International Ophthalmology

, Volume 27, Issue 2, pp 143–148

Vogt–Koyanagi–Harada disease in Hispanic patients

Authors

  • Somsiri Sukavatcharin
    • Doheny Eye Institute
    • Department of OphthalmologyKeck School of Medicine, University of Southern California
  • Julie H. Tsai
    • Doheny Eye Institute
    • Department of OphthalmologyKeck School of Medicine, University of Southern California
    • Doheny Eye Institute
    • Department of OphthalmologyKeck School of Medicine, University of Southern California
Original Paper

DOI: 10.1007/s10792-006-9017-6

Cite this article as:
Sukavatcharin, S., Tsai, J.H. & Rao, N.A. Int Ophthalmol (2007) 27: 143. doi:10.1007/s10792-006-9017-6

Abstract

Purpose

To describe the clinical features of Vogt–Koyanagi–Harada disease (VKH) in Hispanic patients.

Methods

Retrospective review of the records of 48 Hispanic patients diagnosed with VKH. The patients were divided into two groups: patients in the early phase of VKH (n = 11) were those who presented within 1 month after the onset of symptoms; patients in the late or chronic VKH phase (n = 37) were those who presented 6 months after onset of symptoms. Demographic data, clinical features, complications and initial and final visual acuity for each patient were recorded.

Results

All 11 patients in early phase VKH presented with bilateral uveitis (100%). Meningismus was noted in six cases and auditory disturbances in three. Ocular findings for these 11 patients included exudative retinal detachment in ten patients (91%) and marked optic disc edema in one patient. In the late phase VKH, ocular findings included sunset glow fundus in 26 patients (70%), peripheral nummular scars in 27 (73%), and retinal pigment epithelium hyperplasia in seven (19%). Extraocular manifestations noted in this group of patients included vitiligo in four, poliosis in six, and alopecia in five; auditory disturbances were found in four patients. The visual acuity improved in 60–70% of the patients after treatment with corticosteroids alone or in combination with immunosuppressive agents.

Conclusion

Hispanic patients with VKH often present without extraocular changes during early phase of the disease. However, once the disease evolves into the chronic phase, integumentary system involvement may become apparent in some patients.

Keywords

CorticosteroidEarly phase VKHHispanicLate phase VKHVogt–Koyanagi–Harada disease

Introduction

Vogt–Koyanagi–Harada disease (VKH) is found worldwide and primarily affects darkly pigmented races, including Hispanic, Asian, Native American and Asian Indians. The disease is relatively uncommon in whites and African–Americans [1, 2]. It is associated with HLA-DRB1*0405 in Asian populations and with HLA-DRB1*04 subtypes in Hispanic patients [3, 4]. Vogt–Koyanagi–Harada disease appears to be more prevalent in Japan, where it accounts for between 6.8% and 9.2% of all uveitis referrals [5]. In the United States of America, VKH accounts for between 1% and 4% of all uveitis clinic referrals [6, 7]. A series reported by the National Institutes of Health (NIH), Bethesda, Maryland, showed that 50% of VKH patients were white, 35% were African-American, and 13% were Hispanic [8]. In northern California, VKH is seen in Asians (41%), whites (29%), Hispanics (16%) and African–Americans (14%). In contrast, the majority of patients with VKH in southern California are Hispanic (78%), with the remainder coming from the Asian (10%), African–American (6%) and white (3%) populations [9].

Vogt–Koyanagi–Harada disease is known to have varied manifestations in different ethnic groups. For instance, in Japanese patients, dysacusia occurs in 70–80%, poliosis or alopecia in 60%, and vitiligo in 25%; however, dysacusia was noted in 8%, poliosis in 25%, and alopecia in 8% of patients in a series of VKH cases reported from San Francisco [6, 10, 11]. Since the clinical features of VKH vary depending upon the stage of the disease, patients rarely have all of these features during the initial presentation. The difference in proportions of racial groups may thus reflect discrepancies in the populations from which the patients are derived. The purpose of this study is to clarify the clinical features and visual outcomes in Hispanic patients with early and late phase VKH.

Patients and methods

A retrospective review was conducted on the charts of 48 patients diagnosed with VKH who were identified as Hispanic. The patients were divided into two groups. The first group (early phase VKH, n = 11) presented within 1 month after the onset of symptoms, which included headache, decreased vision, photophobia or floaters. The second group (n = 37) included those patients who presented 6 months after the onset of symptoms (chronic or late phase VKH).

Charts were reviewed for demographic data, such as age and gender, and for clinical features, such as ocular and extraocular manifestations in early and late phase VKH. The results of laboratory investigations, such as lumbar puncture, ultrasonography and fluorescein angiography, were also noted. Ocular complications that were noted included cataract, glaucoma, subretinal neovascularization or fibrosis, cystoid macular edema and epiretinal membrane. Visual acuity was documented at the initial and final visits.

Results

Of our 48 Hispanic patients, 18 (38%) were male and 30 (63%) were female. The age at presentation was between 11 years and 73 years (mean 35 ± 13 years). In the early phase VKH group, meningismus was present in six patients (55%), headache in nine (82%), stiff neck in six (55%), fever in two (18%), and nausea and vertigo in one (9%). Auditory disturbances were found in three patients (27%): two (18%) had tinnitus, and one (9%) patient had both tinnitus and hearing loss. Exudative retinal detachment of varying degrees combined with hyperemia of the optic disc was seen in ten patients (91%). One patient presented with marked optic disc swelling along with cells in both the anterior chamber and vitreous (Table 1). All 11 patients in the early phase VKH group had inflammatory cell infiltration in the vitreous, with or without cells in the anterior chamber.
Table 1

Clinical manifestations of VKH in Hispanic patients during early and late phase

Manifestations

Early phase (11 patients) (%)

Late phase (37 patients) (%)

Ocular findings

Bilateral uveitis

11 (100)

37 (100)

Exudative retinal detachment

10 (91)

Optic disc swelling

1 (9)

Sunset glow fundus

26 (70)

Nummular scar

27 (73)

Retinal pigment epithelium hyperplasia

7 (19)

Neurological disorders

Meningismus

6 (55)

Auditory abnormality

3 (27)

4 (11)

Integumentary disorders

 

7 (19)

Vitiligo

4 (11)

Poliosis

6 (16)

Alopecia

5 (14)

Lumbar puncture was performed on two patients. Laboratory analysis of the cerebrospinal fluid showed pleocytosis in both patients. Fluorescein angiography performed on seven patients (64%) revealed multiple pinpoint hyperfluorescent leakage at the level of the retinal pigment epithelium and pooling of dye in the subretinal space. Ultrasonography confirmed diffuse bilateral choroidal thickening and overlying serous retinal detachments in three patients (27%).

On initial presentation all 37 patients in the chronic phase VKH group showed inflammatory cell infiltration of the vitreous and anterior chamber. Twenty-six patients (70%) had sunset glow fundus. Peripheral nummular scars were noted in 27 patients (73%), and retinal pigment epithelium atrophy and hyperplasia were found in seven (19%). Sugiura’s sign was seen in only one patient. One or two integumentary changes were noted in seven patients (19%); vitiligo was seen in four (11%), poliosis in six (16%) and alopecia in five (14%). Auditory disturbances were noted in four patients (11%).

All 48 patients were initially treated with orally administered corticosteroids or corticosteroids combined with immunosuppressive/cytotoxic agents. The starting dose of orally given corticosteroid for patients presenting in the acute phase of VKH was 1–1.5 mg/kg per day. Marked resolution of exudative retinal detachment was seen within 3–6 weeks in nine patients (82%). The remaining two patients (18%) showed resolution by 8–12 weeks. Those patients who presented during the chronic phase of VKH were treated with corticosteroid 1 mg/kg alone (23 patients) or in combination with immunosuppressive agents (14 patients). The immunosuppressive agents used included weekly doses of methotrexate 15–22.5 mg (two patients), azathioprine 100–150 mg (six patients), cyclosporin 2.5–5 mg/kg (five patients) and mycophenolate mofetil 1,000 mg b.i.d. (one patient).

Ocular complications were noted in 24 patients (50%); these included cataract in 17 (35%), glaucoma (with optic disc changes) in 13 (27%), subretinal neovascularization/fibrosis in six (13%), cystoid macular edema in seven (15%) and epiretinal membrane in five patients (10%) (Table 2). The time between onset of symptoms and development of complications varied; cataract developed within 0.1–0.7 years (mean = 0.4 years); glaucoma occurred within 0.1–4 years (mean = 0.5 years) and subretinal neovascularization/fibrosis was noted within 0.8–3 years (median = 1.4 years) after the initial onset of symptoms. The majority of patients showed improved visual acuity with treatment. The initial and final visual acuity of these patients is summarized in Table 3.
Table 2

Ocular complications in 24 patients with VKH

Complication

Number of patients and percentage

Cataract

17 (35)

Glaucoma

13 (27)

Subretinal neovascularization or subretinal fibrosis

6 (13)

Cystoid macular edema

7 (15)

Epiretinal membrane

5 (10)

Table 3

Summary of initial and final visual acuity in Hispanic patients presenting with early and late phase VKH (VA visual acuity)

VA

Early phase (22 eyes)

Late phase (74 eyes)

Initial VA

Final VAa

Initial VA

Final VAb

Number of eyes and percentage

Number of eyes and percentage

20/20 to 20/50

4 (18)

16 (73)

29 (39)

44(60)

20/50 to 20/200

8 (36)

6 (27)

31 (42)

18 (24)

20/200 or less

10 (46)

0

14 (19)

12 (16)

aMedian time at final visit = 11 weeks (range 3–18 weeks)

bMedian time at final visit = 2.5 years (range 0.5–6 years)

Discussion

Most VKH patients in Southern California are Hispanic. These patients typically present with bilateral uveitis associated with serous retinal detachment during the early phase of VKH (Fig. 1). No extraocular changes are usually observed during this phase other than meningismus or other neurologic changes. During the chronic phase of VKH, patients present with ocular changes, including sunset glow fundus, nummular scars, and retinal pigment epithelial hyperplasia (Fig. 2). Cutaneous manifestations that become apparent during this phase include vitiligo, poliosis, and alopecia (Table 1). The clinical features of VKH in Hispanics appear to differ from those described in Japanese patients [2, 11, 12]. For instance, although auditory abnormalities reportedly occur in up to 75% of Japanese patients with VKH [10, 12], auditory disturbances were less common in Hispanics, in both the early and late phases. Only 27% of Hispanic patients who presented in the early phase of VKH, and only 11% of those who presented during the chronic phase, reported tinnitus. Similarly, meningismus appears to be less common in Hispanics (Table 1). However, despite such differences, the ocular findings of bilateral uveitis and serous retinal detachments remain similar to those seen in Japanese patients [12].
https://static-content.springer.com/image/art%3A10.1007%2Fs10792-006-9017-6/MediaObjects/10792_2006_9017_Fig1_HTML.jpg
Fig. 1

(a) Color photograph of the right fundus shows exudative retinal detachment and disc hyperemia in early phase VKH. (b) Fluorescein angiography of the right fundus shows pinpoint hyperfluorescent leakage at the retinal pigment epithelium level and pooling of dye in the subretinal space

https://static-content.springer.com/image/art%3A10.1007%2Fs10792-006-9017-6/MediaObjects/10792_2006_9017_Fig2_HTML.jpg
Fig. 2

Color photograph of the right fundus shows sunset glow fundus with peripheral nummular scars in late phase VKH

The integumentary signs did not develop in Hispanic patients with VKH until the chronic phase of the disease. This is similar to the reported findings for Japanese and other ethnic groups. Although skin involvement was seen in about 19% of Hispanic patients with VKH, by comparison, such manifestations are still less common than in other series that reported an incidence of integumentary disorders ranging from 25% to 60% [2, 6, 7, 11]. This variability in clinical presentation thus underscores the necessity for a broader set of diagnostic criteria, such as that seen in the revised diagnostic criteria developed by the International Uveitis Study Group [13]. Moreover, newer investigation such as indocyanine green angiography may be helpful in demonstrating choroidal inflammatory changes in patients with atypical clinical presentation [14].

The ocular complications of VKH appear to be common in those patients who are not properly treated during the early phase. There are many possible causes of decreased vision in patients with VKH. During episodes of initial or recurrent uveitis, vision may be limited by the inflammation itself, by serous elevation of the neurosensory retina, or, rarely, by cystoid macular edema [15]. Once the inflammation has been controlled, complications such as subretinal fibrosis may develop as long-term complications of VKH [16]. Other issues, such as the development of cataract [17], glaucomatous optic nerve damage [18], widespread alterations in the retinal pigment epithelium (RPE), and loss of choroidal melanocytes may also contribute to visual loss. Thus, it is important to establish an early and accurate diagnosis of VKH [19, 20]. The complication rate seen in the Hispanic patients is similar to that seen in non-Hispanic patients [21], suggesting that the response to systemic therapy is similar in Hispanic and non-Hispanic individuals.

Treatment with systemic corticosteroids is known to alter the clinical features and course of VKH [19, 22]. Treatment can prevent the development of complications and may reduce the frequency of depigmentation in the eyes and other melanocyte-containing systemic organs [19, 20, 23]. Ohno et al. [6] suggested that early administration of corticosteroids may help delay the appearance of extraocular manifestations, which may preclude the development of the full spectrum of disease manifestations.

In conclusion, the current study shows that extraocular manifestations of VKH may differ in Hispanic populations compared with other ethnic groups. In our series of Hispanic patients the extraocular manifestations, including neurological and dermatologic findings, were less common. However, intraocular changes were similar to those reported for other ethnic groups. The overall prognosis for adequately managed cases is fair, with nearly 60–70% of patients having a final visual acuity of 20/50 or better.

Acknowledgment

Supported in part by NIH core grant EY03040 and by a grant from Research to Prevent Blindness, Inc., New York, NY., USA

Copyright information

© Springer Science+Business Media, Inc. 2007