UVEODERMATOLOGIC SYNDROME (VKH-LIKE SYNDROME)

What is UV or VKH-Like Syndrome?

VKH In Humans

In 1906, Vogt described a complex of symptoms associated together, as did Koyanangi in 1929.  They had inflammation of the front of the uvea (the middle layer of the eye with the richest blood supply, includes the iris, aqueous  humor, and choroid); loss of pigment in the skin (vitiligo); hair whitening(poliosis), not only on the head, but eyelashes and brows as well; hair loss (alopecia), and hearing problems.  In 1926, Harada had described patients with inflammation of the back of the uvea, retinal detachment, and cerebrospinal involvement.

Because subsequent reports showed so many patients with overlapping symptoms, medical professionals recognized them as part of one complex, referred to as Vogt-Koyanangi-Harada Disease or VKH. It is most commonly found in Asians and Native Americans, between the ages of 20-50 . The highest reported incidence is in  Japan where it displayed an equal gender distributions.  However, VKH does occur world-wide, and some studies show more women affected than men outside Japan. 

The disease usually progress in stages, first with what is called the prodromal stage which mimics a viral infection with fever,  headache, nausea, vertigo, and sore eyes.  A few days later, the acute uveitic phase begins, and the eye becomes inflamed. 

At first this may be just one, but eventually both eyes are involved, and symptoms progress until the inflammation resolves. 

During the convalescent phase , depigmentation begins.  This may involve the retina, skin, and/or hair.  The progression may be interrupted by the chronic recurrent stage , during which the uveitis returns.  Nodules may form in the iris and complications such as cataracts and glaucoma may also arise.

VKH-Like Syndrome in Dogs

Dogs display a series of symptoms similar to VKH in humans but because the two don't completely correspond, the complex in dogs is referred to as VKH-like or UV (uveodermatologic syndrome). Since they are not established as equivalent, here we will refer to the human disease complex as VKH and the dog one as UV.  The ear and hearing problems common in humans aren't demonstrated in dogs, and males are more likely to be affected.

On the other hand, color loss in the skin (vitiligo) is almost always present, and loss of color in the coat (poliosis) is frequent. Mostly commonly this begins around and under the nose and eyes, as can be seen with the dog pictured here.  It is much easier to see in a dog with dark coloring.  UV and VKH are characterized by the presence of eye and skin problems together.  However, uveitisis usually the first symptom.  It's important to note though that while uveitis is always present in VKH-like complex, uveitis alone does not mean the dog has VKH.

Uveitis is quite common in dogs and can be due to a number of causes.  It can be a complication of a number of tick-bourne diseases (ehrlichiosis, Rocky Mountain Spotted Fever, and Lyme's) as well as brucellosis.  Injuries or trauma, bacterial infections, parasites, and cancer can cause uveitis. It can even be a complication of cataracts or certain surgeries.

Regardless, any kind of eye problem should prompt an immediate visit to a veterinarian.  Untreated uveitis can result in glaucoma, scarring of the components of the eye, and even blindness.

In a study that followed 102 dogs diagnosed with uveitis that was not caused by injury or cataracts, almost a quarter of the dogs had some form of tumor of they eye or systemic tumors, mostly lymphosarcoma, and 17% had clear evidence of an infectious cause, mostly ehrlichia.  This study underscores the importance of an examination and diagnosis before treatment because a significant number of these dogs had some kind of systemic disease.

Massa's study classified about 60% of the uveitis cases as having an unknown cause, which is consistent with reports from practicing veterinary specialists. Just as with VKH in the entire human population, UV is quite uncommon in dogs, and like its human counterpart, it has a definite predilection for certain breeds.  Akitas account for the bulk of the reported cases, but it does occur in their cousin breeds, the Siberian Husky, Alaskan Malamute, and Samoyed . When uveitis shows up in these breeds, especially Akitas, the dog should be watched closely for other VKH symptoms.

Causes

As with many complex diseases, the exact cause of VKH in humans and UV in dogs is unknown.  Studies of the Major Histocompatibility Complex (MHC I and MHC II) are ongoing and could shed light on not only VKH but other autoimmune diseases.  MHC is a chromosomal segment that codes for the body's immune system to recognize body tissue as either foreign or self. This is also referred to as the HLA complex (or human leukocyte antigen, DLA in dogs for Canine leukocyte antigen).

In common with VKH and UV, the body's antibodies attack melanin-containing cells, shared by the skin, hair, eye, meninges, and ear; whereas, in the dog, the meninges and ear may not be involved because they don't have the same composition. Something happens that causes the melanocytes of the eye and skin begin to express an antigen that the immune system brands as foreign.  A recently published study done at UC Davis, details the DLAs (dog leukocyte antigen) found in dogs affected with UV vs dogs in the control group which were not affected by UV.  Another study shedding light on the immune mechanisms in UV found a difference in the types of lymphocytes involved in the autoimmune response. Using immunohistochemical analysis, they examined cells from the eye and from the skin and found that the former involved mostly B-cell lymphocytes; whereas, the latter involved mostly T-cell lymphocytes.  Hopefully this study will spark further investigation.  (Carter, Wallace J., et al. " An immunohistochemical study of uveodermatologic syndrome in two Japanese Akita dogs "

A tendency to occur in families and the association with isolated populations indicates some genetic component to VKH and UV.  Some researchers feel a genetic predisposition is triggered by some sort of infection.  At least one experiment has induced VKH-like symptoms in Akitas by injection of a tyrosinase-related protein, although whether these are identical to VKH in humans isn't clear. 

Treatment and Prognosis

Some features of UV occur with other autoimmune diseases, so the definitive diagnosis is through skin biopsy sent to a dermopathologist.  Since the eye problems are usually the first symptom, and because they pose such a serious risk to the dog's vision, treatment concentrates on treating it.

Uveitis can be treated with anti-inflammatory drugs such as aspirin and corticosteroids as well as ones for ophthalmic and arthritis pain such as indomethacin or profenal.  How and whether corticosteroids are administered depends on the location of the inflammation in the eye and also on whether any ulcerative damage has occurred.  Corticosteroids are contraindicated if any lesions are present in the eye. Medication that causes dilation of the pupil can be used, but not if glaucoma has developed.  This helps relieve pain.

Oral corticosteroids are used to control the other symptoms, but because of the serious side effects associated with large doses, it may be augmented with azathioprine.  Because the effects of this drug take longer to appear, higher doses of the steroids are necessary initially.  Cyclosporin may also be used.

The prognosis for UV dogs is not good in the long run because the disease is chronic and the side effects of the drugs necessary to control pose their own threats to the dog's long-term health.  Careful monitoring is essential and owners must work very carefully with their veterinarian to coordinate treatment.

VKH Syndroom Nederlandse vertaling