Information on the following diseases can be found in the Related Disorders section of this report:

• Alopecia
• Vitiligo
• Glaucoma

Vogt-Koyanagi-Harada syndrome is initially characterized by headaches, very deep pain in the eyes, dizziness (vertigo), and nausea. These symptoms are usually followed in a few weeks by eye inflammation (uveitis) and blurring of vision. This may occur in both eyes at the same time or in one eye first and, a few days later, in the other. The retina may detach and hearing loss may become apparent.

The chronic stage follows in a few weeks. This stage is characterized by changes in the eyes and skin. The changes in the eyes may include loss of color in the layer of the eye filled with blood vessels that nourish the retina (choroid), as well as the development of small yellow nodules in parts of the retina. Skin changes may include the development of smooth, white patches in the skin caused by the loss of pigment-producing cells (vitiligo). These white patches are usually distributed over the head, eyelids and torso. The chronic stage can last for several months to several years.

In many individuals, treatment improves sight and hearing. However, there may be some permanent problems, including vision and hearing deficits, and hair loss with associated loss of color of the hair, eyelashes, and skin. Lasting visual effects may include the development of secondary glaucoma and cataracts.

The exact cause of Vogt-Koyanagi-Harada syndrome is unknown. It is thought by researchers to be an immune response to the human leukocyte antigen (HLA). These are genetic markers located on chromosome 6 that react specifically with a particular antibody. This genetic defect may predispose persons who carry this antigen to develop Vogt-Koyanagi-Harada syndrome.

Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue.

Some researchers also think that there may be a genetic predisposition for the disease since it has occurred in a brother and sister and in a set of twins. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease.

Vogt-Koyanagi-Harada syndrome is a very rare disease that affects males and females in equal numbers. The disorder is more prevalent in Oriental, Hispanic, and American Indian populations than in people who trace their ancestry to northern Europe. Onset typically occurs at around 30 or 40 years of age, but cases have been reported among children as young as four years old.

Symptoms of the following disorders can be similar to those of Vogt-Koyanagi-Harada syndrome or may occur in conjunction with Vogt-Koyanagi-Harada syndrome.

Alopecia is unpredictable hair loss due to an unknown cause. Regrowth of hair may or may not occur. Hair loss is usually confined to the head and face, although the entire body may be involved. (For more information on this disorder, choose "Alopecia" as your search term in the Rare Disease Database.)

Vitiligo is characterized by spots on the skin with decreased pigmentation. These areas are usually sharply demarcated with increased coloring (hyperpigmentation) on the borders, and are often symmetrical in shape. The face, neck, hands, abdomen, and thighs are most often effected. The hair and skin in the area are usually white. The white areas are prone to sunburn and should be protected from sunlight. (For more information on this disorder, choose "Vitiligo" as your search term in the Rare Disease Database.)

Glaucoma may occur as a secondary characteristic of VKH syndrome. It is characterized by increased pressure within the eye. If left untreated the increased pressure may affect the lens and optic nerve of the eye, resulting in eventual blindness. Some symptoms for people to be aware of are: blurred vision, rainbow colored halos around lights, and loss of side vision resulting in "tunnel vision."

Diagnosis
An international group of experts has concluded that at least three of the following four signs should be present for a diagnosis of this disorder:

a. Chronic inflammation of the iris and ciliary body in both eyes (bilateral iridocyclitis)

b. Inflammation of the rear of the eye with the presence of cellular materials (exudative) that have escaped from surrounding cells and permeated the tissues

c. Neurologic signs such as ringing in the ears (tinnitus), neck stiffness, and/or cells in the cerebrospinal fluid (pleocytosis)

d. Dermatological signs such as white patches on the arms or torso, sudden loss of hair (alopecia), or loss of color of the hair, eyelashes or eyelids (poliosis)

In addition, the criteria for diagnosis include that there should be no history of trauma or eye surgery (intraocular surgery).

Treatment
Standard treatment of Vogt-Koyanagi-Harada syndrome is the use of high-dose systemic steroid drugs. Testing used by an ophthalmologist or neurologist to determine if this disease is present include a spinal tap, x-ray of the blood vessels after the injection of dye (angiography), and ultrasound. Other treatment is symptomatic and supportive.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Intravenous immunoglobulin (IVIg) therapy is being studied as a potential treatment option for individuals with Vogt-Koyanagi-Harada syndrome. Initial findings demonstrate that IVIg therapy was effective in improving symptoms associated with the disorder. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with Vogt-Koyanagi-Harada syndrome.

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REVIEW ARTICLES
Damico FM, Kiss S, Young LH. Vogy-Koyanagi-Harada disease. Semin Ophthalmol. 2005;20:183-90.

Stanga PE, Lim JI, Hamilton P. Indocyanine green angiography in chorioretinal diseases: indications and interpretation: an evidence-based update. Ophthalmology. 2003;110:15-21.

Read RW. Vogt-Koyanagi-Harada disease. Ophthalmol Clin North Am. 2002;15:333-41, vii.

Boyd SR, Young S, Lightm,an S. Immunopathology of the noninfectious posterior and intermediate uveitides. Surv Ophthalmol. 2001;46:209-33.

JOURNAL ARTICLES
Bykhovskaya I, Thorne JE, Kempen JH, Dunn JP, Jabs DA. Vogy-Koyanagi disease: clinical outcomes. Am J Ophthalmol. 2005;140:674-8.

Gonzalez-Delgado M, Gonzalez C, Blazquez JI, et al., Intravenous immunoglobulin therapy in Vogt-Koyanagi-Harada syndrome. Neurologia. 2004;19:401-3.

Ganesh SK, Padmaja Babu K, Biswas J. Cataract surgery inpatients with Vogt-Koyanagi-Harada syndrome. J Cataract Refract Surg. 2004;30:95-100.

Sheu SJ, Kou HK, Chen JF. Prognostic factors for Vogt-Koyanagi-Harada disease. J China Med Assoc. 2003;66:148-54.

Kouda N, Sasaki H, Harada S, et al. Early manifestation of vogt-koyanagi-harada disease as unilateral posterior scleritis. Jpn J Ophthalmol. 2002;46:590-93.

Schalenbourg A, Leys A, De Courten C, et al. Corticosteroid-induced central serous chorioretinopathy inpatients with ocular inflammatory disorders. Klin Monatsbla Augenheilkd. 2002;219:264-67.

Imai Y, Sugita M, Nakamura S, et al. Cytokine production and helper T-cell subsets in Vogt-Koyanagi-Harada disease. Cur Eye Res. 2001;22:312-18.

Kamondi A, Szegedi A, Papp A, et al. Vogt-Koyanagi-Harada disease presenting initially as aseptic meningoencephalitis. Eur J Neurol. 2000;7:719-22.

FROM THE INTERNET
Walton RC. Vogt-Koyanagi-Harada Syndrome. emedicine. Last Updated: September 18, 2001. 18pp.
www.emedicine.com/oph/topic459.htm

Choczaj-Kukula A, Janniger CK. Vogt-Koyanagi-Harada Syndrome. emedicine. Last Updated September 15, 2003. 11pp.
www.emedicine.com/derm/topic739.htm

Fattal D. Vogt-Koyanagi-Harada syndrome. Baylor Neurology Case of the Month. 1995-2000 BCM. 6pp.
www.bcm.tmc.edu/neurol/challeng/pat14/summary.html