Download Uveadermatological syndrome (Vogt-Koyanagi- Harada

UVEADERMATOLOGIC SYNDROME IN A SIBERIAN HUSKY
Uveadermatological syndrome (Vogt-KoyanagiHarada-like syndrome) with depigmentation in a
Siberian Husky
M. KIBAR1,2*, O. ASLAN1, K. ARSLAN1
Erciyes University, Faculty of Veterinary Medicine, 38039 Kayseri, TURKEY
Kyrgyzstan Turkey Manas University, Faculty of Veterinary Medicine, 720044 Bishkek, KYRGYZSTAN
1
2
Corresponding author: [email protected]
SUMMARY
RESUME
The aim of this study to present the cytogenetic approach in a case of
uveodermatologic syndrome in a 18-months-old, male, Siberian Husky. This
dog was referred with a history of vision impairment and bilateral redish eyes.
Clinical examination confirmed depigmentation over the lips and mouth
mucosal area. On ophthalmic examination there was bilateral dilated pupilla,
depigmentation of the fundus with visionable choroidal vessels, posterior
uveitis, and loss of vision. A presumptive diagnosis of uveodermatological
syndrome was made. Complete blood counts and biochemical parameters
were normal. The case was cytogenetically evaluated, and GTG (G-bands by
trypsin using Giemsa)-banding was performed. No numerical chromosomal
anomalies were found. Medical treatment consisted in oral and topical
administration of dexamethazone, with 1% syclopantholathydroclorur eye
drop. To depressed immune reaction azathioprine also given by oral route.
Dermatologic signs showed good improvement but the dog remained blind.
Syndrome uvéocutané avec dépigmentation chez un Husky de Sibérie
Keywords: Uvea dermatological
depigmentation, dog
syndrome,
eye,
Le but de cette étude est de présenter l’approche cytogénétique d’un cas de
syndrome uveodermatologique chez un Husky de Sibérie mâle de 18 mois.
Le chien a été présenté avec un historique de baisse de la vision et des yeux
rougeâtres. L’examen clinique a montré une dépigmentation sur les lèvres et
de la muqueuse buccale. A l’examen ophtalmologique, les pupilles étaient en
mydriase, une dépigmentation du fond d’œil avec des vaisseaux choroïdiens
visibles, et une uvéite postérieure ont été identifiés. Une présomption de
syndrome uvéocutané a été évoquée. Les paramètres de la numération et de
la formule sanguine ainsi que ceux de l’examen biochimique sanguin étaient
normaux. Une analyse cytogénétique A été faite à partir du sang périphérique
Giemsa (GTG) a été utilisé baguage. Aucune anomalie chromosomique n’a été
identifiée. Le traitement médical a consisté en l’administration orale et topique
de dexaméthasone, avec un collyre de cyclopantholate 1%. L’azathioprine a été
administrée par voie orale comme immunodépresseur. Signes dermatologiques
ont bien progressé, mais le chien n’a pas retrouvé de vision.
Mots-cles : Syndrome uvéocutané, uvée, dépigmentation
cutanée, chien
Introduction
The Vogt-Koyanagi-Harada syndrome (VKH) is a wellestablished multiorgan disorder that is characterized by
a bilateral, diffuse, granulomatous uveitis associated with
vitiligo, poliosis, alopecia, and meningeal irritation with or
without auditory disturbances [5, 7]. The history, clinical
manifestations, ophthalmic signs and histological changes are
very similar to those seen in humans with VKH disease. As
all the symptoms seen in affected humans are not present in
dogs, the syndrome should be referred to as Vogt-KoyanagiHarada-like (VKH-like) or uveodermatologic syndrome
(UDS) in this species [3, 5].
The aim of this study was to present a case of cytogenetic
approach in a Siberian Husky with uveodermatologic
syndrome.
Case Report
A 18-months-old, male, Siberian Husky dog was referred
with a history of vision impairment and bilateral redish
eyes. Clinical examination confirmed depigmentation and
Revue Méd. Vét., 2014, 165, 1-2, 57-60
ulceration on lip’s, mouth’s, labial mucosal area, and nasal
planum (Fig. 1). The owner reported that the dog vision
was declining. Ophthalmic examination revealed bilateral
conjunctival redness, congestion of the episcleral vessels,
bilateral papillary dilatation, and reddish fundic reflexes
(Fig. 2). Neither aqueous flare, iris hyperemia, nor keratic
precipitates were indicative of anterior uveitis. Menace
response and dazzle reflex were absent on both eyes and
the direct pupillary light reflex was severely decreased
bilaterally. The Schirmer tear test I (SchirmerTranentest,
EickemeyerVet) was normal for both eyes. The intraocular
pressures (IOP) in the both eyes were within normal limits
(OD: 16 mmHg, OS: 15 mmHg, reference value: 10-25
mmHg). The fundus was subalbinotic bilaterally. Posterior
uveitis and loss of vision were determined bilaterally. In the
right eye unilateral bullous retinal detachment was identified
by ultrasonography (SonoSite 180 Plus, SonoSite), (Fig. 3).
The retina was detached over 2700 in the same eye.
57
58
Figure 1: Note buccal mucosa depigmentation and labial mucosa ulceration.
KIBAR (M.) AND COLLABORATORS
Heparinized peripheral dog blood (0.5 ml) was collected
and cultured for chromose analysis by the modified method
of Ozkul [17]. Blood samples were cultured at 37oC for 72
hour in 6 ml RPMI 1640 with Glutamaxand 25 mM HEPES
(Gibco) supplemented with 3 ml of phytohemagglutinin
(PHA), 20 ml of fetal calf serum and 1 ml of penicillin/
streptomycin. After the 72 hour culture period, 0.1 ml of
colcemid solution (10 µg/ml) was added to culture tube
and incubated for 30 min at 37oC. After culture in colcemid
solution, cells were fixed with hypotonic solution (0.075
M KCl) and fixative solution (1:3; glacial acetic acid and
absolute methanol). All chromosome preparations were
stained with GTG (G-bands by trypsin using Giemsa). The
slides were immersed in trypsin solution (Dissolve 0.1 g of
trypsin (1:250) in 100 ml of Gurr Buffer) for 5 to 10 seconds.
After that, slides were rinsed in distilled water and dried at
room temperature and staining in Giemsa dye for 6 min
(5% Giemsa with Gurr Buffer) was performed. After the dog
blood culture had been obtained and the slides prepared,
Giemsa banding was applied to the chromosomes (Fig. 4). In
the present case no numerical chromosomal anomalies were
found.
Figure 2: Both eyes of a 18-months-old male Siberian Husky dog. Note the
bilateral mydriasis and reddish fundic reflexes.
Figure 4: Metaphases spread of dog (2n= 78)
Treatment was instituted with azathioprine (Imuran,
GlaxoSmithkline), 2 mg/kg, PO, q24h and dexamethasone
(Onadron, IE Ulagay), 1.25 mg/kg, PO, q24h. Topical 0.1%
dexamethasone ophthalmic solution (Dekort, Deva) OU, q4h
was also added to the treatment protocol. Subconjunctival
triamcinolone (Kenakort-A, Deva) was injected bilaterally,
10 mg, only once. Topical 1% cyclopentolate (Sikloplejin,
Abdi Ibrahim), a cycloplegic compound, was topically
applied to the eyes every 4 to 24 h.
Figure 3: Ultrasonographic view of retinal detachment in right eye.
Upon follow-up, a thorough ophthalmic examination
revealed that the retina still remaining detached. The plan
was to institute biweekly check-ups to determine if the retina
would reattach, if vision will be restored and repigmentation
will start.
Revue Méd. Vét., 2014, 165, 1-2, 57-60
UVEADERMATOLOGIC SYNDROME IN A SIBERIAN HUSKY
Discussion
There is no marked sex predisposition for UDS even
though a trend towards males has been described [7, 11, 12].
Barros and coworkers described the disease in 13 of 21 Akitas
(61.9%) aged between 13 and 30 months [1] while Morgan
reported a mean age of 2.8 years for affected dogs [15]. In
case reported here, dog was 18 months old, and according to
history dog was not blind when he was puppy.
The syndrome in humans is described as being of genetic
origin, involving multible hereditary factors [8, 12]. The
cause of the disease in dogs is still undetermined but a role for
immune system has been suggested, with melanocytes being
the target cells. But it has been reported that an inflammatory
condition of autoimmune origin in which cytotoxic T cell
target melanocytes was present in genetically susceptible
individuals [5]. The immune-mediated mechanism is
unknown, however sensitization to melanocytic antigens by
means of cutaneous injury or possible viral infection has been
assumed [3, 19]. The highest incidence appears among the
Akita, suggesting breed predisposition and perhaps genetic
transmission [1, 4, 12]. Our result could indicate that UDS
(VKH-like syndrome) with depigmentation in a Husky is
not associated with numerical chromosomal abnormalities.
However in clinical cases, for detail screening, FISH
(fluorescence in-situ hybridization) technique may be used.
FISH is very powerfull molecular cytogenetic analysis that
can be used for detected molecular translocations, deletions
or duplications.
Clinical signs are characterized by depigmentation of the
skin at the nasal planum and mucocutaneous junctions of the
mouth, eyelids, scrotum and perianal region [6, 7, 16]. Hair
loss in several parts of the derma and secondary pyodermitis
has also been reported [12]. In this case generalized poliosis,
depigmentation on superior and inferior mucocutaneous
junctions of lips, mouth, buccal mucosa, and nasal planum,
as well as dermatitis was presented. There were ulceration
and depigmentation on labial mucosa. There was no alopecia
in the present dog.
Ophthalmic signs include bilateral panuveitis with
exudative retinal detachments, diminished or absent pupillary
light reflexes, blepharospasm, and photophobia, anterior
uveitis, hyphema, keratic precipitates and chorioretinitis
[1, 12]. Affected dogs not necessarily present with bilateral
uveitis. It has been shown that in dogs with heterochromia
irides (i.e. 2 different colored irises), it is possible for only 1 eye
to show signs of UDS. This is most likely due to asymmetrical
uveal pigmentation [18, 20]. In this case bilateral uveitis was
present and associated with absent pupillary light response.
In additionally, fundus was subalbinotic bilaterally. Posterior
uveitis and loss of vision were determined. On ophthalmic
examination, all abnormalities were bilateral.
Revue Méd. Vét., 2014, 165, 1-2, 57-60
59
Ultrasonography is an important screening tool to
evaluate the posterior segment of the eye [13, 21]. If the
view is obscured by intraocular bleeding, an ultrasound
examination should be performed to determine the retinal
detachment [9]. In the case reported here, a unilateral
bullous retinal detachment was identified in the right eye.
The retina was detached over 2700 in this eye, but no retinal
detachment was diagnosed in the left eye.
There are two main medications involved in the treatment
of UDS. Corticosteroids decrease inflammation within the
eye, stabilize blood-aqueous barrier, and suppress the autoimmune response [20]. If glucocorticoids are not effective at
controlling the syndrome or if adverse side effects occur, an
immunosuppressant drug e.g. azathioprine, cyclosporine can
be added to the treatment regimen [14].
Treatment to control the inflammation with rapid
and aggressive topical and systemic administration
of immunosuppressors can result in marked clinical
improvement of the ocular and skin lesions [12]. The
case here in described underwent a combined initial
immunosupressive therapy with dexamethasone and
azothioprine which was gradually tapared. In addition,
topical dexamethasone and cyclopanholate were applied.
The maintenance therapy consisted of oral azathioprine on
alternate-day long-term therapy. A rapid improvement of the
cutaneous clinical signs was observed with the therapy and
repigmentation started after 2 months of treatment.
Poor vision outcome has been reported in dogs because
of the uveal inflammation, retinal detachment, and several
ocular complications which often lead to visiual loss [3, 7,
12]. Visual prognosis depends on an early diagnosis and
aggressive and prolonged immunosupressive therapy [2, 7].
In this case, loss of vision was maintained with the long-term
therapy.
In conclusion, diagnosis of uveodermatological syndrome
needs a carefully clinical examination and treatment should
be started immediately and aggressively to get marked
clinical positive response of dermal and visual lesions.
Acknowledgements
This study presented as an abstract at the Eurobiotech 2012
Agricultural Symposium, Kayseri, Turkey, 2012. Scientific
committe was evaluated by 2nd best poster presentation.
References
1. BARROS P.S.M., SAFATLE A.M.V., MALERBA T.A.,
YRIO K., ALVARENGA J., LARSSON M.H.M.A.:
Uveitis and dermal depigmentation (Vogt–Koyanagi–
Harada-like syndrome) in Akita dogs I. Clinical aspects.
Braz. J. Vet. Res. Anim. Sci., 1991, 28, 75–79.
60
2. BOLDY K.L., FURLONG R.C., HOLLAND G.N.:
Uveodermatologic syndrome in the dog: clinical
characteristics and treatment of a disorder similar to
human Vogt–Koyanagi–Harada syndrome. Vet. Focus,
1989, 1, 112–114.
3. CĂTOI C., ZOTESCU M., BABA A.I., GAL A., RUS I.V.:
Vogt-Koyanagi-Harada-Like syndrome in a German
Shepherd dog. Bulletin USAMV-CN., 2007, 64, 83-87
4. COLLINS B.K., MOORE C.P.: Diseases and surgery of
the canine anterior uvea. In: K.N. Gelatt (éd.): Veterinary
Ophthalmology, 3rd edition, Lippincott, Williams and
Wilkins, Philadelphia, 1999, 755-762.
5. DAMICO F.M., BEZERRA F.T., SILVA G.C., GASPARIN
F., YAMAMOTO J.H.: New insights into Vogt-KoyanagiHarada disease. Arq. Brasil. Oftal., 2009, 72, 413-420.
6. FURLONG R.C., BOLDY K.L., HOLLAND G.N.,
STEINMETZ R.L., FOOS R.Y.: Uveodermatologic
syndrome in dogs: a model of Vogt-Koyanagi-Harada
syndrome. Invest. Ophthalmol. Vis. Sci., 1989, 30, 86.
7. HERRERA H.D., DUCHENE A.G.: Uveodermatologic
syndrome (Vogt-Koyanagi-Harada-like syndrome)
with generalized depigmentation in a Dachshund. Vet.
Ophthalmol., 1998, 1, 47-51.
8. GOLDBERG A.C., YAMAMOTO J.H., CHIARELLA
J.M., MARIN M.L., SIBINELLI M., NEUFELD R.,
HIRATA C.E., OLIVALVES E., KALIL J.: HLA-DRFB1
0405 is the predominant allele in Brazilian patients with
Vogt–Koyanagi–Harada disease. Hum. Immunol., 1998,
59, 183–188.
9. GUMPENBERGER M., KOLM G.: Ultrasonographic
and computed tomographic examinations of the avian
eye: physiologic appearance, pathologic findings, and
comparative biometric measurement. Vet. Radiol.
Ultrasound., 2006, 47, 492-502.
10. GUSTAVSSON I.: The chromosomes of the dog.
Hereditas., 1964, 51, 187–189.
11. KERN T.J., WALTON D.K., RIIS R.C., MANNING T.O.,
LARATTA L.J., DZIEZYC J.: Uveitis associated with
KIBAR (M.) AND COLLABORATORS
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
poliosis and vitiligo in six dogs. J. Am. Vet. Med. Assoc.,
1985, 187, 408–414.
LAUS J.L., SOUSA M.G., CABRAL V.P., MAMEDE F.V.,
TINUCCI-COSTA, M.: Uveodermatologic syndrome in
a Brazilian Fila dog. Vet. Ophthalmol., 2004, 7, 193-196.
MCLAUGHLIN S.A., RENDER J.A., BRIGHTMAN
A.H., WHITELEY H.E., HELPER L.C., SHADDUCK
J.A.: Intraocular findings in three dogs and one cat with
chronic glaucoma. J. Am. Vet. Med. Assoc., 1987, 191,
1443-1445.
MINODA H., SAKAI J., SUIGIURA M.: High incidence
of Epstein–Barr virus replication in B lymphocytes in
Vogt–Hoyanagi–Harada disease. Nihon Ganka Gakkai
Zasshi., 1999, 103, 289–296.
MORGAN RV.: Vogt-Koyanagi-Harada syndrome in
humans and dogs. Compend. Contin. Educ. Pract. Vet.,
1989, 11, 1211-1218.
MURPHY C.J., BELLHORN R.W., THIRKILL C.:
Anti-retinal antibodies associated with Vogt-KoyanagiHarada-like syndrome in a dog. J. Am. Anim. Hosp.
Assoc., 1991, 27, 399-402.
OZKUL, Y.: Localization of CO4107 Marker, CTR1 and
Wilson (ATP7B) BAC Clones on Dog Chromosomes.
Turk. J. Vet. Anim. Sci., 2005, 29, 945-949.
PYE C.C.: Uveodermatologic syndrome in an Akita.
Can. Vet. J., 2009, 50, 861-864.
RATHINAM S.R., NAMPERUMALSAMY P., NOZIK
R.A., CUNNINGHAM E.T.JR.: Vogt–Koyanagi–Harada
syndrome after cutaneous injury. Ophthalmol., 1999,
106, 635–638.
SIGLE K.J., MCLELLAN G.J., HAYNES J.S., MYERS
R.K., BETTS D.M.: Unilateral uveitis in a dog with
uveodermatologic syndrome. J. Am. Vet. Med. Assoc.,
2006, 228, 543–548.
THOMAS R., NAVIN S., SINGH T., CHAKRABARTI S.:
A tiger with glaucoma. Br. J. Ophtalmol., 2006, 90, 1549.
Revue Méd. Vét., 2014, 165, 1-2, 57-60