History
Patients with Vogt-Koyanagi-Harada (VKH) disease usually initially present to an ophthalmologist for ocular problems, including sudden loss of vision, ocular pain, and photophobia. Hearing disturbances and dizziness may be present. After weeks or months, most patients notice cutaneous signs (eg, hair loss, poliosis, vitiligo). [1, 2]
Four clinical stages have been described in VKH disease, consisting of the prodromal stage, uveitic stage, chronic stage, and recurrent stage.
Prodromal stage
The prodrome typically lasts for 7-10 days and is characterized by flu-like symptoms, such as the following:
-
Fever
-
Headache
-
Meningismus
-
Nausea
-
Vertigo
-
Orbital pain
-
Tinnitus
CSF pleocytosis occurs in more than 80% of patients during this stage. Photophobia and tearing may develop, and patients also may note that their skin and hair are sensitive to touch during this stage.
Uncommon manifestations during the prodrome include cranial nerve palsies and optic neuritis. Some patients may not develop or report the symptoms characteristic of the prodrome.
Uveitic/acute stage
The acute uveitic stage follows the prodromal stage by several days in most patients and typically lasts for several weeks. During this stage, the most common symptom is acute bilateral blurring of vision. [1, 2] As many as 70% of patients present with bilateral blurring of vision; in most of the remaining patients, the fellow eye is involved within several days.
Clinically, this stage manifests as bilateral posterior uveitis with retinal edema, exudative retinal detachments, optic disc hyperemia or edema, posterior choroid thickening, and, eventually, serous retinal detachments. Often, an accompanying anterior uveitis characterized by mutton-fat keratic precipitates and iris nodules is present. At this stage, an accompanying anterior uveitis can occur. The intraocular pressure may be elevated because of forward rotation of the lens-iris diaphragm.
Chronic stage
This convalescent stage typically occurs several weeks after the acute stage and can continue for months afterward. [4] During the chronic stage, ocular and dermatologic manifestations are common. Depigmentation of the choroid begins within the first 3 months after the onset of the disease, resulting in the sunset glow fundus. Areas of hyperpigmentation also may develop in the fundus. Dalen-Fuchs nodules may be seen in the peripheral and midperipheral retina. These nodules are small, yellow lesions that typically are located in the midperiphery of the retina. Eventually, the lesions fade and become atrophic.
Dermatologic changes include vitiligo and poliosis of the lashes, eyebrows, and hair. Other signs of depigmentation include the Sugiura sign (perilimbal depigmentation), more common in patients of Japanese descent. [52] The vitiligo tends to be distributed symmetrically over the head, eyelids, and trunk.
Recurrent stage
During the recurrent stage, patients may develop recurrent or chronic anterior uveitis. In some patients, low-grade choroidal inflammation may accompany the anterior uveitis, which may require indocyanine green angiography for visualization. [53] Recurrent posterior uveitis with serous retinal detachment is rare. Patients treated inadequately with corticosteroids and/or immunomodulator therapy for 6 months or less may be at higher risk for recurrent serous retinal detachment. [54] At this stage, the anterior uveitis typically is of granulomatous nature, with the presence of mutton fat keratic precipitates and Koeppe/Busacca nodules. [55]
Ocular complications are relatively common during this stage and include cataracts, glaucoma, choroidal neovascularization, and subretinal fibrosis.
Physical Examination
Patients suspected of having VKH disease should undergo a thorough physical examination to determine whether cutaneous, neurologic, and ophthalmic manifestations of the disorder exist.
Cutaneous manifestations
Sensitivity to touch of the hair and skin may be noted during the prodromal stage, while vitiligo, poliosis, and alopecia typically develop during the chronic stage. Vitiligo often is distributed symmetrically over the head, face, and trunk. The sacral region is a common site for the development of vitiligo. Poliosis may involve the scalp hair, eyebrows, and eyelashes.
Neurologic manifestations
Meningeal signs develop during the prodromal stage; they include meningismus, headache, and occasional confusion. CSF pleocytosis is relatively common during the prodrome.
Focal neurologic signs include the following:
-
Cranial nerve palsies
-
Hemiparesis
-
Transverse myelitis
-
Ciliary ganglionitis
Inner ear disorders, including dysacusis, tinnitus, and vertigo, occur in as many as 75% of patients. Cochlear hearing loss occurs mainly in high-frequency ranges. Inner ear dysfunction improves several months after onset in most patients.
Ophthalmic manifestations
Visual acuity may be decreased markedly in both eyes at the onset of the uveitic stage. Patients may present with unilateral loss of vision, but most develop bilateral disease within the first 10 days following onset.
Ocular adnexa involvement includes poliosis of the scalp, eyebrows, or eyelashes, which may develop during the convalescent stage of VKH disease. Vitiligo also may occur on the eyelids and face during this stage.
Anterior segment
Anterior-segment manifestations include the following:
-
Perilimbal vitiligo (Sugiura sign) - One of the earliest manifestations of depigmentation; uncommon, except in Japanese patients
-
Granulomatous or nongranulomatous anterior uveitis - May occur; Busacca nodules, Koeppe nodules, and mutton-fat keratic precipitates are characteristic of granulomatous anterior uveitis
-
Posterior synechiae - May be noted, especially in chronic cases; pupillary membrane formation is relatively common
Some patients may present with a shallow anterior chamber due to edema and infiltration of the ciliary body, with forward rotation of the lens-iris diaphragm and possible angle-closure glaucoma. Glaucoma may occur secondary not only to angle closure but also to pupillary block, or it may arise in association with chronic uveitis.
Cataracts may develop as a result of chronic inflammation and/or chronic corticosteroid therapy.
Posterior segment
Anterior vitreous cells may be noted, especially in patients with severe anterior uveitis. Optic disc hyperemia or edema may be present.
A study by Nakao et al indicated that a patient’s age and optic disc morphology, not the severity of inflammation, are associated with optic disc swelling in VKH disease. The retrospective, observational study included 58 patients (116 eyes), with 16 patients (32 eyes) demonstrating disc edema. Patients with disc swelling had a mean age of 58.9 years, compared with 41.4 years for those without swelling. Other factors, such as intraocular pressure, refractive error, and the cup-to-disc ratio, as well as the ratio of the disc-macula distance to the disc diameter, also differed between patients with swelling and those without it. [50]
One of the earliest retinal manifestations of VKH disease is retinal edema, which often is located within the posterior pole. This typically is followed by the development of bilateral, multifocal serous retinal detachments. The detachments occur most commonly in the inferior retina.
Bilateral, multifocal serous detachments in a patient with Vogt-Koyanagi-Harada disease. Disc hyperemia is evident in the right eye.
During the chronic stage of the disease, the serous detachments resolve and retinal pigment epithelium (RPE) alterations are common, including depigmentation, demarcation lines, and areas of hyperpigmentation.
The fundus of Asian and Hispanic patients may develop the characteristic red-orange appearance of the sunset-glow fundus, although this is relatively uncommon in other groups of patients. Areas of hyperpigmentation also are common and reflect changes occurring at the level of the RPE. Subretinal fibrosis, RPE migration, and disciform scars also may occur.
Neovascularization of the disc and retina may develop and can result in vitreous hemorrhage. Choroidal neovascularization of the macula may occur in the chronic stage and can result in profound loss of visual acuity.
-
Bilateral, multifocal serous detachments in a patient with Vogt-Koyanagi-Harada disease. Disc hyperemia is evident in the right eye.
-
Fluorescein angiography of the left eye in a patient with Vogt-Koyanagi-Harada disease. Midphase is shown on the left, with multiple areas of hyperfluorescence at the level of the retinal pigment epithelium (RPE). Late phase on the same angiogram (right) reveals multiple placoid areas of hyperfluorescence at the level of the RPE and pooling of dye in the areas of serous detachment.
-
Patient with progressive dysacusis and recent onset of visual loss. Fundus photo shows a large, multifocal serous detachment of the right eye. B-scan ultrasonography reveals posterior choroidal thickening with an overlying retinal detachment.
-
Patient with progressive dysacusis and recent onset of visual loss is shown here following 6 weeks of systemic corticosteroid therapy. Diffuse depigmentation of the choroid with retinal pigment epithelium migration is seen. Residual retinal striae are present in the peripapillary region. B-scan ultrasonography shows resolution of retinal detachment and choroidal thickening.
