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1. Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI)

Author

Giorgio Walter Canonica, MD, Francesco Blasi, PhD, Pierluigi Paggiaro, MD, Enrico Heffler, PhD, Fulvio Braido, MD, Luisa Brussino, PhD, Giulia Scioscia, PhD, Cristina Cardini, MsC, Chiara Oriecuia, MsC, Isabella Sala, MsC, Vincenzo Bagnardi, PhD, Cecilia Calabrese, PhD, Gianna Camiciottoli, MD, Giovanna Elisiana Carpagnano, PhD, Stefano Centanni, PhD, Angelo Guido Corsico, PhD, Maria Teresa Costantino, MD, Claudia Crimi, PhD, Alice D'Adda, MD, Simona D’Alò, MD, Maria D'Amato, PhD, Corrado D'Andria, MD, Stefano Del Giacco, MD, Fabiano Di Marco, PhD, Nicola Cosimo Facciolongo, MD, Alessandro Farsi, MD, Manuela Latorre, PhD, Manlio Milanese, PhD, Eustachio Nettis, MD, Eleonora Nucera, MD, Giovanni Passalacqua, MD, Girolamo Pelaia, MD, Laura Pini, MD, Luisa Ricciardi, PhD, Fabio Luigi Massimo Ricciardolo, PhD, Luca Richeldi, PhD, Erminia Ridolo, PhD, Pierachille Santus, PhD, Nicola Scichilone, PhD, Gianenrico Senna, MD, Giuseppe Spadaro, MD, Antonio Spanevello, MD, and Paolo Tarsia, MD

Subjects
Severe asthma, Clinical remission, Inhaled therapy, Biologics, Registry, Immunologic diseases. Allergy, RC581-607
Abstract

Background: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment. Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR. Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement. Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment. Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714).

Published
2025
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2. Perceptions of the impact of individual allergic rhinitis symptoms: A survey of ARIA clinical experts

Author

Sara Gil-Mata, MD, Tatiana Teixeira, MD, Anna Bedbrook, BSc, Jean Bousquet, PhD, Bernardo Sousa-Pinto, PhD, Rafael José Vieira, MD, Julijana Asllani, Habib Douagui, Estrella Asayag, Castro Maria Elizabeth, Carlos D. Crisci, René Maximiliano Gomez, Juan Carlos Ivancevich, Edgardo Jares, Jorge Fernando Máspero, Pablo Moreno, Hugo Eduardo Neffen, Mario Emilio Zernotti, Sinthia Bosnic-Anticevich, Kristin Chahhoud Carson, Biljana Cvetkovski, Janet M. Davies, Vicky Kritikos, Robyn O'Hehir, Brian Oliver, House Rachel Tan, Jessica Tattersall, Celia Zubrinich, Werner Aberer, Verena Niederberger-Leppin, Isabella Pali-Schöll, Virginie Doyen, Didier Ebo, Renaud Louis, Philippe Rombaux, Sophie Scheire, Kazi Bennoor, Bruno A. Barreto, Paulo Camargos, Herberto Jose Chong-Neto, Alvaro A. Cruz, Jane da Silva, Guidacci Marta, José Angelo Rizzo, Nelson Rosario Filho, Sarquis Serpa Faradiba, Dirceu Solé, Marilyn Urrutia-Pereira, George Christoff, Mandazhieva-Pepelanova Mariana, Odjakova Cvetanka, Todor A. Popov, Dilyana Vicheva, do Ceu Teixeira Maria, Jacques Bouchard, Jan Brozek, Derek K. Chu, Judah Denburg, Thomas Eiwegger, Paul K. Keith, Teresa To, Susan Waserman, Nancy Abusada, Emilio Alvarez Cuesta, Mario A. Calvo-Gil, Maria Antonieta Guzmán, Tamara Pérez Gomez, Wing Kin Wong Gary, Luo Zhang, Luis Caraballo, Alfonso Cepeda Sarabia, Dieudonné Nyembue, Manuel Soto-Martinez, Neven Miculinic, Davor Plavec, Constantinos Pitsios, Panayiotis Yiallouros, Petr Panzner, Milan Sova, Martina Vachova, Carsten Bindslev-Jensen, Ronald Dahl, Hans-Jorgen Malling, Lars Münter, Lars K. Poulsen, Suppli Ulrik Charlotte, Line Kring Tannert, Bassam Mahboub, Laila Salameh, Ivan Cherrez-Ojeda, de Guevara Karla Robles, Rasha Hassan El-Owaidy, Zeinab A. El-Sayed, Shereen Saad El-Sayed, Elham Hossny, Badr Eldin Mostafa, Kaja Julge, Nils Eric Billo, Patrik Eklund, Marina Erhola, Tari Haahtela, Jussi Karjalainen, Mika Makela, Sanna Toppila-Salmi, Erkka Valovirta, Tuula Vasankari, Isabella Annesi-Maesano, Isabelle Bossé, Melisande Bourgoin-Heck, Denis Charpin, André Coste, Frédéric de Blay, Philippe Devillier, Alain Didier, Anh Tuan Dinh-Xuan, Jean-François Fontaine, Jocelyne Just, Rachel Nadif, Nhân Pham-Thi, Bernard Pigearias, Nicolas Roche, Van Ganse Eric, Ekaterine Chkhartishvili, Amiran Gamkrelidze, Maia Gotua, Sven Becker, Karl-Christian Bergmann, Thomas Bieber, Randolf Brehler, Roland Buhl, Adam M. Chaker, Ulf Darsow, Eckard Hamelmann, Joachim Heinrich, Thomas Keil, Ludger Klimek, Pavel Kolkhir, Susanne Lau, Marcus Maurer, Ralph Mösges, Angelos Neou, Oliver Pfaar, Johannes Ring, Martin Wagenmann, Torsten Zuberbier, Aiste Ramanauskaite, Anja Lingnau, Demetrios Christou, Sophia Neisinger, Xenophon Aggelidis, Jannis Constantinidis, Maria Dimou, Christos Grigoreas, Trisevgeni Kapsali, Michael Katotomichelakis, Stelios Loukides, Michael Makris, Emmanouil Manousakis, Nikolaos Mikos, Aris Pagkalos, Nikolaos G. Papadopoulos, Vasileios Papanikolaou, Giannis Paraskevopoulos, Konstantina Piskou, Emmanuel Prokopakis, Fotios Psarros, Konstantinos Samitas, Sofia Stamataki, Evangelia Stefanaki Lina, Ekaterini Syrigou, Ioanna Tsiligianni, Mina Vallianatou, Dimitrios Vourdas, Paraskevi Xepapadaki, Aspasia Karavelia, Fanny Wai San Ko, Gary Wong, Andor Hirschberg, Helga Kraxner, Kristof Nekam, Stephen Lane, Menachem Rottem, Cristina Artesani Maria, Simona Barbaglia, Bianca Beghé, Beatrice Bilo Maria, Attilio Boner, Matteo Bonini, Sergio Bonini, Fulvio Braido, Luisa Brussino, G Walter Canonica, Lorenzo Cecchi, Giorgio Ciprandi, Enrico Compalati, Gennaro D'Amato, Giulia De Feo, Stefano Del Giacco, Alessandro Fiocchi, Enrico Heffler, Carlo Lombardi, Riccardo Monti, Antonella Muraro, Eustachio Nettis, Stefania Nicola, Giovanni Passalacqua, Vincenzo Patella, Francesca Puggioni, Giovanni Rolla, Antonino Romano, Nicola Scichilone, Massimo Triggiani, Teresa Ventura Maria, Giovanni Viegi, Cristina Boccabella, Mattia Giovannini, Anand Mahesh Padukudru, Tomohisa Iinuma, Ken Ohta, Yoshitaka Okamoto, Kimihiro Okubo, Ruby Pawankar, Daiju Sakurai, Maho Suzukawa, Masao Yamaguchi, Zhanat Ispayeva, Yoon-Seok Chang, Hae-Sim Park, Mona Al-Ahmad, Ieva Cirule, Ineta Grisle, Carla Irani, Philip Rouadi, Fares Zaitoun, Ruta Dubakiene, Regina Emuzyte, Violeta Kvedariene, Brigita Gradauskiene, Arunas Valiulis, Markus Ollert, Farah Hannachi, Dejan Dokic, Amir Hamzah Abdul Latiff, Baharudin Abdullah, S.P. Palaniappan, Kent Woo, Stephen Montefort, Martín Bedolla Barajas, María del Carmen Costa Domínguez, Jesús Guillermo Espinoza Contreras, Jose Miguel Fuentes Pèrez, José Luis Gálvez Romero, María de la Luz Hortensia García Cruz, Sandra González Diaz, Yunuen Rocío Huerta Villalobos, Désiree E. Larenas-Linnemann, Jorge Agustin Luna-Pech, Juan José Matta Campos, Daniela Rivero Yeverino, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Battur Lkhagvaa, Sandra Mavale-Manuel, Abrantes Nunes Elizabete, Niels Chavannes, Wytske J. Fokkens, Gerard Koppelman, Anke-Hilse Maitland-van der Zee, Sietze Reitsma, Ramanathan Chandrasekharan, Osman Yusuf, Maria Susana Repka-Ramirez, Juan Carlos Sisul, José E. Gereda, Marysia T. Recto, Slawomir Bialek, Artur Bialoszewski, Marta Chelminska, Radoslaw Gawlik, Ewa Jassem, Marek Jutel, Piotr Kuna, Maciej Kupczyk, Marcin Moniuszko, Marek Niedoszytko, Filip Raciborski, Jan Romantowski, Boleslaw Samolinski, Krzysztof Specjalski, Pedro Carreiro Martins, Jaime Correia de Sousa, Elisio Costa, Joao A. Fonseca, Olga Lourenço, Mario Morais-Almeida, Margarida Pereira Ana, Frederico Regateiro, Carlos Robalo Cordeiro, Jose Rosado Pinto, Bernardo Sousa-Pinto, Luis Taborda Barata, Ana Maria Todo-Bom, José Vieira Rafael, Daniela Carvalho, Maryam Ali Al-Nesf, Ioana Agache, Camelia Berghea Elena, Roxana Bumbacea, Diana Deleanu, Florin Mihaltan, Carmen Panaitescu Bunu, Musa Khaitov, Leyla Namazova-Baranova, Elena Vishneva, Ali Alshaikh Nada, Sanja Dimic-Janjic, Branislava Milenkovic, De Yun Wang, Martin Hrubiško, Natalija Edelbaher, Maja Jošt, Peter Kopac, Mitja Košnik, Nika Lalek, Antonija Poplas Susic, Irma Rozman Sinur, Tanja Soklic Košak, Nadja Triller, Katja Triller, Jure Urbancic, Mihaela Zidarn, Michael Levin, Paul Potter, Heather Zar, Isam Alobid, Aram Anto, Joan Bartra, Irina Bobolea, Paloma Campo, Vicky Cardona, Maria Carriazo Ana, José Antonio Castillo Vizuete, Tomas Chivato, Ignacio Jesus Davila Gonzalez, Joaquim Mullol, Antonio Nieto Garcia, César Picado, Santiago Quirce, Joaquin Sastre, Leticia de las Vecillas, Mikael Benson, Inger Kull, Marianne van Hage, Magnus Wickman, Nikolai Khaltaev, Yousser Mohammad, Pongsakorn Tantilipikorn, Pakit Vichyanond, Cemal Cingi, Bilun Gemicioglu, Ozlem Goksel, Omer Kalayci, Ali Fuat Kalyoncu, Cem Meço, Koyuncu Ilgim Vardaloglu, Arzu Yorgancioglu, Deniz Eyice Karabacak, Bruce Kirenga, Ian Michael Adcock, Hasan S. Arshad, Mike Bewick, Christine Bond, Christopher Brightling, Andrew Bush, Moïses Calderon, Kian Fan Chung, Adnan Custovic, Ratko Djukanovic, Stephen Durham, John Farrell, David Halpin, Michael Hyland, Sebastian Johnston, Brian Lipworth, Alla Nakonechna, David Price, Graham Roberts, Dermot Ryan, Jürgen Schwarze, Aziz Sheikh, Mike Shields, Samantha Walker, Sian Williams, Igor Kaidashev, Andrii Igorevich Kurchenko, Vladyslav Tsaryk, David Bernstein, Jonathan A. Bernstein, Thomas B. Casale, Sharon Chinthrajah, Mark Dykewicz, Gailen D. Marshall, Eli O. Meltzer, Robert M. Naclerio, Alkis Togias, Elina Toskala, Dana Wallace, Dennis M. Williams, Barbara Yawn, Fernan Caballero-Fonseca, Lan Le Thi Tuyet, and Tran Thien Quan Vu

Subjects
Allergic rhinitis, Survey, Professional-patient relation, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Published
2024
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3. Profiling severe asthma: Any relevance for age? An analysis from Severe Asthma Network Italy (SANI) cohort

Author

Marco Caminati, MD, Alessandro Marcon, PhD, Rachele Vaia, MD, Gianenrico Senna, MD, Matteo Maule, MD, Pierpaolo Marchetti, MD, Jessica Miotti, MD, Giuseppe Argentino, MD, Francesco Blasi, MD, PhD, Giorgio W. Canonica, MD, Enrico M. Heffler, MD, PhD, Pierluigi Paggiaro, MD, Andrea Vianello, MD, PhD, Gabriella Guarnieri, MD, Luisa Brussino, MD PhD, S.S.D.D.U, Cecilia Calabrese, MD PhD, Gianna Camiciottoli, MD, Giovanna E. Carpagnano, MD PhD, Stefano Centanni, MD PhD, Angelo G. Corsico, MD PhD, Maria T. Costantino, MD, Claudia Crimi, MD PhD, Alice D'adda, MD, Simona D'alo, MD, Maria D'amato, MD PhD, Stefano Del Giacco, MD, Fabiano Di Marco, MD PhD, Nicola C. Facciolongo, MD, Manuela Latorre, MD PhD, Eustachio Nettis, MD, Eleonora Nucera, MD, Giovanni Passalacqua, MD, Girolamo Pelaia, MD, Laura Pini, MD PhD, Luisa Ricciardi, MD, Luca Richeldi, MD, Erminia Ridolo, MD PhD, Pierachille Santus, MD PhD, Nicola Scichilone, MD, Giulia Scioscia, MD PhD, Giuseppe Spadaro, MD, Antonio Spanevello, MD PhD, and Paolo Tarsia, MD PhD

Subjects
Severe asthma, Aging, Comorbidities, Lung function, Asthma control, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Published
2024
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5. Managing Patients with Hypereosinophilic Syndrome: A Statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC)

Author

Marco Caminati, Luisa Brussino, Matilde Carlucci, Palma Carlucci, Lucia Federica Carpagnano, Cristiano Caruso, Lorenzo Cosmi, Simona D’Amore, Stefano Del Giacco, Aikaterini Detoraki, Mario Di Gioacchino, Andrea Matucci, Ilaria Mormile, Francescopaolo Granata, Gabriella Guarnieri, Mauro Krampera, Matteo Maule, Eustachio Nettis, Stefania Nicola, Silvia Noviello, Fabrizio Pane, Cristina Papayannidis, Paola Parronchi, Girolamo Pelaia, Erminia Ridolo, Francesca Wanda Rossi, Gianenrico Senna, Massimo Triggiani, Angelo Vacca, Emanuele Vivarelli, Alessandra Vultaggio, and Amato de Paulis

Subjects
eosinophils, hypereosinophilia, hypereosinophilic syndrome, mepolizumab, management, network, Cytology, QH573-671
Abstract

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Published
2024
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6. Systemic drug-related intertriginous and flexural exanthema-like eruption after Oxford-AstraZeneca COVID-19 vaccine

Author

Danilo Di Bona, Andrea Miniello, and Eustachio Nettis

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Systemic drug-related intertriginous and flexural exanthema (SDRIFE) is an adverse drug reaction which manifests as a symmetrical erythematous rash involving the skin folds after systemic drug exposure. A vast array of possible side effects associated with administration of different anti-SARS-CoV-2 vaccines have been reported in literature since the beginning of the COVID-19 pandemic, but only few times SDRIFE-like eruptions have been described in this context. We discuss here a case of SDRIFE-like eruption following the second dose of Oxford-Astrazeneca Vaxzevria vaccine.

Published
2022
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7. A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative

Author

Torsten Zuberbier, Amir Abdul Latiff, Xenofon Aggelidis, Matthias Augustin, Radu‐Gheorghe Balan, Christine Bangert, Lisa Beck, Thomas Bieber, Jonathan A. Bernstein, Marta Bertolin Colilla, Alejandro Berardi, Anna Bedbrook, Carsten Bindslev‐Jensen, Jean Bousquet, Marjolein deBruin‐Weller, Dayanne Bruscky, Betul Buyuktiryaki, Giorgio Walter Canonica, Carla Castro, Natia Chanturidze, Herberto Jose Chong‐Neto, Chia‐Yu Chu, Leena Chularojanamontri, Michael Cork, Roberta F. J. Criado, Laia Curto Barredo, Adnan Custovic, Ulf Darsow, Arben Emurlai, Ana dePablo, Stefano DelGiacco, Giampiero Girolomoni, Tanja Deleva Jovanova, Mette Deleuran, Nikolaos Douladiris, Bruno Duarte, Ruta Dubakiene, Esben Eller, Batya Engel‐Yeger, Luis Felipe Ensina, Nelson Rosario Filho, Carsten Flohr, Daria Fomina, Wojciech Francuzik, Maria Laura Galimberti, Ana M. Giménez‐Arnau, Kiran Godse, Charlotte Gotthard Mortz, Maia Gotua, Michihiro Hide, Wolfram Hoetzenecker, Nicolas Hunzelmann, Alan Irvine, Carolyn Jack, Ioanna Kanavarou, Norito Katoh, Tamar Kinaciyan, Emek Kocatürk, Kanokvalai Kulthanan, Hilde Lapeere, Susanne Lau, Mariana Machado Forti Nastri, Michael Makris, Eli Mansour, Alexander Marsland, Mara Morelo Rocha Felix, Ana Paula Moschione Castro, Eustachio Nettis, J. F. Nicolas, Audrey Nosbaum, Mikaela Odemyr, Niki Papapostolou, Claudio A. S. Parisi, Sushil Paudel, Jonny Peter, Prakash Pokharel, Luis Puig, Tamara Quint, German Dario Ramon, Frederico Regateiro, Giampaolo Ricci, Cristine Rosario, Cansin Sackesen, Peter Schmid‐Grendelmeier, Esther Serra‐Baldrich, Kristina Siemens, Cathrine Smith, Petra Staubach, Katarina Stevanovic, Özlem Su‐Kücük, Gordon Sussman, Simona Tavecchio, Natasa Teovska Mitrevska, Diamant Thaci, Elias Toubi, Claudia Traidl‐Hoffmann, Regina Treudler, Zahava Vadasz, Ingrid vanHofman, Maria Teresa Ventura, Zhao Wang, Thomas Werfel, Andreas Wollenberg, Ariana Yang, Yik Weng Yew, Zuotao Zhao, Ricardo Zwiener, and Margitta Worm

Subjects
atopic dermatitis, eczema, guidance, ICP, integrated care pathways, multidisciplinary, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Introduction The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Published
2023
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8. Novel approach to idursulfase and laronidase desensitization in type 2 and type 1 S mucopolysaccharidosis (MPS)

Author

Federico Spataro, Fabio Viggiani, Domenico Giorgio Macchia, Valentina Rollo, Albina Tummolo, Patrizia Suppressa, Carlo Sabba’, Maria Pia Rossi, Lucia Giliberti, Francesco Satriano, Eustachio Nettis, Danilo Di Bona, Maria Filomena Caiaffa, Rita Fischetto, and Luigi Macchia

Subjects
Enzyme replacement therapy, ERT, Scheie syndrome, Hunter syndrome, Drug allergy, Allergen immunotherapy, Medicine
Abstract

Abstract Background: Idursulfase and laronidase are drugs used to treat Hunter syndrome (mucopolysaccharidosis type 2) and Scheie syndrome (mucopolysaccharidosis type 1 S), respectively. These are rare lysosomal storage disorders, leading to accumulation of glycosaminoglycans within lysosomes. Failure of early recognition of the disease and/or delay in starting the appropriate treatment result in severe clinical impairment and death. For almost 20 years, enzyme replacement therapy with recombinant proteins has represented the first line therapeutic option. However, administration of idursulfase and laronidase is associated with infusion-related hypersensitivity reactions, in approx. 20% of patients. In these patients, rapid desensitization by intravenous administration protocols has been used in order to avoid treatment discontinuation. This approach proved effective and safe. However, long-term tolerance could not be achieved. Thus, we decided to combine rapid desensitization with allergen immunotherapy-like desensitization. Results: Two patients with Hunter syndrome and one patient with Scheie syndrome developed severe allergy to idursulfase and laronidase, respectively, preventing them from continuing the otherwise indispensable therapy. In all three patients, the possible IgE-mediated nature of the reactions suffered was suggested by positive skin tests with the two enzymes, respectively. By devising 12-step, 3-dilution rapid desensitization protocols, we resumed the enzyme replacement therapy. However, the prolonged time required for administration (a not negligible pitfall, since therapy should be given weekly for life) and the persistent occurrence of reactions (mild but still requiring anti-allergic medication at full dosage) led us to combine rapid desensitization with a compact 11-step, 24-day allergen immunotherapy-like desensitization protocol. Thus, idursulfase and laronidase were injected subcutaneously, with a 500-fold increase from step 1 to step 11 for idursulfase and a 222-fold increase for laronidase. This strategy led to restoration of long-term tolerance, allowing weekly intravenous therapy administration under standard conditions, according to the manufacturer instructions, in the absence of side effects and with only precautionary low-dose premedication. Conclusion: Rapid desensitization is a suitable and safe option in the case of idursulfase and laronidase allergy. Combination with subcutaneous allergen immunotherapy-like desensitization afforded restoration of enzyme replacement therapy given by the normal administration schedule, by inducing sustained tolerance.

Published
2022
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9. Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life

Author

Eustachio Nettis, Luisa Brussino, Vincenzo Patella, Laura Bonzano, Aikaterini Detoraki, Elisabetta Di Leo, Maria Maddalena Sirufo, Cristiano Caruso, Fabio Lodi Rizzini, Mariaelisabetta Conte, Mona-Rita Yacoub, Massimo Triggiani, Erminia Ridolo, Luigi Macchia, Giovanni Rolla, Raffaele Brancaccio, Amato De Paulis, Giuseppe Spadaro, Danilo Di Bona, Angela Maria D’Uggento, Lia Ginaldi, Francesco Gaeta, Eleonora Nucera, Kliljeda Jaubashi, Danilo Villalta, Lorenzo Dagna, Domenico Ciotta, Francesco Pucciarini, Diego Bagnasco, Giorgio Celi, Fulvia Chieco Bianchi, Lorenzo Cosmi, Maria Teresa Costantino, Maria Angiola Crivellaro, Simona D’Alò, Pietro del Biondo, Stefano Del Giacco, Mario Di Gioacchino, Linda Di Pietro, Elisabetta Favero, Sebastiano Gangemi, Gabriella Guarnieri, Enrico Heffler, Maria Stefania Leto Barone, Carla Lombardo, Francesca Losa, Andrea Matucci, Paola Lucia Minciullo, Paola Parronchi, Giovanni Passalacqua, Stefano Pucci, Oliviero Rossi, Lorenzo Salvati, Michele Schiappoli, Gianenrico Senna, Andrea Vianello, Alessandra Vultaggio, Yang Baoran, Cristoforo Incorvaia, and Giorgio Walter Canonica

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. Methods We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). Results In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. Conclusions These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Published
2022
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10. Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder

Author

Ester Di Agosta, Lorenzo Salvati, Monica Corazza, Ilaria Baiardini, Francesca Ambrogio, Luisa Angileri, Elettra Antonelli, Federica Belluzzo, Domenico Bonamonte, Laura Bonzano, Raffaele Brancaccio, Paolo Custurone, Aurora De Marco, Aikaterini Detoraki, Adriana Di Guida, Elisabetta Di Leo, Marta Fantò, Filippo Fassio, Silvia Mariel Ferrucci, Caterina Foti, Rosella Gallo, Alessia Gatta, Fabrizio Guarneri, Lucia Guidolin, Katharina Hansel, Donatella Lamacchia, Carla Lombardo, Paola Lucia Minciullo, Maddalena Napolitano, Alessandro Pannofino, Andrea Paravisi, Roberta Parente, Maria Passante, Cataldo Patruno, Diego Peroni, Cristina Quecchia, Natale Schettini, Giuseppe Spadaro, Luca Stingeni, Daniele Tarrini, Marta Tramontana, Eustachio Nettis, and Oliviero Rossi

Subjects
Quality of life, Atopic dermatitis, Allergic contact dermatitis, Hereditary angioedema, Cutaneous mastocytosis, Urticaria, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.

Published
2021
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11. Angioedema associated with dipeptidyl peptidase-IV inhibitors

Author

Nicoletta Cassano, Eustachio Nettis, Elisabetta Di Leo, Francesca Ambrogio, Gino A. Vena, and Caterina Foti

Subjects
Dipeptidyl peptidase-IV inhibitors, Gliptins, Angioedema, Angiotensin-converting enzyme inhibitors, Bradykinin, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are a class of oral antidiabetic agents. Postmarketing reports have documented the occurrence of angioedema in patients treated with gliptins and it was found that these drugs increased the risk of angioedema in patients concurrently treated with angiotensin-converting enzyme inhibitors (ACEIs). The aim of this manuscript is to provide an overview of the risk of angioedema associated with gliptins. Methods The keywords used for the literature search in the PubMed database included “angioedema” and “dipeptidyl peptidase”, “gliptins”, or the name of each DPP-IV inhibitor. Articles in English published up to December 2020 were taken into consideration. Results The available data appear to rule out a higher risk of angioedema associated with gliptin monotherapy and have revealed an increased susceptibility in patients simultaneously treated with gliptins and ACEIs. However, one single multicenter phase IV trial and case reports, even if very limited in number, have shown that angioedema can also occur during treatment with DPP-IV inhibitors without the concomitant use of ACEIs. The involvement of other drugs and drug interactions has occasionally been suggested. In a few patients, deficiency of enzymes involved in bradykinin catabolism was detected and this finding can constitute a risk factor for angioedema exacerbated by treatment with DPP-IV inhibitors. Conclusions This risk of angioedema associated with the use of gliptins has mostly been related to the concurrent administration of ACEIs, and has been considered rare, but it might be underestimated and underreported. The role of additional risk factors or drug interactions deserves further investigations. Caution should be taken when considering the use of DPP-IV inhibitors in patients treated with ACEIs or presenting with other known risk factors for angioedema.

Published
2021
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12. Allergic contact dermatitis from vitamins: A systematic review

Author

Caterina Foti, Gianfranco Calogiuri, Eustachio Nettis, Aurora De Marco, Luca Stingeni, Katharina Hansel, Danilo Di Bona, Palma Carlucci, Paolo Romita, and Annick Barbaud

Subjects
allergic contact dermatitis, fat‐soluble vitamins, hydro‐soluble vitamins, lymphocyte transformation test, multivitamins, patch test, Medicine
Abstract

Abstract Background and Aims Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. Methods This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. Results A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. Conclusion ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered “natural” and therefore “safe” ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis.

Published
2022
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13. Dupilumab elicits a favorable response in type-2 inflammatory comorbidities of severe atopic dermatitis

Author

Eustachio Nettis, Lucia Masciopinto, Elisabetta Di Leo, Nicola De Candia, Marcello Albanesi, Danilo Di Bona, Nicola Quaranta, and Luigi Macchia

Subjects
Monoclonal antibody, Precision medicine, Asthma, Nasal polyps, Rhinoconjuctivitis, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background This case is the first report describing rapid, successful treatment of severe atopic dermatitis (AD) and comorbid type-2 inflammatory diseases in the same patient, with dupilumab treatment, with no side-effects. Case presentation We report on effects of dupilumab in a patient with severe AD, a long-standing history of a mild, perennial allergic rhino-conjunctivitis, moderate asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Conclusions Patients suffering from AD, asthma, allergic rhinitis and CRSwNP may be eligible for dupilumab single treatment that is possibly advantageous also from the pharmaco-economic standpoint.

Published
2021
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14. Microbiota and IL-33/31 Axis Linkage: Implications and Therapeutic Perspectives in Atopic Dermatitis and Psoriasis

Author

Laura Bonzano, Francesco Borgia, Rossella Casella, Andrea Miniello, Eustachio Nettis, and Sebastiano Gangemi

Subjects
microbiota, IL-33, IL-31, cytokines, psoriasis, atopic dermatitis, Microbiology, QR1-502
Abstract

Microbiome dysbiosis and cytokine alternations are key features of atopic dermatitis (AD) and psoriasis (PsO), two of the most prevalent and burdensome pruritic skin conditions worldwide. Interleukin (IL)-33 and IL-31 have been recognized to be major players who act synergistically in the pathogenesis and maintenance of different chronic inflammatory conditions and pruritic skin disorders, including AD and PsO, and their potential role as therapeutic targets is being thoroughly investigated. The bidirectional interplay between dysbiosis and immunological changes has been extensively studied, but there is still debate regarding which of these two factors is the actual causative culprit behind the aetiopathological process that ultimately leads to AD and PsO. We conducted a literature review on the Pubmed database assessing articles of immunology, dermatology, microbiology and allergology with the aim to strengthen the hypothesis that dysbiosis is at the origin of the IL-33/IL-31 dysregulation that contributes to the pathogenesis of AD and PsO. Finally, we discussed the therapeutic options currently in development for the treatment of these skin conditions targeting IL-31, IL-33 and/or the microbiome.

Published
2023
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15. Safety of measles, mumps, and rubella vaccine in egg allergy: in vivo and in vitro management

Author

Stefania Magistà, Marcello Albanesi, Nada Chaoul, Danilo Di Bona, Elisabetta Di Leo, Eustachio Nettis, Maria Filomena Caiaffa, and Luigi Macchia

Subjects
Vaccine adverse reaction, Food allergy, Drug allergy, Anaphylaxis, B-cell proliferation assay, Flow cytometry, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Egg allergy is the second most prevalent form of food allergy in childhood. In spite of the evidence accumulated, inoculating egg allergy children with attenuated vaccines grown on chick embryo cell cultures, such as the measles, mumps, and rubella (MMR) vaccine, is regarded (erroneously) as potentially dangerous or even anaphylactogenic, by many. An issue perceived as particularly conflicting also by Health Professionals. Case presentation A 15-year-old boy, with a history of severe egg allergy in early infancy, who was still sensitized to egg allergens, including baked egg, had never received MMR vaccination, in fear of possible anaphylaxis, in spite of the fact that this vaccination is mandatory in the first year of life, in Italy. Because of that, he was not allowed to attend school, longer, and was referred to us in order to assess the potential risk of MMR vaccination. Upon thorough allergologic workup, sensitization to MMR vaccine components was excluded by an in vivo approach, consisting in skin prick tests, intradermal tests, and subcutaneous injection test, corroborated by vaccine-specific B-lymphocyte proliferation assay, ex vivo. T-cell proliferation in response to MMR vaccine was also excluded. Eventually, the boy was inoculated with MMR vaccine and was readmitted to school. Conclusions The diagnostic strategy adopted appears feasible and easy-to-perform and may be adopted in controversial cases (as the one reported), characterized by previous severe allergic reactions to egg. The B-lymphocyte proliferation assay we developed may represent a useful and reliable tool not only in research but also in clinical practice.

Published
2020
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16. Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology

Author

Eustachio Nettis, Caterina Foti, Marina Ambrifi, Ilaria Baiardini, Leonardo Bianchi, Alessandro Borghi, Marco Caminati, Giorgio Walter Canonica, Marco Casciaro, Laura Colli, Giselda Colombo, Monica Corazza, Antonio Cristaudo, Giulia De Feo, Ornella De Pita’, Mario Di Gioacchino, Elisabetta Di Leo, Filippo Fassio, Sebastiano Gangemi, Alessia Gatta, Katharina Hansel, Enrico Heffler, Cristoforo Incorvaia, Maddalena Napolitano, Cataldo Patruno, Silvia Peveri, Paolo Daniele Pigatto, Cristina Quecchia, Anna Radice, Giuseppe Alvise Ramirez, Paolo Romita, Franco Rongioletti, Oliviero Rossi, Eleonora Savi, Gianenrico Senna, Massimo Triggiani, Myriam Zucca, Enrico Maggi, and Luca Stingeni

Subjects
Acute urticaria, Chronic urticaria, Angioedema, Guidelines, Antihistamines, Corticosteroids, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12–22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6–16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1–1.5 cases/1000 inhabitants/year. Methods We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. Conclusions The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Published
2020
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17. miRNAs’ Cross-Involvement in Skin Allergies: A New Horizon for the Pathogenesis, Diagnosis and Therapy of Atopic Dermatitis, Allergic Contact Dermatitis and Chronic Spontaneous Urticaria

Author

Raffaele Brancaccio, Giuseppe Murdaca, Rossella Casella, Teresa Loverre, Laura Bonzano, Eustachio Nettis, and Sebastiano Gangemi

Subjects
miRNA, atopic dermatitis, chronic spontaneous urticaria, allergic contact dermatitis, antagomirs, cytokines, Biology (General), QH301-705.5
Abstract

Skin inflammation is a common underlying feature of atopic dermatitis, allergic contact dermatitis and chronic spontaneous urticaria. The pathogenetic mechanisms have not been fully elucidated. The purpose of this study was to examine whether miRNA, by regulating inflammatory mechanisms through the modulation of innate and adaptive immune responses, could play a major role in the pathogenesis of these skin conditions. We conducted a narrative review using the Pubmed and Embase scientific databases and search engines to find the most relevant miRNAs related to the pathophysiology, severity and prognosis of skin conditions. The studies show that miRNAs are involved in the pathogenesis and regulation of atopic dermatitis and can reveal an atopic predisposition or indicate disease severity. In chronic spontaneous urticaria, different miRNAs which are over-expressed during urticaria exacerbations not only play a role in the possible response to therapy or remission, but also serve as a marker of chronic autoimmune urticaria and indicate associations with other autoimmune diseases. In allergic contact dermatitis, miRNAs are upregulated in inflammatory lesions and expressed during the sensitization phase of allergic response. Several miRNAs have been identified as potential biomarkers of these chronic skin conditions, but they are also possible therapeutic targets.

Published
2023
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18. Focus on the role of substance P in chronic urticaria

Author

Gino A. Vena, Nicoletta Cassano, E. Di Leo, G. F. Calogiuri, and Eustachio Nettis

Subjects
Substance P, Chronic urticaria, Chronic spontaneous urticaria, Neuropeptides, Mast cells, Basophils, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Emerging data have strengthened the importance of substance P (SP) as a proinflammatory mediator in human pathology. A role for SP in the pathogenesis of urticaria has long been hypothesized. Methods Literature data regarding the possible role of SP in chronic urticaria/chronic spontaneous urticaria (CSU) have been reviewed and summarized in this manuscript. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database. Articles in English published up to July 2018 were taken into consideration. Results Recent studies in patients with CSU have demonstrated that circulating levels of SP are significantly elevated, in correlation with disease severity, and that SP-positive basophils are upregulated. SP has been shown to trigger degranulation in basophils derived from CSU patients. Moreover, SP can be involved in pseudoallergic reactions and may act as a histamine-releasing factor in a subset of patients with CSU. Current evidence suggests that the biological activity of SP can be exerted not only through the conventional NK-1 receptor but also through the recently identified Mas-related G protein-coupled receptors. MRGPRX2 can cause mast cell activation and has been found to be upregulated in the skin of patients with severe chronic urticaria. Conclusions Many findings seem to support the pathogenic involvement of SP in chronic urticaria/CSU. However, further studies are necessary to elucidate the role of SP as a mediator in CSU pathogenesis and a potential new therapeutic target.

Published
2018
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19. Rapid desensitization for brentuximab vedotin (Adceteris®) allergy: a case report

Author

Attilio Di Girolamo, Marcello Albanesi, Alessandro Sinisi, Eustachio Nettis, Danilo Di Bona, Maria Filomena Caiaffa, and Luigi Macchia

Subjects
Anti CD30, Auristatin-E, Hodgkin lymphoma, Desensitization, Monoclonal antibodies, Drug allergy, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Brentuximab vedotin (BV) is an antibody–drug conjugate formed by an anti-CD30 chimeric IgG1 conjugated with monomethyl-auristatin-E. BV targets the CD30+ cells, which characterize Hodgkin lymphoma as well as anaplastic large cell lymphoma. Once bound to the CD30+ cells BV exerts its cytotoxic effect via the monomethyl-auristatin-E moiety. So far, accounts on immediate adverse reactions to BV remain anecdotal. Moreover, few reports exist on desensitization for BV. Case presentation A 20-year old male patient was diagnosed with Hodgkin lymphoma in July 2014. The first line treatment with adriblastine, bleomicine, vinblastine and dacarbazine lead to a partial remission. Thus, a treatment with BV was started. However, during the second BV infusion, he developed generalized urticaria and dyspnea. In order not to discontinue the treatment with BV, we performed a thorough allergological workup and designed a 12-step rapid desensitization protocol. Overall the desensitization procedure was well tolerated and no major adverse reactions occurred. Conclusion Rapid desensitization is a suitable and safe option in the case of BV allergy and prevents the BV treatment withdrawal.

Published
2018
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20. Hypersensitivity reactions due to black henna tattoos and their components: are the clinical pictures related to the immune pathomechanism?

Author

Gianfranco Calogiuri, Elisabetta Di Leo, Lavjay Butani, Stefano Pizzimenti, Cristoforo Incorvaia, Luigi Macchia, and Eustachio Nettis

Subjects
Para-phenylenediamine, Henna tattoo, Black henna, Contact dermatitis, Allergy, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by temporary black henna tattoos has become a serious health problem worldwide. Different patterns of sensitization with various clinical aspects are described in literature due to PPD associated to henna tattoo and these manifestations are likely correlated with the immunological and dermatological pathomechanisms involved. Henna is the Persian name of the plant Lawsonia inermis, Fam. Lythraceae. It is a woody shrub that grow in regions of North Africa, South Asia, India and Sri Lanka. Nowadays it is rather frequent to see temporary “tattoos” performed with henna. To make tattoos darker and long-lasting PPD has been associated to henna in tattoo drawings mixtures, so obtaining “black henna”. In these years there has been a rise of contact sensitization to PPD and in medical literature an increased number of cases have been reported on temporary henna tattoo application. Here we review the various clinical patterns related to PPD and henna tattoo, to investigate the possible link between clinic-morphological pictures and the immunological response to PPD and henna. The literature underlines that different clinical manifestations are related to black henna containing PPD, and its derivative products may cause delayed-type as well as immediate-type reactions. Further studies are needed to investigate the relationship between clinical and morphological aspects of PPD contact dermatitis and the T cell subsets predominance.

Published
2017
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22. Allergenius, an expert system for the interpretation of allergen microarray results

Author

Giovanni Melioli, Clive Spenser, Giorgio Reggiardo, Giovanni Passalacqua, Enrico Compalati, Anthi Rogkakou, Anna Maria Riccio, Elisabetta Di Leo, Eustachio Nettis, and Giorgio Walter Canonica

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background An in vitro procedure based on a microarray containing many different allergen components has recently been introduced for use in allergy diagnosis. Recombinant and highly purified allergens belonging to different allergenic sources (inhalants, food, latex and hymenoptera) are present in the array. These components can either be genuine or cross-reactive, resistant or susceptible to heat and low pH, and innocuous or potentially dangerous. A large number of complex and heterogeneous relationships among these components has emerged, such that sometimes these interactions cannot be effectively managed by the allergist. In the 1960s, specialized languages and environments were developed to support the replacement of human experts with dedicated decision-making information systems. Currently, expert systems (ES) are advanced informatics tools that are widely used in medicine, engineering, finance and trading.Methods We developed an ES, named Allergenius ®, to support the interpretation of allergy tests based on microarray technology (ImmunoCAP ISAC ®). The ES was implemented using Flex, a LPA Win-Prolog shell. Rules representing the knowledge base (KB) were derived from the literature and specialized databases. The input data included the patient’s ID and disease(s), the results of either a skin prick test or specific IgE assays and ISAC results. The output was a medical report.Results The ES was first validated using artificial and real life cases and passed all in silico validations. Then, the opinions of allergists with experience in molecular diagnostics were compared with the ES reports. The Allergenius reports included all of the allergists’ opinions and considerations, as well as any additional information.Conclusions Allergenius is a trustable ES dedicated to molecular tests for allergy. In the present version, it provides a powerful method to understand ISAC results and to obtain a comprehensive interpretation of the patient’s IgE profiling. Keywords: 3 TO 10 DIFFERENT ImmunoCAP ISAC, Allergen microarray, Artificial intelligence, Expert system, ISAC interpretation, Genuine component, Cross-reactive component, Computer supported diagnosis

Published
2014
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23. The Employment of Leukotriene Antagonists in Cutaneous Diseases Belonging to Allergological Field

Author

Eustachio Nettis, Maddalena D'Erasmo, Elisabetta Di Leo, Gianfranco Calogiuri, Vincenzo Montinaro, Antonio Ferrannini, and Angelo Vacca

Subjects
Pathology, RB1-214
Abstract

Leukotrienes (LTs) are potent biological proinflammatory mediators. LTC4, LTD4, and LTE4 are more frequently involved in chronic inflammatory responses and exert their actions binding to a cysteinyl-LT 1 (CysLT1) receptor and a cysteinyl-LT 2 (CysLT2) receptor. LTs receptor antagonists available for clinical use demonstrate high-affinity binding to the CysLT1 receptor. In this paper the employment of anti-LTs in allergic cutaneous diseases is analyzed showing that several studies have recently reported a beneficial effects of these agents (montelukast and zafirlukast as well as zileuton) for the treatment of some allergic cutaneous related diseases-like chronic urticaria and atopic eczema although their proper application remains to be established.

Published
2010
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24. Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study

Author

Gabriella Fabbrocini, L Bonzano, Silvia Ferrucci, S Ribero, Simona Tavecchio, Giovanni Pellacani, Steven Paul Nisticò, C Detoraki, Franco Rongioletti, Cataldo Patruno, Paolo Romita, Eustachio Nettis, Viviana Piras, Michela Ortoncelli, M Carbonara, Giulia Calabrese, Danilo Di Bona, E. Di Leo, Luigi Macchia, Caterina Foti, G Argenziano, Maddalena Napolitano, Nettis, E, Ferrucci, S M, Ortoncelli, M, Pellacani, G, Foti, C, Di Leo, E, Patruno, C, Rongioletti, F, Argenziano, G, Macchia, L, Tavecchio, S, Napolitano, M, Ribero, S, Bonzano, L, Romita, P, Di Bona, D, Nisticò, S P, Piras, V, Calabrese, G, Detoraki, C, Carbonara, M, Fabbrocini, G, Nettis, E., Ferrucci, S. M., Ortoncelli, M., Pellacani, G., Foti, C., Di Leo, E., Patruno, C., Rongioletti, F., Argenziano, G., Macchia, L., Tavecchio, S., Napolitano, M., Ribero, S., Bonzano, L., Romita, P., Di Bona, D., Nistico, S. P., Piras, V., Calabrese, G., Detoraki, C., Carbonara, M., and Fabbrocini, G.

Subjects
Adult, medicine.medical_specialty, Immunology, Population, Dupilumab, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Interquartile range, Internal medicine, Humans, Immunology and Allergy, Medicine, Eosinophilia, Multicenter real-life study, education, Retrospective Studies, Atopic dermatitis, education.field_of_study, business.industry, Conjunctiviti, Retrospective cohort study, Dermatology Life Quality Index, Immunoglobulin E, Conjunctivitis, Atopic dermatiti, medicine.disease, Clinical trial, Treatment Outcome, 030228 respiratory system, Multicentric real-life study, medicine.symptom, business, Human
Abstract

BACKGROUND Dupilumab has been demonstrated to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, evidence of real-world experience with dupilumab in a broader population is limited to date. METHODS Adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at ten Italian academic centers, were included in the study. Physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index, DLQI) and serological markers [immunoglobulin (Ig) E and eosinophil count] after 16 weeks were analyzed. RESULTS We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median ± interquartile percentage change from baseline to 16 weeks of treatment in the EASI score was -87.5±22.0 (p

Published
2022
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26. Secondary prevention of latex allergy

Author

Eustachio Nettis, Rossella Casella, Cristoforo Incorvaia, and Andrea Miniello

Subjects
Latex Hypersensitivity, Fruit, Immunology, Secondary Prevention, Immunology and Allergy, Humans, Immunotherapy, Rubber
Abstract

The present review addresses the secondary prevention in healthcare worker, healthcare setting, and in patients outside the healthcare setting.There is sufficient knowledge of the broad aetiology of latex allergy for secondary preventive programmes to be widely adopted. Currently, avoidance of latex-containing surgical products is mandatory in the care of sensitized patients. They should also have a list of occult sources of natural rubber latex exposure and cross-reacting fruits. During all health-care procedures latex allergic patients should be treated in a 'latex-free' environment. Specific sublingual immunotherapy has been suggested as a suitable therapeutic option. It can be offered, in addition to symptomatic treatment, to selected patients, when avoidance measures are not feasible or effective. The use of omalizumab could also be extended as an adjunct to latex immunotherapy.Despite of the progress made in the secondary prevention of latex allergy, the disease still continues to be a global health problem.

Published
2022

27. Promising Use of the New Biologics in the Management of Drug-Induced Hypersensitivity Reactions: Preliminary Approaches

Author

Gianfranco Calogiuri, Eustachio Nettis, Angelo Vacca, Luigi Macchia, Caterina Foti, and Knut Brockow

Subjects
Drug, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Omalizumab, Cellular level, Antibodies, Monoclonal, Humanized, Etanercept, Drug Hypersensitivity, Drug treatment, Anti-Allergic Agents, medicine, Animals, Humans, Immunology and Allergy, media_common, Biological Products, Tumor Necrosis Factor-alpha, business.industry, Interleukin-17, Disease Management, Infliximab, Drug induced hypersensitivity, Immunology, business, Immunosuppressive Agents, medicine.drug
Abstract

Biologics are an innovative class of drugs that can selectively influence immunological responses at a cellular level. Although their use is usually restricted to some specific diseases, such as autoimmune pathologies and tumors, their “off-label” administration has increased widely in the last years. Drug treatment may induce hypersensitivity reactions which currently lack any gold standard therapy but maybe a future field of application for biologics. Agents like anti-IgE (Omalizumab) and Tumor Necrosis Factor-α inhibitors might be used in immediate-type and cell-mediated hypersensitivity caused by medications, respectively, and the first trials in that direction are being reported in the literature. In fact, the refined immunological mechanisms involved in the pathogenesis of drug hypersensitivity might respond successfully to this new class of drugs.

Published
2020
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28. Omalizumab for the Treatment of Persistent Drug Induced Urticaria Elicited by Thienopyridines: A Case Report

Author

Nicholas G. Kounis, Luigi Macchia, Eustachio Nettis, Alessandro Mandurino-Mirizzi, Angelo Vacca, Elisabetta Di Leo, Caterina Foti, and Gianfranco Calogiuri

Subjects
Pharmacology, Prasugrel, Thienopyridine, business.industry, medicine.medical_treatment, Immunology, General Medicine, Omalizumab, 030204 cardiovascular system & hematology, medicine.disease, Clopidogrel, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Drug-induced urticaria, Anesthesia, Coronary stent, Thienopyridines, medicine, Immunology and Allergy, cardiovascular diseases, business, Ticagrelor, medicine.drug
Abstract

The anti-IgE Omalizumab may be helpful to treat clopidogrel hypersensitivity without stopping thienopyridine administration in patients requirining continuous antiplatellet therapy after coronary stent placement.

Published
2020
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29. Dupilumab-Associated Conjunctivitis in Patients With Atopic Dermatitis: A Multicenter Real-Life Experience

Author

Lorenzo Salvati, Aikaterini Detoraki, Cristiano Caruso, Raffaele Brancaccio, Eustachio Nettis, Mario DI GIOACCHINO, and Laura Bonzano

Subjects
Adult, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, business.industry, Incidence, Immunology, MEDLINE, Atopic dermatitis, Antibodies, Monoclonal, Humanized, Conjunctivitis, medicine.disease, Dupilumab, Dermatology, Dermatitis, Atopic, Italy, Risk Factors, Prevalence, Humans, Immunology and Allergy, Medicine, Female, In patient, business
Published
2020
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30. Efficacy of dupilumab in atopic comorbidities associated with moderate‐to‐severe adult atopic dermatitis

Author

Eustachio Nettis, Elisabetta Di Leo, Vincenzo Patella, Laura Bonzano, M Carbonara, Carla Lombardo, Aikaterini Detoraki, Giorgio Walter Canonica, and Luigi Macchia

Subjects
Adult, medicine.medical_specialty, business.industry, Immunology, Dermatology Life Quality Index, Atopic dermatitis, Antibodies, Monoclonal, Humanized, medicine.disease, Dupilumab, Eczema Area and Severity Index, Dermatitis, Atopic, Treatment Outcome, Double-Blind Method, Quality of life, Asthma Control Questionnaire, Internal medicine, Quality of Life, medicine, Humans, Immunology and Allergy, Observational study, Prospective Studies, business, Asthma
Abstract

Background Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. Methods This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. Results We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient-Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five-item Asthma Control Questionnaire scores) and disease-related QoL (measured using the Asthma QoL Questionnaire scores). Thirty-five patients (28.5%) developed conjunctivitis during the study period. Conclusion These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD.

Published
2020
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31. Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey

Author

Silvia Ferrucci, Paolo D. Pigatto, Antonio Cristaudo, Eustachio Nettis, Patrizia Pepe, Angelo V. Marzano, Maria Teresa Fierro, Riccardo Asero, Annalisa Patrizi, Luca Stingeni, Ornella De Pità, Gino A. Vena, Giampiero Girolomoni, Nunzio Crimi, Giovanni Genovese, Annamaria Offidani, Caterina Foti, Nicoletta Cassano, and Paolo Dapavo

Subjects
medicine.medical_specialty, Urticaria, Pilot survey, MEDLINE, Dermatology, Omalizumab, Histamines antagonists, Group B, Surveys and Questionnaires, Health care, Chronic urticaria, Physicians’ practice patterns, Histamines antagonists, Adrenal cortex hormones, Omalizumab, Cyclosporine, Medicine, Humans, Medical prescription, business.industry, Adrenal cortex hormones, Cyclosporine, Chronic urticaria, Clinical Practice, Infectious Diseases, Cross-Sectional Studies, Family medicine, Chronic Disease, Physicians’ practice patterns, business
Abstract

Background The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. Objectives This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU on clinical practice. Methods A study-specific questionnaire was administered to a group of physicians (n=21) with a specialist interest in CSU from different areas of Italy (Group A) and also to other physicians (n=25) who manage CSU only occasionally in their clinical activity (Group B). Results In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. Conclusions These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Published
2022

32. Idiopathic nonhistaminergic angioedema: A single-center real-life experience from Italy

Author

Eustachio Nettis, Angelo Vacca, Luigi Macchia, Vito Racanelli, and Elisabetta Di Leo

Subjects
Adult, Male, medicine.medical_specialty, Angioedema, business.industry, Immunology, Comorbidity, Omalizumab, Middle Aged, Single Center, Dermatology, Italy, medicine, Humans, Immunology and Allergy, Female, Public Health Surveillance, medicine.symptom, business, Tranexamic acid, Retrospective Studies, medicine.drug
Published
2019
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33. Chronic urticaria reveals JAK2V617F positive essential thrombocythemia

Author

Marco Zurlo, Francesco Satriano, Marcello Albanesi, Maria Filomena Caiaffa, Danilo Di Bona, Luigi Macchia, Stefania Magistà, Elena Minenna, Eustachio Nettis, and Nada Chaoul

Subjects
medicine.medical_specialty, business.industry, medicine, Immunology and Allergy, Dermatology, business, Chronic urticaria
Published
2021

34. Sustained Drug-related Reaction With Eosinophilia and Systemic Symptoms (DRESS) Triggered by Low Molecular Weight Heparins in COVID-19: Management and Precision Diagnosis

Author

Maria Filomena Caiaffa, Maria Pia Foschino Barbaro, Lucia Anna Giliberti, Eustachio Nettis, Danilo Di Bona, Marcello Albanesi, Maria Pia Rossi, Nada Chaoul, Luigi Macchia, and Elena Minenna

Subjects
Drug, Coronavirus disease 2019 (COVID-19), business.industry, media_common.quotation_subject, Immunology, Immunology and Allergy, Medicine, Eosinophilia, Dermatology, medicine.symptom, business, media_common
Abstract

Background. Low molecular weight heparins (LMWHs) are administered routinely to COVID-19 patients. Systemic reactions to LMWHs (both IgE-mediated and non IgE-mediated) are considered rare. Particularly, a single case of drug-related reaction with eosinophilia and systemic symptoms (DRESS) due to enoxaparin has been described in the literature. Here, we report on the first case of DRESS related to administration of fondaparinux.Case presentation. An elderly woman was diagnosed with COVID-19, during the “first wave” of the pandemics in Italy, and treated with enoxaparin (for anti-coagulation). A DRESS syndrome developed after two weeks (RegiSCAR score = 7). Enoxaparin was considered the culprit drug and replaced with the fully synthetic LMWH fondaparinux. At the same time, high-dosage prednisone was added to the therapy. The DRESS slowly subsided and the patient survived. Upon recovery and corticosteroid washout, a lymphocyte proliferation test for both LMWHs was performed, yielding a positive response not only for enoxaparin but also for fondaparinux. Conclusions. By lymphocyte proliferation test we demonstrated that both enoxaparin and fondaparinux were implicated in this case of DRESS, occurring in an elderly COVID-19 patient. In retrospect, the choice of using a sustained high-dose corticosteroid treatment while maintaining anti-coagulation by fondaparinux proved to be right. Ultimately, the patient recovered from both DRESS and COVID-19.

Published
2021
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35. Orofacial granulomatosis: Clinical and therapeutic features in an Italian cohort and review of the literature

Author

Mauro Cancian, Stefania Loffredo, Giovanni Pellacani, Giovanni Rolla, Amato de Paulis, Filomena Maio, Luigi Giovanni Cremonte, Massimo Triggiani, Gianfranco Vitiello, Roberta Parente, Paola Parronchi, Riccardo Senter, Giuseppe Spadaro, Davide Firinu, Eustachio Nettis, Laura Bonzano, Maria Bova, Donatella Lamacchia, Elisa Boni, Francesco Arcoleo, Angelica Petraroli, Stefano Del Giacco, Luisa Brussino, Aikaterini Detoraki, Maria Rosaria Galdiero, Galdiero, M. R., Maio, F., Arcoleo, F., Boni, E., Bonzano, L., Brussino, L., Cancian, M., Cremonte, L., Del Giacco, S. R., De Paulis, A., Detoraki, A., Firinu, D., Lamacchia, D., Loffredo, S., Nettis, E., Parente, R., Parronchi, P., Pellacani, G., Petraroli, A., Rolla, G., Senter, R., Triggiani, M., Vitiello, G., Spadaro, G., and Bova, M.

Subjects
0301 basic medicine, medicine.medical_specialty, Delayed Diagnosis, Immunology, orofacial granulomatosis, granulomatous cheiliti, Inflammatory bowel disease, Granulomatosis, Orofacial, Atopy, 03 medical and health sciences, 0302 clinical medicine, orofacial granulomatosi, granulomatous cheilitis, Italian registries, Melkersson-Rosenthal syndrome, Cervical lymphadenopathy, Melkersson–Rosenthal syndrome, medicine, Immunology and Allergy, Humans, Granulomatosis, Orofacial, Tumor Necrosis Factor Inhibitor, Italy, Tumor Necrosis Factor Inhibitors, Melkersson-Rosenthal Syndrome, business.industry, Delayed Diagnosi, Soft tissue, medicine.disease, Dermatology, 030104 developmental biology, 030228 respiratory system, Cohort, Italian registrie, Orofacial granulomatosis, Sarcoidosis, medicine.symptom, business, Human
Abstract

Background Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10 different Italian centers and summarized the most recent literature data. Methods A review of patients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG. Results Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lips, and 28.2% suffered from Melkersson-Rosenthal syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG. Oral aphthosis and cervical lymphadenopathy were also described. The mean diagnostic delay was 3.4 years. Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them. Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%), and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results. Anti-TNF-α and anti-IgE monoclonal antibodies were used in 6 (15.4%) and 1 (2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response. Conclusions OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial, management is difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establish registry databases and address challenges of long-term management.

Published
2021

36. Chronic spontaneous urticaria in clinical practice: a pilot survey about attitudes and perceptions on assessment, diagnostic work-up and dietary management

Author

Antonio Cristaudo, Annamaria Offidani, Giovanni Genovese, Paolo Dapavo, Silvia Ferrucci, Eustachio Nettis, Annalisa Patrizi, Paolo D. Pigatto, Patrizia Pepe, Maria Teresa Fierro, Riccardo Asero, Ornella De Pità, Caterina Foti, Angelo V. Marzano, Nicoletta Cassano, Nunzio Crimi, Gino A. Vena, Luca Stingeni, and Giampiero Girolomoni

Subjects
medicine.medical_specialty, Urticaria, MEDLINE, Pilot survey, Dermatology, Assessment, Clinical practice, Guidelines, Quality of life, Surveys and Questionnaires, Laboratory examinations, medicine, Humans, Chronic Urticaria, Medical prescription, Disease severity, business.industry, Dietary management, Chronic spontaneous urticaria, Anti-thyroid autoantibodies, Work-up, Diet, Clinical Practice, Infectious Diseases, Cross-Sectional Studies, Attitude, Family medicine, Chronic Disease, Quality of Life, business
Abstract

BACKGROUND Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The 0bjectives is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures. METHODS A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (Group A; n=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (Group B; n=25). RESULTS The EAACI/GA²LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P

Published
2021

37. Efectiveness and Safety of Long‑Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real‑Life Observational Study

Author

Cataldo, Patruno, Gabriella, Fabbrocini, Giuseppe, Longo, Giuseppe, Argenziano, Silvia Mariel Ferrucci, Luca, Stingeni, Ketty, Peris, Michela, Ortoncelli, Annamaria, Offidani, Giuseppe Fabrizio Amoruso, Marina, Talamonti, Girolomoni, Giampiero, Teresa, Grieco, Michela, Iannone, Eustachio, Nettis, Caterina, Foti, Franco, Rongioletti, Monica, Corazza, Michele Delli Veneri, and Maddalena, Napolitano

Subjects
Dupilumab, Atopic Dermatitis, A Multicenter Real‑Life Observational Study, Atopic Dermatitis, Dupilumab, A Multicenter Real‑Life Observational Study
Published
2021

38. Long-term effectiveness of dupilumab up to 52 weeks in atopic dermatitis in 253 adult patients

Author

Silvia Ferrucci, Simona Tavecchio, L Bonzano, Luigi Macchia, Giulia Calabrese, Maddalena Napolitano, Steven Paul Nisticò, Caterina Foti, Aikaterini Detoraki, Katharina Hansel, Giuseppe Argenziano, Giovanni Pellacani, Paolo Romita, Michela Ortoncelli, Franco Rongioletti, Luca Stingeni, E. Di Leo, Gabriella Fabbrocini, Simone Ribero, M Carbonara, Cataldo Patruno, Eustachio Nettis, Viviana Piras, Danilo Di Bona, Nettis, E, Fabbrocini, G, Ortoncelli, M, Pellacani, G, Argenziano, G, Di Leo, E, Patruno, C, Stingeni, L, Foti, C, Rongioletti, F, Macchia, L, Tavecchio, S, Napolitano, M, Ribero, S, Bonzano, L, Calabrese, G, Di Bona, D, Nisticò, S P, Hansel, K, Romita, P, Piras, V, Carbonara, M, Detoraki, A, Ferrucci, S M, Nettis, E., Fabbrocini, G., Ortoncelli, M., Pellacani, G., Argenziano, G., Di Leo, E., Patruno, C., Stingeni, L., Foti, C., Rongioletti, F., Macchia, L., Tavecchio, S., Napolitano, M., Ribero, S., Bonzano, L., Calabrese, G., Di Bona, D., Nistico, S. P., Hansel, K., Romita, P., Piras, V., Carbonara, M., Detoraki, A., and Ferrucci, S. M.

Subjects
Adult, medicine.medical_specialty, Adult patients, business.industry, Eczema, Interleukin, Dermatology, Atopic dermatitis, medicine.disease, Antibodies, Monoclonal, Humanized, Dupilumab, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Monoclonal, Medicine, Humans, business
Abstract

Dupilumab, an inhibitor of interleukin (IL)-4/13 activity, is a biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD)1 . Our aim was to assess the long-term effectiveness and safety of dupilumab in a clinical real-life setting.

Published
2021

39. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author

Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.

Subjects
MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

Published
2020
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40. Hypersensitivity to Vitamins with a Focus on Immediate-Type Reactions: Food or Drug Allergy?

Author

Eustachio Nettis, Caterina Foti, Calogiuri Gianfranco, Angelo Vacca, Lene H. Garvey, Francesco Casciaro, and Shirina Alsowaidi

Subjects
Vitamin, business.industry, Endocrinology, Diabetes and Metabolism, Drug allergy, Food fortification, Physiology, Vitamins, medicine.disease, Hypervitaminosis, Drug Hypersensitivity, chemistry.chemical_compound, chemistry, Food allergy, Pellagra, Dietary Supplements, medicine, Immunology and Allergy, Animals, Humans, business, Adverse effect, Food Hypersensitivity, pernicious anemia
Abstract

Vitamins are essential substances for normal cell functions, growth, and development. However, they cannot be produced by the human organism, so intake must be through the diet. Vitamin deficiency causes the onset of different diseases, ranging from pellagra to pernicious anemia, which can be corrected by reintroducing the missing vitamin form. To supply the right amount of vitamins to the body, every vitamin naturally occurring in foodstuff has been identified, extracted and synthetically produced, thus allowing either food fortification with these compounds or their pharmaceutical production. Furthermore, the increased importance attributed nowadays to body wellness and the pursuit of a permanent status of health at all costs has greatly encouraged a high consumption of vitamin supplements in modern society, since vitamin megadoses may be responsible for adverse or toxic effects. However, excessive vitamins can induce hypervitaminosis. In the USA, a national survey confirmed that 52% of adult Americans take at least one or more supplement products, vitamins and minerals being the most popular supplements in that country. Although vitamins are widespread natural substances, they may induce immediate or delayed type hypersensitivity reactions. Such adverse events are still underestimated and poorly recognized because only single cases have been reported in the literature, and no general review has yet investigated the mechanisms underlying sensitization to each vitamin, the diagnosis, and the management strategies adopted for vitamin hypersensitivity. Although delayed-type reactions to different vitamins are described in the literature, in our review, attention has been focused mainly on immediate- type reactions. Due to the importance of vitamins, further information regarding the above aspects (pathomechanisms, diagnosis and management) would be highly desirable to focus the state of the art on this particular, underestimated form of allergy, thus increasing allergists' awareness on these elusive hypersensitivity reactions.

Published
2020

41. Maintenance-Phase Subcutaneous Immunotherapy with House Dust Mites Induces Cyclic Immunologic Effects

Author

Luigi Macchia, Lucia Anna Giliberti, Eustachio Nettis, Maria Filomena Caiaffa, Danilo Di Bona, Nada Chaoul, Maria Pia Rossi, and Marcello Albanesi

Subjects
Allergy, biology, Regulatory T cell, business.industry, Immunology, General Medicine, Natural killer T cell, Immunoglobulin E, medicine.disease, Immune tolerance, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Immune system, 030228 respiratory system, medicine, biology.protein, Immunology and Allergy, Cytotoxic T cell, 030223 otorhinolaryngology, business, B cell
Abstract

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment of respiratory allergies including house dust mite (HDM) and Hymenoptera venom allergy. During the build-up phase, the allergen is administered weekly at increasing doses, while during the maintenance phase, it is administered at a fixed high dose every 4 weeks. Upon SCIT injection, the allergen is driven to the draining lymph nodes where it most likely induces an immune response. Immunologic changes are thus supposedly induced at each injection. Objectives: It is now established that SCIT induces tolerance in the long term, but the precise underlying immunologic mechanisms remain unclear. Therefore, we wanted to analyze the immunologic changes induced in both innate and adaptive immune cells at each individual SCIT administration during the maintenance phase in HDM-allergic patients. More specifically, we wondered whether the changes in regulatory T cell (Treg) and IgE+ B cell percentages, which are observed at the end of a 3-year course of SCIT, already occurred during the maintenance phase and whether these possible changes were sustained. Methods: We enrolled 6 patients suffering from HDM allergic rhinitis and undergoing maintenance HDM SCIT for 18–24 months. The same SCIT extract was used for all patients. We collected blood samples at 5 time points: T1 (immediately before a given SCIT injection), T2 (9 days after T1), T3 (29 days after T1 and right before the successive administration), T4 (39 days after T1), and T5 (61 days after T1 and just before the next injection). Six non-allergic age-matched healthy individuals were used as controls. Using flow cytometry, we assessed the following cell subsets in peripheral blood mononuclear cells: CD4 and CD8 T cells, Tregs, B cells, IgE+ B cells, NK and NKT cells, and total and activated basophils. Results: HDM-allergic patients displayed increased percentages of CD4 and CD8 T cells and NK cells compared to healthy controls. In contrast, NKT cells, total B cells, and basophils were diminished. These differences were maintained throughout the time course and seemed to be independent of the periodical SCIT injections. On the contrary, Treg percentages were significantly reduced in all HDM-allergic patients at T1. However, they increased at T2 and T4 (9 days after each SCIT injection) but decreased again at T3 and T5, just before the next one, resulting in cyclic changes. IgE+ B cells were significantly increased at T1, even more increased after each administration (T2, T4), and went back to their initial levels at T3 and T5, also resulting in a cyclic pattern. Conclusions: Our data suggest that during the SCIT maintenance phase, cycles of expansion/contraction of Tregs and IgE+ B cells occur at each SCIT injection. Therefore, the sustained induction of immune tolerance by SCIT, through the increase of Tregs, seems to depend on the periodical exposure to the allergen, at least during the early steady state.

Published
2019
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42. Planned omalizumab discontinuation in CSU management as a sustainable strategy: A 2-year real-life study

Author

Donato Paolino, Elena Minenna, Danilo Di Bona, Eustachio Nettis, Luigi Macchia, Antonella Lovecchio, Maria Cristina Nizi, Marcello Albanesi, Maria Filomena Caiaffa, and Erminia Ridolo

Subjects
medicine.medical_specialty, Urticaria, business.industry, Sustainable strategy, Immunology, Treatment outcome, Stopping rule, MEDLINE, Omalizumab, Discontinuation, Chronic disease, Treatment Outcome, Anti-Allergic Agents, Chronic Disease, Immunology and Allergy, Medicine, Humans, business, Intensive care medicine, Life study, medicine.drug
Published
2020

43. EAACI/GA2LEN/EDF/WAO-Leitlinie für die Definition, Klassifikation, Diagnose und das Management der Urtikaria — konsentierte, deutschsprachige Übersetzung

Author

Mario Sánchez-Borges, Margarida Gonçalo, Elias Toubi, Ricardo Niklas Werner, Gordon Sussman, I V Danilycheva, Ana Giménez-Arnau, Corinna Dressler, Stefanie Rosumeck, Bettina Wedi, Clive Grattan, Christian Vestergaard, Franziska Ruëff, Zuotao Zhao, Karin Hartmann, Kanokvalai Kulthanan, Alexander Nast, Eustachio Nettis, Jacques Hébert, Imke Reese, Torsten Zuberbier, P. Mathelier-Fusade, Petra Staubach, Michihiro Hide, Hanneke Oude-Elberink, Thilo Jakob, Zenon Brzoza, M. Magerl, Thomas Werfel, Luis Felipe Ensina, Raisa Meshkova, Hans F. Merk, Markus Ollert, Kiran Godse, Jonathan A. Bernstein, Tabi A. Leslie, Amir Hamzah Abdul Latiff, Timothy J. Craig, Martin Metz, Peter Schmid-Grendelmeier, Hagen Ott, Sarbjit S. Saini, Roberta Buense Bedrikow, Constance H. Katelaris, Emek Kocatürk, Eckard Hamelmann, Riccardo Asero, Jürgen Grabbe, Knut Brockow, Diane Baker, Barbara Ballmer-Weber, Désirée Larenas-Linnemann, Allen P. Kaplan, Randolf Brehler, Werner Aberer, Alexander Kapp, Joachim W. Fluhr, Carsten Bindslev-Jensen, Martin K. Church, Marcus Maurer, Giorgio Walter Canonica, and Gino A. Vena

Subjects
Gynecology, 030207 dermatology & venereal diseases, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, 030228 respiratory system, business.industry, Immunology and Allergy, Medicine, business
Abstract

Diese evidenz- und konsensbasierte Leitlinie wurde entsprechend den Methoden der Cochrane und der Grading of Recommendations Assessment, Development and Evaluation (GRADE)-Arbeitsgruppen entwickelt. Die Leitlinien-Konferenz fand am 1. Dezember 2016 statt. Sie ist eine gemeinsame Initiative der European Academy of Allergology and Clinical Immunology (EAACI), dem von der EU gegrundeten Global Allergy and Asthma European Network (GA2LEN), dem European Dermatology Forum (EDF) und der World Allergy Organization (WAO) mit 48 teilnehmenden Delegierten aus 42 nationalen und internationalen Gesellschaften. Die Leitlinie ist von der European Union of Medical Specialists (UEMS) akzeptiert worden. Urtikaria ist eine haufige, mastzellabhangige Erkrankung, die mit Quaddeln, Angioodemen oder beidem einhergeht. Die Lebenszeitpravalenz der akuten Urtikaria liegt bei circa 20 %. Chronische spontane Urtikaria (CSU) und andere chronische Formen der Urtikaria sind belastend, beeintrachtigen die Lebensqualitat und haben einen negativen Einfluss auf die Leistungsfahigkeit in Beruf und Schule. Diese Leitlinie umfasst die Definition und Klassifikation der Urtikaria unter Berucksichtigung der jungsten Fortschritte in der Identifikation von Ursachen, Auslosefaktoren und Pathomechanismen. Daruber hinaus skizziert sie evidenzbasierte, diagnostische und therapeutische Ansatze fur die verschiedenen Subtypen der Urtikaria.

Published
2018
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44. Omalizumab chronic spontaneous urticaria

Author

Giorgio Walter Canonica, Eustachio Nettis, Fabio Lodi Rizzini, Luca Cegolon, Elisabetta Di Leo, and Aikaterini Detoraki

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, biology, business.industry, Immunology, Treatment outcome, Retrospective cohort study, Skin test, Omalizumab, Immunoglobulin E, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Refractory, Internal medicine, biology.protein, Immunology and Allergy, Medicine, Observational study, In patient, business, medicine.drug
Abstract

Background Omalizumab is a recombinant anti-immunoglobulin E (IgE) antibody used in the treatment of patients with chronic spontaneous urticaria (CSU). Objective This multicentric study assessed the safety and efficacy of omalizumab in patients (n=322) with CSU refractory to second-generation antihistamines, also investigating predictors of poor treatment outcome and time lag to response to anti-IgE therapy by serum auto-reactivity. Methods This retrospective observational study comprised a 4-week pretreatment period, a 24-week treatment period with omalizumab (300 mg/month), and a 16-week follow-up period. Primary efficacy endpoints were mean and median change in 7-day urticaria activity score (UAS7), weekly itch severity score (ISS), and hive score from baseline to 4-, 12-, and 24-week values. Secondary endpoints included the proportion of patients (defined “responders”) with well-controlled urticaria (UAS7 ≤ 6) and complete treatment response (UAS7=0). Safety in terms of side effects was also assessed. Results Omalizumab significantly and consistently reduced the mean UAS7, ISS, and hive score from baseline to weeks 4, 12, and 24, with a clear decreasing trend over time. At the end of the treatment period (week 24), 84.2% of patients had a UAS7 score of 6 or less and 66.7% had a UAS7 of 0. Higher pretreatment IgE levels were less likely to be associated with poor treatment response (ie, UAS7 > 6). Patients with a positive autologus serum skin test (ASST) were significantly more likely to be “slow responders” to omalizumab treatment (ie, response beyond 8 days since omalizumab administration) than ASST-negative patients (P Conclusion Monitoring baseline characteristics of patients before introduction of omalizumab therapy may help to predict treatment outcome in CSU patients.

Published
2018
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45. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria

Author

Luis Felipe Ensina, Markus Magerl, Sarbjit S. Saini, Kiran Godse, Bettina Wedi, C. Katelaris, Marcus Maurer, Barbara Ballmer-Weber, Elias Toubi, G.W. Canonica, Gordon Sussman, Corinna Dressler, Zenon Brzoza, Jonathan A. Bernstein, Torsten Zuberbier, Christian Vestergaard, Carsten Bindslev-Jensen, R. Y. Meshkova, Margarida Gonçalo, Peter Schmid-Grendelmeier, Tabi A. Leslie, Martin K. Church, Ricardo Niklas Werner, Gino A. Vena, Allen P. Kaplan, Alexander Kapp, Alexander Nast, Eustachio Nettis, Zuotao Zhao, R Buense Bedrikow, Kanokvalai Kulthanan, P. Mathelier-Fusade, Petra Staubach, Emek Kocatürk, Diane Baker, Riccardo Asero, Werner Aberer, Hanneke Oude-Elberink, Ana Giménez-Arnau, Stefanie Rosumeck, Timothy J. Craig, D. Larenas-Linnemann, Clive Grattan, Michihiro Hide, I V Danilycheva, Martin Metz, Jacques Hébert, A H Abdul Latiff, Mario Sánchez-Borges, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
medicine.medical_specialty, Consensus, Evidence-based practice, hives, Urticaria, Immunology, MEDLINE, Disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, evidence-based, immune system diseases, medicine, Humans, Immunology and Allergy, media_common.cataloged_instance, Angioedema, European union, skin and connective tissue diseases, wheal, Asthma, media_common, Health Services Needs and Demand, business.industry, angioedema, Research, Disease Management, Guideline, Hives, medicine.disease, Europe, 030228 respiratory system, consensus, Family medicine, Ligelizumab, medicine.symptom, business, Wheal, Evidence-based, medicine.drug
Abstract

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Published
2018
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46. Patch test with sorbitan sesquioleate in Italian consecutive patients: A 1‐year multicenter SIDAPA study

Author

Rosella Gallo, Antonio Cristaudo, Cataldo Patruno, Eustachio Nettis, Donatella Schena, Fabrizio Guarneri, Nicola Milanesi, Leonardo Bianchi, Monica Corazza, Paolo D. Pigatto, Marta Tramontana, Paolo Romita, Katharina Hansel, Luca Stingeni, and Caterina Foti

Subjects
Male, SIDAPA baseline series, medicine.medical_specialty, Socio-culturale, Dermatology, Surface-Active Agents, Humans, Immunology and Allergy, Medicine, fragrance mix, patch test, SIDAPA baseline series, sorbitan sesquioleate, fragrance mix, patch test, sorbitan sesquioleate, Hexoses, business.industry, Patch test, Allergens, Middle Aged, Patch Tests, Italy, Dermatitis, Allergic Contact, Sorbitan Sesquioleate, Female, business
Published
2019
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47. Critical appraisal of the unmet needs in the treatment of chronic spontaneous urticaria with omalizumab: an Italian perspective

Author

Antonio Cristaudo, Paolo D. Pigatto, Giampiero Girolomoni, Eustachio Nettis, Patrizia Pepe, Giorgio Walter Canonica, Maria Teresa Fierro, Riccardo Asero, Oliviero Rossi, and Angelo V. Marzano

Subjects
chronic spontaneous urticaria, medicine.medical_specialty, Urticaria, Immunology, Histamine Antagonists, Alternative medicine, Omalizumab, Immunoglobulin E, chronic spontaneous urticaria, omalizumab, second-generation H1-antihistamines, treatment recommendations, Unmet needs, second-generation H-1-antihistamines, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, omalizumab, treatment recommendations, Chronic Disease, Clinical Trials as Topic, Immunotherapy, Italy, Practice Guidelines as Topic, Intensive care medicine, second-generation H1-antihistamines, biology, business.industry, Histamine antagonists, Dermatology, Critical appraisal, Chronic disease, 030228 respiratory system, biology.protein, business, medicine.drug
Abstract

The humanized anti-IgE antibody omalizumab has been available for patients with chronic spontaneous urticaria (CSU) in Italy since 2015. This review summarizes the unresolved issues and unmet therapeutic needs associated with omalizumab and discusses practical recommendations for its use in the management of CSU.Although modern second-generation H1-antihistamines are the standard of care for patients with CSU, adjunctive treatments (including omalizumab) may be required for effective control of symptoms in many patients. Evidence from clinical trials and experience from daily clinical practice suggest that the use of omalizumab in patients with CSU who have inadequate response to H1-antihistamines remains challenging.Based on current international guidelines, omalizumab labelling information and our experience in clinical practice, we provide treatment recommendations regarding the use of omalizumab in patients with CSU. These include: optimal treatment duration, the use of concomitant antihistamine therapy, the definition and management of disease relapse after treatment, and the management of patients with late or no response to treatment.

Published
2017
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49. Omalizumab retreatment in patients with chronic spontaneous urticaria: a systematic review of published evidence

Author

Eustachio Nettis, Chiara Tontini, Riccardo Asero, Sebastiano Gangemi, Oliviero Rossi, and Alessandro Tonacci

Subjects
medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, business.industry, education, Omalizumab, Dermatology, humanities, Chronic urticaria, Retreatment, Therapy, Treatment Outcome, Anti-Allergic Agents, medicine, Immunology and Allergy, Humans, In patient, Chronic Urticaria, business, medicine.drug
Abstract

Summary A systematic review of the current literature on retreatment with omalizumab of patients with relapsing chronic spontaneous urticaria was performed. Published evidence shows that retreatment is safe and clinically effective, and that time to complete clinical response reduces as the number of retreatments increases.

Published
2020

50. Reading of Patchtest Reactions

Author

Alberico Motolese, Daniele Paolo Pigatto, Eustachio Nettis, Gianni Angelini, and Caterina Foti

Subjects
medicine.medical_specialty, Allergic reaction, Erythema, business.industry, Photopatch test, Digital palpation, media_common.quotation_subject, False Negative Reactions, Patch test, Dermatology, Reading (process), medicine, Itching, medicine.symptom, business, media_common
Abstract

The scrupulous reading of the patch test reactions must be made by using a magnifying glass, carrying out digital palpation, and assessing symptoms. Allergic test reaction is characterized by itching, erythema, papules, and vesicles; generally there is also a reaction outside the area where the test substance has been applied. After making qualitative-quantitative assessment, positive reactions are classified according to well-established criteria. Positive allergic reactions must be differentiated from false-positive results. The possibility of false-negative results and mixed (irritant and allergic) and doubtful reactions must be considered. Patch and photopatch testing can involve some side effects.

Published
2020
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