Vogt–Koyanagi–Harada disease

A. Sandhya -

Vogt–Koyanagi–Harada disease is a rare multisystem autoimmune inflammatory disease that affects melanocyte-rich pigmented structures, such as eye, inner ear, meninges, skin and hair.
Autoimmune disorders are caused when the cells (antibodies, lymphocytes, etc.) involved in the body's natural defense system fighting against invading organisms, suddenly begin to attack the body's healthy tissue.
Vogt–Koyanagi–Harada disease is also an autoimmune disorder caused due to an abnormal immune response of the immune system, in which the body attacks its own pigment cells (melanocytes) in the eye, ear, meninges, and skin.
VKH disease is noninfectious uveitis (Uveitis is inflammation of the uvea, the middle layer of the eye between the retina and the sclera (white of the eye)) affecting, more frequently, individuals of pigmented skin, such as Asians, Middle Easterners, Hispanics and Native Americans. It is very infrequent among persons of African descent
Generally, adult and middle-aged patients aged 20–50, are affected. It has also been reported in childhood or old age and the female to male ratio is 2:1 i.e. twice as many females affected as males.

Its main features are loss of vision and hearing, ringing in the ears, vertigo, weakness on one side of the body, confusion, abdominal pain, malaise and severe bilateral granulomatous panuveitis (inflammation throughout the uveal tract in the eye).
Initially, Vogt–Koyanagi–Harada disease was described as an uveomeningoencephalitic syndrome,
VKH syndrome, is named after one German and two Japanese researchers who published independently early in the 20th century,

Etiology

  • The exact cause of VKH disease is unknown, but the symptoms are thought to be due to an abnormal response of the immune system to the body's own cells.
  • The disease may be caused due to an autoimmune aggression against antigens associated with melanocytes in a genetically susceptible individual after a virus infection trigger
  • Genetic factors are also involved and it may be caused due to genetic predisposition. A person may carry a gene for the disease but it may not be expressed unless something in the environment triggers the disease.
  • The disease may be an immune response to the human leukocyte antigen (HLA).
  • The genetic defect may also cause persons who carry this antigen to develop Vogt-Koyanagi-Harada disease.

Symptoms

It is a multisystem disease that is a combination of ophthalmological, neurological, and dermatological signs and symptoms.
Ophthalmological symptoms-- very deep pain in the eyes, blurred vision, panuveitis, cataract, glaucoma, floaters
Neurological symptoms-- tinnitus, neck stiffness, cranial nerve or central nervous system symptoms or cerebrospinal fluid pleocytosis,  headache,
Dermatological symptoms-- vitiligo, alopecia and poliosis of the lashes, eyebrows and scalp hair

Symptoms will vary from person to person and these symptoms may appear in 4 phases:
Early phase, uveitis phase, convalescent phase, and recurrent phase

Early or prodromal phase symptoms may include

  • headache
  • confusion
  • dizziness (vertigo)
  • very deep pain in the eyes,
  • photophobia
  • fever
  • malaise
  • neck stiffness
  • nausea and vomiting
  • hearing loss
  • ringing in the ears (tinnitus)
  • scalp and general skin sensitivity

Uveitis phase
It occurs a few weeks after the early phase and the symptoms may include:

  • blurred vision in one or both eyes
  • inflammation of the eyes (panuveitis)
  • floating spots in the vision (floaters) that are signs of retinal detachment
  • development of small yellow nodules in parts of the retina

Convalescent phase -- usually occurs a few weeks to months after the uveitis phase.
In this phase, symptoms may include:

  • patches of white skin (vitiligo)
  • patches of white hair, eyelashes, and eyebrows (poliosis)
  • hair loss (alopecia)

Recurrent or chronic phase occurs in about half of the people with VKH disease. Symptoms may include:

  • Clouding of the lens (cataracts)
  • Build-up of pressure in the eyes (glaucoma)
  • Abnormal blood vessels growth under the retina (choroidal neovascularization)
  • Most people with VKH disease develop symptoms in both eyes.

On the basis of the symptoms, the disease is categorized into three types: Complete, Incomplete, and Probable
a. Complete VKH disease: The complete form of the disease includes neurologic symptoms such as ringing in the ears (tinnitus), neck stiffness, and/or cells in the cerebrospinal fluid (pleocytosis) as well as dermatological symptoms 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), and diffuse choroiditis in both eyes that may lead to serous retinal detachments. Inflammation of the iris and ciliary body may develop in some patients.

b. Incomplete VKH disease: similar eye disease as patients with complete VKH disease and patients may have either the neurologic manifestations or dermatological symptoms.

c. Probable VKH disease: similar eye disease as patients with complete VKH disease but without neurologic and dermatological symptoms.

Diagnosis

Diagnosis of VKH disease is based on the symptoms, clinical exam, eye exam and imaging studies. It is easy to diagnose and can be treated effectively in most cases.
The disease can be diagnosed with the latest imaging techniques like,
Fluorescein angiography (FA) -- can help differentiate VKHD from other conditions.
Indocyanine green choroidal angiography -- (ICGA) helps the study of choroidal vasculature and the understanding of the pathophysiology of chorioretinal inflammatory disorders.
Optical coherence tomography (OCT) -- helps to know unique features of multifocal serous retinal detachment in acute VKHD with cystic spaces and membranous structures continuous to the ellipsoid zone (internal and external segments junction of the photoreceptors).
Optical coherence tomography angiography (OCTA) -- is a non-invasive, new technique that allows visualization of retinal and choroidal blood flow, and it has many potential applications in understanding the pathophysiology behind retinal and choroidal disease.
Enhanced depth imaging–OCT (EDI-OCT): EDI-OCT is a non-invasive and quantitative method and can be used to assess the degree of choroidal inflammatory reactions.
Ocular ultrasonography (US) -- High-definition ocular US may help knowing choroidal thickening in subclinical VKHD and may also aid in monitoring response to treatment, most notably in the presence of media opacities
Electroretinogram (ERG) -- can be helpful in monitoring disease course as well as in demonstrating the degree of functional compromise due to the inflammatory damage to retinal components
Ultrasonography and lumbar puncture -- for CSF analysis, and Lumbar puncture is useful in confirming the diagnosis of VKHD in the acute stage only.
Audiological testing is recommended for auditory symptoms.
FA and ICGA are the primary diagnostic modalities and OCT, OCT-A, and EDI-OCT are useful in distinguishing this condition from other uveitides in a non-invasive manner.
Ultrasonography can be used to detect the choroidal thickening and serves as an alternative in the examination where the EDI-OCT is not available, although it is less precise.

Treatment

VKH disease is treated with Oral corticosteroid therapy that involves early and aggressive treatment with systemic corticosteroids (steroids) to stop the inflammation quickly.

High-dose systemic steroid drugs are used initially and often followed by immunosuppressive therapy in which Immunosuppressive drugs are used.

Biological response modifiers (BRMs) are effective in the management of uveitis refractory to treatment with conventional immunosuppression. The main benefit of biologic response modifiers may be their faster onset of action.

Understanding treatment response may help better understand the pathophysiology of this disease.
Early recognition and treatment can prevent progression to chronic convalescent and chronic recurrent stages of the disease

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