ACKNOWLEDGEMENT Management Team: MEHTA CHILDREN S HOSPITAL: Primary consultant and Paediatric Rheumatologist: Dr.Mahesh Janarthanan Paediatric Nephrol

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1 USUAL & UNUSUAL PRESENTATION OF SLE IN SIBLINGS Dr S K SATHISH KUMAR DNB paediatrics trainee Department of pediatrics Mehta children s hospital

2 ACKNOWLEDGEMENT Management Team: MEHTA CHILDREN S HOSPITAL: Primary consultant and Paediatric Rheumatologist: Dr.Mahesh Janarthanan Paediatric Nephrologist: Dr.M.Vijayakumar & Dr.Prahalad Pediatric hematologist: Dr.Sarala Rajajee Consultant Pathologist: Dr.Anila Abraham Kurien KKCTH: v Paediatric nephrologist: Dr.Sairam v Paediaric intensivist: Dr.Bala Ramachandran v Paediatric surgeon: Dr.Senthil Ganesh

3 SIBLING 1 15 yr old adolescent girl presented in 2nd week of May with v c/o Recurrent low grade fever v Joint pain & oral ulcers v Paleness of the body v Rash over nose & the fingers v Hair loss v h/o loss of appetite and weight (52 à 43kg) in 4 months.

4 HISTORY Past history: Nil significant Antenatal and natal : FTNVD, B.W-3kg Developmental : Normal Family history:

5 GENERAL EXAMINATION She was conscious, alert, febrile (T-100 F) Pallor(+) Malar Rash (+) Hypopigmented rashes over the fingers (+) Oral ulcer (+) No icterus/cyanosis/clubbing/ln/edema BP: 120/80 mmhg Wt : 41.5 kg at 5th centile (CDC ) Ht : cm at 25th centile (CDC )

6 MALAR RASH & HYPOPIGMENTED RASH OVER FINGERS

7 SYSTEMIC EXAMINATION CVS: S1S2 +, no murmur RS: BAE +, NVBS P/A: soft, no organomegaly CNS: HF-normal, NFND.

8 INVESTIGATIONS TC : 2700 cells/cu.mm (leucopenia) DC : P 59% L 32% HB : 7.5gm% (anaemia) PLT : 1.5 Lakhs/cu.mm ESR :110 mm/hr ( ) Spot urine PCR: 0.20 (normal) DCT: Negative Sr.albumin: 2.5 gm%

9 INVESTIGATIONS.. Complements: C3-0.3 ( ); C ( ) Anticardiolipin: IgM positive, IgG-negative Lupus anticoagulant: positive LDH: 408 Bone marrow study: reactive marrow ANA- strong positive(1:1280), homogeneous pattern Anti - ds DNA-positive(1:20) Echo- Normal

10 ACR CRITERIA- 1ST SIBLING 1. Malar rash 7. Renal manifestations 2. Discoid rash 8. Seizure or psychosis 3. Photosensitivity 9. Hematologic manifestations 4. Oral or nasal ulcer 5. Arthritis 6. Serositis 10. Immunologic abnormalities 11. Positive antinuclear antibody test result

11 DIAGNOSIS & MANAGEMENT She was diagnosed as SLE (5 out of 11 ACR criteria) with typical features. She was treated with IV steroids initially and changed to oral steroids, azathioprine and hydroxychloroquine, SPF-60 for local application and she is doing well.

12 SIBLING 2 10 yr old girl studying 5th std brought to op ( ) with c/o fever for 1 wk with h/o sore throat Investigated for infective cause which was not contributory 2 days latter presented with rash (HSP like) and joint pain.

13 INVESTIGATIONS II week: she was investigated for connective tissue disorder as the elder sibling also had SLE & parents are also anxious. Investigations : Hb : 9.8 gm% (Anaemia) TC : 4350 cells/cu.mm (leucopenia) DC: P 39% L 55% ESR : 66 mm/hr ( )

14 INVESTIGATIONS CRP: 0.6(neg) Blood urea : 29 mg/dl Sr.creatinine : 0.7 mg/dl Ferritin : 40 ng/ml Iron : 69 ug/dl TIBC : 182 ug/dl RA factor : Negative

15 INVESTIGATIONS CXR : normal ANA : strong positive (1:1000), homogenous pattern Anti ds-dna : positive DCT : Negative CPK : 151 U/L LDH : 343 U/L C3 : 0.3 gm/l ( ) C4 : 0.46 gm/l ( )

16 DIAGNOSIS Anticardiolipin antibody : IgG+ve, IgM-ve Lupus anticoagulant : Negative Diagnosis of SLE was made and started with low dose steroids - 20mg prednisolone & HCQ.

17 I ADMISSION 2-3 days after steroids: severe abdominal pain, loose stools of 2 episodes and B/L pedal edema. BP:160/80 mmhg P/A: Distended, generalised tenderness(+)? Acute abdomen? Infectious etiology. Surgical opinion sought NPO Steroids were withheld & iv antibiotics started.

18 COURSE IN HOSPITAL USG abd: B/L renomegaly with increased renal cortical echoes with moderate ascites Anti hypertensive started after nephro opinion Day 2 of admission : Developed seizure 3 episodes one after other (?hypertension induced) requiring fosphenytoin and shifted to picu. In PICU multiple antihypertensive (Enalapril, Atenolol, Methyldopa, prazosin and Amlodipine) were given. CT brain: normal. ECHO: mild pericardial effusion.!!! Dilemma regarding giving steroids at this stage? Surgical cause or infectious cause?

19 MANAGEMENT.. IV methyl prednisolone 10 mg/kg/dose given showed dramatic improvement in abdominal pain, no seizure. CT angio of abdomen: B/L enlarged kidneys & hypoattenuation renal cortex. Hypoattenuation of spleen?vasculitis, mild peritoneal & pericardial fluid. Upper GI endoscopy: Erosive gastritis. Hence 30 mg/kg of prednisolone was given for 3 days. I dose cyclophosphamide 500mg/sq.m.

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21 RENAL BIOPSY?? Renal biopsy deferred and planned during 2nd dose of cyclophosphamide therapy.

22 SIBLING 2 READMISSION Again the 2nd sibling admitted ( ) for edema, headache and cola coloured urine who was on multiple anti-ht drug for hypertension evaluation. At admission she had stable vitals, BP:160/100 mmhg, B/L pedal edema, periorbital puffiness, rashes(+) over face. Wt: 30.9 kg>25th centile (CDC 2000) Ht: 135 cm>25th centile (CDC 2000)

23 INVESTIGATIONS HB: 7.6 gm% (Anemia) PCV: 21.8% TC: 2700 cells/cu.mm (Leucopenia) DC: P 56% L 34% E 1% M 9% PLT: 2.07 Lakhs/cu.mm ESR: 30mm ½hr / 74mm 1hr ( ) RBC: 2.83 million cells/cu.mm

24 INVESTIGATIONS Urea : 21 mg/dl Creatinine : 0.5 mg/dl Na+ :139 meq/l K+ : 4.1 meq/l Cl : 104 meq/l Hco3 : 23 meq/l Ca+ : 7.4 mg/dl

25 INVESTIGATIONS.. Serum Albumin : 2.1 gm% ( ) SGOT : 18 IU/L SGPT : 27 IU/L Urine Albumin: ++ Pus cells: plenty Urine RBC: Plenty Epithelial cells: 6-8/HPF

26 INVESTIGATIONS.. Urine spot PCR : 128.6/15.5 (8.3) ( ) 24 hr urine protein: 1446 Sr. cholesterol: 256 Renal biopsy: Necrotising vasculitis. Treated with steroids, antihypertensives (T.Nifedipine retard, T.Aten, T.Apressol, T.Envas) & HCQ and cyclophosphamide monthly.

27 RENAL BIOPSY REPORT Renal medulla. MICROSCOPIC DESCRIPTION They appear normocellular, with patent capillary loops. No endocapillary proliferation seen. No spikes or double contours are seen over the basement membrane. No necrotising lesions or crescent formation identified. Two arteries included in this biopsy show transmural fibrinoid necrosis. There is edema and dense inflammatory infiltrate in the surrounding tissue.

28 ARTERY WITH FIBRINOID NECROSIS

29 LIGHT MICROSCOPY- NORMAL GLOMERULUS

30 ELECTRON MICROSCOPIC PICTURE

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32 ACR CRITERIA-2ND SIBLING 1. Malar rash 7. Renal manifestations 2. Discoid rash 8. Seizure or psycosis 3. Photosensitivity 9. Hematologic manifestations 4. Oral or nasal ulcer 5. Arthritis 10. Immunologic abnormalities 6. Serositis 11. Positive antinuclear antibody test result

33 DIFFERENCES IN PRESENTATION Sibling 1 (15yrs - F) c/f: recurrent fever, joint pain, rash, hair loss, loss of appetite, oral ulcer, loss of weight over 4 months, normal BP. Sibling 2 (10yrs - F) c/f: fever, throat pain for 1wk, HSP like rash, severe abdominal pain, arthralgia, serositis, hypertensive seizures.

34 SIBLING 1 SIBLING 2 Inv: anaemia, leukopenia, raised ESR, ANA & Anti ds DNA-positive, Anticardiolipin & Lupus anticougulant was positive. Hypocomplementemia. Inv: anaemia, leukopenia, raised ESR, ANA & Anti ds DNA-positive, Anticardiolipin AB +ve, Lupus anticoagulant negative. Hypocomplementemia. Spot urine PCR-normal. Non aggressive & gradually progressive. Spot urine PCR-elevated. Renal biopsy: necrotising vasculitis. Aggressive & rapidly progressive.

35 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) INTRODUCTION: The first written description of Lupus was in 13th century. Rogerius named the disease using latin word for wolf as the cutaneous manifestation is similar to wolf bite. SLE is a chronic autoimmune disease characterised by multisystem involvement and the presence of circulating autoantibodies directed against self antigen.

36 ETIOLOGY & EPIDEMIOLOGY Genetic, hormonal & environmental exposures Prevalence in children: 1-6/1,00,000 M:F=1:9 Positive ANA is 95-99% sensitive but poor specificity Anti ds-dna more specific correlates with disease progresssion & nephritis Diagnosis normally made with help of ACR criteria

37 CLINICAL PRESENTATION Most of the children presents with chronic symptoms, small percentage tend to present aggressively Some chidren can have fatal systemic disease resulting from widespread acute vasculitis i.e., lupus crisis

38 LUPUS NEPHRITIS CLASSIFICATION Class 1 - Minimal mesangial lupus nephritis Class II - Mesangial proliferative lupus nephritis Class III Focal lupus nephritis(active and chronic; proliferative and sclerosing) Class IV Diffuse lupus nephritis( active and chronic; proliferative and sclerosing; segmental and global) Class V Membranous lupus nephritis Class VI Advanced sclerosis lupus nephritis

39 LITERATURE REVIEW 1. Alarco n-segovia et.al: Studied 1177 lupus patient for familial aggregation and other autoimmune disease in SLE patients from GLADEL cohort. 37 sibling had SLE, 7 offsprings and 25 parents of them had SLE. 2. R Hal Scofield Genetics of SLE: Disease tend to occur in families -Siblings of SLE patients have a risk of about 2% -Even identical twins with SLE are concordant for disease in only 25% of cases

40 HIGHLIGHTS IN THIS CASE PRESENTATION v Sibling presented at the same time with contrast clinical picture elder one with typical chronic features and younger sibling with acute aggressive disease with features of lupus crisis. v High index of suspicion is needed for early diagnosis of this type of disease and aggressive management is needed to avoid morbidity and mortality.

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