VKH (Vogt-Koyanagi-Harada Syndrome)

Transcript VKH (Vogt-Koyanagi-Harada Syndrome)

Vogt-Koyanagi-Harada Syndrome

Prof. dr. Ph. Kestelyn

VKH Disease

•

Multisystem disease

•

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

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

 

VKH (Vogt-Koyanagi-Harada Syndrome)

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

• • • •

VKH (Vogt-Koyanagi-Harada Syndrome) Epidemiology

• • • • 2 nd to 4 th

VKH (Vogt-Koyanagi-Harada Syndrome) Clinical course

• • • •

4 phases

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



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 © 2008 Universitair Ziekenhuis Gent 13

Ophthalmological examination

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)

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

• Subretinal / fibrosis / RPE alterations / disciform scars

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

• 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



• • • • 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

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;27:201 Abu El-Asrar et al: Eye 2008;22:1124

VKH (Vogt-Koyanagi-Harada Syndrome)

Transcript VKH (Vogt-Koyanagi-Harada Syndrome)

Vogt-Koyanagi-Harada Syndrome

Prof. dr. Ph. Kestelyn

VKH Disease

VKH (Vogt-Koyanagi-Harada Syndrome)

VKH (Vogt-Koyanagi-Harada Syndrome)

4 phases

Case report

Ophthalmological examination

Fundoscopy:

Fluo-angiography:

VKH (Vogt-Koyanagi-Harada Syndrome) Pathogenesis

VKH (Vogt-Koyanagi-Harada Syndrome) Pathology

VKH Prognosis

Thank you !

Directory