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This page has been put together to give both patients and doctors a better understanding of VKH, Vogt-Koyanagi-Harada syndrome. Due to its rareity, finding good information can be difficult. When I was admitted to hospital during attacks of VKH I always took a laminated and bound copy of the information below. It proved invaluable as most of the doctors I saw had never heard of VKH and had no idea how to treat it. I hope the information is as helpfull for you as it has been for me.

Below is information that is very usefull to print off and keep:


Background

Vogt-Koyanagi-Harada (VKH) syndrome is a rare systemic disease involving various melanocyte-containing organs. Bilateral uveitis associated with cutaneous, neurologic, and auditory abnormalities characterizes this syndrome. As first described by Vogt in 1906 and Koyanagi in 1929, predominantly anterior uveitis associated with poliosis, vitiligo, and auditory disturbances characterizes Vogt-Koyanagi syndrome. In 1926, Harada reported a patient with idiopathic uveitis affecting the posterior segment with retinal detachment and meningeal irritation. At present, these 2 disorders are considered variations of a single entity referred to as Vogt-Koyanagi-Harada syndrome or uveoencephalitis.

Pathophysiology

The etiologic and pathogenic factors in VKH syndrome remain unclear. The clinical course of VKH syndrome with an influenzalike episode suggests a viral or postinfectious origin. Some studies invoke a possible role of Epstein-Barr virus reactivation in this disease (Sunakawa, 1985). Although a viral cause has been proposed, no virus has been isolated or cultured from patients with VKH syndrome. Morris and Schlaegel found viruslike inclusion bodies in the subretinal fluid of a patient with VKH syndrome.

Clinical and experimental data continue to support an immunologic etiology. An autoimmune reaction seems to be directed against an antigenic component shared by uveal, dermal, and meningeal melanocytes, possibly tyrosinase or a tyrosinase-related protein.

Single reports of patients developing VKH syndrome after cutaneous injury have been noted, as well as 2 cases of this condition occurring after BCG therapy for melanoma and 1 case following surgery of metastatic malignant melanoma. Recently, a case of this syndrome was reported to be linked to malignant lymphoma.

Immunologic analysis of cerebrospinal fluid (CSF) lymphocytes in VKH syndrome and studies of human uveal melanocytes show that uveal pigment can stimulate lymphocyte cultures from patients with VKH syndrome. Lymphocytes of peripheral blood and CSF from these patients may reveal in vitro cytotoxicity against allogenic melanoma cells.

Circulating antibodies against a retinal photoreceptor region have been detected in patients with this disorder.

The possibility that VKH syndrome has an autoimmune pathogenesis is supported by the statistically significant frequency of HLA-DR4, an antigen commonly associated with other autoimmune diseases. VKH syndrome has been closely associated with HLA-B54, HLA-DR4, and HLA-DR53 in Japanese patients; with HLA-DR4, HLA-DRw53, and HLA-DQw3 in subjects of Native American ancestry; with HLA-DR1 and HLA-DR4 in Hispanic patients living in southern California; and with HLA-DR4 and HLA-DQw7 in Chinese patients. HLA-DR4 also was found to be significantly related to VKH syndrome in white Europeans, specifically in Italian patients. These findings confirm the possibility of immunogenic predisposition and the decisive role of HLA-DR4 antigen in the development of the disease.

Recent data indicate that patients with VKH syndrome are sensitized to melanocyte epitopes and display a peptide-specific Th1 cytokine response. Patients bearing HLA-DRB1*0405 recognize a broader melanocyte-derived peptide repertoire, so the presence of this allele increases susceptibility to the development of VKH disease.

Frequency:

United States
VKH syndrome is rare. No precise data are available regarding frequency of the disease.

International
VKH syndrome is rare but widely distributed.

Mortality/Morbidity

VKH syndrome is not associated with mortality. Acute disturbances in hearing and vision may occur, and the cutaneous changes may be permanent.

Race

VKH syndrome occurs more frequently in individuals with darker pigmentation (eg, persons of Asian, Native American, Latin American, or black heritage). The manifestations of VKH syndrome in whites resembles those in the Japanese population. However, cutaneous signs are much more rare.

Sex

Women appear to be affected more frequently than men.

Age

The onset of VKH syndrome has been reported to range from 10-52 years, with a maximum frequency in the thirties. Although often unrecognized, VKH syndrome may affect children.

History


VKH syndrome is usually preceded by a prodromal stage of nonspecific symptoms including headache, vertigo, nausea, nuchal rigidity, vomiting, and low-grade fever that may last a few days. Patients 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).

Physical

The American Uveitis Society has recommended that, in addition to an absence of prior trauma or surgery, at least 3 of the following 4 criteria be met to confirm the diagnosis of VKH syndrome:

Bilateral iridocyclitis

Posterior uveitis, which may include exudative retinal detachment, optic nerve swelling, or atrophy of the retinal pigment epithelium

CSF pleocytosis or evidence of tinnitus, dysacusis, headache or meningismus, or cranial nerve involvement

Cutaneous findings of vitiligo, alopecia, or poliosis

The classic course of VKH syndrome consists of the following 3 phases:

In the meningoencephalitis phase, the degree of neurologic symptoms may vary. Generalized muscle weakness, hemiparesis, hemiplegia, dysarthria, and aphasia have been reported. Most of the neurologic symptoms have been directly attributed to changes in CSF (eg, pleocytosis, increased pressure, protein levels), inflammatory arachnoiditis, or resulting subarachnoidal adhesions. Mental changes ranging from mild confusion to psychosis may occur.

The ophthalmic-auditory phase is characterized by common features such as decreased visual acuity, eye pain, eye irritation, and loss of vision. Dysacusis (usually bilateral) and tinnitus develop in 50% of patients.

The convalescent phase is characterized by cutaneous signs developing after uveitis begins to subside, usually within 3 months from the onset of the disease. Although cutaneous signs typically occur several weeks to months after the onset of ocular inflammation, skin changes have sometimes been observed many years before uveitis appeared. Pigmentary changes tend to be permanent.

Poliosis, which occurs in 90% of patients, involves the eyebrows and eyelashes and, occasionally, the scalp and body hair. Poliosis affects 50% of patients and usually appears after the onset of alopecia, which may be patchy or diffuse.

Vitiligo manifests in 63% of patients and is often symmetric. Most patients have perilimbal vitiligo (Sugiura sign). Atypical variants of vitiligo with inflammatory raised borders and plaque-type inflammatory erythema have also been reported.

Halo nevi may be present.

Causes

The cause of VKH syndrome is unknown, but a viral factor has been suggested in the pathogenesis. An autoimmune reaction to melanocytes with the involvement of T-cell–mediated cytotoxicity and apoptosis is postulated. Although almost all instances of VKH syndrome are sporadic, and familial cases are rare, some authors suggest that the condition may be inherited, probably as an autosomal recessive trait. Numerous data demonstrate the association of HLA-DR4 antigen and VKH syndrome in different racial groups. According to recent studies, the major factor contributing to susceptibility for the disease is presence of the DRB*0405 allele (Goldberg, 1998).

Lab Studies

For quick diagnosis and early treatment, VKH syndrome requires a multidisciplinary management strategy involving dermatologists and ophthalmologists.
Perform neurologic examination with lumbar puncture to detect associated abnormalities.
Detailed CSF cell analysis is necessary. Changes in the CSF include pleocytosis with the presence of melanin-laden macrophages (specific for the syndrome and helpful in confirming the diagnosis), increased protein levels, and increased pressure.
Imaging Studies

Standardized A-scan and contact B-scan echography, performed by ophthalmologist
Procedures

Perform fluorescein angiography, which shows multiple hypofluorescent areas in the retina at the level of the retinal pigment epithelium.
Perform indocyanine green choroidal angiography.
Audiometry may reveal sensorineural hearing loss.
Histologic Findings

A skin biopsy specimen taken a month after the onset of ocular symptoms will likely reveal a mononuclear infiltrate concentrated in the area of hair follicles and sweat glands, consisting mostly of T lymphocytes with a small number of B cells. In depigmented skin, the absence of melanin, as anticipated in vitiligo, can be noted. Vasodilatation in the dermis, pigment-laden macrophages, and a lymphocytic infiltrate have also been described.

Medical Care

For pigmentary changes, treatment options mirror those for vitiligo.
For eye inflammatory changes, treatment includes systemic corticosteroids, with an average initial dose of 80-100 mg of oral prednisone per day. Early, aggressive use of systemic corticosteroids and a gradual tapering of drug dosage for 6 months after presentation are recommended to prevent progression and development of complications. Some authors recommend pulse corticosteroid therapy.
In patients whose conditions fail to respond to high-dose corticosteroid (oral or intravenous) therapy or who develop significant adverse effects, immunosuppression with cyclosporine or other antimetabolites (eg, azathioprine, cyclophosphamide, methotrexate [MTX]) may be required.
Topical and periocular corticosteroids are used. Cycloplegic-mydriatic eye drops are used symptomatically.

Surgical Care

Surgical therapy for glaucoma is necessary in some patients. Surgical intervention includes laser iridotomy, surgical iridectomy, and trabeculectomy.
Consultations

Ophthalmologists and neurologists must be consulted.

Further Outpatient Care

Follow routine outpatient care guidelines.

Complications

Long-term complications include reversible and irreversible vision loss, intraocular pressure elevation, glaucoma, and cataracts.
Ocular complications are more severe in children than in adults, leading to rapid deterioration in vision.

Prognosis

Pigmentary changes are usually permanent.
Final visual outcome depends on the rapidity and appropriateness of treatment.
Hearing is restored completely in most patients.

Good health to you all

Danielle Jessica

VKH support

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