1. Review current understanding of VKH as a uveo-meningeal autoimmune syndrome
2. Highlight the clinical classification and implications for disease pathophysiology
3. Propose an immune-tolerization treatment strategy

VKH has 4 clinical phases: 1) flu-like prodrome with meningeal involvement, 2) uveitic phase, 3) convalescent phase with skin/choroidal depigmentation, 4) recurrent anterior uveitis. Harada described retinal detachments with CSF pleocytosis in 1926. Harada’s syndrome was merged with Vogt and Koyanagi’s description of nontraumatic uveitis with systemic manifestations including poliosis and vitiligo. Now thought to represent autoimmunity against melanocytes, the pathophysiology of VKH remains an active area of research.

Case presentation, chart review, PubMed literature search

A 36-year-old man with hypothyroidism presented with acute vision loss, bilateral tinnitus, and meningismus but otherwise normal neurologic exam. Ophthalmologic exam revealed bilateral exudative retinal detachments. CSF showed lymphocytic pleocytosis (129 WBCs, 96% lymphocytes) with predominantly CD5+ cells on flow cytometry. MRI brain showed minimally increased periventricular T2/FLAIR signal and mildly increased pachymeningeal enhancement. Infectious work up including CSF cultures, gram stain, meningoencephalitis panel, syphilis screening, fungal culture, QuantiFERON, CMV PCR, Bartonella screening was negative. An HLA-typing panel was sent and returned positive for HLA-DR4. The patient received 3 days high dose IV steroids and was discharged on oral Prednisone 60 mg daily. On follow up with ophthalmology, his visual acuity improved in the left eye and worsened on the right. He was started on mycophenolate mofetil.

VKH is a vision-threatening autoimmune disease against melanocytes with known genetic risk factors including HLA-DR4. Molecular mimicry triggered by viral infection is a proposed disease mechanism. The exact autoantigen is unknown, but tyrosinase-related-protein(TRP) may mimic cytomegalovirus envelope-glycoprotein-H.

To test the molecular mimicry hypothesis, we postulate a noninflammatory mRNA vaccine to tolerize the immune system against TRP in an experimental autoimmune uveitis model, as was recently described for the treatment of experimental autoimmune encephalomyelitis.