Vogt–Koyanagi–Harada Disease

Overview

Vogt–Koyanagi–Harada (VKH) disease is a rare, multisystem autoimmune disorder that primarily affects melanin-rich tissues, including the eyes, skin, ears, and central nervous system. It is characterized by bilateral granulomatous uveitis, often accompanied by neurologic and integumentary symptoms such as meningitis, hearing loss, vitiligo, and alopecia. VKH is more common in individuals with darker skin tones, such as Asians, Hispanics, Middle Easterners, and Native Americans. If not promptly treated, it can lead to permanent visual impairment.

Causes

VKH disease is believed to be caused by an autoimmune response against melanocytes — the pigment-producing cells found in the eyes, skin, inner ear, and meninges. Although the exact trigger is unknown, genetic predisposition and environmental factors may contribute. Key causes and risk factors include:

• Autoimmunity: Immune-mediated attack on melanocyte antigens

• Genetic susceptibility: Associations with certain HLA types, particularly HLA-DR4

• Viral triggers: Infections may act as catalysts in genetically predisposed individuals

Symptoms

VKH disease progresses through four clinical stages: prodromal, acute uveitic, convalescent, and chronic recurrent. Symptoms vary depending on the stage:

• Prodromal stage:

  • Headache

  • Meningismus (neck stiffness, photophobia)

  • Tinnitus and hearing disturbances

  • Fever and malaise

• Acute uveitic stage:

  • Bilateral blurred vision

  • Photophobia and eye pain

  • Serous retinal detachment

  • Redness and visual field defects

• Convalescent stage:

  • Depigmentation of the choroid ("sunset glow fundus")

  • Vitiligo (white skin patches)

  • Alopecia (hair loss)

  • Poliosis (whitening of eyelashes or eyebrows)

• Chronic recurrent stage:

  • Recurrent granulomatous anterior uveitis

  • Complications such as cataracts or glaucoma

Diagnosis

Diagnosis of VKH disease is based on clinical presentation, ocular findings, and exclusion of other causes of uveitis. Diagnostic steps include:

• Ophthalmologic examination: Slit-lamp exam reveals granulomatous anterior uveitis; fundus exam may show serous retinal detachments

• Fluorescein angiography: Reveals pinpoint hyperfluorescence and subretinal fluid

• Optical coherence tomography (OCT): Detects retinal detachment and subretinal fluid

• Lumbar puncture: May show pleocytosis in cerebrospinal fluid during the prodromal phase

• Audiometry: Evaluates sensorineural hearing loss

• Exclusion of infectious or neoplastic causes: Including syphilis, tuberculosis, and lymphoma

Treatment

Early and aggressive immunosuppressive therapy is essential in VKH to prevent chronic complications and preserve vision. Treatment includes:

• Systemic corticosteroids: High-dose oral or intravenous steroids are the first-line treatment

• Immunosuppressive agents: Azathioprine, cyclosporine, or mycophenolate mofetil may be added for steroid-sparing effect or recurrent disease

• Biologic therapy: Anti-TNF agents or other biologics may be considered in refractory cases

• Topical corticosteroids: Used for anterior segment inflammation

• Supportive care: Management of intraocular pressure, cataracts, and other complications

Prognosis

With early diagnosis and appropriate immunosuppressive therapy, many patients with VKH can achieve good visual outcomes. However, delayed or inadequate treatment increases the risk of chronic recurrent inflammation and vision loss. Long-term follow-up is essential, as recurrence is common and complications such as cataracts, glaucoma, and choroidal neovascularization may occur. Lifelong monitoring and occasional adjustments in therapy are often necessary to maintain disease control and preserve quality of life.