Download Vogt-Koyanagi-Harada Syndrome

Chiombon. Chua. Corpuz. Cua. David. De Vera.
Detera. Diaz. Din. Dizon. Eugenio. Evangelista.
INTERESTING CASE
1
General Data
 CT
 29/Female
 DOA: 03 August 2010
2
Chief Complaint
Blurring of Vision
3
History of Present Illness
13 days PTA
(07/21/10)
• Ocular pruritus , OS
• Eye pain, OS
• Blurring of vision, OS
• Flashes of light
4
History of Present Illness
• Sought consult
• A> Conjunctivitis
• Prescribed with Tobradex
7 days PTA
• Partial relief of the itchiness and
redness
• Persistence of blurring of
vision, OS
5
History of Present Illness
• Followed up
• A> Glaucoma suspect
• (IOP 20mmhg)
5 days PTA
• Prescribed with Betaxolol
HCL
• did not provide relief
6
History of Present Illness
• Blurring of vision of OD
• Headache
• Sought consult at our
3 days PTA institution
7
Past Medical History
 Allergies: none
 No previous illnesses, hospitalizations and
blood transfusions
 TB exposure: (-)
 Injuries: Burn 2nd and 3rd degree burns (1992)
 Medications: none
8
Personal and Social History
 Diet: Mixed
 Smoking: 3.5 pack years
 Alcohol: 2 bottles of beer/day from 23-27
years
 Substance abuse: Denies illicit drug use
9
Family History
 Diabetes Mellitus- Grandmother
 Glaucoma- (-)
 Hypertension – (-)
 Cancer – (-)
10
Review of Systems

(-) Weight change , (-) fever & chills

(-) rashes; (-)pruritus;(-) bruising

(-) dizziness; syncope

(-) blurring of vision, eye discharge

(-) hearing changes; pain; discharge; vertigo;

(-) epistaxis; obstruction; nasal discharge, gum bleeding; oral ulcers

(-) cough, (-) dyspnea, (-) night sweats

(-) chest pain; (-)dyspnea on exertion; (-)PND; (-)palpitations

(-) abdominal pain; (-)dysphagia, (-)nausea, (-)vomiting,(-) Dyspepsia

(-)diarrhea, (-) constipation (-) indigestion, (- flatulence

(-) frequency; urgency; dysuria; nocturia; dribbling

(-) arthralgia/arthritis (-) trauma; (-)back pain
11
Physical Examination
•
Conscious, Coherent, Ambulatory, not in Cardiorespiratory distress
•
Vital signs: 110/80, PR 74 Regular, RR: 20, Temp 36.6 C
•
Warm, moist skin, no active dermatoses (+) Scars, both upper extremeties
•
Pink palpebral conjunctiva, anicteric sclerae, pupils L= 3-4mm, RTL, R= 2-3
mm RTL anisocoric, slightly hyperemic conjunctiva
•
Septum midline, turbinates not congested, no nasoaural discharge,
impacted cerumen
•
Moist buccal mucosa, no oral and palatal lesions, nonhyperemic posterior
pharyngeal wall, tonsils not enlarged
•
No limitation of neck movement, no palpable cervical lymphadenopathy
•
(-) thyroid gland enlargement
•
No breast mass palpated, no discharge
•
Thorax: no deformities, no intercostal and subcostal retractions,
symmetrical chest expansion, equal tactile fremiti, resonant, clear and equal
breath sounds
12
Physical Examination
•Adynamic precordium, AB at the 5th LICS MCL, no LV heave, thrills,
no lifts, s1 louder than s2 at the apex, s2 louder than s1 at the base, no
murmurs
13
Physical Examination
 Globular abdomen, Normoactive bowel
sounds, (-) bruits, (-) tenderness, guarding,
masses, (-) Murphy’s sign, Nonpalpable
gallbladder, Traube’s space not obliterated
 Pulses full and equal, (-) cyanosis, edema,
clubbing
14
Eye Examination
Visual Acuity
Right Eye
Left Eye
Without Correction
20/50, J12
20/200, J12
Pin hole
20/30
20/50
Amsler Grid
(+) Scotoma on OU
(+) Metamorphopsia
15
Eye Examination
External eye examination:
 Eyelids: non tender
 Lashes: not matted
 Conjunctiva: Hyperemic
 Sclera: anicteric
 Cornea: Clear
 Anterior Chamber: deep
 Lens: Clear
 Pupils: Anisocoric L= 3-4mm, RTL, R= 2-3 mm RTL
 Iris: Pigmented
16
Eye Examination
 EOM: Full and equal
 Fundoscopy:
 (+) ROR
 (+) Blurred disc Margins , OU
 (+) Serous Retinal Detachment, OU
 (+) Hyperemia of choroid
 Tonometry: 18mmHg OU
 Fluorescein angiography: hyperfluoresence of
optic disc
17
NeuroExam
 Conscious, coherent, oriented to 3 spheres, able to follow





commands, GCS 15 E4V5M6
(-) Anosmia, anisocoric pupils L= 3-4mm, RTL, R= 2-3
mm RTL; Can smile, frown, raise eyebrows, uvula
midline, can shrug shoulders, turn head from side to side
against resistance tongue deviated to right. Motor exam:
RUE: 5/5, RLE:5/5, LUE and LLE 5/5.
Reflexes: ++
Cerebellar- can do APST, FTNT with ease, No tremors
No sensory deficit
(-) Babinski, Nuchal rigidity, Brudzinski, Kernig’s sign
18
Initial Assessment
 Incomplete Vogt-Koyanagi-Harada Disease,
Acute uveitic stage
 r/o TB Uveitis
19
Uveitis
 is inflammation of the Uvea Tract, middle
section of the eye.
 Uvea Tract has three parts:
 the Iris (the colored part of the eye)
 Ciliary body (behind the iris, accomodation,
aqueous humor)
 Choroid (the vascular lining tissue underneath the
Retina).
20
DIFFERENTIAL DIAGNOSIS
Our Patient
Sympathetic
Ophthalmia
(-) History of Trauma
(-) Previous TB exposure
Previous History of Trauma , Previous Infection of
perforating eye injury
Tuberculosis
Sees “Flashes of light”
Redness
Blurred Vision
Photophobia
Redness
Blurred vision
Floaters
(+) ROR
Soft yellow white exudates
(+) Blurred disc Margins in the deep layer of the
, OU
Retina
(+) Serous Retinal
Detachment, OU
(+) Hyperemia of
choroid
(+) Hypreflouresence of
optic disc
Tuberculosis
Unilateral Cases of ocular
involvement
Granulomatous keratic
precipitates or choroidal
granulomas are present
21
Incomplete Vogt-Koyanagi-Harada
Disease, Acute uveitic stage
r/o TB uveitis
22
DIAGNOSTICS
23
Laboratories
 CBC
 Chest X-ray
 AFB smear
 PPD
24
CBC
HGB
126
Seg
0.52
RBC
4.03
Lymph
0.44
HCT
0.38
Eosin
0.04
MCV
94
ESR
8.0
MCH
31.3
MCHC
33.3
RDW
12.30
MPV
7.40
PLT
255
WBC
7.90
Neut
0.52
25
Chest X-ray
 Lung fields are clear
 The heart is not enlarged
 Both hemidiaphragm and costophrenic sulci
are intact
 Impression: No significant chest findings
26
AFB Stain
 No Acid Fast Bacilli seen in 300 oil immersion
fields on both routine and concentration
methods
27
Therapeutics
 Methylprednisolone 1mg/kg/day per IV for 3
days
 Ranitidine 150mg/tab, 1 tab OD
 Tropicamide eyedrops 1gtt BID
 CaC03 + Vit D 1 tab OD
28
Course in the wards
 On admission:
 CBC with Platelet, PPD, Chest X-ray, and ESR
were requested.
 Tropicamide eyedrops OU was also started.
 On the 2nd hospital day
 Referred to Rheumatology
 Plans for induction of high-dose steroids
29
Course in the Wards
 On the 3rd Hospital day:
 PPD test was started
Visual Acuity
Right Eye
Left Eye
Without Correction
20/50, J12
20/200, J12
 On the 4th Hospital day
 Methylprednisolone 1g/kg to run for 1 hour for 3
days.
30
Course in the wards
 On the 5th hospital day, visual acuity of the
patient improved:
Visual Acuity
Right Eye
Left Eye
Without Correction
20/40
20/70
 (-) Hyperemia of the Conjunctiva
 (-) PPD test
 Patient was given 2nd dosage of
Methylprednisolone 1mg/kg/IV to run for 1 hour
 CaC03 + Vit D 1 tab OD was started
31
Course in the wards
 On the 6th hospital day
Visual Acuity
Right Eye
Left Eye
Without Correction
20/40
20/40
 Patient received last dose of
Methylprednisolone 1mg/kg/IV to run for 1
hour.
32
Course in the wards
 7th hospital day
 Prednisone 20mg/tab 1 tab OD was started
Visual Acuity
Right Eye
Left Eye
Without Correction
20/40
20/40
33
Course in the wards
 8th hospital day
Visual Acuity
Right Eye
Left Eye
Without Correction
20/40
20/40
 Indirect Fundoscopy: Decrease in macular
edema, decrease in vitreous cell and optic
nerve hyperemia
 Patient was discharged
34
DISCUSSION
VOGT-KOYANAGIHARADA DISEASE
35
Vogt-Koyanagi-Harada disease
 Inflammatory condition of autoimmune
nature in which cytotoxic T cell target
melanocytes (eyes, inner ears, skin)
 Described by Persian Physician (Ali-ibn-Isa
940-1010 AD) –Poliosis + eye inflammation
 1932- Combined disorders described by Vogt,
Koyanagi and Harada manifestations were
under the same disease process
36
New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009;72(3):413-20
Epidemiology
 Predilection for more darkly pigmented
races: Asians, Hispanics, American Indians
 6.8-9.2% of all Uveitis referrals in Japan
37
Vogt-Koyanagi-Harada disease
Classification
 International Nomenclature Committee
Revised Diagnostic Criteria
 Classification:
 Complete VKH disease
 Incomplete VKH disease
 Probable VKH disease
38
New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009;72(3):413-20
Applicability of the 2001 revised diagnostic criteria in Brazilian Vogt-Koyanagi-Harada disease patients
Arq Bras Oftalmol. 2008;71(1):67-70
39
Vogt-Koyanagi-Harada disease
Stages
 Prodromal stage
 Acute uveitic stage
 Convalescent stage
 Chronic recurrent stage
40
Stages
Prodromal
Acute Uveitic Stage
Mimics viral
Infection
Bilateral blurring of vision
Ocular pain secondary to
Ciliary spasm
Fever
Neurological
Symptoms
Multifocal Choroidtis
Multifocal detachment
of the sensory retina
Exudative retinal
detachment
Convalsecent stage
Vitiligo
Alopecia
Poliosis
Uveal depigmentation
Sunset glow
Foci of
hyperpigmentation of
RPE
Chronic Recurrent
stage
43% in 1st three
months
52% in 1st six
months
Glaucoma
Cataract
Subretinal
Fibrosis
41
Pathophysiology
Vogt-Koyonagi-Harada
Disease
42
Vogt-Koyanagi-Harada disease
Autoimmunity Against
Melanocytes
 Clinical features of choroidal and skin depigmentation
 Transmission electron microscopy (early stage): close
contact between melanocytes and lymphocytes in the
uvea
 Histopathology (end stage): disappearance of choroidal
melanocytes, and
 Immunohistochemistry (end stage): T and B
lymphocytes in the choroid
43
New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009;72(3):413-20
Vogt-Koyanagi-Harada disease
Autoimmunity Against
Melanocytes
 Role of CD4+ T cells
 Cytotoxic leukocytes against melanoma cells in peripheral blood
and CSF
 Cytotoxic CD4 and CD8 T lymphocytes against human
melanocytes are present in the peripheral blood.
 Activated CD4+ T cells in depigmented skin and melanin-laden
macrophages d in CSF
44
New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009;72(3):413-20
Vogt-Koyanagi-Harada disease
Autoimmunity Against
Melanocytes
 Immunogenetics
 HLA-DR4/DR53
 secondary association with HLA-DR1 involving a
shared sequence linked to susceptibility to
rheumatoid arthritis.
 HLA-DRB1*0405
45
New insights into Vogt-Koyanagi-Harada disease. Arq Bras Oftalmol. 2009;72(3):413-20
Pathophysiology
46
Clinical findings in acute phase
of VKH
Figure 1 - A & B: Fundus
pictures of both eyes show
disc hyperemia, whiteyellowish choroidal lesions,
and localized exudative
retinal detachments; C & D:
Fluorescein angiographies of
both eyes show pin-point
hyperfluorescence and dye
pooling corresponding to
areas of retinal detachments;
E & F: Indocyanine green
angiographies show areas of
diffuse hyperfluorescence,
dark spot, and “hot-spots”
New insights into Vogt-KoyanagiHarada disease. Arq Bras Oftalmol.
2009;72(3):413-20
47
Clinical findings in chronic
phase of VKH
Figure 2 – A & B: Fundus
pictures of both eyes show
diffuse retinal
depigmentation and
peripapillary fibrosis;
C & D: Fluorescein
angiographies of both eyes
show diffuse window retinal
pigment epithelium defects;
E & F: Indocyanine green
angiographies
show dark spots and diffuse
late hyperfluorescence
suggestive of disease activity
New insights into Vogt-KoyanagiHarada disease. Arq Bras Oftalmol.
2009;72(3):413-20
48
Treatment- Corticosteroids
For most patients with bilateral serous detachments and severe visual
loss, begin therapy with systemic prednisone
Severe Cases
 use intravenous methylprednisolone (up to 1 g/d) for several days
before beginning oral prednisone (1 mg/kg/d)
Corticosteroids
 anti-inflammatory properties and modify the body's immune
response to diverse stimuli
 the length of treatment and subsequent taper must be
individualized for each patient
Treatment- Systemic
Corticosteroids
Prednisone
• Decrease inflammation
– reversing increased capillary permeability and suppressing PMN
activity
• DOSE
– 1-1.5 mg/kg/d PO qd initially
– Severe cases with profound loss of vision and bilateral serous
detachments may require up to 2 mg/kg/d
– length of treatment and tapering individualized for each patient
• not be less than 3 mo to avoid recurrence
• CI: hypersensitivity; viral infection; peptic ulcer disease;
hepatic dysfunction; connective tissue infections; fungal or
tubercular skin infections; GI disease
Treatment- Topical
Corticosteroids
Prednisone Acetate
•
For the treatment of associated anterior uveitis
•
Decreases inflammation by suppressing migration of polymorphonuclear
leukocytes and reversing increased capillary permeability
DOSE:
•
Instill1 gtt into conjunctival sac
•
dosing frequency is based upon severity of inflammation
–
Severe inflammation may require dosing every hour
– moderate-to-mild anterior uveitis, dosing at 4-6 times daily may be sufficient
– taper over an appropriate period to avoid rebound inflammation
Precaution: hypertension, cataract formation with long-term use, decrease
frequency to avoid adrenal insufficiency
CI: Documented hypersensitivity; viral, fungal, or tubercular infections; cataract and
glaucoma
Treatment- Cycloplegics
Tropicamide
 parasympatholytic that produces short acting mydriasis and cycloplegia
 Instillation of a long-acting cycloplegic agent can relax any ciliary muscle
spasm that can cause a deep aching pain and photophobia
 used to treat anterior uveitis, decreasing risk of posterior synechiae and
decreasing inflammation in the anterior chamber of the eye
Side Effects
 transient stinging and a slight and transient rise in intraocular pressure
 cause redness or conjunctivitis (inflammation) and also blurs vision for a
short while after instillation
Tropicamide is preferred over Atropine

Atropine has a longer half-life, causing prolonged dilation and blurry vision for up to a week
Treatment- Homatropine
Homatropine
• Blocks responses of sphincter muscle of iris and muscle of
ciliary body to cholinergic stimulation, inducing mydriasis
in 10-30 min and cycloplegia in 30-90 min
• last up to 48 h
• Individuals with heavily pigmented irides may require larger
doses
DOSE: 1-2 gtt of 2% or 1 gtt of 5% solution up to qid to induce
cycloplegia and relieve ciliary spasm
CI: Documented hypersensitivity; narrow-angle glaucoma
Precaution: elderly persons w/ increased intraocular pressure;
toxic anticholinergic systemic adverse effects can occur but
are rare when used sparingly
TreatmentImmunosuppressives
For those patients who fail to respond to high-dose
systemic corticosteroids or develop intolerable adverse
effects, immunodulatory therapy
 Cyclosporine
 Mycophenolate mofetil
 Azathioprine
 Tacrolimus
 Cyclophosphamide
55