a rare case of lupus retinopathy
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A RARE CASE OF LUPUS RETINOPATHY IN A CHILD
WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
(CASE REPORT)
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ABBREVIATIONS• ACR : The American College of Rheumatology• ALT : alanine aminotransferase • ANA : antinuclear antibodies• Anti ds-DNA: anti double stranded-deoxyribonucleic acid antibodies• Anti-RNP : anti- ribonucleoprotein • APA : anti-phospholipid antibodies • AST : aspartate aminotransferase • BW : body weight• DLE : discoid lupus erythematosus • GP : general practitioner • HLA : human leukocyte antigen• IU/L : international units per litre • KCS : keratoconjunctivitis sicca • LE: lupus erythematosus • mEq : mili equivalent• MSCT : multi slice computed tomogtraphy • PUK : peripheral ulcerative keratitis • SLE : systemic lupus erythematosus • USG : ultrasonography
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INTRODUCTION
• Lupus erythematosus is a basic term of diseases combined:– clinical manifestations – characteristic pattern of polyclonal B cell
autoimmunity• Systemic lupus erythematosus (SLE)
is LE form of the disease involving multiple organ systems
Lehman TJA, et al (2002); Blodi BA (2002); Klein-Gitelman, et al (2007); Sivaraj RR, at al (2007); Tutuncu ZN, et al (2007), Akib AA, et al (2010)
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…INTRODUCTION• The cause of SLE is still unknown,
interaction :– genetic factors, – acquired factors, and – environmental factors immune dysregulation
autoreactive persistent immune B and T lymphocytes
immune complexes tissue precipitationdefective of clearance mechanism
Lehman TJA, et al (2002); Blodi BA (2002); Klein-Gitelman, et al (2007); Sivaraj RR, at al (2007); Tutuncu ZN, et al (2007), Akib AA, et al (2010)
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…INTRODUCTION
• The incidence of lupus in children is not known – varies by location and ethnicity– female predominance 4:1 to 8:1– onset before 8 y.o. unusual
• Indonesia not available data– approx. 10.000 - 50.000 cases–<1% under 15 y.o.
Klein-Gitelman, et al (2007); Rus V, et al (2007); Danchenko N, et al (2006); Komalig FM, et al (2008); Yayasan Lupus Indonesia (2011)
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…INTRODUCTION
• The diagnosis of SLE is based on clinical and laboratory
criteria of ACR4 out of 11 criteria are present
diagnosis of SLE can be made• Organs often exposed
joints, skin, kidney, brain, liver, eye; basic lesions vasculitis
Hochberg MC (1997); Klein-Gitelman MS, et al (2007)
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…INTRODUCTION
• Ocular manifestations in SLE – 1/3 cases– sometimes potentially sight threatening – affect almost any part of the eye and
visual pathway – also caused by drugs used in the
treatment– 70% dryness
Sivaraj RR, at al (2007); Rosenbaum J, et al (2007); Fox R, et al (2002); Ushiyama O, et al (2000)
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…INTRODUCTION
• Ocular manifestations in SLE – Retinal pathologies 10% cases, but
rare in children– Optic neuritis and optic atrophy is rare
usually due to vasculitis of the vessels of optic disc
Sivaraj RR, at al (2007); Rosenbaum J, et al (2007); Fox R, et al (2002); Ushiyama O, et al (2000); Akib AA, et al (2010)
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…INTRODUCTION
• The purpose of this paper present a rare case of lupus retinopathy in a child with SLE
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CASE REPORT
• A, female, 8 y.o, 19 kgs– came to Pediatric Outpatient Clinic on
May 25th, 2011– chief complaint of fever– referred by a GP in Tuban – diagnosed as suspicious of SLE
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…CASE REPORT
• History:– fever 5 months before– accompanied w/ non-productive cough,
headache, fatigue, rashes on back & face, – hospitalized w/ dx: typhoid fever, for 7
days discharged– A few days later fever again + fatigue,
malaise, anemic, loss of appetite, hair fall, & joints pain
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…CASE REPORT
• taken to several doctors, fever (+) until 1 molast GP checked ANA test (+) referred to Dr. Soetomo Hospital
• rash on face since 7 months– disappeared in several days – 2 months later erupt again + rash on
her back more light red on sunray exposure
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…CASE REPORT• blurred vision since 3 mo. ago
– getting worse– not accompanied with pain and trauma – no ocular pain even with eye movement – dryness and redness of the eye was not found.
• headache (+), • chest pain, abdominal pain, nausea and
vomiting, cough, dispnea, edema, seizure, pareses, behavioral disturbance (-)
• defecation and urination: normal
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…CASE REPORT
• px was the only child of family• mother diabetic (-), hypertension (-),
nor taking any drugs and traditional herbs during pregnancy
• delivered spontaneously per vaginam, aterm, by midwife, BW 2500 g
• immunizations up to date.• growth and development normal
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…CASE REPORT
• Physical examination –weak, alert girl– BW: 19 kgs, BH: 119 cms– BP: 100/60 mmHg, pulse: 126 tpm, RR: 20
tpm, tax : 38.1oC– head & neck: • anemia (+), jaundice (-), cyanotic (-), dispnea
(-), lymph node enlargement (-)• malar rash (+), discoid rash (+), visual acuity
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• Figure 1. The photographs of the patient show: (a) malar rash ;(b) oral ulcer; (c) and discoid rash
…CASE REPORT
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• Figure 2. Rashes on the patient’s upper and lower extremities and ears; discoid lesions on back
…CASE REPORT
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…CASE REPORT
• chest: symmetric, retraction (-)– The heart sound normal, murmur (-)– breath sound was normal
• abdomen: distended (-), ascites (-)– liver palp. 2 x 2 x 4 cm, spleen was not
palp– bowel sound was normal, meteorism (-) – discoid lesions (+) her back
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…CASE REPORT• extremities: warm, red, and dry– maculopapular rashes (+) on upper &lower
limb– edema (-) – external genital: normal
• neurological exam: normal• lab results (in Tuban)– Hb: 6 g/dL, ESR: 140-155 mm/hour, AST 103,
ALT 97 IU/L, ANA weak positive, titre 1:32
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…CASE REPORT• the patient was fulfilled 6 of 11 ACR
criterions: – malar rash– discoid rash– photosensitivity– oral ulcer– hematologic disorder– positive of ANA test
diagnosis of systemic lupus erythematosus (SLE) established
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…CASE REPORT
• For further investigation of SLE planning dx:– work-up for anemia – work-up for hepatitis– urinalysis– feces analysis– renal and liver function test– C-reactive protein
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…CASE REPORT
• For further investigation of SLE planning dx:– electrocardiography– chest roentgenogram– abdominal ultrasono-graphy (USG)– head CT-scan– blood, urine, and fecal culture– consult to Ophthalmology Department
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…CASE REPORT
• Initial therapy:–methylprednisolone pulse 500 mg in 100
mL i.v– ampicillin-sulbactam 150 mg q.i.d. i.v – azathioprine 30 mg b.i.d p.o– acetaminophen as needed– sun-block cream during the day, and
hidrocortison 1% cream during bedtime– diet of 1500 kcal/day
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…CASE REPORT• On 2nd day of admission, – Lab result:• Hb 6,5 g/dL • SI 118 µg/dL• TIBC 263 µg/dL• SGOT 395• SGPT 182 IU/L• BUN 10 mg/dL • SC 0,5 mg/dL
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…CASE REPORT• On 2nd day of admission,
Examination of ophthalmology department : – visual acuity were: 1/60 and 1/60
Fundus examination showed: – fundus reflex (N)– margins of both optic discs: clear– pallor of both optic discs (+)– retinal bleeding (-)– exudates (+)– macular reflexes – atrophy and sheating of vascular (+)
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…CASE REPORT
• On 2nd day of admission,
The temporary conclusion pale optic discs DD atrophic optic nerve Suggestion further examinations at ophthalmology outpatient clinic
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…CASE REPORT
• On 4th day of admission–methylprednisolone pulse stopped– followed by prednisone tablets 3-3-2
(~2mg/kgBW/day) – urine and fecal culture revealed no
bacterial growth/sterile
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…CASE REPORT
• On 5th day of admission, – Echocardiography: • mild dilatation on left atrium and ventricle• mild mitral regurgitation• dilated cardiomyopathy suggestion of three next month evaluation.
– The abdominal USG: non-specific hepatomegaly
no specific treatment was given due to these results
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…CASE REPORT
• On 6th day of admission– Lab results: • Hb 8,6 g/dL• LE-cell (-)• anti ds-DNA (+): 147,1 units/mL• C3 < 28 mg/dL
– examination on Opthalmology Outpatient Clinic:• visual acuity: 1/60 and 1/60• ocular motility: (N); no pain
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…CASE REPORT– examination on Opthalmology Outpatient
Clinic:• Funduscopy : – fundus reflex (N)–margins of both optic discs: clear –pallor of both optic discs (+)– retinal bleeding (-)–soft exudates (+) cotton-wool spots–macular reflexes –atrophy and sheating of vascular (+)
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…CASE REPORT
Conclusions:bilateral optic atrophy and bilateral retinal vasculitis due to systemic lupus erythematosus
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…CASE REPORT
–On 7th day of admission, • CXR: normal lungs and heart• head MSCT-scan: normal• lab: –SGOT 94 IU/L–SGPT 85 IU/L –Na: 136 mEq/L; K: 3,9 mEq/L; Cl: 100
mEq/L–blood culture : sterile AB stopped
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…CASE REPORT
–On 7th day of admission, • CXR: normal lungs and heart; • head MSCT-scan: normal• lab: –SGOT 94 IU/L–SGPT 85 IU/L–HBsAg: (-) –Na: 136 mEq/L; K: 3,9 mEq/L; Cl: 100
mEq/L–blood culture : sterile AB stopped
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…CASE REPORT• On 21st day of admission, – prednison was tapered-off to 2-2-2 tablets
per day• On 27th day of admission, – Lab results: • Hb11,2 g/dL, L 5200/µ; Tr sufficient, • Diff count 0/0/0/48/52/0; ESR 18 mm/hour• Alb 3,8 mg/dL, • BUN 8 mg/dL; SC 0,5 mg/dL • Na 138 mEq/L; Ca 8,7 mg/dL; K 3,9 mEq/L; Cl
104 mEq/L; P 2,4 mg/dL
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…CASE REPORT• On On 29th day of admission, – the patient’s condition was good, – BP100/60 mmHg, pulse 92 tpm, RR 22 tpm,
tax 36.8oC. – patient was discharged with suggestions: • prednisone 2-2-1 p.o. tapered 5mg (1
tablet)/week• azathioprine 3x20mg should be continued• attend to Pediatric Allergy-Immunology
Outpatient Clinic on next two weeks
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DISCUSSION• SLE
interaction :– genetic factors, – acquired factors,
and – environmental
factors
Blodi BA (2002); Klein-Gitelman, et al (2007); Tutuncu ZN, et al (2007), Akib AA, et al (2010)
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…DISCUSSION• some target organs
– musculoskeletal: arthritis – skin: malar rash– renal: glomerulonephritis – cardiovascular:
pericarditis– neurologic: seizure– pulmonary: pleuritic pain– hematologic: anemia– digestive system: oral
ulcer, dysphagia, anorexia, ascites, perotinitis
– eye: keratitis, retinopathy, optic neuropathyKlein-Gitelman, et al (2007); Tutuncu ZN, et al (2007); Fox R, et al (2002)
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…DISCUSSION• The diagnosis of SLE is based on clinical
and laboratory criterions proposed by the American College of Rheumatology (ACR).
• In our case, 7 of 11 creterions were fullfilled the diagnose of systemic lupus erythematosus could be established
Klein-Gitelman, et al (2007); Rosenbaum J, et al (2007); Hochberg MC (1997)
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Criterionn Our case1. Malar Rash +2. Discoid rash +3. Photosensitivity +4. Oral ulcers +5. Nonerosive Arthritis -
6. Pleuritis or Pericarditis -
Criterionn Our case7. Renal Disorder -
8. Neurologic Disorder -
9. Hematologic Disorder +10. Immunologic Disorder
+
11. Positive Antinuclear Antibody
+
Table 1. Our case compared with ACR criterions
…DISCUSSION
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…DISCUSSION• Ocular manifestations:– Anterior segments• Usually not sight threatening• Symptoms: foreign body sensation, itching,
photophobia, heaviness of the eyelids, redness
– Posterior segments• Might be sight threatening
Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION
Anterior Segments Clinical manifestationExternal ocular Keratoconjunctivitis sicca (KCS)
Secondary Sjögren’s syndromeAdnexal involvement Discoid lupus erythematosus (DLE) of the eyelids
Periorbital edema, tendernessCorneal involvement Superficial punctate keratopathy
Recurrent epithelial erosionsPeripheral ulcerative keratitis (PUK)Interstitial stromal keratitisCorneal endothelitis (keratoendothelitis)
Conjunctival involvement Chronic conjunctivitisHypertrophic, papillomatous conjunctival lesions
Scleral involvement EpiscleritisScleritis (anterior-posterior, diffuse-nodular, necrotizing)
Uveal involvement Uveitis (anterior-posterior, granulomatous-nongranulomatous)
Table 2. Manifestations of SLE on anterior segments of eye (Peponis, 2006)
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…DISCUSSIONPosterior Segments
Clinical manifestation
Retinal involvement Cotton-wool spotsRetinal edema, ischemia, hard exudates, hemorrhagesRetinal vasculitisCentral retinal artery occlusion, cilioretinal artery occlusionRetinal vein occlusion (central or branch)Proliferative retinopathy, retinal neovascularizationPseudoretinitis pigmentosa-like retinopathy
Choroidal involvementMultifocal serous detachments of the retinal pigment epithelium (RPE) and neural retinaChoroidal neovascularizationCentral serous chorioretinopathy (CSR)Ciliochoroidal effusions
Table 3. Manifestations of SLE on posterior segments of eye (Peponis, 2006)
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…DISCUSSIONPosterior Segments
Clinical manifestation
Neuro-ophthalmological involvement
Optic nerve involvement (papillitis, ischemic optic neuropathy, retrobulbar optic neuritis)Ocular motor nerve palsiesVisual disturbances (amaurosis fugax, cortical blindness, visual field defects)Pupillary abnormalities (light-near dissociation, Horner’s syndrome)Gaze abnormalities (internuclear ophthalmoplegia, one-and-a-half syndrome)Nystagmus, ocular flutterPseudotumor cerebriMiller–Fisher syndrome
Other rare ophthalmic involvements Orbital myositis
Orbital pseudotumorOrbital apex syndrome
Table 3. Manifestations of SLE on anterior segments of eye (continued)
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…DISCUSSIONIn our case, – blurred vision (+) – ocular pain (-) – red of eyes (-)– dryness of eyes (-)– visual acuity about 1/60 on both eyes– fundus examination: bilateral pallor optic
discs optic atrophy, soft exudates cotton-wool spots, decreasing macular reflexes, and sheathing on retinal vascular
retinal & neuro-opht implication was the prominent manifestation in this case
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…DISCUSSION– Painless and gradually loss of vision on
both eyes ischemic optic neuropathy • may due to occlusion of the small vessels of
the optic nerves demyelination or axonal necrosis.
– Sheathing on vessels may due to severe vasculitis• possibility of involvement of anti-phospholipid
antibodies must be considered• unfortunately immunologic examination for this
antibody did not perform due to financial problem
Blodi BA, et al (2002); Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION– Choroidopathies should be considered in
this patient– The best examination to identify is
fluorescein fundus angiography (FFA). – In our case, it was not performed • due to financial problem• lack of experience to do this procedure on a
child in Dr. Soetomo Hospital
Blodi BA, et al (2002); Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION– The treatment regimen, depends on
• the affected target organs • disease severity
– Sun exposure should be minimized and include use of a sunscreen
– Corticosteroids control symptoms and autoantibody production in lupus• started on 1-2 mg/kg/24hr of oral prednisone in
divided daily doses• severe patient methylprednisolone 25-30
mg/kg/24hr intravenously for three consecutive days followed by prednisone orally
Klein-Gitelman, et al (2007); Akib AA, et al (2010); Bartels CM, et al (2011)
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…DISCUSSION– Azathioprine has been used as
immunosuppressant and corticosteroid sparing agent
– Treatment of microangiopathic changes on retinopathy chosen in the context of the systemic disease.
Klein-Gitelman, et al (2007); Blodi BA, et al (2002); Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION– Higher daily dosages of up to 2
mg/kg/day of oral prednisone have been used in patients with retinal vasculitis.
– In some cases, especially of asymmetrical ocular involvement, systemic corticosteroid may be supplemented with regional corticosteroid injection (triamcinolone acetonide, 40 mg/mL, in sub-Tenon or peribulbar injections)
Blodi BA, et al (2002); Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION– In our case, the treatments includes:• methylprednisolone pulse 500 mg in 100 mL
normal saline drip (~25mg/kg/24hr) i.v. 3 days, prednisone tablets 3-3-2 (or equal to 2mg/kgBW/day); • ampicillin-sulbactam 150 mg q.i.d.
intravenously; • azathioprine 30 mg b.i.d p.o; • acetaminophen 200 mg t.i.d p.o, as needed • sun-block cream during the day, and
hidrocortison 1% cream during bedtime
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…DISCUSSION– In our case, after these treatments:• general condition getting better• appetite became normal• complaints of headache and joint
pain• malar rash was thinner• laboratory indices improved (Hb , ESR )• unfortunately visual acuity was still
1/60 for both eyes
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…DISCUSSION• Hallegua and Wallace (2002): – elevated liver enzymes are common on SLE, – one fourth is accompanied with liver
engorgement – no specific treatment
• D’Cruz, Khamashta, and Hughes (2002):– the most common cardiac manifestations in
SLE is pericarditis – myocardial involvement occurred about 2%
to 10% of patients may improve with corticosteroid therapy
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…DISCUSSION– In our case, other manifestations of SLE
in our case included:• Hepatic manifestations elevated of serum
transaminases and enlarged liver. • Cardiac disease dilated cardiomyopathy• No specific treatment was given
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…DISCUSSION– SLE is characterized by remission and
exacerbation (flare)– Exacerbation is development of any new
signs and/or symptom that is in necessary for change of the treatment, caused by:• UV exposure, infection, • some drugs such as: aromatic-forming
antibiotics (penicillin, sulfa, tetracycline), salt of aurum, phenothiazine, and anticonvulsants, • pregnancy
Akib aa, et al (2010); Mosca M, et al (2006)
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…DISCUSSION–Measurement of the disease activity is
based on scoring system –many disease activity indices – SLE Disease Activity Index (SLEDAI), and
revised versions as SLEDAI-2K and Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA)-SLEDAI the most common adapted indices in more countries, includes Indonesia
Akib aa, et al (2010); Mosca M, et al (2006); American College of Rheumatology (2011)
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…DISCUSSION– Scoring must be done periodically• usually every 3 or 6 months• change of disease activity presents.
– Visual prognosis on ocular disease is depending on part or tissue involved.• Anterior segment disease usually not
accompanied with loss of vision or blindness,• posterior segment involvement frequently
has poor visual outcome.
Blodi BA, et al (2002); Rosenbaum J, et al (2007); Peponis V, et al (2006)
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…DISCUSSION– In our case, • the most involved organ is eyes • posterior segment affected as retinopathy
and optic atrophy• the prognosis of her visual competence is
not good• visual rehabilitation should be prepared
due to high possibilities of blindness. • overall disease activity should be
measured on periodic monitoring, although the prognosis is dubious ad malam
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SUMMARY
• A rare case of lupus retinopathy and optic atrophy in a child with SLE has been presented.
• Chief complaints of fever, rash, and loss of vision.
• Based on the history, physical examination, laboratory data diagnosis of systemic lupus erythematosus was established.
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…SUMMARY
• By ophthalmologic examination the ocular seemed to be the most involved target organ on the patient
• The manifestations were retinal vasculitis and optic atrophy.
• The treatment of intravenous, followed by oral corticosteroid improved her general status and laboratory indices, but not for her sight or retinal impairment.
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…SUMMARY
• Activity of the disease or flare can be assessed by several scoring system.
• Visual prognosis is bad due to optic atrophy and severe retinal vasculitis, so need to be prepared for visual rehabilitation.
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THANK YOU
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Funduscopy on June 6th , 2011
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Funduscopy on October 5th 2011
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Chest X-ray
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Echocardiography
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Abdominal ultrasonography
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Thoracolumbal & knee joints x-ray
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Head MSCT
Figure 1 Model of SLE-associated genetic variants in the immune response
Deng, Y. & Tsao, B. P. (2010) Genetic susceptibility to systemic lupus erythematosus in the genomic era
Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2010.176
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SLEDAI
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SLEDAI
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SLEDAI
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Anatomy of the eye
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Anatomy of the eye
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Anatomy of the eye
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Polyclonal
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LE cell
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Complement system
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Normal fundus
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Nutritional status
BW: 19kgs;IBW: 20kgs;%IBW:95%
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