Cargando…

New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been...

Descripción completa

Detalles Bibliográficos
Autores principales: Abu El-Asrar, Ahmed M., Van Damme, Jo, Struyf, Sofie, Opdenakker, Ghislain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632721/
https://www.ncbi.nlm.nih.gov/pubmed/34869409
http://dx.doi.org/10.3389/fmed.2021.705796
_version_ 1784607805346414592
author Abu El-Asrar, Ahmed M.
Van Damme, Jo
Struyf, Sofie
Opdenakker, Ghislain
author_facet Abu El-Asrar, Ahmed M.
Van Damme, Jo
Struyf, Sofie
Opdenakker, Ghislain
author_sort Abu El-Asrar, Ahmed M.
collection PubMed
description Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.
format Online
Article
Text
id pubmed-8632721
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86327212021-12-02 New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease Abu El-Asrar, Ahmed M. Van Damme, Jo Struyf, Sofie Opdenakker, Ghislain Front Med (Lausanne) Medicine Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease. Frontiers Media S.A. 2021-11-12 /pmc/articles/PMC8632721/ /pubmed/34869409 http://dx.doi.org/10.3389/fmed.2021.705796 Text en Copyright © 2021 Abu El-Asrar, Van Damme, Struyf and Opdenakker. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Abu El-Asrar, Ahmed M.
Van Damme, Jo
Struyf, Sofie
Opdenakker, Ghislain
New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title_full New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title_fullStr New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title_full_unstemmed New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title_short New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
title_sort new perspectives on the immunopathogenesis and treatment of uveitis associated with vogt-koyanagi-harada disease
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632721/
https://www.ncbi.nlm.nih.gov/pubmed/34869409
http://dx.doi.org/10.3389/fmed.2021.705796
work_keys_str_mv AT abuelasrarahmedm newperspectivesontheimmunopathogenesisandtreatmentofuveitisassociatedwithvogtkoyanagiharadadisease
AT vandammejo newperspectivesontheimmunopathogenesisandtreatmentofuveitisassociatedwithvogtkoyanagiharadadisease
AT struyfsofie newperspectivesontheimmunopathogenesisandtreatmentofuveitisassociatedwithvogtkoyanagiharadadisease
AT opdenakkerghislain newperspectivesontheimmunopathogenesisandtreatmentofuveitisassociatedwithvogtkoyanagiharadadisease