Vogt–Koyanagi–Harada disease

Autoimmune multisystem inflammatory disorder affecting eyes, ears, skin, and CNS

Vogt–Koyanagi–Harada disease
Synonyms	Vogt–Koyanagi–Harada syndrome, uveomeningitis syndrome, uveomeningoencephalitic syndrome
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Field	Ophthalmology, Neurology, Dermatology, Immunology
Symptoms	Eye pain, redness, vision loss, tinnitus, vertigo, headache, meningismus, skin depigmentation, hair whitening
Complications	Permanent vision loss, hearing impairment, chronic uveitis
Onset	Young to middle-aged adults (20–50 years)
Duration	Chronic, recurrent
Types	Complete, incomplete, probable VKH
Causes	Autoimmune response targeting melanocytes
Risks	Genetic predisposition (HLA-DR4), ethnicity (Asian, Hispanic, Native American descent)
Diagnosis	Clinical evaluation, fluorescein angiography, lumbar puncture, imaging studies
Differential diagnosis	Sympathetic ophthalmia, sarcoidosis, systemic lupus erythematosus, multiple sclerosis
Prevention	None known
Treatment	Corticosteroids, immunosuppressants, biologics
Medication	Prednisone, azathioprine, cyclosporine, infliximab
Prognosis	Generally good with prompt treatment; delayed treatment may result in severe vision impairment
Frequency	Rare
Deaths	Rare

Vogt–Koyanagi–Harada disease (VKH disease) is a multisystem, chronic inflammatory disorder of presumed autoimmune origin, primarily affecting tissues containing melanin, particularly the eyes, ears, skin, and central nervous system. The disease is characterized by bilateral diffuse uveitis, neurologic involvement, auditory disturbances, and dermatological manifestations, such as vitiligo, poliosis, and alopecia.

Signs and symptoms

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Characteristic poliosis (whitening) of eyelashes in VKH

VKH disease progresses through four clinical phases, each marked by distinctive symptoms:

Prodromal phase

This initial phase typically lasts a few days and often resembles a viral illness, characterized by:

• Fever
• Headache
• Meningismus (neck stiffness, photophobia, headache)
• Auditory symptoms (tinnitus, vertigo, hypoacusis)
• Sensitivity of hair and skin to touch
• Orbital pain, photophobia, excessive tearing

Acute uveitic phase

This phase occurs shortly after the prodromal period and lasts several weeks, characterized primarily by severe bilateral uveitis:

• Eye redness and pain
• Sudden vision loss or blurred vision
• Anterior chamber inflammation
• Optic disc edema
• Serous retinal detachment

Convalescent phase

During this stage, inflammation subsides but skin and hair changes become evident:

• Vitiligo (especially in the sacral region)
• Poliosis (white patches of hair, notably eyelashes)
• Alopecia (hair loss)
• Improvement of visual acuity, though residual damage can remain

Chronic recurrent phase

Intermittent episodes of uveitis recur months to years later, which can result in:

• Permanent visual impairment or blindness
• Chronic inflammation requiring ongoing immunosuppressive therapy

Causes

VKH disease is presumed to be an autoimmune response against melanocyte-associated antigens. Melanocytes, which produce the pigment melanin, are targeted, leading to inflammation and destruction of pigmented tissues in eyes, skin, and auditory structures.

Risk factors

The following increase susceptibility to VKH disease:

• Ethnicity: More common in Asian, Hispanic, Native American, and Middle Eastern populations
• Genetic predisposition, particularly association with the HLA-DR4 allele
• Age and gender: Commonly affects young to middle-aged adults (20–50 years), more frequently in females

Pathophysiology

Autoimmune inflammation targets melanocyte-containing tissues, leading to granulomatous inflammation. In the eyes, this leads to severe uveitis, retinal detachment, and possible vision loss. Similar inflammatory processes affect the meninges, inner ear, and skin, causing characteristic symptoms across multiple organ systems.

Diagnosis

Diagnosis of VKH is clinical, based on symptoms and exclusion of other diseases, supported by:

• Ophthalmic examination, including fluorescein angiography
• Lumbar puncture showing CSF pleocytosis
• Imaging (MRI) to exclude other neurologic disorders
• Audiometric testing for hearing abnormalities

The diagnosis is classified as complete, incomplete, or probable VKH based on specific clinical and laboratory criteria.

Differential diagnosis

Conditions considered during differential diagnosis include:

• Sympathetic ophthalmia
• Sarcoidosis
• Systemic lupus erythematosus (SLE)
• Multiple sclerosis
• Acute disseminated encephalomyelitis (ADEM)

Treatment

Early diagnosis and aggressive treatment improve prognosis significantly. Treatment focuses on controlling inflammation and preventing permanent organ damage:

• High-dose corticosteroids (oral prednisone or intravenous methylprednisolone)
• Immunosuppressive agents (azathioprine, cyclosporine, methotrexate)
• Biological agents (e.g., infliximab) for refractory cases
• Regular follow-up to monitor ocular inflammation and disease recurrence

Complications

Potential complications of VKH disease include:

• Chronic uveitis leading to cataracts, glaucoma, and vision loss
• Permanent hearing impairment
• Neurological deficits or cognitive impairment due to chronic CNS inflammation

Prognosis

The prognosis for VKH disease is generally favorable with prompt initiation and adequate duration of immunosuppressive therapy. Delayed diagnosis or inadequate treatment increases the risk of permanent visual impairment and hearing loss. Lifelong monitoring and management are typically required.

Epidemiology

VKH disease is considered rare globally, though prevalence varies significantly by ethnicity. It is more common among populations with increased melanin content, including Asian, Hispanic, Native American, and Middle Eastern communities. Women are affected more frequently than men, with peak onset occurring between ages 20 and 50.

History

VKH disease is named after ophthalmologists who described the condition independently:

• Alfred Vogt (Swiss, 1906) described anterior uveitis and depigmentation.
• Yoshizo Koyanagi (Japanese, 1929) reported similar ocular and dermatologic symptoms.
• Einosuke Harada (Japanese, 1926) described the neurologic and audiological manifestations.

Research

Current research is exploring:

• Genetic susceptibility factors and biomarkers for early diagnosis
• Mechanisms of autoimmune response against melanocytes
• Improved therapeutic approaches using biologic agents and targeted immunotherapies

See also

• Autoimmune disease
• Uveitis
• Poliosis
• Vitiligo
• Alopecia

External links

• Vogt–Koyanagi–Harada Disease – NORD
• Vogt-Koyanagi-Harada Syndrome – EyeWiki (AAO)