Vogt-Koyanagi-Harada Disease Clinical Presentation
- Author: R Christopher Walton, MD; Chief Editor: Hampton Roy, Sr, MD more...
Patients with VKH disease usually initially present to an ophthalmologist for ocular problems, including sudden loss of vision, ocular pain, and photophobia. Hearing disturbances and dizziness may be present. After weeks or months, most patients notice cutaneous signs (eg, hair loss, poliosis, vitiligo).
Four clinical stages have been described in VKH disease, consisting of the prodromal stage, uveitic stage, chronic stage, and recurrent stage.
The prodrome typically lasts for a few days and is characterized by the following signs:
CSF pleocytosis occurs in more than 80% of patients during this stage. Photophobia and tearing may develop, and patients also may note that their skin and hair is sensitive to touch during this stage.
Uncommon manifestations during the prodrome include cranial nerve palsies and optic neuritis. Some patients may not develop or report the symptoms characteristic of the prodrome.
The acute uveitic stage follows the prodromal stage by several days in most patients and typically lasts for several weeks. During this stage, the most common symptom is acute bilateral blurring of vision. As many as 70% of patients present with bilateral blurring of vision; in most of the remaining patients, the fellow eye is involved within several days.
Clinically, this stage manifests as bilateral posterior uveitis with retinal edema, optic disc hyperemia or edema, and, eventually, serous retinal detachments. Often, an accompanying anterior uveitis characterized by mutton-fat keratic precipitates and iris nodules are present. The intraocular pressure may be elevated because of forward rotation of the lens-iris diaphragm.
During the chronic stage, ocular and dermatologic manifestations are common. Depigmentation of the choroid begins within the first 3 months after the onset of the disease. Areas of hyperpigmentation also may develop in the fundus. Dalen-Fuchs nodules may be seen in the peripheral and midperipheral retina. These nodules are small, yellow lesions that typically are located in the midperiphery of the retina. Eventually, the lesions fade and become atrophic.
Dermatologic changes include vitiligo and poliosis of the lashes, eyebrows, and hair. The vitiligo tends to be distributed symmetrically over the head, eyelids, and trunk. The duration of the chronic stage is typically several months, but it may last for many years.
During the recurrent stage, patients may develop recurrent or chronic anterior uveitis. In some patients, low-grade choroidal inflammation may accompany the anterior uveitis, which may require indocyanine green angiography for visualization. Recurrent posterior uveitis with serous retinal detachment is rare. Patients treated with corticosteroids and/or immunomodulator therapy for 6 months or less may be at higher risk for recurrent serous retinal detachment.
Ocular complications are relatively common during this stage and include cataracts, glaucoma, choroidal neovascularization, and subretinal fibrosis.
Patients suspected of having VKH disease should undergo a thorough physical examination to determine whether cutaneous, neurologic, and ophthalmic manifestations of the disorder exist.
Sensitivity to touch of the hair and skin may be noted during the prodromal stage, while vitiligo, poliosis, and alopecia typically develop during the chronic stage. Vitiligo often is distributed symmetrically over the head, face, and trunk. The sacral region is a common site for the development of vitiligo. Poliosis may involve the scalp hair, eyebrows, and eyelashes.
Meningeal signs develop during the prodromal stage; they include meningismus, headache, and occasional confusion. CSF pleocytosis is relatively common during the prodrome.
Focal neurologic signs include the following:
Cranial nerve palsies
Inner ear disorders, including dysacusis, tinnitus, and vertigo, occur in as many as 75% of patients. Cochlear hearing loss occurs mainly in high-frequency ranges. Inner ear dysfunction improves several months after onset in most patients.
Visual acuity may be decreased markedly in both eyes at the onset of the uveitic stage. Patients may present with unilateral loss of vision, but most develop bilateral disease within the first 10 days following onset.
Ocular adnexa involvement includes poliosis of the scalp, eyebrows, or eyelashes, which may develop during the convalescent stage of VKH disease. Vitiligo also may occur on the eyelids and face during this stage.
Anterior-segment manifestations include the following:
Perilimbal vitiligo (Sugiura sign) - One of the earliest manifestations of depigmentation; uncommon, except in Japanese patients
Granulomatous or nongranulomatous anterior uveitis - May occur; Busacca nodules, Koeppe nodules, and mutton-fat keratic precipitates are characteristic of granulomatous anterior uveitis
Posterior synechiae - May be noted, especially in chronic cases; pupillary membrane formation is relatively common
Some patients may present with a shallow anterior chamber due to edema and infiltration of the ciliary body, with forward rotation of the lens-iris diaphragm and possible angle-closure glaucoma. Glaucoma may occur secondary not only to angle closure but also to pupillary block, or it may arise in association with chronic uveitis.
Cataracts may develop as a result of chronic inflammation and/or chronic corticosteroid therapy.
Anterior vitreous cells may be noted, especially in patients with severe anterior uveitis. Optic disc hyperemia or edema may be present.
A study by Nakao et al indicated that a patient’s age and optic disc morphology, not the severity of inflammation, are associated with optic disc swelling in VKH disease. The retrospective, observational study included 58 patients (116 eyes), with 16 patients (32 eyes) demonstrating disc edema. Patients with disc swelling had a mean age of 58.9 years, compared with 41.4 years for those without swelling. Other factors, such as intraocular pressure, refractive error, and the cup-to-disc ratio, as well as the ratio of the disc-macula distance to the disc diameter, also differed between patients with swelling and those without it.
One of the earliest retinal manifestations of VKH disease is retinal edema, which is often located within the posterior pole. This typically is followed by the development of bilateral, multifocal serous retinal detachments. The detachments occur most commonly in the inferior retina. (See the image below.)
During the chronic stage of the disease, the serous detachments resolve and retinal pigment epithelium (RPE) alterations are common, including depigmentation, demarcation lines, and areas of hyperpigmentation.
The fundus of Asian and Hispanic patients may develop the characteristic red-orange appearance of the sunset-glow fundus, although this is relatively uncommon in other groups of patients. Areas of hyperpigmentation are also common and reflect changes occurring at the level of the RPE. Subretinal fibrosis, RPE migration, and disciform scars also may occur.
Neovascularization of the disc and retina may develop and can result in vitreous hemorrhage. Choroidal neovascularization of the macula may occur in the chronic stage and can result in profound loss of visual acuity.
Andreoli CM, Foster CS. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin. 2006 Spring. 46(2):111-22. [Medline].
Rajendram R, Evans M, Rao NA. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin. 2005 Spring. 45(2):115-34. [Medline].
Yang P, Ren Y, Li B, Fang W, Meng Q, Kijlstra A. Clinical characteristics of Vogt-Koyanagi-Harada syndrome in Chinese patients. Ophthalmology. 2007 Mar. 114(3):606-14. [Medline].
Usui Y, Goto H, Sakai J, Takeuchi M, Usui M, Rao NA. Presumed Vogt-Koyanagi-Harada disease with unilateral ocular involvement: report of three cases. Graefes Arch Clin Exp Ophthalmol. 2009 Aug. 247(8):1127-32. [Medline].
da Silva FT, Damico FM, Marin ML, Goldberg AC, Hirata CE, Takiuti PH, et al. Revised diagnostic criteria for vogt-koyanagi-harada disease: considerations on the different disease categories. Am J Ophthalmol. 2009 Feb. 147(2):339-345.e5. [Medline].
PATTISON EM. UVEOMENINGOENCEPHALITIC SYNDROME (VOGT-KOYANAGI-HARADA). Arch Neurol. 1965 Feb. 12:197-205. [Medline].
Vogt A. Frühzeitiges Ergrauen der Zilien und Bemerkungen uber den sogenannten plötzlichen Eintritt dieser Veranderung. Klin Monatsbl Augenheilk. 1906;44:228-42.
Harada E. On the acute diffuse choroiditis. Acta Soc Ophthalmol Jpn. 1926;30:356-78.
Koyanagi Y. Dysakusis, Alopecia und Poliosis bei schwerer Uveitis nicht traumatischen Ursprungs. Klin Monatsbl Augenheilk. 1929;82:194-211.
Babel J. Syndrome de Vogt-Koyanagi. Schweiz Med Wochenscher. 1932;44:1136.
Read RW, Holland GN, Rao NA, Tabbara KF, Ohno S, Arellanes-Garcia L, et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature. Am J Ophthalmol. 2001 May. 131(5):647-52. [Medline].
Nordlund JJ, Albert D, Forget B, Lerner AB. Halo nevi and the Vogt-Koyanagi-Harada syndrome. Manifestations of vitiligo. Arch Dermatol. 1980 Jun. 116(6):690-2. [Medline].
Kondo I, Yamagata K, Yamaki K, Sakuragi S. [Analysis of the candidate antigen for Harada's disease]. Nihon Ganka Gakkai Zasshi. 1994 Jun. 98(6):596-603. [Medline].
Yamaki K, Gocho K, Hayakawa K, Kondo I, Sakuragi S. Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease. J Immunol. 2000 Dec 15. 165(12):7323-9. [Medline].
Hashimoto T, Takizawa H, Yukimura K, Ohta K. Vogt-Koyanagi-Harada disease associated with brainstem encephalitis. J Clin Neurosci. 2009 Apr. 16(4):593-5. [Medline].
Gloddek B, Lassmann S, Gloddek J, Arnold W. Role of S-100beta as potential autoantigen in an autoimmune disease of the inner ear. J Neuroimmunol. 1999 Nov 1. 101(1):39-46. [Medline].
El-Asrar AM, Struyf S, Kangave D, Al-Obeidan SS, Opdenakker G, Geboes K, et al. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis. Clin Immunol. 2011 May. 139(2):177-84. [Medline].
Chi W, Yang P, Li B, Wu C, Jin H, Zhu X, et al. IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. J Allergy Clin Immunol. 2007 May. 119(5):1218-24. [Medline].
Yang Y, Xiao X, Li F, Du L, Kijlstra A, Yang P. Increased IL-7 expression in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2012 Feb. 53(2):1012-7. [Medline].
Kluger N, Mura F, Guillot B, Bessis D. Vogt-koyanagi-harada syndrome associated with psoriasis and autoimmune thyroid disease. Acta Derm Venereol. 2008. 88(4):397-8. [Medline].
Al Hemidan AI, Tabbara KF, Althomali T. Vogt-Koyanagi-Harada associated with diabetes mellitus and celiac disease in a 3-year-old girl. Eur J Ophthalmol. 2006 Jan-Feb. 16(1):173-7. [Medline].
Suzuki H, Isaka M, Suzuki S. Type 1 diabetes mellitus associated with Graves' disease and Vogt-Koyanagi-Harada syndrome. Intern Med. 2008. 47(13):1241-4. [Medline].
Najman-Vainer J, Levinson RD, Graves MC, Nguyen BT, Engstrom RE Jr, Holland GN. An association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome. Am J Ophthalmol. 2001 May. 131(5):615-9. [Medline].
Matsuo T, Masuda I, Ota K, Yamadori I, Sunami R, Nose S. Vogt-Koyanagi-Harada syndrome in two patients with immunoglobulin A nephropathy. Acta Med Okayama. 2007 Oct. 61(5):305-9. [Medline].
Hashida N, Kanayama S, Kawasaki A, Ogawa K. A case of vogt-koyanagi-harada disease associated with malignant lymphoma. Jpn J Ophthalmol. 2005 May-Jun. 49(3):253-6. [Medline].
Sunakawa M, Okinami S. Epstein-Barr virus-related antibody pattern in uveitis. Jpn J Ophthalmol. 1985. 29(4):423-8. [Medline].
SCHLAEGEL TF Jr, MORRIS WR. VIRUSLIKE INCLUSION BODIES IN SUBRETINAL FLUID IN UVEO-ENCEPHALITIS. Am J Ophthalmol. 1964 Dec. 58:940-5. [Medline].
Tabbara KF. Vogt-Koyanagi-Harada syndrome after cutaneous injury. Ophthalmology. 1999 Oct. 106(10):1854-5. [Medline].
Rathinam SR, Namperumalsamy P, Nozik RA, Cunningham ET Jr. Vogt-Koyanagi-Harada syndrome after cutaneous injury. Ophthalmology. 1999 Mar. 106(3):635-8. [Medline].
Donaldson RC, Canaan SA Jr, McLean RB, Ackerman LV. Uveitis and vitiligo associated with BCG treatment for malignant melanoma. Surgery. 1974 Nov. 76(5):771-8. [Medline].
Sober AJ, Haynes HA. Uveitis, poliosis, hypomelanosis, and alopecia in a patient with malignant melanoma. Arch Dermatol. 1978 Mar. 114(3):439-41. [Medline].
Accorinti M, Pirraglia MP, Corsi C, Caggiano C. Vogt-Koyanagi-Harada disease after head trauma. Eur J Ophthalmol. 2007 Sep-Oct. 17(5):847-52. [Medline].
Yi X, Yang P, Sun M, Yang Y, Li F. Decreased 1,25-Dihydroxyvitamin D3 level is involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Mol Vis. 2011 Mar 9. 17:673-9. [Medline]. [Full Text].
Levinson RD, Du Z, Luo L, Holland GN, Rao NA, Reed EF, et al. KIR and HLA gene combinations in Vogt-Koyanagi-Harada disease. Hum Immunol. 2008 Jun. 69(6):349-53. [Medline].
Horie Y, Takemoto Y, Miyazaki A, Namba K, Kase S, Yoshida K, et al. Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients. Mol Vis. 2006 Dec 20. 12:1601-5. [Medline].
Hou S, Yang P, Du L, Zhou H, Lin X, Liu X, et al. Small ubiquitin-like modifier 4 (SUMO4) polymorphisms and Vogt-Koyanagi-Harada (VKH) syndrome in the Chinese Han population. Mol Vis. 2008. 14:2597-603. [Medline]. [Full Text].
Davis JL, Mittal KK, Freidlin V, Mellow SR, Optican DC, Palestine AG, et al. HLA associations and ancestry in Vogt-Koyanagi-Harada disease and sympathetic ophthalmia. Ophthalmology. 1990 Sep. 97(9):1137-42. [Medline].
Pivetti-Pezzi P, Accorinti M, Colabelli-Gisoldi RA, Pirraglia MP. Vogt-Koyanagi-Harada disease and HLA type in Italian patients. Am J Ophthalmol. 1996 Dec. 122(6):889-91. [Medline].
Goldberg AC, Yamamoto JH, Chiarella JM, Marin ML, Sibinelli M, Neufeld R, et al. HLA-DRB1*0405 is the predominant allele in Brazilian patients with Vogt-Koyanagi-Harada disease. Hum Immunol. 1998 Mar. 59(3):183-8. [Medline].
Abad S, Monnet D, Caillat-Zucman S, Mrejen S, Blanche P, Chalumeau M, et al. Characteristics of Vogt-Koyanagi-Harada disease in a French cohort: ethnicity, systemic manifestations, and HLA genotype data. Ocul Immunol Inflamm. 2008 Jan-Feb. 16(1):3-8. [Medline].
Chee SP, Jap A, Bacsal K. Prognostic factors of Vogt-Koyanagi-Harada disease in Singapore. Am J Ophthalmol. 2009 Jan. 147(1):154-161.e1. [Medline].
Ostergaard J, Goldschmidt E, Andersen N. Vogt-Koyanagi-Harada syndrome in a Greenlandic Inuit. Acta Ophthalmol. 2008 Aug. 86(5):576-8. [Medline].
Ohguro N, Sonoda KH, Takeuchi M, Matsumura M, Mochizuki M. The 2009 prospective multi-center epidemiologic survey of uveitis in Japan. Jpn J Ophthalmol. 2012 Sep. 56(5):432-5. [Medline].
Nussenblatt RB. Clinical studies of Vogt-Koyanagi-Harada's disease at the National Eye Institute, NIH, USA. Jpn J Ophthalmol. 1988. 32(3):330-3. [Medline].
Berker N, Ozdamar Y, Soykan E, Ozdal P, Ozkan SS. Vogt-Koyanagi-Harada syndrome in children: report of a case and review of the literature. Ocul Immunol Inflamm. 2007 Jul-Aug. 15(4):351-7. [Medline].
Nakao K, Abematsu N, Mizushima Y, Sakamoto T. Optic disc swelling in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2012 Apr. 53(4):1917-22. [Medline].
Read RW, Yu F, Accorinti M, Bodaghi B, Chee SP, Fardeau C, et al. Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2006 Jul. 142(1):119-24. [Medline].
Bacsal K, Wen DS, Chee SP. Concomitant choroidal inflammation during anterior segment recurrence in Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2008 Mar. 145(3):480-486. [Medline].
Errera MH, Fardeau C, Cohen D, Navarro A, Gaudric A, Bodaghi B, et al. Effect of the duration of immunomodulatory therapy on the clinical features of recurrent episodes in Vogt--Koyanagi--Harada disease. Acta Ophthalmol. 2011 Jun. 89(4):e357-66. [Medline].
Nakao K, Abematsu N, Mizushima Y, Sakamoto T. Optic disc swelling in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2012 Apr. 53(4):1917-22. [Medline].
Pahk PJ, Todd DJ, Blaha GR, Soukiasian SH, Landmann DS, Craven DE, et al. Intravascular lymphoma masquerading as Vogt-Koyanagi-Harada syndrome. Ocul Immunol Inflamm. 2008 May-Jun. 16(3):123-6. [Medline].
Kitaichi N, Matoba H, Ohno S. The positive role of lumbar puncture in the diagnosis of Vogt-Koyanagi-Harada disease: lymphocyte subsets in the aqueous humor and cerebrospinal fluid. Int Ophthalmol. 2007 Apr-Jun. 27(2-3):97-103. [Medline].
Ondrey FG, Moldestad E, Mastroianni MA, Pikus A, Sklare D, Vernon E, et al. Sensorineural hearing loss in Vogt-Koyanagi-Harada syndrome. Laryngoscope. 2006 Oct. 116(10):1873-6. [Medline].
Arellanes-García L, Hernández-Barrios M, Fromow-Guerra J, Cervantes-Fanning P. Fluorescein fundus angiographic findings in Vogt-Koyanagi-Harada syndrome. Int Ophthalmol. 2007 Apr-Jun. 27(2-3):155-61. [Medline].
Wu W, Wen F, Huang S, Luo G, Wu D. Indocyanine green angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi-Harada disease. Graefes Arch Clin Exp Ophthalmol. 2007 Jul. 245(7):937-40. [Medline].
Chee SP, Jap A, Cheung CM. The prognostic value of angiography in Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2010 Dec. 150(6):888-93. [Medline].
da Silva FT, Hirata CE, Sakata VM, Olivalves E, Preti R, Pimentel S, et al. Indocyanine green angiography findings in patients with long-standing Vogt-koyanagi-Harada disease: a cross-sectional study. BMC Ophthalmol. 2012 Aug 13. 12(1):40. [Medline].
Maruko I, Iida T, Sugano Y, Oyamada H, Sekiryu T, Fujiwara T, et al. Subfoveal choroidal thickness after treatment of Vogt-Koyanagi-Harada disease. Retina. 2011 Mar. 31(3):510-7. [Medline].
Lohman BD, Gustafson CA, McKinney AM, Sarikaya B, Silbert SC. MR imaging of Vogt-Koyanagi-Harada syndrome with leptomeningeal enhancement. AJNR Am J Neuroradiol. 2011 Oct. 32(9):E169-71. [Medline].
Han HJ, Kim HY, Park JH, Lee EJ, Kim do G, Shin DI. Magnetic resonance imaging of pachymeningeal enhancement in Vogt-Koyanagi-Harada disease. Neurol Sci. 2010 Dec. 31(6):785-8. [Medline].
Kim SJ, Yu HG. The use of low-dose azathioprine in patients with Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm. 2007 Sep-Oct. 15(5):381-7. [Medline].
Agarwal M, Ganesh SK, Biswas J. Triple agent immunosuppressive therapy in Vogt-Koyanagi-Harada syndrome. Ocul Immunol Inflamm. 2006 Dec. 14(6):333-9. [Medline].
Choudhary A, Harding SP, Bucknall RC, Pearce IA. Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory eye disease. J Ocul Pharmacol Ther. 2006 Jun. 22(3):168-75. [Medline].
Nussenblatt RB, Palestine AG, Chan CC. Cyclosporin A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents. Am J Ophthalmol. 1983 Sep. 96(3):275-82. [Medline].
Yamaguchi Y, Otani T, Kishi S. Tomographic features of serous retinal detachment with multilobular dye pooling in acute Vogt-Koyanagi-Harada disease. Am J Ophthalmol. 2007 Aug. 144(2):260-5. [Medline].
Tellier Z. Human immunoglobulins in intraocular inflammation. Ann N Y Acad Sci. 2007 Sep. 1110:337-47. [Medline].
González-Delgado M, González C, Blázquez JI, Salas-Puig J, Castro J, Hernández-Lahoz C. [Intravenous immunoglobulin therapy in Vogt-Koyanagi-Harada syndrome]. Neurologia. 2004 Sep. 19(7):401-3. [Medline].
Wang Y, Gaudio PA. Infliximab therapy for 2 patients with Vogt-Koyanagi-Harada syndrome. Ocul Immunol Inflamm. 2008 Jul-Aug. 16(4):167-71. [Medline].
Kahn P, Weiss M, Imundo LF, Levy DM. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006 May. 113(5):860-4.e2. [Medline].
Moreker MR, Lodhi SA, Pathengay A. Role of intravitreal triamcinolone as an adjuvant in the management of Vogt-Koyanagi-Harada disease. Indian J Ophthalmol. 2007 Nov-Dec. 55(6):479-80. [Medline]. [Full Text].
Perente I, Utine CA, Cakir H, Kaya V, Tutkun IT, Yilmaz OF. Management of ocular complications of Vogt-Koyanagi-Harada syndrome. Int Ophthalmol. 2009 Feb. 29(1):33-7. [Medline].