Vogt–Koyanagi–Harada syndrome

What is Vogt–Koyanagi–Harada syndrome?

Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem disease that presents with a combination of ophthalmological, neurological, and dermatological signs and symptoms.

• The main defining clinical finding of VKH is severe bilateral granulomatous panuveitis (inflammation throughout the uveal tract in the eye).
• Cutaneous features include vitiligo, alopecia areata, and poliosis (white hair).
• Neurological features include meningism (symptoms of meningitis with no inflammation), hearing loss, and tinnitus.

Vitiligo 

Vitiligo 

Vitiligo + psoriasis 

Who gets Vogt–Koyanagi–Harada syndrome?

VKH is reported to have significant regional and global variation [1]. VKH is more prevalent in patients with a darker skin pigmentation than in Caucasians and people of Turkish descent. Patients with VKH are most commonly of Asian, Hispanic, Indian, Native American, or Mediterranean origin [2]. There are twice as many females affected by VKH as males [3].

VKH is mainly diagnosed in adult and middle-aged patients aged 20–50, although onset in childhood or old age has also been reported [4–6].

What causes Vogt–Koyanagi–Harada syndrome?

The exact cause of VKH is yet to be established. It is an autoimmune inflammatory condition mediated by CD4+ T cells targeting melanocytes [7,8]. Genetic predisposition and/or an unspecified exposure to a virus may be involved [1].

What are the clinical features of Vogt-Koyanagi-Harada syndrome?

Classically, VKH has four clinical stages. The clinical features vary, depending on ethnic group. Dermatological features are most often noted in the chronic convalescent stage [1].

The prodromal stage

The prodromal stage of VKH may mimic viral infection and lasts for 1–2 weeks [2]. The symptoms are mainly neurological, and include:

• Headache
• Neck stiffness
• Photophobia
• Fever
• Orbital pain
• Scalp and general skin sensitivity
• Focal neurological deficits (eg, cranial nerve palsy).

Auditory symptoms include:

• Hearing loss (particularly for higher frequencies)
• Discomfort when exposed to sounds at normal volume
• Vertigo
• Tinnitus [2].

The acute stage

The acute stage of VKH affects the eye and lasts for several weeks [2].

• The main symptom of the acute stage of VKH is blurred vision in both eyes [1].
• Ophthalmological findings are panuveitis or posterior uveitis, with multifocal serous retinal detachments [2].
• Early recognition and treatment can prevent progression to chronic convalescent and chronic recurrent stages of the disease [7].

The chronic convalescent stage

Many patients with acute VKH go on to the chronic convalescent stage of VKH, about 3–4 months after the onset of the disease [9,10]. This usually lasts for some months or years [1,2].

• Ophthalmological findings of the chronic convalescent phase of VKH include non-granulomatous panuveitis and depigmentation of the choroid (the middle coat of the eye), with a bright orange fundus (a 'sunset glow') [10,11].
• The dermatological findings are poliosis of the eyebrows and eyelashes, vitiligo, and alopecia areata [1].

The chronic recurrent stage

25% of patients with acute VKH develop the chronic recurrent phase of the disease 6–9 months after initial presentation [1,2].

• Ophthalmological findings are recurrent granulomatous anterior uveitis and choroidal thickening.
• Vitiligo and alopecia areata may have phases of relapse and remission.

What are the dermatological findings in Vogt–Koyanagi–Harada syndrome?

About 30% of patients with VKH develop dermatological findings [12]. Vitiligo, poliosis, and alopecia areata usually occur in the chronic convalescent stage of the disease [13].

What are the complications of Vogt–Koyanagi–Harada syndrome?

Patients with VKH can develop complications that threaten or impair vision, such as:

• Retinal detachment in the acute phase [2]
• Secondary glaucoma in the chronic phase (45% of VKH cases)
• Cataracts (42% of cases [11,14,15])
• Subretinal fibrosis (40% of cases [16]).

How is Vogt-Koyanagi-Harada syndrome diagnosed?

The diagnostic criteria for VKH include inflammation of both eyes without evidence of another ocular disease, a history of trauma, or ocular surgery [17].

There are three distinct categories of the disease [17]:

1. Complete VKH — where there is bilateral ocular involvement (with detailed criteria depending on the stage of disease), plus neurological and dermatological signs; neurological signs may resolve, whereas dermatological signs do not precede the onset of uveitis.
2. Incomplete VKH — where the ophthalmological findings are as for patients with complete VKH, plus either neurological or dermatological signs.
3. Probable VKH — where the ophthalmological findings are as for patients with complete VKH, but without neurological or dermatological signs.

What is the differential diagnosis for Vogt–Koyanagi–Harada syndrome?

Differential diagnoses for the ophthalmological signs and symptoms of the disease include:

• Prior trauma — including sympathetic ophthalmia (inflammation of the conjunctiva or the eyeball; sympathetic ophthalmia can have an almost identical clinical picture to VKH, including its dermatological manifestations [18]
• Infection — including bacterial or fungal infection, tuberculosis or syphilis [1]
• Malignancy — such as intraocular lymphoma, systemic lymphoma, or leukaemia [1]
• Inflammatory disease — including bilateral posterior scleritis, sarcoidosis, or lupus choroidopathy (degradation of the eye coating due to lupus) [1].

What is the treatment for Vogt–Koyanagi–Harada syndrome?

­Acute VKH should be treated aggressively with a systemic corticosteroid (minimum treatment duration is 6 months), combined with a corticosteroid-sparing agent, such as ciclosporin, methotrexate, or mycophenolate mofetil [1]. Anti–tumour necrosis factor alpha (TNF) agents or other biological agents can be considered in patients who do not respond to corticosteroids combined with corticosteroid-sparing agents [1].

The aim of treatment is to dampen the inflammatory response and to prevent ocular complications, such as sunset glow fundus, cataracts, glaucoma, and choroidal neovascularisation [1].

What is the outcome for Vogt–Koyanagi–Harada syndrome?

Better visual outcomes are described in those patients who undergo prompt and aggressive treatment of VKH. However, a significant proportion of patients still develop vision-impairing complications. Cataracts and glaucoma often require surgical management [1,2].

Favourable prognostic factors include good initial visual acuity and initiation of treatment in the acute rather than chronic recurrent stage of the disease [11,15,19].