Vogt-Koyanagi-Harada (VKH) disease is a rare, multisystem autoimmune disorder. It occurs when the immune system mistakenly attacks healthy cells containing melanin, primarily affecting melanin-pigmented tissues throughout the body. This autoimmune response can lead to various symptoms and complications, particularly impacting vision.
What is Vogt-Koyanagi-Harada Disease?
Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder where the immune system attacks its own melanin-producing cells, called melanocytes. This leads to inflammation in melanin-rich areas. The disease is not contagious, and its exact trigger remains unknown.
The primary tissues affected include the eyes, inner ear, skin, and central nervous system. In the eyes, the uvea and retina are particularly susceptible. The inner ear can experience dysfunction, and the skin may show pigmentation changes. Central nervous system involvement often includes the meninges, the protective membranes around the brain and spinal cord.
Symptoms and Disease Progression
Symptoms of Vogt-Koyanagi-Harada disease are diverse and progress through distinct phases. Ocular symptoms often include bilateral uveitis, an inflammation of the eye’s middle layer, leading to blurred vision, eye pain, and light sensitivity (photophobia). Exudative retinal detachments, where fluid accumulates under the retina, and optic disc swelling (hyperemia or edema) are also common.
Neurological manifestations can appear early, presenting as headaches, neck stiffness (meningismus), and sometimes meningitis. Auditory symptoms include ringing in the ears (tinnitus), dizziness (vertigo), and hearing loss (hypoacusis). These neurological and auditory signs may precede ocular involvement.
Dermatological changes usually develop later. These include vitiligo (patches of skin losing pigment), poliosis (whitening of hair, eyelashes, or eyebrows), and hair loss (alopecia).
The disease typically unfolds in four phases:
Prodromal Phase: Often mimics a viral infection, with flu-like symptoms such as fever, headache, and general malaise, lasting days to weeks.
Acute Uveitic Phase: Marked by the onset of ocular symptoms, particularly bilateral panuveitis and vision loss, alongside neurological symptoms.
Convalescent Phase: Sees the development of dermatological manifestations like vitiligo and poliosis, as well as depigmentation of the fundus, giving it a “sunset glow” appearance.
Chronic Recurrent Phase: May involve persistent or recurring ocular inflammation, potentially leading to complications like cataracts and glaucoma.
How VKH is Diagnosed and Why it Happens
Diagnosing Vogt-Koyanagi-Harada disease relies on clinical observations and specific diagnostic criteria. These criteria require the absence of a history of penetrating ocular trauma or surgery before uveitis onset, and no other evidence suggesting different ocular diseases. Bilateral ocular involvement is a key feature, with early manifestations including diffuse choroiditis, often detected as focal areas of subretinal fluid or bullous serous retinal detachments.
Imaging techniques confirm diagnosis and monitor disease activity. Fundus fluorescein angiography (FFA) can show delayed choroidal perfusion, multifocal pinpoint leakage, and pooling within subretinal fluid, along with optic nerve staining. Optical coherence tomography (OCT) detects and quantifies subretinal fluid. B-mode ocular ultrasound reveals diffuse choroidal thickening and serous retinal detachments.
The underlying mechanism of VKH disease is an autoimmune response where T-cells mistakenly target melanocytes, the cells producing melanin pigment. While the exact trigger is not fully understood, genetic predispositions play a significant role. There is a strong association with certain Human Leukocyte Antigen (HLA) types, particularly HLA-DR4 and HLA-DQ4, among affected individuals in various populations, including Asian, Hispanic, and Native American groups. This genetic susceptibility, combined with potential environmental factors like viral infections, is thought to initiate the autoimmune process.
Treatment Approaches for VKH
Treatment for Vogt-Koyanagi-Harada disease focuses on controlling inflammation, preserving vision, and preventing long-term complications. Early and aggressive systemic therapy is recommended to achieve these goals.
Corticosteroids are the primary first-line treatment for suppressing acute inflammation. They can be administered systemically, often starting with high-dose intravenous methylprednisolone, followed by oral prednisone. Local corticosteroid applications, such as eye drops or injections around the eye, may manage anterior uveitis.
For long-term management, especially in cases resistant to corticosteroids or to reduce steroid side effects, immunomodulatory therapy (IMT) is often introduced early. These immunosuppressive drugs dampen the immune system’s activity. Commonly used agents include methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil. Newer biologic agents, such as adalimumab and infliximab, which target specific inflammatory pathways, have also shown promise in refractory cases. The choice of agent and treatment duration are tailored to the patient’s response and disease severity.