Skip to main content

Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients

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.

Peer Review reports

Background

The Vogt-Koyanagi-Harada (VKH) disease is a bilateral granulomatous panuveitis with potential systemic involvements: neurological disorders (cerebrospinal fluid analysis shows pleiocytosis in about 80% of cases), otological disorders (hearing loss, dizziness (70%) and tinnitus (42%)) and dermatological disorders such as vitiligo, poliosis and alopecia (10 to 63%) [1]. The disease is mediated by Th1 lymphocytes targeting melanocytes [2]. The origin of this affection remains unknown, though many infectious triggers have been hypothesized [2,3,4]. The association with HLA DR4/ HLA DRB1–04*05 has been reported in the Japanese population [5]. VKH disease mainly affects subjects from East and South East Asia, as well as Amerindian and Hispanic patients [1, 6]. Median age at diagnosis is around 40. Only few studies are available to estimate prevalence of ethnic characteristics in the European population [7,8,9,10]. The aim of this study was to describe patients’ epidemiological characteristics in clinical French referral centers.

Methods

Study design

This retrospective, multicentric-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 (Lyon University Hospital, Rothschild Hospital Foundation in Paris, Nancy University Hospital). Data was collected in each center. At the Nancy University Hospital cases carrying the diagnosis code “other chorioretinitis and other iridocyclitis” were collected from the Department of Medical Information in France and all cases of VKH disease were selected. At the Lyon University Hospital and at the Rothschild Hospital Foundation in Paris cases were selected by doctors managing patients with a suspect diagnosis. The selected cases met the revised diagnostic criteria for VKH disease: report of an international nomenclature committee [11]. Four patients were excluded because of missing data. As the data was retrospectively collected the Jarde law was not appliable and no consent was requested.

Patient selection

Among patients with a possible VKH disease diagnosis was reported by the Medical Data Department and physicians; those with a definite diagnosis based on the revised diagnostic criteria for Vogt-Koyanagi-Harada disease, report of an international committee on nomenclature, were included [11]. As a matter of fact, ophthalmic criteria are clinical and paraclinical: a bilateral ocular involvement depending on the stage of disease. Indeed, early manifestations of the disease are choroiditis (with or without anterior granulomatous uveitis, vitreous inflammatory reaction, or optic disc hyperhemia), which may be manifest as focal areas of subretinal fluid or bullous polycyclic exudative retinal detachments. Paraclinical investigations can contribute to make the diagnosis:

  • fluorescein angiography showing focal delayed choroidal perfusion, multiple areas of pinpoint leakage, large placoid areas of hyperfluorescence, pooling within subretinal fluid, and optic nerve taining,

  • ICGA (indocyanin green angiography) is generally employed in the study of choroidal vasculature choroidal stroma and evolutionary monitoring of the disease [12],

  • Enhanced-depth imaging spectral-domain OCT improves the visualization of the choroid and its thickness [13, 14].

Late manifestations of the disease are signs of ocular depigmentation: either sunset glow fundus, Sugiura sign or other ocular signs including nummular chorioretinal depigmented scars, retinal pigment epithelium clumping and/or migration, or recurrent or chronic anterior uveitis.

Contrarily to the chronic form of the disease, patients are diagnosed at the early stage of disease or at acute early onset of the disease when diagnosis and treatment are performed within 3 weeks of symptoms [15].

The presentation was considered as “complete” when the patient presented an ocular involvement with both neurological or otologic and dermatological involvement; as “incomplete” if the patient presented with an ocular involvement and another involvement whether otologic, neurological or dermatological and as “possible” if the ocular presentation only was present. Differential diagnoses, especially infectious and inflammatory ones were excluded by no harmonized investigations, mainly: Lyme’s disease, syphilis and HIV serologies, search for tuberculosis (Mantoux tuberculin skin test or interferon-gamma release assays), and search for sarcoidosis (angiotensin converting enzyme and chest computed tomography).

A pleiocytosis was defined by > 10 cells/mm3 at the cerebrospinal fluid analysis.

A treatment failure was defined as the presence of an ophthalmic inflammatory manifestation in at least one eye (recurrence or chronic inflammation) with corticosteroid therapy tapering or withdrawal leading to therapeutic intensification (increase of corticosteroid therapy or addition of an immunosuppressive agent) [16].

Data collection

Data was collected from December 2016 to April 2017 on an internet-based survey on WebQuest or sent by internet available in Supplementary File. Patients showing a VKH disease from January 2000 to March 2017 were included.

Statistical analysis

Quantitative variables are presented as mean +/− standard deviation or as median and range and were compared using analysis of variance. Qualitative variables are presented as number and percentage and were compared using a Chi2 test (or Fischer’s exact test if the criteria for a Chi2 test were not fulfilled). A value of p < 0.05 was considered as significant. Statistical analysis was realized with R 3.3.1 statistical software (http://www.r-project.org).

Results

Forty-one patients (25 women and 16 men) were included. The main characteristics are reported in Table 1.

Table 1 Main epidemiological characteristics

Mean age at diagnosis was 38.7 years (10–74) and the median of follow-up was 29.7 months (1–140). North African was the main represented ethnicity 58% (24/41) followed by South East Asian 49% (20/41), Caucasian 20% (8/41) and Hispanic 2% (1/41). Thirty patients were diagnosed at the acute early onset stage of the disease (73%). Nine patients had a complete presentation (22%), 19 an incomplete presentation (46%) and 13 had a possible syndrome (32%). All patients with a dermatological manifestation were diagnosed at the late stage of the disease. First entry in the medical care system was mainly by the Ophthalmology department (92%, 37/41) and patients were mostly followed by both Ophthalmology and Internal Medicine departments (61%, 25/41).

Ophthalmic manifestations

Main ophthalmic manifestations were: exudative detachment of the neurosensory retina (75%, 31/41) at the fundus examination (Fig. 1) or at the optical coherence tomography (Fig. 2), hyperfluorescent leaking dots pinpoints on the fluorescein angiography (44%, 18/41) (Fig. 3) and peripapillary atrophy and depigmented small atrophic lesions at the level of retinal pigment epithelium or Sunset glow fundus (41%, 17/41). The main results of ophthalmic clinical examination and investigations are described in Table 2.

Fig. 1
figure1

Exudative detachment of the neurosensory retina seen on fluorescein angiography, right eye

Fig. 2
figure2

Exudative detachment of the neurosensory retina seen on the optical coherence tomography, right eye

Fig. 3
figure3

Hyperfluorescent leaking dots « pinpoints » on the fluorescein angiography, left eye

Table 2 Patient’s presentation

The average of initial visual acuity was 4.6/10 for the right eye and 4.9/10 for the left one.

Extra-ophthalmic manifestations

Two patients first complained of a neurological and auditory involvement. Nine patients had a meningismus (22%). The analysis of cerebrospinal fluid was performed on 30/41 patients: among them 19 showed a lymphocytic pleiocytosis (63%). A cerebral imaging was performed on 71% of the patients (27/38) including 26 cerebral Magnetic Resonance Imaging, which did not find any specific abnormality. Seventeen patients complained of auditory and vestibular manifestations (41%): hearing loss (24%, 12/41) and tinnitus (22%, 9/41). The audiogram was performed on 22 patients and showed a hearing loss in 8 of them (36%). Eleven patients had dermatological manifestations (27%) including alopecia (5/11), vitiligo (4/11) and poliosis (6/11).

HLA association

Among ten tested patients four were positive to HLA DRB1–04*05; one was positive to HLA DR4 out of nine tested.

Treatments and prognosis

All but four patients were treated with high doses of corticosteroid therapy, 1 mg/kg/d prednisone or equivalent by oral route with progressive tapering (Table 3).

Table 3 Treatments and prognosis

A parenteral route was first used for 66% of patients (27/41). Only one patient was treated with local corticotherapy; 11 patients (27%) received an associated immunosuppressive treatment; 6 patients started with corticosteroids associated to immunosuppressive treatment at the very beginning of treatment, and 5 patients were treated with immunosuppressive treatment after a first line of corticosteroids alone: Azathioprine (n = 7), Ciclosporine (n = 1) and Mycophenolate mofetil (n = 3). Five patients were treated with biological therapies (infliximab and adalimumab) (12%) as a third therapeutic line for 3 of them. Patients without recurrence were treated during less than a year. Relapse occurred in 44% of patients (18/41) at mean corticosteroid dose of 15 mg/day [1–80] and at mean 13 months after the beginning of treatment [1–48]. The 23 patients who did not relapse were followed on an average 21 month-follow-up period and the 18 patients who relapsed were followed on an average of 40.9 months (p < 0.01). Complications occurred (Table 3).

Population from Maghreb

As for the main symptom (Table 4) (p = 0.8) and the HLA type (p = 1) there was not any significant difference between patients from Maghreb and other patients.

Table 4 Distinction of population from Maghreb

In the population from Maghreb, we found trends toward more women (18/24 versus 7/17 (p = 0.06)) and younger age (34 versus 44 years at diagnosis (p = 0.06)) as compared to other populations with borderline statistical significances.

Discussion

VKH disease is a rare disease and most of epidemiological data has been described for Asiatic, Hispanic, and Amerindian populations but not so for patients from Northern Africa. To our knowledge, our study is the second largest French cohort [8, 10, 17]. The low prevalence of the disease in Europe explains the low number of patients by center [18].

Apart from ethnicity, epidemiological data is the same as that of other populations’ [2, 6] with 60% of women and a mean age 38.7 at diagnosis. In our study the prevalence of the association with HLA DR4/ HLA DRB1–04*05 agrees with the literature data, the presence of this allele being associated with a higher risk of developing this disease.

As described by Lavezzo et al. and Ohno et al., the meningeal involvement is variable (63% of cases) like the clinical meningismus [1, 19]. In our study cerebral imaging did not find any significant sign, since its role is not defined in VKH disease. Although this investigation is normal in most cases, it seems relevant to exclude differential diagnoses. The otologic involvement in our population is the same as that of non-Hispanic populations’ [6]. This involvement is typical (75% of cases with a mean hearing loss of 30 dB) but seldom symptomatic [6]. While VKH disease could usually be confidently diagnosed by uveitis specialists based on ocular presentations, a search of systematical involvement, in particular an audiogram and/or a lumbar puncture, might be helpful for physicians who are less familiar with this disease. The prevalence of cutaneous involvement is closed to the non-Japanese populations’ [20]. Skin involvement prevails in pigmented populations from 10 to 63% [6]. Poliosis, vitiligo and alopecia are late manifestations of the disease. Most of our patients were diagnosed at an early stage, but a specific attention should be given to the extra ophthalmic manifestations at diagnosis of first ophthalmological manifestation and during follow-up to avoid a late-stage diagnosis. In our study, we did not notice any delay between the first manifestation of the disease and the ophthalmic involvement that led to the ophthalmic examination, but most of our patients presented the ophthalmic signs first (93%, 38/41).

Sasamoto et al. had a better outcome with high doses of systemic corticosteroid therapy [21]. Oral prednisone equivalent is usually prescribed initially at a dosage of 1 to 1.5 mg/kg/day with progressive tapering [17, 22]. In serious situations, methylprednisolone can be used at 1 g/day for 3 to 5 days [2]. The corticosteroid therapy duration is not codified, but in our study a few patients showed persistent inflammation signs at 6 months [21]. Treatment should be adapted to each patient depending on the clinical outcome. An early cessation is associated with an elevated rate of treatment failure [23]. Surprisingly, in our study treatment failures occurred from 1 to 48 months after the beginning of treatment, with a mean of 13 months, at a high level of corticosteroid of 15 mg a day, though the literature suggests a decrease of corticosteroid therapy with a minimal duration of 6 months [24]. Nevertheless, we believe that prognosis should have been different if immunosuppressive therapy had been initiated at first line [25, 26].

The sooner the diagnosis, the better the disease outcome (visual acuity ≥5/10 after treatment) [1]. This data was found in our cohort with a positive average profit by eye after treatment. An immunosuppressive treatment was introduced in 27% of cases as first line of treatment or in case of failure. Ciclosporine, Azathioprine, Cyclophosphamide, Methotrexate and Mycophenolate mofetil are active therapeutics in this disease [2, 27,28,29]. A recent Mexican study did not find benefit to adding early immunosuppressive treatment in terms of final visual acuity or of development of visually significant complications [25]. In contrast, other studies found a preeminence of immunosuppressive agents (Mycophenolate mofetil, Ciclosporine A, Methotrexate, and Azathioprine) over corticosteroids alone, while others were more reserved [26, 30]. Finally, biological therapies are used in non-infectious uveitis including VKH disease [31] but the treatment length in VKH disease is still debated.

Patients diagnosed at early stage presented mainly unilateral loss of visual acuity (p = 0.01). They were treated more often with bolus of corticosteroid (p < 0.01) and second line agents (p < 0.01). Compared to patients who were diagnosed at the early stage of disease, patients diagnosed at the chronic stage of the disease were treated longer: 36 months instead of 20 (p < 0.01). Complications were also more frequent in this group.

As in other French series, our study included most patients from Maghreb among a multiethnic population [8, 10]. Our prognosis seems better than in North African studies, which are more homogeneous as for ethical origin. Alaoui et al. reported about 8 women: 5 were cured without any relapse and only two were still treated with corticosteroids. Khairallah et al. found a good outcome for 59% of patients maintaining a visual acuity of 20/40 or better [32]. Boutimzine et al. observed 87.5% of patients with a visual acuity of 5/10 or better after a mean follow-up of 6 years [33]. We failed to find any significant clinical difference in the Maghreb population, but for age and gender trends. However, we report here one of the largest case reports about Maghreb to our knowledge [32,33,34] suggesting a higher prevalence in this population. Indeed, initial clinical presentation seems more severe in this population, especially the ophthalmic presentation, even if we did not find any clinical significance [35]. In our study the initial visual acuity was low, and this data was associated with a worse prognosis factor [36]. Surprisingly, as opposed to Read et al. who observed 51% of complication with 27% of glaucoma, or to Pandey et al. who observed a glaucoma cumulative incidence of 11.7%, we noticed a lower rate of relapse (44%) and complication like glaucoma (5%), which is known to be a severe one [37]. Larger multiethnic studies are needed to explore the severity of the disease according to ethnic origins.

Our study has several limitations. The first is related to the retrospective design of the study, namely missing data; the second limitation is due to non-harmonized diagnoses strategies within the 3 university Hospitals; the third one is due to the small sample size: HLA type was only performed on 10 patients. Complications were also noted for a few patients. Furthermore, we did not notice the necessary time to make a diagnosis after the beginning of symptoms and the necessary time to treat patients. Finally, the treatment was individualized due to the lack of guidelines concerning this disease at time of diagnosis. The high recurrence rate of 44% could be due to sample bias (close follow-up, tertiary centers). Nonetheless, it is the second largest French cohort reported to date [8, 10, 17].

Conclusion

VKH disease is a rare affection, more present in Asian, Hispanic, and Amerindian populations but in North African populations as well. In French studies patients originated from Maghreb represent a significant proportion, but all ethnicities could and should be involved. Accordingly, we should not limit our vision to patients’ ethnic origins, but diagnosis should be brought up particularly when ophthalmic manifestations are associated to neurological, otologic and/or dermatological signs.

Availability of data and materials

Not applicable.

Abbreviations

HLA:

Human Leukocyte Antigen

ICGA:

Indocyanin Green Angiography

OCT:

Optical Coherence Tomography

VKH:

Vogt-Koyanagi-Harada

References

  1. 1.

    Lavezzo MM, Sakata VM, Morita C, Rodriguez EEC, Abdallah SF, da Silva FTG, et al. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes. Orphanet J Rare Dis. 2016;11:29.

    Article  Google Scholar 

  2. 2.

    Greco A, Fusconi M, Gallo A, Turchetta R, Marinelli C, Macri GF, et al. Vogt-Koyanagi-Harada syndrome. Autoimmun Rev. 2013;12:1033–8.

    CAS  Article  Google Scholar 

  3. 3.

    Minoda H, Sakai J, Sugiura M, Imai S, Osato T, Usui M. High inducibility of Epstein-Barr virus replication in B lymphocytes in Vogt-Koyanagi-Harada disease. Nippon Ganka Gakkai Zasshi. 1999;103:289–96.

    CAS  PubMed  Google Scholar 

  4. 4.

    Sugita S, Takase H, Kawaguchi T, Taguchi C, Mochizuki M. Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int Ophthalmol. 2007;27:87–95.

    Article  Google Scholar 

  5. 5.

    Shi T, Lv W, Zhang L, Chen J, Chen H. Association of HLA-DR4/HLA-DRB1*04 with Vogt-Koyanagi-Harada disease: a systematic review and meta-analysis. Sci Rep. 2014;4:6887.

    CAS  Article  Google Scholar 

  6. 6.

    Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol. 1995;39:265–92.

    CAS  Article  Google Scholar 

  7. 7.

    Abad S, Monnet D, Caillat-Zucman S, Mrejen S, Blanche P, Chalumeau M, et al. Characteristics of Vogt-Koyanagi-Harada disease in a French cohort: ethnicity, systemic manifestations, and HLA genotype data. Ocul Immunol Inflamm. 2008;16:3–8.

    CAS  Article  Google Scholar 

  8. 8.

    Guenoun J-M, Parc C, Dhote R, Brezin AP. Vogt-Koyanagi-Harada disease: clinical features, therapy and long-term visual outcome in a Caucasian and African population. J Fr Ophtalmol. 2004;27:1013–6.

    Article  Google Scholar 

  9. 9.

    Pivetti-Pezzi P, Accorinti M, Colabelli-Gisoldi RA, Pirraglia MP. Vogt-Koyanagi-Harada disease and HLA type in Italian patients. Am J Ophthalmol. 1996;122:889–91.

    CAS  Article  Google Scholar 

  10. 10.

    Touitou V, Escande C, Bodaghi B, Cassoux N, Wechsler B, Lemaitre C, et al. Diagnostic and therapeutic management of Vogt-Koyanagi-Harada syndrome. J Fr Ophtalmol. 2005;28:9–16.

    CAS  Article  Google Scholar 

  11. 11.

    Read RW, Holland GN, Rao NA, Tabbara KF, Ohno S, Arellanes-Garcia L, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature. Am J Ophthalmol. 2001;131:647–52.

    CAS  Article  Google Scholar 

  12. 12.

    Stanga PE, Lim JI, Hamilton P. Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update. Ophthalmology. 2003;110:15–21.

    Article  Google Scholar 

  13. 13.

    Vasconcelos-Santos DV, Sohn EH, Sadda S, Rao NA. Retinal pigment epithelial changes in chronic Vogt-Koyanagi-Harada disease: fundus autofluorescence and spectral domain-optical coherence tomography findings. Retina. 2010;30:33–41.

    Article  Google Scholar 

  14. 14.

    Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147:811–5.

    Article  Google Scholar 

  15. 15.

    Hedayatfar A, et al. "revised diagnostic criteria" for Vogt-Koyanagi-Harada disease fail to improve disease management. J Current Ophthalmol. 2018;31:1–7.

    Article  Google Scholar 

  16. 16.

    Sakata VM, da Silva FT, Hirata CE, de Carvalho JF, Yamamoto JH. Diagnosis and classification of Vogt-Koyanagi-Harada disease. Autoimmun Rev. 2014;13:550–5.

    CAS  Article  Google Scholar 

  17. 17.

    Errera M-H, Fardeau C, Cohen D, Navarro A, Gaudric A, Bodaghi B, et al. Effect of the duration of immunomodulatory therapy on the clinical features of recurrent episodes in Vogt--Koyanagi--Harada disease. Acta Ophthalmol. 2011;89:e357–66.

    CAS  Article  Google Scholar 

  18. 18.

    Prete M, Dammacco R, Fatone MC, Racanelli V. Autoimmune uveitis: clinical, pathogenetic, and therapeutic features. ClinExpMed. 2016;16:125–36.

    CAS  Google Scholar 

  19. 19.

    Ohno S, Char DH, Kimura SJ, O’Connor GR. Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 1977;83:735–40.

    CAS  Article  Google Scholar 

  20. 20.

    Rosen E. Uveitis, with poliosis, vitiligo, alopecia and dysacusia. Vogt-Koyanagi syndrome. Arch Ophthalmol. 1945;33:281–92.

    Article  Google Scholar 

  21. 21.

    Sasamoto Y, Ohno S, Matsuda H. Studies on corticosteroidtherapy in Vogt-Koyanagi-Harada disease. Ophthalmologica. 1990;201:162–7..

    CAS  Article  Google Scholar 

  22. 22.

    Read RW, Yu F, Accorinti M, Bodaghi B, Chee S-P, Fardeau C, et al. Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2006;142:119–24.

    CAS  Article  Google Scholar 

  23. 23.

    Lai TYY, Chan RPS, Chan CKM, Lam DSC. Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease. Eye Lond Engl. 2009;23:543–8.

    CAS  Article  Google Scholar 

  24. 24.

    Abu El-Asrar AM, Dosari M, Hemachandran S, Gikandi PW, Al-Muammar A. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of sunset glow fundus in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Acta Ophthalmol. 2017;95:85–90.

    CAS  Article  Google Scholar 

  25. 25.

    Concha-Del Rio LE, Gomez L, Arellanes-Garcia L. Corticotherapy vs. Corticotherapy plus immunosuppressive therapy in acute Vogt-Koyanagi-Harada disease. Arch Soc Espanola Oftalmol. 2018;93:225–30.

    CAS  Article  Google Scholar 

  26. 26.

    Paredes I, Ahmed M, Foster CS. Immunomodulatory therapy for Vogt-Koyanagi-Harada patients as first-line therapy. Ocul Immunol Inflamm. 2006;14:87–90.

    CAS  Article  Google Scholar 

  27. 27.

    Suhler EB, Thorne JE, Mittal M, Betts KA, Tari S, Camez A, et al. Corticosteroid-Related Adverse Events Systematically Increase with Corticosteroid Dose in Noninfectious Intermediate, Posterior, or Panuveitis: Post Hoc Analyses from the VISUAL-1 and VISUAL-2 Trials. Ophthalmology. 2017;124:1799-807.

  28. 28.

    Sheppard J, Joshi A, Betts KA, Hudgens S, Tari S, Chen N, et al. Effect of Adalimumab on visual functioning in patients with noninfectious intermediate uveitis, posterior uveitis, and Panuveitis in the VISUAL-1 and VISUAL-2 trials. JAMA Ophthalmol. 2017;135:511–8.

    Article  Google Scholar 

  29. 29.

    Rao NA. Treatment of Vogt-Koyanagi-Harada disease by corticosteroids and immunosuppressive agents. Ocul Immunol Inflamm. 2006;14:71–2.

    Article  Google Scholar 

  30. 30.

    Urzua CA, Velasquez V, Sabat P, Berger O, Ramirez S, Goecke A, et al. Earlier immunomodulatory treatment is associated with better visual outcomes in a subset of patients with Vogt-Koyanagi-Harada disease. Acta Ophthalmol. 2015;93:e475–80.

    CAS  Article  Google Scholar 

  31. 31.

    Feurer E, Bielefeld P, Saadoun D, Seve P. Uveites et biotherapies. Rev Med Interne. 2015;36:107–16.

    CAS  Article  Google Scholar 

  32. 32.

    Khairallah M, Zaouali S, Messaoud R, Chaabane S, Attia S, Ben Yahia S, et al. The spectrum of Vogt-Koyanagi-Harada disease in Tunisia, North Africa. Int Ophthalmol. 2007;27:125–30.

    Article  Google Scholar 

  33. 33.

    Boutimzine N, Laghmari A, Ouazzani I, Ibrahimy W, Mohcine Z. Vogt-Koyanagi-Harada syndrome. Epidemiological, clinical and disease progression aspects. Twenty cases. J Fr Ophtalmol. 1998;21:746–54.

    CAS  PubMed  Google Scholar 

  34. 34.

    Alaoui F-Z, Benamour S, El Kabli H, Amraoui A. Vogt-Koyanagi-Harada syndrome. Eight cases. Rev Med Interne. 2007;28:250–4.

    Article  Google Scholar 

  35. 35.

    Sakata VM, da Silva FT, Hirata CE, Marin MLC, Rodrigues H, Kalil J, et al. High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose orticosteroids. Graefes Arch Clin Exp Ophthalmol. 2015;253:785–90.

    CAS  Article  Google Scholar 

  36. 36.

    Read RW, Rechodouni A, Butani N, Johnston R, LaBree LD, Smith RE, et al. Complications and prognostic factors in Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2001;131:599–606.

    CAS  Article  Google Scholar 

  37. 37.

    Pandey A, Balekudaru S, Venkatramani DV, George AE, Lingam V, Biswas J. Incidence and Management of Glaucoma in Vogt Koyanagi Harada disease. J Glaucoma. 2016;25:674–80.

    Article  Google Scholar 

Download references

Acknowledgements

We thank the department of Ophthalmology of the Rotschild Hospital Foundation, the department of Internal Medicine in Lyon, the department of Internal Medicine in Nancy and Pr Angioi-Duprez of the Nancy Ophthalmological department.

We thank Mrs. Jocelyne Wuibout (PhD) for her careful reading of the manuscript in English.

Funding

Nothing to declare.

Author information

Affiliations

Authors

Contributions

KD drafted the manuscript. KD, SR and RJ collected data from Nancy patients, GCR, TS and CT collected data from Rotschild patients, MGV and PS collected data from Lyon patients. CT revised the ophthalmological data. SR, GCR, TS, CT, MGV, PS and RJ revised it critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to K. Diallo.

Ethics declarations

Ethics approval and consent to participate

This study received approval from the Committee for the Protection of Persons of the Civil Hospices of Lyon, local ethics committee, in February 2019 (No 19–31).

Consent for publication

As the data collected were retrospective, Jarde law, formerly known as “biomedical research” or “common care”, was not appliable and no consent was requested.

Competing interests

Pr P. Sève has received honorarium from ABBVIE for lectures and advisory boards.

All other authors have no conflict of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

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.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Diallo, K., Revuz, S., Clavel-Refregiers, G. et al. Vogt-Koyanagi-Harada disease: a retrospective and multicentric study of 41 patients. BMC Ophthalmol 20, 395 (2020). https://doi.org/10.1186/s12886-020-01656-x

Download citation

Keywords

  • Vogt-Koyanagi-Harada
  • Uveitis
  • Poliosis
  • North African