PanOph

Vogt-Koyanagi-Harada Disease

UveaTetradHigh YieldAlso: VKH Disease, VKH Syndrome

Key Points

  • •VKH is a T-cell mediated autoimmune attack against melanocytes — affecting the uvea, skin, hair, inner ear, and meninges.
  • •The four clinical phases are: prodromal (flu-like, headache), acute uveitic (bilateral exudative RD), convalescent (depigmentation: sunset glow, poliosis, vitiligo), and chronic recurrent (granulomatous anterior uveitis).
  • •Early aggressive immunosuppression with SLOW steroid taper (minimum 6 months) is critical — premature taper is the most common cause of recurrence.
  • •ICGA (dark dots) is the most sensitive imaging modality for choroidal involvement; EDI-OCT for monitoring choroidal thickness.

Hallmark Features(Tetrad)

1

Bilateral granulomatous panuveitis

2

Poliosis and vitiligo

3

Sensorineural hearing loss

4

Meningeal signs (headache, CSF pleocytosis)

Finder Clues

Bilateral granulomatous panuveitisPoliosis (whitening of eyelashes/eyebrows/hair)VitiligoSensorineural hearing lossHeadache and meningismusExudative retinal detachmentSunset glow fundusDisc edema/hyperemiaAlopeciaTinnitus
1. Definition

Bilateral granulomatous panuveitis with exudative retinal detachments, associated with integumentary (skin/hair) and neurological manifestations. T-cell mediated autoimmune response against melanocyte antigens.

2. Genetics

Strong HLA association: HLA-DRB1*0405 is the most strongly associated allele. More common in pigmented races (Asian, Hispanic, Middle Eastern, Native American, Indian subcontinent). No Mendelian inheritance pattern — polygenic susceptibility with environmental triggers.

3. Pathogenesis

Immune mechanism:

  • T-cell mediated autoimmune response targeting melanocyte antigens (tyrosinase, TRP-1, TRP-2, gp100)
  • CD4+ T helper cells (Th1-mediated) attack melanocytes, causing granulomatous inflammation
  • A viral trigger has been hypothesized but not confirmed

Target tissues:

  • Uvea — primary ocular target due to its high melanocyte density
  • Skin and hair — poliosis, vitiligo, alopecia
  • Inner ear — sensorineural hearing loss
  • Meninges — headache, CSF pleocytosis

Ocular pathology:

  • Diffuse choroidal thickening leading to exudative retinal detachment

Four-stage clinical course:

  1. Prodromal
  2. Acute uveitic
  3. Convalescent
  4. Chronic recurrent
4. Clinical Features

Phase 1 — Prodromal (days):

  • Flu-like symptoms, headache, meningismus, fever
  • Orbital pain, tinnitus, dysacusis
  • CSF shows lymphocytic pleocytosis

Phase 2 — Acute uveitic (weeks):

  • Bilateral posterior uveitis with multifocal exudative retinal detachments
  • Disc hyperemia/edema, choroidal thickening
  • Anterior segment: granulomatous KPs (mutton-fat), anterior chamber cells, iris nodules (Koeppe and Busacca)
  • Dalen-Fuchs nodules may begin forming (sub-RPE granulomas)

Phase 3 — Convalescent (weeks-months):

  • Depigmentation phase:
  • Sunset glow fundus — orange-red depigmented fundus
  • Sugiura sign — perilimbal vitiligo (earliest depigmentation sign)
  • Dalen-Fuchs nodules — sub-RPE granulomas (between RPE and Bruch's membrane), more prominent in this phase
  • Poliosis, vitiligo, alopecia

Phase 4 — Chronic recurrent:

  • Recurrent anterior granulomatous uveitis
  • Complications: cataract, glaucoma, subretinal fibrosis, choroidal neovascularization
5. Ocular Manifestations

Acute phase:

  • Bilateral diffuse choroiditis with multifocal serous/exudative retinal detachments (bullous)
  • Disc edema/hyperemia, vitritis

Imaging findings:

  • FA — pinpoint hyperfluorescent spots at RPE level with pooling in subretinal space
  • ICGA — dark dots (choroidal granulomas) — most sensitive imaging modality
  • OCT — subretinal fluid with septae, choroidal thickening

Anterior segment:

  • Granulomatous KPs (mutton-fat)
  • Anterior chamber cells and flare
  • Iris nodules, posterior synechiae

Convalescent phase:

  • Sunset glow fundus
  • Dalen-Fuchs nodules
  • Peripapillary atrophy, nummular chorioretinal scars

Complications:

  • Cataract (42%)
  • Glaucoma (27%)
  • Subretinal fibrosis
  • CNVM
  • Phthisis in severe untreated cases
6. Systemic Manifestations

Neurological/auditory:

  • Headache, meningismus
  • CSF lymphocytic pleocytosis — 80%
  • Sensorineural hearing loss — 75%
  • Tinnitus, vertigo
  • Cranial nerve palsies (rare)

Integumentary (convalescent/chronic phase):

  • Poliosis — whitening of eyelashes, eyebrows, scalp hair
  • Vitiligo — patchy skin depigmentation
  • Alopecia
  • Sugiura sign — perilimbal depigmentation, earliest integumentary sign, typically appearing approximately 1 month after the uveitic stage

These integumentary changes may be transient and can recover with treatment.

7. Diagnosis

Revised Diagnostic Criteria (RDC, 2001):

Complete VKH requires all of:

  1. No history of penetrating ocular trauma/surgery
  2. Bilateral ocular involvement
  3. Neurological/auditory findings
  4. Integumentary findings

Incomplete VKH:

  • Ocular + either neurological/auditory OR integumentary

Probable VKH (ocular only):

  • Bilateral ocular findings without extraocular manifestations

Investigations:

  • FA — pinpoint hyperfluorescent leaks with subretinal dye pooling
  • ICGA — dark dots (choroidal granulomas) — most sensitive test
  • EDI-OCT — choroidal thickening, subretinal fluid with septae
  • Ultrasound B-scan — diffuse choroidal thickening, exudative RD
  • Lumbar puncture — CSF lymphocytic pleocytosis (prodromal/acute phase)
  • Audiometry — sensorineural hearing loss
8. Differential Diagnosis

Key differentials:

  • Sympathetic ophthalmia — requires history of penetrating ocular trauma/surgery (key differentiator)
  • Posterior scleritis — unilateral, T-sign on ultrasound
  • Central serous chorioretinopathy — unilateral, no inflammation
  • Sarcoidosis — less choroidal involvement, hilar lymphadenopathy
  • Primary intraocular lymphoma — vitreous cells, sub-RPE deposits
  • APMPPE — young patients, self-limited
  • Uveal effusion syndrome
  • Tuberculosis — granulomatous uveitis but typically unilateral or asymmetric
9. Management

Early aggressive immunosuppression is the cornerstone.

Acute phase:

  • IV methylprednisolone pulse — 1 g/day x 3 days
  • Followed by oral prednisolone 1-1.5 mg/kg/day
  • Slow taper over a minimum of 6 months (many experts recommend 9+ months) — premature taper is the most common cause of recurrence

Steroid-sparing immunosuppressive therapy (IMT):

  • Indicated for: steroid-dependent disease, recurrence during taper, steroid intolerance
  • Options:
  • Mycophenolate mofetil
  • Azathioprine
  • Cyclosporine
  • Methotrexate
  • Biologics (adalimumab, infliximab) for refractory cases
  • Some experts now advocate first-line IMT with steroids to reduce recurrence rates

Anterior uveitis:

  • Topical steroids and cycloplegics

Complication management:

  • Cataract surgery — during quiescent phase
  • Glaucoma medications/surgery as needed
  • Anti-VEGF for CNVM
10. Prognosis

Good outcomes with early treatment:

  • >60% achieve 20/40 or better with steroid monotherapy; early combination with IMT yields superior outcomes

Poor prognostic factors:

  • Delayed treatment (>2 weeks from onset)
  • Inadequate initial steroid dosing
  • Premature steroid taper
  • Chronic recurrent disease
  • Development of complications (subretinal fibrosis, CNVM, glaucoma)

Other considerations:

  • Sunset glow fundus develops in ~50-80% and indicates chronic subclinical choroidal inflammation
  • Recurrence rate 40-70% with inadequate treatment duration
  • Early IMT initiation may reduce recurrence
  • Integumentary and auditory manifestations are often partially or fully reversible with treatment

Clinical Pearls

1

Sugiura sign (perilimbal vitiligo) is the earliest depigmentation sign and is particularly common in Japanese patients — look for it at approximately 1 month after uveitic onset.

2

Sunset glow fundus on examination indicates chronic subclinical choroidal inflammation and is NOT a sign of disease inactivity — these patients need ongoing monitoring and possible IMT.

3

VKH can be confused with sympathetic ophthalmia — the key differentiator is the absence of prior penetrating ocular trauma/surgery in VKH.

Mnemonics

VKH Tetrad

U—Uveitis (bilateral granulomatous panuveitis)

S—Skin (poliosis, vitiligo, alopecia)

E—Ear (sensorineural hearing loss, tinnitus)

M—Meninges (headache, CSF pleocytosis)

Four organ system involvement in VKH disease

VKH Four Phases

P—Prodromal (flu-like, headache)

A—Acute uveitic (exudative RD, disc edema)

C—Convalescent (sunset glow, poliosis, vitiligo)

R—Recurrent (chronic anterior uveitis, complications)

Sequential clinical stages of VKH

References

  1. textbookKanski's Clinical Ophthalmology: A Systematic Approach— Elsevier (2020)
  2. paperRevised Diagnostic Criteria for Vogt-Koyanagi-Harada Disease: Report of an International Committee on Nomenclature— American Journal of Ophthalmology (2001)
  3. paperVogt-Koyanagi-Harada Disease: Review of a Rare Autoimmune Disease Targeting Antigens of Melanocytes— Orphanet Journal of Rare Diseases (2016)
  4. textbookUveitis: Fundamentals and Clinical Practice— Elsevier (2010)
Was this helpful?
← PreviousTakayasu Arteritis