European Journal of Ophthalmology / Vol. 17 no. 5, 2007 / pp.

847-852

SHORT COMMUNICATION

Vogt-Koyanagi-Harada disease after head

trauma
M. ACCORINTI, M.P. PIRRAGLIA, C. CORSI, C. CAGGIANO

Department of Ophthalmology, Ocular Immunovirology Service, University of Roma “La Sapienza,” Roma -
Italy

P URPOSE . To report two cases of Vogt-Koyanagi-Harada disease after closed head trauma.
M ETHODS . Case report.
R ESULTS . Two patients, one male and one female, developed headache, dysacusis, vertigo, tinnitus,
and hair hypersensitivity shortly after a closed head trauma and, 10 and 18 days later, a bilateral
uveitis with papillitis and exudative retinal detachment in one and a bilateral mild uveitis with mac-
ular exudative detachment in the other. The ocular lesions resolved with intravenous high-dose
steroid therapy, but recurred after reduction of the dosages, requiring further steroid therapy. The
course of the disease in both patients, with the appearance of fundus depigmentation and pigment
clumping, and the occurrence of a concomitant ocular and auditory relapse in one, were typical of
Vogt-Koyanagi-Harada disease.
C ONCLUSIONS . Vogt-Koyanagi-Harada disease may appear after a closed head trauma suggesting that
even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response with-
in the eye. (Eur J Ophthalmol 2007; 17: 847-52)

K EY W ORDS . Vogt-Koyanagi-Harada disease, Head trauma, Uveitis

Accepted: June 12, 2007

INTRODUCTION stages: prodromal, uveitic, convalescent, and recurrent.

The prodromal stage is characterized by the onset of a
Vogt-Koyanagi-Harada (VKH) disease is a severe bilateral flu-like syndrome with headache, nausea, vertigo, fever,
diffuse uveitis with systemic involvement characterized by meningismus, tinnitus, neurosensorial dysacusis, and or-
skin lesions and meningeal and neurologic irritation (1, 2). bital pain. Up to 80% of patients also showed cere-
Its etiology is unknown, although a viral infection hypoth- brospinal fluid lymphocytic pleocytosis, which usually dis-
esis has been proposed after the isolation by polymerase appeared within 8 weeks (1). Cranial neuropathies,
chain reaction of Epstein-Barr virus genome in the cere- hemiparesis, aphasia, and transverse myelitis have been
brospinal fluid (3, 4) and after the demonstration of anti- rarely described (11). Skin involvement in this stage is lim-
cytomegalovirus antibody production in anterior chamber ited to a particular sensitivity of hair and skin. The uveitic
(5). The most accepted pathogenetic mechanism consid- stage (second stage) follows after some days and is char-
ers the disease a cellular immune process against acterized by a predominant posterior involvement with
melanocytes or against a common antigen expressed and multifocal choroiditis, papillitis, and circumscribed retinal
shared by the skin, the eye, meninges, and ear (6-8). A edema, usually evolving into exudative retinal detach-
genetic predisposition has also been postulated, with an ment. Inflammation eventually involves the anterior seg-
increased prevalence of the HLA DR4 antigen in patients ment, with cells and flare in the anterior chamber. The
with VKH disease of different ethnic groups (Chinese, third stage, or convalescence, follows after many weeks,
Japanese, Hispanic, Brazilian) (1, 8, 9) and in Italians (10). and is characterized by the onset of integumentary (polio-
The clinical course of VKH is usually divided into four sis involving the eyebrows, eyelashes, and scalp hair,

© Wichtig Editore, 2007 1120-6721/847-06$15.00/0

Vogt-Koyanagi-Harada disease after head trauma

alopecia, and vitiligo) and choroidal depigmentation. Oph- phy results were normal, thus excluding that a primary
thalmoscopy reveals typical sunset glow-fundus and the cerebral disorder was the cause of the head trauma. Ten
appearance of multiple, small well-circumscribed spots of days later she complained of headache, dysacusis, verti-
chorioretinal atrophy and retinal pigment epithelium mi- go, and visual acuity reduction. She was readmitted to the
gration. During the recurrent stage, the fourth stage, a same hospital and was diagnosed with bilateral uveitis
panuveitis with a predominant anterior segment involve- with papillitis and exudative retinal detachment (Fig. 1).
ment not very responsive to steroid therapy is the hall- The administered therapy was methylprednisolone 1.5
mark. High dose steroid therapy may alter the clinical mg/kg/day for 5 days, 0.8 mg/kg/day for 10 days, 0.4
course of the disease, not allowing the onset of the symp- mg/kg/day for 15 days, 0.08 mg/kg/day for 15 days, and
toms of the later stages. According to the revised criteria then 0.08 mg/kg twice weekly. The patient reported a
for the diagnosis of VKH disease (12) the absence of ocu- complete resolution of the signs and symptoms of uveitis
lar injury is necessary to fit the new diagnostic criteria, in and a restoration of visual acuity. Because of the onset of
order to differentiate VKH from sympathetic ophthalmia, a some side effects (fatigue, leg edema) the patient decided
similar disease occurring after penetrating injuries of the to stop the medication in August 2003 and, 1 month later,
eye (13). Nevertheless there are some reports on the oc- the uveitis reappeared and the patient was admitted to
currence of VKH after cutaneous injuries (14), supporting our department. Clinical examination at that time dis-
the hypothesis that a sensitization of patients may be in- played the following in both eyes: visual acuity 1/10, non-
duced by trauma on other melanocyte-containing tissues. granulomatous keratic precipitates, flare 1+, cell 1+, sub-
The aim of this study is to report the clinical course of two capsular and nuclear cataract, 3+ vitreous cells and 2+
patients who presented a typical picture of VKH after a opacities, hyperemia and swelling of the optic disk, pig-
closed head trauma. ment clumping in the macular area, and exudative retinal
detachment predominantly localized inferiorly. A complete
work-up for uveitis was unremarkable. Audiometric exam-
Case reports ination displayed a neurosensorial hypoacousia. She was
administered methylprednisolone 1 g/day for 3 days intra-
Case 1 venously in combination with atropine 1% eye drops
twice daily, dexamethasone 0.2% eye drops 6 times/day
In June 2003, a 69-year-old woman had a car accident, in in both eyes. The steroids were then administered orally
which her head struck the car windshield. She was imme- starting with prednisone 1 mg/kg/day for 4 days, 0.75
diately examined at an emergency room of a regional hos- mg/kg/day for 14 days, and slowly tapered. Visual acuity
pital and neurologic examination and computed tomogra- was restored to 6/10 and 9/10 in the right and left eye,

A B

Fig. 1 - Case 1. Bilateral papillitis and exudative retinal detachment at onset (A = right eye, B = left eye).

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A B

Fig. 2 - Case 1. Classic pigmentation of the macular area after uveitis and exudative retinal detachment resolution (A = right eye, B = left eye).

respectively. No signs of anterior uveitis were detected hypersensitivity, and tinnitus, and a few days later of bilater-
and the fundus displayed the classic pigmentation al hyperemia and visual acuity reduction. He was examined
clumping in the macular area (Fig. 2). Four months later, for the first time by a general ophthalmologist on December
while she was taking prednisone 12.5 mg/day, she com- 23. The diagnosis was bilateral macular edema and the pa-
plained of visual acuity reduction in both eyes. The clini- tient was administered betamethasone 8 mg/day for 4 days
cal examination showed a slight macular edema in the and 4 mg/day for 8 days, then deflazacort 6 mg/day, in
right eye (RE). Visual acuity was 6/10 in RE and 8/10 in combination with acetazolamide 500 mg/day. On December
the left eye (LE). Because of the patient’s refusal to in- 30, optical coherence tomography (OCT) was performed,
crease the steroid therapy appropriately, 17.5 mg/day of showing a bilateral exudative macular detachment (Fig. 3).
prednisone and a peribulbar injection of triamcinolone In January 2004, the patient complained of further visual
acetonide 40 mg in RE were administered with complete acuity reduction and OCT showed increasing macular ede-
resolution of the uveitis and visual acuity restoration. In ma. The patient received steroid therapy with deflazacort 60
September 2004, while taking prednisone 7.5 mg/day, mg/day (approximately 0.75 mg/kg) and any attempted fur-
she again complained of visual acuity reduction in LE. ther reduction was followed by a deterioration of visual acu-
Visual acuity was 3/10 and an anterior uveitis with ex- ity and increase of auditory symptoms. He was admitted to
tensive synechiae in mydriasis and a papillitis were pre- our service on February 25, 2004. Visual acuity was 10/10 in
sent. Steroids were then given at a dose of 25 mg/day in both eyes with a myopic correction. No anterior uveitis was
combination with topical therapy. Visual acuity was re- detectable, but a few cells in the vitreous and a slight macu-
stored in 20 days and no further relapses have been de- lar edema were present. There was also neurosensorial hy-
tected since October 2005. No changes in the audio- poacousia. A complete work-up for uveitis was unremark-
metric examination were detected throughout the able, nuclear magnetic resonance of the brain was normal,
follow-up, nor the appearance of cutaneous changes. and a steroid treatment with methylprednisolone 1 g/day for
The steroid therapy was slowly tapered and stopped in 3 days was administered. Thereafter oral steroids were
September 2005. given at a loading dose of prednisone 0.5 mg/kg/day for
10 days then decreasing by 5 mg/day every 10 days. Two
Case 2 months later, the visual acuity was 10/10 in both eyes
with no correction and no further macular edema was de-
A 48-year-old man had accidental domestic trauma, hitting tectable (Fig. 4). In September 2004, the patient com-
his head against a door, on December 5, 2003. On Decem- plained of tinnitus and hypoacousia. An audiometric ex-
ber 15, he complained of general malaise, headache, hair amination confirmed the deterioration of neurosensorial

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Vogt-Koyanagi-Harada disease after head trauma

A B

Fig. 3 - Case 2. Optical coherence tomography scanning of serous retinal detachment 10 days after the onset of ocular symptoms (A = right
eye, B = left eye).

A B

Fig. 4 - Case 2. Optical coherence tomography scanning of resolution of the macular exudative detachment after steroid therapy (A = right eye,
B = left eye).

A B

Fig. 5 - Case 2. Fundus photography in January 2004 (A = right eye, B = left eye).

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A B

Fig. 6 - Case 2. Fundus photography in April 2005 (A = right eye, B = left eye): diffuse depigmentation.

hypoacousia. Ophthalmic examination also displayed mild head trauma. The clinical course of the ocular disease is
anterior uveitis (cells ±, flare ±). The patient was taking very typical of VKH disease in Patient 1. The other patient
prednisone 5 mg on alternate days and therapy with might have a much less acceptable diagnosis of VKH at a
prednisone 25 mg/day in combination with topical treat- first instance. Nevertheless we could not disregard the
ment for uveitis was restored. Auditory and ocular symp- possibility that a prompt and prolonged steroid therapy
toms resolved in 15 days and then a slow tapering of could have decapitated the natural course of the VKH, al-
prednisone therapy was done. Steroid therapy was dis- lowing a prompt resolution of the ocular lesions as well as
continued in January 2005 and no further uveitis or audi- preventing further development of extraocular signs (i.e.,
tory relapses have been detected. No cutaneous signs of cutaneous lesions). Nine months after the head trauma
the disease appeared during the follow-up. A progressive and the onset of the ocular symptoms, and while he was
depigmentation of the fundus appeared over time in ab- taking 5 mg/day of prednisone, the patient developed a
sence of ophthalmoscopic or angiographic findings of oc- concomitant auditory and ocular relapse which respond
ular relapses (Figs. 5 and 6). promptly to an increase of the daily dose of steroids. Fur-
thermore, in the subsequent follow-up, the appearance of
a progressive depigmentation of the fundus in absence of
DISCUSSION ophthalmoscopic and angiographic findings of ocular re-
lapses may stress the possibility that this patient may be
VKH disease is a systemic disease of unknown etiology. diagnosed with VKH. The temporal relationship between
The pathogenetic mechanism recognizes a cellular im- the head trauma and the ocular symptoms observed in
mune response against melanocytes (1, 6, 7). Usually the two patients (10 and 18 days) may be considered suf-
there is a prodromal stage characterized by neurologic ficient to allow the onset of an immune reaction against
symptoms (1, 2). In our cases the neurologic symptoms melanocytes, as has been demonstrated in patients with
reported at onset were headache, which, unfortunately, VKH (6, 7). A possible hypothesis is that the head trauma
was not adequately defined, and neurosensorial hypoa- induced, perhaps by concussive mechanisms on
cousia. This last finding is usually uncommon after a melanocytic-containing cells, exposure of the antigen to
closed head trauma, being reported in only 16% of 50 the immune system and therefore the onset of the dis-
children after sustaining head trauma (15). None of our ease. Although a coincident onset of VKH disease in pa-
patients had, as shown by computed tomography or nu- tients with head trauma should be considered, other re-
clear magnetic resonance of the brain, any primary cere- ports of the onset of VKH after trauma in other
bral disorders that may have led to the accidents with the tissue-containing melanocytes, such as skin injuries fol-

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Vogt-Koyanagi-Harada disease after head trauma

lowed by local vitiligo and some weeks after by the onset ther investigated in all patients with a diagnosis of VKH in
of ocular manifestations typical of VKH (14), clearly indi- order to eventually redefine the diagnostic criteria of the
cates the possibility that a nonocular trauma may induce disease.
a typical VKH disease. The real incidence of VKH after
trauma in nonocular sites has never been investigated; Proprietary interest: None.

neither is a sufficient long-term follow-up of the so-called

post-traumatic features available in order to define partic-
ular findings of this disease.
Reprint requests to:
In conclusion, these two cases seem clinically to repre- Massimo Accorinti, MD
sent typical VKH disease. The temporal relationship with a Dipartimento di Scienze Oftalmologiche
closed head trauma may suggest that a trauma in Servizio Speciale di Immunovirologia Oculare
Università degli Studi di Roma “La Sapienza”
melanocyte-containing tissue may induce an inflammato-
Viale del Policlinico 155
ry response within the eye. This possibility, and the other 00161 Rome, Italy
report on VKH occurring after skin injuries, should be fur- [email protected]

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