Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

Henrique A Mayrink Giardini, Monica Bocchia, Franco Franceschini, Paolo Sfriso, Carmelo Gurnari, Alejandra de-la-Torre, Alessandra Renieri, Guillermo Ruiz-Irastorza, Edoardo Conticini, Claudia Fabiani, Luca Cantarini, Bruno Frediani, Eduardo Martin-Nares, Corrado Campochiaro, Lorenzo Dagna, Jessica Sbalchiero, Ombretta Viapiana, Rosetta Vitetta, Federico Caroni, Giulia Casamassima, Derya Yildirim, Alicia Callisto, Mark Beecher, Laura Pelegrín, Adriana Soto-Peleteiro, Alessandra Milanesi, Ibrahim Vasi, Alberto Cauli, Francesca Della Casa, Alessia Fiorenza, Germán Mejia-Salgado, Alessandro Tomelleri, Alberto Balistreri, Isabele Parente de Brito Antonelli, Pravin Hissaria, Riccardo Bixio, Florenzo Iannone, Matteo Piga, Amato De Paulis, Paola Triggianese, Gian Marco Tosi, Alex Fonollosa, Piero Ruscitti, Francesco Ciccia, José Hernández-Rodríguez, Verónica Gómez-Caverzaschi, Ewa Wiesik-Szewczyk, Ilaria Mormile, Giuseppe Lopalco, Chiara Baggio, Antonio Vitale, Valeria Caggiano, Gaafar Ragab, Jurgen Sota, Abdurrahman Tufan, Sara Monti, Sara Bindoli, Micol Frassi, Francesca Crisafulli, Perla Ayumi Kawakami-Campos, Andrea Hinojosa-Azaola

Journal: Seminars in arthritis and rheumatism 2024;66():152430

PMID: 38554594

Abstract

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Copyright © 2024. Published by Elsevier Inc.

Address: Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy.; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Brescia, Italy.; Division of Immunology, Transplants and Infectious Diseases, Università Vita-Salute San Raffaele, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS Ospedale San Raffaele, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Milan, Italy.; Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, Australia; Department of Immunopathology, SA Pathology, Adelaide, Australia.; Rheumatology Unit, Department of Medicine, University of Padua, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Padua, Italy.; Clinical Unit of Autoinflammatory Diseases, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic of Barcelona [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], University of Barcelona, Barcelona, Spain.; Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Leioa, Biscay, Spain; Autoimmune Diseases Unit, Biocruces Bizkaia Health Research Institute, Barakaldo, Biscay, Spain.; Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Pavia, Italy; Department of Internal Medicine and Therapeutics, Università di Pavia, Italy.; Department of Internal Medicine, Division of Rheumatology, Gazi University Hospital, Ankara, Turkiye.; Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy.; Rheumatology Division, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil.; Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Policlinic Hospital, University of Bari, Bari, Italy.; Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Italy.; Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, Italy.; Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy.; Unit of Rheumatology, ASL VC Sant' Andrea Hospital, Vercelli 13100, Italy.; Neuroscience Research Group (NEUROS), NeuroVitae Center, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.; Department of Ophthalmology, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, University of the Basque Country, Barakaldo, Spain.; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy; Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena 53100, Italy.; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy; Medical Genetics, Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.; Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, National Research Institute, Warsaw, Poland.; Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, Australia.; Department of Ophthalmology, Institut Clínic d'Oftalmologia (ICOF), Hospital Clinic de Barcelona, University of Barcelona, Institut de Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.; Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy.; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.; Department of Ophthalmology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt; Faculty of Medicine, Newgiza University, 6th of October City, Egypt.; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.; Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy; Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy.; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy; Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.; Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy. Electronic address: [email protected].; Rheumatology Unit, Policlinico "Le Scotte", Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, viale Bracci 16, Siena 53100, Italy; Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy. Electronic address: [email protected].

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