Vogt-Koyanagi-Harada Disease: a Retrospective and Multicentric Study of 41 Patients K
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Diallo et al. BMC Ophthalmology (2020) 20:395 https://doi.org/10.1186/s12886-020-01656-x RESEARCH ARTICLE Open Access Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients K. Diallo1* , S. Revuz2, G. Clavel-Refregiers3, T. Sené3, C. Titah4, M. Gerfaud-Valentin5, P. Seve5 and R. Jaussaud1 Abstract Background: East and South East Asian subjects as well as Amerindians and Hispanic subjects are predominantly affected by Vogt-Koyanagi-Harada disease. In Europe, only few studies have described the clinical features and treatment of this disease, especially in France. Methods: This retrospective case series was based on data collected from patients with a VKH disease diagnosed from January 2000 to March 2017, provided by three French Tertiary Centers. Results: Forty-one patients (16 men and 25 women) were diagnosed: average age at diagnosis was 38.7 years. Patients were mainly from Maghreb (58%), but ethnic origins were multiple. Pleiocytosis was observed in 19 cases (63%) and 17 out of 41 patients showed audio vestibular signs (41%), and 11 showed skin signs (27%). Thirty-four were treated with corticosteroids (83%), 11 with an immunosuppressant treatment (27%) and 5 with biological therapy drugs (13%). Relapse was observed in 41% patients, even though final average visual acuity had improved. We did not find any significant clinical difference in the population from Maghreb compared to other populations, but for age and sex trends, since there was a majority of younger women. Conclusion: We report here the second largest French cohort reported to date to our knowledge. The multiethnicity in our study suggests that VKH disease should be evoked whatever patients’ ethnicity. Keywords: Vogt-Koyanagi-Harada, Uveitis, Poliosis, North African Background with HLA DR4/ HLA DRB1–04*05 has been reported The Vogt-Koyanagi-Harada (VKH) disease is a bilateral in the Japanese population [5]. VKH disease mainly granulomatous panuveitis with potential systemic in- affects subjects from East and South East Asia, as well volvements: neurological disorders (cerebrospinal fluid as Amerindian and Hispanic patients [1, 6]. Median age analysis shows pleiocytosis in about 80% of cases), oto- at diagnosis is around 40. Only few studies are available logical disorders (hearing loss, dizziness (70%) and tinnitus to estimate prevalence of ethnic characteristics in the (42%)) and dermatological disorders such as vitiligo, polio- European population [7–10]. The aim of this study was sis and alopecia (10 to 63%) [1]. The disease is mediated by to describe patients’ epidemiological characteristics in Th1 lymphocytes targeting melanocytes [2]. The origin of clinical French referral centers. this affection remains unknown, though many infectious triggers have been hypothesized [2–4]. The association Methods Study design * Correspondence: [email protected] 1Department of Internal Medicine, Nancy University Hospital, Nancy, France This retrospective, multicentric-case series was based on Full list of author information is available at the end of the article data collected from patients with a VKH disease © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Diallo et al. BMC Ophthalmology (2020) 20:395 Page 2 of 8 diagnosed from January 2000 to March 2017 provided early onset of the disease when diagnosis and treatment by three French tertiary Centers (Lyon University Hos- are performed within 3 weeks of symptoms [15]. pital, Rothschild Hospital Foundation in Paris, Nancy The presentation was considered as “complete” when University Hospital). Data was collected in each center. the patient presented an ocular involvement with both At the Nancy University Hospital cases carrying the neurological or otologic and dermatological involvement; diagnosis code “other chorioretinitis and other iridocy- as “incomplete” if the patient presented with an ocular clitis” were collected from the Department of Medical involvement and another involvement whether otologic, Information in France and all cases of VKH disease were neurological or dermatological and as “possible” if the selected. At the Lyon University Hospital and at the Roth- ocular presentation only was present. Differential diagno- schild Hospital Foundation in Paris cases were selected by ses, especially infectious and inflammatory ones were doctors managing patients with a suspect diagnosis. The se- excluded by no harmonized investigations, mainly: Lyme’s lected cases met the revised diagnostic criteria for VKH dis- disease, syphilis and HIV serologies, search for tubercu- ease: report of an international nomenclature committee losis (Mantoux tuberculin skin test or interferon-gamma [11]. Four patients were excluded because of missing data. release assays), and search for sarcoidosis (angiotensin As the data was retrospectively collected the Jarde law was converting enzyme and chest computed tomography). not appliable and no consent was requested. A pleiocytosis was defined by > 10 cells/mm3 at the cerebrospinal fluid analysis. Patient selection A treatment failure was defined as the presence of an Among patients with a possible VKH disease diagnosis ophthalmic inflammatory manifestation in at least one was reported by the Medical Data Department and eye (recurrence or chronic inflammation) with cortico- physicians; those with a definite diagnosis based on the re- steroid therapy tapering or withdrawal leading to thera- vised diagnostic criteria for Vogt-Koyanagi-Harada disease, peutic intensification (increase of corticosteroid therapy report of an international committee on nomenclature, or addition of an immunosuppressive agent) [16]. were included [11]. As a matter of fact, ophthalmic criteria are clinical and paraclinical: a bilateral ocular involvement Data collection depending on the stage of disease. Indeed, early manifesta- Data was collected from December 2016 to April 2017 tions of the disease are choroiditis (with or without anterior on an internet-based survey on WebQuest or sent by granulomatous uveitis, vitreous inflammatory reaction, or internet available in Supplementary File. Patients show- optic disc hyperhemia), which may be manifest as focal ing a VKH disease from January 2000 to March 2017 areas of subretinal fluid or bullous polycyclic exudative ret- were included. inal detachments. Paraclinical investigations can contribute to make the diagnosis: Statistical analysis Quantitative variables are presented as mean +/− standard – fluorescein angiography showing focal delayed deviation or as median and range and were compared choroidal perfusion, multiple areas of pinpoint using analysis of variance. Qualitative variables are pre- leakage, large placoid areas of hyperfluorescence, sented as number and percentage and were compared pooling within subretinal fluid, and optic nerve using a Chi2 test (or Fischer’s exact test if the criteria for a taining, Chi2 test were not fulfilled). A value of p <0.05 was – ICGA (indocyanin green angiography) is generally considered as significant. Statistical analysis was realized employed in the study of choroidal vasculature with R 3.3.1 statistical software (http://www.r-project.org). choroidal stroma and evolutionary monitoring of the disease [12], – Enhanced-depth imaging spectral-domain OCT Results improves the visualization of the choroid and its Forty-one patients (25 women and 16 men) were in- thickness [13, 14]. cluded. The main characteristics are reported in Table 1. Mean age at diagnosis was 38.7 years (10–74) and the Late manifestations of the disease are signs of ocular median of follow-up was 29.7 months (1–140). North depigmentation: either sunset glow fundus, Sugiura sign African was the main represented ethnicity 58% (24/41) or other ocular signs including nummular chorioretinal followed by South East Asian 49% (20/41), Caucasian depigmented scars, retinal pigment epithelium clumping 20% (8/41) and Hispanic 2% (1/41). Thirty patients were and/or migration, or recurrent or chronic anterior diagnosed at the acute early onset stage of the disease uveitis. (73%). Nine patients had a complete presentation (22%), Contrarily to the chronic form of the disease, patients 19 an incomplete presentation (46%) and 13 had a pos- are diagnosed at the early stage of disease or at acute sible syndrome (32%). All patients with a dermatological Diallo et al. BMC Ophthalmology (2020) 20:395 Page 3 of 8 Table 1 Main epidemiological characteristics Characteristics Patients n/41 (%) – Means p Gender - women 25/41 (61)