Vogt-Koyanagi-Harada Disease 

  • Author: R Christopher Walton, MD; Chief Editor: Hampton Roy Sr, MD   more...
 
Updated: Apr 14, 2010
 

Background

Vogt-Koyanagi-Harada (VKH) disease is a multisystem disorder characterized by granulomatous panuveitis with exudative retinal detachments that is often associated with neurologic and cutaneous manifestations. VKH disease occurs more commonly in patients with a genetic predisposition to the disease, including Asian, Middle Eastern, Hispanic, and Native American populations. Several human leukocyte antigen (HLA) associations have been found in patients with VKH disease, including HLA-DR4, HLA-DR53, and HLA-DQ4.[1, 2, 3, 4, 5]

Independently, Vogt, Koyanagi, and Harada described several patients during a 20-year period with bilateral uveitis, exudative retinal detachments, neurologic abnormalities, and disorders of the integument. Despite differences in their patients, the manifestations appeared to represent a spectrum of disease and several authors suggested that the disorder should be termed Vogt-Koyanagi-Harada syndrome.

With such a wide spectrum of the disease, typical cases of VKH disease are uncommon. To help clarify the diagnostic features of VKH disease, an International Committee on Nomenclature established revised criteria for the diagnosis of VKH disease. The revised criteria defined 3 categories of disease: complete VKH, incomplete VKH, and probable VKH. Common to all forms of VKH disease are the requirements that: (1) patients have no prior history of ocular trauma or surgery, (2) patients have no evidence of another ocular disease based upon clinical or laboratory evidence, and (3) patients have bilateral ocular involvement. Additional criteria for each form of the disease are outlined below.

Complete VKH disease

Early manifestations of complete VKH disease include diffuse choroiditis that may include serous retinal detachment or focal areas of subretinal fluid. Patients without these findings must have diffuse choroidal thickening by ultrasonography with fluorescein angiographic abnormalities, including focal areas of delayed choroidal perfusion, multifocal pinpoint leakage, areas of placoid hyperfluorescence, pooling of subretinal fluid, and optic nerve staining.

Late manifestations of complete VKH disease include evidence of previous early manifestations of the disease, as outlined above, with ocular depigmentation and nummular chorioretinal scars, retinal pigment epithelium (RPE) clumping and migration, or anterior uveitis.

Patients with complete VKH disease must also have evidence of neurologic and auditory findings as well as integumentary signs. However, the neurologic and auditory manifestations may have resolved before an ophthalmic examination. The neurologic and auditory manifestations include meningismus (but not headache alone), tinnitus, and cerebrospinal fluid pleocytosis. Integumentary signs include alopecia, poliosis, and vitiligo. However, these integumentary signs should not occur prior to the onset of ocular signs and central nervous system signs.

Incomplete VKH disease

Patients with incomplete VKH disease are similar to those with complete VKH disease, but patients with incomplete VKH disease do not have both the neurologic and auditory manifestations and the integumentary signs. To be diagnosed with incomplete VKH disease, patients must have either the neurologic and auditory manifestations or the integumentary signs.

Probable VKH disease

Patients with probable VKH disease include those with isolated ocular disease.

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Pathophysiology

The pathogenesis of VKH disease is uncertain. However, the wide spectrum of findings in this disorder suggests a central mechanism to account for the multisystem manifestations. Inflammation and loss of melanocytes has been described in a number of tissues, including the skin, inner ear, meninges, and uvea. These histopathologic changes suggest an infectious or autoimmune basis for the disease.

VKH disease currently is considered to be a cell-mediated autoimmune disease directed against melanocytes. Yamaki and coworkers have shown that the tyrosinase-related proteins, TRP1 and TRP2, can induce disease in Lewis rats that is similar to VKH disease in humans.[6] These findings suggest that the tyrosinase family proteins induce VKH disease.[7]

Genetics

The strong association between VKH disease and certain racial and ethnic groups suggests that the disorder may have an immunogenetic predisposition.[8] HLA typing can be useful to identify these common genetic factors. As a result, several HLA haplotypes appear to be more common in certain populations with VKH disease. Among Japanese patients, HLA-DR4, HLA-DR53, and HLA-DQ4 are associated strongly with the disease. In Chinese patients, HLA associations are seen with HLA-DR4, HLA-DR53, and HLA-DQ7. In a mixed group of American patients, Davis and coworkers found an association with HLA-DR4 and HLA-DR53, while HLA-DR1 and HLA-DR4 were reported in Hispanic patients living in southern California.[9]

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Epidemiology

Frequency

United States

VKH disease is uncommon, but it may be seen in Asian, Middle Eastern, Hispanic, and Native American populations. VKH disease is extremely uncommon in whites. In a report from the National Eye Institute, Nussenblatt and coworkers noted that 50% of their patients were Caucasian, 35% were African American, and 13% were Hispanic; however, most patients had remote Native American ancestry.[10]

International

VKH disease commonly is seen in Asian (primarily from eastern and southeastern Asia), Middle Eastern, and Hispanic populations.

Mortality/Morbidity

  • Neurologic manifestations: Many of the neurologic manifestations may persist for weeks. Most signs and symptoms resolve with corticosteroid therapy, although severe meningoencephalitic impairment has been reported.
  • Cutaneous manifestations: Most of the integumentary changes, including alopecia, poliosis, and vitiligo, persist despite therapy.
  • Auditory manifestations: Inner ear manifestations typically respond to corticosteroid therapy within weeks to months.

Race

Historically, VKH disease is reported to be more common in darkly pigmented races. However, individuals with VKH disease most likely have an immunogenetic predisposition that is probably more common in certain ethnic groups with increased skin pigmentation, such as Asian, Middle Eastern, Hispanic, and Native American populations. Also, VKH disease is distinctly uncommon in Africans, reaffirming that skin pigmentation alone is not a predisposing factor in the pathogenesis of the disease.

  • In Japan, VKH disease represents 7-8% of all patients with uveitis.
  • This disorder rarely is seen in Northern European individuals.

Sex

Females are more commonly affected than males. The female-to-male ratio in most large series is 2:1.

Age

VKH disease affects individuals aged 20-50 years, most frequently during the third decade. Yet, children as young as 4 years have been reported with VKH disease.

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Contributor Information and Disclosures
Author

R Christopher Walton, MD  Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Specialty Editor Board

John D Sheppard Jr, MD, MMSc  Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Ophthalmology Residency Research Program Director, Eastern Virginia Medical School; President, Virginia Eye Consultants

John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Steve Charles, MD  Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians & Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong

Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society

Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

Lance L Brown, OD, MD  Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

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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. Mid phase is shown on the left with multiple areas of hyperfluorescence at the level of the retinal pigment epithelium. Late phase of the same angiogram (right) reveals multiple placoid areas of hyperfluorescence at the level of the retinal pigment epithelium 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.
 
 
 
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