Vogt–Koyanagi–Harada disease (VKH) is a multisystem disease of presumed autoimmune cause that affects melanin-pigmented tissues. The most significant manifestation is bilateral, diffuse uveitis, which affects the eyes. VKH may variably also involve the inner ear, with effects on hearing, the skin, and the meninges of the central nervous system. Signs and symptoms
Overview
The disease is characterised by bilateral diffuse uveitis, with pain, redness and blurring of vision. The eye symptoms may be accompanied by a varying constellation of systemic symptoms, such as auditory (tinnitus, vertigo, and hypoacusis), neurological (meningismus, with malaise, fever, headache, nausea, abdominal pain, stiffness of the neck and back, or a combination of these factors; meningitis, CSF pleocytosis, cranial nerve palsies, hemiparesis, transverse myelitis and ciliary ganglionitis), and cutaneous manifestations, including poliosis, vitiligo, and alopecia. The vitiligo often is found at the sacral region. Phases
The sequence of clinical events in VKH is divided into four phases - prodromal, acute uveitic, convalescent, and chronic recurrent.The prodromal phase may have no symptoms, or may mimic a nonspecific viral infection, marked by flu-like symptoms that typically last for a few days. Fever, headache, nausea, meningismus, dysacusia (discomfort caused by loud noises or a distortion in the quality of the sounds being heard), tinnitus, and/or vertigo may occur. Eye symptoms can include orbital pain, photophobia, and tearing. The skin and hair may be sensitive to touch. Cranial nerve palsies and optic neuritis are uncommon.The acute uveitic phase occurs a few days later and typically lasts for several weeks.
Friedel-Crafts cyclization of the olefin with the equivalent of PPA then gives the thiopyran (3). Acylation with acetyl chloride in the presence of aluminium chloride gives the methyl ketone (4). Reaction of the enolate of that ketone with diethyl chlorophosphate gives the enol phosphate 5 as a transient intermediate. This eliminates diethyl phosphite in the presence of excess base to give the corresponding acetylene 6. The anion from the reaction of the acetylene with base is then used to displace chlorine from Ethyl 6-chloronicotinate (7). This reaction affords the coupling product tazarotene (8). == References ==