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

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

doi:10.1016/j.semarthrit.2024.152430

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

Semin Arthritis Rheum. 2024 Jun:66:152430. doi: 10.1016/j.semarthrit.2024.152430. Epub 2024 Mar 18.

Authors

Antonio Vitale¹, Valeria Caggiano¹, Eduardo Martin-Nares², Micol Frassi³, Lorenzo Dagna⁴, Pravin Hissaria⁵, Paolo Sfriso⁶, José Hernández-Rodríguez⁷, Guillermo Ruiz-Irastorza⁸, Sara Monti⁹, Abdurrahman Tufan¹⁰, Matteo Piga¹¹, Henrique A Mayrink Giardini¹², Giuseppe Lopalco¹³, Ombretta Viapiana¹⁴, Amato De Paulis¹⁵, Paola Triggianese¹⁶, Rosetta Vitetta¹⁷, Alejandra de-la-Torre¹⁸, Alex Fonollosa¹⁹, Federico Caroni²⁰, Jurgen Sota¹, Edoardo Conticini¹, Jessica Sbalchiero¹, Alessandra Renieri²¹, Giulia Casamassima²¹, Ewa Wiesik-Szewczyk²², Derya Yildirim¹⁰, Andrea Hinojosa-Azaola², Francesca Crisafulli³, Franco Franceschini³, Corrado Campochiaro⁴, Alessandro Tomelleri⁴, Alicia Callisto²³, Mark Beecher²³, Sara Bindoli⁶, Chiara Baggio⁶, Verónica Gómez-Caverzaschi⁷, Laura Pelegrín²⁴, Adriana Soto-Peleteiro⁸, Alessandra Milanesi⁹, Ibrahim Vasi¹⁰, Alberto Cauli¹¹, Isabele Parente de Brito Antonelli¹², Florenzo Iannone¹³, Riccardo Bixio¹⁴, Francesca Della Casa²⁵, Ilaria Mormile²⁵, Carmelo Gurnari²⁶, Alessia Fiorenza¹⁷, Germán Mejia-Salgado¹⁸, Perla Ayumi Kawakami-Campos²⁷, Gaafar Ragab²⁸, Francesco Ciccia²⁹, Piero Ruscitti³⁰, Monica Bocchia²⁰, Alberto Balistreri³¹, Gian Marco Tosi³², Bruno Frediani¹, Luca Cantarini³³, Claudia Fabiani³⁴

Affiliations

¹ 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.
² Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
³ 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.
⁴ 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.
⁵ Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, Australia; Department of Immunopathology, SA Pathology, Adelaide, Australia.
⁶ Rheumatology Unit, Department of Medicine, University of Padua, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Padua, Italy.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ Department of Internal Medicine, Division of Rheumatology, Gazi University Hospital, Ankara, Turkiye.
¹¹ Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy.
¹² Rheumatology Division, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil.
¹³ Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Policlinic Hospital, University of Bari, Bari, Italy.
¹⁴ Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Italy.
¹⁵ 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.
¹⁶ 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.
¹⁷ Unit of Rheumatology, ASL VC Sant' Andrea Hospital, Vercelli 13100, Italy.
¹⁸ Neuroscience Research Group (NEUROS), NeuroVitae Center, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
¹⁹ Department of Ophthalmology, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, University of the Basque Country, Barakaldo, Spain.
²⁰ 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.
²¹ 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.
²² 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.
²³ Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, Australia.
²⁴ 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.
²⁵ Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy.
²⁶ 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.
²⁷ Department of Ophthalmology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
²⁸ 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.
²⁹ Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
³⁰ Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
³¹ 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.
³² 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.
³³ 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].
³⁴ 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].

PMID: 38554594
DOI: 10.1016/j.semarthrit.2024.152430

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.

Keywords: AIDA network VEXAS registry; Autoinflammatory diseases; Myelodysplastic syndrome; Relapsing polychondritis; Scleritis; Uveitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Child
Eye Diseases / epidemiology
Female
Hereditary Autoinflammatory Diseases / diagnosis
Humans
Male
Middle Aged
Orbital Diseases
Polychondritis, Relapsing / complications
Polychondritis, Relapsing / diagnosis
Polychondritis, Relapsing / epidemiology
Registries*
Scleritis / diagnosis
Scleritis / epidemiology
Young Adult