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-Ping Hsiao, Chia-Yu Chu P90 Diagnosis of allergic reactions to eye drops Maria Vazquez De La Torre, Natalia Blanca-Lopez, Diana Perez-Alzate, Maria Isabel Garcimartin, Francisco Javier Ruano, Maria Luisa Somoza, Elisa Haroun, Gabriela Canto P91 Diagnostic approach in suspected hypersensitivity reactions to corticosteroids Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas

Background: Worldwide, beta-lactam antibiotics can commonly cause hypersensitivity reactions (HR) with various clinical pictures from minor affections like maculopapular exanthema (MPE) and urticaria to severe cutaneous adverse reactions (SCAR) and anaphylaxis. Currently, two different concepts provide rational explanations how a drug can initiate a drug HR by activating human T cells-the hapten concept and the pharmacological interaction with immune receptor (p-i) concept. In this study, we investigated the relationship between the reactivity pattern of drug-reacting T cells found in the peripheral blood of allergic patients and their clinical picture.

Open Access
Clinical and Translational Allergy Background: The Auckland Anaesthetic Allergy Clinic is jointly provided by the Departments of Anaesthesia and Immunology. All patients referred following perioperative anaphylaxis are skin prick tested with chlorhexidine 2 %. This review describes the clinical features of the cases in which a diagnosis of allergic anaphylaxis to chlorhexidine was made during the period January 2012 to December 2015. Materials and methods: Patient data and clinic test results were archived on a simple Excel spreadsheet. These were reviewed by the author and a chart review of the chlorhexidine anaphylaxis cases was undertaken. Results: A total of 14 patients were diagnosed with chlorhexidine allergy during the period (11 male and 3 female). The following manifestations of anaphylaxis were documented: hypotension (12 patients), tachycardia (9), flushing (7), facial swelling (4), urticaria (3), bronchospasm (2), piloerection (2), agitation (1), generalized swelling (1). Four patients had CPR during their anaphylaxis, nine patients had a grade 3 reaction and one patient had a grade 1 reaction. Twelve of the 14 patients received adrenaline. Anaphylaxis followed the insertion of a chlorhexidine impregnated central venous line in seven cases, urethral catheterization with chlorhexidine containing gel in three and following topical exposure only in four cases. Skin testing was performed 30-130 days after the anaphylaxis event. All of the patients diagnosed with chlorhexidine allergy developed a wheal >3 mm after a s prick test with 2 % chlorhexidine (range 3-20 mm). The specific IgE for Chlorhexidine was obtained in 11 of the 14 cases and in 10 of the 11 it was elevated. During the same period 219 other patients were seen at our clinic and all received skin prick tests for chlorhexidine 2 %. All of these patients had completely negative tests with a no wheal and no flare. Conclusions: This data shows that patients with chlorhexidine anaphylaxis demonstrate typical signs but that hypotension is the most common manifestation. Convincing skin testing results along with specific IgE testing and the clinical history provided the basis of the diagnosis. Chlorhexidine is used in our region for skin preparation prior to anaesthetic and surgical procedures and four anaphylaxis cases resulted from topical exposure to chlorhexidine. Our data also suggests that a skin prick test with 2 % chlorhexidine in alcohol is a satisfactory method of skin testing. Keywords: Chlorhexidine; Skin prick testing; Specific IgE; Anaphylaxis Clin Transl Allergy 2016, 6(Suppl 3):31 study was to characterize patients (pts) with DIA and their drug allergy work-up. Materials and methods: Systematic review of all pts with clinical history compatible with DIA reported to our drug allergy center in the last 5 years. All pts were investigated according to ENDA/EAACI recommendations, through skin testing and in vitro tests (whether standardized tests available) and DPT (when indicated). Results: A total of 114 pts were included: mean age 41.5 (SD ± 16.8) years, 10 % <18 years, 68 % female, 72 % atopic and 23 % had asthma. Median age of first anaphylactic episode was 36.5 years [1;74], and 19 pts had recurrent DIA. The main causes were NSAID (50 pts) [acetylsalicylic acid (15), ibuprofen (13), metamizol (13), diclofenac (9), paracetamol (3), etodolac, ketorolac and clonixin (one each)] and AB (46 pts) [BL (37), quinolones (4), macrolides (3), fosfomycin (1) and minocycline (1)]. Other drug agents found: neuromuscular blocking drugs (five pts), proton pump inhibitors (five pts), carboplatin (three pts), corticosteroids (two pts), local anesthetics (two pts), ranitidine, midazolam and patent blue (1pt each). There was a predominance of mucocutaneous manifestations (96 %), followed by respiratory (80 %) and cardiovascular (45 %) symptoms. In 25 % of pts the reaction occurred in hospital setting and 12 % had intraoperative anaphylaxis. DIA was supported in 72 pts (63 %), through skin tests in 62 and the remaining by in vitro tests or DPT. Considering the severity of reactions and the lack of standardized tests for some drugs, patients whose DIA was based on clinical history were successfully challenged with alternative drugs. Conclusions: NSAID and AB were responsible for the majority of DIA. Anaphylactic reactions were reported at any age. The heterogeneity of mechanisms involved, the severity of clinical reactions and the lack of standardized in vivo and/or in vitro tests do not allow to confirm the diagnosis in all cases. Patients with DIA should be evaluated in specialized centers in order to perform accurate diagnosis, to prevent recurrence and to find safe alternatives. Keywords: Anaphylaxis; Drug allergy; NSAID; Antibiotics Background: Intraoperative anaphylactic reactions are a diagnostic challenge. The chronology of the administration of the multiple drugs and the beginning of the reaction are important in identifying the culprit drug. Patent blue V is a well known cause of perioperative anaphylaxis This dye is a member of the triarylmethane family, which also includes isosulfan blue and methylene blue. Is used for staging breast cancer, identifying sentinel lymph nodes. The frequency of reactions is around 0.24-1.1 %. It can be also found in food (food additive E-131) and cosmetics. Report: We describe the case of a woman 65 years-old with a ductal carcinoma of the left breast, who suffered hypotension (85/60), bronchospasm with hypoxemia, urticaria, angioedema of the face, tongue and epiglottis after the administration through the nipple of colorant patent blue V. Anaesthetic induction was done with fentanyl, propofol and rocuronium. Adrenaline, bronchodilators, antihistamines, corticosteroids and vasopressive drugs were administered, being admitted in the ICU. The levels of tryptase were 8.5 µg/ ml 20 min after the beginning of the reaction, 16.6 µg/ml at 2 h and 3.23 µg/ml at 48 h. One month after the reaction cutaneous tests were done, being positive for patent blue V (intradermal reaction at 1/10) and negative for suxamethonium, cis-atracurium, rocuronium, fentanyl, propofol, midazolam, povidone-iodine and latex. It was the first time the patient received this dye or any similar dye as a drug.
Intraoperative anaphylactic shock due to allergy to patent blue V was diagnosed. The future use of this dye was prohibited and an advise to avoid stuff which contains this product was given to the patient. A suspicion of sensitization through foods or cosmetics is possible as the patient reacted the first time she received this drug. How this report contributes to current knowledge: This case confirms previous descriptions of reactions with patent blue V: reaction with the first exposition and severe allergic reactions, with hypotension and raise in tryptase levels. Cutaneous test are useful in the diagnostic and standardized concentrations have been described by ENDA.
Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Kounis Syndrome (KS), the occurrence of acute coronary events as consequence of allergic or hypersensitivity reactions has been described for years. It is still relatively unknown and consequently underdiagnosed, leading to inadequate treatment and subsequent morbidity. There are three subtypes of KS: type I which occurs in patients without predisposing cardiovascular factors; type II which occurs in patients with cardiovascular risk factors; and type III by stent thrombosis. Report: A 55 year old man, a smoker with type II Diabetes, was admitted to our hospital for myocardial infarction (MI) after taking two pills of diclofenac 75 mg for left leg pain. He complained of immediate generalized pruritus, malaise, constrictive radiating chest pain, dyspnea, dizziness and sweating. He was assessed by the mobile medical team on site as being agitated, hypotensive (BP: 96/74 mmHg) and with generalized wheezing on chest auscultation. Aggressive fluid resuscitation, nebulized salbutamol and IV corticosteroids improved his status on route to the ER; he was also treated with acetylsalicylic acid 250 mg and sublingual isosorbide dinitrate 5 mg. Epinephrine was not given. ECG confirmed NSTEMI with an elevated troponin I (0.59 ng/ml). Serum tryptase was not measured. He was admitted to the Coronary ICU and cardiac catheterization showed mild coronary artery disease. He recalled a previous reaction to diclofenac, with immediate generalized pruritus. The patient recovery was uneventful. He was then referred to our Drug Allergy Unit. Oral challenge with meloxicam 15 mg was negative and he was instructed to avoid NSAID's other than meloxicam. How this report contributes to current knowledge: MI in the setting of anaphylaxis is underreported. Clinicians should be aware of this possible complication even in patients without cardiovascular risk factors in order to diagnose and treat it early. Also, the WAO Anaphylaxis guidelines recommend a minimum 4 h observation period after anaphylaxis, 8-10 h if there is respiratory or cardiovascular compromise during the reaction. This allows not only for detection and treatment of biphasic reactions, but also of secondary cardiovascular events.
Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images.
Background: Allergy work-up to identify the causative agent in patients experiencing peri-operative anaphylaxis is challenging. Patients have multiple exposures over a short time period; Paperbased records from remote hospitals are often unavailable to the allergist; and diagnostic testing for many drugs is either unavailable or sub-optimal. Report: A 56-year-old man with debilitating osteoarthritis required hip replacements in order to work. He had no chronic medical co-morbidities, but labeled penicillin allergy following a childhood reaction during prolonged antibiotics for osteomyelitis. He was referred for testing after three operations in a remote private South African hospital. Peri-operative anaphylaxis, confirmed with serial tryptase measurement, occurred in the 1st and 3rd surgeries. Possible offending agents included: propofol, midazolam, bupivacaine, fentanyl, clindamycin and cyclokapron. Apparently, in the uneventful 2nd surgery, the drugs were the same except cyclokapron was omitted. Cleaning agents used were unknown. In vitro specific IgE testing was negative to latex but elevated (5.49 kUA/l) for chlorhexidine; Skin testing was positive with chlorhexidine and intradermal testing generated systemic symptoms and required treatment. CAST ELISA testing was negative to propofol and bupivacaine. Clindamycin in vitro testing was unavailable and in vivo testing is not recommended. The likely offending agent was chlorhexidine, and the patient was anxious to return to work, thus, although each anesthetic chart was not available for detailed review, repeat surgery proceeded. Unfortunately, he experienced recurrent anaphylaxis despite a chlorhexidine free theatre. Several months later the anesthetic charts from all four operations were acquired, and it was clear that an additional offending agent was likely clindamycin. Avoidance of both clindamycin and chlorhexidine resulted in a safe surgery. Subsequent testing allowed the patient to be 'de-labeled' as penicillin allergic. How this report contributes to current knowledge: Dual sensitivity is described in about 2 % of peri-operative anaphylaxis cases. Thus, even if a possible causative agent is identified, it remains mandatory a conduct a detailed review of all anesthetic charts; however, this can pose a major challenge in countries were records remain paper-based. The use of alternative drugs in patients carrying a penicillin allergy label can carry significant morbidity.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Fixed drug eruptions (FDE) are characterized by welldemarcated skin and/or mucosal lesions beginning a few minutes to several hours after drug exposure and that reappear at the exact location on re-exposure to the offending drug. Aminopenicillins are among those drugs most commonly associated with FDE. Non-pigmenting FDE (NPFDE) is an FDE type that leaves no residual pigmentation. Report: The authors report the case of a non-atopic 5 years-old boy, presenting two reproducible episodes of cutaneous lesions (erythematous pruritic plaques) located to the genital area, occurring a few hours after medication with amoxicillin for upper airways infection. The antibiotic was changed to a non-beta-lactam drug with progressive symptoms resolution, leaving no residual skin pigmentation. There was a previous exposure to amoxicillin with tolerance. After the second episode, the child has already been medicated with a second generation cephalosporin (cefaclor) and tolerated this drug. Following the first evaluation in our Allergy Department, the child was assessed in the Drug Allergy Unit. No skin tests (intradermal with late reading) were performed due to age-related constraints. A controlled re-challenge with oral amoxicillin in the age-recommended intake-dose was performed. Five hours after the end of oral challenge, the child began to develop a cutaneous exanthema and returned to the hospital for medical assessment as it was recommended. On physical examination, we observed swelling and erythematous plaques affecting the inferior part of penis, the scrotum and the perianal region; the child's mother confirmed that the lesions presented the same location as that of the two previous episodes. Taking these findings into account, the final diagnosis was multiple fixed drug eruption. The child was treated with oral antihistamine and corticosteroid, with complete resolution in 3 days. How this report contributes to current knowledge: To the authors' knowledge, this is the third case reported of this type of drug eruption in the paediatric age.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images.
Background: Surgery associated allergic reactions have been extensively studied and culprit agents have been pointed on several reports. Nevertheless last decade changes in pharmacological protocols resulted in the increase of possible implicated drugs. In the other hand, other invasive procedures (diagnostic/therapeutic) have been increasing in frequency and are also related to allergic events. Our aim was to seek for new agents involved in perioperative allergy as well as characterize reactions occurring due to other invasive procedures Materials and methods: We reviewed the medical records of 28 patients referred to our clinic for allergic reaction associated to an invasive procedure in the last 2 years regarding administered drugs, type of reaction and results of the allergological workup. Results: In our study group, 21 were female and 7 male, mean age was 54.7 years (2-84).
Fourteen were studied for procedures with general anesthesia related adverse events: six anaphylatic reactions, six urticaria/angioedema, one bronchospasm and one hypotension. Positive relevant results were obtained in 13 patients: one skin prick test (SPT) to metamizol, two intradermal skin tests (IDT) to midazolam, one to tramadol, three to ondansetron, one to rocuronium, one to atracurium, two to vecuronium, two to metamizol, one basophil activation test (BAT) to metamizol. One patient was positive to both to atracurium and vecuronium and one patient had no positive tests. In nine patients reactions were associated to invasive procedures with local anesthesia. Positive results were one IDT and BAT to verapamil (anaphylaxis) and one patch test to iodixanol (maculopapular rash) in two patients submitted to coronary angiography. Six patients with adverse reactions during dental treatment and one during a carpal tunnel surgery had no positive tests. Five patients had been submitted to procedures without use of any anesthetic: one with local erythema after an esteroid intra-articular infiltration had a positive patch test to betamethasone dipropionate; one with an anaphylactic reaction during a colonoscopy had a positive BAT to metamizol used as analgesic; one with acute urticaria after contrast injection for a thyroid TC had IDT positive to iomeprol. Two patients had a negative workup. Conclusions: Comparing to previous published series ondansetron seems to be emerging as an important agent in perioperative allergy. Invasive procedures other than major surgeries are associated to allergic reactions both immediate and non-immediate, some of them being severe. Keywords: Perioperative allergy; Invasive medical procedures; Drug hypersensitivity Background: Beta-lactam antibiotics remain one of the most effective treatments of bacterial infections and are the most frequently prescribed antibiotic in children. Allergic reactions to these antibiotics are common. Nevertheless, strategies for peadiatric antibiotic allergy testing and management remain poorly defined, including issues around the need for skin testing prior to oral provocation challenges (OPC; 2-dose) and the value of prolonged courses with the culprit antibiotic after the successful administration of an initial supervised dose. Materials and methods: To address these issues, we performed a retrospective cross-sectional analysis of children (6 months-16 years) with an antibiotic allergy label who presented to a tertiary pediatric hospital in Western Australia from 2006 to 2015. Data collection included results of skin prick (SPT), intradermal testing (IDT) and OPCs, outcome of 5-day antibiotic courses, type of initial reaction, confounding illnesses and co-existing allergies. The data was analysed using Mann-Whitney U for continuous data and Fishers exact test for categorical data. Results: We performed 207 beta lactam antibiotic tests in 172 children. In 82 (39.6 %) cases OPCs were performed without preceding Clin Transl Allergy 2016, 6(Suppl 3):31 skin testing (Group 1); three OPCs (3.7 %) were unsuccessful with one child with anaphylaxis. In 125 (60.4 %) cases skin testing was performed (Group 2). Of these, 22 cases (17.6 %) were positive by SPT or IDT; these children were deemed to have confirmed antibiotic allergy. The remaining 103 cases proceeded to OPC; 4 (3.8 %) reacted to OPC, including two children with anaphylaxis. Finally, 152 cases (from Group 1 or 2) received a 5 day course with the culprit antibiotic. This resulted in a rash in nine children (5.9 %) during the course. In both groups confounding illnesses, initial reaction, gender and co-existing allergies did not predict testing outcome. Conclusions: In our cohort, the rate of allergy confirmed by skin testing was significantly higher than for those who underwent a direct challenge (17.6 vs. 3.7 %). The rate of reactivity to OPC was comparable for Group 1 and 2. These data further supports that performing direct supervised OPC with the culprit drug in children may be safe and potentially may avoid the need for resource intensive skin testing. Extended courses with the culprit drug should be considered, allowing confirmation of non-immediate reactions such as cutaneous reactions. Keywords: Allergy; Antibiotic; Anaphylaxis Background: Patients or parents reported drug allergy in children is more common than the true drug allergy incidence. The aim of our study was to evaluate the clinical pattern of patient/parent reported drug hypersensitivity reactions and results of diagnostic evaluation. Materials and methods: 15 children who were tested for drug allergy in 2015 were included in the study: eight boys (53.3 %) and seven girls (46.7 %), age range 1-15 years. We analysed causes, clinical pattern of reported drug hypersensitivity reactions and results of diagnostic evaluation. Results: 26 drug hypersensitivity reactions were reported. Three drug hypersensitivity reactions were reported in four children, two reactions-in three children. The main suspected drugs were antibiotics 17 (65.4 %), NSAIDs-5 (19.2 %) cases, local anaesthetics-4 (15.4 %) cases. Amoxicillin was the most frequently suspected drug (six (23.1 %) cases). 8 (30.8 %) reactions appeared during 1 h. Skin symptoms were reported in 24 (92.3 %) cases: maculopapular rash-20 (76.9 %), angioedema-5 (19.2 %) cases. Respiratory and cardiovascular symptoms were reported in two cases (7.7 %). Drug provocation test was positive only for one child, who experienced angioedema after nimesulide and ibuprofen intake, and drug provocation test was positive to ibuprofen. Conclusions: The most common suspected drugs were antibiotics, especially amoxicillin. Skin was the most frequently affected and maculopapular rash was the most common symptom. Drug provocation test was positive only for one patient. Background: Delayed urticaria and maculopapular eruptions associated with antibiotics are the most common reasons for referral to our pediatric drug allergy clinic. In this context, several studies point to the limited usefulness of skin tests, even to b-lactam antibiotics, with some authors advocating the use of drug provocation test without the need for other previous diagnostic procedures. Our aim was to describe the cases followed in our department in which this diagnostic approach was used (exclusive drug provocation test). Materials and methods: Retrospective analysis of medical records from children referred to our drug allergy clinic due to suspected hypersensitivity to antibiotics, who reported nonimmediate cutaneous reactions (urticaria or maculopapular eruption) without signs of severity or systemic involvement. All children underwent provocation test with the suspected drug without conducting previous skin tests. The drug provocation test was extended to include the number of days of treatment reported at index reaction. Data was collected regarding gender of patients, age at the drug reaction, drug involved, symptoms reported on the reaction and results of the drug provocation test. Results: We evaluated 213 children of which 50 % (n = 107) were male, with a median age of 3 years (6 months-17 years) at the time of reaction. In 97 % (n = 206) of the cases the involved antibiotics were b-lactam (amoxicillin-clavulanic acid in 92 patients, amoxicillin in 89 and cephalosporins in five cases). Only three children had positive drug provocations tests. In all cases the symptoms were similar to those previously reported and easily controlled with oral antihistamine. Conclusions: Performing an exclusive drug provocation test in children with suspected hypersensitivity to antibiotics, who present with nonimmediate cutaneous reactions without signs of severity, proved to be a safe and effective approach. Background: Patients with a sulfonamide allergy or penicillins (PCN) may be at increased risk for reactions to other drugs. However, the studies were conducted in adults without PCN skin testing (PST) to confirm a PCN allergy. We conducted a study to determine if pediatric patients with a history of PCN allergy and a positive PST were at an increased risk for multiple drug allergies. Materials and methods: Children (<18 years) with a history of PCN allergy were evaluated with PST and reviewed for basic demographic, PST results, and other medication allergies listed in the allergy module in the electronic medical record. A univariate logistic regression analysis was employed to calculate the odds ratio (OR) and the 95 % confidence interval (CI). P value of 0.05 or less was considered statistically significant. The Institutional Review Board (IRB) approved the study. Results: 778 children underwent penicillin skin test. 703 (90.4 %) of 778 patients had a negative PST, 66 (8.5 %) were positive, and 9 (1.1 %) were equivocal. The overall mean ± standard deviation (SD) age of the study group was 5 ± 3.5 years. Three hundred and sixty-seven (47.1 %) were females. 703 children (90.4 %) had a negative PST, 66 patients (8.5 %) positive PST, and 9 (1.1 %) equivocal PST. 181 (23 %) of 778 patients reported a history of multiple drug allergies. Among the 181 patients reporting a history of multiple drug allergies, 81 (45 %) were female and 100 (55 %) were male. Males were 1.6 times (95 % CI 0.8-1.6, p = 0.5) more likely than females to report multiple drug allergies, although not statistically significant. 14 (21 %) of 66 patients with a positive PST reported multiple drug allergies compared to 167 (23 %) of 712 (p = 0.76) patients with a negative PST. Those patients with multiple drug allergies and a history of PCN allergy, cephalosporin [15 % (114 of 778)] was the most common medication listed in the allergy module. Other medication listed in the medication allergy modules were 10 % (79) macrolide antibiotics, 9 % (71) sulfonamides, 0.4 % (3) quinolones, and 1 % (9) nonsteroidal anti-inflammatory drugs (NSAIDS).
Background: Drug hypersensitivity reactions (DHR) is defined "unwanted and harmful reactions occurring to drugs prescribed dose" by World Health Organization (WHO). DHR is an important health problem because of causing life-threatening condition, extending the length of stay in hospital and increasing the cost of treatment. The aim of this study was to determine the prevalence of self-reported DHR among students at the university. Materials and methods: A structured questionnaire was carried out to students of Celal Bayar University in Manisa, Turkey. Results: 2086 students have participated in our study. 1217 (58.3 %) of them were women, 869 (41.7 %) were male. The mean prevalance of self-reported DHR was 5.3 % (111/2086). Drug allergy incidence of students (male/female) was 3.5 and 6.7 %, respectively (p < 0.001). The most common allergic reactions were rash 52.2 %, cardiovascular reactions 12.6 % and respiratory reactions 11.7 %. Aforementioned two systems involvement were 23.4 %. The most frequently involved drugs were antibiotics 52.2 % (n: 58) and analgesics 24.3 % (n: 27). Conclusions: The diagnosis of drug allergy is based on a detailed history of the onset of symptoms/signs' relationship between the appearance of symptoms and drug use. Misinterpretations just based on the DHR story can effect the individual treatment options. A definitive diagnosis can be easily reachable with a complete clinical history, standardized skin tests and drug provocation tests. Therefore we can recommend that doctors should be more informed about the managements of DHR due to self-reported DHR is highly prevalant just like shown in this study. Keywords: Drug hypersensitivity; Prevalence Background: Epidemiologic data on drug induced anaphylaxis (DIA) in pediatric age is lacking. The aim of this study is to define the actual rate of drug induced anaphylactic reactions in childhood together with the severity and culprit drug patterns. Materials and methods: Patients with a history of drug hypersensitivity reaction (DHR) referred between January 2012-December 2015 were included. After filling out an European Network for Drug Allergy (ENDA) questionnaire, initial skin tests and/or provocation tests were performed for the offending drug. The severity of anaphylactic reactions was determined as mild, moderate and severe according to EAACI guidelines on anaphylaxis in childhood. Results: Among 627 children and adolescents referred due to a DHR, diagnostic work-up was completed in 532 patients. 103 (19.3 %) of them [54.4 % male, median age (interquartile range; 9.6 years (5.3-13.3)] had anaphylaxis in the history and diagnostic tests revealed that 75 (14.1 % of all evaluated patients, 72.8 % of all patients with a DIA) of them were actually hypersensitive to the offending drug. The culprit drugs responsible from actual DIA were antibiotics (36 %), NSAIDs (22.7 %), chemotherapeutics (20 %), biologicals (6.7), anesthetic agents (5.3 %), enzyme therapy (4 %) and others. Majority of the patients with actual DIA reported moderate (38.7 %) and severe (37.3 %) drug induced anaphylactic reactions. History of chronic disease (44 vs. 17.9 %, p = 0.014), concomitant intake of other drugs regularly (40 vs. 7.1 %, p = 0.001), cyanosis (23 vs. 3.6 %, p = 0.022) and hospitalization (56.2 vs. 17.9, p = 0.001) due to the suspected DIA and use of chemotherapeutics as the culprit drug (20 vs. 0 %, p = 0.01) were more frequent, whereas use of antibiotics was less frequent (71.4 vs. 36 %, p = 0.001) in patients with actual DIA compared to nonhypersensitive patients. Atopic disease, atopy or family history of atopy or drug hypersensitivity did not have an impact on actual DIA. It is important to note that actual DIA was more frequent in children younger than 10 years of age compared to older adolescents (81.5 vs. 63.3 %, p = 0.038). Conclusions: During childhood, any history of DIA reaction may not be an actual DHR, however young age, existence of chronic Background: We report a protocol for desensitisation to valaciclovir. Report: A woman in her 40 s developed generalised urticaria on the second or third day of her initial course of acyclovir (administered five times daily) for newly diagnosed genital herpes. The urticaria continued to cause distress despite substitution to valaciclovir for a further few days. Antiviral medication was ceased. The rash resolved over 2 weeks with the use of anti-histamines. For more than a decade since then, she has experienced frequent and prolonged confirmed herpetic recurrences, more often present than not. The attacks had a marked viral prodrome and significantly affected her lifestyle. Recurrent genital herpes may be treated with suppressive antiviral therapy if frequent. Supervised direct challenge to valaciclovir was an option but desensitisation was favoured because it required a single clinic visit and, of relevance to the patient, likely entailed less risk. We identified reports of desensitisation to acyclovir but not valaciclovir. The final treatment dose of acyclovir (usually 400 mg) differs from that of valaciclovir (500 mg). Acyclovir therapy requires multiple doses per day, whereas valaciclovir requires only a single daily dose. We developed and present a 14-dose oral desensitisation protocol that was administered over 3.5 h (Fig. 1). The first 10 doses were valaciclovir in suspension and the final four doses were prepared from a 500 mg tablet. The patient tolerated the procedure with no ill effect. There has not been a single herpetic recurrence in the 12 months since the treatment commenced. How this report contributes to current knowledge: Desensitisation to valaciclovir may be performed where suppressive therapy for herpes is indicated.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Modafinil is a 2-benzhydrylsulfinylethanamide molecule, belonging to a class of medications called wakefulness promoting agents used to treat excessive sleepiness caused by narcolepsy (a condition that causes excessive daytime sleepiness) or shift work sleep disorder. Another use is to prevent excessive sleepiness caused by obstructive sleep apnea/hypopnea syndrome. It acts as a blocker of a type of molecule called the dopamine transporter. Rare occurrences including severe cutaneous adverse reactions, as erythema multiforme, SJS, TEN and DRESS, affecting adults and children and probably allergic, have been reported. Rare cases of angioedema and multiorgan hypersensitivity reactions have also been described. Report: The authors describe a case of a 27 year-old male with the diagnosis of narcolepsy medicated with modafinil 100 mg in an increasing dosage. Four days after beginning the medication, he complained of generalized pruritus, maculopapular exanthema and angioedema of upper and lower limbs. No analytical changes were found in the acute phase. He was treated with intravenous corticosteroid and antihistamines and, 4 days after complete recovery, the drug was re-introduced with reproducible signs and symptoms arising 12 h after the intake of 100 mg of modafinil. Because this was the only therapeutic option for the patient he was referred to our Allergy Department for desensitization. A suspension of 1 mg/ml (100 mg/100 ml) was prepared and a "tailor made" desensitization protocol was started with an initial dose of 1 mg, followed by doubling doses, taken with 1 h intervals. The cumulative dose reached on the first day was 15 mg, 85 mg on the second and 100 mg on the third and fourth days. For safety reasons, 100 mg/day were taken in the first week followed by an increase, to the intended doses (Neurology prescription) in the following weeks: 100 + 100 mg on the second week, 100 + 200 mg on the third week and 200 + 200 mg on the fourth and on, as chronic treatment. After we have achieved tolerance to a dose of 100 mg, the slowly increase to the targeted dose of 200 mg twice a day was well tolerated. The patient is still on the same therapeutic scheme with no further reactions. How this report contributes to current knowledge: As far as we know this is the first case describing a desensitization protocol to modafinil.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Although desensitization in immediate type hypersensitivity reactions due to chemotherapeutics is well described and standardized for many drugs, common protocols in delayed type hypersensitivity reactions (DHR) are not standardized. Our aim is to evaluate the usefulness of the 16-day desensitization protocol which we had recently described for capasitabine in DHRs caused by various oral chemotherapeutic drugs. Materials and methods: We applied our slow desensitization protocol which started with 1/100 of the target dose and was completed in 16 days with slow incremental doses in patients who had experienced DHR due to various oral chemotherapeutic drugs. Results: Four patients (two female, two male) who were referred to our clinic for desensitization were included. The mean age was 55 ± 22.25 years. The culprit drugs were pazopanib, nilotinib and lenalidomide. The mean reaction time after the initiation of the drug was 7.5 ± 2.08 days and the reaction types were maculopapular rush (MPR) in two patients and generalized morbiliform rushes (GMR) in two patients. Two patients who had experienced MPR caused by lenalidomide completed the protocols without any reactions. However, the other two patients developed pruritus and rush on the 9th and the 15th days of the desensitization protocols. After the reactions were treated with methylprednisolone, the doses were decreased to the last tolerated doses and gradually increased afterwards. One of them completed the desensitization in 28 days. However, the second patient could tolerate almost the ¾ of the targeted dose. Conclusions: This sixteen-day protocol seems to be a useful guide for the desensitization in delayed type hypersensitivity reactions especially in MPR in oral chemotherapeutics. However, the protocol can be modified in some patients. Keywords: Delayed type hypersensitivity reactions; Desensitization Background: Etoposide is a chemotherapy agent used to treat malignant conditions. Because of the repeated use of this drug in within time intervals for cancer treatment, there is a high chance as with any chemotherapeutic agent to induce hypersensitivity reactions (HSR). It is reported to induce HSR in 6 % of the patients. Report: We present two cases. First is a 7 year old female patient with acute myeloid leukemia (AML). She had previously received two courses of treatment with etoposide. In the second course, with the first administration she had a reaction consisted with facial erythema and severe dyspnea. When evaluated in our hospital, she needed treatment with etoposide for autologous stem-cell transplantation. The second patient was an 8 year old male with refractory acute lymphoid leukemia (ALL-B) that had received six doses of treatment with etoposide. In the last dose, he reported pharyngeal obstruction and chest erythema. When evaluated in our hospital, he needed salvage chemotherapy containing etoposide followed by allogenic stem-cell transplantation. We performed skin prick test with Etoposide, using commercially available drug solution for intravenous use. In both patients the test was negative. Because Etoposide was the most suitable chemotherapeutic option for both patients, we decided to administer the drug using a desensitization protocol. Castells (2) developed a protocol for desensitization to drugs with a 12 steps infusion of the target dose. In the first case we had to add one step to this protocol because of the dose needed. She received premedication treatment and 400 mg of Etoposide in a 13 steps protocol, twice in consecutive days. She had no HSR, the transplantation went well and she is now in complete remission. In the second patient we followed the 12 step protocol with premedication treatment and the patient was able to receive the target dose (150 mg). We did three desensitization protocols with the total dose, in three consecutive days. He had no HSR and he continues in follow up in our hospital. How this report contributes to current knowledge: Patients with HSR to etoposide, in which this drug is the most adequate chemotherapeutic option for such a severe disease, the desensitization protocol is a treatment that proved to be effective in order to administer the treatment.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Any cancer drug can potentially trigger a hypersensitivity reaction (HSR), particularly chemotherapy agents and monoclonal antibodies. The more frequent drugs inducing HSR are the platins (IgE-mediated reactions) and taxanes (non-immunological reactions). Desensitisation protocols must be considered when there is no valid and effective alternative treatment. This is especially relevant for cancer patients who are thus able to continue their first line treatment. The aim was to describe the experience of an Immunoallergology Department with desensitization to chemotherapy agents. Materials and methods: Retrospective review of charts of oncology patients desensitized in the Immunoallergology Department of CHUC in the last 5 years. Results: There were a total of 72 desensitisation procedures corresponding to 15 patients treated (11 female) during the period in question, with a mean age of 56 years (range 28-73 years). The patients had ovarian cancer (eight patients), lung cancer (three patients), colon cancer (2), rectal cancer (1) and breast cancer (1). The HSR were all with moderate to severe immediate reactions: rash, urticaria, laryngeal stridor, bronchospasm, syncope and anaphylaxis (six patients). Eleven patients were desensitized to platins (carboplatin n = 6, cisplatin = 3, oxaliplatin n = 2), three to taxanes (docetaxel n = 2, nabpaclitaxel n = 1) and one to monoclonal antibodies (panitumumab). In the total of 72 desensitisation procedures, the range of desensitisation procedures for patient was 17 (maximum) to 2 (minimum) treatmens with carboplatin. There were five desensitisation procedures in 2011, 12 in 2012, 19 in 2013, 18 in 2014 and also in 2015. In the 72 desensitisation did not have any reaction in 59 procedures (82 %) and in the others, the reactions were milder than the initial HSR (only one patient had anaphylaxis in the third desensitization with cisplatin). All patients received their daily programmed dose. Five patients discontinued the desensitization programme (three patients due to progression of the oncological disease, one patient due to neurological toxicity and another for anaphylaxis during de desensitization). Conclusions: In the majority of patients, desensitization procedures allowed safe reBackground of chemotherapy agents in Immunoallergology centers with experience. This approach must be considered by Oncologic doctors in the treatment of specific oncologic patients with previous history of HSR to these drugs. Keywords: Drug desensitisation; Oncology; Chemotherapy agents; Platins; Taxanes Background: Filgrastim is a recombinant human granulocyte colonystimulating factor (G-CSF) and is used to prevent or treat neutropenia that is generally associated with chemotherapy. Anaphylatic reactions to filgrastim are rarely reported and there is only one published successful desensitization protocol in a patient with immediate hypersensitivity to filgrastim. Report: We describe a case of a 47-year-old woman with ductal breast carcinoma receiving chemotherapy with doxorubicin, cyclophosphamide and docetaxel. She developed chemotherapy induced neutropenia for which she was started on SC filgrastim [300 mcg] days after the chemotherapy cycle, given once a day, for four consecutive days. Ten minutes after the 4th dose of filgrastim, she developed facial erythema, labial angioedema, dyspnea and colicky abdominal pain. These symptoms quickly reversed spontaneously in 48 h. Subsequently, filgrastim was withdrawn and anaphylaxis work-up was done. A 5-step desensitization protocol was performed using sequential doses intravenously: 15, 30, 60, 80, 115 to a cumulative dose of 300 mcg diluted in 20 ml of saline over approximately 3 h. In the following day she received 300 mcg in two steps with success and in 3rd day in one without any reaction. How this report contributes to current knowledge: In summary, we present a successful desensitization protocol for filgrastim in a patient with a previous life-threatening immediate hypersensitivity reaction.
Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Mucopolysaccharidosis VI or Maroteaux-Lamy Syndrome (MPS VI) is a lysosomal storage disorder caused by deficiency of arylsulfatase B. The enzyme replacement therapy (ERT) with galsulfase is so far the only specific treatment for MPS VI. Infusion-related reactions (IRR) to ERT can occur and can be severe, precluding further ERT. However, the interruption of ERT can accelerate the disease progression and precipitate earlier death. The aim of this study is to report IRR to galsulfase in a MPS VI Brazilian patient, and his treatment reestablishiment after desensitization. Materials and methods: a 7 year-old male started presenting symptoms such as dyspnea and itch during his 44th infusion. No improvement was observed with premedication (corticosteroids and antihistamines) in the folowing infusion. ERT were stopped for 4 weeks and the patient underwent skin tests (prick and intradermal). Skin prick test was performed using the straight concentration of galsulfase and Intradermal tests with progressive dilutions. Skin tests were also performed in 10 healthy subjects and in a MPS VI patient without IRR, to rule out a skin irritant effect, since skin tests with galsulfase have not been standardized. Results: Patient presented a positive skin prick test, suggesting an IgE-mediated reaction. Therefore, a rapid desensitization protocol was generated. Three solutions (each 250 ml 0.9 % sodium chloride-1:100, 1:10 and 1:1 respectively) were delivered in 12 consecutive steps at an increasing infusion rate. Pre-medications were used to block different allergy pathways. This protocol has succeeded for 6 months, when during the 22th infusion he started to present wheals in the beginning of the third bag. A new protocol was developed (four bags-16 steps), but the patient still had symptoms. A 75 mg omalizumab (Omab) monthly was introduced. Ten days after the Omab, a new infusion using the same desensitization protocol was performed with no reaction. Conclusions: To our knowledge, we are the first group to use an adapted 12-step desensitization protocol to galsufase with omalizumab. The protocol has shown to be safe and effective for the patient receiving the enzyme in the recommended dose. Management of these reactions with desensitization can provide first line therapy and permit continued ERT. Keywords: Omalizumab; Desensitization Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Rapid drug desensitization (RDD) induces a temporary tolerance to biological drugs inducing hypersensitivity reactions (HSRs) but data are limited regarding use of this outside of the USA. Therefore in this study we aimed to report our data with RDD to rituximab, infliximab, cetuximab and trastuzumab. Materials and methods: The study was conducted as a retrospective chart review of patients with symptoms of HSRs to biological agents to which RDD have been performed between January 2012 and January 2016. HSRs were classified as Grade I, II and III based on their severity. Skin prick/intradermal tests were performed with implicated biologicals. The 12-step RDD protocol developed at Brigham and Women Hospital was used Results: Study group consisted of 11 female and four men (mean age: 54, 21 ± 11 years). Majority of the study subjects (66.6 %) were using the biological agents for the treatment of malign diseases. Twelve subjects had experienced HSR to rituximab, three had HSR to cetuximab, infliximab and trastuzumab respectively. HSR to cetuximab, infliximab and trastuzumab occurred during first infusion and all were Grade III, 11 of 12 subjects with rituximab hypersensitivity had reaction during first infusion, nine had Grade II and three had Grade III. Of the 15 patients, 86.6 % had respiratory symptoms, 66.6 % had cardiovascular, 60 % had cutaneous symptoms, and 40 % had gastrointestinal symptoms. Skin tests with rituximab were done on eight patients, only three resulted in positive in 1/100 dilutions of intradermal tests, and skin tests were negative on either prick or intradermal tests with other biologicals. Of 88 RDD, 81 desensitizations with rituximab, five desensitizations with cetuximab, and one desensitization with infliximab and one desensitization with trastuzumab were done. There were nine breakthrough reactions (10.1 %) in seven subjects, which were all associated with rituximab and less severe than initial reactions. Of breakthrough reactions, 55.5 % were cutaneous, followed by cardiovascular (33 %), respiratory (22.2 %), and gastrointestinal (11.1 %) symptoms. Reactions mainly occurred at step 12, and all were successfully under-controlled and except single desensitization, all desensitization procedures were completed with full target dose. Conclusions: We found RDD is safe and effective, to our knowledge, in the largest series of biological including Rituximab in our country. Background: Delayed type hypersensitivity reactions are mediated by cells rather than by antibodies. They can be life-threatening and classically constitute a contraindication to desensitization (DZT). However, in selected cases of uncomplicated exanthemas, when the culprit drug is irreplaceable or more effective, this option might be considered. Methotrexate (MTX) is a folic acid antagonist with a major role in the treatment of B cell acute lymphoblastic leukemia (ALL). The authors describe a successful DZT to a high dose of IV MTX associated to inthrathecal administration, following a delayed-type hypersensitivity reaction. Report: We report a case of a 12 year old boy under B cell ALL treatment. He was scheduled to receive four cycles of MTX 8000 mg IV perfusion over 24 h (10 % on the 1st hour, 90 % over the remaining 23 h, with a constant concentration), followed by inthrathecal administration of MTX 12 mg, cytarabine 30 mg and prednisolone 10 mg. He complained of an intensely pruritic morbilliform exanthema in his abdomen arising 72 h after completion of the first treatment. The rash resolved with anti histamines and oral and topic corticosteroids, over a period of 10 days with severe residual hyperpigmentation. No renal or liver function analytical changes were found during this episode. Because no alternative treatment was available for his specific type of leukemia, a decision to perform DZT was made. The patient (60 kg) was pretreated with montelukaste 10 mg, starting 2 days before chemotherapy (QT); prednisolone 60 mg was started the day before QT and maintained over 4 days in decreasing doses. He was admitted and a 14 step DZT protocol to MTX was performed. The doses administered were doubled in each step until the 14th step, with a cumulative dose of 1671 mg of MTX infused over a period of 4.5 h. The remaining dose, until the target dose of 8000 mg was infused at a small rate during 24.5 h. This procedure was followed by triple inthrathecal treatment, including MTX. The patient was able to reach the target dose without any reaction. He has now completed 3 of the 4 scheduled cycles. How this report contributes to current knowledge: To our knowledge this is the first description of a successful DZT to such a high dose of MTX in a delayed type reaction. The IV DZT protocol also made Clin Transl Allergy 2016, 6(Suppl 3):31 recruited patients. Using the case report data, we analyzed rates for concomitant infectious disease (tuberculosis, hepatitis, AIDS, influenza infection, and herpes simplex infection, etc.), and compared the severity (severe phenotypes or outcomes) and the mean period to onset of the ADRs between patients with and without infectios diseases. Results: For SJS/TEN cases, the rate of infectious diseases was 51 %, of which 31 % was the cases caused by a primary suspected drug. The rates of severe phenotype TEN, ocular involvement and permanent damage were significantly higher (p < 0.05) and the mean period of onset of SJS/TEN was significantly shorter in the infectious patients' group compared with non-infectious group. The rate of infectious diseases in myopathy was 23 %, of which 12 % was the cases caused by a primary suspected drug. The rates of severe phenotype and permanent damage were higher and the mean period of onset of myopathy was shorter in the myopathy patients with infectious disease than those without infection, although these differences were not statistically significant. Conclusions: This study indicated that the incidence and the severity of SJS/TEN and myopathy are associated with the concomitant infectious disease, especially in the cases of SJS/TEN, which might reflect a greater contribution of immune system as a mechanism of occurrence.
Background: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is rare, but the most severe of all adverse drug reactions due to a high mortality, which is almost 50 % in TEN. Good evaluation of risk factors is essential for efficient pharmacovigilance. Materials and methods: From January 2003 to December 2012 the international Registry of Severe Cutaneous Adverse Reactions (RegiS-CAR) included 1096 cases of SJS/TEN collected in seven countries (France, Germany, Israel, Italy, Netherlands, Spain, United Kingdom). The diagnoses and dates of onset were validated by an expert group, blinded for any information on exposures. Causality was established by using the specific algorithm ALDEN that had previously shown a good correlation with the results of a case-control analysis in an earlier systematic collection of several hundred cases. Results: In terms of overall causality assessment, at least one medication was evaluated as the «probable» or «very probable» cause in 744/1096 cases (68 %). A medication cause was determined as «possible» in 209 cases (19 %), as «unlikely» in 68 cases (6.2 %) and "very unlikely" in 57 cases (5.2 %). 18 patients (1.6 %) denied any exposure to medications. The five medications most often incriminated («probable» or «very probable» causality) were allopurinol (n = 187; 17 %), sulfamethoxazole (n = 80), lamotrigine (n = 76), carbamazepine (n = 51), phenytoin (n = 42). There were substantial differences between reactions developing among hospitalized and community patients, e.g. older age, exposure to a substantially higher number of drugs and a noticeable role for metamizole among inhospital cases in Germany. In both groups (inhospital and community cases) we identified a signal for proton pump inhibitors. Conclusions: In spite of prior warnings in medical journals and towards regulatory agencies, allopurinol is still the principal cause of SJS/TEN in Europe, as it was 10 years ago. Off-label prescription of allopurinol for asymptomatic hyperuricemia has not decreased. Sulfamethoxazole and other anti-infective sulfonamides are still frequent inducers of SJS/TEN. Lamotrigine is now the third cause and the first one among antiepileptic drugs, independent of new indications such as bipolar disorder. Finally, it is important to note that at least 13 % of SJS/TEN-cases have no drug cause. Investigation of other possible causes of such «idiopathic cases», e.g. infections, should be a priority. Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but severe reactions with blisters and erosions of skin and mucosae. Most often SJS/TEN is induced by drugs, less frequently by infections, whereas some cases are "idiopathic". Severity is determined by skin detachment related to the body surface area (BSA): SJS < 10 %, TEN >30 %, and SJS/TEN-overlap 10-30 % of BSA. The high mortality rate is due to severity as well as age of the patient. Survivors frequently suffer from long-term sequelae, particularly of the mucosae. Materials and methods: In order to evaluate frequency and extent of late sequelae in patients with SJS/TEN, a cohort study was performed. Patients with a validated diagnosis of SJS/TEN, who were included in the international Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) between 2003 and 2007, were asked to answer a follow-up questionnaire. Results: 112/233 completed follow-up questionnaires could be analyzed. 62 patients were diagnosed with SJS, 35 with SJS/TEN-overlap, and 15 with TEN. The mean age is 44 years, and approx. 60 % are women. More than 90 % of the patients suffer from sequelae after 5 years, while the percentage increases with severity of the reaction. Less than 50 % were able to completely return to their normal daily activities. Sequelae mainly affect skin (73 %), mucosa (57 %) and nails (52 %). Chronic sequelae of the eyes (67 %) are the main issue for the patients. They include increased photosensitivity, dry eyes, ingrowing eyelashes (trichiasis), excessive watery eyes (epiphora), inflammatory cicatrization up to blindness. Furthermore, patients describe sleep disturbances and nightmares (29 %). In addition, they are afraid of drug use (65 %), and 56 % of the patients avoid taking drugs, which may have a negative impact on their health. Although many patients consider professional psychological support helpful (54 %), only 9 % had received it. Conclusions: This evaluation shows that the majority of patients who survived SJS/TEN suffer from long-term sequelae. An interdisciplinary approach is not only important in the acute stage of the disease, but also after discharge from the hospital, including regular check-ups by specialists for these rare severe reactions. Background: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening mucocutaneous reactions, predominantly drug-induced. In addition to these high mortality rates, early and late physical complications are common. No studies were conducted on the emotional status or the general Health-Related Quality of Life among survivors of SJS/TEN. We aimed to characterize the long-term emotional complications and health-related quality of life among SJS/TEN survivors. Materials and methods: Patients older than 18 years who survived SJS/TEN were assessed using various parameters. Emotional assessment was conducted by three validated questionnaires: Impact of Events Scale-Revised, General Health Questionnaire, and Hospital Anxiety and Depression Scale. Health-Related Quality of Life was assessed by three validated questionnaires: Dermatology Life Quality Index, EQ-5D, Skindex-29 and one specially designed for the study. Results: Our cohort consists of 17 patients with mean 51.6 ± 74.7 months (median = 9, range 1-228) following SJS/TEN. Eleven out of 17 (65 %) were found to have symptoms of post-traumatic stress (Impact of Events Scale-Revised, mean = 22.4 ± 19.9) and 5 (29 %) met the criteria for post-traumatic stress disorder, 12 (71 %) had psychological distress (General Health Questionnaire, mean total score = 4.6 ± 4.2) and 11 (65 %) had symptoms of a psychiatric clinical disorder (Hospital Anxiety and Depression Scale, mean total score = 14.5 ± 8.4). The Dermatology Life Quality Index indicated a moderate to extremely large effect on the lives of 9 (53 %) participants (mean total score = 6.9 ± 7.6). Skindex-29 indicated a mildsevere effect on Health-Related Quality of Life in 10 (59 %) participants (mean = 24.6 ± 21.5). Participants rated their general health at a mean of 66.2/100 ± 18.1 (EQ-5D VAS). Fourteen (82 %) participants reported that SJS/TEN decreased their current quality of life. Twelve (71 %) reported that SJS/TEN influenced their current emotional status. Eleven (65 %) reported that SJS/TEN influenced their current everyday activities.
Background: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered the most severe types of cutaneous adverse reactions to drugs, with high morbidity and mortality rates. We aimed to characterize the long-term physical complications among SJS/TEN survivors. Materials and methods: Patients older than 18 years who survived SJS/TEN were assessed by an interview and by skin, oral mucous membrane and detailed ophthalmic exam. Results: Our cohort consists of 17 patients with mean 51.6 ± 74.7 months (median = 9, range 1-228) following SJS/TEN. The most commonly reported symptom among survivors was chronic fatigue/weakness (76 %). The most common cutaneous signs were post-inflammatory dyspigmentation in 77 % of participants, scars (46 %), and milia (15 %). The most common cutaneous symptoms were pruritus (53 %), photosensitivity (35 %), and dry skin (24 %). In the ophthalmic exam, dry eyes were the most common finding in 44 %. Other identified signs were: lid adhesions/symblepharon (33 %), chronic ocular surface inflammation (33 %), loss of visual acuity (22 %), chronic conjunctivitis (22 %), keratinization of the tarsal conjunctiva (22 %), lachrymal duct scarring (22 %), blindness (11 %), photophobia (11 %), ectropian and trichiasis (11 %), corneal abrasions/ulcers (11 %), conjunctival synechiae (11 %), and corneal neovascularization (11 %). The most commonly reported ocular symptoms were dry eyes in 47 % of participants; other symptoms included photophobia (35 %), loss of visual acuity (35 %), and ocular pain (24 %). Hair loss and nail loss were reported in 53 and 35 % of participants a few months after TEN, respectively. Other less common complications included genital synechiae in 18 % of female survivors, lupus (12 %), renal dysfunction (12 %), and fibromyalgia (6 %). Tinnitus, tenderness on soles of feet, abnormal ECG, and vocal cord dysfunction were each reported in 6 % of participants. Background: The combination of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) with haemophagocytic lymphohistiocytosis (HLH) is life-threatening and usually fatal in adults. We report a rare case of a 36 year old male who survived these concomitant illnesses. Report: The patient presented with a 1 week history of fevers and flu-like symptoms, with onset of a mucocutaneous rash on day five. He was admitted to a tertiary intensive care unit (ICU) with a diagnosis of SJS/TEN (20-25 % of total body surface area). The potentially implicated drugs (ibuprofen, codeine and amoxicillin) were promptly withdrawn, and he received immunosuppressive therapy with methylprednisolone, intravenous immunoglobulin and cyclosporin combined with supportive ICU care. He continued to systemically deteriorate at a time when his skin lesions stabilised. Recognition of hyperferritinemia (40,900 µg/l), unremitting fevers and pancytopenia in a critically ill patient, clinched the diagnosis of HLH which was confirmed on bone marrow biopsy. He received treatment with the HLH-94 chemotherapy protocol (including etoposide and dexamethasone). Sequential skin patch tests to ibuprofen and amoxicillin, performed 6 months post-discharge, were negative (codeine patches were not available). The patient's negative patch tests were interpreted with caution, due to previous chemotherapy and the unavoidable delays to testing, both of which may have led to T lymphocyte depletion and Clin Transl Allergy 2016, 6(Suppl 3):31 false negative patch test results. The patient was advised to strictly avoid all non-steroidal anti-inflammatories, aspirin, codeine and amoxicillin (he had tolerated other opiates and beta-lactams in hospital). How this report contributes to current knowledge: To our knowledge, this is the first report of an adult surviving a severe episode of HLH and SJS/TEN overlap (rather than SJS alone). This case highlights (1) the potential for HLH to coexist with SJS/TEN and the importance of early recognition and treatment, (2) the difficulties in interpreting patch tests in patients who have received marrow ablative therapies, and (3) the complexities of providing recommendations on drug avoidance to patients with severe cutaneous adverse drug reactions and negative patch test results. In vitro lymphocyte proliferation assays may be a useful alternative diagnostic tool in this clinical setting.
Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Exposure to anti-tuberculosis drugs (ATDs) isoniazid (INH), ethambutol (ETB), pyrazinamide (PZA) and/or rifampicin (RIF) is associated with a mild elevation of liver enzymes that occasionally develops into severe liver injury. We have reported that INH-specific CD4+ T-cell clones circulate in patients with ATD-related liver injury, which suggests that the adaptive immune system is involved in the disease pathogenesis. This study details the nature of the drug antigen-specific T-cell response that develops in a fatal case of ATD-related liver failure. Materials and methods: Peripheral blood mononuclear cells were isolated from a patient who had a severe liver reaction to ATD medications, ALT 514 IU/l and Bilirubin 30 mg/dl. A lymphocyte transformation test (LTT) and IFNγ-ELISPOT assay using ATDs were performed and clones were generated from ATDs by serial dilution. Drug-specific clones were identified in terms of cross-reactivity and dose-responsiveness and then characterized in terms of CD phenotype and cytokine secretion. Results: Positive LTT against multiple drugs (INH, ETB, PZA, RIF, and activated ester of isonicotinic acid which forms isonicotinic amide adducts in the cell culture system) was observed. Over 700 T-cell clones were generated from INH, ETB, PZA, RIF or activated ester of isonicotinic acid treated peripheral blood mononuclear cells. Antigenspecific proliferative responses of CD4 +/CD8+ clones were identified with only ETB and RIF. Clones were highly specific and did not crossreact with other ATDs. Clones are activated to proliferate and secrete cytotoxic mediators (granzyme B, perforin) and effector cytokines (IFN-γ, Il-13). Conclusions: In conclusion, cytotoxic ETB and RIF-specific T-cell clones have been identified in patient with ATD-related severe liver failure. Background: Acute Interstitial Nephritis (AIN) is often drug induced and the most frequently implicated drugs are Non-steroidal antiinflamatory drugs (NSAIDs) and antibiotics. We report the case of a patient with AIN induced by Ibuprofen. Report: A 74 year-old-female was admitted at emergency department with a 10-day history of malaise, anorexia, nausea, diffuse myalgias, fever (38 °C) and flank pain, treated with Paracetamol, Ibuprofen and Ciprofloxacin for suspected Pyelonephritis, by her attending physician. At admission she was febrile (38 °C) and prostrated. Laboratory studies revealed: leukocytosis, acute kidney injury (serum creatinine 5.8 mg/ dl, blood urea nitrogen 178 mg/dl) and positive C-reactive Protein; urinalysis with leucocituria, proteinuria and hematuria; negative blood culture. Chest X-ray and ultra sound of kidneys were normal. Treatment with Paracetamol, Ibuprofen and Ciprofloxacin was discontinued and she started Meropenem and intravenous fluids. Renal function improved and she was discharged after 3 days. One year later she was admitted to hospital with similar clinical presentation and diagnosed with AIN. Ten days prior to this admission she was treated with Ciprofloxacin and Ibuprofen for Phlebitis. After these two episodes she was again treated with Ciprofloxacin with good tolerance. She was then referred to our Drug Allergy Clinic for suspected hypersensitivity to Ibuprofen. Lymphocyte transformation test (LTT) with Ibuprofen was positive (stimulation index of 13.4 at 10 µg/ml). Drug provocation test (DPT) with the suspected drug was not performed. DPT and long-term challenge with alternative drugs (Paracetamol and Etoricoxib) were both negative. How this report contributes to current knowledge: Renal biopsy is the only definitive method to establish the diagnosis of AIN. However, when diagnosis seems likely, a probable precipitating drug can be easily withdrawn or patient improves readily after withdrawal of the suspected drug, biopsy can be avoidable. Challenge with the suspected drug remains the gold standard for diagnosis of drug hypersensitivity. Since AIN is a severe hypersensitivity reaction, DPT with the suspected drug is contra-indicated. The obvious time relationship between Ibuprofen treatment and reaction development in both episodes, the reproducible clinical presentation and positive LTT, suggests Ibuprofen has been the culprit drug. In cases of severe reactions LTT seems to be a valuable diagnostic tool.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Epidermal growth factor receptor inhibitors (EGFRIs) are used for treatment of advanced lung, pancreatic, colorectal, and head and neck cancers. Cetuximab is a monoclonal antibody that competitively binds to the extracellular domain of EGFR and blocks cytoplasmic-domain phosphorilation. It is characterized by frequent cutaneous adverse reactions (CARs) including acneiform rash (AR), desquamation, xerosis, pruritus, hair abnormalities, paronychia, changes in nails, mucositis, increased growth of facial hair and eyelashes, and teleangiectasias. AR usually appears between day 2 and week 6 after cetuximab Background. According to the National Cancer Institute Common Toxicity Criteria, severity of toxicity of AR is graded into five grades, and according to EGFRI-induced AR severity score into mild, moderate and severe toxicity. Prophylactic antibiotic treatment with doxycycline 100 mg bid for the first 6 weeks is recommended. Therapeutic plan includes use of gradebased skin treatment algorithm: (a) mild toxicity-local therapy with corticosteroids or antibiotics, (b) moderate toxicity-local therapy with addition of oral antibiotic, and (c) severe toxicity-cetuximab Clin Transl Allergy 2016, 6(Suppl 3):31 dose lowering and therapy for moderate toxicity with an addition of a methyprednisolone dose pack. If therapy is ineffective within 2-4 weeks, it is necessary to discontinue cetuximab treatment. Report: We present two male patients with metastatic colorectal cancer who developed papulopustular lesions on the sebum-rich areas of the face, scalp and trunk accompanied by pruritus and burning sensations (grade 2/3 or moderate toxicity), 1-3 weeks after Background of cetuximab. One patient developed desquamation of the palms. Comedones, primary acne lesions, were lacking. There was no sign of superinfection. Patients were treated with doxycycline 2 × 100 mg bid for 2 weeks, followed by 1 × 100 mg, until the end of cetuximab therapy. Local therapy included clindamycin lotion, hydrocortisone/oxytetracycline ointment, benzoyl peroxide suspension and emollients. After 3 weeks of treatment, significant improvement of AR severity was achieved and there was no need for cetuximab dose reduction. How this report contributes to current knowledge: Studies have demonstrated positive correlation between treatment efficacy and CARs for EGFRI. Since frequency and severity of skin lesions are dosedependent, a gradual increase in dose until CARs develop might be a good strategy to maximize the efficacy of EGFRI.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. The patient has given written informed consent for the publication research. Results: A 81 years old woman, diagnosed of hypertension, treated for 3 years with losartan 100 mg/d. After starting treatment she refers chronic diarrhea and since 2 years ago worsening diarrhea, abdominal pain and weight loss. The patient was treated at the emergency service twice for 3-4 daily episodes of watery, nonbloody diarrhea associated with abdominal bloating. The patient failed conservative management including gluten-free diet, oral antibiotic and corticosteroid. Additionally to diarrheal syndrome, the patient showed hoarseness and cough. Allergologic study: immediate and delayed prick test and specific IgE were negative for food. A colonoscopy with colonic biopsies revealed evidence of microscopic colitis. Treatment: Losartan withdrawal, achieving complete remission in 4 weeks. The case has been reported to Spanish Postmarketing Surveillance System. How this report contributes to current knowledge: The allergist should keep in mind this possible and rare ADR in patients treated with losartan (ARA II) showing enteropathy, as discontinuing losartan leads to clinical improvement. This enteropathy case is very similar to SSE described in 2012 related to olmesartan.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Granuloma annulare (GA) is a benign inflammatory dermatosis affecting predominantly females. The disease etiology and pathophysiology remain unclear. Trauma, association with diabetes mellitus and medicamentous genesis have been suspected. Pathogenic mechanisms include cell-mediated immunity (type IV), macrophage activation, and cytokine-mediated degradation of connective tissue. Report: Herein we present a 56-years-old male Caucasian patient who developed skin lesions on the back of the hand 3 months after initiation of therapy with canakinumab as a part of a clinical trail for treatment of coronary artery disease. Upon admission the skin changes involved the dorsum of the hand and were presented by annular papules and plaques, the largest 3 cm in diameter with depressed center and elevated and infiltrated borders. The patient had no other relevant history of present or past disease beyond the coronary artery diseases and elevated serum cholesterol levels. He took no other medication prior or during the disease onset. Based on the clinical findings the diagnosis of GA was coined. Cryotherapy with liquid nitrogen was performed. Canakinumab was withdrawn. Skin lesions resolved within the 2 weeks later. No new lesions appeared during the 6 months follow up. How this report contributes to current knowledge: Canakinumab is a IL-1 beta monoclonal antibody used in rheumatology and in the treatment of autoinflammatory syndrome. Recently it was tested in coronary artery disease, gout and COPD. As a new drug, its safety profile and unwanted adverse events are still to be challenged. In the described case we present the development of cutaneous reaction coinciding with the drug Background. Drug-induced GA has been described in the literature, e.g. after allopurinol, amlodipine, TNF-alpha inhibitors, gold, and interferon therapy. As far as we are aware no previous reports exist on the association between canakinumab therapy and GA. Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. His general physical examination was unremarkable, without any signs of heart failure. Complete blood count (CBC) revealed leucocytosis with slightly eosinophilia and elevated troponin and CRP. ECG showed no changes in ST/T segment. Echocardiography revealed minimal pericardial effusion for up to 4 mm. Initial right pneumonia was observed on X-ray. He was treated with amoxicillin/clavulanic acid, azithromycin and ibuprofen. Fifth day of hospitalization the signs of disease became more prominent: CBC revealed 19.2 × 10 9 /l leucocytes with 11.2 × 10 9 /l eosinophils and troponin level was doubled. Pulse doses of corticosteroids (CS) (methylprednisolone 500 mg i.v.) were started and other therapy was discontinued. Seven hours later patient was asymptomatic, leucocytes were normal with slightly eosinophilia. Pulse doses of CS were continued up to 3 days when converted to oral CS. Endomyocardial biopsy showed no inflammation. Coronarography revealed two-vessel CAD, treated with percutaneous coronary intervention. How this report contributes to current knowledge: One of the most common cause of EM reported in literature is drug HS. In our patient HCT is a potential cause. Symptoms, levels of troponin, ECG and echocardiographic changes were more suggestive for EM than CAD. Endomyocardial biopsy revealed no EM but it was performed third day after pulse dosage of intra-venous CS, when symptoms completely vanished. It should be also noted that EM is a focal disease and biopsy doesn't have to prove the diagnosis. It is more obvious that CAD was co-finding, as symptoms of CAD could not be resolved using CS, and troponin levels would not fall second day after initiating therapy. CBC with eosinophilic drop powers that hypothesis. Early administration of systemic CS is necessary regardless of underlying causes, as delayed treatment may result in fatal outcomes.

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Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: Two mechanisms of drug-induced haemolysis have been described. Usually both, extravascular and intravascular haemolysis, are caused by drug dependent antibodies (ddAb). Extravascular haemolysis presents with mild and less severe clinical symptoms of anaemia, whereas intravascular haemolysis usually manifests with a rapid destruction of red blood cells caused by antibody-mediated complement activation leading to acute clinical symptoms. Interestingly more than 50 % of all piperacillin-induced immune haemolytic anaemia (PIHA) cases investigated at a reference laboratory in Germany were patients with cystic fibrosis (CF). Therefore the investigated hypothesis of this study is a higher prevalence for PIHA in patients with CF as for the general population. Additionally risk factors for PIHA are systematically assessed. Materials and methods: Included were all patients with CF older than 12 years who were admitted to the hospital for antibiotic treatment. Past transplantation was an exclusion criterion. Blood samples were obtained in the beginning and at the end of a given intravenous treatment. Direct antiglobulin test (DAT) and indirect antiglobulin test (IAT) were performed using standard techniques. For positive samples an antibody differentiation was done. DdAb were investigated using gel technique. Thus we prepared a 1 mg/ml drug solution or used ex vivo antigens, respectively and incubated it for 30 min in presence of patients' plasma and group O RBCs. The individual prior exposure to piperacillin and information concerning atopy and microbiology are documented. Results: In the ongoing trial 2 out of 20 patients developed a PIHA. This is a high prevalence compared to the general expectation of approximately 1:1,000,000. Both had ddAb but no complement activation. This is typical for extravascular haemolysis. Clinical symptoms of haemolysis were mild but there was a drop of haemoglobin by 4 mg/ dl. The study will be finished by April 2016. Conclusions: These results suggest a higher prevalence of PIHA in patients with CF than expected in the general population. This is backed by several case reports. Possibly this is due to the exposure to piperacillin. Therefore PIHA should be considered when treating patients with CF. Background: Pemphigus foliaceus (PF) is a benign variety of pemphigus (P) characterized by acantholysis in the upper part of epidermis, induced by immunoglobulin G (IgG) autoantibodies (mainly IgG4 subclass) targeting desmoglein -1 (dsg-1). Clinical expression of PF is based on the presence of scaly and crusted erosions on an erythematous base, flaccid blisters, minor or no involvement of mucous membranes and with seborrheic distribution and aspect of the lesions in early stages of the disease. PF is classified into four types: endemic (fogo selvagem), idiopathic, erythematosus (Senear-Usher syndrome) and drug-induced. Drugs triggering or inducing PF reported in literature are penicillamine, bucilamine, captopril, lisinopril, enalapril, fosinopril, candesartan, tipronin and rifampicin. Report: A 45-year-old woman presented with facial erythema, multiple erythematous papules and plaques, few scaly plaques, shallow erosions and superficial blisters on an erythematous base localized on the upper chest and upper back in "V" distribution, acompanied by pain and burning sensation. Mucous membranes were spared. Lesions appeared 2 months after initiating systemic therapy with medroxyprogesterone acetate 10 mg daily for 14 days per month for metrorrhagia. Biopsy revealed subcorneal cleft within the upper epidermis with acantholytic keratynocytes. Direct immunofluorescence (DIF) of perilesional skin showed intercellular, intraepithelial IgG. Indirect immunofluorescence (IIF) showed intercellular, intraepithelial IgG, with higher fluorescent intensity in the upper dermis. The diagnosis of possible drug induced PF was presumed based on clinical, histological and immunological grounds. The suspected culprit drug-progesterone was discontinued. Treatment with high-potency topical corticosteroid (betamethasone) in combination with gentamicin ointment twice daily was started. After 4 weeks of treatment, lesions resolved almost completely. Close follow-up was recommended. How this report contributes to current knowledge: Although PF often occurs spontaneously, it may be triggered by certain medications. A case of localized PF induced by topical imiquimod treatment has been recently reported, based on an unknown mechanism of acantholysis, probably due to antibodies to dsg-1. Drug as a trigger must be suspected in every newly diagnosed P. Indentification and elimination of triggering drug may soothe the clinical symptoms and shorten the treatment.

Consent:
Written informed consent was obtained from the patient for publication of this abstract and any accompanying images.
Background: Subjects responding to several NSAIDs including ASA are considered cross-hypersensitive, whereas those responding to only one NSAID with tolerance to other chemically unrelated NSAIDs are considered selective responders. However, in some cases, patients that develop immediate reactions to several NSAIDs are classified as cross-hypersensitive without assessing ASA tolerance. Report: A 70 year-old woman, without allergic history, referred that in 1996 she developed two episodes of urticaria less than an hour after paracetamol intake. Three years after, she had developed three episodes of urticaria 90 min after dipyrone intake. At that time she was allergologically evaluated: intradermal test (ID) with dipyrone (2 mg/ ml) and paracetamol (0.1 mg/ml) were positive. She was challenged with ASA showing tolerance at full therapeutic doses (500 mg). In 2012, she suffered from an episode of facial angioedema and pruritus in the tongue after celecoxib intake. She reported previous tolerance to this drug on many occasions. In September 2014, she was re-evaluated: ID to paracetamol was negative (0.1 mg/ml), and ID and basophil activation test (BAT) to dipyrone were positive. Drug challenges: 60 min after achieving a cumulative dose of paracetamol 300 mg, she developed generalized pruritus and urticaria. Two weeks later, she presented pruritus in the tongue and ears, nasal itching and obstruction, and wheals in the neck after provocation with a cumulative dose of 100 mg of celecoxib, with no changes in FEV1 values. After another interval of 2 weeks tolerance to etoricoxib was observed at full therapeutic doses. Two weeks later the patient tolerated ASA and ibuprofen during controlled challenge until therapeutic doses. In addition, around 2 months later the patient received two independent 2 days treatment courses with these drugs, separated by a 2 weeks time interval. How this report contributes to current knowledge: Subjects may develop an immediate response to a number of different NSAIDs, including some COX-1 and/or selective COX-2 inhibitors but tolerate strong COX-1 inhibitors. This case shows the importance of testing for ASA tolerance when confronted by a patient who responds to several chemically unrelated NSAIDs.

Consent:
Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Background: The most important drug involved in hypersensitivity drug reactions (HDR) are NSAIDs. Two mechanisms are involved: immunological sensitization (specific IgE or T-cell) and pharmacological (COX-1 inhibition). Paracetamol, one of the drug most highly consumed all over the world, has been implicated in HDR. The contribution these mechanisms in HDR to paracetamol is not well known. We studied a large group of patients who developed one/several episodes indicative HDR to paracetamol. Materials and methods: Patients with reactions to paracetamol were classified as cross-hypersensitivity (CH) if they responded to two others NSAIDS not chemically related including ASA. If only paracetamol was implicated, drug provocation test (DPT) with ASA was required: if positive, they were included as CH and if negative, as selective responders (SR). In cases who reported respiratory symptoms, nasal provocation test with L-ASA were performed. Atopy status was also assessed with prick test to inhalant allergens. required a positive DPT for diagnosis. Nasal challenge with L-ASA was positive in 19 (82.6 %) patients with clinical history suggestive of NERD. Within SR group, 56 cases (90.32 %) were SNIUAA (reaction less than 24), being anaphylaxis the most frequent clinical entity (29 (51.78 %), followed by urticaria/angioedema (16; 28.57 %), angioedema (6; 10.71 %), urticaria (4; 7.14 %) and fixed drug eruption (1; 1.78 %). A total of 18 (32.14 %) patients required a positive DPT to paracetamol for diagnosis. The remaining six (9.67 %) cases were SNIDHR as they had the reaction more than 24 h after paracetamol administration: four (66.66 %) maculopapular exanthema and two (33.33 %) exanthema with desquamation. One patient had respiratory symptoms and was confirmed as SR. Conclusions: These data indicate that when patients develop a HDR to paracetamol after carried out the allergological work-up, the 80 % of patients who developed a positive response were CH with a lower proportion being SR. DPT was needed in more than 20 % of cases to achieve the diagnosis. . 14 medications containing paracetamol were reported. ENDA questionnaires were completed, patch and drug provocation tests (DPTs) were performed to confirm the diagnosis. Results: We adapted our clinical cases to the new classification of hypersensitivity to NSAIDs and divided our patients into five categories. 53 cases (47 patients) were nonimmunologically mediated (cross-reactive) hypersensitivity reactions to NSAIDs: four cases of "NSAIDs-exacerbated respiratory disease", four cases of "NSAIDs-exacerbated cutaneous disease" and other 45 cases (39 patients) of "NSAIDs-induced urticaria/ angioedema (NIUA)". 86 cases (75 patients) were immunologically mediated (non-cross-reactive) hypersensitivity reactions to NSAIDs: 63 cases (55 patients) of "Single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA)" and 23 cases (20 patients) of "Single-NSAID-induced delayed hypersensitivity reactions (SNIRD)". 10 cases of bronchospasm without underlying chronic airway respiratory diseases and 62 cases of anaphylaxis, maculopapular rash and other hypersensitivity reactions induced not only by paracetamol but also by other NSAIDs could not be classified according to the criteria of this classification. Only 25 (13.7 %) patients (mostly SNIUAA (ten patients) and SNIRD (seven patients)) underwent further allergological work-up with suspected causative drug. Only seven (28 %) of them (three SNIUAA, two NIUA and two SNIRD), had true paracetamol hypersensitivity. For one patient hypersensitivity was demonstrated by patch test, and for six by DPTs. 6 out of 7 positive test results occurred as skin reactions. Conclusions: True hypersensitivity to paracetamol is rare. In our research, only patients with skin reactions in their clinical history, mostly SNIUAA, were confirmed to be hypersensitive to this drug. Background: Arylpropionic acid derivatives are the most commonly prescribed and consumed NSAIDs and very often obtained without medical prescription. From these the most common is ibuprofen. Within the group of hypersensitivity reactions to NSAIDs, these drugs are progressively involved and include those mediated by specific immunological mechanisms and those classically classified as crossintolerance reactions. Within the first category, IgE mediates or T cell specific responses may occur. We present a series of cases with an immediate selective response to ibuprofen and other arylpropionic derivatives confirmed by drug provocation tests (DPT). In addition to demonstrate selectivity of the response to these drugs we assessed cross-reactivity between them. Materials and methods: Subjects who reported symptoms indicative of an hypersensitivity reaction to an NSAIDs were evaluated. A DPT with ASA was carried out to rule out cross-intolerance (non allergic hypersensitivity). Imputability of the different aryl propionic derivatives and assessment of cross-reactivity was carried out by drug provocation tests. Serum tryptase was quantized in peripheral blood at 2 and 24 h post episode and in the affected skin by immunohistochemistry at the moment of the appearance of the reaction. Results: All subjects included had good tolerance to ASA. After proceeding with the aryl propionic acid derivative challenge, 42 cases were classified as selective immediate responders. Ibuprofen was the drug most frequently involved, followed by naproxen and desketoprofen. We found cases than only responded to one single drug and others who responded to several, confirming cross-reactivity. Quantitation of tryptase levels in peripheral blood and skin biopsies were indicative of an immediate selective response with the involvement of mast cell activation. Background: Exposure to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAID) may exacerbate respiratory disease (asthma, rhinitis), cutaneous diseases (urticaria and angioedema in patients with chronic urticaria, trigger urticaria, angioedema and anaphylaxis in patients without underlying diseases. We made a hypothesis that alternate regulation of cyclooxigenase-2 (COX-2) mRNA expression may predispose patients to ASA-induced exacerbations.

Materials and cons:
We performed a prospective study of 40 subjects (mean age 49 years, 27 women) who had suspected hypersensitivity to ASA or other NSAID. 20 subjects had asthma (10 of them also nasal polyposis). We performed provocation tests (nasal and/or oral) with ASA in all of them. In 14 subjects tests were positive (eight nasal). Gene expression was analyzed in whole blood sample using real-time RT PCR just before ASA provocation and 4 h after provocation. We also included six Hymenoptera venom allergic patients which were followed after systemic reaction (SR) during VIT failure and four healthy control subjects. Results: We found significantly important increase of COX-2 mRNA expression in patients with ASA provocation test (p = 0.004). There was no difference in ASA tolerant patients. COX-1 expression was comparable between ASA tolerant and hypersensitive patients and showed no dynamic during provocation. There were no changes in COX-2 expression in subjects with SR during VIT or in healthy control subjects.

Conclusions:
Main findings in our study are: (1) after provocation with ASA COX-2 expression is increased in subjects with Aspirin intolerance in comparison with subjects who tolerate Aspirin; (2) during allergic reaction like SR in VIT failure we found no difference in COX-2 expression; (3) all subjects that were positive on ASA provocation test had asthma and/or nasal polyposis. Keywords: Asthma/rhinitis; Hypersensitivity to acetylsalicylic acid; COX-2 MRNA expression Background: Diclofenac is a phenylacetic acid derivative belonging to the group of arylcarboxylic acids. NSAIDs have been reported as the 2nd most frequent cause of drug-induced anaphylaxis and diclofenac was the only NSAID significantly associated with anaphylaxis. However, some doubts remain about the pathophysiology of these reactions. Here we describe a case series of anaphylaxis probably induced by diclofenac. Materials and methods: Retrospective analysis of patients with suspected anaphylaxis to diclofenac studied in our DAU, who underwent skin tests (ST). Records were analyzed for clinical signs and symptoms, severity of reactions, ST and oral challenges (OC). ST were performed with commercially available IV formulation of diclofenac, in a concentration of 25 mg/ml, diluted from 1 × 10 −4 to 1/1 for IDT and 1/1 for SPT. Results: A total of 33 patients were enrolled in the final analysis. Mean age was 50(± 12.75) years, 22(68.8 %) were women, 6(18.2 %) were atopic. The time elapsed until the reaction was less than 1 h in 26(83.2 %) cases. Seventeen patients had grade 4 anaphylaxis and ten had history of re-exposure with reproducible symptoms. Nineteen patients (62.7 %) reported reactions only to diclofenac (single-reactors) and 12 to other NSAIDs (multiple reactors) (eight to acetylsalicylic acid, two to aceclofenac). Twelve single-reactors (63.2 %) had positive ST (two with systemic symptoms during the procedure). Only four multiple reactors (33.3 %) had positive tests. Only one diagnostic OC was performed in order to clarify a doubtful history and it was positive. OC with alternative drugs were performed in 29 patients, with meloxicam in 17 and etoricoxib in 9. Two patients had skin symptoms during the alternative OC and both were from the multiple reactors group. Conclusions: We report a large series of anaphylaxis to diclofenac assessed by skin tests. As the majority of NSAIDs hypersensitivity reactions are considered to be due to a non-immunologic mechanism, non-irritative concentrations to IDT and specific IgE's are not available. Characteristics such as the severity and time of reaction, single-reactor status and systemic symptoms during skin tests suggest IgE-dependent hypersensitivity in this study. The value of intradermal tests and their non-irritative concentrations remain to be determined doubtful history and it was positive. Keywords: Diclofenac anaphylaxis mechanism reactions worldwide. It is generally assumed that inhibition of cyclooxygenase 1 (COX-1) enzyme by the offending drugs plays a relevant pathogenic role in multiple NSAID reactors. It is generally expected tolerability to preferential/selective COX-2 inhibitors among patients with NSAIDs hypersensitivity. Materials and methods: We reviewed the medical records and selected patients referred to our drug allergy unit in the past 5 years, with history of reproducible hypersensitivity reactions to NSAIDs COX-1 inhibitors and positive oral challenge (OC) with etoricoxib, a selective COX-2 inhibitor, and/or to meloxicam, a preferential COX-2 inhibitor. Results: Inclusion criteria were met in 15 patients, aged 28-68 (47 ± 13 years-old), 12 females. Seven patients were atopic. Eight patients had asthma, five chronic rhinosinusitis and nasal polyposis and three patients had chronic urticaria. The primary NSAIDs hypersensitivity reactions were: eight urticaria and angioedema; four anaphylaxis and three asthma exacerbation. Eight patients presented a positive OC with meloxicam: four with immediate urticaria and angioedema; three with late-onset of angioedema and one with asthma exacerbation. One patient with late-onset angioedema to meloxicam also had a late-onset of angioedema with etoricoxib. Eight subjects had positive OC with etoricoxib: five with immediate urticarial, two with late-onset angioedema and one with anaphylactic reaction. Conclusions: Based on the results of previous studies, it could be tempting to prescribe COX-2 inhibitors in cases of multiple reactors to NSAIDs COX-1 inhibitors, without establishing its tolerance in a proper setting. However, these data strongly suggest that, before prescribing an alternative NSAIDs, a provocation test should always be performed. Background: History of NSAIDs hypersensitivity is common in some patients with coronary artery disease who are in need for coronary angioplasty. These patients require dual antiplatelet therapy to avoid in-stent thrombosis, and full evaluation of NSAIDs allergy. We present a cohort of patients with acute coronary syndrome undergoing aspirin desensitization to evaluate the short-and long-term efficacy and safety Materials and methods: We developed a dynamic protocol that is based on both the patient characteristics and onset of reaction after NSAIDs. This challenge/desensitization protocol is shorter than previously published ones. The objective is to asses short and long-term efficacy and safety prior to stent placement Results: A total of 19 patients with history of NSAIDs allergy were challenged with different doses of Aspirin. All patients tolerated the oral protocol at different timings of 30-45-90-120 min. The dosage given ranges between (21, 41, 81 and 162 mg) of aspirin given by mouth after premedication with montelukast. We had two patients reacting during the procedure and one during a 6 h-follow-up. All reactions were limited to the skin. All patients tolerated the required dose of aspirin within 60-150 min. Those requiring urgent catheterization were desensitized within 90 min. Background: Oral drug challenge (ODC) is the gold standard for the diagnosis of hypersensitivity reactions to non-steroidal anti-inflammatory (NSAIDs). If suspicion of respiratory symptoms, the ODC might include a lung function evaluation (LFE). Aim: To evaluate the lung function volumes during ODC to NSAIDs performed in our department between 2010 and 2015. Materials and methods: One-hundred and ten ODCs with NSAIDs under LFE were performed. An alternative drug was tested in 77 of the patients (70 %) whereas 33 were diagnostic tests (30 %). The drugs tested were meloxicam (n = 46, 41.8 %); acetylsalicylic acid (19, 17.4 %); etoricoxib (16, 14.6 %); nimesulide (15, 13.6 %); ibuprofen (4, 3.6 %); celecoxib (3, 2.7 %); metamizol (3, 2.7 %); acetaminophen (3, 2.7 %) and diclofenac (1, 0.9 %). The criteria for a positive ODC were: a decrease in FEV1 ≥ 20 % of baseline, a decrease of MMEF75/25 ≥ 25 % of baseline or when major symptoms occurred. Statistical analysis based on independent sample t test and paired t test. Results: Seventy-nine patients were female (71.8 %) (44.8 ± 15.6 years) and 31 were male (28.2 %) (40.5 ± 16.4 years). Sixty-two patients had a previous diagnosis of asthma (56.4 %), 18 of which with diagnosis of NSAID-exacerbated respiratory disease (NERD) (16.4 %). ODC was positive in seven cases (four by decrease of volumes and three by reported symptoms): five alternatives and two diagnostic (four with meloxicam; one ibuprofen, one metamizol; one etoricoxib), two patients with no previous asthma diagnosis. Taking into consideration the whole population tested, we observed statistically significant decreases in FEV1 and FVC values at 30 and 120 min after medication versus baseline; and also a decrease in volumes at 30, 60, 120, 180 and 240 min after the second dose vs baseline (p < 0.05). When comparing alternative versus diagnostic ODCs, we found statistically significant differences in the measurement of FEV1 at 1 h after the second dose (p < 0.05). Conclusions: The number of positive ODCs was low (6.36 %). Patients with asthma have an increased risk of reaction even with alternative NSAIDs. There was a statistically significant decrease in FEV1 at almost all timepoints after NSAIDs compared to baseline, even including negative challenges in the analysis. This suggests that NSAIDs might have a general effect to reduce FEV1. Keywords: NSAID; NSAID-exacerbated respiratory disease; Asthma

P62 Prevalence and incidence of analgesic hypersensitivity reactions in Colombia
Pablo Andrés Miranda 1 , Bautista De La Cruz Hoyos 2 Background: Aspirin-exacerbated respiratory disease (AERD) is diagnosed clinically through a positive oral graded aspirin challenge. Upon confirming aspirin hypersensitivity, aspirin desensitization and treatment has been proven to reduce recurrence of nasal polyposis and asthma symptoms. However, negative aspirin challenges have been reported to occur in otherwise aspirin allergic individuals ("silent challenges") after intake of antihistamines, leukotriene blockers, or oral corticosteroids. We sought to determine whether recent endoscopic sinus surgery (ESS) also affects reactions to aspirin challenge in patients with AERD. Materials and methods: 19 AERD patients underwent two aspirin challenges: one before and the other after (within 8 weeks) their most recent ESS. Reactions to aspirin were evaluated by changes in forced expiratory volume in 1 s (FEVl, percent predicted), nasal peak flow (NPF), and fraction of exhaled nitric oxide (FeNO).

Results:
Decreased time between ESS and challenge was associated with decreased frequency of positive reactions: all 19 patients with a history averaging 32 months (IQR 9-72) since last ESS, reacted to aspirin. In contrast, only 10 (52.6 %) of these patients, challenged on average of 1.1 months (IQR 0.8-1.4) after ESS, reacted to aspirin. Nine patients (47.4 %) had no clinically apparent reaction to aspirin challenge after recent ESS. In the 10 patients who had a positive challenge after recent ESS, the decrease in FEV1 during this challenge was less than during the baseline challenge before ESS: −8.9 ± 1.2 vs. −19.7 ± 3.7 % (p < 0.01), respectively. NPF decrease was also smaller during the challenge after recent ESS than before recent ESS, −11.1 ± 5.1 vs. −25.5 ± 6.2 % (p < 0.01), respectively. FeNO significantly decreased in all patients during the first challenge (−22.2 % (IQR −50.6 to −20.9)) and decreased only in those who had positive challenges after recent ESS (−32. 5  Background: Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) has been classified by Ayuso et al. into different phenotypes. Multiple NSAID-induced urticaria-angioedema (MNSAID-UA) is presumably related to cyclo-oxygenase 1 (COX -1) inhibition. Patients with MNSAID-UA have reactions to multiple chemically unrelated molecules while usually they tolerate low COX-1 inhibitors. Report: We report the case of a 32 years old man who experienced several episodes of angioedema of lips and face after intake of acetylsalicylic acid (ASA), in one occasion associated to the intake of paracetamol. Diagnosis of MNSAID-UA was confirmed by oral drug provocation test (DPT) to ibuprofen, a strong COX-1 inhibitor chemically unrelated to ASA, that induced labial angioedema. DPT with alternative drugs, defined as low COX-1 inhibitors, was then performed. Angioedema also appeared with nimesulide and paracetamol. Instead, the patient tolerated imidazole salicylate. How this report contributes to current knowledge: Low COX-1 inhibitors as paracetamol and nimesulide not always are tolerated by patients with MNSAID-UA. This report confirms the safe use of imidazol salicylate in patients with hypersensitivity to ASA presumably due to non-interference with the cyclo-oxygenase pathway.

Consent:
Written informed consent was obtained from the patient for publication of this abstract and any accompanying images.   (25) were negative in all patients tested. LTT performed in 12 patients (five exanthema, one urticaria/ angioedema, three vasculitis and three DRESS) was positive in four, negative in five, doubtful in two and undetermined in one. DPT was positive in 2 out of 11 and long term challenge in 2 out of 8. Four patients were submitted to desensitization: three developed reaction during the procedure, confirming diagnosis; two were able to tolerate treatment. AH was confirmed in 10 (35 %), considered probable in six (21 %), excluded in seven (24 %) and inconclusive in six patients. Among confirmed AH patients, all were DR and 80 % had started Allopurinol recently (≤10 days). Conclusions: As previously described in the literature, our study suggests that AH is rare, usually presents with delayed cutaneous symptoms and can be related to recent Background of Allopurinol. In the diagnostic workup of suspected AH, DPT remains the gold-standard while patch tests appear to be unhelpful. We discuss the usefulness of TTL, which seems promising, especially in SCAR where DPT is contraindicated. Background: Patients frequently report antibiotic allergies, however only about 10 % of labelled patients have a true allergy. This study investigates the documentation of antibiotic "allergy" labels (AALs) and the effect of labelling on clinical outcomes in an adult tertiary hospital in Australia.

Materials and methods:
We performed a retrospective single-centre cross-sectional analysis of 737 inpatients in a major teaching hospital in Western Australia. All patients were captured in the 2013 and 2014 National Antimicrobial Prescribing Surveys (NAPS). NAPS is an annual audit of Australian health services, led by The Australian Commission on Safety and Quality in Health Care, to assess volume and appropriateness of antimicrobial prescribing. Data collected by detailed chart review, included antibiotic adverse drug reactions (ADRs), antibiotic cost, prescribing appropriateness, prevalence of multi-drug resistant organisms, length of stay, intensive care admission and readmissions. Results: Complete data were captured for 687 patients. 278 (40 %) were aged 70 or above, 322 (47 %) were female and 279 (41 %) were prescribed antibiotics at the time of audit. AALs were recorded in 122 (18 %) of all patients. The majority of AALs were penicillin labels (n = 87; 71 %). Details of the clinical reactions to the culprit antibiotic were documented for 80 of 141 (57 %) individual allergy labels: 61 described symptoms consistent with drug allergies and 19 were non-specific symptoms. Five patients were receiving an antibiotic that would be considered contraindicated according to their documented allergy status. Females and older patients were significantly more likely to have an AAL (gender: OR 2.54, 95 % CI = 1.69-3.82, p < 0.001; for a one standard deviation (19.6 years) increase in age: OR 1.31, 95 % CI = 1.06-1.60, p = 0.007). Patients with AALs had significantly more hospital readmissions within 4 weeks (p = 0.001) and 6 months (p = 0.025) of discharge, compared with unlabelled patients independent of age and gender. The majority of patients with AALs (84 %) who were readmitted had a diagnosis of an infection.
Conclusions: This first Australian study shows that purported AALs are common but poorly documented in hospital records. Patients with AALs are significantly more likely to require readmissions. There may be a role for antibiotic allergy delabelling to mitigate the clinical and associated economic burdens for patients with invalid allergy labels. Keywords: Antibiotic; Allergy; Adverse drug reactions; Delabelling Clin Transl Allergy 2016, 6(Suppl 3):31 not been defined. The aim of this study was to find whether drugresponsive T cell response was detectable in patients with ATD-related DRESS and characterize the mechanistic features of the T-cell response.

Materials and methods:
A lymphocyte transformation test (LTT) was performed using peripheral blood mononuclear cells (PBMCs) from ATD-induced DRESS patients. Subsequently, drug-specific T-cell clones were generated from the hypersensitive patients. We measured the drug-specific proliferative responses and interferon-gamma (IFNγ) secretion. Anti-human class I and class II blocking antibodies were used to analyze HLA-restricted T-cell response.
Results: Strong proliferative responses to isoniazid or rifampicin were detectable in the patient with DRESS by LTT. Isoniazid/rifampicinspecific T-cell clones were generated from blood of the patients, but not pyrazinamide or ethambutol. The T cell clones proliferated and secreted IFNγ when stimulated with isoniazid or rifampicin. They did not cross-react with each other. T-cell responses were blocked in the presence of anti-human class II antibodies. Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially life threatening condition. DRESS preceding toxic epidermal necrolysis (TEN) has only been reported with three cases to date.

Report:
A 31 year old lady presented with a 3 day history of fever, morbilliform rash, cervical lymphadenopathy and facial oedema. 5 weeks prior she had been diagnosed with rheumatoid arthritis (RA) and commenced on hydroxychloroquine and sulfasalazine. Investigations showed an eosinophilia, elevated liver function tests (LFTs) and high inflammatory markers. Infectious screen including viral tests was negative. A clinical diagnosis of DRESS was made, all RA drugs were ceased and she was started on high dose oral corticosteroids. During admission she developed a marked lymphocytosis, neutrophilia and eosinophilia with worsening LFTs and coagulopathy. The rash, LFTs and leukocytosis gradually improved and she was discharged on day 9 to continue on high dose oral steroids. She presented 3 days later with worsening of her rash, high fevers and right upper quadrant abdominal pain associated with worsening of LFTs, anaemia and thrombocytopenia. 3 doses of IV methylprednisolone were administered. Haemophagocytic lymphohistiocytosis was considered given a high ferritin and hypofibrinogenaemia although bone marrow examination showed reactive changes but no evidence of haemophagocytosis. There was again improvement in rash, facial swelling and laboratory markers, and she was discharged to continue high dose steroids. She re-presented 7 days later with return of fevers, rash, jaundice and deterioration in her LFTs. Cyclosporin was added but ceased after 4 days due to concerns regarding worsening LFTs. Liver biopsy showed submassive central necrosis and prominent bile duct damage. Ganciclovir was added following an equivocal PCR for HHV-6 on the liver biopsy tissue and she was considered for liver transplant if her liver failure worsened. On day 40 her LFTs had improved but she developed mucosal ulceration involving the mouth, eyes and genitals with bullous skin lesions involving 80 % of the body surface which was Nikolsky sign positive. Skin biopsy was consistent with TEN. She was transferred to the ICU for aggressive management and intravenous immunoglobulin but deteriorated and passed away the next day. How this report contributes to current knowledge: Here, we present a fatal case of DRESS with fulminant liver failure followed by extensive TEN despite immunosuppression and broad anti-microbial cover.
Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. Results: Fourty seven cases of DRESS were included in our study: 27 men and 20 women, with a mean age of 47 years ± 19. Antiepileptics drugs (18 cases: 15 carbamazepine, 2 phenobarbital, and 1 lamorigine) were the most frequent responsible drugs in our study followed by antibiotics (12: 6 betalactams, 4 glycopeptides, 1 cotrimoxazole and 1 ethambutol), allopurinol (10) and salazopyrin (7). All patients had pruritic maculopapular rash involving more than 50 % of their body surface area. Mucosal involvement was observed mainly with antiepileptics drugs (five cases) and allopurinol (four cases). Lymphadenopathy was more frequent with salazopyrin and antiepileptics drugs (55 % each). Eosinophilia was observed in 90 % of cases with allopurinol, 66 % with antibiotics and antiepileptics drugs, and 57 % with salazopyrin. Atypical lymphocytosis was observed only in eight cases. Liver was the most common organ affected (74.5 %) in our series. The most frequent type of liver injury was: cytolytic with antibiotics and allopurinol (58 and 30 % respectively) and mixed with salazopyrin and allopurinol (57 and 50 % respectively). Renal failure was observed in all cases induced by allopurinol. Pulmonary involvement was observed in five cases (three with salazopyrin and two with antiepileptic drugs). The mean incubation period was similar in the four groups of incriminated drugs. The outcome was favorable after drug withdrawal in 95.7 % of cases. Two patients with DRESS induced by allopurinol died because of multiple organ failure. Skin tests (patch or intradermal tests) were done in 33 cases. 75 % of skin tests with antiepileptics drugs and antibiotics were positive. Skin tests with salazopyrin and allopurinol were all negative. Conclusions: Throughout this study, we point out the variability of DRESS clinical characteristics according to the culprit drug in one hand and the usefulness of skin tests with salazopyrin and allopurinol in the other hand.