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Ophthalmological examination revealed a marked loss of visual acuity in both eyes&#59; anterior pole biomicroscopy revealed Tyndall phenomenon with posterior synechiae &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Nonscarring diffuse alopecia was also observed on the scalp&#44; together with poliosis of the right eyebrow &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A and B&#41;&#46; The results of the blood workup&#8212;complete blood count&#44; biochemistry&#44; clotting&#44; protein analysis&#44; antibodies to antinuclear antigen and extractable nuclear antigen&#44; serology for syphilis and viruses &#40;hepatitis A&#44; B&#44; and C viruses&#59; human immunodeficiency virus&#59; Epstein-Barr virus&#59; cytomegalovirus&#41;&#44; and thyroid hormones&#8212;were negative or normal&#46; Cerebral magnetic resonance imaging ruled out meningeal or encephalic disease&#46; Histocompatibility testing was positive for HLA-DR4 and HLA-DR53&#46; These findings enabled a diagnosis of Vogt-Koyanagi-Harada disease to be confirmed&#46; Treatment with intravenous methylprednisolone &#40;1<span class="elsevierStyleHsp" style=""></span>g&#41; was prescribed for 3 days&#44; with subsequent oral administration tapered over 12 weeks&#46; The patient&#39;s clinical condition improved considerably&#44; not only in terms of systemic manifestations&#44; but also with complete resolution of the alopecia&#46; However&#44; the new hair remained whitish-gray in color &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Vogt-Koyanagi-Harada disease&#44; which was first reported in 1951&#44; is a rare systemic inflammatory disorder mediated by T lymphocytes acting against pigmented cells in the uvea&#44; skin&#44; inner ear&#44; and leptomeninges&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It has an incidence of 6&#46;5 cases per million and is more common in Hispanic and Native American individuals and Asian women aged between 20 and 50 years&#46; Although its etiology is unknown&#44; immunogenetic analysis suggests a strong association with some HLA antigens &#40;DR4&#44; DRB1&#44; and DR53&#41; and genes of the tyrosinase family that cause susceptibility to the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It is associated with various infectious diseases and other disorders whose pathogenic mechanisms are of immunological origin&#44; such as autoimmune thyroid disease&#44; psoriasis&#44; linear immunoglobulin A bullous dermatosis&#44; and inflammatory vitiligo as a consequence of the destruction of melanocytes by cytotoxic CD8<span class="elsevierStyleSup">&#43;</span> T lymphocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis is based essentially on clinical manifestations&#44; as there are no specific confirmatory tests&#44; and the diagnostic criteria include dermatologic findings &#40;alopecia&#44; poliosis&#44; and vitiligo&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Typical extracutaneous clinical manifestations include disorders of the eyes &#40;bilateral granulomatous uveitis&#44; retinal detachment&#44; and loss of vision&#41; and neurological and auditory conditions &#40;headache&#44; aseptic meningitis&#44; vertigo&#44; nystagmus&#44; and hypoacusis&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Alopecia can be seen in 70&#37; of cases within weeks or months after the onset of ocular symptoms&#46; It resolves completely after a variable period&#46; Alopecia and the poliosis traditionally reported by ophthalmologists were recently considered to be alopecia areata with subsequent growth of white hair&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Vitiligo affects almost half of all cases&#59; it is often symmetrical and the pigmentary changes may be permanent&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Early high-dose systemic corticosteroids are the treatment of choice in patients with active Vogt-Koyanagi-Harada disease&#46; In cases of recurrent or corticosteroid-refractory disease&#44; other immunosuppressive agents such as ciclosporin&#44; cyclophosphamide&#44; or azathioprine can be added to the treatment&#46; A favorable response has been reported with adalimumab and rituximab in refractory cases&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Prognosis is relatively benign&#44; and although the most common complications are visual&#44; total blindness is now rare&#46; Patients may also experience personality disorders&#44; psychosis&#44; and deafness&#44; as occurred in the Spanish painter Francisco de Goya when creating his famous black paintings&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Hern&#225;ndez-Bel P&#44; et al&#46; Enfermedad de Vogt-Koyanagi-Harada&#46; Una entidad poco conocida para el dermat&#243;logo&#46; Actas Dermosifiliogr&#46; 2013&#59;104&#58;529-31&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tyndall phenomenon with the presence of posterior synechiae characteristic of anterior uveitis&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#44; Diffuse rapid-onset alopecia on the scalp&#46; B&#44; Poliosis of the left eyebrow&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Major Criteria</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; No history of penetrating eye trauma or surgery before the episode of uveitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; No clinical or analytical evidence suggestive of other eye diseases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#46; Bilateral ocular involvement &#40;choroiditis&#44; uveitis&#44; inflammatory vitreous reaction&#44; serous retinal detachment&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&#46; Neurological and auditory findings &#40;meningism&#44; tinnitus&#44; pleocytosis in cerebrospinal fluid&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5&#46; Dermatologic findings &#40;alopecia&#44; poliosis&#44; vitiligo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>6&#46; Hypoxia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>7&#46; Central nervous system depression&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>8&#46; Petechiae&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Minor Criteria</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>9&#46; Tachycardia &#40;&#62;<span class="elsevierStyleHsp" style=""></span>120 beats per minute&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>10&#46; Fever &#40;temperature &#62;<span class="elsevierStyleHsp" style=""></span>39<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>11&#46; Unexplained anemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>12&#46; Thrombocytopenia &#40;platelet count &#60;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0040" class="elsevierStylePara elsevierViewall">We are grateful to our colleagues from the dermatology and ophthalmology departments who participated in the diagnosis and management of the patients&#46;</p>"
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Vol. 104. Núm. 6.
Páginas 529-531 (julio - agosto 2013)
Vol. 104. Núm. 6.
Páginas 529-531 (julio - agosto 2013)
Case and Research Letter
Open Access
Vogt-Koyanagi-Harada Disease: A Disorder Unfamiliar to Dermatologists
Enfermedad de Vogt-Koyanagi-Harada. Una entidad poco conocida para el dermatólogo
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P. Hernández-Bela,
Autor para correspondencia
pablohernandezbel@hotmail.com

Corresponding Author.
, J. Monterob, L. Hernández-Belb, A. Torrijos-Aguilarc
a Servicio de Dermatología, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
b Servicio de Oftalmología, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
c Servicio de Dermatología, Hospital Provincial de Castellón, Castellón, Spain
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To the Editor:

Vogt-Koyanagi-Harada disease is a rare condition that is characterized by bilateral uveitis, meningitis, auditory symptoms, and skin disorders such as vitiligo, poliosis, and alopecia.1 This report aims to draw attention to a condition that is widely discussed in the literature yet unfamiliar to dermatologists.

We present the case of a 37-year-old man from Bolivia who was seen in the emergency department with vertigo, headache, eye pain, and loss of vision in both eyes that had begun a week earlier. Three months later he was referred to the dermatology department with rapid-onset alopecia of the scalp. Physical examination revealed horizontal rotatory nystagmus at rest and on looking upward and to the right. Ophthalmological examination revealed a marked loss of visual acuity in both eyes; anterior pole biomicroscopy revealed Tyndall phenomenon with posterior synechiae (Fig. 1). Nonscarring diffuse alopecia was also observed on the scalp, together with poliosis of the right eyebrow (Fig. 2, A and B). The results of the blood workup—complete blood count, biochemistry, clotting, protein analysis, antibodies to antinuclear antigen and extractable nuclear antigen, serology for syphilis and viruses (hepatitis A, B, and C viruses; human immunodeficiency virus; Epstein-Barr virus; cytomegalovirus), and thyroid hormones—were negative or normal. Cerebral magnetic resonance imaging ruled out meningeal or encephalic disease. Histocompatibility testing was positive for HLA-DR4 and HLA-DR53. These findings enabled a diagnosis of Vogt-Koyanagi-Harada disease to be confirmed. Treatment with intravenous methylprednisolone (1g) was prescribed for 3 days, with subsequent oral administration tapered over 12 weeks. The patient's clinical condition improved considerably, not only in terms of systemic manifestations, but also with complete resolution of the alopecia. However, the new hair remained whitish-gray in color (Fig. 3).

Figure 1.

Tyndall phenomenon with the presence of posterior synechiae characteristic of anterior uveitis.

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Figure 2.

A, Diffuse rapid-onset alopecia on the scalp. B, Poliosis of the left eyebrow.

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Figure 3.

Complete resolution of alopecia after treatment, with growth of whitish-gray hair.

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Vogt-Koyanagi-Harada disease, which was first reported in 1951, is a rare systemic inflammatory disorder mediated by T lymphocytes acting against pigmented cells in the uvea, skin, inner ear, and leptomeninges.1

It has an incidence of 6.5 cases per million and is more common in Hispanic and Native American individuals and Asian women aged between 20 and 50 years. Although its etiology is unknown, immunogenetic analysis suggests a strong association with some HLA antigens (DR4, DRB1, and DR53) and genes of the tyrosinase family that cause susceptibility to the disease.2 It is associated with various infectious diseases and other disorders whose pathogenic mechanisms are of immunological origin, such as autoimmune thyroid disease, psoriasis, linear immunoglobulin A bullous dermatosis, and inflammatory vitiligo as a consequence of the destruction of melanocytes by cytotoxic CD8+ T lymphocytes.2–4

Diagnosis is based essentially on clinical manifestations, as there are no specific confirmatory tests, and the diagnostic criteria include dermatologic findings (alopecia, poliosis, and vitiligo) (Table 1). Typical extracutaneous clinical manifestations include disorders of the eyes (bilateral granulomatous uveitis, retinal detachment, and loss of vision) and neurological and auditory conditions (headache, aseptic meningitis, vertigo, nystagmus, and hypoacusis).5

Table 1.

Diagnostic Criteria of Vogt-Koyanagi-Harada Disease.

Major Criteria 
1. No history of penetrating eye trauma or surgery before the episode of uveitis 
2. No clinical or analytical evidence suggestive of other eye diseases 
3. Bilateral ocular involvement (choroiditis, uveitis, inflammatory vitreous reaction, serous retinal detachment) 
4. Neurological and auditory findings (meningism, tinnitus, pleocytosis in cerebrospinal fluid) 
5. Dermatologic findings (alopecia, poliosis, vitiligo) 
6. Hypoxia 
7. Central nervous system depression 
8. Petechiae 
 
Minor Criteria 
9. Tachycardia (>120 beats per minute) 
10. Fever (temperature >39°C) 
11. Unexplained anemia 
12. Thrombocytopenia (platelet count <150×109/L) 

Alopecia can be seen in 70% of cases within weeks or months after the onset of ocular symptoms. It resolves completely after a variable period. Alopecia and the poliosis traditionally reported by ophthalmologists were recently considered to be alopecia areata with subsequent growth of white hair.6 Vitiligo affects almost half of all cases; it is often symmetrical and the pigmentary changes may be permanent.

Early high-dose systemic corticosteroids are the treatment of choice in patients with active Vogt-Koyanagi-Harada disease. In cases of recurrent or corticosteroid-refractory disease, other immunosuppressive agents such as ciclosporin, cyclophosphamide, or azathioprine can be added to the treatment. A favorable response has been reported with adalimumab and rituximab in refractory cases.7 Prognosis is relatively benign, and although the most common complications are visual, total blindness is now rare. Patients may also experience personality disorders, psychosis, and deafness, as occurred in the Spanish painter Francisco de Goya when creating his famous black paintings.8

Acknowledgments

We are grateful to our colleagues from the dermatology and ophthalmology departments who participated in the diagnosis and management of the patients.

References
[1]
K. Igawa, H. Endo, H. Yokozeki, K. Nishioka, T. Kawaguchi.
Alopecia in Vogt-Koyanagi-Harada syndrome.
J Eur Acad Dermatol Venereol, 20 (2006), pp. 236-238
[2]
N. Kluger, F. Mura, B. Guillot, D. Bessis.
Vogt-Koyanagi-Harada syndrome associated with psoriasis and autoimmune thyroid disease.
Acta Derm Venereol, 88 (2008), pp. 397-398
[3]
S. Yanagihara, N. Mizuno, A. Naruse, C. Tateishi, D. Tsuruta, M. Ishii.
Linear immunoglobulin A/immunoglobulin G bullous dermatosis associated with Vogt-Koyanagi-Harada disease.
J Dermatol, 38 (2011), pp. 798-801
[4]
D. Tsuruta, T. Hamada, H. Teramae, H. Mito, M. Ishii.
Inflammatory vitiligo in Vogt-Koyanagi-Harada disease.
J Am Acad Dermatol, 44 (2001), pp. 129-131
[5]
R.W. Read, G.N. Holland, N.A. Rao, K.F. Tabbara, S. Ohno, L. Arellanes-García, et al.
Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.
Am J Ophthalmol, 131 (2001), pp. 647-652
[6]
W.M. Haque, M.R. Mir, S. Hsu.
Vogt-Koyanagi-Harada syndrome: Association with alopecia areata.
Dermatol Online J, 15 (2009), pp. 10
[7]
R. Dolz-Marco, R. Gallego-Pinazo, M. Díaz-LLopis.
Rituximab in refractory Vogt-Koyanagi-Harada disease.
J Ophthalmic Inflamm Infect, 1 (2011), pp. 177-180
[8]
L.M. Vargas.
The black paintings and the Vogt-Koyanagi-Harada syndrome.
J Fla Med Assoc, 82 (1995), pp. 533-534

Please cite this article as: Hernández-Bel P, et al. Enfermedad de Vogt-Koyanagi-Harada. Una entidad poco conocida para el dermatólogo. Actas Dermosifiliogr. 2013;104:529-31.

Copyright © 2012. Elsevier España, S.L. and AEDV
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