eMedicine Specialties > Ophthalmology > Unclassified Disorders

Vogt-Koyanagi-Harada Disease: Differential Diagnoses & Workup

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

Updated: Jan 5, 2008

Differential Diagnoses

Acute Multifocal Placoid Pigment Epitheliopathy
Sarcoidosis
Chorioretinopathy, Central Serous
Scleritis
Epimacular Membrane
Sudden Visual Loss
Glaucoma, Uveitic
Synechia, Peripheral Anterior
Headache, Migraine
Tuberculosis
Lyme Disease
Uveitis, Anterior, Granulomatous
Multifocal Choroidopathy Syndromes
Uveitis, Intermediate
Ocular Manifestations of Syphilis
White Dot Syndromes
Papilledema
Retinal Detachment, Exudative

Other Problems to Be Considered

Sympathetic ophthalmia
Intraocular lymphoma
Bilateral diffuse uveal melanocytic proliferation
Metastatic carcinoma
Idiopathic uveal effusion syndrome
Benign reactive lymphoid hyperplasia
Toxemia of pregnancy

Workup

Laboratory Studies

  • The diagnosis of VKH disease is based upon a constellation of clinical signs and symptoms with no confirmatory tests. However, several diagnostic procedures may be useful in establishing the diagnosis, including fluorescein angiography, ultrasonography, examination of the CSF, magnetic resonance imaging, and electrophysiologic testing.
  • Examination of the CSF: This test is not necessary in typical cases of VKH disease but may be useful in cases with atypical manifestations. More than 80% of patients with VKH disease exhibit a transient CSF pleocytosis consisting primarily of lymphocytes during the first several weeks of the disease. The pleocytosis resolves within 8 weeks of onset in most patients.
  • HLA typing: Although a number of HLA associations with VKH disease have been documented, HLA typing is not diagnostic of the syndrome and is not routinely recommended.

Imaging Studies

  • Fluorescein angiography
    • Acute VKH disease: Multiple pinpoint areas of leakage at the level of the RPE overlying areas of choroiditis are visible during the arteriovenous phase. In the early and mid phases of the angiogram, radial folds of the choroid may be visible as alternating dark and light bands of fluorescence. During the later phases of the angiogram, the pinpoint areas gradually enlarge and stain the adjacent subretinal and sub-RPE fluid. Multiple serous retinal detachments with pooling of dye often are seen in the late phases of the study. Other less common findings include retinal vascular leakage and optic disc staining.
    • Recovery phase of VKH disease (after treatment with systemic corticosteroids): Most of the acute phase abnormalities, including exudative retinal detachment and disc edema, resolve during this period. Fluorescein angiography may show persistent pinpoint areas of leakage and disc staining. Some patients may exhibit window defects and areas of mottled background hyperfluorescence.
    • Chronic VKH disease: This is characterized clinically by depigmentation of the choroid. With angiography, signs of RPE atrophy are visible, such as a moth-eaten appearance, multiple window defects, and areas of alternating hyperfluorescence and hypofluorescence. Additional findings include choroidal neovascularization, retinochoroidal and arteriovenous anastomoses, and neovascularization of the disc. Macular edema is rare in this disorder but may be seen in the chronic phase.
  • Optical coherence tomography (OCT): Serous retinal detachments with subretinal septa may be visible, especially early in the disease.  OCT may be useful to monitor serous detachments and response to therapy.
  • Indocyanine green angiography
    • Acute VKH disease: Indocyanine green angiography findings include delay of choriocapillaris perfusion as well as fuzzy and indistinct choroidal vessels, multiple hypofluorescent dark spots during the intermediate and late phase, and disc hyperfluorescence during the late phase.
    • Recovery phase of VKH disease (after treatment with systemic corticosteroids): Most of the acute abnormalities resolve during this period. However, some of the hypofluorescent dark spots may persist for weeks.
    • Chronic VKH disease: Findings include hypofluorescent areas during the intermediate and late phases.
  • Ultrasonography: The most characteristic finding is diffuse, low-to-medium reflective thickening of the posterior choroid. Additional findings include serous retinal detachments, mild thickening of the sclera and/or episclera adjacent to areas of choroidal thickening, and mild vitreous opacities. These ultrasonography features may be useful in monitoring the response to therapy.
  • MRI: This imaging study may be useful in discriminating the sclera from the choroid and retina. With T1- and T2-weighted images, the sclera is hypointense and allows differentiation between VKH disease and posterior scleritis. During the active phase of the disease, the choroid is thickened visibly and enhances following administration of gadolinium.

Other Tests

  • Electrophysiologic testing demonstrates nonspecific abnormalities in VKH disease; however, they may be useful in monitoring the progression of the disease.
    • Electroretinogram (ERG): During the early stages of the disease, the a and b wave amplitudes of the ERG may be depressed mildly. This may persist for extended periods but often recover to near normal levels during the chronic stages of the disease.
    • Electro-oculogram (EOG): During the early stages of the diseases, the light peak of the EOG may be depressed but returns toward normal with recovery and the chronic stages of the diseases.

Histologic Findings

In most cases, histopathology has shown nongranulomatous inflammation with a plasma cell infiltrate of the uvea. Lymphocytes, multinucleated giant cells, and epithelioid cells have been described in the uvea of patients with VKH disease.

Many of the giant cells and epithelioid cells contain melanin pigment. In many cases, the choriocapillaris is not involved in the inflammatory process; however, in eyes with chronic disease, inflammation may be seen in the choriocapillaris and retina. Also, in eyes with chronic VKH disease, there is loss of choroidal melanocytes.

More on Vogt-Koyanagi-Harada Disease

Overview: Vogt-Koyanagi-Harada Disease
Differential Diagnoses & Workup: Vogt-Koyanagi-Harada Disease
Treatment & Medication: Vogt-Koyanagi-Harada Disease
Follow-up: Vogt-Koyanagi-Harada Disease
Multimedia: Vogt-Koyanagi-Harada Disease
References
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Further Reading

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Keywords

Vogt-Koyanagi-Harada syndrome, VKH syndrome, VKH disease, Harada disease, Vogt-Koyanagi syndrome, uveoencephalitis, uveomeningitis, granulomatous panuveitis

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Contributor Information and Disclosures

Author

R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Diseases Service, Assistant Department of Ophthalmology, Assistant Dean for Graduate Medical Education and Continuing 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.

Medical Editor

John D Sheppard, Jr, MD, MMSc, Associate Professor of Ophthalmology, Microbiology and Immunology, Director for Thomas R Lee Center for Ocular Pharmacology, Director, Uveitis Service, Eastern Virginia School of Medicine; Consulting Staff, 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 Uveitis Society, Association for Research in Vision and Ophthalmology, and Contact Lens Association of Ophthalmologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
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

CME Editor

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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