Vogt Koyanagi Harada Syndrome

Ernawati Hidayat

, Milka Wulansari

, Yosep Ferdinand Rahmat Sugianto

, Galih Sari Damayanti

Meira Dewi Kusuma Astutik

Department of Derrmatovenereology, Faculty of Medicine,

Diponegoro University/Dr.Kariadi Hospital

Department of Anatomic Pathology, Faculty of Medicine, Diponegoro University/Dr.Kariadi Hospital

*Corresponding author

Keywords: VKH, vitiligo, uveitis

Abstract: Vogt-Koyanagi-Harada syndrome (VKHS) is a rare autoimmune disorder involving pigmented multiorgan.

VKHS reported 6-8% in Asia,1-4 % in North America, and 2-4 % in Brazil of all uveitis. Diagnosis is made

based on American Uveitis Society (AUS) criteria; no history of eye trauma, and minimum 3 of 4 signs:

bilateral chronic iridocyclitis, uveitis, neurologic signs (tinnitus, neck stiffness, CNS symptoms), and

dermatologic signs (alopecia, poliosis, vitiligo). A 51-year-old female presented with generalized

hypopigmented-non pruritic patches since 8-year-old. Visual impairment was reported one month before.

Patches of white hair were found on the forehead and eyelashes. Tinnitus and frequent headache were

reported. There was no history of eye trauma. Ophthalmologic examination revealed bilateral panuveitis and

retinal detachment on the right eye. Histopathologic examination showed no melanin pigment in the basal

layer. The patient was treated with systemic methyl-prednisolone and topical steroid creams. Prognosis is ad

malam for ad sanam and ad cosmeticam. The diagnosis was based on AUS criteria and histopathologic

examination. The precise etiology for VKHS is challenging to establish. Treatment required long term

steroid administration and routine follow up to assess the progression of this disease.

1 INTRODUCTION

Vogt Koyanagi Harada Syndrome (VKHS), initially

described as an uveomeningoencephalitic syndrome,

is a rare granulomatous inflammatory disease that

affects pigmented structures, such as eye, inner ear,

meninges, skin, and hair (Geel et al, 2016; Lavezzo

et al, 2016). The disease is defined as a non-

infectious, bilateral, and granulomatous panuveitis

that occurs with or without extraocular

manifestations, and it typically affects young adults

(Ando et al, 2018).

In 1906, Vogt reported a patient

with atraumatic, idiopathic uveitis, poliosis, and

alopecia, a syndrome that in time would be

associated with his name. In 1926, Harada reported

five cases of bilateral posterior uveitis and retinal

detachment. In 1929, Koyanagi reported 16 patients

with headache, fever, dysgeusia, vitiligo, poliosis,

alopecia, bilateral anterior uveitis with occasional

exudative retinal detachment. Koyanagi published a

review article associating the posterior eye

involvement unequivocally with auditory and

integumentary manifestations. In 1932, Babel

suggested that these cases represented a single

entity, which was then named Vogt-Koyanagi-

Harada Disease (Geel et al, 2016; Lavezzo et al,

2016; Ando et al, 2018).

VKHS more frequently affects individuals of

pigmented skin, such as Asians, Middle Easterners,

Hispanics, and Native Americans (Ando et al, 2018;

O’Keefe et al, 2018; Silpa-Archa et al, 2016; Emily

et al, 2018).

The incidence of VKHS varies. Among

all cases of uveitis, it was reported 6-8% in Asia,1-4

% in North America, and 2-4 % in Brazil of all

uveitis. In China, VKHS is one of the most common

uveitis entities. In the United States, the incidence of

VKHS is approximately 1.5 to 6 per 1 million

patients, while in Japan, it is seen in approximately

800 new patients each year. Most studies have found

that women were affected more frequently than men

and that most patients were in the second to fifth

decades of life at the onset of the disease. However,

children and the elderly may also be affected.

Women account for 55 to 78 % of VKHS patients in

348

Hidayat, E., Wulansari, M., Sugianto, Y., Damayanti, G. and Astutik, D.

Vogt Koyanagi Harada Syndrome.

DOI: 10.5220/0009988503480351

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 348-351

ISBN: 978-989-758-469-5

the United States and approximately 38 % in Japan,

showing a global variation in gender predilection

(Lavezzo et al, 2016; Giannakourasa et al, 2017).

The exact etiology of VKHS is still a matter of

inquiry. The most accepted mechanism involves

autoimmune aggression against antigens associated

with melanocytes in a genetically susceptible

individual after a virus infection trigger.

Immunological and histopathological studies suggest

that VKH is an autoimmune inflammatory condition

mediated by CD4þ T cells that target melanocytes.

These activated T cells likely initiate the

inflammatory process through generation of

cytokines, IL 17 and IL 23,35 in individuals with

altered tolerance to melanocytes from deficient T

regulatory cells (Lavezzo et al, 2016; Emily et al,

2018; Baltmr et al, 2017).

Diagnosis is made based on American Uveitis

Society (AUS) criteria; no history of eye trauma or

surgery, and minimum 3 of 4 signs: Bilateral chronic

iridocyclitis, posterior uveitis (multifocal exudative

retinal or RPE detachments; disc hyperemia or

edema; or “sunset glow fundus”, which is a yellow-

orange appearance of the fundus due to

depigmentation of the RPE and choroid), Neurologic

signs (tinnitus, neck stiffness, cranial nerve or

central nervous system symptoms or cerebral spinal

fluid pleocytosis) and Cutaneous findings (alopecia,

poliosis or vitiligo) (Geel et al, 2016; Lavezzo et al,

2016; O’Keefe at al, 2017; Coutinho et al, 2017).

Early diagnosis and prompt immunosuppressive

treatment with corticosteroids and other

immunosuppressives can halt the progression and

prevent recurrence and vision loss. The mainstay of

treatment of VKHS is prompt, high-dose systemic

corticosteroids, followed by slow tapering of oral

corticosteroids throughout a minimum 6-month

period (Lavezzo et al, 2016; Joanne et al, 2014).

Localized lesions of vitiligo can be treated with a

high-potency fluorinated corticosteroid for 1–2

months. Treatment can be gradually tapered to a

lower potency corticosteroid (Birlea et al, 2012).

2 CASE

A 12-year-old girl came to Dermato-venereology

Departement Dr.Kariadi Hospital with generalized

hypopigmented-non pruritic patches since 8-year-

old. Visual impairment was reported one month

before. Patches of white hair were found on the

forehead and eyelashes. Tinnitus and frequent

headache were reported. There was no history of eye

trauma or surgery. Ophthalmologic examination

revealed bilateral panuveitis and retinal detachment

on the right eye. No similar history or symptoms in

his family. Physical examination showed body

height 165 cm, and bodyweight 65kg, blood pressure

is 120/70 mmHg, respiratory rate 18x/m, heart rate

88x/m, and axilla temperature 36°C. Skin lesions are

generalized hypopigmented macules, poliosis on

forehead and eyelashes.

The routine laboratory examination result was

typical. Histopathologic examination showed no

melanin pigment on the basal layer. The working

diagnosis is Vogt Koyanagi Harada Syndrome. The

patient was given oral methylprednisolone 16mg 2-

0-1 long term and followed by tapering off and

fluticasone propionate 0,05%/ twice daily.

Prognosis, quo ad sanam dubia ad malam, quo ad

kosmetikam dubia ad malam.

Figure 1. Generalized hypopigmented patches

Figure 2. Histopathologic examination A) no melanin

pigment on the basal layer. B) Hyperkeratosis and no

melanin pigment

3 DISCUSSION

The diagnosis of Vogt Koyanagi Harada Syndrome

in the patient was established by history, physical

examination, and histopathological examination.

Anamnesis a 51-year-old female presented with

generalized hypopigmented-non pruritic patches

since 8-year-old. Visual impairment was reported

B

Vogt Koyanagi Harada Syndrome

349

one month before. Patches of white hair were found

on the forehead and eyelashes. Tinnitus and frequent

headache were reported. There was no history of eye

trauma or surgery. Ophthalmologic examination

revealed bilateral panuveitis and retinal detachment

on the right eye. No similar history or symptoms in

his family. VKHS presents clinically in 4 different

phases: prodromal, acute uveitis, convalescent, and

chronic recurrent.

The prodromal phase may present a viral

infection and last anywhere between a few days to a

few weeks. In this phase, before ocular involvement,

clinical manifestations are predominantly

extraocular and include headache (82%),

meningismus (55%), fever (18%), nausea (9%),

vertigo (9%), orbital pain, auditory disturbances,

photophobia, and tinnitus. However, some patients

present with typical clinical features of VKH

without the prodromal symptoms. The acute uveitic

phase is following the prodromal phase, blurring of

vision develops in patients in both eyes, although the

involvement of 1 eye may be delayed. The

convalescent phase is Several weeks to months after

the acute uveitic phase, depigmentation of the

choroid, vitiligo, and poliosis occurs. The

convalescent phase usually lasts for months. Chronic

recurrent intraocular inflammation develops in some

of the patients and is characterized by exacerbations

of granulomatous anterior uveitis that is usually

resistant to systemic steroid therapy. This chronic

recurrent phase usually develops 6 to 9 months after

initial presentation and is also marked by

complications such as retinal pigment epithelium

(RPE) proliferation, subretinal fibrosis subretinal

neovascular membranes, posterior subcapsular

cataract, posterior synechiae, open-angle glaucoma

and, occasionally, angle-closure glaucoma, as well

as band keratopathy

(Lavezzo et al, 2016; Silpa-

Archa et al, 2016)

Physical examination revealed skin lesions are

generalized hypopigmented macules, poliosis on

forehead and eyelashes. Based on literature VKHS

have founded skin and hair changes: alopecia,

vitiligo, and poliosis.(Geel et al, 2016;Lavezzo et al,

2016; Silpa-Archa et al, 2016)

Histopathologic examination, in this case,

showed no melanin pigment in the basal layer. A

skin biopsy is rarely necessary to confirm the

diagnosis of vitiligo. Generally, histology shows an

epidermis devoid of melanocytes in lesional areas

and sometimes sparse dermal, perivascular, and

perifollicular lymphocytic infiltrates at the margins

of early vitiligo lesions and active lesions, consistent

with cell-mediated immune processes destroying

melanocytes in situ.(Birlea et al,2012)

The patient was given oral methylprednisolone

16mg 2-0-1 long term and followed by tapering off

and fluticasone propionate 0,05% cream/ twice

daily. Based on literature treatment of VKHS is

prompt, high-dose systemic corticosteroids,

administered either orally (prednisone 1–1.5 mg/kg

per day) or through a short course of intravenous

delivery (methylprednisolone 1000 mg per day,

intravenously, during 3 days), followed by slow

tapering of oral corticosteroids throughout a

minimum 6-month period. Timing to initiate

therapy, corticosteroid dosing, and duration of

therapy are the key factors in reducing the chance of

recurrences. (Lavezzo et al, 2016.Joanne et al,2014)

Localized lesions of vitiligo can be treated with a

high-potency fluorinated corticosteroid (e.g.,

clobetasol propionate ointment, 0.05%) for 1–2

months. Treatment can be gradually tapered to a

lower potency corticosteroid (e.g., hydrocortisone

butyrate cream, 0.1%). (Birlea et al,2012) Prognosis,

quo ad sanam dubia ad malam, quo ad kosmetikam

dubia ad malam.

4 CONCLUSION

Has been reported a case of Vogt Koyanagi Harada

Syndrome in a 51-year-old female presented with

generalized hypopigmented-non pruritic patches

since 8-year-old. Visual impairment was reported

one month before. Patches of white hair were found

on the forehead and eyelashes. Tinnitus and frequent

headache were reported. Physical examination

revealed Skin lesions are generalized

hypopigmented macules, poliosis on forehead and

eyelashes. Histopathologic examination, in this case,

showed no melanin pigment in the basal layer. The

mainstay of treatment of VKHS is prompt, high-

dose systemic corticosteroids, followed by slow

tapering of oral corticosteroids throughout a

minimum 6-month period.

Localized lesions of

vitiligo can be treated with a high-potency

fluorinated corticosteroid for 1–2 months. Treatment

can be gradually tapered to a lower potency

corticosteroid. Prognosis quo ad sanam dubia ad

malam, quo ad kosmetikam dubia ad malam.

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

350

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