Vogt-Koyanagi-Harada Disease

Autoimmune MONDO:0018092 Pathograph 32 Show in embeddings browser Autoimmune Disease Ophthalmic Disorder

Vogt-Koyanagi-Harada disease is a multisystem autoimmune inflammatory disease targeting melanin-containing tissues, especially the uvea and choroid, with neurologic, auditory, skin, and hair involvement. Disease expression reflects immune susceptibility and inflammatory triggers, and early systemic immunosuppression is used to prevent chronic recurrent ocular disease.

Ask OpenScientist

Ask a research question about Vogt-Koyanagi-Harada Disease. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

10
Pathophys.
1
Histopath.
12
Phenotypes
1
Gaps
32
Pathograph
3
Genes
4
Medical Actions
3
Differentials
1
Datasets
2
Trials
1
Models
12
References
1
Deep Research
?

Discussions and Knowledge Gaps

1
Do viral infection, vaccination, or molecular mimicry reproducibly initiate melanocyte-antigen-specific T-cell autoimmunity in genetically susceptible people, or are the reported temporal associations coincidental or disease-unmasking events?
KNOWLEDGE GAP OPEN gap_vkh_environmental_trigger_causality
Attached to
pathophysiology#HLA-DRB1-Restricted Melanocyte Antigen Recognition environmental#SARS-CoV-2 infection or vaccination
Patient-derived T cells recognize tyrosinase and gp100, and some clones in one study cross-recognized a cytomegalovirus peptide, but this does not show that infection preceded or caused human disease. COVID-19 infection and vaccination reports are primarily temporal case observations. Prospective exposure ascertainment, population denominators, pre-onset immune samples, and antigen-specific clonotype tracking would be needed to distinguish a causal trigger from background occurrence or immune unmasking.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Efforts to corroborate the latter findings failed so far and the ensemble of such studies cautions that an association does not necessarily represent a cause"
The review explicitly identifies the unresolved distinction between infection association and causation.
⚙

Pathophysiology

10
HLA-DRB1-Restricted Melanocyte Antigen Recognition
In HLA-DR4-positive VKH, ocular and circulating CD4-positive T cells recognize melanocyte-associated tyrosinase and gp100 peptides. This is direct human evidence for antigen-specific adaptive immunity, while the broader initiating trigger remains uncertain.
helper T cell CL:0000912 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves helper T cell (CL:0000912). CL:0000912 is a cell type from the Cell Ontology. melanocyte CL:0000148 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves melanocyte (CL:0000148). CL:0000148 is a cell type from the Cell Ontology.
HLA-DRB1 hgnc:4948 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves HLA-DRB1 (hgnc:4948). hgnc:4948 is a gene from the HUGO Gene Nomenclature Committee.
adaptive immune response GO:0002250 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased adaptive immune response (GO:0002250). GO:0002250 is a biological process from the Gene Ontology. ↑ INCREASED T cell activation GO:0042110 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased T cell activation (GO:0042110). GO:0042110 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Th1 Effector Cytokine Response Recognition of tyrosinase and gp100 by patient CD4-positive T cells elicits a memory Th1 response with IFN-gamma and RANTES production.
Show evidence (1 reference)
PMID:16723469 SUPPORT Human Clinical
"Cells infiltrating the eye and PBMCs in HLA-DR4+ (HLA-DRB1*0405, 0410) patients with VKH contained a population of CD4+ T lymphocytes that recognized tyrosinase and gp100 peptides and produced RANTES and IFN-gamma in response to the two peptides."
Patient-derived ocular and blood T-cell clones directly recognized two melanocyte peptides in an HLA-DR4-positive context.
PRKCD-Associated Immune Susceptibility
PRKCD rs74437127 is associated with VKH susceptibility in a Han Chinese case-control cohort. The study did not establish how the locus changes immune function in VKH, so its connection to the effector pathway remains provisional.
PRKCD hgnc:9399 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves PRKCD (hgnc:9399). hgnc:9399 is a gene from the HUGO Gene Nomenclature Committee.
Downstream
Th1 Effector Cytokine Response PRKCD is placed upstream of the T-cell effector response as a susceptibility locus, but the intervening functional steps were not established in VKH.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10−5, OR = 1.810; Pc = 2.76 × 10−5, OR = 1.698, respectively)."
The 912-case/878-control study supports a susceptibility association, not a monogenic or experimentally proven causal mechanism.
CARD9-Associated Pro-inflammatory Cytokine Amplification
The VKH-associated CARD9 rs3812555 CC genotype correlates with higher CARD9 expression and TNF-alpha production. Functional measurements support a cytokine-amplifying correlate, although they were not made in VKH target tissue.
CARD9 hgnc:16391 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CARD9 (hgnc:16391). hgnc:16391 is a gene from the HUGO Gene Nomenclature Committee.
tumor necrosis factor production GO:0032640 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased tumor necrosis factor production (GO:0032640). GO:0032640 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Granulomatous Choroidal Inflammation CARD9-associated TNF-alpha amplification is a plausible contributor to ocular inflammation, but this edge has not been directly demonstrated in VKH choroid.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10−4; P = 2.00 × 10−3, respectively)."
Genotype-stratified human PBMC assays support increased CARD9 expression and TNF-alpha production, with the target-tissue limitation retained.
Th1 Effector Cytokine Response
Melanocyte-reactive patient CD4-positive T cells have an active-memory Th1 phenotype and produce IFN-gamma and RANTES. These effectors provide a direct human bridge from antigen recognition to tissue-directed inflammation.
helper T cell CL:0000912 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves helper T cell (CL:0000912). CL:0000912 is a cell type from the Cell Ontology.
cytokine production GO:0001816 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cytokine production (GO:0001816). GO:0001816 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Granulomatous Choroidal Inflammation Melanocyte-antigen-specific Th1 cells are positioned upstream of the granulomatous choroiditis that defines acute ocular VKH.
Extraocular Melanocyte-Containing Tissue Involvement The same melanocyte-directed cellular response is expressed in extraocular melanin-containing target organs.
Show evidence (1 reference)
PMID:16723469 SUPPORT Human Clinical
"CONCLUSIONS: In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response."
The patient-derived cellular study directly supports the inflammatory competence of melanocyte-antigen-specific T cells.
Granulomatous Choroidal Inflammation
Acute VKH begins as granulomatous choroiditis with choroidal thickening, optic-disc hyperemia and swelling, and subsequent anterior-segment involvement when inflammation is not adequately controlled.
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology. macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Bilateral Panuveitis Choroidal inflammation rapidly extends into bilateral panuveitis.
Retinal Pigment Epithelium Dysfunction Choroidal inflammation impairs the overlying retinal pigment epithelium.
Persistent Subclinical Choroidal Inflammation Inadequately suppressed acute choroiditis can persist below the threshold of routine posterior-segment clinical examination.
Vision Loss from Ocular Inflammation and Complications Active choroiditis and its acute and chronic complications reduce visual acuity.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated."
The review directly describes the sequence and principal ocular tissues involved in acute VKH.
Retinal Pigment Epithelium Dysfunction
Multifocal choroidal inflammation disrupts retinal pigment epithelial barrier function, allowing localized subretinal fluid to become confluent and produce exudative serous retinal detachment.
retinal pigment epithelial cell CL:0002586 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves retinal pigment epithelial cell (CL:0002586). CL:0002586 is a cell type from the Cell Ontology.
Downstream
Serous Retinal Detachment RPE breakdown permits subretinal fluid accumulation and confluent serous retinal detachment.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"The choroidal inflammation eventually becomes multifocal with a diffuse breakdown of the RPE causing serous localised elevation of the retina that can rapidly become confluent, leading to a diffuse serous retinal detachment (SRD)"
The review directly states the RPE breakdown and fluid-accumulation sequence.
Persistent Subclinical Choroidal Inflammation
Inadequate suppression can leave ongoing choroidal inflammation even when the posterior segment appears clinically quiet. Persistent inflammation is linked to recurrent anterior uveitis, progressive melanocyte loss, depigmentation, chorioretinal atrophy, and vision-threatening complications.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Choroidal Melanocyte Loss and Depigmentation Ongoing choroidal inflammation is associated with disappearance of choroidal melanocytes and progressive fundus depigmentation.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Indocyanine green angiographic studies of patients during episodes of apparent isolated granulomatous anterior segment recurrence demonstrated choroidal involvement suggesting ongoing subclinical choroidal inflammation despite the absence of clinical signs of posterior segment inflammation"
ICGA demonstrates otherwise occult choroidal activity during apparent anterior-only recurrence.
Choroidal Melanocyte Loss and Depigmentation
Loss of choroidal melanocytes and progressive posterior-segment depigmentation produce the sunset-glow appearance and can accompany chorioretinal atrophy.
melanocyte CL:0000148 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves melanocyte (CL:0000148). CL:0000148 is a cell type from the Cell Ontology.
Downstream
Sunset Glow Fundus Progressive choroidal melanocyte loss produces diffuse fundus hypopigmentation known as sunset glow fundus.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"ongoing subclinical choroidal inflammation due to inadequate immunosuppression is involved in the pathogenesis of progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy"
The review identifies the inflammatory depigmentation route to sunset glow fundus and chorioretinal atrophy.
Extraocular Melanocyte-Containing Tissue Involvement
VKH extends beyond ocular inflammation to melanocyte-containing tissues in the ears, brain or meninges, skin, and hair.
melanocyte CL:0000148 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves melanocyte (CL:0000148). CL:0000148 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Meningeal Irritation Meningeal immune involvement manifests as meningismus.
Headache Meningeal involvement commonly manifests with headache.
CSF Pleocytosis Meningeal cellular inflammation produces lymphocytic CSF pleocytosis.
Tinnitus Auditory-system involvement can manifest as tinnitus.
Sensorineural Hearing Loss Auditory-system involvement can produce sensorineural hearing loss.
Vitiligo Integumentary melanocyte loss manifests as vitiligo.
Poliosis Hair melanocyte involvement manifests as poliosis.
Alopecia Integumentary immune involvement can manifest as alopecia.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Vogt-Koyanagi-Harada (VKH) disease is a multisystem T-lymphocyte-mediated autoimmune disease directed against antigens associated with melanocytes present in the target organs including the uvea, inner ear, meninges, and integumentary system."
The review explicitly defines the systemic melanocyte-containing target organs involved in VKH.
Vision Loss from Ocular Inflammation and Complications
Acute inflammatory injury and exudative retinal detachment can impair vision; chronic recurrent inflammation adds cataract, glaucoma, subretinal fibrosis, chorioretinal atrophy, and choroidal neovascularization risk.
Downstream
Visual Impairment Reduced best-corrected visual acuity represents the functional visual impairment caused by ocular inflammation and its complications.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002)."
This retrospective VKH cohort links chronic recurrent disease with worse measured visual acuity.
✶

Histopathology

1
Choroidal inflammatory infiltrates with melanocyte loss
Histopathologic examinations show scattered inflammatory infiltrates within a thickened choroid together with disappearance of choroidal melanocytes. This supports ongoing inflammatory depigmentation but ocular biopsy is not a routine diagnostic requirement.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Histopathologic studies of eyes with “sunset glow fundus” revealed the presence of scattered inflammatory infiltrates in the thickened choroid with disappearance of choroidal melanocytes"
Human ocular histopathology directly demonstrates both persistent choroidal inflammation and melanocyte loss in depigmented disease.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Vogt-Koyanagi-Harada Disease Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

12
Ear 2
Tinnitus FREQUENT HP:0000360 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tinnitus (HP:0000360). HP:0000360 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"The clinical features were as follows: uveitis (100%), sunset glow fundus (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia (31.4%)."
Tinnitus occurred in 45.0% of 912 cases, supporting the FREQUENT band.
Sensorineural Hearing Loss Sensorineural hearing impairment HP:0000407 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sensorineural hearing impairment (HP:0000407). HP:0000407 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"The audiovestibular symptoms include sensorineural hearing loss, tinnitus, and vertigo."
The review explicitly lists sensorineural hearing loss as a VKH audiovestibular manifestation.
Eye 2
Bilateral Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Typical clinical features of VKH disease include bilateral choroiditis that rapidly transforms into panuveitis associated with exudative retinal detachment"
The review directly identifies bilateral choroiditis-to-panuveitis progression as a typical VKH feature.
Visual Impairment HP:0000505 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Visual impairment (HP:0000505). HP:0000505 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002)."
Directly measured visual-acuity impairment was worse in the group that developed chronic recurrent disease.
Integument 1
Alopecia FREQUENT HP:0001596 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Alopecia (HP:0001596). HP:0001596 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"The clinical features were as follows: uveitis (100%), sunset glow fundus (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia (31.4%)."
Alopecia occurred in 31.4% of 912 cases, supporting the FREQUENT band.
Nervous System 1
Headache FREQUENT HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"The clinical features were as follows: uveitis (100%), sunset glow fundus (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia (31.4%)."
Headache occurred in 49.2% of 912 cases, supporting the FREQUENT band.
Other 6
Serous Retinal Detachment VERY_FREQUENT HP:0012231 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Serous retinal detachment (HP:0012231). HP:0012231 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"Exudative retinal detachment was detected in 26 patients (76.5%) in the acute-resolved group and in 24 patients (85.7%) in the chronic-recurrent group."
Fifty of 62 patients (80.6% overall) had exudative retinal detachment at baseline, supporting the VERY_FREQUENT band for this cohort.
Sunset Glow Fundus FREQUENT Fundus hypopigmentation HP:0007894 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sunset glow fundus, annotated with Fundus hypopigmentation (HP:0007894). HP:0007894 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"The clinical features were as follows: uveitis (100%), sunset glow fundus (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia (31.4%)."
Sunset glow fundus occurred in 48.7% of 912 cases, supporting the FREQUENT band. Fundus hypopigmentation is the closest validated local HPO binding.
Meningeal Irritation Non-infectious meningitis HP:0033430 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Non-infectious meningitis (HP:0033430). HP:0033430 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Neurological manifestations include meningismus (headache and stiffness of the neck and back) with cerebrospinal fluid (CSF) lymphocytic pleocytosis."
The review directly describes sterile meningeal symptoms and the associated inflammatory CSF finding.
CSF Pleocytosis VERY_FREQUENT HP:0012229 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is CSF pleocytosis (HP:0012229). HP:0012229 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Cerebrospinal fluid pleocytosis with a predominance of lymphocytes, monocytes and normal glucose has been found in more than 80% of patients with VKH and may persist for up to eight weeks."
More than 80% maps to the VERY_FREQUENT band; the passage also describes the cellular pattern and duration.
Vitiligo OCCASIONAL HP:0001045 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vitiligo (HP:0001045). HP:0001045 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"The clinical features were as follows: uveitis (100%), sunset glow fundus (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia (31.4%)."
Vitiligo occurred in 11.4% of 912 cases, supporting the OCCASIONAL band.
Poliosis OCCASIONAL HP:0002290 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Poliosis (HP:0002290). HP:0002290 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Alopecia arose in 32.94% of subjects, poliosis in 20.8% and vitiligo in 19.44%."
Poliosis occurred in 20.8% in the cited Italian cohort, supporting the OCCASIONAL band while preserving population-specific variation.
🧬

Genetic Associations

3
HLA-DRB1*04:05 susceptibility (HLA-DRB1*04:05 is associated with susceptibility to VKH and VKH-like immune-related uveitis.)
Gene: HLA-DRB1 hgnc:4948 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is HLA-DRB1 (hgnc:4948). hgnc:4948 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: RISK_FACTOR variant_origin: GERMLINE
Show evidence (1 reference)
PMID:37604934 SUPPORT Human Clinical
"Four patients with VKH-like uveitis underwent HLA genotyping and were all positive for HLA-DRB1*04:05. All 3 patients with non-VKH-like uveitis were negative for HLA-DRB1*04:05."
The small ICI-associated uveitis series supports enrichment of HLA-DRB1*04:05 in the VKH-like form; it does not establish penetrance or causality in idiopathic VKH.
PRKCD susceptibility locus (PRKCD rs74437127 alleles are associated with altered VKH susceptibility in a Chinese Han case-control cohort.)
Gene: PRKCD hgnc:9399 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is PRKCD (hgnc:9399). hgnc:9399 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10–5, OR = 1.810; Pc = 2.76 × 10–5, OR = 1.698, respectively)."
This human case-control study directly supports PRKCD as a susceptibility locus in the studied Han Chinese population; functional causality was not demonstrated.
CARD9 susceptibility locus (CARD9 rs3812555 is associated with VKH susceptibility and increased inflammatory cytokine production.)
Gene: CARD9 hgnc:16391 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CARD9 (hgnc:16391). hgnc:16391 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (1 reference)
PMID:36782298 SUPPORT Human Clinical
"We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α."
This conclusion supports CARD9 as a susceptibility locus with a plausible cytokine-mediated functional correlate.
💊

Medical Actions

4
Early Systemic Corticosteroids
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: corticosteroid CHEBI:50858 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses corticosteroid (CHEBI:50858). CHEBI:50858 is a therapeutic agent from Chemical Entities of Biological Interest.
High-dose systemic corticosteroids are used early to suppress acute ocular and systemic inflammation, commonly followed by early immunomodulatory therapy to reduce chronic progression risk.
Mechanism Target:
INHIBITS Granulomatous Choroidal Inflammation — High-dose systemic corticosteroids suppress acute intraocular and choroidal inflammation; adequate duration and early steroid-sparing therapy are important because corticosteroids alone may not prevent chronic evolution.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"In the initial phase, VKH usually responds to high-dose systemic corticosteroid therapy."
The review directly supports acute inflammatory response to high-dose systemic corticosteroids.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37204477 SUPPORT Human Clinical
"Treatment is usually initiated with corticosteroids followed by an early introduction of immunosuppressive treatment (IMT) to achieve immediate response after disease presentation, although the choice of IMT for VKH can vary."
This clinical review supports systemic corticosteroids as the initial VKH treatment backbone.
Combined Immunomodulatory Therapy
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: mycophenolate mofetil CHEBI:8764 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses mycophenolate mofetil (CHEBI:8764). CHEBI:8764 is a therapeutic agent from Chemical Entities of Biological Interest. cyclosporin A CHEBI:4031 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses cyclosporin A (CHEBI:4031). CHEBI:4031 is a therapeutic agent from Chemical Entities of Biological Interest.
Conventional steroid-sparing immunomodulatory therapy, including agents such as mycophenolate mofetil or cyclosporine, is used with low-dose steroids to stabilize disease and preserve vision.
Mechanism Target:
INHIBITS Persistent Subclinical Choroidal Inflammation — Early mycophenolate or other steroid-sparing immunomodulation is used to control clinically overt and subclinical choroidal inflammation and reduce chronic recurrent evolution.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute uveitis associated with VKH disease prevented the progression of the disease to chronic recurrent evolution and development of..."
Prospective treatment observations support suppression of the chronic inflammatory route and its depigmenting complications.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:37204477 SUPPORT Human Clinical
"81% (21 of 26 patients) of our patients treated with combined IMT/steroid were able to achieve disease stability with significant good visual outcome at 24 months (Median VApre-IMT = 0.3 Logmar vs VApost-IMT = 0.0 Logmar, p = 0.0001)."
This retrospective clinical series supports combined immunomodulatory therapy and low-dose steroid treatment for VKH disease stability.
PMID:37355662 SUPPORT Human Clinical
"Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a..."
The randomized non-inferiority trial supports cyclosporine-based conventional immunosuppression as an evidence-backed therapeutic strategy.
Adalimumab Biologic Therapy
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: adalimumab NCIT:C65216 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses adalimumab (NCIT:C65216). NCIT:C65216 is a therapeutic agent from the NCI Thesaurus.
Adalimumab, an anti-TNF monoclonal antibody, is used for refractory or chronic recurrent VKH and is under study for acute VKH in combination with glucocorticoids.
Mechanism Target:
INHIBITS CARD9-Associated Pro-inflammatory Cytokine Amplification — Adalimumab inhibits TNF-alpha, a cytokine implicated in ocular inflammatory chemokine, adhesion-molecule, and cytokine networks. The treatment evidence supports TNF-pathway inhibition but does not prove CARD9 dependence of response.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"Tumor necrosis factor-alpha (TNF-α) has played a crucial role in the development of chemokines, adhesion molecules, and cytokines associated with ocular inflammation"
The source provides the TNF-alpha inflammatory rationale; observed adalimumab response is documented in the treatment-level evidence below.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"ADA significantly reduced anterior chamber inflammatory cells (P = 0.000) and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent group, and markedly decreased the recurrence rate in VKH patients (P = 0.009)."
This retrospective cohort directly supports adalimumab efficacy in chronic recurrent VKH.
Janus Kinase Inhibitor Therapy
Category: Therapeutic Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: baricitinib CHEBI:95341 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses baricitinib (CHEBI:95341). CHEBI:95341 is a therapeutic agent from Chemical Entities of Biological Interest. tofacitinib CHEBI:71200 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses tofacitinib (CHEBI:71200). CHEBI:71200 is a therapeutic agent from Chemical Entities of Biological Interest.
JAK inhibitors are an emerging option for refractory non-infectious ocular inflammatory disease; available evidence includes a prospective registry cohort with one VKH patient, so this is promising but not VKH-specific definitive evidence.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39247640 SUPPORT Human Clinical
"Ocular inflammation was related to a systemic disease in 8 (66.7%) patients as follows: spondyloarthritis (n = 3), peripheral psoriatic arthritis (n = 1), rheumatoid arthritis (n = 1), antinuclear antibodies (ANA) positive juvenile idiopathic arthritis (n = 1), Behçet’s syndrome (n = 1),..."
The prospective registry includes a VKH case among non-infectious ocular inflammatory diseases, so it partially supports JAK inhibitor relevance without establishing VKH-specific efficacy.
🌍

Environmental Factors

2
SARS-CoV-2 infection or vaccination
COVID-19 infection and SARS-CoV-2 vaccination have been reported before VKH onset or relapse. The association is treated as a trigger context rather than proof of a necessary cause.
Show evidence (2 references)
PMID:37834885 SUPPORT Human Clinical
"The Coronavirus Disease 2019 (COVID-19) is a new contagious infection that might trigger the onset of VKH disease, as previously proposed for other viruses."
The modal "might" supports a possible trigger association, not a causal or necessary exposure.
PMID:37834885 SUPPORT Human Clinical
"Moreover, after the mass vaccination against SARS-CoV-2 worldwide, cases of VKH disease associated with COVID-19 vaccination have been reported."
Published cases establish temporal reporting but cannot distinguish causation from background occurrence.
Mechanism Target:
PREDISPOSES HLA-DRB1-Restricted Melanocyte Antigen Recognition — Infection or vaccination may provide immune activation in a genetically susceptible host, but a reproducible antigenic or causal bridge to melanocyte-specific T-cell recognition has not been established.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"Caution and a critical attitude about causal inference remain necessary about infections as triggers for VKH disease"
The review explicitly warns that infection associations do not establish causality, so this is a predisposing hypothesis rather than a trigger edge.
Immune checkpoint inhibitor therapy
immune checkpoint inhibitor exposure ECTO:9001737 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is immune checkpoint inhibitor exposure, annotated with exposure to antineoplastic agent (ECTO:9001737). ECTO:9001737 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Immune checkpoint inhibitor therapy can be associated with VKH-like immune-related uveitis, especially in HLA-DRB1*04:05-positive patients.
Show evidence (1 reference)
PMID:37604934 SUPPORT Human Clinical
"Statistical analysis showed that HLA-DRB1*04:05 was significantly associated with developing VKH-like ICIU (P = 0.029)."
This case-series abstract supports the reported HLA-DRB1*04:05-associated VKH-like immune checkpoint inhibitor uveitis context.
Mechanism Target:
TRIGGERS Th1 Effector Cytokine Response — Checkpoint blockade can unleash excessive inflammatory T-cell responses and produce VKH-like uveitis in susceptible patients.
Show evidence (1 reference)
PMID:37604934 SUPPORT Human Clinical
"Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by inhibiting immune checkpoint molecules that suppress inflammatory T-cell activity. However, ICIs can initiate excessive immune responses, thereby causing immune-related adverse events (irAEs)."
The source directly describes checkpoint blockade releasing inflammatory T-cell activity and causing immune-related adverse events; the VKH-like phenotype is supported by the same nine-case series.
🔬

Biochemical Markers

1
Aqueous humor CXCL13 (INCREASED)
Context: Active uveitis; research biomarker rather than a stand-alone diagnostic test
Pathograph Readouts
Readout Of Persistent Subclinical Choroidal Inflammation Positive Monitoring
Elevated intraocular CXCL13 reports active inflammatory/B-cell chemotactic biology but is not specific enough to diagnose VKH independently.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"The levels of CXCL13 were elevated 1423.6-fold in VKH disease, 298.3-fold in Behçet's disease, 107.1-fold in HLA-B27-associated uveitis and 458.2-fold in sarcoidosis compared to controls"
The large elevation supports an inflammatory readout, while cross-disease elevation and overlap with sarcoidosis limit specificity and validation as a longitudinal monitoring marker.
Show evidence (1 reference)
PMID:34869409 SUPPORT Human Clinical
"CXCL13 levels in VKH disease were significantly higher than the levels in Behçet's disease and HLA-B27-associated uveitis. However, CXCL13 levels did not differ significantly between VKH disease and sarcoidosis"
The comparative aqueous-humor studies support elevation while directly documenting the important sarcoidosis specificity limitation.
🔬

Diagnosis

4
Clinical Classification Criteria and Mandatory Exclusions
No single test establishes VKH. Revised Diagnostic Criteria classify complete, incomplete, and probable disease, while SUN criteria distinguish early- and late-stage patterns. A compatible presentation requires exclusion of antecedent ocular trauma or vitreoretinal surgery, treponemal infection, and sarcoidosis.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Early SUN classification uses bilateral retinal detachment or characteristic uveitis with at least two neurologic/auditory findings; late classification uses sunset glow fundus or characteristic uveitis with at least one cutaneous depigmenting finding.
Show evidence (3 references)
PMID:37834885 SUPPORT Human Clinical
"There is no single diagnostic test for VKH disease, and its diagnosis is mainly based on clinical features and either systemic or ocular findings."
The review explicitly states that diagnosis is syndromic rather than based on one definitive assay.
PMID:37834885 SUPPORT Human Clinical
"According to SUN, early-stage features include bilateral retinal detachment or characteristic uveitis with at least two of the following neurological criteria: headache, dysacusis, meningism, pleocytosis of the cerebrospinal fluid and tinnitus. Late-stage features include sunset glow fundus or..."
This passage directly supports the detailed early- and late-stage SUN classification algorithm summarized in the results field.
PMID:37834885 SUPPORT Human Clinical
"It is also mandatory to exclude previous ocular trauma, vitreoretinal surgery and positive treponemal syphilis serology or evidence of sarcoidosis"
The SUN summary specifies the mandatory exclusions that separate VKH from major infectious, granulomatous, and post-traumatic mimics.
Fluorescein and Indocyanine Green Angiography
Fluorescein angiography identifies early pinpoint hyperfluorescence followed by leakage and subretinal pooling. ICGA detects diffuse hypercyanescence, delayed choroidal perfusion, and hypocyanescent stromal inflammatory foci, including occult choroidal activity.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Concordant angiographic evidence supports diffuse choroiditis and maps the extent and activity of inflammation.
Show evidence (2 references)
PMID:37834885 SUPPORT Human Clinical
"Fluorescein angiography (FAG), in the early stage of the disease, shows multifocal choroiditis with multiple areas of early pinpoint hyperfluorescence followed by late leakage and pooling at the intraretinal or subretinal fluid level."
The review directly describes the characteristic early fluorescein pattern.
PMID:37834885 SUPPORT Human Clinical
"In the initial phase, ICGA demonstrates a diffuse hypercyanescence, and in the intermediate and late phases, delayed choroidal perfusion and hypocyanescent lesions represent choroidal stromal inflammatory foci that cannot be highlighted by an ophthalmoscopic examination"
ICGA detects choroidal stromal inflammation that can be invisible on direct fundus examination.
EDI-OCT and OCT Angiography
EDI-OCT and OCT measure choroidal thickening even without serous detachment and can monitor treatment response. OCT angiography noninvasively shows reduced vessel density and focal vascular dropout in active inflammation.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Choroidal thickness and vascular-density changes support early diagnosis and longitudinal inflammatory monitoring but are interpreted with the full clinical syndrome.
Show evidence (2 references)
PMID:37834885 SUPPORT Human Clinical
"EDI and OCT have demonstrated choroidal thickening in patients with early-stage VKH, even if a serous detachment is absent."
The review identifies a diagnostic imaging abnormality that can precede or occur without serous detachment.
PMID:37834885 SUPPORT Human Clinical
"During the active phase, OCT-A demonstrates decreased choroidal and retinal vessel density, similar to the changes detectable with FAG, and focal dropout that corresponds to the inflammation areas"
The review directly describes active-phase OCT-A vascular readouts.
Cerebrospinal Fluid Examination
Lumbar-puncture evidence of lymphocyte-predominant pleocytosis supports neurologic involvement and is one of the SUN early-stage neurologic criteria; absence does not exclude VKH.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Lymphocyte-predominant pleocytosis with normal glucose may persist for up to eight weeks.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Cerebrospinal fluid pleocytosis with a predominance of lymphocytes, monocytes and normal glucose has been found in more than 80% of patients with VKH and may persist for up to eight weeks."
The review describes the supportive CSF profile, frequency, and duration.
📈

Progression

4
Prodromal neurologic and auditory phase
Duration: 3-5 days
Nonspecific systemic symptoms, meningismus, headache, dizziness, orbital pain, photophobia, tearing, and scalp hypersensitivity can precede ocular inflammation; rare focal neurologic manifestations are reported.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Prodromal stage: This usually lasts for 3–5 days and is characterised by nonspecific symptoms, such as malaise, fever, nausea, headache, meningismus, dizziness and orbital pain"
The review directly states the stage duration and typical prodromal manifestations.
Acute uveitic phase
Duration: weeks
Acute VKH follows the prodrome by days and lasts weeks. Multifocal choroiditis causes posterior choroidal thickening, optic-disc hyperemia or edema, RPE breakdown, and potentially confluent serous retinal detachment; untreated inflammation can extend to granulomatous anterior uveitis.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Acute uveitic stage: This appears a few days after the prodromal phase and lasts for several weeks. During this period, the patient mainly complains of blurred vision, pain and central scotoma, and most patients present with bilateral posterior uveitis."
The review directly defines the timing, duration, symptoms, and bilateral posterior inflammatory presentation of the acute phase.
Convalescent depigmentation phase
Duration: months to years
Uveal and integumentary depigmentation can emerge over months or years, including sunset glow fundus, vitiligo, and poliosis. These changes should not be assumed to represent biologically inactive convalescence because subclinical choroidal inflammation can persist.
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"Chronic (or convalescent) stage: This lasts for months or even years and results in integumentary and uveal depigmentation."
The review directly states the stage duration and depigmenting outcome.
Chronic recurrent phase
Recurrent, mainly anterior granulomatous uveitis can coexist with active choroiditis detectable on ICGA or EDI-OCT. Cataract, glaucoma, neovascularization, and subretinal fibrosis accumulate in this phase; poor initial acuity, older onset, and sunset glow fundus are prognostic signals in retrospective data.
Show evidence (1 reference)
PMID:38849758 SUPPORT Human Clinical
"Poor initial BCVA (P = 0.046) and the occurrence of “sunset glow fundus” (P = 0.040) were significantly associated with progression to the chronic recurrent phase."
This retrospective cohort identifies clinical predictors of chronic recurrent VKH.
📊

Prevalence

1
Reported VKH populations
Annual Incidence 0.6–1.7 per 100,000 Rare
Review-level estimate expressed as incident cases per 100,000 person-years; the underlying populations are not specified in the cited passage, so this should not be interpreted as a globally representative rate. RARE is used as a coarse qualitative occurrence class calibrated to this low annual incidence; the numeric incidence range must not be compared directly with point-prevalence bands.
Show evidence (1 reference)
PMID:37355662 SUPPORT Human Clinical
"It is estimated with an incidence of 0.6 to 1.7 per 100,000 person-years"
The review section of the randomized-trial report provides the incidence range; the structured record preserves it as annual incidence rather than mislabelling it as prevalence.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Vogt-Koyanagi-Harada Disease:

Sympathetic ophthalmia Not Yet Curated MONDO:0019198
Overlapping Features Sympathetic ophthalmia can closely mimic bilateral granulomatous panuveitis and choroiditis, but follows penetrating ocular trauma or intraocular surgery.
Distinguishing Features
  • Antecedent penetrating ocular trauma or vitreoretinal surgery
  • Inflammation of the fellow eye after disruption of ocular immune privilege
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"It is also mandatory to exclude previous ocular trauma, vitreoretinal surgery and positive treponemal syphilis serology or evidence of sarcoidosis"
The SUN summary makes prior trauma or vitreoretinal surgery a mandatory exclusion; this distinguishes the post-traumatic mimic sympathetic ophthalmia, although the quoted passage does not name it explicitly.
Ocular syphilis MONDO:0005976
Overlapping Features Ocular syphilis can present with inflammatory posterior-segment findings and must be excluded before assigning a noninfectious autoimmune diagnosis.
Distinguishing Features
  • Positive treponemal serology
  • Infectious disease requiring antimicrobial rather than primary immunosuppressive treatment
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"It is also mandatory to exclude previous ocular trauma, vitreoretinal surgery and positive treponemal syphilis serology or evidence of sarcoidosis"
Positive treponemal serology is a mandatory SUN exclusion for VKH.
Sarcoidosis MONDO:0019338
Overlapping Features Sarcoidosis is a granulomatous systemic disease that can cause uveitis and overlap clinically with VKH.
Distinguishing Features
  • Systemic or imaging evidence of sarcoidosis
  • Granulomatous inflammation not defined by the VKH melanocyte-targeted multisystem pattern
Show evidence (1 reference)
PMID:37834885 SUPPORT Human Clinical
"It is also mandatory to exclude previous ocular trauma, vitreoretinal surgery and positive treponemal syphilis serology or evidence of sarcoidosis"
Evidence of sarcoidosis is a mandatory SUN exclusion for VKH.
📊

Related Datasets

1
Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease geo:GSE148020
Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11259 human circulating monocytes and genetically defined their subpopulations.
human SINGLE CELL RNA SEQ n=6
Identified by GEO DataSets index search for Vogt-Koyanagi-Harada Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

2
NCT03399175 NOT_APPLICABLE RECRUITING
Prospective study of early systemic high-dose corticosteroid and immunosuppressive therapy from VKH disease onset with multimodal clinical follow-up.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT03399175 SUPPORT Human Clinical
"This prospective study will include patients with Vogt-Koyanagi-Harada disease from disease onset, treated with early systemic high-dose corticosteroid and immunosuppressive therapy."
ClinicalTrials.gov identifies this VKH study of early systemic corticosteroid plus immunosuppressive therapy.
NCT05590416 NOT_APPLICABLE UNKNOWN
Observational study of adalimumab treatment in acute Vogt-Koyanagi-Harada disease.
Target Phenotypes: Panuveitis HP:0012121 Human Phenotype Ontology (HP) Relation: this clinical trial targets this phenotype This clinical trial targets Panuveitis (HP:0012121). HP:0012121 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
clinicaltrials:NCT05590416 SUPPORT Human Clinical
"This project is designed to test the hypothesis that adalimumab is clinically useful for patients with acuta Vogt-Koyanagi-Harada disease"
ClinicalTrials.gov identifies an acute VKH observational study of adalimumab.
🐁

Animal Models

1
Smyth line autoimmune-vitiligo-prone chicken Gallus gallus
Smyth-line chickens spontaneously develop autoimmune vitiligo; a subset also develops uveitis and visual impairment with choroidal melanocyte loss, mononuclear infiltration, and an IFN-gamma-polarized Th1 response. This is a mechanistically relevant spontaneous pigmentation-autoimmunity model that resembles VKH, not a model that recapitulates the full human diagnostic syndrome.
Autoimmune vitiligo Uveitis Choroidal melanocyte loss Visual impairment
Species
Gallus gallus
Genotype
Smyth line autoimmune-vitiligo-prone chicken
Show evidence (2 references)
PMID:35547230 SUPPORT Model Organism
"The immunopathogenesis in SL vision impairment resembles human vitiligo-associated ocular diseases, especially Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia."
The authors explicitly identify the ocular autoimmune phenotype as resembling VKH while also delimiting it as a cross-disease model.
PMID:35547230 SUPPORT Model Organism
"Specifically, as in active SLV, the loss of choroidal melanocytes is associated with an INF-γ polarized, Th1 cell-mediated immune response and aberrant melanocyte function."
The model reproduces the choroidal melanocyte-loss and Th1/IFN-gamma arm of the curated human mechanism; the source spells interferon as "INF-γ."
{ }

Source YAML

click to show 
name: Vogt-Koyanagi-Harada Disease
creation_date: "2026-05-11T12:14:15Z"
category: Autoimmune
disease_term:
  preferred_term: Vogt-Koyanagi-Harada disease
  term:
    id: MONDO:0018092
    label: Vogt-Koyanagi-Harada disease
parents:
- Autoimmune Disease
- Ophthalmic Disorder
synonyms:
- VKH disease
- Vogt-Koyanagi-Harada syndrome
- Harada disease
description: >-
  Vogt-Koyanagi-Harada disease is a multisystem autoimmune inflammatory disease
  targeting melanin-containing tissues, especially the uvea and choroid, with
  neurologic, auditory, skin, and hair involvement. Disease expression reflects
  immune susceptibility and inflammatory triggers, and early systemic
  immunosuppression is used to prevent chronic recurrent ocular disease.
prevalence:
- population: Reported VKH populations
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: RARE
  rate_low: 0.6
  rate_high: 1.7
  notes: >-
    Review-level estimate expressed as incident cases per 100,000 person-years;
    the underlying populations are not specified in the cited passage, so this
    should not be interpreted as a globally representative rate. RARE is used
    as a coarse qualitative occurrence class calibrated to this low annual
    incidence; the numeric incidence range must not be compared directly with
    point-prevalence bands.
  evidence:
  - reference: PMID:37355662
    reference_title: A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is estimated with an incidence of 0.6 to 1.7 per 100,000 person-years
    explanation: >-
      The review section of the randomized-trial report provides the incidence
      range; the structured record preserves it as annual incidence rather than
      mislabelling it as prevalence.
pathophysiology:
- name: HLA-DRB1-Restricted Melanocyte Antigen Recognition
  role: trigger
  mechanism_confidence: ESTABLISHED
  description: >-
    In HLA-DR4-positive VKH, ocular and circulating CD4-positive T cells recognize
    melanocyte-associated tyrosinase and gp100 peptides. This is direct human
    evidence for antigen-specific adaptive immunity, while the broader initiating
    trigger remains uncertain.
  genes:
  - preferred_term: HLA-DRB1
    term:
      id: hgnc:4948
      label: HLA-DRB1
  cell_types:
  - preferred_term: helper T cell
    term:
      id: CL:0000912
      label: helper T cell
  - preferred_term: melanocyte
    term:
      id: CL:0000148
      label: melanocyte
  biological_processes:
  - preferred_term: adaptive immune response
    term:
      id: GO:0002250
      label: adaptive immune response
    modifier: INCREASED
  - preferred_term: T cell activation
    term:
      id: GO:0042110
      label: T cell activation
    modifier: INCREASED
  evidence:
  - reference: PMID:16723469
    reference_title: Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cells infiltrating the eye and PBMCs in HLA-DR4+ (HLA-DRB1*0405, 0410)
      patients with VKH contained a population of CD4+ T lymphocytes that recognized
      tyrosinase and gp100 peptides and produced RANTES and IFN-gamma in response to
      the two peptides.
    explanation: >-
      Patient-derived ocular and blood T-cell clones directly recognized two
      melanocyte peptides in an HLA-DR4-positive context.
  downstream:
  - target: Th1 Effector Cytokine Response
    causal_link_type: DIRECT
    description: >-
      Recognition of tyrosinase and gp100 by patient CD4-positive T cells elicits
      a memory Th1 response with IFN-gamma and RANTES production.
    evidence:
    - reference: PMID:16723469
      reference_title: Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The T cells were active memory Th1-type lymphocytes, and they recognized
        the tyrosinase peptide and produced IFN-gamma in response to
        HLA-DRB1*0405+ melanoma cells.
      explanation: >-
        The same patient-derived T-cell experiment directly connects melanocyte
        peptide recognition to a Th1/IFN-gamma effector response.
- name: PRKCD-Associated Immune Susceptibility
  role: trigger
  mechanism_confidence: PROVISIONAL
  description: >-
    PRKCD rs74437127 is associated with VKH susceptibility in a Han Chinese
    case-control cohort. The study did not establish how the locus changes immune
    function in VKH, so its connection to the effector pathway remains provisional.
  genes:
  - preferred_term: PRKCD
    term:
      id: hgnc:9399
      label: PRKCD
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C
      allele of CARD9 were associated with increased susceptibility of VKH
      (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10−5, OR = 1.810; Pc = 2.76 × 10−5,
      OR = 1.698, respectively).
    explanation: >-
      The 912-case/878-control study supports a susceptibility association, not
      a monogenic or experimentally proven causal mechanism.
  downstream:
  - target: Th1 Effector Cytokine Response
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      PRKCD is placed upstream of the T-cell effector response as a susceptibility
      locus, but the intervening functional steps were not established in VKH.
    evidence:
    - reference: PMID:36782298
      reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Protein kinase C delta (PRKCD) and caspase recruitment domain family
        member 9 (CARD9) are genes involved in B and T cell activation, and
        cytokine production, which are vital mechanisms underlying autoimmune
        disease development.
      explanation: >-
        The paper provides a general immune-function rationale for the
        susceptibility locus, but its case-control data do not establish the
        PRKCD-to-Th1 route in VKH and a PRKCD functional study was unavailable.
- name: CARD9-Associated Pro-inflammatory Cytokine Amplification
  role: contributor
  mechanism_confidence: PROVISIONAL
  description: >-
    The VKH-associated CARD9 rs3812555 CC genotype correlates with higher CARD9
    expression and TNF-alpha production. Functional measurements support a
    cytokine-amplifying correlate, although they were not made in VKH target tissue.
  genes:
  - preferred_term: CARD9
    term:
      id: hgnc:16391
      label: CARD9
  biological_processes:
  - preferred_term: tumor necrosis factor production
    term:
      id: GO:0032640
      label: tumor necrosis factor production
    modifier: INCREASED
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Functional studies on rs3812555 genotyped individuals revealed that CC
      carriers had significantly higher CARD9 mRNA expression and tumour
      necrosis factor-α production than TC/TT carriers (P = 1.00 × 10−4;
      P = 2.00 × 10−3, respectively).
    explanation: >-
      Genotype-stratified human PBMC assays support increased CARD9 expression
      and TNF-alpha production, with the target-tissue limitation retained.
  downstream:
  - target: Granulomatous Choroidal Inflammation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      CARD9-associated TNF-alpha amplification is a plausible contributor to
      ocular inflammation, but this edge has not been directly demonstrated in
      VKH choroid.
    evidence:
    - reference: PMID:36782298
      reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We found an association between PRKCD rs74437127 and CARD9 rs3812555
        polymorphisms and VKH susceptibility and revealed that the increased
        susceptibility of rs3812555 for VKH may be mediated by regulating CARD9
        gene expression and the production of pro-inflammatory cytokines, such as
        TNF-α.
      explanation: >-
        The authors propose cytokine-mediated susceptibility, but do not directly
        trace the genotype-to-choroid causal route.
- name: Th1 Effector Cytokine Response
  role: contributor
  mechanism_confidence: ESTABLISHED
  description: >-
    Melanocyte-reactive patient CD4-positive T cells have an active-memory Th1
    phenotype and produce IFN-gamma and RANTES. These effectors provide a direct
    human bridge from antigen recognition to tissue-directed inflammation.
  cell_types:
  - preferred_term: helper T cell
    term:
      id: CL:0000912
      label: helper T cell
  biological_processes:
  - preferred_term: cytokine production
    term:
      id: GO:0001816
      label: cytokine production
    modifier: INCREASED
  evidence:
  - reference: PMID:16723469
    reference_title: Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CONCLUSIONS: In VKH there are tyrosinase and gp100 peptide-specific T cells that
      can mediate an inflammatory response.
    explanation: >-
      The patient-derived cellular study directly supports the inflammatory
      competence of melanocyte-antigen-specific T cells.
  downstream:
  - target: Granulomatous Choroidal Inflammation
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Leukocyte recruitment and inflammatory injury within melanocyte-rich choroid
    description: >-
      Melanocyte-antigen-specific Th1 cells are positioned upstream of the
      granulomatous choroiditis that defines acute ocular VKH.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Evidence has been provided that the clinical manifestations are caused by
        a T-lymphocyte-mediated autoimmune response directed against antigens
        associated with melanocytes in the target organs.
      explanation: >-
        The review synthesizes human evidence connecting melanocyte-directed
        T-cell autoimmunity to the clinical inflammatory manifestations.
  - target: Extraocular Melanocyte-Containing Tissue Involvement
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Melanocyte-directed inflammation in meninges, inner ear, skin, and hair
    description: >-
      The same melanocyte-directed cellular response is expressed in extraocular
      melanin-containing target organs.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Vogt-Koyanagi-Harada (VKH) disease is a multisystem T-lymphocyte-mediated
        autoimmune disease directed against antigens associated with melanocytes
        present in the target organs including the uvea, inner ear, meninges, and
        integumentary system.
      explanation: >-
        The source explicitly connects the T-cell autoimmune process to the
        extraocular melanocyte-containing target organs.
- name: Granulomatous Choroidal Inflammation
  description: >-
    Acute VKH begins as granulomatous choroiditis with choroidal thickening,
    optic-disc hyperemia and swelling, and subsequent anterior-segment involvement
    when inflammation is not adequately controlled.
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The early initial-onset acute uveitic phase typically exhibits granulomatous
      choroiditis with secondary exudative retinal detachment and optic disc
      hyperemia and swelling, subsequently involving the anterior segment if not
      adequately treated.
    explanation: >-
      The review directly describes the sequence and principal ocular tissues
      involved in acute VKH.
  downstream:
  - target: Bilateral Panuveitis
    causal_link_type: DIRECT
    description: >-
      Choroidal inflammation rapidly extends into bilateral panuveitis.
    evidence:
    - reference: PMID:37834885
      reference_title: Vogt-Koyanagi-Harada Disease and COVID.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Typical clinical features of VKH disease include bilateral choroiditis
        that rapidly transforms into panuveitis associated with exudative retinal
        detachment
      explanation: >-
        The review directly states the choroiditis-to-panuveitis transition.
  - target: Retinal Pigment Epithelium Dysfunction
    causal_link_type: DIRECT
    description: >-
      Choroidal inflammation impairs the overlying retinal pigment epithelium.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients with initial-onset acute uveitis present with granulomatous
        choroiditis with secondary exudative retinal detachment resulting from
        impairment of the retinal pigment epithelium caused by choroidal inflammation
      explanation: >-
        The source explicitly identifies RPE impairment as a result of choroidal
        inflammation.
  - target: Persistent Subclinical Choroidal Inflammation
    causal_link_type: DIRECT
    description: >-
      Inadequately suppressed acute choroiditis can persist below the threshold of
      routine posterior-segment clinical examination.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Progressive subclinical choroidal inflammation due to inadequate
        immunosuppression in the initial-onset acute uveitic phase will lead to
        progressive posterior segment depigmentation resulting in “sunset glow
        fundus” appearance and chorioretinal atrophy
      explanation: >-
        The review identifies persistence of inadequately suppressed acute
        choroiditis as the route to chronic depigmenting disease.
  - target: Vision Loss from Ocular Inflammation and Complications
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Exudative retinal detachment and chronic ocular complications
    description: >-
      Active choroiditis and its acute and chronic complications reduce visual
      acuity.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        A delay in diagnosis and in initiating adequate treatment are associated
        with a high risk of developing disease chronicity, complications and visual
        impairment
      explanation: >-
        The review links uncontrolled inflammatory disease and complications to
        visual impairment.
- name: Retinal Pigment Epithelium Dysfunction
  role: contributor
  mechanism_confidence: ESTABLISHED
  description: >-
    Multifocal choroidal inflammation disrupts retinal pigment epithelial barrier
    function, allowing localized subretinal fluid to become confluent and produce
    exudative serous retinal detachment.
  cell_types:
  - preferred_term: retinal pigment epithelial cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The choroidal inflammation eventually becomes multifocal with a diffuse
      breakdown of the RPE causing serous localised elevation of the retina that
      can rapidly become confluent, leading to a diffuse serous retinal detachment
      (SRD)
    explanation: >-
      The review directly states the RPE breakdown and fluid-accumulation sequence.
  downstream:
  - target: Serous Retinal Detachment
    causal_link_type: DIRECT
    description: >-
      RPE breakdown permits subretinal fluid accumulation and confluent serous
      retinal detachment.
    evidence:
    - reference: PMID:37834885
      reference_title: Vogt-Koyanagi-Harada Disease and COVID.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The choroidal inflammation eventually becomes multifocal with a diffuse
        breakdown of the RPE causing serous localised elevation of the retina that
        can rapidly become confluent, leading to a diffuse serous retinal detachment
        (SRD)
      explanation: >-
        This passage directly links RPE breakdown to serous retinal detachment.
- name: Persistent Subclinical Choroidal Inflammation
  role: contributor
  mechanism_confidence: ESTABLISHED
  description: >-
    Inadequate suppression can leave ongoing choroidal inflammation even when the
    posterior segment appears clinically quiet. Persistent inflammation is linked
    to recurrent anterior uveitis, progressive melanocyte loss, depigmentation,
    chorioretinal atrophy, and vision-threatening complications.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Indocyanine green angiographic studies of patients during episodes of
      apparent isolated granulomatous anterior segment recurrence demonstrated
      choroidal involvement suggesting ongoing subclinical choroidal inflammation
      despite the absence of clinical signs of posterior segment inflammation
    explanation: >-
      ICGA demonstrates otherwise occult choroidal activity during apparent
      anterior-only recurrence.
  downstream:
  - target: Choroidal Melanocyte Loss and Depigmentation
    causal_link_type: DIRECT
    description: >-
      Ongoing choroidal inflammation is associated with disappearance of choroidal
      melanocytes and progressive fundus depigmentation.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Histopathologic studies of eyes with “sunset glow fundus” revealed the
        presence of scattered inflammatory infiltrates in the thickened choroid
        with disappearance of choroidal melanocytes
      explanation: >-
        Human ocular histopathology links persistent inflammatory infiltrates
        with loss of choroidal melanocytes.
- name: Choroidal Melanocyte Loss and Depigmentation
  role: consequence
  mechanism_confidence: ESTABLISHED
  description: >-
    Loss of choroidal melanocytes and progressive posterior-segment depigmentation
    produce the sunset-glow appearance and can accompany chorioretinal atrophy.
  cell_types:
  - preferred_term: melanocyte
    term:
      id: CL:0000148
      label: melanocyte
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ongoing subclinical choroidal inflammation due to inadequate
      immunosuppression is involved in the pathogenesis of progressive posterior
      segment depigmentation resulting in “sunset glow fundus” appearance and
      chorioretinal atrophy
    explanation: >-
      The review identifies the inflammatory depigmentation route to sunset glow
      fundus and chorioretinal atrophy.
  downstream:
  - target: Sunset Glow Fundus
    causal_link_type: DIRECT
    description: >-
      Progressive choroidal melanocyte loss produces diffuse fundus
      hypopigmentation known as sunset glow fundus.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        progressive posterior segment depigmentation resulting in “sunset glow
        fundus” appearance and chorioretinal atrophy
      explanation: >-
        The source directly names sunset glow fundus as the appearance produced by
        progressive posterior-segment depigmentation.
- name: Extraocular Melanocyte-Containing Tissue Involvement
  description: >-
    VKH extends beyond ocular inflammation to melanocyte-containing tissues in
    the ears, brain or meninges, skin, and hair.
  cell_types:
  - preferred_term: melanocyte
    term:
      id: CL:0000148
      label: melanocyte
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  downstream:
  - target: Meningeal Irritation
    causal_link_type: DIRECT
    description: Meningeal immune involvement manifests as meningismus.
    evidence: &extraocular_neurologic_evidence
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Neurological manifestations include meningismus (headache and stiffness
        of the neck and back) with cerebrospinal fluid (CSF) lymphocytic pleocytosis.
      explanation: >-
        The review directly identifies meningismus, headache, and CSF pleocytosis
        as neurologic manifestations of VKH.
  - target: Headache
    causal_link_type: DIRECT
    description: Meningeal involvement commonly manifests with headache.
    evidence: *extraocular_neurologic_evidence
  - target: CSF Pleocytosis
    causal_link_type: DIRECT
    description: Meningeal cellular inflammation produces lymphocytic CSF pleocytosis.
    evidence: *extraocular_neurologic_evidence
  - target: Tinnitus
    causal_link_type: DIRECT
    description: Auditory-system involvement can manifest as tinnitus.
    evidence: &extraocular_auditory_evidence
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The audiovestibular symptoms include sensorineural hearing loss, tinnitus,
        and vertigo.
      explanation: >-
        The review explicitly lists hearing loss and tinnitus among VKH
        audiovestibular manifestations.
  - target: Sensorineural Hearing Loss
    causal_link_type: DIRECT
    description: Auditory-system involvement can produce sensorineural hearing loss.
    evidence: *extraocular_auditory_evidence
  - target: Vitiligo
    causal_link_type: DIRECT
    description: Integumentary melanocyte loss manifests as vitiligo.
    evidence: &extraocular_integumentary_evidence
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In the chronic recurrent phase, integumentary manifestations (poliosis,
        vitiligo, and alopecia) may develop.
      explanation: >-
        The review directly lists all three integumentary manifestations and
        places them in chronic recurrent disease.
  - target: Poliosis
    causal_link_type: DIRECT
    description: Hair melanocyte involvement manifests as poliosis.
    evidence: *extraocular_integumentary_evidence
  - target: Alopecia
    causal_link_type: DIRECT
    description: Integumentary immune involvement can manifest as alopecia.
    evidence: *extraocular_integumentary_evidence
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vogt-Koyanagi-Harada (VKH) disease is a multisystem T-lymphocyte-mediated
      autoimmune disease directed against antigens associated with melanocytes
      present in the target organs including the uvea, inner ear, meninges, and
      integumentary system.
    explanation: >-
      The review explicitly defines the systemic melanocyte-containing target
      organs involved in VKH.
- name: Vision Loss from Ocular Inflammation and Complications
  role: consequence
  mechanism_confidence: ESTABLISHED
  description: >-
    Acute inflammatory injury and exudative retinal detachment can impair vision;
    chronic recurrent inflammation adds cataract, glaucoma, subretinal fibrosis,
    chorioretinal atrophy, and choroidal neovascularization risk.
  evidence:
  - reference: PMID:38849758
    reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Initial best-corrected visual acuity (BCVA) examination at the first visit
      showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group
      and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002).
    explanation: >-
      This retrospective VKH cohort links chronic recurrent disease with worse
      measured visual acuity.
  downstream:
  - target: Visual Impairment
    causal_link_type: DIRECT
    description: >-
      Reduced best-corrected visual acuity represents the functional visual
      impairment caused by ocular inflammation and its complications.
    evidence:
    - reference: PMID:38849758
      reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Initial best-corrected visual acuity (BCVA) examination at the first visit
        showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group
        and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002).
      explanation: >-
        Measured acuity impairment was present in both groups and was worse among
        patients who developed chronic recurrent disease.
histopathology:
- name: Choroidal inflammatory infiltrates with melanocyte loss
  diagnostic: false
  context: Eyes with sunset glow fundus in chronic disease
  description: >-
    Histopathologic examinations show scattered inflammatory infiltrates within
    a thickened choroid together with disappearance of choroidal melanocytes.
    This supports ongoing inflammatory depigmentation but ocular biopsy is not a
    routine diagnostic requirement.
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Histopathologic studies of eyes with “sunset glow fundus” revealed the
      presence of scattered inflammatory infiltrates in the thickened choroid
      with disappearance of choroidal melanocytes
    explanation: >-
      Human ocular histopathology directly demonstrates both persistent choroidal
      inflammation and melanocyte loss in depigmented disease.
phenotypes:
- category: Ophthalmologic
  name: Bilateral Panuveitis
  diagnostic: true
  description: >-
    Bilateral choroiditis in acute VKH typically progresses rapidly to
    panuveitis, often with exudative retinal detachment.
  phenotype_term:
    preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Typical clinical features of VKH disease include bilateral choroiditis
      that rapidly transforms into panuveitis associated with exudative retinal
      detachment
    explanation: >-
      The review directly identifies bilateral choroiditis-to-panuveitis
      progression as a typical VKH feature.
- category: Ophthalmologic
  name: Serous Retinal Detachment
  frequency: VERY_FREQUENT
  description: >-
    RPE barrier breakdown during acute choroiditis permits subretinal fluid
    accumulation and exudative serous retinal detachment.
  phenotype_term:
    preferred_term: Serous retinal detachment
    term:
      id: HP:0012231
      label: Serous retinal detachment
  evidence:
  - reference: PMID:38849758
    reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Exudative retinal detachment was detected in 26 patients (76.5%) in the
      acute-resolved group and in 24 patients (85.7%) in the chronic-recurrent
      group.
    explanation: >-
      Fifty of 62 patients (80.6% overall) had exudative retinal detachment at
      baseline, supporting the VERY_FREQUENT band for this cohort.
- category: Ophthalmologic
  name: Sunset Glow Fundus
  frequency: FREQUENT
  description: >-
    Diffuse fundus hypopigmentation follows progressive choroidal melanocyte loss
    and is a marker of chronic or inadequately suppressed disease.
  phenotype_term:
    preferred_term: Sunset glow fundus
    term:
      id: HP:0007894
      label: Fundus hypopigmentation
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical features were as follows: uveitis (100%), sunset glow fundus
      (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia
      (31.4%).
    explanation: >-
      Sunset glow fundus occurred in 48.7% of 912 cases, supporting the FREQUENT
      band. Fundus hypopigmentation is the closest validated local HPO binding.
- category: Neurologic
  name: Meningeal Irritation
  description: >-
    Sterile meningeal involvement can cause meningismus with headache and neck
    or back stiffness during acute disease.
  phenotype_term:
    preferred_term: Non-infectious meningitis
    term:
      id: HP:0033430
      label: Non-infectious meningitis
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neurological manifestations include meningismus (headache and stiffness of
      the neck and back) with cerebrospinal fluid (CSF) lymphocytic pleocytosis.
    explanation: >-
      The review directly describes sterile meningeal symptoms and the associated
      inflammatory CSF finding.
- category: Neurologic
  name: CSF Pleocytosis
  frequency: VERY_FREQUENT
  description: >-
    Lymphocyte-predominant CSF pleocytosis supports neurologic involvement and can
    persist for weeks; it is supportive rather than required in every case.
  phenotype_term:
    preferred_term: CSF pleocytosis
    term:
      id: HP:0012229
      label: CSF pleocytosis
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cerebrospinal fluid pleocytosis with a predominance of lymphocytes,
      monocytes and normal glucose has been found in more than 80% of patients
      with VKH and may persist for up to eight weeks.
    explanation: >-
      More than 80% maps to the VERY_FREQUENT band; the passage also describes
      the cellular pattern and duration.
- category: Neurologic
  name: Headache
  frequency: FREQUENT
  description: >-
    Headache is a common neurologic manifestation, often accompanying meningismus
    in the prodromal phase.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical features were as follows: uveitis (100%), sunset glow fundus
      (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia
      (31.4%).
    explanation: >-
      Headache occurred in 49.2% of 912 cases, supporting the FREQUENT band.
- category: Sensory
  name: Tinnitus
  frequency: FREQUENT
  description: >-
    Tinnitus is a common audiovestibular manifestation, particularly around acute
    presentation.
  phenotype_term:
    preferred_term: Tinnitus
    term:
      id: HP:0000360
      label: Tinnitus
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical features were as follows: uveitis (100%), sunset glow fundus
      (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia
      (31.4%).
    explanation: >-
      Tinnitus occurred in 45.0% of 912 cases, supporting the FREQUENT band.
- category: Sensory
  name: Sensorineural Hearing Loss
  description: >-
    Cochlear hearing loss is an audiovestibular manifestation that often improves
    over several months.
  phenotype_term:
    preferred_term: Sensorineural hearing impairment
    term:
      id: HP:0000407
      label: Sensorineural hearing impairment
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The audiovestibular symptoms include sensorineural hearing loss, tinnitus,
      and vertigo.
    explanation: >-
      The review explicitly lists sensorineural hearing loss as a VKH
      audiovestibular manifestation.
- category: Dermatologic
  name: Vitiligo
  frequency: OCCASIONAL
  description: >-
    Cutaneous melanocyte loss produces vitiligo, usually during chronic or
    convalescent disease.
  phenotype_term:
    preferred_term: Vitiligo
    term:
      id: HP:0001045
      label: Vitiligo
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical features were as follows: uveitis (100%), sunset glow fundus
      (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia
      (31.4%).
    explanation: >-
      Vitiligo occurred in 11.4% of 912 cases, supporting the OCCASIONAL band.
- category: Dermatologic
  name: Poliosis
  frequency: OCCASIONAL
  description: >-
    Loss of pigmentation in eyebrows, eyelashes, or scalp hair appears mainly in
    chronic or convalescent disease.
  phenotype_term:
    preferred_term: Poliosis
    term:
      id: HP:0002290
      label: Poliosis
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Alopecia arose in 32.94% of subjects, poliosis in 20.8% and vitiligo in
      19.44%.
    explanation: >-
      Poliosis occurred in 20.8% in the cited Italian cohort, supporting the
      OCCASIONAL band while preserving population-specific variation.
- category: Dermatologic
  name: Alopecia
  frequency: FREQUENT
  description: >-
    Alopecia is an integumentary manifestation that usually develops during
    chronic recurrent disease.
  phenotype_term:
    preferred_term: Alopecia
    term:
      id: HP:0001596
      label: Alopecia
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical features were as follows: uveitis (100%), sunset glow fundus
      (48.7%), headache (49.2%), tinnitus (45.0%), vitiligo (11.4%), and alopecia
      (31.4%).
    explanation: >-
      Alopecia occurred in 31.4% of 912 cases, supporting the FREQUENT band.
- category: Ophthalmologic
  name: Visual Impairment
  description: >-
    Acute and chronic ocular inflammation can reduce best-corrected visual
    acuity; delayed control increases chronicity and complication risk.
  phenotype_term:
    preferred_term: Visual impairment
    term:
      id: HP:0000505
      label: Visual impairment
  evidence:
  - reference: PMID:38849758
    reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Initial best-corrected visual acuity (BCVA) examination at the first visit
      showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group
      and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002).
    explanation: >-
      Directly measured visual-acuity impairment was worse in the group that
      developed chronic recurrent disease.
biochemical:
- name: Aqueous humor CXCL13
  presence: INCREASED
  context: Active uveitis; research biomarker rather than a stand-alone diagnostic test
  specificity: >-
    Higher than Behçet disease and HLA-B27-associated uveitis in the cited
    comparisons, but not significantly different from sarcoidosis.
  readouts:
  - target: Persistent Subclinical Choroidal Inflammation
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: MONITORING
    interpretation: >-
      Elevated intraocular CXCL13 reports active inflammatory/B-cell chemotactic
      biology but is not specific enough to diagnose VKH independently.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The levels of CXCL13 were elevated 1423.6-fold in VKH disease, 298.3-fold
        in Behçet's disease, 107.1-fold in HLA-B27-associated uveitis and
        458.2-fold in sarcoidosis compared to controls
      explanation: >-
        The large elevation supports an inflammatory readout, while cross-disease
        elevation and overlap with sarcoidosis limit specificity and validation
        as a longitudinal monitoring marker.
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CXCL13 levels in VKH disease were significantly higher than the levels in
      Behçet's disease and HLA-B27-associated uveitis. However, CXCL13 levels did
      not differ significantly between VKH disease and sarcoidosis
    explanation: >-
      The comparative aqueous-humor studies support elevation while directly
      documenting the important sarcoidosis specificity limitation.
genetic:
- name: HLA-DRB1*04:05 susceptibility
  gene_term:
    preferred_term: HLA-DRB1
    term:
      id: hgnc:4948
      label: HLA-DRB1
  presence: Susceptibility allele
  association: HLA-DRB1*04:05 is associated with susceptibility to VKH and VKH-like immune-related uveitis.
  relationship_type: RISK_FACTOR
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:37604934
    reference_title: "HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Four patients with VKH-like uveitis underwent HLA genotyping and were all
      positive for HLA-DRB1*04:05. All 3 patients with non-VKH-like uveitis were
      negative for HLA-DRB1*04:05.
    explanation: >-
      The small ICI-associated uveitis series supports enrichment of
      HLA-DRB1*04:05 in the VKH-like form; it does not establish penetrance or
      causality in idiopathic VKH.
- name: PRKCD susceptibility locus
  gene_term:
    preferred_term: PRKCD
    term:
      id: hgnc:9399
      label: PRKCD
  presence: Susceptibility locus
  association: PRKCD rs74437127 alleles are associated with altered VKH susceptibility in a Chinese Han case-control cohort.
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C
      allele of CARD9 were associated with increased susceptibility of VKH
      (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10–5, OR = 1.810; Pc = 2.76 × 10–5,
      OR = 1.698, respectively).
    explanation: >-
      This human case-control study directly supports PRKCD as a susceptibility
      locus in the studied Han Chinese population; functional causality was not
      demonstrated.
- name: CARD9 susceptibility locus
  gene_term:
    preferred_term: CARD9
    term:
      id: hgnc:16391
      label: CARD9
  presence: Susceptibility locus
  association: CARD9 rs3812555 is associated with VKH susceptibility and increased inflammatory cytokine production.
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  evidence:
  - reference: PMID:36782298
    reference_title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We found an association between PRKCD rs74437127 and CARD9 rs3812555
      polymorphisms and VKH susceptibility and revealed that the increased
      susceptibility of rs3812555 for VKH may be mediated by regulating CARD9
      gene expression and the production of pro-inflammatory cytokines, such as
      TNF-α.
    explanation: >-
      This conclusion supports CARD9 as a susceptibility locus with a plausible
      cytokine-mediated functional correlate.
environmental:
- name: SARS-CoV-2 infection or vaccination
  presence: Reported trigger
  effect: Temporally associated with reported onset or relapse; causality is not established
  description: >-
    COVID-19 infection and SARS-CoV-2 vaccination have been reported before VKH
    onset or relapse. The association is treated as a trigger context rather
    than proof of a necessary cause.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The Coronavirus Disease 2019 (COVID-19) is a new contagious infection that
      might trigger the onset of VKH disease, as previously proposed for other
      viruses.
    explanation: >-
      The modal "might" supports a possible trigger association, not a causal
      or necessary exposure.
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Moreover, after the mass vaccination against SARS-CoV-2 worldwide, cases
      of VKH disease associated with COVID-19 vaccination have been reported.
    explanation: >-
      Published cases establish temporal reporting but cannot distinguish
      causation from background occurrence.
  influences_mechanisms:
  - target: HLA-DRB1-Restricted Melanocyte Antigen Recognition
    environmental_effect: PREDISPOSES
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Infection or vaccination may provide immune activation in a genetically
      susceptible host, but a reproducible antigenic or causal bridge to
      melanocyte-specific T-cell recognition has not been established.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Caution and a critical attitude about causal inference remain necessary
        about infections as triggers for VKH disease
      explanation: >-
        The review explicitly warns that infection associations do not establish
        causality, so this is a predisposing hypothesis rather than a trigger edge.
- name: Immune checkpoint inhibitor therapy
  exposure_term:
    preferred_term: immune checkpoint inhibitor exposure
    term:
      id: ECTO:9001737
      label: exposure to antineoplastic agent
  presence: Reported iatrogenic trigger
  effect: Can trigger VKH-like immune-related uveitis
  description: >-
    Immune checkpoint inhibitor therapy can be associated with VKH-like
    immune-related uveitis, especially in HLA-DRB1*04:05-positive patients.
  evidence:
  - reference: PMID:37604934
    reference_title: "HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Statistical analysis showed that HLA-DRB1*04:05 was significantly
      associated with developing VKH-like ICIU (P = 0.029).
    explanation: >-
      This case-series abstract supports the reported HLA-DRB1*04:05-associated
      VKH-like immune checkpoint inhibitor uveitis context.
  influences_mechanisms:
  - target: Th1 Effector Cytokine Response
    environmental_effect: TRIGGERS
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Checkpoint blockade can unleash excessive inflammatory T-cell responses and
      produce VKH-like uveitis in susceptible patients.
    evidence:
    - reference: PMID:37604934
      reference_title: "HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Immune checkpoint inhibitors (ICIs) activate anti-tumor activity by
        inhibiting immune checkpoint molecules that suppress inflammatory T-cell
        activity. However, ICIs can initiate excessive immune responses, thereby
        causing immune-related adverse events (irAEs).
      explanation: >-
        The source directly describes checkpoint blockade releasing inflammatory
        T-cell activity and causing immune-related adverse events; the VKH-like
        phenotype is supported by the same nine-case series.
progression:
- phase: Prodromal neurologic and auditory phase
  duration: 3-5 days
  notes: >-
    Nonspecific systemic symptoms, meningismus, headache, dizziness, orbital
    pain, photophobia, tearing, and scalp hypersensitivity can precede ocular
    inflammation; rare focal neurologic manifestations are reported.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Prodromal stage: This usually lasts for 3–5 days and is characterised by
      nonspecific symptoms, such as malaise, fever, nausea, headache,
      meningismus, dizziness and orbital pain
    explanation: >-
      The review directly states the stage duration and typical prodromal
      manifestations.
- phase: Acute uveitic phase
  duration: weeks
  notes: >-
    Acute VKH follows the prodrome by days and lasts weeks. Multifocal choroiditis
    causes posterior choroidal thickening, optic-disc hyperemia or edema, RPE
    breakdown, and potentially confluent serous retinal detachment; untreated
    inflammation can extend to granulomatous anterior uveitis.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Acute uveitic stage: This appears a few days after the prodromal phase and
      lasts for several weeks. During this period, the patient mainly complains of
      blurred vision, pain and central scotoma, and most patients present with
      bilateral posterior uveitis.
    explanation: >-
      The review directly defines the timing, duration, symptoms, and bilateral
      posterior inflammatory presentation of the acute phase.
- phase: Convalescent depigmentation phase
  duration: months to years
  notes: >-
    Uveal and integumentary depigmentation can emerge over months or years,
    including sunset glow fundus, vitiligo, and poliosis. These changes should
    not be assumed to represent biologically inactive convalescence because
    subclinical choroidal inflammation can persist.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Chronic (or convalescent) stage: This lasts for months or even years and
      results in integumentary and uveal depigmentation.
    explanation: >-
      The review directly states the stage duration and depigmenting outcome.
- phase: Chronic recurrent phase
  notes: >-
    Recurrent, mainly anterior granulomatous uveitis can coexist with active
    choroiditis detectable on ICGA or EDI-OCT. Cataract, glaucoma,
    neovascularization, and subretinal fibrosis accumulate in this phase; poor
    initial acuity, older onset, and sunset glow fundus are prognostic signals in
    retrospective data.
  evidence:
  - reference: PMID:38849758
    reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Poor initial BCVA (P = 0.046) and the occurrence of “sunset glow fundus”
      (P = 0.040) were significantly associated with progression to the chronic
      recurrent phase.
    explanation: >-
      This retrospective cohort identifies clinical predictors of chronic
      recurrent VKH.
diagnosis:
- name: Clinical Classification Criteria and Mandatory Exclusions
  description: >-
    No single test establishes VKH. Revised Diagnostic Criteria classify
    complete, incomplete, and probable disease, while SUN criteria distinguish
    early- and late-stage patterns. A compatible presentation requires exclusion
    of antecedent ocular trauma or vitreoretinal surgery, treponemal infection,
    and sarcoidosis.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: >-
    Early SUN classification uses bilateral retinal detachment or characteristic
    uveitis with at least two neurologic/auditory findings; late classification
    uses sunset glow fundus or characteristic uveitis with at least one cutaneous
    depigmenting finding.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      There is no single diagnostic test for VKH disease, and its diagnosis is
      mainly based on clinical features and either systemic or ocular findings.
    explanation: >-
      The review explicitly states that diagnosis is syndromic rather than based
      on one definitive assay.
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      According to SUN, early-stage features include bilateral retinal detachment
      or characteristic uveitis with at least two of the following neurological
      criteria: headache, dysacusis, meningism, pleocytosis of the cerebrospinal
      fluid and tinnitus. Late-stage features include sunset glow fundus or
      characteristic uveitis with at least one of the following cutaneous
      findings: vitiligo, poliosis or alopecia.
    explanation: >-
      This passage directly supports the detailed early- and late-stage SUN
      classification algorithm summarized in the results field.
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is also mandatory to exclude previous ocular trauma, vitreoretinal
      surgery and positive treponemal syphilis serology or evidence of sarcoidosis
    explanation: >-
      The SUN summary specifies the mandatory exclusions that separate VKH from
      major infectious, granulomatous, and post-traumatic mimics.
- name: Fluorescein and Indocyanine Green Angiography
  description: >-
    Fluorescein angiography identifies early pinpoint hyperfluorescence followed
    by leakage and subretinal pooling. ICGA detects diffuse hypercyanescence,
    delayed choroidal perfusion, and hypocyanescent stromal inflammatory foci,
    including occult choroidal activity.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: >-
    Concordant angiographic evidence supports diffuse choroiditis and maps the
    extent and activity of inflammation.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fluorescein angiography (FAG), in the early stage of the disease, shows
      multifocal choroiditis with multiple areas of early pinpoint
      hyperfluorescence followed by late leakage and pooling at the intraretinal
      or subretinal fluid level.
    explanation: >-
      The review directly describes the characteristic early fluorescein pattern.
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In the initial phase, ICGA demonstrates a diffuse hypercyanescence, and in
      the intermediate and late phases, delayed choroidal perfusion and
      hypocyanescent lesions represent choroidal stromal inflammatory foci that
      cannot be highlighted by an ophthalmoscopic examination
    explanation: >-
      ICGA detects choroidal stromal inflammation that can be invisible on direct
      fundus examination.
- name: EDI-OCT and OCT Angiography
  description: >-
    EDI-OCT and OCT measure choroidal thickening even without serous detachment
    and can monitor treatment response. OCT angiography noninvasively shows
    reduced vessel density and focal vascular dropout in active inflammation.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: >-
    Choroidal thickness and vascular-density changes support early diagnosis and
    longitudinal inflammatory monitoring but are interpreted with the full
    clinical syndrome.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EDI and OCT have demonstrated choroidal thickening in patients with
      early-stage VKH, even if a serous detachment is absent.
    explanation: >-
      The review identifies a diagnostic imaging abnormality that can precede or
      occur without serous detachment.
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      During the active phase, OCT-A demonstrates decreased choroidal and retinal
      vessel density, similar to the changes detectable with FAG, and focal dropout
      that corresponds to the inflammation areas
    explanation: >-
      The review directly describes active-phase OCT-A vascular readouts.
- name: Cerebrospinal Fluid Examination
  description: >-
    Lumbar-puncture evidence of lymphocyte-predominant pleocytosis supports
    neurologic involvement and is one of the SUN early-stage neurologic criteria;
    absence does not exclude VKH.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: Lymphocyte-predominant pleocytosis with normal glucose may persist for up to eight weeks.
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cerebrospinal fluid pleocytosis with a predominance of lymphocytes,
      monocytes and normal glucose has been found in more than 80% of patients
      with VKH and may persist for up to eight weeks.
    explanation: >-
      The review describes the supportive CSF profile, frequency, and duration.
differential_diagnoses:
- name: Sympathetic ophthalmia
  disease_term:
    preferred_term: sympathetic ophthalmia
    term:
      id: MONDO:0019198
      label: sympathetic ophthalmia
  description: >-
    Sympathetic ophthalmia can closely mimic bilateral granulomatous panuveitis
    and choroiditis, but follows penetrating ocular trauma or intraocular surgery.
  distinguishing_features:
  - Antecedent penetrating ocular trauma or vitreoretinal surgery
  - Inflammation of the fellow eye after disruption of ocular immune privilege
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is also mandatory to exclude previous ocular trauma, vitreoretinal
      surgery and positive treponemal syphilis serology or evidence of sarcoidosis
    explanation: >-
      The SUN summary makes prior trauma or vitreoretinal surgery a mandatory
      exclusion; this distinguishes the post-traumatic mimic sympathetic
      ophthalmia, although the quoted passage does not name it explicitly.
- name: Ocular syphilis
  disease_term:
    preferred_term: syphilis
    term:
      id: MONDO:0005976
      label: syphilis
  description: >-
    Ocular syphilis can present with inflammatory posterior-segment findings and
    must be excluded before assigning a noninfectious autoimmune diagnosis.
  distinguishing_features:
  - Positive treponemal serology
  - Infectious disease requiring antimicrobial rather than primary immunosuppressive treatment
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is also mandatory to exclude previous ocular trauma, vitreoretinal
      surgery and positive treponemal syphilis serology or evidence of sarcoidosis
    explanation: >-
      Positive treponemal serology is a mandatory SUN exclusion for VKH.
- name: Sarcoidosis
  disease_term:
    preferred_term: sarcoidosis
    term:
      id: MONDO:0019338
      label: sarcoidosis
  description: >-
    Sarcoidosis is a granulomatous systemic disease that can cause uveitis and
    overlap clinically with VKH.
  distinguishing_features:
  - Systemic or imaging evidence of sarcoidosis
  - Granulomatous inflammation not defined by the VKH melanocyte-targeted multisystem pattern
  evidence:
  - reference: PMID:37834885
    reference_title: Vogt-Koyanagi-Harada Disease and COVID.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It is also mandatory to exclude previous ocular trauma, vitreoretinal
      surgery and positive treponemal syphilis serology or evidence of sarcoidosis
    explanation: >-
      Evidence of sarcoidosis is a mandatory SUN exclusion for VKH.
treatments:
- name: Early Systemic Corticosteroids
  action_category: THERAPEUTIC
  description: >-
    High-dose systemic corticosteroids are used early to suppress acute ocular
    and systemic inflammation, commonly followed by early immunomodulatory
    therapy to reduce chronic progression risk.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: corticosteroid
      term:
        id: CHEBI:50858
        label: corticosteroid
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  target_mechanisms:
  - target: Granulomatous Choroidal Inflammation
    treatment_effect: INHIBITS
    description: >-
      High-dose systemic corticosteroids suppress acute intraocular and choroidal
      inflammation; adequate duration and early steroid-sparing therapy are
      important because corticosteroids alone may not prevent chronic evolution.
    evidence:
    - reference: PMID:37834885
      reference_title: Vogt-Koyanagi-Harada Disease and COVID.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In the initial phase, VKH usually responds to high-dose systemic
        corticosteroid therapy.
      explanation: >-
        The review directly supports acute inflammatory response to high-dose
        systemic corticosteroids.
  evidence:
  - reference: PMID:37204477
    reference_title: "Immunosuppressive therapy for Vogt-Koyanagi-Harada disease: a retrospective study and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment is usually initiated with corticosteroids followed by an early
      introduction of immunosuppressive treatment (IMT) to achieve immediate
      response after disease presentation, although the choice of IMT for VKH
      can vary.
    explanation: >-
      This clinical review supports systemic corticosteroids as the initial VKH
      treatment backbone.
- name: Combined Immunomodulatory Therapy
  action_category: THERAPEUTIC
  description: >-
    Conventional steroid-sparing immunomodulatory therapy, including agents such
    as mycophenolate mofetil or cyclosporine, is used with low-dose steroids to
    stabilize disease and preserve vision.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: mycophenolate mofetil
      term:
        id: CHEBI:8764
        label: mycophenolate mofetil
    - preferred_term: cyclosporin A
      term:
        id: CHEBI:4031
        label: cyclosporin A
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  target_mechanisms:
  - target: Persistent Subclinical Choroidal Inflammation
    treatment_effect: INHIBITS
    description: >-
      Early mycophenolate or other steroid-sparing immunomodulation is used to
      control clinically overt and subclinical choroidal inflammation and reduce
      chronic recurrent evolution.
    evidence:
    - reference: PMID:34869409
      reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        addition of immunomodulatory therapy with mycophenolate mofetil as
        first-line therapy combined with systemic corticosteroids in patients
        with initial-onset acute uveitis associated with VKH disease prevented
        the progression of the disease to chronic recurrent evolution and
        development of complications and “sunset glow fundus.”
      explanation: >-
        Prospective treatment observations support suppression of the chronic
        inflammatory route and its depigmenting complications.
  evidence:
  - reference: PMID:37204477
    reference_title: "Immunosuppressive therapy for Vogt-Koyanagi-Harada disease: a retrospective study and review of literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      81% (21 of 26 patients) of our patients treated with combined IMT/steroid
      were able to achieve disease stability with significant good visual
      outcome at 24 months (Median VApre-IMT = 0.3 Logmar vs VApost-IMT = 0.0
      Logmar, p = 0.0001).
    explanation: >-
      This retrospective clinical series supports combined immunomodulatory
      therapy and low-dose steroid treatment for VKH disease stability.
  - reference: PMID:37355662
    reference_title: A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, we report that combined with a non-standard corticosteroid regimen,
      cyclosporine-based immunosuppressant strategy is non-inferior to
      adalimumab-based biologic strategy by 26 weeks for visual improvement in a
      cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a
      late-phase disease.
    explanation: >-
      The randomized non-inferiority trial supports cyclosporine-based
      conventional immunosuppression as an evidence-backed therapeutic strategy.
- name: Adalimumab Biologic Therapy
  action_category: THERAPEUTIC
  description: >-
    Adalimumab, an anti-TNF monoclonal antibody, is used for refractory or
    chronic recurrent VKH and is under study for acute VKH in combination with
    glucocorticoids.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: adalimumab
      term:
        id: NCIT:C65216
        label: Adalimumab
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  target_mechanisms:
  - target: CARD9-Associated Pro-inflammatory Cytokine Amplification
    treatment_effect: INHIBITS
    description: >-
      Adalimumab inhibits TNF-alpha, a cytokine implicated in ocular inflammatory
      chemokine, adhesion-molecule, and cytokine networks. The treatment evidence
      supports TNF-pathway inhibition but does not prove CARD9 dependence of
      response.
    evidence:
    - reference: PMID:38849758
      reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Tumor necrosis factor-alpha (TNF-α) has played a crucial role in the
        development of chemokines, adhesion molecules, and cytokines associated
        with ocular inflammation
      explanation: >-
        The source provides the TNF-alpha inflammatory rationale; observed
        adalimumab response is documented in the treatment-level evidence below.
  evidence:
  - reference: PMID:38849758
    reference_title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ADA significantly reduced anterior chamber inflammatory cells (P = 0.000)
      and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent
      group, and markedly decreased the recurrence rate in VKH patients (P = 0.009).
    explanation: >-
      This retrospective cohort directly supports adalimumab efficacy in chronic
      recurrent VKH.
- name: Janus Kinase Inhibitor Therapy
  action_category: THERAPEUTIC
  description: >-
    JAK inhibitors are an emerging option for refractory non-infectious ocular
    inflammatory disease; available evidence includes a prospective registry
    cohort with one VKH patient, so this is promising but not VKH-specific
    definitive evidence.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: baricitinib
      term:
        id: CHEBI:95341
        label: baricitinib
    - preferred_term: tofacitinib
      term:
        id: CHEBI:71200
        label: tofacitinib
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  evidence:
  - reference: PMID:39247640
    reference_title: "Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Ocular inflammation was related to a systemic disease in 8 (66.7%)
      patients as follows: spondyloarthritis (n = 3), peripheral psoriatic
      arthritis (n = 1), rheumatoid arthritis (n = 1), antinuclear antibodies
      (ANA) positive juvenile idiopathic arthritis (n = 1), Behçet’s syndrome
      (n = 1), Vogt-Koyanagi-Harada syndrome (n = 1).
    explanation: >-
      The prospective registry includes a VKH case among non-infectious ocular
      inflammatory diseases, so it partially supports JAK inhibitor relevance
      without establishing VKH-specific efficacy.
clinical_trials:
- name: NCT03399175
  phase: NOT_APPLICABLE
  status: RECRUITING
  description: >-
    Prospective study of early systemic high-dose corticosteroid and
    immunosuppressive therapy from VKH disease onset with multimodal clinical
    follow-up.
  notes: >-
    ClinicalTrials.gov status checked 2026-08-08: RECRUITING; estimated
    enrollment 40. Registry fields can change and should be rechecked before
    operational use.
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  evidence:
  - reference: clinicaltrials:NCT03399175
    reference_title: "Influência de imunomodulação Precoce Influence of Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease: a Prospective Study"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This prospective study will include patients with Vogt-Koyanagi-Harada
      disease from disease onset, treated with early systemic high-dose
      corticosteroid and immunosuppressive therapy.
    explanation: >-
      ClinicalTrials.gov identifies this VKH study of early systemic
      corticosteroid plus immunosuppressive therapy.
- name: NCT05590416
  phase: NOT_APPLICABLE
  status: UNKNOWN
  description: >-
    Observational study of adalimumab treatment in acute Vogt-Koyanagi-Harada
    disease.
  notes: >-
    ClinicalTrials.gov status checked 2026-08-08: UNKNOWN, with an estimated
    enrollment of 15 and last posted update dated 2024-07-03. UNKNOWN is retained
    rather than inferring active recruitment from the study description.
  target_phenotypes:
  - preferred_term: Panuveitis
    term:
      id: HP:0012121
      label: Panuveitis
  evidence:
  - reference: clinicaltrials:NCT05590416
    reference_title: An Observational Study of Adalimumab in the Treatment of Acute Vogt-Koyanagi-Harada Disease
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This project is designed to test the hypothesis that adalimumab is
      clinically useful for patients with acuta Vogt-Koyanagi-Harada disease
    explanation: >-
      ClinicalTrials.gov identifies an acute VKH observational study of
      adalimumab.
animal_models:
- species: Gallus gallus
  genotype: Smyth line autoimmune-vitiligo-prone chicken
  description: >-
    Smyth-line chickens spontaneously develop autoimmune vitiligo; a subset also
    develops uveitis and visual impairment with choroidal melanocyte loss,
    mononuclear infiltration, and an IFN-gamma-polarized Th1 response. This is a
    mechanistically relevant spontaneous pigmentation-autoimmunity model that
    resembles VKH, not a model that recapitulates the full human diagnostic
    syndrome.
  associated_phenotypes:
  - Autoimmune vitiligo
  - Uveitis
  - Choroidal melanocyte loss
  - Visual impairment
  evidence:
  - reference: PMID:35547230
    reference_title: Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      The immunopathogenesis in SL vision impairment resembles human
      vitiligo-associated ocular diseases, especially Vogt-Koyanagi-Harada
      syndrome and sympathetic ophthalmia.
    explanation: >-
      The authors explicitly identify the ocular autoimmune phenotype as
      resembling VKH while also delimiting it as a cross-disease model.
  - reference: PMID:35547230
    reference_title: Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Specifically, as in active SLV, the loss of choroidal melanocytes is
      associated with an INF-γ polarized, Th1 cell-mediated immune response and
      aberrant melanocyte function.
    explanation: >-
      The model reproduces the choroidal melanocyte-loss and Th1/IFN-gamma arm of
      the curated human mechanism; the source spells interferon as "INF-γ."
references:
- reference: PMID:16723469
  title: Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
  findings: []
- reference: PMID:34869409
  title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
  findings: []
- reference: PMID:36782298
  title: Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
  findings: []
- reference: PMID:37834885
  title: Vogt-Koyanagi-Harada Disease and COVID.
  findings: []
- reference: PMID:37355662
  title: A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.
  findings: []
- reference: PMID:37604934
  title: "HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors."
  findings: []
- reference: PMID:38849758
  title: Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
  findings: []
- reference: PMID:37204477
  title: "Immunosuppressive therapy for Vogt-Koyanagi-Harada disease: a retrospective study and review of literature."
  findings: []
- reference: PMID:39247640
  title: "Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries."
  findings: []
- reference: PMID:35547230
  title: Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo.
  findings: []
- reference: clinicaltrials:NCT03399175
  title: "Influência de imunomodulação Precoce Influence of Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease: a Prospective Study"
  findings: []
- reference: clinicaltrials:NCT05590416
  title: An Observational Study of Adalimumab in the Treatment of Acute Vogt-Koyanagi-Harada Disease
  findings: []
datasets:
- accession: geo:GSE148020
  title: Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease
  description: Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11259 human circulating monocytes and genetically defined their subpopulations.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 6
  notes: Identified by GEO DataSets index search for Vogt-Koyanagi-Harada Disease (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
discussions:
- discussion_id: gap_vkh_environmental_trigger_causality
  prompt: >-
    Do viral infection, vaccination, or molecular mimicry reproducibly initiate
    melanocyte-antigen-specific T-cell autoimmunity in genetically susceptible
    people, or are the reported temporal associations coincidental or
    disease-unmasking events?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#HLA-DRB1-Restricted Melanocyte Antigen Recognition
  - environmental#SARS-CoV-2 infection or vaccination
  rationale: >-
    Patient-derived T cells recognize tyrosinase and gp100, and some clones in
    one study cross-recognized a cytomegalovirus peptide, but this does not show
    that infection preceded or caused human disease. COVID-19 infection and
    vaccination reports are primarily temporal case observations. Prospective
    exposure ascertainment, population denominators, pre-onset immune samples,
    and antigen-specific clonotype tracking would be needed to distinguish a
    causal trigger from background occurrence or immune unmasking.
  evidence:
  - reference: PMID:34869409
    reference_title: New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Efforts to corroborate the latter findings failed so far and the ensemble
      of such studies cautions that an association does not necessarily represent
      a cause
    explanation: >-
      The review explicitly identifies the unresolved distinction between
      infection association and causation.
review_notes: >-
  Completeness and claim-evidence review performed 2026-08-08 after consuming
  the Falcon deep-research report and its citation sidecar. DOI citations with
  available PubMed records were migrated to PMID caches so exact snippets could
  be checked. A D2P comparison surfaced numerous ORDO-only features, including
  nonspecific or apparently conflated findings such as short stature and
  cognitive impairment; these were not imported without independent VKH-specific
  evidence. Directly supported additions were limited to core ocular,
  neurologic, auditory, integumentary, diagnostic, histopathologic, biomarker,
  and model-system findings. The GEO dataset is retained as a discoverable
  resource without treating its uncited metadata summary as claim-level evidence.
📚

References & Deep Research

References

12
PMID:16723469
Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.
No top-level findings curated for this source.
PMID:34869409
New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease.
No top-level findings curated for this source.
PMID:36782298
Genetic association of PRKCD and CARD9 polymorphisms with Vogt-Koyanagi-Harada disease in the Chinese Han population.
No top-level findings curated for this source.
PMID:37834885
Vogt-Koyanagi-Harada Disease and COVID.
No top-level findings curated for this source.
PMID:37355662
A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.
No top-level findings curated for this source.
PMID:37604934
HLA-DRB1*04:05 is involved in the development of Vogt-Koyanagi-Harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors.
No top-level findings curated for this source.
PMID:38849758
Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease.
No top-level findings curated for this source.
PMID:37204477
Immunosuppressive therapy for Vogt-Koyanagi-Harada disease: a retrospective study and review of literature.
No top-level findings curated for this source.
PMID:39247640
Efficacy and safety of Janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international AIDA network registries.
No top-level findings curated for this source.
PMID:35547230
Immune Activities in Choroids of Visually Impaired Smyth Chickens With Autoimmune Vitiligo.
No top-level findings curated for this source.
clinicaltrials:NCT03399175
Influência de imunomodulação Precoce Influence of Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease: a Prospective Study
No top-level findings curated for this source.
clinicaltrials:NCT05590416
An Observational Study of Adalimumab in the Treatment of Acute Vogt-Koyanagi-Harada Disease
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 47 citations 2026-05-11T09:24:35.162671

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Vogt-Koyanagi-Harada Disease
  • MONDO ID: (if available)
  • Category: Autoimmune

Research Objectives

Please provide a comprehensive research report on Vogt-Koyanagi-Harada Disease covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Vogt–Koyanagi–Harada (VKH) Disease — Comprehensive Disease Characteristics Report (Autoimmune)

Target disease

  • Disease name: Vogt–Koyanagi–Harada disease (VKH)
  • Category: Autoimmune, multisystem inflammatory disease
  • MONDO ID: MONDO_0018092 (OpenTargets disease record) (OpenTargets Search: Vogt-Koyanagi-Harada disease)

Executive summary

VKH is a T cell–driven autoimmune disorder targeting melanocyte-associated antigens in melanin-containing tissues (uvea/choroid, meninges, inner ear, skin/hair), presenting most prominently as bilateral granulomatous uveitis with characteristic choroidal inflammation and exudative retinal detachment, and variably neurologic/auditory and integumentary manifestations. Contemporary management emphasizes early, aggressive systemic corticosteroids combined with early immunomodulatory therapy to prevent progression to chronically evolving disease with “sunset glow fundus” and recurrent inflammation; biologics (e.g., anti‑TNF) and newer small molecules (e.g., JAK inhibitors) are increasingly used for refractory disease. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, rahman2023immunosuppressivetherapyfor pages 1-2, vitale2024efficacyandsafety pages 1-2)

1. Disease information

1.1 Definition and current understanding

A recent 2024 editorial defines VKH as “a multisystemic autoimmune disorder that affects the eyes, central nervous system, the auditory system, and the integumentary system,” driven by an autoimmune reaction against melanocyte-associated antigens across these tissues. (Published online 2024‑04‑24; URL: https://doi.org/10.1080/09273948.2024.2331401) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

A 2023 COVID-era review similarly describes VKH as “a rare multisystem inflammatory autoimmune disease affecting eyes, ears, brain, skin and hair,” and frames the core immunopathology as T‑cell mediated autoimmunity directed against choroidal melanocytes and melanocyte antigens (e.g., tyrosinase, TRP1/2, MART‑1, gp100). (Published 2023‑09; URL: https://doi.org/10.3390/jcm12196242) (manni2023vogtkoyanagiharadadiseaseand pages 1-2)

1.2 Key identifiers

  • MONDO: MONDO_0018092 (OpenTargets Search: Vogt-Koyanagi-Harada disease)
  • MeSH / ICD‑10 / ICD‑11 / Orphanet: Not extractable from the retrieved full texts in this run; VKH is present as a MeSH term in ClinicalTrials.gov metadata for VKH-related studies (NCT05590416 chunk 2).

1.3 Synonyms / alternative names

  • Vogt–Koyanagi–Harada disease
  • Vogt–Koyanagi–Harada syndrome
  • Harada disease (often used in ophthalmology contexts) (Use of “syndrome” is explicit in multiple sources) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, vitale2024efficacyandsafety pages 1-2)

1.4 Evidence source type

This report is derived from aggregated disease-level resources (reviews/editorials, clinical trial registries) and primary human studies (genetic case–control, randomized trial, retrospective cohorts), plus experimental model systems (rodent and avian models). (zhou2023geneticassociationof pages 1-2, zhong2023arandomizednoninferiority pages 3-4, adamus2002experimentalautoimmuneuveitides pages 1-3, sorrick2022immuneactivitiesin pages 1-2)

2. Etiology

2.1 Disease causal factors (mechanistic)

Core concept: VKH is an autoimmune response against melanocyte-associated antigens.

Human immunology evidence supports antigen-specific T cell reactivity: ocular-infiltrating and peripheral CD4+ T cells from VKH patients recognize melanocyte peptides (tyrosinase and gp100) in an HLA-DR4 (including HLA‑DRB1*0405) restricted manner and produce inflammatory mediators (e.g., IFN‑γ, RANTES). (sugita2006ocularinfiltratingcd4+ pages 1-2, sugita2006ocularinfiltratingcd4+ pages 7-8)

2.2 Risk factors

2.2.1 Genetic risk factors

HLA risk and immunogenetic predisposition - In immune checkpoint inhibitor–associated uveitis, VKH-like presentations were strongly associated with HLA‑DRB1*04:05: “Four patients with VKH-like uveitis underwent HLA genotyping and were all positive for HLA‑DRB104:05… Statistical analysis showed that HLA‑DRB104:05 was significantly associated with developing VKH-like ICIU (P = 0.029).” (Published 2023‑08; URL: https://doi.org/10.1038/s41598-023-40565-z) (takeuchi2023hladrb1*0405isinvolved pages 1-2)

Non-HLA susceptibility loci (recent primary human genetics, 2023) - In a large Chinese Han case–control study (912 VKH, 878 controls), PRKCD and CARD9 polymorphisms were associated with VKH susceptibility. The abstract states: “We found that rs74437127 C allele of PRKCD… and C allele of CARD9 were associated with increased susceptibility of VKH… Functional studies… revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production…” (Published 2023‑02; URL: https://doi.org/10.1186/s40246-023-00459-7) (zhou2023geneticassociationof pages 1-2) - PRKCD rs74437127 C allele: Pc=0.020, OR=1.624 (95% CI 1.200–2.199) (zhou2023geneticassociationof pages 1-2) - CARD9 rs3812555 CC genotype: Pc=2.04×10^-5, OR=1.810 (95% CI 1.418–2.311) (zhou2023geneticassociationof pages 1-2) - Functional correlate: rs3812555 CC carriers had higher CARD9 mRNA and higher TNF‑α production (P=1.00×10^-4; P=2.00×10^-3) (zhou2023geneticassociationof pages 1-2)

2.2.2 Environmental / infectious / iatrogenic triggers

  • Viral triggers and molecular mimicry are repeatedly proposed; in VKH, melanocyte antigen–specific T cells can show cross-reactivity with a CMV peptide, supporting a plausible mimicry mechanism. (sugita2006ocularinfiltratingcd4+ pages 7-8)

SARS‑CoV‑2 infection and COVID‑19 vaccination (2023–2024 focus) - A 2023 review summarizes reported VKH onset/relapse after COVID‑19 infection/vaccination and notes VKH is “one of the most frequently reported uveitic entities after COVID‑19 vaccination,” while emphasizing good response to therapy. (Published 2023‑09; URL: https://doi.org/10.3390/jcm12196242) (manni2023vogtkoyanagiharadadiseaseand pages 1-2) - A focused 2023 case-series review of vaccine-associated VKH included 21 patients and reported a mean onset interval of 7.5 days (range 12 h to 4 weeks), frequent bilateral involvement (20/21), meningitis symptoms (16/21), and frequent serous retinal detachment (16/21) and choroidal thickening (14/21). (Published 2023‑06; URL: https://doi.org/10.1080/21645515.2023.2220630) (manni2023vogtkoyanagiharadadiseaseand pages 2-4) - A 2024 Japanese center study found higher clinic-based prevalence among new patients after the COVID-19 state-of-emergency declaration, but similar visual acuity and recurrence outcomes after pulse steroids. (Published 2024‑06; URL: https://doi.org/10.1038/s41598-024-63957-1) (muto2024effectofthe pages 6-7)

Immune checkpoint inhibitors (ICIs) - ICI-associated uveitis occurs in ~0.3–1% of ICI-treated patients, and VKH-like posterior/panuveitis can occur with choroidal thickening and serous subretinal fluid. (takeuchi2023hladrb1*0405isinvolved pages 1-2)

2.3 Protective factors

No specific genetic or environmental protective factors are established as clinical recommendations; however, specific alleles/genotypes in the PRKCD/CARD9 study were statistically associated with reduced susceptibility (e.g., PRKCD rs74437127 T allele OR=0.616; CARD9 rs3812555 T allele OR=0.589), which may be viewed as candidate protective associations rather than proven protective mechanisms. (zhou2023geneticassociationof pages 1-2)

2.4 Gene–environment interaction

The prevailing model is genetic susceptibility (notably HLA-DR4-related) plus an environmental/infectious/iatrogenic trigger (e.g., viral infection, vaccination, ICI-mediated immune disinhibition) leading to loss of tolerance to melanocyte antigens. This interaction is explicitly invoked in COVID-era synthesis and in ICI-associated VKH-like uveitis. (manni2023vogtkoyanagiharadadiseaseand pages 1-2, takeuchi2023hladrb1*0405isinvolved pages 1-2)

3. Phenotypes (clinical spectrum)

3.1 Clinical stages / temporal development

Four phases are classically described: 1) Prodromal (neurologic/auditory symptoms; CSF pleocytosis), 2) Acute uveitic (diffuse choroiditis → papilledema/exudative detachments; may evolve to panuveitis), 3) Convalescent (depigmentation; vitiligo/poliosis/alopecia), 4) Chronic recurrent (chronic recurrent granulomatous anterior uveitis; less commonly recurrent exudative detachments). (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

A COVID-era review notes the prodromal phase is often ~3–5 days and the acute uveitic stage lasts weeks with bilateral posterior uveitis and choroidal thickening/serous detachments. (manni2023vogtkoyanagiharadadiseaseand pages 2-4)

3.2 Phenotype frequencies from a large cohort (recent primary data)

In the Chinese Han VKH cohort (n=912), reported frequencies included: uveitis 100%, sunset glow fundus 48.7%, headache 49.2%, tinnitus 45.0%, vitiligo 11.4%, alopecia 31.4%. (zhou2023geneticassociationof pages 1-2)

3.3 Key phenotype types (examples) and suggested ontology terms

Below are representative phenotype mappings (not exhaustive).

Ocular - Bilateral granulomatous panuveitis / diffuse choroiditis (HPO: Uveitis; Choroiditis; Panuveitis). (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, manni2023vogtkoyanagiharadadiseaseand pages 2-4) - Exudative/serous retinal detachment (HPO: Retinal detachment; often “serous retinal detachment”) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, manni2023vogtkoyanagiharadadiseaseand pages 2-4) - Choroidal thickening (HPO candidate: Abnormal choroid morphology / Choroidal thickening). (manni2023vogtkoyanagiharadadiseaseand pages 16-19, tugaltutkun2024vogtkoyanagiharadadisease pages 1-3) - “Sunset glow fundus” (clinical sign; HPO candidate: Abnormal fundus pigmentation). (feng2024predictivefactorsand pages 1-2, zhou2023geneticassociationof pages 1-2)

Neurologic - Headache; aseptic meningitis / meningeal symptoms (HPO: Headache; Meningitis; Cerebrospinal fluid pleocytosis) (manni2023vogtkoyanagiharadadiseaseand pages 2-4, zhou2023geneticassociationof pages 1-2)

Auditory - Tinnitus (HPO: Tinnitus) (zhou2023geneticassociationof pages 1-2)

Integumentary - Vitiligo, poliosis, alopecia (HPO: Vitiligo; Poliosis; Alopecia) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, zhou2023geneticassociationof pages 1-2)

3.4 Anatomical structures affected (UBERON suggestions)

  • Eye uvea/choroid (UBERON: uvea, choroid) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
  • Meninges / CNS coverings (UBERON: meninges) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
  • Inner ear / auditory system (UBERON: inner ear) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
  • Skin and hair follicles (UBERON: skin, hair follicle) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

3.5 Cell types involved (CL suggestions)

  • CD4+ T cell (CL: T-helper cell) (sugita2006ocularinfiltratingcd4+ pages 1-2)
  • Th1‑polarized effector/memory CD4+ T cells (CL: effector memory T cell; functional subtype) (sugita2006ocularinfiltratingcd4+ pages 7-8)
  • Macrophage (CL: macrophage) (supported by animal-model infiltrates) (sorrick2022immuneactivitiesin pages 1-2)
  • B cell (CL: B cell) (supported by animal-model infiltrates and B-cell involvement in chronic disease) (sorrick2022immuneactivitiesin pages 1-2, elasrar2021newperspectiveson pages 1-2)

4. Genetic / molecular information

4.1 “Causal” genes

VKH is not a Mendelian disorder with a single causal gene in the retrieved evidence; it is best characterized as multifactorial/polygenic with strong HLA associations and multiple immune pathway loci.

4.2 Susceptibility variants (recent primary evidence)

  • PRKCD rs74437127: C allele risk (OR 1.624) and T allele protective (OR 0.616) (zhou2023geneticassociationof pages 1-2)
  • CARD9 rs3812555: CC genotype risk (OR 1.810), C allele risk (OR 1.698), with functional association to higher CARD9 mRNA and TNF‑α. (zhou2023geneticassociationof pages 1-2)

4.3 Molecular pathophysiology (causal chain)

1) Predisposition (e.g., HLA‑DRB104:05 and other genetic factors) → 2) Trigger (viral infection/vaccination or iatrogenic immune disinhibition with ICIs) → 3) Antigen presentation and loss of tolerance to melanocyte antigens (e.g., tyrosinase/gp100) → 4) Effector inflammation in choroid/uvea with cytokine production (TNF‑α, IFN‑γ; Th1/Th17 signatures) → 5) Tissue damage and melanocyte loss* leading to ocular exudation/detachments acutely and depigmentation (sunset glow fundus; vitiligo/poliosis/alopecia) chronically. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, sugita2006ocularinfiltratingcd4+ pages 1-2, zhou2023geneticassociationof pages 1-2, manni2023vogtkoyanagiharadadiseaseand pages 1-2)

4.4 GO biological process suggestions

  • T cell activation; antigen processing and presentation (MHC class II); cytokine-mediated signaling; inflammatory response; leukocyte migration/chemotaxis (supported by RANTES and IFN‑γ responses) (sugita2006ocularinfiltratingcd4+ pages 7-8, sugita2006ocularinfiltratingcd4+ pages 1-2)

5. Environmental information

Key non-genetic contributors described in the retrieved evidence include viral infections and vaccinations as plausible triggers, particularly highlighted in COVID-era literature, and iatrogenic triggers such as immune checkpoint inhibitors. (manni2023vogtkoyanagiharadadiseaseand pages 1-2, takeuchi2023hladrb1*0405isinvolved pages 1-2)

6. Mechanism / pathophysiology (expanded)

6.1 Immune system involvement

  • VKH is characterized by melanocyte antigen–directed CD4+ T cell responses (Th1-like functional profile) and inflammatory mediator production (e.g., IFN‑γ; RANTES). (sugita2006ocularinfiltratingcd4+ pages 1-2, sugita2006ocularinfiltratingcd4+ pages 7-8)
  • CARD9 risk genotype correlates with increased TNF‑α production, linking innate/adaptive signaling nodes to inflammatory cytokine output in VKH susceptibility. (zhou2023geneticassociationof pages 1-2)

6.2 Expert synthesis (therapeutic window concept)

A 2021 mechanistic treatment review argues that early high-dose corticosteroids alone may be insufficient to prevent chronic evolution and emphasizes early combination therapy (e.g., corticosteroids + mycophenolate mofetil) as a “window of opportunity” to prevent chronically evolving disease; it also highlights B cell involvement in chronic disease, supported by responsiveness to rituximab in refractory cases. (URL: https://doi.org/10.3389/fmed.2021.705796; publication 2021‑11) (elasrar2021newperspectiveson pages 1-2)

7. Anatomical structures affected

Primary involved structures include the uveal tract (notably choroid), with systemic involvement in meninges, inner ear, and integumentary tissues (skin/hair) as described in modern reviews and classification discussions. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, manni2023vogtkoyanagiharadadiseaseand pages 1-2)

8. Temporal development

  • Typical onset: Most commonly in adults (2nd–5th decades), with prodromal systemic symptoms possible before ocular disease. (manni2023vogtkoyanagiharadadiseaseand pages 1-2, manni2023vogtkoyanagiharadadiseaseand pages 2-4)
  • Course: May resolve with early therapy or evolve into chronically recurrent disease with anterior granulomatous uveitis and depigmentation. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

9. Inheritance and population

9.1 Inheritance

Best classified as multifactorial/polygenic, with strong HLA class II associations and additional immune gene contributions (PRKCD/CARD9). (zhou2023geneticassociationof pages 1-2, takeuchi2023hladrb1*0405isinvolved pages 1-2)

9.2 Population demographics / geographic distribution

  • VKH is more frequent in pigmented populations (e.g., Asians, Middle Easterners, Hispanics, Native Americans) and relatively rare in Europe; women often predominate and onset is typically in the 2nd–5th decades. (manni2023vogtkoyanagiharadadiseaseand pages 1-2, li2023bibliometricanalysisof pages 1-2)

9.3 Recent epidemiology statistics available in retrieved literature

  • Puerto Rico cohort (n=24) suggested seasonality: 50% onset in fall vs 12.5% in spring (P=0.043). (Published 2023‑02; URL: https://doi.org/10.1080/09273948.2022.2029499) (amaral2023; retrieved but not fully evidence-scanned in this run)
  • True population incidence/prevalence per 100,000 for VKH specifically was not obtained from the retrieved full texts; available numbers in retrieved COVID-era review include vaccine-induced uveitis incidence (8–13/100,000/year) but this is not VKH-specific. (manni2023vogtkoyanagiharadadiseaseand pages 2-4)

10. Diagnostics

10.1 Clinical diagnostic criteria and recent comparisons

Diagnosis is clinical with multimodal imaging support; multiple criteria sets are discussed. In a Chinese case–control comparison summarized in 2024, sensitivities differed substantially: CDCV 92.2%, RDC 66.7%, SUN-C 54.3%, with high specificity across sets. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, tugaltutkun2024vogtkoyanagiharadadisease media 234f6a18, tugaltutkun2024vogtkoyanagiharadadisease media dc9f8533)

10.2 Imaging and laboratory findings (real-world implementation)

Imaging hallmarks in acute disease include choroidal thickening and subretinal fluid on OCT/EDI‑OCT, pinpoint hyperfluorescence/leakage patterns on fluorescein angiography, and hypocfluorescent dots/patches on ICGA. (manni2023vogtkoyanagiharadadiseaseand pages 16-19)

OCTA monitoring (recent development) - In an acute VKH series summarized in 2024, 93.8% of eyes had “dark foci”/flow voids in choriocapillaris and Sattler’s layer at presentation, decreasing with therapy and reduced choroidal thickness, supporting OCTA as a noninvasive monitoring tool. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3, tugaltutkun2024vogtkoyanagiharadadisease media 234f6a18, tugaltutkun2024vogtkoyanagiharadadisease media dc9f8533)

CSF pleocytosis may be present in prodromal/neurologic phase and was reported in vaccine-associated cases (CSF pleocytosis in 7/21 in one review). (manni2023vogtkoyanagiharadadiseaseand pages 2-4)

10.3 Differential diagnosis

Not systematically extracted in the retrieved texts; the 2024 editorial notes OCTA patterns may help differentiate atypical VKH from entities such as APMPPE in some contexts. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

11. Outcome / prognosis

11.1 Prognostic factors (2024 cohort data)

A 2024 retrospective cohort (Beijing Tongren Hospital; 62 patients, 2020–2023) identified factors associated with chronic recurrence: - Chronic-recurrent group had worse initial BCVA (1.38±0.54 vs 0.64±0.29 logMAR; P=0.002) and higher sunset glow fundus prevalence (64.3% vs 23.5%; P=0.001). (Published 2024‑06; URL: https://doi.org/10.1186/s12886-024-03511-9) (feng2024predictivefactorsand pages 1-2) - Logistic regression predictors included older age at onset (P=0.042) and sunset glow fundus (P=0.037). (feng2024predictivefactorsand pages 1-2)

11.2 COVID/vaccine-associated prognosis

A 2023 synthesis reports favorable short-term outcomes in reported COVID infection/vaccination-associated cases, with high corticosteroid responsiveness and mean visual acuity ~20/32 in short-term follow-up. (manni2023vogtkoyanagiharadadiseaseand pages 20-22)

12. Treatment (current practice, evidence, and trials)

12.1 Standard pharmacotherapy and strategy

A 2023 retrospective series abstract states: “Treatment is usually initiated with corticosteroids followed by an early introduction of immunosuppressive treatment (IMT).” (URL: https://doi.org/10.1186/s12348-023-00333-6; publication 2023‑05) (rahman2023immunosuppressivetherapyfor pages 1-2)

Evidence for early combination IMT - In 26 patients (20-year retrospective), 81% (21/26) treated with combined IMT/low-dose steroids achieved disease stability with improved median VA from 0.3 logMAR to 0.0 logMAR at 24 months (p=0.0001). MMF was commonly used but 50% of MMF-treated patients did not achieve disease control. (rahman2023immunosuppressivetherapyfor pages 1-2)

12.2 Biologics and comparative effectiveness (high-impact 2023 randomized trial)

A 26-week randomized non-inferiority trial (ChiCTR2100043061; 110 randomized) compared a cyclosporine-based immunosuppressant strategy vs an adalimumab-based biologic strategy (both with corticosteroids). The abstract states: “we assigned 110 patients… to cyclosporine-based immunosuppressant strategy… or adalimumab-based biologic strategy… The primary outcome is change from baseline in best-corrected visual acuity at week 26… P < 0.001 for non-inferiority.” (Published 2023‑06; URL: https://doi.org/10.1038/s41467-023-39483-5) (zhong2023arandomizednoninferiority pages 1-2) Key quantitative outcomes: - BCVA improvement: 11.2 letters (95% CI 7.5–14.9) vs 6.3 letters (3.1–9.6); difference 4.9 (0.2–9.5) with one-sided P<0.001 for non-inferiority. (zhong2023arandomizednoninferiority pages 1-2) - Serious adverse events: 0.70 vs 1.21 events per patient-year (lower in cyclosporine strategy). (zhong2023arandomizednoninferiority pages 1-2)

12.3 Adalimumab in chronic-recurrent VKH (2024 observational evidence)

Adalimumab significantly reduced anterior chamber and vitreous inflammatory cells and reduced recurrence rate (P=0.009) in a 2024 retrospective cohort of chronic-recurrent VKH. (feng2024predictivefactorsand pages 1-2)

12.4 JAK inhibitors (recent real-world prospective registry cohort, 2024)

A prospective AIDA network cohort (n=12; included 1 VKH case) found complete ocular control in 12/12 after starting JAK inhibitors and a marked reduction in flare incidence from 125 to 28.6 episodes per 1,000 person-months (incidence rate ratio 4.37; 95% CI 1.3–14.7; p=0.02). (Published 2024‑08‑23; URL: https://doi.org/10.3389/fmed.2024.1439338) (vitale2024efficacyandsafety pages 1-2)

12.5 Clinical trials (real-world implementations and ongoing studies)

  • NCT03399175 (University of São Paulo; recruiting): early high-dose corticosteroid + immunosuppressive therapy with multimodal imaging and functional testing; primary outcome includes scotopic ERG variation (6–12 months). (NCT03399175 chunk 1)
  • URL: https://clinicaltrials.gov/study/NCT03399175 (NCT03399175 chunk 1)
  • NCT05590416 (Tianjin Medical University; recruiting): prospective cohort comparing adalimumab + glucocorticoids vs traditional therapy in acute VKH (onset <1 month); primary outcomes include logMAR BCVA change and recurrence rate at 24 weeks. (NCT05590416 chunk 1)
  • URL: https://clinicaltrials.gov/study/NCT05590416 (NCT05590416 chunk 1)

12.6 MAXO (Medical Action Ontology) term suggestions (representative)

  • Systemic glucocorticoid therapy
  • Immunosuppressive therapy / immunomodulatory therapy (e.g., mycophenolate mofetil, azathioprine, cyclosporine)
  • Tumor necrosis factor inhibitor therapy (adalimumab)
  • Janus kinase inhibitor therapy (baricitinib, tofacitinib, upadacitinib)
  • Multimodal ocular imaging (OCT, ICGA, FA, OCTA) for monitoring (these actions are supported as real-world implementations in the cited studies) (rahman2023immunosuppressivetherapyfor pages 1-2, vitale2024efficacyandsafety pages 1-2, tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)

13. Prevention

13.1 Primary prevention

No established primary prevention exists for VKH in the retrieved evidence.

13.2 Secondary/tertiary prevention (preventing chronic evolution and complications)

The actionable prevention strategy is early recognition and prompt systemic therapy to prevent chronic recurrence and sunset glow fundus; multiple sources emphasize early treatment improves outcomes. (rahman2023immunosuppressivetherapyfor pages 1-2, manni2023vogtkoyanagiharadadiseaseand pages 8-10)

13.3 Vaccination considerations (COVID era)

Despite case reports of VKH onset/relapse after vaccination, expert synthesis emphasizes that good therapeutic response and benefit–risk considerations should not discourage vaccination, while recommending vigilance and early treatment in predisposed subjects. (manni2023vogtkoyanagiharadadiseaseand pages 1-2, manni2023vogtkoyanagiharadadiseaseand pages 20-22)

14. Other species / natural disease

A spontaneous autoimmune pigmentation disorder model (Smyth line chicken) shows systemic melanocyte autoimmunity with ocular involvement resembling VKH and sympathetic ophthalmia; infiltrating leukocytes include CD4+, CD8+ T cells, B cells, and macrophages, and cytokine profiles suggest Th1 polarization. (Published 2022‑04; URL: https://doi.org/10.3389/fmed.2022.846100) (sorrick2022immuneactivitiesin pages 1-2)

15. Model organisms

15.1 Induced experimental VKH-like uveitis models

  • Experimental melanin-protein induced uveitis (EMIU) and related models show that immunization with tyrosinase-related proteins 1 and 2 in rats can produce VKH-like inflammatory changes, supporting melanocyte antigens as mechanistic drivers and providing a platform for antigen-specific therapy concepts. (adamus2002experimentalautoimmuneuveitides pages 1-3)

15.2 Spontaneous model relevant to VKH mechanisms

  • Smyth line chicken autoimmune vitiligo with uveitis/vision impairment offers a spontaneous model to interrogate systemic anti-melanocyte immunity and timing of immune infiltration preceding overt disease. (sorrick2022immuneactivitiesin pages 1-2)

Recent developments and latest research highlights (2023–2024 prioritized)

1) Diagnostic criteria modernization and imaging-based definition of choroidal involvement: CDCV criteria sensitivity 92.2% vs RDC 66.7% vs SUN-C 54.3% in a Chinese case-control comparison summarized in 2024, with explicit incorporation of EDI-OCT/ICGA in some modern criteria. (2024‑04‑24; https://doi.org/10.1080/09273948.2024.2331401) (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3) 2) COVID-19 era trigger literature: systematic compilation of post-infection and post-vaccine VKH, with rapid onset intervals and high corticosteroid responsiveness, supporting continued surveillance rather than a change in standard management. (2023‑09; https://doi.org/10.3390/jcm12196242) (manni2023vogtkoyanagiharadadiseaseand pages 1-2) 3) Head-to-head strategy trial evidence: cyclosporine-based strategy non-inferior to adalimumab-based strategy for 26-week visual improvement, informing real-world decision-making when selecting conventional immunosuppression vs biologics. (2023‑06; https://doi.org/10.1038/s41467-023-39483-5) (zhong2023arandomizednoninferiority pages 1-2) 4) Newer therapeutics: prospective registry evidence supporting JAK inhibitors for refractory non-infectious ocular inflammation including VKH. (2024‑08‑23; https://doi.org/10.3389/fmed.2024.1439338) (vitale2024efficacyandsafety pages 1-2)

Data table of high-yield facts

Domain Specific finding (with numbers where available) Source (first author year journal) Publication date URL Evidence context ID
Identifiers/Definition VKH is a multisystem autoimmune disorder affecting the eyes, central nervous system, auditory system, and integumentary system; disease course includes prodromal, acute uveitic, convalescent, and chronic recurrent phases. Tugal-Tutkun 2024 Ocular Immunology and Inflammation 2024-04-24 https://doi.org/10.1080/09273948.2024.2331401 (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
Genetics In 912 VKH cases vs 878 controls, PRKCD rs74437127 C allele increased susceptibility (Pc=0.020, OR=1.624, 95% CI 1.200–2.199), while T allele was protective (Pc=0.020, OR=0.616, 95% CI 0.455–0.833). Zhou 2023 Human Genomics 2023-02 https://doi.org/10.1186/s40246-023-00459-7 (zhou2023geneticassociationof pages 1-2)
Genetics CARD9 rs3812555 CC genotype and C allele increased VKH susceptibility (Pc=2.04×10^-5, OR=1.810, 95% CI 1.418–2.311; Pc=2.76×10^-5, OR=1.698, 95% CI 1.362–2.118), whereas TC genotype and T allele were protective (Pc=7.85×10^-5, OR=0.559; Pc=2.76×10^-5, OR=0.589). CC carriers had higher CARD9 mRNA and TNF-α production (P=1.00×10^-4; P=2.00×10^-3). Zhou 2023 Human Genomics 2023-02 https://doi.org/10.1186/s40246-023-00459-7 (zhou2023geneticassociationof pages 1-2)
Phenotypes & staging In the 912-patient VKH cohort, phenotype frequencies were: uveitis 100%, sunset glow fundus 48.7%, headache 49.2%, tinnitus 45.0%, vitiligo 11.4%, alopecia 31.4%. Zhou 2023 Human Genomics 2023-02 https://doi.org/10.1186/s40246-023-00459-7 (zhou2023geneticassociationof pages 1-2)
Genetics / Triggers In immune checkpoint inhibitor-associated uveitis, 5/9 cases were VKH-like and 4/9 non-VKH-like; among genotyped patients, 4/4 VKH-like were HLA-DRB1*04:05 positive vs 0/3 non-VKH-like, with significant association (P=0.029). Uveitis incidence in ICI-treated patients is reported as ~0.3–1%. Takeuchi 2023 Scientific Reports 2023-08 https://doi.org/10.1038/s41598-023-40565-z (takeuchi2023hladrb1*0405isinvolved pages 1-2)
Triggers Proposed triggers include viral infection and vaccination; review identified 4 young post-COVID infection VKH cases (all female; mean age 30 ± 5.43 years; mean onset ~19.8 days after infection), and summarized 33 new-onset post-vaccine cases. Manni 2023 Journal of Clinical Medicine 2023-09 https://doi.org/10.3390/jcm12196242 (manni2023vogtkoyanagiharadadiseaseand pages 8-10, manni2023vogtkoyanagiharadadiseaseand pages 16-19)
Triggers For COVID-19 vaccine-associated VKH review, 21 patients were identified (9 male, 12 female; median age 45 years, range 19–78); 14/21 after first dose, 8/21 after second; mean interval to symptoms 7.5 days; 20/21 bilateral; 16 had meningitis symptoms; 16 serous retinal detachment; 14 choroidal thickening; all received corticosteroids; mean recovery time 2 months. Xu 2023 Human Vaccines & Immunotherapeutics 2023-06 https://doi.org/10.1080/21645515.2023.2220630 (manni2023vogtkoyanagiharadadiseaseand pages 2-4)
Phenotypes & staging Typical acute features include bilateral choroiditis/panuveitis, exudative retinal detachment, meningismus/CSF pleocytosis, auditory and integumentary signs. Prodromal phase lasts ~3–5 days before acute uveitic stage developing over weeks. Manni 2023 Journal of Clinical Medicine 2023-09 https://doi.org/10.3390/jcm12196242 (manni2023vogtkoyanagiharadadiseaseand pages 2-4)
Diagnostics/Imaging Comparison of criteria in Chinese case-control study: Chinese Diagnostic Criteria for VKH (CDCV) sensitivity 92.2%, vs Revised Diagnostic Criteria (RDC) 66.7% and SUN classification criteria 54.3%; all three had high specificity without significant differences. Tugal-Tutkun 2024 Ocular Immunology and Inflammation 2024-04-24 https://doi.org/10.1080/09273948.2024.2331401 (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
Diagnostics/Imaging For acute VKH monitoring with OCTA, 93.8% of eyes had scattered dark foci in choriocapillaris and Sattler’s layer at presentation; follow-up in 30 eyes showed reduction in dark foci with decreasing choroidal thickness after treatment. Tugal-Tutkun 2024 Ocular Immunology and Inflammation 2024-04-24 https://doi.org/10.1080/09273948.2024.2331401 (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3)
Treatment In a 26-patient retrospective VKH series, treatment shifted from steroid monotherapy to combined immunosuppressive therapy (IMT)/low-dose steroid. 81% (21/26) treated with combined IMT/steroid achieved disease stability with improved median VA from 0.3 logMAR to 0.0 logMAR at 24 months (p=0.0001). Rahman 2023 Journal of Ophthalmic Inflammation and Infection 2023-05 https://doi.org/10.1186/s12348-023-00333-6 (rahman2023immunosuppressivetherapyfor pages 1-2)
Treatment In the same series, MMF monotherapy was most common (13/19 IMT-treated; 68%) and was well tolerated, but 50% of MMF-treated patients did not achieve disease control. Average time from diagnosis to IMT initiation was 2.1 months; average time to steroid-sparing effect was 5 months. Rahman 2023 Journal of Ophthalmic Inflammation and Infection 2023-05 https://doi.org/10.1186/s12348-023-00333-6 (rahman2023immunosuppressivetherapyfor pages 1-2)
Prognosis / Prognostic factors In 62 VKH patients (34 acute-resolved, 28 chronic-recurrent), chronic-recurrent patients were older (49.00 ± 16.43 vs 38.29 ± 15.46 years) and had worse initial BCVA (1.38 ± 0.54 vs 0.64 ± 0.29 logMAR; P=0.002). Complications occurred in 41.7% vs 29.4% (P=0.006), and sunset glow fundus in 64.3% vs 23.5% (P=0.001). Feng 2024 BMC Ophthalmology 2024-06 https://doi.org/10.1186/s12886-024-03511-9 (feng2024predictivefactorsand pages 1-2)
Prognosis / Prognostic factors Predictors of progression to chronic-recurrent VKH included poor initial BCVA (P=0.046) and sunset glow fundus (P=0.040); logistic regression identified older age at onset (P=0.042) and sunset glow fundus (P=0.037) as significant predictors. Feng 2024 BMC Ophthalmology 2024-06 https://doi.org/10.1186/s12886-024-03511-9 (feng2024predictivefactorsand pages 1-2)
Treatment In chronic-recurrent VKH, adalimumab significantly reduced anterior chamber inflammatory cells (P=0.000), vitreous inflammatory cells (P=0.001), and recurrence rate (P=0.009). Feng 2024 BMC Ophthalmology 2024-06 https://doi.org/10.1186/s12886-024-03511-9 (feng2024predictivefactorsand pages 1-2)
Treatment In a prospective AIDA network cohort of 12 adults with non-infectious ocular inflammatory disease (including 1 VKH case), 4 received baricitinib, 1 tofacitinib, and 7 upadacitinib; mean treatment duration was 8.6 ± 5.5 months. Vitale 2024 Frontiers in Medicine 2024-08-23 https://doi.org/10.3389/fmed.2024.1439338 (vitale2024efficacyandsafety pages 1-2)
Treatment With JAK inhibitors, ocular disease control was complete in 12/12 patients; flare incidence fell from 125 to 28.6 episodes per 1,000 person-months, incidence rate ratio 4.37 (95% CI 1.3–14.7, p=0.02) for pre- vs post-JAK periods. Vitale 2024 Frontiers in Medicine 2024-08-23 https://doi.org/10.3389/fmed.2024.1439338 (vitale2024efficacyandsafety pages 1-2)
Prognosis / Prognostic factors Early corticosteroid use is associated with better outcomes; rapid early visual acuity improvement predicts better final VA, while greater relapse number is associated with more complications and worse visual prognosis. Manni 2023 Journal of Clinical Medicine 2023-09 https://doi.org/10.3390/jcm12196242 (manni2023vogtkoyanagiharadadiseaseand pages 8-10)
Clinical trials NCT03399175: single-group interventional prospective study, University of São Paulo; 40 participants; started 2015-03-23; recruiting. Tests early high-dose systemic corticosteroid + immunosuppressive therapy in acute VKH with ≥12-month follow-up using FA, ICGA, EDI-OCT, ERG, autofluorescence, perimetry, contrast sensitivity, and QoL. Primary outcome: scotopic ERG variation between 6 and 12 months. Yamamoto 2015 ClinicalTrials.gov 2015-03-23 start; recruiting https://clinicaltrials.gov/study/NCT03399175 (NCT03399175 chunk 1)
Clinical trials NCT05590416: single-center prospective observational cohort, Tianjin Medical University; 15 participants; recruiting; compares adalimumab (80 mg loading, then 40 mg every 2 weeks) + glucocorticoids vs traditional therapy in acute VKH onset <1 month. Primary outcomes: change in logMAR BCVA and recurrence rate at 24 weeks; secondary outcomes include SUN anterior chamber cell grade and prednisone exposure. Zhang 2021 ClinicalTrials.gov 2021-06-01 start; recruiting https://clinicaltrials.gov/study/NCT05590416 (NCT05590416 chunk 1)

Table: This table compiles high-yield, citable findings on Vogt-Koyanagi-Harada disease across genetics, triggers, phenotypes, diagnostics, treatment, prognosis, and ongoing trials. It is designed to support rapid evidence-backed drafting of a comprehensive disease report.

Limitations of this report (evidence gaps from this run)

  • ICD‑10/ICD‑11 and MeSH descriptor IDs were not retrieved from dedicated ontology sources (e.g., ICD/MeSH browsers) within the accessible full texts; the report therefore provides MONDO and trial-level MeSH categorization only. (OpenTargets Search: Vogt-Koyanagi-Harada disease, NCT05590416 chunk 2)
  • True population-based VKH incidence/prevalence (per 100,000) was not captured in the retrieved full texts; additional targeted epidemiology sources would be required.
  • Quality-of-life instrument outcomes (e.g., NEI-VFQ, SF-36) were not available in retrieved papers; only trial registry mentions QoL questionnaires. (NCT03399175 chunk 1)

References

  1. (OpenTargets Search: Vogt-Koyanagi-Harada disease): Open Targets Query (Vogt-Koyanagi-Harada disease, 0 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  2. (tugaltutkun2024vogtkoyanagiharadadisease pages 1-3): Ilknur Tugal-Tutkun, Derrick P. Smit, Ahmed M. Abu El-Asrar, Carl P. Herbort, and Jennifer E. Thorne. Vogt-koyanagi-harada disease. Ocular Immunology and Inflammation, 32:363-366, Apr 2024. URL: https://doi.org/10.1080/09273948.2024.2331401, doi:10.1080/09273948.2024.2331401. This article has 12 citations and is from a peer-reviewed journal.

  3. (rahman2023immunosuppressivetherapyfor pages 1-2): Najiha Rahman, Jose Carlo M Artiaga, Konstantinos Bouras, Joshua Luis, Angela Rees, and Mark Westcott. Immunosuppressive therapy for vogt-koyanagi-harada disease: a retrospective study and review of literature. Journal of Ophthalmic Inflammation and Infection, May 2023. URL: https://doi.org/10.1186/s12348-023-00333-6, doi:10.1186/s12348-023-00333-6. This article has 24 citations and is from a peer-reviewed journal.

  4. (vitale2024efficacyandsafety pages 1-2): Antonio Vitale, Judith Palacios-Olid, Valeria Caggiano, Gaafar Ragab, José Hernández-Rodríguez, Laura Pelegrín, Germán Mejía-Salgado, Laura Zarate-Pinzón, Stefano Gentileschi, Jurgen Sota, Alex Fonollosa, Ester Carreño, Carla Gaggiano, Rana Hussein Amin, Alberto Balistreri, Javier Narváez, Gian Marco Tosi, Bruno Frediani, Luca Cantarini, Alejandra de-la-Torre, and Claudia Fabiani. Efficacy and safety of janus kinase inhibitors in non-infectious inflammatory ocular diseases: a prospective cohort study from the international aida network registries. Frontiers in Medicine, Aug 2024. URL: https://doi.org/10.3389/fmed.2024.1439338, doi:10.3389/fmed.2024.1439338. This article has 29 citations.

  5. (manni2023vogtkoyanagiharadadiseaseand pages 1-2): Priscilla Manni, Maria Carmela Saturno, and Massimo Accorinti. Vogt-koyanagi-harada disease and covid. Journal of Clinical Medicine, 12:6242, Sep 2023. URL: https://doi.org/10.3390/jcm12196242, doi:10.3390/jcm12196242. This article has 8 citations.

  6. (NCT05590416 chunk 2): Xiaomin Zhang. A Study of Adalimumab in Acute Vogt-Koyanagi-Harada Disease. Tianjin Medical University. 2021. ClinicalTrials.gov Identifier: NCT05590416

  7. (zhou2023geneticassociationof pages 1-2): Chunya Zhou, Shiya Cai, Yuhong Xie, Zhen Zeng, Jun Zhang, Guannan Su, Qiuying Wu, Xingsheng Ye, Qingfeng Cao, Peizeng Yang, and Jianmin Hu. Genetic association of prkcd and card9 polymorphisms with vogt–koyanagi–harada disease in the chinese han population. Human Genomics, Feb 2023. URL: https://doi.org/10.1186/s40246-023-00459-7, doi:10.1186/s40246-023-00459-7. This article has 3 citations and is from a peer-reviewed journal.

  8. (zhong2023arandomizednoninferiority pages 3-4): Zhenyu Zhong, Lingyu Dai, Qiuying Wu, Yu Gao, Yanlin Pu, Guannan Su, Xiaorong Lu, Fuxiang Zhang, Chong Tang, Yao Wang, Chunjiang Zhou, and Peizeng Yang. A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for vogt-koyanagi-harada disease. Nature Communications, Jun 2023. URL: https://doi.org/10.1038/s41467-023-39483-5, doi:10.1038/s41467-023-39483-5. This article has 16 citations and is from a highest quality peer-reviewed journal.

  9. (adamus2002experimentalautoimmuneuveitides pages 1-3): GRAZYNA ADAMUS and CHI-CHAO CHAN. Experimental autoimmune uveitides: multiple antigens, diverse diseases. International Reviews of Immunology, 21:209-229, Jan 2002. URL: https://doi.org/10.1080/08830180212068, doi:10.1080/08830180212068. This article has 85 citations and is from a peer-reviewed journal.

  10. (sorrick2022immuneactivitiesin pages 1-2): Jordan Sorrick, Wilson Huett, Kristen A. Byrne, and Gisela F. Erf. Immune activities in choroids of visually impaired smyth chickens with autoimmune vitiligo. Frontiers in Medicine, Apr 2022. URL: https://doi.org/10.3389/fmed.2022.846100, doi:10.3389/fmed.2022.846100. This article has 4 citations.

  11. (sugita2006ocularinfiltratingcd4+ pages 1-2): Sunao Sugita, Hiroshi Takase, Chikako Taguchi, Yasuhisa Imai, Koju Kamoi, Tatsushi Kawaguchi, Yoshiharu Sugamoto, Yuri Futagami, Kyogo Itoh, and Manabu Mochizuki. Ocular infiltrating cd4+ t cells from patients with vogt-koyanagi-harada disease recognize human melanocyte antigens. Investigative ophthalmology & visual science, 47 6:2547-54, Jun 2006. URL: https://doi.org/10.1167/iovs.05-1547, doi:10.1167/iovs.05-1547. This article has 202 citations and is from a domain leading peer-reviewed journal.

  12. (sugita2006ocularinfiltratingcd4+ pages 7-8): Sunao Sugita, Hiroshi Takase, Chikako Taguchi, Yasuhisa Imai, Koju Kamoi, Tatsushi Kawaguchi, Yoshiharu Sugamoto, Yuri Futagami, Kyogo Itoh, and Manabu Mochizuki. Ocular infiltrating cd4+ t cells from patients with vogt-koyanagi-harada disease recognize human melanocyte antigens. Investigative ophthalmology & visual science, 47 6:2547-54, Jun 2006. URL: https://doi.org/10.1167/iovs.05-1547, doi:10.1167/iovs.05-1547. This article has 202 citations and is from a domain leading peer-reviewed journal.

  13. (takeuchi2023hladrb10405isinvolved pages 1-2): Masaki Takeuchi, Akira Meguro, Jutaro Nakamura, Rei Chikagawa, Raiga Osada, Etsuko Shibuya, Yukiko Hasumi, Norihiro Yamada, Mami Ishihara, and Nobuhisa Mizuki. Hla-drb104:05 is involved in the development of vogt–koyanagi–harada disease-like immune-related adverse events in patients receiving immune checkpoint inhibitors. Scientific Reports, Aug 2023. URL: https://doi.org/10.1038/s41598-023-40565-z, doi:10.1038/s41598-023-40565-z. This article has 17 citations and is from a peer-reviewed journal.

  14. (manni2023vogtkoyanagiharadadiseaseand pages 2-4): Priscilla Manni, Maria Carmela Saturno, and Massimo Accorinti. Vogt-koyanagi-harada disease and covid. Journal of Clinical Medicine, 12:6242, Sep 2023. URL: https://doi.org/10.3390/jcm12196242, doi:10.3390/jcm12196242. This article has 8 citations.

  15. (muto2024effectofthe pages 6-7): Tetsuya Muto, Masaaki Sakamoto, Shoichiro Kusuda, Yasuo Haruyama, Shigeki Machida, Shinichiro Imaizumi, and Tetsuju Sekiryu. Effect of the covid-19 pandemic on vogt–koyanagi–harada disease. Scientific Reports, Jun 2024. URL: https://doi.org/10.1038/s41598-024-63957-1, doi:10.1038/s41598-024-63957-1. This article has 5 citations and is from a peer-reviewed journal.

  16. (manni2023vogtkoyanagiharadadiseaseand pages 16-19): Priscilla Manni, Maria Carmela Saturno, and Massimo Accorinti. Vogt-koyanagi-harada disease and covid. Journal of Clinical Medicine, 12:6242, Sep 2023. URL: https://doi.org/10.3390/jcm12196242, doi:10.3390/jcm12196242. This article has 8 citations.

  17. (feng2024predictivefactorsand pages 1-2): Hui Feng, Weixin Chen, Jianzhu Yang, Haorong Kong, Hongyu Li, Yuan He, and Hong Wang. Predictive factors and adalimumab efficacy in managing chronic recurrence vogt-koyanagi-harada disease. BMC Ophthalmology, Jun 2024. URL: https://doi.org/10.1186/s12886-024-03511-9, doi:10.1186/s12886-024-03511-9. This article has 9 citations and is from a peer-reviewed journal.

  18. (elasrar2021newperspectiveson pages 1-2): Ahmed M. Abu El-Asrar, Jo Van Damme, Sofie Struyf, and Ghislain Opdenakker. New perspectives on the immunopathogenesis and treatment of uveitis associated with vogt-koyanagi-harada disease. Frontiers in Medicine, Nov 2021. URL: https://doi.org/10.3389/fmed.2021.705796, doi:10.3389/fmed.2021.705796. This article has 34 citations.

  19. (li2023bibliometricanalysisof pages 1-2): Liangpin Li, Liyun Yuan, Xueyan Zhou, Xia Hua, and Xiaoyong Yuan. Bibliometric analysis of the vogt‒koyanagi‒harada disease literature. International Ophthalmology, 43:4137-4150, Aug 2023. URL: https://doi.org/10.1007/s10792-023-02815-x, doi:10.1007/s10792-023-02815-x. This article has 2 citations and is from a peer-reviewed journal.

  20. (tugaltutkun2024vogtkoyanagiharadadisease media 234f6a18): Ilknur Tugal-Tutkun, Derrick P. Smit, Ahmed M. Abu El-Asrar, Carl P. Herbort, and Jennifer E. Thorne. Vogt-koyanagi-harada disease. Ocular Immunology and Inflammation, 32:363-366, Apr 2024. URL: https://doi.org/10.1080/09273948.2024.2331401, doi:10.1080/09273948.2024.2331401. This article has 12 citations and is from a peer-reviewed journal.

  21. (tugaltutkun2024vogtkoyanagiharadadisease media dc9f8533): Ilknur Tugal-Tutkun, Derrick P. Smit, Ahmed M. Abu El-Asrar, Carl P. Herbort, and Jennifer E. Thorne. Vogt-koyanagi-harada disease. Ocular Immunology and Inflammation, 32:363-366, Apr 2024. URL: https://doi.org/10.1080/09273948.2024.2331401, doi:10.1080/09273948.2024.2331401. This article has 12 citations and is from a peer-reviewed journal.

  22. (manni2023vogtkoyanagiharadadiseaseand pages 20-22): Priscilla Manni, Maria Carmela Saturno, and Massimo Accorinti. Vogt-koyanagi-harada disease and covid. Journal of Clinical Medicine, 12:6242, Sep 2023. URL: https://doi.org/10.3390/jcm12196242, doi:10.3390/jcm12196242. This article has 8 citations.

  23. (zhong2023arandomizednoninferiority pages 1-2): Zhenyu Zhong, Lingyu Dai, Qiuying Wu, Yu Gao, Yanlin Pu, Guannan Su, Xiaorong Lu, Fuxiang Zhang, Chong Tang, Yao Wang, Chunjiang Zhou, and Peizeng Yang. A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for vogt-koyanagi-harada disease. Nature Communications, Jun 2023. URL: https://doi.org/10.1038/s41467-023-39483-5, doi:10.1038/s41467-023-39483-5. This article has 16 citations and is from a highest quality peer-reviewed journal.

  24. (NCT03399175 chunk 1): Joyce Hisae Yamamoto. Early Immunosuppressive Therapy on the Course of Vogt-Koyanagi-Harada Disease. University of Sao Paulo. 2015. ClinicalTrials.gov Identifier: NCT03399175

  25. (NCT05590416 chunk 1): Xiaomin Zhang. A Study of Adalimumab in Acute Vogt-Koyanagi-Harada Disease. Tianjin Medical University. 2021. ClinicalTrials.gov Identifier: NCT05590416

  26. (manni2023vogtkoyanagiharadadiseaseand pages 8-10): Priscilla Manni, Maria Carmela Saturno, and Massimo Accorinti. Vogt-koyanagi-harada disease and covid. Journal of Clinical Medicine, 12:6242, Sep 2023. URL: https://doi.org/10.3390/jcm12196242, doi:10.3390/jcm12196242. This article has 8 citations.