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| Vogt–Koyanagi–Harada disease | |
|---|---|
| Other names | Vogt–Koyanagi–Harada syndrome, uveomeningitis syndrome, uveomeningoencephalitic syndrome[1] |
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| Dermatologic manifestation of VKH | |
| Specialty | Ophthalmology  |
Vogt–Koyanagi–Harada disease (VKH) is a multisystem disease of presumedautoimmune cause that affectsmelanin-pigmented tissues. The most significant manifestation is bilateral, diffuseuveitis, which affects the eyes.[2][3] VKH may variably also involve theinner ear, with effects on hearing, the skin, and themeninges of thecentral nervous system.[2][3][4][5][6]
The disease is characterised by bilateral diffuse uveitis, with pain, redness andblurring of vision. The eye symptoms may be accompanied by a varying constellation of systemic symptoms, such as auditory (tinnitus,[6]vertigo,[6] andhypoacusis), neurological (meningismus, with malaise, fever, headache, nausea, abdominal pain, stiffness of the neck and back, or a combination of these factors;[6]meningitis,[4]CSFpleocytosis,cranial nervepalsies,hemiparesis,transverse myelitis andciliary ganglionitis[6]), and cutaneous manifestations, includingpoliosis,vitiligo, andalopecia.[4][5][6] The vitiligo often is found at thesacral region.[6]
The sequence of clinical events in VKH is divided into four phases - prodromal, acute uveitic, convalescent, and chronic recurrent.[2][5][6]
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.[6] 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.[6][7] Eye symptoms can includeorbital pain,photophobia, and tearing.[6] The skin and hair may be sensitive to touch.[6][7]Cranial nervepalsies andoptic neuritis are uncommon.[6]
The acute uveitic phase occurs a few days later and typically lasts for several weeks.[6] This phase is heralded by bilateralpanuveitis causing blurring of vision.[6] In 70% of VKH cases, the onset of visual blurring is bilaterally contemporaneous; if initially unilateral, the other eye is involved within several days.[6] The process can include bilateral granulomatous anterior uveitis, variable degree of vitritis, thickening of the posterior choroid with elevation of the peripapillary retinal choroidal layer, optic nervehyperemia andpapillitis, and multiple exudativebullous serousretinal detachments.[2][5][6]
The convalescent phase is characterized by gradual tissue depigmentation of skin withvitiligo andpoliosis, sometimes with nummular depigmented scars, as well asalopecia and diffusefundus depigmentation resulting in a classic orange-red discoloration ("sunset glow fundus"[5][8][7]) and retinal pigment epithelium clumping and/or migration.[2][6]
The chronic recurrent phase may be marked by repeated bouts of uveitis, but is more commonly a chronic, low-grade, often subclinical, uveitis that may lead togranulomatous anterior inflammation,cataracts,glaucoma, and ocular hypertension.[2][3][5][6] Full-blown recurrences, though, are rare after the acute stage is over.[8]Dysacusia may occur in this phase.[7]
Although sometimes a viral infection, or skin or eye trauma precedes an outbreak,[6] the exact underlying initiator of VKH disease remains unknown.[4] VKH is attributed, however, to aberrantT-cell-mediated immune response directed against self-antigens found onmelanocytes.[3][4][6] Stimulated byinterleukin 23 (IL-23),T helper 17 cells andcytokines, such asinterleukin 17, appear to target proteins in the melanocytes.[8][9]
Affected individuals are typically 20 to 50 years old.[3][4] The female-to-male ratio is 2:1.[4][5][6] By definition, affected people have no history of either surgical or accidental oculartrauma.[3] VKH is more common in Asians, Latinos, Middle Easterners, American Indians, and Mexican Mestizos; it is much less common in Caucasians and in Blacks from sub-Saharan Africa.[3][4][5][6]
VKH is associated with a variety of genetic polymorphisms that relate to immune function. For example, it has been associated withhuman leukocyte antigens (HLA) HLA-DR4 and DRB1/DQA1,[10]copy-number variations ofcomplement component 4,[10] a variantIL-23R locus[10] and with various other non-HLA genes.[10] HLA-DRB1*0405 in particular appears to play an important susceptibility role.[2][4][8][6]
If tested in the prodromal phase,cerebrospinal fluidpleocytosis is found in more than 80% of cases,[6][7] with mainlylymphocytes.[7] This pleocytosis resolves in about 8 weeks even if chronic uveitis persists.[7]
Functional tests may includeelectroretinogram andvisual field testing.[2] Diagnostic confirmation and an estimation of disease severity may involve imaging tests such asretinography,fluorescein orindocyanine green angiography,optical coherence tomography andultrasound.[2][5][9][7] For example, indocyanine green angiography may detect continuingchoroidalinflammation in the eyes without clinical symptoms or signs.[5][8] Ocular MRI may be helpful[6] and auditory symptoms should undergo audiologic testing.[6] Histopathology findings from eye and skin are discussed by Walton.[6]
The diagnosis of VKH is based on the clinical presentation; the diagnostic differential is extensive, and includessympathetic ophthalmia,sarcoidosis, primary intraocularB-cell lymphoma, posteriorscleritis, uveal effusion syndrome, tuberculosis, syphilis, and multifocal choroidopathy syndromes.[3][6]
Based on the presence of extraocular findings, such as neurological, auditory, and integumentary manifestations, the "revised diagnostic criteria" of 2001[2][11] classify the disease as complete (eyes along with both neurological and skin), incomplete (eyes along with either neurological or skin), or probable (eyes without either neurological or skin) .[1][3][5][6][11] By definition, for research homogeneity purposes, the two exclusion criteria are previous ocular penetrating trauma or surgery, and other concomitant ocular disease similar to VKH disease.[2][6][11]
The acute uveitis phase of VKH is usually responsive to high-dose oralcorticosteroids; parenteral administration is usually not required.[2][3][6] However, ocular complications may require asubtenon[6] or intravitreous injection of corticosteroids[4][6] orbevacizumab.[9] In refractory situations, otherimmunosuppressives such ascyclosporine,[2][3] ortacrolimus,[9]antimetabolites (azathioprine,mycophenolate mofetil ormethotrexate[9]), or biological agents such asintravenous immunoglobulins (IVIG) orinfliximab may be needed.[2][6]
Visualprognosis is generally good with prompt diagnosis and aggressiveimmunomodulatory treatment.[2][3][8] Inner ear symptoms usually respond to corticosteroid therapy within weeks to months; hearing usually recovers completely.[6] Chronic eye effects such ascataracts,glaucoma, andoptic atrophy can occur.[6] Skin changes usually persist despite therapy.[6]
VKH syndrome is named for ophthalmologistsAlfred Vogt from Switzerland andYoshizo Koyanagi andEinosuke Harada from Japan.[12][13][14][15] Several authors, including Arabic doctor Mohammad-al-Ghâfiqî in the 12th century, as well as Jacobi, Nettelship, and Tay in the 19th century, had described poliosis, neuralgias, and hearing disorders.[15] This constellation was probably often due tosympathetic ophthalmia, but likely included examples of VKH.[15] Koyanagi's first description of the disease was in 1914, but was preceded by Jujiro Komoto, professor of ophthalmology at the University of Tokyo, in 1911.[15] A much later article, published in 1929, definitively associated Koyanagi with the disease.[15] Harada's 1926 paper is recognized for its comprehensive description of what is now known as Vogt–Koyanagi–Harada disease.[15]
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