Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Ana Maria Martins, Dirceu Solé P27 Rapid drug desensitization with biologicals: one-center experience with four biologicals Sevim Bavbek, Resat Kendirlinan, Pamir Çerçi, Seda Tutluer, Sadan Soyyigit, Zeynep Çelebi Sözener, Ömür Aydin, Reyhan Gümüsburun P28 Successful desensitization to a high dose of methotrexate in a delayed type hypersensitivity reaction Josefina Cernadas, Leonor Carneiro-Leão, Fabrícia Carolino, Marta Almeida Poster Walk 4: SJS (P29–P38) P29 Assessment of impact of infection on drug-induced severe cutaneous adverse reactions and rhabdomyolysis using the Japanese adverse drug event report database Kimie Sai, Takuya Imatoh, Ryosuke Nakamura, Chisato Fukazawa, Yasushi Hinomura, Yoshiro Saito P30 Characterization of erythema multiforme and severe cutaneous adverse reactions hospitalizations Bernardo Sousa-Pinto, Cláudia Correia, Lídia Gomes, Sara Gil-Mata, Luís Araújo, Luís Delgado P31 Effects of infection on incidence/severity of SJS/TEN and myopathy in Japanese cases analyzed by voluntary case reports Ryosuke Nakamura, Kimie Sai, Takuya Imatoh, Yoshimi Okamoto-Uchida, Koji Kajinami, Kayoko Matsunaga, Michiko Aihara, Yoshiro Saito P32 Efficacy of tumor necrosis factor—a antagonists in Stevens–Johnson syndrome and toxic epidermal necrolysis: a randomized controlled trial and immunosuppressive effects evaluation Chuang-Wei Wang, Shih-Chi Su, Shuen-Iu Hung, Hsin-Chun Ho, Chih-Hsun Yang, Wen-Hung Chung P33 Evolution of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis in Europe: analysis of 10 years RegiSCAR-Study Maren Paulmann, Ariane Dunant, Maja Mockenhaupt, Peggy Sekula, Martin Schumacher, Sylvia Kardaun, Luigi Naldi, Teresa Bellón, Daniel Creamer, Cynthia Haddad, Bruno Sassolas, Bénédicte Lebrun-Vignes, Laurence Valeyrie-Allanore, Jean-Claude Roujeau P34 Long-term sequelae in patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: a 5-year analysis Maren Paulmann, Carmen Kremmler, Peggy Sekula, Laurence Valeyrie-Allanore, Luigi Naldi, Sylvia Kardaun, Maja Mockenhaupt P35 Major emotional complications and decreased health related quality of life among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Anthony Feinstein, Rena Hashimoto, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P36 Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients: treatment and outcome Naoko Takamura, Yumiko Yamane, Setsuko Matsukura, Kazuko Nakamura, Yuko Watanabe, Yukie Yamaguchi, Takeshi Kambara, Zenro Ikezawa, Michiko Aihara P37 Severe physical complications among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Rena Hashimoto, Hall Chew, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P38 Stevens–Johnson syndrome/toxic epidermal necrolysis combined with haemophagocytic lymphohistiocytosis: a case report Brittany Knezevic, Una Nic Ionmhain, Allison Barraclough, Michaela Lucas, Matthew Anstey Poster Walk 5: Other organs/unexpected immune reactions (P39–P47) P39 A case report of patient with anti-tuberculosis drug-related severe liver failure Toru Usui, Xiaoli Meng, John Farrell, Paul Whitaker, John Watson, Neil French, Kevin Park, Dean Naisbitt P40 Acute interstitial nephritis induced by ibuprofen Ana Castro Neves, Susana Cadinha, Ana Moreira, J. P. Moreira Da Silva P41 Cetuximab induced acneiform rash—two case reports Daniela Ledic Drvar, Sandra Jerkovic Gulin, Suzana Ljubojevic Hadzavdic, Romana Ceovic P42 Enteropathy associated with losartan Ana Montoro De Francisco, Talía De Vicente Jiménez, Amelia García Luque, Natalia Rosado David, José Mª Mateos Galván P43 Granuloma annulare after therapy with canakinumab Razvigor Darlenski P44 Hypersensitivity eosinophilic myocarditis or acute coronary syndrome? Case report Dario Gulin, Jozica Sikic, Jasna Cerkez Habek, Sandra Jerkovic Gulin, Edvard Galic P45 Piperacillin-induced immune haemolytic anaemia: a severe and frequent complication of antibiotic treatment in patients with cystic fibrosis Philip Specht, Doris Staab, Beate Mayer, Jobst Roehmel P46 Progesterone triggered pemphigus foliaceus: case report Sandra Jerkovic Gulin, Caius Solovan, Anca Chiriac P47 Ramipril: triggered generalized pustular psoriasis Paola Djurinec, Kresimir Kostovic, Mirna Bradamante, Sandra Jerkovic Gulin, Romana Ceovic Poster Walk 6: NSAIDs (P48–P56) P48 Aspirin desensitization in cardiovascular disease—Portuguese experience Jose Pedro Almeida, Joana Caiado, Elisa Pedro, Pedro Canas Da Silva, Manuel Pereira Barbosa P49 Asthma and/or rhinitis to NSAIDs with good tolerance to ASA Gador Bogas, Natalia Blanca-López, Diana Pérez-Alzate, Inmaculada Doña, José Augusto Agúndez, Elena García-Martín, José Antonio Cornejo-García, Cristobalina Mayorga, María José Torres, Gabriela Canto, Miguel Blanca P50 Clinical characteristics of 196 patients with non-steroidal anti-inflammatory drug (NSAIDs) hypersensitivity Sengül Aksakal, Aytül Zerrin Sin, Zeynep Peker Koç, Fatma Düsünür Günsen, Ömür Ardeniz, Emine Nihal Mete Gökmen, Okan Gülbahar, Ali Kokuludag P51 Development of immediate hypersensitivity to several NSAIDs maintaining good tolerance to ASA Natalia Pérez-Sánchez, Natalia Blanca-López, Diana Pérez-Alzate, Gador Bogas, Inmaculada Doña, María Salas, María José Torres, Miguel Blanca, Gabriela Canto P52 Diagnosis of hypersensitivity reactions to paracetamol in a large series of cases Inmaculada Doña, Maria Salas, Francisca Gomez, Natalia Blanca-Lopez, Diana Perez-Alzate, Gador Bogas, Esther Barrionuevo, Maria Jose Torres, Inmaculada Andreu, Miguel Ángel Miranda, Gabriela Canto, Miguel Blanca P53 Hypersensitivity to paracetamol according to the new classification of hypersensitivity to NSAIDs Gabija Didžiokaite, Olesia Gaidej, Simona Kašinskaite, Violeta Kvedariene P54 Ibuprofen and other aryl propionic derivates can induce immediate selective hypersensitivity responses Diana Perez-Alzate, Natalia Blanca-López, Maria Isabel Garcimartin, Inmaculada Doña, Maria Luisa Somoza, Cristobalina Mayorga, Maria Jose Torres, Gador Bojas, Jose Antonio Cornejo-Garcia, Maria Gabriela Canto, Miguel Blanca P55 Subjects developing immediate responses to several NSAIDs can be selective with good tolerance to ASA Natalia Blanca-Lopez, Diana Pérez-Alzate, Francisco Javier Ruano Perez, Inmaculada Doña, Maria Luisa Somoza, Inmaculada Andreu, Miguel Angel Miranda, Cristobalina Mayorga, Maria Jose Torres, Jose Antonio Cornejo-Garcia, Miguel Blanca, Maria Gabriela Canto P56 Utility of low-dose oral aspirin challenges for diagnosis of aspirin exacerbated respiratory disease Elina Jerschow, Teresa Pelletier, Zhen Ren, Golda Hudes, Marek Sanak, Esperanza Morales, Victor Schuster, Simon D. Spivack, David Rosenstreich Poster Walk 7: NSAID 2 (P57–P65) P57 Alternate regulation of cyclooxygenase-2 (COX-2) MRNA expression may predispose patients to aspirin-induced exacerbations Renato Erzen, Mira Silar, Nissera Bajrovic, Matija Rijavec, Mihaela Zidarn, Peter Korosec P58 Anaphylaxis to diclofenac: what about the underlying mechanism? Leonor Carneiro-Leão, Fabrícia Carolino, Luís Amaral, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P59 COX-2 inhibitors: are they always a safe alternative in hypersensitivity to nonsteroidal anti-inflammatory drugs? Luis Amaral, Fabricia Carolino, Eunice Castro, Josefina Cernadas P60 Management of patients with history of NSAIDs reactions prior to coronary angioplasty Mona Al-Ahmad, Tito Rodriguez P61 Oral drug challenge with non-steroidal anti-inflammatory drug under spirometric control: clinical series of 110 patients João Pedro Azevedo, Emília Faria, Beatriz Tavares, Frederico Regateiro, Ana Todo-Bom P62 Prevalence and incidence of analgesic hypersensitivity reactions in Colombia Pablo Andrés Miranda, Bautista De La Cruz Hoyos P63 Recent endoscopic sinus surgery lessens reactions during aspirin challenge in patients with aspirin exacerbated respiratory disease Teresa Pelletier, Waleed Abuzeid, Nadeem Akbar, Marc Gibber, Marvin Fried, Weiguo Han, Taha Keskin, Robert Tamayev, Golda Hudes, Simon D. Spivack, David Rosenstreich, Elina Jerschow P64 Safe use of imidazole salycilate in a case of multiple NSAIDs induced urticaria-angioedema Elisa Boni, Marina Russello, Marina Mauro P65 Selective hypersensitivity reactions to ibuprofen—seven years experience Marta Ferreira Neto Poster Walk 8: Epidemiological methods (P66–P72) P66 Allopurinol hypersensitivity: a 7-year review Lise Brosseron, Daniela Malheiro, Susana Cadinha, Patrícia Barreira, J. P. Moreira Da Silva P67 Antibiotic allergy labelling is associated with increased hospital readmission rates in Australia Brittany Knezevic, Dustin Sprigg, Michelle Trevenen, Jason Seet, Jason Trubiano, William Smith, Yogesh Jeelall, Sandra Vale, Richard Loh, Andrew Mclean-Tooke, Michaela Lucas P68 Experts’ opinions on severe cutaneous adverse drug reactions-report of a survey from the 9th international congress on cutaneous adverse drug reactions 2015 Roni P. Dodiuk-Gad, Cristina Olteanu, Wen-Hung Chung, Neil H. Shear P69 HLA-A*31-positive AGEP with carbamazepine use and other severe cutaneous adverse drug reactions (SCARs) detected by electronic medical records screening Sabine Müller, Ursula Amstutz, Lukas Jörg, Nikhil Yawalkar, Stephan Krähenbühl P70 Patients with suspected drug allergy: a specific psychological profile? Eunice Dias-Castro, Ana Leblanc, Laura Ribeiro, Josefina R. Cernadas P71 Use of an electronic device and a computerized mathematic algorithm to detect the allergic drug reactions through the analysis of heart rate variability Arantza Vega, Raquel Gutierrez Rivas, Ana Alonso, Juan Maria Beitia, Belén Mateo, Remedios Cárdenas, Juan Jesus Garcia-Dominguez P72 Variation in ERAP influences risk for HLA-B*57:01 positive abacavir hypersensitivity Rebecca Pavlos, Kaija Strautins, Ian James, Simon Mallal, Alec Redwood, Elizabeth Phillips Poster Walk 9: DRESS/AGEP (P73–P81) P73 A clinical case of DRESS syndrome in a child after administration of amoxicillin-clavulanic acid Rita Aguiar, Anabela Lopes, Ana Neves, Maria Do Céu Machado, M. A. Pereira-Barbosa P74 Acute generalized exanthematous pustulosis (AGEP) induced by mesalazine, reliable and oftenly used drug to treat inflammatory bowel disease Ceyda Tunakan Dalgiç, Emine Nihal Mete Gökmen, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Ali Kokuludag, Aytül Zerrin Sin P75 Changes of blood plasmacytoid dendritic cells, myeloid dendritic cells, and basophils during the acute stage of drug reaction with eosinophilia and systemic symptoms (DRESS) and other drug eruptions Shao-Hsuan Hsu, Yung-Tsu Cho, Che-Wen Yang, Kai-Lung Chen, Chia-Yu Chu P76 Characterization of isoniazid/rifampicin-specific t-cell responses in patients with DRESS syndrome Young-Min Ye, Gyu-Young Hur, Hae-Sim Park, Seung-Hyun Kim P77 DRESS syndrome secondary to sulfasalazine with delayed TEN: a case presentation Syed Ali, Michaela Lucas, Peter N. Hollingsworth, Andrew P. C. Mclean-Tooke P78 Drug rash with eosinophilia and systemic symptoms (DRESS) features according to the culprit drug Zohra Chadly, Nadia Ben Fredj, Karim Aouam, Haifa Ben Romdhane, Naceur A. Boughattas, Amel Chaabane P79 Drug reaction with eosinophilia and systemic symptoms induced by allopurinol: not always easy to diagnose Marina Lluncor Salazar, Beatriz Pola, Ana Fiandor, Teresa Bellón, Elena Ramírez, Javier Domínguez Ortega, Santiago Quirce, Rosario Cabañas P80 Drug reaction with eosinophilia and systemic symptoms syndrome induced by two drugs simultaneously: a case report Krasimira Baynova, Marina Labella, Manuel Prados P81 The drug reaction with eosinophilia and systemic symptoms (DRESS) induced by the second-line antituberculosis drugs and Epstein–Barr virus infection Agne Ramonaite, Ieva Bajoriuniene, Brigita Sitkauskiene, Raimundas Sakalauskas Poster Walk 10: Miscellaneous drug hypersensitivity (P82–P91) P82 A case of cycloserine-induced lichenoid drug eruption confirmed with a lymphocatye transformation test Jae-Woo Kwon, Shinyoung Park P83 Allergic reaction to topical eye drops: 5 years’ retrospective study in a drug allergy unit Diana Silva, Leonor Carneiro Leão, Fabricia Carolino, Eunice Castro, Josefina Cernadas P84 Allergy to heparins Diana Perez-Alzate, Natalia Blanca-López, Maria Luisa Somoza Alvarez, Maria Garcimartin, Maria Vazquez De La Torre, Francisco Javier Ruano Pérez, Elisa Haroun, Gabriela Canto Diez P85 Allopurinol-induced adverse drug reactions Katinka Ónodi-Nagy, Ágnes Kinyó, Lajos Kemény, Zsuzsanna Bata-Csörgo P86 Analysis of a population with immediate hypersensitivity to corticosteroids: an 11 year review Joana Sofia Pita, Emília Faria, Rosa Anita Fernandes, Ana Moura, Nuno Sousa, Carmelita Ribeiro, Carlos Loureiro, Ana Todo Bom P87 Anaphylaxis against mivacurium in a 12-months old boy at first-time exposure Wolfgang Pfützner P88 Antihistamine-exacerbated chronic spontaneous urticaria: a paradox? Nadine Marrouche, Clive Grattan P89 Anti-osteoporotic agents-induced cutaneous adverse drug reactions in Asians Yu-En Chen, Chun-Bing Chen, Wen-Hung Chung, Yu-

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old