Vogt-Koyanagi-Harada syndrome

Source: KANSKI

VKH syndrome is an idiopathic multisystem autoimmune disease featuring inflammation of melanocyte-containing tissues such as the uvea, ear and meninges.

k/as Uveomeningeal syndrome
 

Pathogenesis

Autoimmune process directed against melanocytes which could be initiated by infectious agent in genetically susceptible individual.

- VKH predominantly affects Hispanics, Japanese and pigmented individuals. 

- In different racial groups the disease is associated with HLA- DR1 and HLA-DR4, suggesting a common immunogenic predisposition. 

(The disease is comparatively more common in Japanese who are usually positive for HLA-DR4 and DW15.) 

Possible trigger factors include cutaneous injury or a viral infection which may lead to sensitization of melanocytes.
It is an idiopathic multisystem disorder which includes cutaneous, neurological and ocular lesions.

- Female are more affected.

- Most present within 2nd to 5th decade.

In practice, VKH can be subdivided into

Vogt-Koyanagi disease, characterized mainly by skin changes and anterior uveitis,
(Skin + Ant uveitis)

Harada disease, in which neurological features and exudative retinal detachments predominate.
(CNS + Exud RD)

1. Cutaneous lesions include: alopecia, poliosis and vitiligo.
2. Neurological lesions are in the form of meningism, encephalopathy
3. Auditory features: tinnitus, vertigo and deafness.
4. Ocular features are bilateral chronic granulomatous anterior uveitis, posterior uveitis: multifocal choroiditis and exudative retinal detachment. 

Phases

1. Prodromal phase lasting a few days is characterized by neurological and auditory manifestations.

• Meningismus causing headache and neck stiffness.
• Encephalopathy is less frequent and may manifest with convulsions, paresis and cranial nerve palsies.
• Auditory features include tinnitus, vertigo and deafness.
• CSF- pleocystosis.

2. Acute uveitic phase follows soon thereafter and

• It is characterized by bilateral granulomatous anterior or multifocal posterior uveitis and exudative retinal detachments.
• Anterior uveitis
  -AC cells
  -KPs- small & large
           -Granulomatous
  -Iris nodules
  -Synechiae
• Posterior uveitis- -Exud RD -Dalen Fuch’s nodules
  -Sunset glow fundus (depigmented fundus)
  -NV
  -Vitritis
  -H’age
  -Edema- optic disc & macula

3. Convalescent phase follows after several weeks of acute phase.
It is characterized by depigmentary changes of skin and choroid.

• Localized alopecia, poliosis and vitiligo.
• Focal depigmented fundus lesions (sunset glow fundus) - Choroidal depigmentation
• Appears as orange-red discolouration of the fundus – sunset glow.
• Depigmented limbal lesions (Sugiura sign) 
•  perilimbal vitiligo

4. Chronic-recurrent phase is characterized by smouldering anterior uveitis with exacerbations.
(Smoldering panuveitis with frequent exacerbation of acute granulomatous anterior uveitis including iris nodules seen) 

Ant uveitis is more prominent.

• Mutton Fat KPs
• Koeppe nodules
• Post synechiae
• Gonioscopy-Depigmented CB

                        -NV in ac angle

Posterior uveitis-

• Retinal vasculitis
• Subretinal NV- H’age

Uveitis

Anterior uveitis is usually non-granulomatous during the acute phase: iris nodules and posterior synechiae.

Posterior uveitis occurs in patients with Harada disease and is frequently bilateral.

In chronological order the findings are as follows:

• Diffuse choroidal infiltration and papillitis.
• Multifocal detachments of the sensory retina and disc oedema.
• The chronic phase shows diffuse RPE atrophy (sunset glow fundus) which may be associated with small peripheral atrophic spots.
• (inflammation become multifocal, with multiple area of sub-retinal fluid accumulation and multiple serous detachments - hallmark feature of VKH.) 

Complications: Choroidal neovascular membrane-CNVM and subretinal fibrosis. (cataract, glaucoma)


Modified diagnostic criteria for VKH syndrome

1. No history of penetrating ocular trauma or surgery
2. Absence of other ocular disease entities.
3. Bilateral uveitis – bilateral ocular involvement.
4. Neurological and auditory manifestations
5. Integumentary findings, (not preceding onset of central nervous system or ocular disease), such as alopecia, poliosis and vitiligo

In complete VKH, criteria 1-5 must be present.

In incomplete VKH, criteria 1-3 and either 4 or 5 must be present.

In probable VKH (isolated ocular disease), criteria 1-3 must be present.

Investigations:

· FFA: 

Acute phase shows multifocal numerous punctate hyperfluorescent dots (leakage) at the level of RPE, which gradually enlarge and stain the subretinal fluid. pooling of dye within the subretinal space and optic disc staining in late phase.

Chronic phase shows areas of hyperfluorescence due to RPE window defects without progressive staining.

· Ultrasonography: 

 Diffuse thickening of the posterior choroid and Serous retinal detachment.

· CSF analysis shows pleocytosis (with predominant small lymphocytes) in about 80% of patients within 1 week and 97% within 3 weeks of disease onset and which resolve within 8 weeks.

· lCGA during the acute phase of the disease shows regularly-distributed hypofluorescent spots, most of which remain hypofluorescent during the late phase of the angiogram although a few may become isofluorescent. The late phase also shows diffuse hyperfluorescence over the posterior pole. Eyes with retinal detachment show hyperfluorescent areas as seen on FA. ICGA is useful in monitoring the evolution of the choroidal inflammation and the effect of therapy.

Treatment

Corticosteroids

• Systemic steroids are the mainstay of treatment.
• It administered topically, periocularly and systemically ( in high dose)
• high-dose oral prednisolone (60-100 mg/day) that may be augmented with 3-day intravenous pulse therapy with methylprednisolone (500-1000 mg/day).
• Early aggressive use of oral steroid ( 1-2 mg/kg) followed by slow tapering over next 3-6 months may reduce incidence of chronic disease.

Immunosuppressive drugs

• Methotrexate, azathioprine, and cyclosporine should considered for recurrent and resistant cases.
• Steroid-resistant patients may require ciclosporin.
• Azathioprine 1-3 mg/kg/day
• Cyclophosphamide 1-3 mg/kg/day
• Cyclosporine 2.5 mg/kg/day

-Prognosis depends on early recognition and aggressive control of the early stages of the disease.
-Late diagnosis or incorrect initial therapy is more likely to be associated with a guarded prognosis.
(with only 50% of patients having a final visual acuity better than 6/12.)

Differential diagnosis of bilateral exudative retinal detachments

• Carcinoma metastatic to the choroid.
• Uveal effusion syndrome.
• Posterior scleritis.
• Eclampsia.
• Central serous retinopathy.
• Age-related wet macular degeneration.