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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%