Vogt-Koyanagi-Harada (VKH) syndrome is a rare autoimmune disease that affects melanin-containing tissues like the eyes, inner ears, skin, and brain. It is characterized by bilateral uveitis and can cause vision loss. The disease occurs in phases including prodromal, acute uveitic, convalescent, and recurrent. Treatment involves high-dose corticosteroids for at least 6 months to reduce inflammation and recurrence risk. Immunosuppressants may be needed for resistant cases. Prognosis depends on factors like early treatment, treatment duration, and presence of complications. Strict monitoring is needed due to risk of vision threatening complications.

1. Vogt-Koyanagi-Harada
(VKH)
Marwa Abo Elmaaty Besar
Lecturer Of Internal Medicine
(Rheumatology Immunology Unit)
(Pediatric Rheumatology)

2. Definition:-
• Vogt-Koyanagi-Harada (VKH) syndrome or uveo-encephalitis.
• Is a rare systemic disease of melanocyte containing organs (the eye,
inner ear, meninges, skin and hair).
• Is an uncommon systemic syndrome characterized by intraocular
inflammation, associated cutaneous, auditory and neurological
abnormalities.
Herbort CP,etal 2007
Rao NA,etal2010

3. History:
• In 1906, Alfred Vogt in Switzerland first described “a patient with
premature whitening of eyelashes of sudden onset and bilateral subacute
iridocyclitis”
• Harada (1926) reported a case series with bilateral serous retinal
detachment in association with cerebrospinal fluid (CSF) pleocytosis.
• (1929), Koyanagi published a review article associating unequivocally the
posterior eye involvement with auditory and integumentary
manifestations.
• 1932, Babel suggested these cases represented a single entity, then named
Vogt-Koyanagi-Harada Disease.
• Francisco José Goya y Lucientes (1746–1828) Its main features were loss of
vision and hearing, ringing in the ears, vertigo, weakness on one side of the
body, confusion, abdominal pain and malaise.

4. Epidemiology:
• Diverse populations (e.g. Asian, Arab, Hispanic, and Native
American).
• Female preponderance, female to male ratio of 2:1.2.
• The typical age is 20 - 50 years, However, rarely the disease may
present in children as well.
Expert Rev. 568 Ophthalmol. 7(6), (2012)

5. Pathogenesis:
• The exact aetiology of VKHD is still a matter of enquiry.
• The most accepted mechanism involves an autoimmune aggression
against antigens associated with melanocytes in a genetically
susceptible individual after a virus infection trigger.
• (Epstein-Barr virus)(cytomegalovirus)
• Concerning innate inflammatory cytokines such as IL-6.
• Cellular and humoral autoimmunity against retinal
components;
(CD4+ T lymphocytes) (IL17, IL23, IL21)
Sugita et al.2007

7. Histopathologic aspects
• Vary according to the stage of disease:
• The primary pathological feature of VKHD; diffuse thickening of the
uveal tract (more prominent in the juxta papillary choroid).
• In the acute stage there is a granulomatous process, choroidal infiltrate
• During the convalescent stage, there is a no granulomatous
inflammation, “sunset glow fundus”
• During chronic recurrent stage, a granulomatous choroiditis with
damage of choriocapillaris.

8. Clinical features:-
• The clinical course of VKH is divided into four clinical phases,
• Prodromal phase
• Present with headache, mild fever, photophobia.
• Symptoms and signs of meningoencephalitis (headache, vertigo,
photophobia, tinnitus)
• Lumbar puncture; lymphocytic pleocytosis, proteins and increased
cerebrospinal pressure.
• Lasts for a few days to weeks with variable severity, 50%.
• This patient did not give the history of this phase or did not notice this
phase.
Rao NA,etal2010

9. • The uveitic phase
• Occur 3 to 5 days of prodromal, lasts a number of weeks.
• It is this phase in which most patients come for medical consultation.
• Presented with bilateral red eye and decreased vision-right more than
the left,(70%).
• Ocular signs; bilateral posterior uveitis with retinal edema, papillitis,
serous retinal detachments, iridocyclitis, mutton-fat keratic precipitate
and iris nodules and raised IOP.
• Presented with bilateral posterior uveitis with serous retinal
detachment in the right eye.

10. • The uveitic phase
• Otolaryngology symptoms usually associated ocular symptoms.
• Dysacusis, decreased hearing and vertigo 70%, Tinnitus 45%.
• Immunomediated sensorineural hearing loss, bilateral, asymmetrical
and reversible.
• Testing; neurosensory hearing loss, which responded to the treatment
2-3 months.

11. • The convalescent phase
• 80% of patients.
• This follows the uveitic phase 2-3 months.
• Associated with tissue depigmentation; vitiligo and poliosis,
• Sugiura’s sign (perilimbal vitiligo) is the earliest depigmentation to occur,
presenting itself one month after the uveitic stage.
• From brunette to blonde,
• Exaggerated reddish glow fundus “sunset glow fundus”

12. • The recurrent phase
• 17-73% patients.
• Signs of recurrent uveitis (anterior segment without clinically
detectable posterior involvement)
• Ocular complications (cataract, glaucoma, retinal detachment,
subretinal membranes and fibrosis)

13. Complications:-
• (Da Silva et al.2009) divided VKHD patients in two groups,.
• Early stage: patients who presented with symptoms < 4 weeks.
• Late stage: patients first seen after 4 weeks disease onset, had
more ocular complications and relapses.
• Ocular complications, e.g. cataract, glaucoma and choroidal
neovascularization (CNV)
• Other less common, cystoid macular edema, pseudotumoral RPE
proliferation, band-shaped keratopathy, optic disc atrophy and phthisis
bulbi.

14. Diagnosis
• Mainly clinical.
• No specific lab tests are present….
• OCT findings pre-treatment and 3 months after treatment.
• Fluorescein angiography (FA) findings ;
• Acute uveitic stage
• Help differentiate VKHD from other conditions
• Indocyanine green angiography (ICGA); most useful imaging modality
to monitor response to the treatment.

16. Differential Diagnosis

17. The American Uveitis Society (AUS) in 1978 and the Sugiura’s Criteria In 1976.
Diagnostic criteria:

18. 2001 by the International Nomenclature Committee,
the Revised Diagnostic Criteria (RDC).

19. Management:
• systemic corticosteroids
• The mainstay of treatment,
• High dose systemic corticosteroids, or
• A short course of intravenous methylprednisolone (1000 mg per
day, intravenously, during 3 days),
• Followed by slow tapering throughout a minimum 6-month period.
• Minimum of 6-month systemic and/or immunosuppressive drug
therapy in diminishing recurrence frequency and severity.
• The final treatment duration varies according to the presence of
inflammation.
Errera et al 2011 Lai et al 2009

20. • Immunosuppressive therapy
• Indicated in corticosteroid refractory or intolerant cases.
• Recent literature is pointing out to the deleterious effect on visual function
of chronic relentless choroidal inflammation and a trend to an earlier start
on systemic immunosuppression.
• Antimetabolites , cyclosporine and biological agents as first-line therapy.
• Antimetabolites (methotrexate, azathioprine and mycophenolate mofetil)
• Alkylating agents (cyclophosphamide); resistant and refractory cases.
• The choice on drug availability, cost, and tolerability than on drug-specific
efficacy on VKHD.
• Biological agent; Infliximab and Rituximab
• New biological therapy; Secukinumab and Gevokizumab.
Paredes I etal2006
Niccoli L etal2009

22. • Intravitreal drug therapy
• (triamcinolone, bevacizumab and fluocinolone acetonide)
• A first line treatment for acute VKHD, controversial??? Or
• An adjunct treatment in chronic and/or recurrent stages of the
disease.
• Follow up:
• Follow up: (FA, ICGA, OCT) to assess choroidal inflammation.
• Tend to resolve in 4 months.
Park HS, etal.2011

23. Lavezzo et al. Orphanet Journal of Rare Diseases (2016) 11:29

24. Prognosis;
• A much more serious illness;
> 50 % chronicity and 50 % at least one complication.
• Prognostic factor;
• Related to treatment: Late instauration, Treatment < 6 months,
Treatment suboptimal dose.
• Related to the patient: Younger age, Presence of HLA-DRB1*0405/0410.
• Related to the disease: Poor visual acuity at presentation, Presence of
complications in the initial presentation, Increased number of
recurrences.
Al-Kharashi AS,etal.2007

25. Reference:-
• Sugita S, Takase H, Kawaguchi T, Taguchi C, Mochizuki M. Cross reaction between tyrosinase peptides
and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int
Ophthalmol. 2007;27(2–3):87–95.
• Lai TY, Chan RP, Chan CK, Lam DS. Effects of the duration of initial oral corticosteroid treatment on
the recurrence of inflammation in Vogt- Koyanagi-Harada disease. Eye (Lond). 2009;23(3):543–8.125.
• Paredes I, Ahmed M, Foster CS. Immunomodulatory therapy for Vogt- Koyanagi-Harada patients as
first-line therapy. Ocul Immunol Inflamm. 2006; 14(2):87–90.
• Niccoli L, Nannini C, Cassara E, Gini G, Lenzetti I, Cantini F. Efficacy of infliximab therapy in two
patients with refractory Vogt-Koyanagi-Harada disease. Br J Ophthalmol. 2009;93(11):1553–4.
• Al-Kharashi AS, Aldibhi H, Al-Fraykh H, Kangave D, Abu El-Asrar AM. Prognostic factors in Vogt-
Koyanagi-Harada disease. Int Ophthalmol. 2007; 27(2–3):201–10.
• Park HS, Nam KY, Kim JY. Intravitreal bevacizumab injection for persistent serous retinal detachment
associated with Vogt-Koyanagi-Harada disease. Graefes Arch Clin Exp Ophthalmol. 2011;249(1):133–
6.
• Errera MH, Fardeau C, Cohen D, Navarro A, Gaudric A, Bodaghi B, et al. Effect of the duration of
immunomodulatory therapy on the clinical features of recurrent episodes in Vogt–Koyanagi–Harada
disease. Acta Ophthalmol. 2011;89(4):e357–66.