Vitiligo on Vogt-Koyanagi-Harada Disease

Meiza

, Irvin Aldikha

, Renni Yuniati

, Radityastuti

, Meira Dewi Kusuma Astuti

Department of Dermatovenereology, Faculty of Medicine Diponegoro University / Dr. Kariadi General Hospital

Department of Pathological Anatomy Faculty of Medicine Diponegoro University / Dr. Kariadi General Hospital

*Telephone: 081360022801; email: meiza.dvjan18@gmail.

Keywords: Vogt-Koyanagi-Harada Disease, vitiligo, poliosis

Abstract: Vogt-Koyanagi-Harada (VKH) disease is a rare granulomatous inflammatory disease that affects the

pigmented structure. The etiopathogenic of this syndrome remains unclear; itis proposed as an autoimmune

disorder. Diagnosis of VKH is made based on least 3 of the following four criteria of The American Uveitis

Society (Bilateral iridocyclitis, posterior uveitis, neurological sign, cutaneous findings of vitiligo, poliosis or

alopecia) and an absence of prior trauma or surgery. Treatment for repigmentation of vitiligo is non-surgical

and/or surgical, which yield good result. This case report is aimed to give more understanding of the

diagnosis and management of vitiligo on VKH. A 47-year-old male with the complaint of white spots

presented previously on the face for three weeks. The patient was referred from the ophthalmology

department with bilateral iridocyclitis and panuveitis. There was no hearing loss. From the physical

examination, hypopigmented macules and poliosis were found on the eyebrows. Histopathological

examination supported the diagnosis of vitiligo. The patient was treated with methylprednisolone tablet 16

mg 2-0-1, and fluticasone propionate cream 0.05% every 12 hours on the affected skin. The prognosis of

this patient was quo ad vitam ad bonam quo ad sanam ad malam and quo ad cosmeticam dubia ad bonam.

In this case, we found 3 of the four criteria of diagnosis is Bilateral iridocyclitis, posterior uveitis, cutaneous

findings of vitiligo, and poliosis. The patient was given high potency topical corticosteroids twice daily and

oral corticosteroid. It showed significant clinical improvement after four months.

1 INTRODUCTION

Vogt Koyanagi Harada Disease is a rare

granulomatous inflammation that can affect

pigmentation structure, where the main target is a

cell which contains melanin on eyes, inner ear, brain

membrane, skin, and hair (Lavezzo et al, 2016;

Sakata et al, 2014; Anstery, 2010). In the beginning,

VKH disease be conceived as an

uveomeningoencephalitis syndrome (Lavezzo et al,

2016).

In 1906, Swiss’s ophthalmologist residency

student Alfred Vogt described the disease as

bilateral subacute iridocyclitis with early bleaching

on eyelashes. In 1926, Einosuke Harada reported 5

cases with posterior bilateral uveitis and retina

exfoliation after the inflammation is decreased.

Close with that time in 1929, Koyanagi published an

article that explained the pathogenesis of the disease,

includes prodromal phase, acute uveitis phase with

the involvement of posterior segment, the recovery

phase followed by hearing and skin manifestation. In

1932, Babel advised this disease is on the same form

with later named Vogt Koyanagi Harada (Lavezzo et

al, 2016; Sakata et al, 2014; Anstery, 2010).

Vogt Koyanagi Harada disease often affects the

individual with darkly pigmented people such as in

Asia, Hispanic, Origin American and Hindian and

Brazilian (Lavezzo et al, 2016; Burkholder, 2015;

Bilgic et al, 2014; Su et al, 2018).

Most of the

research informed that woman affected more than a

man with ratio 2:1 (Lavezzo et al, 2016; Burkholder,

2015; Bilgic et al, 2014; Ng el al, 2014).

Most of the

patients are on the second to fifth decade of the life

with a peak of the event on third and fourth

(Lavezzo et al, 2016; Burkholder, 2015; Bilgic et al,

2014; Bayer, 2016). Elderly and children can be

affected by the disease, and although it is rare, one

author reported that the youngest patient is three

years old girl (Lavezzo et al, 2016; Burkholder,

2015; Bayer, 2016). The prevalence and incidence of

VKH is a rare disease. In the USA the incidence of

VKH is about 1,5 – 6 cases per 1 million patients

while in Japan is about 800 new cases annually

(Lavezzo et al, 2016).

Meiza, ., Aldikha, I., Yuniati, R., Radityastuti, . and Astuti, M.

Vitiligo on Vogt-Koyanagi-Harada Disease.

DOI: 10.5220/0009989803890393

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 389-393

ISBN: 978-989-758-469-5

389

Etiology and pathogenesis of Vogt Koyanagi

Harada suspected to be a systemic autoimmune

disease which clearly unknown (Lavezzo et al, 2016;

Burkholder, 2015; Su et al, 2018). The Vogt

Koyanagi Harada may be systemic autoimmune

disease on melanosis that affects mainly on eyes,

inner ear, and brain membrane and skin (Lavezzo et

al, 2016; Su et al, 2018).

An author has reported a

case that one of the triggers of this disease is an

infectious agent such as Epstein-Barr Virus &

Cytomegalovirus. Trauma on the skin can be one of

the etiology of the disease, even though the

causative relationship between the virus and the

disease have not been established yet (Lavezzo et al,

2016; Burkholder, 2015; Ng et al, 2014).

The diagnosis of VKH disease was based on the

American Uveitis Society (AUS) criteria. The

physical examination also some criteria that have

been made to be diagnostic approachment (Lavezzo

et al, 2016; Sakata et al, 2014).

The diagnosis of

Vogt Koyanagi Harada disease was based on criteria

made by American Uveitis Society (AUS) criteria on

1978 and Sigiura

’

s criteria on 1976 (Lavezzo et al,

2016).

American Uveitis Society recommend,

without history of trauma and eyes surgery

procedure , at least there are 3 or 4 other criteria to

diagnose VKH disease, which are iridocyclitis

bilateral, posterior uveitis, neurology abnormality,

and skin abnormality likes vitiligo, poliosis, or

alopecia. The accurate diagnosis of VKH disease

can prevent complication (Bilgic et al, 2014).

The active and adequate treatment on early phase

can reduce the risk to recurrent. The early treatment

and aggressive corticosteroid are the best treatment

for this disease on acute uveitis phase, and also

corticosteroid treatment on this acute phase can

reduce the risk of lost sight permanently (Lavezzo et

al, 2016; Sakata et al, 2014; Burkholder, 2015; Ng et

al, 2014). The dosage of systemic corticosteroid is

given by oral is prednisone 1-1.5 mg/KgBB/Day, or,

methylprednisolone 1 gr/day for three days.

Treatment with corticosteroid must reduce slowly

and last at least for six months (Lavezzo et al, 2016;

Ng et al, 2014). The treatment for skin

depigmentation is the same with vitiligo treatment

(Bayer, 2016).

2 CASE

A 47 years old man, came with complaint of having

some white spots for three weeks ago. The white

spots appear on the face, It has been starting from

the chin and spreading through cheek, nose, and

forehead, the white spots are not itchy, and the

patient did not apply topical regimen to the spots.

His eyelashes had been starting to bleach when he

came to the hospital. The patient was referred from

the ophthalmology department. One year prior, the

patient suffered from fever, pain on eyes, and blurry

sight, headache without a history of trauma or eyes

surgery. In the ophthalmology department, the

patient is diagnosed with panuveitis and iridocyclitis

bilateral. On that time, there were no hearing

symptoms of ear buzzing and had no white spots on

face. The wound on the Genitalia was denied, no

similar history or symptoms in his family. General

condition was compos mentis, weel nourished with

height 165cm and weight 63kg, blood pressure is

120/80mmHg, respiratory rate 18x/m, and heart rate

is 80x/m, and axilla temperature is 37

C. Physical

examination, dermatology status is found

hypopigmented macules on face and poliosis on

dermatologic examination.

On laboratory testing the hemoglobin was 15

gr%; leucocytes 5.500/mm

; eritrocytes 4,3

juta/mm

; trombocytes 231.000/mm

; ureum 15

mg/dl; creatinin 0,8 mg/dl; SGOT 14 U/I; SGPT 45

U/I. VDRL and TPHA are negative.

The histopathologic examination found flat

sprained epithelial, creatine, follicular plugging, and

melamine pigment is not equal, stroma subepithelial

plain, contain sebaceous gland that suitable of

vitiligo. Diagnosis of this patient was Vogt

Koyanagi Harada disease. The treatment of vitiligo

to this patient is active potential topical

corticosteroid fluticasone 0,05 % applied every 12

hours on the face, and a systemic corticosteroid is

metilprednisolon 16 mg tab 2-0-1.

Repigmentation was found in the first month of

observation. Good clinical improvement was

observed after four-month.

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

390

Figure 1. (A) Examination on

the first

month (B) Examination on

the fourth

month

Figure 2. Microscopic histopathology

3 DISCUSSION

Vogt Koyanagi Harada (VKH) disease shows some

manifestation, in clinical side VKH disease, has 4

phases, an early phase is a prodromal phase or called

meningoencephalitis phase, which happens for 3-5

days with a flu-like syndrome, fever, headache,

orbital pain, hearing problems, tinnitus and

neurology symptoms. On this phase, the

cerebrospinal fluid test will show limonitic

pleocytosis that happens for some weeks.

In this case, patient had suffered from prodromal

phase such as fever, pain in eyes, headache for 1

week, afterward patient had the second phase which

was acute uveitis generally happens on the 3th days

until 5th days from prodromal phase and occurs for

some weeks until several months, with blurry vision,

photophobia, pain on eyes, loss of vision in one or

both of eyes. The patient was diagnosed with

panuveitis, and iridocyclitis bilateral by the

ophthalmologist with clinical symptoms is a blurry

vision, but the patient has no dysacusis, tinnitus, or

other hearing problem. The 3rd phase or

convalescence phase occurs some weeks after acute

uveitis phase. This phase started with

depigmentation, progressive tissue; on this stage,

there is skin involvement with vitiligo appearance,

poliosis, and alopecia. The clinical symptoms on the

skin occur for some months or even some years.

(Lavezzo et al, 2016;Sakata et al,2014; Burkholder,

2015; Bilgic et al, 2014)

Vitiligo develops on 19-90% cases, vitiligo

usually symmetrical and can occur in every area of

the body likes on face and back area are the most

common. The histopathologic finding showed there

was no melanosis. Poliosis occurs most on

eyebrows, eyelashes, and scalp. Alopecia can occur

as areata alopecia or diffuse hair loss (Burkholder,

2015; Bilgic et al, 2014;Ng JY et al,2014) On the

third phase, and this patient had vitiligo that was

spreading, followed by poliosis on eyebrows.

The diagnosis of Vogt Koyanagi Harada was

based on clinical symptoms. Some criteria have been

made to achieve the diagnostic, include America

Uveitis Society on1978, Sugiura on 1976. On 1999,

an international workshop for some expert made

diagnosis revision, the criteria published on 2001

which has three categories such as Complete Vogt

Koyanagi Harada disease, Incomplete Vogt

Koyanagi Harada, and suspect Vogt Koyanagi

Harada. (Lavezzo et al, 2016;Sakata et

al,2014;Anstery et al,2010)

Vitiligo on Vogt-Koyanagi-Harada Disease

391

From these three categories, there are absolute

requirements: bilateral eyes problem, no history of

trauma or eyes surgery.(Burkholder, 2015)

Revised Diagnosis Criteria on the international

workshop I in 2001

Complete disease (Criteria 1-5 must be found)

1. There is no history of ocular trauma or surgery

before the initial onset of uveitis

2. There is no clinical evidence that shows other eye

diseases

3. The involvement of both eyes

a. Rapid disease manifestations

- Diffuse choroiditis

- Alternatively, the characteristics of

fluorescein angiography and echography

findings are diffuse choroidal

thickening

b. Slow disease manifestations

- History of previous uveitis with the

characteristics described above

Ocular depigmentation (fundus sunset

glow, Sugiura sign)- and other ocular signs

(nummular chorioretinal scar, pigmented

epithelial clots or recurrent or chronic

anterior uveitis)

4. Symptoms of nerves and symptoms of hearing

5. Integumentary symptoms (alopecia, vitiligo, or

poliosis)

Incomplete disease (Criteria 1 to 3 plus one of 4 or 5

must be found)

Possible disease (Isolated eye disease, criteria 1 to 3

must be found)

This patient was suitable with the incomplete

Vogt Koyanagi Harada disease are met. This patient

has no history of penetrating ocular trauma and

surgery at the onset of uveitis and no laboratory

results that support other eye diseases.

Differential diagnosis with Alezzandrini's

syndrome can be ruled out. Alezzandrini syndrome

is characterized by ipsilateral facial vitiligo, with

unilateral taporetinal regeneration of the eyes, white

hair, poliosis, and hearing loss. Vitiligo facials and

poliosis in the eyebrows and eyelashes usually occur

after several years of abnormalities in the eye.

(Anstery et al,2010;Bilgic et al,2014;Bleue,2016)

this patient found facial vitiligo accompanied by

poliosis in the eyebrows and panuveitis with

bilateral iridocyclitis.

Treatment of vitiligo in Vogt

Koyanagi Harada disease can be treated according to

vitiligo.(Bayer,2016) The main goal of vitiligo

therapy is repigmentation, while the secondary goals

include stabilization of the disease to stop the loss of

functional melanocytes, and ensure adequate

psychosocial care and quality of life. (Bleue,2016)

Specific therapy for vitiligo repigmentation can be

done surgically and non-surgical.

Grafting can be done surgically such as punch

grafts, blister grafts, split-thickness skin grafts, and

hair follicle grafts. Surgical therapy is only

recommended for patients with a stable history of

the disease for the past 6-24 months and should only

be used for small size lesions. The surgical

procedure is generally followed by a 3-4 week

phototherapy procedure. (Bleue,2016;Stanca et

al,2012)

Topical treatments can be given, including

corticosteroids topical, calcineurin inhibitors,

calcipotriol, topical vitamin D analogs. Physical

therapy with UVB, PUVA, laser excimer. Systemic

therapy with corticosteroid use. (Bayer, 2016;Bleue,

2016;Stanca et al,2012).

Corticosteroids are the first-line therapy for

localized vitiligo and are highly recommended for

faces or small size lesions, and for children, the

benefit of corticosteroid is easy to use low cost

compared to PUVA. PUVA has proven to be less

effective and has more side effects compared to

UVB. (Bleue,2016;Stanca et al,2012)

The prognosis of this patient was quo ad vitam

ad bonam, quo ad sanam dubia ad malam, quo ad

cosmetikam dubia ad malam. Inadequate treatment

is the main factor associated with worse prognosis.

Improvements in visual impairment depend on the

rapid and precise management, and ocular symptoms

are usually right. Disorder of the skin may be

permanent last longer. (Bilgic et al,2014;Stanca et

al,2012)

4 CONCLUSION

A case of patient vitiligo in Vogt Koyanagi Harada

disease was reported in a 47-year-old male patient,

and Physical examination found hypopigmented

macules on the face and poliosis on the eyebrows.

Histopathologic examination was suitable with

vitiligo. Vogt Koyanagi Harada disease Therapy

with systemic and topical corticosteroid after four

months gave good clinical result. The prognosis of

the patient was quo ad vitam ad bonam, quo ad

sanam dubia ad malam, quo ad cosmetikam dubia ad

malam

REFERENCES

Anstery AV. 2010. Disorders of skin colour. In: Burns T,

Breatnach S, Cox N, Griffith C, editors. Rook

’

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

392



Textbook Of Dermatology, 8

edition. Weat Sussex:

Blackwell Publishing.. p.58.45-46

Bayer ML. 2016. Successful Treatment of Vitiligo

Associated with Vogt–Koyanagi. 1-2

Bilgic O. Abuzer G. Kaya K. 2014. Vogt-Koyanagi-

Harada Disease in an Adolescent Boy. Pediatric

Dermatology. 99–101.

Bleue R, Eberlein B. 2018. Therapeutic management of

vitiligo. Deutsche Dermatologische Gesellschaft

(DDG). 1-5

Burkholder MB. 2015. Vogt–Koyanagi–Harada disease.

Curr Opin Ophthalmol. 26:506–11.

Lavezzo MM, Sakata VM, Morita C, et.al. 2016. Vogt-

Koyanagi-Harada disease: review of a rare

autoimmune disease targeting antigens of

melanocytes. Orphanet J Rare Dis.11(29):1-21.

Ng JY, Luk OJ, Lai YY, et.al. 2014. Influence of

molecular genetics in Vogt-Koyanagi-Harada disease.

Journal of Ophthalmic Inflammation and Infection.

4(20):1-12

Sakata VM, Silva FT, Hirata CE, et.al. 2014. Diagnosis

and classification of Vogt–Koyanagi–Harada disease.

Autoimmunity Reviews. 1-6.

Stanca AB, Richard AS, David AN. 2012. Vitiligo. In:

Wollf, K, et.al. Gold Smith L, Katz S, Gilchrest, Palle

A, Editors. Fitzpatrick’s Dermatology In General

Medicine.8

edition. New York: Mc. Graw Hill. p.

792-803

Su E, Oza. SV, Latkany P. 2018. A case of recalcitrant

pediatric Vogt-Koyanagi-Harada disease successfully

controlled with adalimumab. Journal of the Formosan

Medical Association. 1-6

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