1 1© 2008 universitair ziekenhuis gent 1 vogt-koyanagi-harada syndrome prof. dr. ph. kestelyn

11© 2008 Universitair Ziekenhuis Gent© 2008 Universitair Ziekenhuis Gent 1

Vogt-Koyanagi-Harada Syndrome

Prof. dr. Ph. Kestelyn

22© 2008 Universitair Ziekenhuis Gent

• Multisystem disease

• Chronic, bilateral, granulomatous panuveitis associated with central nervous system, auditory and integumentary manifestations

VKH Disease

Moorthy et al: Surv Ophthalmol 1995; 39:265 (review)Read et al: Am J Ophthalmol 2001;131:647


VKH (Vogt-Koyanagi-Harada Syndrome)

• Systemic disorder eyes/ears meninges skin


VKH (Vogt-Koyanagi-Harada Syndrome)

• First description: 12th century Mohammad-al-Ghafiqi • Vogt: 1906 one case• Koyanagi: 1923 six cases• Harada: 1926 posterior uveitis and pleocytosis of CSF

Vogt-Koyanagi-Harada or VKH


VKH (Vogt-Koyanagi-Harada Syndrome)Epidemiology

• more prevalent in darker skinned ethnic groups• common

in Japan in people from Mediterranean origin in American Indians/Africans in Indians

• 2nd to 4th decade• approx. 15% < 16 in Turkey and Saudi Arabia

• more prevalent in darker skinned ethnic groups• common

in Japan in people from Mediterranean origin in American Indians/Africans in Indians

• 2nd to 4th decade• approx. 15% < 16 in Turkey and Saudi Arabia


4 phases• prodromal• acute uveitic• convalescent or chronic• chronic recurrent

VKH (Vogt-Koyanagi-Harada Syndrome)Clinical course


VKH (Vogt-Koyanagi-Harada Syndrome)Systemic Findings

• Prodromal stage headache, orbital pain neck stiffness neurologic symptoms

lumbar puncture: pleocytosis in 80% (lymphocytes ↑, monocytes ↑, normal glucose)


VKH (Vogt-Koyanagi-Harada Syndrome)Auditory Findings

• concurrent with ocular findings• hearing loss for higher frequencies• dysacousia• tinnitus• objective signs > subjective symptoms

• audiology


VKH (Vogt-Koyanagi-Harada Syndrome)Skin lesions

• sensitivity to touch of hair and skin (active phase)• vitiligo/poliosis (convalescent phase)• alopecia• seen in ¾ of patients


VKH (Vogt-Koyanagi-Harada Syndrome)Ocular Findings

• bilateral disease• granulomatous panuveitis• AS involvement

often nongranulomatous in acute phase iris nodules and mutton fat KP’s in chronic or recurrent

disease

• shallowing of the AC + IOP ↑ inflammatory swelling of ciliary body pupillary block

surgical iridectomy mandatory formation of AS chronic glaucoma


VKH (Vogt-Koyanagi-Harada Syndrome)Ocular Findings

• perilimbal vitiligo (Sugiura’s sign) • poliosis ( loss of lashes and regrowth of depigmented white

lashes)


VKH (Vogt-Koyanagi-Harada Syndrome)Ocular Findings (posterior)

Acute phase

• swelling of the optic nerve• important vitreous reaction• exsudative retinal detachment• yellow-white retinal lesions in the

periphery (Dalen-Fuchs nodules?)


Case report

female, 22 years old

Ethiopian (in Belgium since 20 months)

bilateral loss VA (RE 1 month, LE 1 week), photophobia, orbital pain

general history : unremarkable

ocular history : unremarkable

no medication


Ophthalmological examination

VA: OD: CF 2m, no Parinaud 10

OS: CF 3m, no Parinaud 10

SLE: OD: flare, cells +(+), fine precipitates

OS: flare, cells +

IOP: OU: 14 mmHg


Fundoscopy:


VKH (Vogt-Koyanagi-Harada Syndrome)Ocular Findings (posterior)

convalescent or chronic phase

• neovascularisation of retina/optic nerve recurrent vitreous hemorrhages

• often intraretinal NV of the macula• reactive proliferation of the RPE:

scars, RPE clumping


VKH (Vogt-Koyanagi-Harada Syndrome)Ocular Findings (late)

• “sunset glow” fundus = depigmentation of the posterior pole (RPE + choroid)



• Subretinal / fibrosis / RPE alterations / disciform scars



• subretinal/fibrosis/disciform scars/RPE alterations


VKH (Vogt-Koyanagi-Harada Syndrome)Natural history

• isolated posterior disease (Harada)• isolated ocular forms (probable VKH)• clinical course

severe ocular inflammation depigmentation quiescence

anterior + posterior inflammation depigmentation recurrent anterior disease

chronic ongoing inflammation


VKHDiagnosis

• clinical findings• FA/ICG• ultrasound• lumbar puncture


VKH (Vogt-Koyanagi-Harada Syndrome)FA in VKH

Acute phase:

• numerous punctate hyperfluorescent dots RPE level• staining of subretinal fluid• optic nerve leakage

Convalescent phase:

• window defects, CNV, subretinal fibrosis


Fluo-angiography:


VKH (Vogt-Koyanagi-Harada Syndrome)ICG findings in VKH

• early choroidal stromal vessel hyperfluorescence• hypofluorescent dark dots• fuzzy vessels (vasculitis) • disc hyperfluorescence


Ultrasound:

thickening of the posterior choroid

serous retinal detachment

no T- sign


VKH (Vogt-Koyanagi-Harada Syndrome)Pathogenesis

• antigen driven immune response• antigen = human melanocyte?• T-cell mediated specific killing against P-36 melanoma cell

line (Maezawa et al)• sequence of tyrosinase family proteins induces proliferation

of lymphocyte in VKH patients• injection of tyrosinase + gp 100 injection in Lewis rats

produces animal model of VKH(Sugita et al)• identification of several T-cell lines against tyrosinase and

tyrosinase related protein (Gocho et al)


VKH (Vogt-Koyanagi-Harada Syndrome)Pathogenesis

• certain racial groups.

• immunogenetic predisposition.

• strong association with HLA-DR4 and HLA-DRw53 with the most significant risk allele being HLA-DRB1*0405.

• causative pathogenic antigen binds with HLA-DRB1*0405 molecule which presents the antigen to T cells to activate them.

Fang and Wang: Curr Eye Res 2008;33:517 (review).Read et al: Curr Opin Ophthalmol 2000;11:437 (review).Yamaki et al: Int Ophthalmol Clin 2002;42:13 (review).


VKH (Vogt-Koyanagi-Harada Syndrome)Pathology

• granulomatous panuveitis.

• lymphocytes, epitheloid cells, few plasma cells, multinucleated giant cells.

• epitheloid cells and giant cells contain melanin pigment.


VKH (Vogt-Koyanagi-Harada Syndrome)Treatment

• systemic corticosteroids intravenous pulse therapy oral treatment (2 mg/kg/day)

• no difference pulse ↔ high dose oral (Read et al)• better little outcome high dose steroids > low dose

(Miyanaga et al)• duration ~ inflammatory activity• slow taper over 1 year period

• topical treatment for anterior uveitis


VKH (Vogt-Koyanagi-Harada Syndrome)Treatment

• slow taper over 1 year period or ~ inflammatory activity• consider adding cyclosporine to reduce side effects of high

dose steroids• mofetil mycofenolate ? • adalimumab (Humira)?


VKH Prognosis• visual prognosis is generally favorable.

• 87.5% achieved V.A. of ≥20/40.

• high-dose systemic corticosteroids for >9 months with slow tapering significantly improves the prognosis and decreases risk of recurrence.

• age older than 18 years is significantly associated with the development of complications.

• visual prognosis is generally favorable in children.

Al-Kharashi, Abu El-Asrar: Int Ophthalmol 2007;27:201Abu El-Asrar et al: Eye 2008;22:1124


Thank you !

1 1© 2008 universitair ziekenhuis gent 1 vogt-koyanagi-harada syndrome prof. dr. ph. kestelyn

Documents

vkh slide

harada syndrome epidemiology

case koyanagi

cases harada

ghafiqi vogt

kestelyn slide

chronic glaucoma slide

saudi arabia slide