OUTCOME OF A NATIONAL COHORT OF PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS

1. OUTCOME OF A NATIONAL COHORT OF PEDIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS N Gorodnitski, PJ Hashkes, M Mukamel, S Padeh, R Brik, J Barash, D Mevorach, Y Berkun, Z Tauber, J Press, L Harel, P Navon, Y Naparstek, Y Uziel, Pediatric Rheumatology Study Group of Israel

2. INTRODUCTION • The clinical manifestations of childhood SLE • range from mild constitutional symptoms to progressive • involvement of all target organs. • A difference in clinical manifestations are • related to genetic and environmental factors. • We present a large unique national series • of the Israeli SLE children.

3. OBJECTIVES To describe the clinical manifestations and outcomes of a national Israeli cohort of pediatric patients with systemic lupus erythematosus (SLE).

4. METHODS • Patients were identified from the Israeli national • registry of children with rheumatic diseases who • were diagnosed and followed between 1987-2003. • A retrospective charts data analysis on all cases • meeting the ACR diagnostic criteria of childhood • onset SLE.

5. Web site internet access for data entry

6. ACR Criteria

7. Laboratory assessment

8. Growth parameters Therapy

9. JSLE SLEDAI

10. Damage Index

12. METHODS • Descriptive analysis of demographic • initial and anytime clinical manifestations • SLE disease activity index (SLEDAI) • SLE collaborating clinics/ACR (SLICC/ACR) • disease damage scores

13. RESULTS AT DIAGNOSIS -102 patients 81% females Mean age - 13.3 ± 2.6 years (range 6.9 - 17.7) Median age – 13.4 PRINTO - 557 patients – 39 countries 82% females Median age – 12.2

14. At Diagnosis Initial clinical manifestations: Hematological - 94% Malar rash - 49% Musculoskeletal (non erosive arthritis)-45% Renal involvement - 41% Oral or nasal ulcerations - 21% Serositis -16%. (pleuritis 13, pericarditis – 6) CNS - 7%

15. Initial clinical manifestations HSC Canadian study Our Study Hematological - 94% - -- Malar rash - 49% - 68 Musculoskeletal -45% - 61 Renal involvement - 41% - 51 Oral or nasal ulcerations - 21% - 29 Serositis -16%. - 15 CNS - 7% - 15

16. Clinical manifestations any time At presentation % any time % Hematological - 94% 100 Malar rash - 49% 56 Musculoskeletal -45% 58 Renal involvement - 41% 53 Oral or nasal ulcerations - 21% 26 Serositis -16%. 19 CNS - 7% 8

17. Renal-41% 27 had biopsies DPGN – 15 MPGN - 4 Mesangial – 5 Focal segmental – 6 Some had more than 1 biopsy Nephrotic syndrome – 2 1 had renal transplant

18. Hematological - 94% Anemia– 77% Leukopenia < 5000 – 53% Lymphopenia < 1500 – 47% Thrombocytopenia < 150000 - 35% ESR – 70mm/h (PRINTO -57) Mean HgB – 10.9 g/dL (PRINTO -10.9) Mean lymphocyte count - 1450

19. CNS - 7% Psychosis –3 Seizures –4 Pseudotumor - 3 Ataxia – cerebelitis – 3 Chorea – 1 TIA – 2 Brain infarction - 1 CT – 5 patients – 1 infarction, EEG – 1 slow activity

20. At Diagnosis Mean SLEDAI -17.2 ± 9.0 (range 2 - 60). Median - 17 TREATMENT - 80 children (80%) started therapy with corticosteroids, 19 (19%) with immunosuppressive drugs. PRINTO – Median SLEDAI - 17

21. 1 YEARS FOLLOW UP -83 children Mean SLEDAI of 8.2 ± 8.0 (range 0 - 46). TREATMENT- 55 (66%) were still on corticosteroids 27 (32%) were on immunosuppressive drugs

22. 3 YEARS FOLLOW UP - 60 children Mean SLEDAI of 9.5 ± 7.3 (range 0 - 36). TREATMENT - 44 (73%)were on corticosteroids 23 (38%) were on immunosuppressive drugs. Mean SLICC/ACR damage index was 0.4 ± 1.1 (0 - 7). HSC – 1.76 (3.3 years)

23. 5 YEAR FOLLOW UP -44 children Mean SLEDAI of 6.7 ± 5.2 (0 - 21). TREATMENT - 28 (64%) of them were on steroids 22 (50%) on immunosuppressive drugs. Mean SLICC/ACR damage index was 0.5 ± 1.2 (0 - 7). Death - 1 Chronic Renal Failure – 5

24. SUMMARY Major organ involvement Renal -53% Serositis -19%. CNS - 8% Malar rash, arthritis – most common signs Laboratory – hematological most common

25. CONCLUSIONS The 5-year outcome of our national pediatric SLE cohort was in general good, with a progressive decrease in the disease activity (SLEDAI) score. Damage index was very low after 5 years. It is possible that relatively early and prolonged use of immunosuppressive medications in many patients led to the good outcome. Mean SLICC/ACR was 0.4 ± 1.1 (0 - 7). HSC – 1.76 (3.3 years)  (Cumulative disease activity over time – the single most predictor of damage. Immunosuppressive was protective - A@R 2002)

26. FUTURE ONGOING STUDY • Comparison between adult and pediatric • SLE manifestations • SLERI data (represent whole country) vs. • pediatric national data • Canadian – cSLE more active than aSLE • cSLE – more aggressive therapy (more treatment • complications) • Same disease organ outcome In Israel? Next HIPAK meeting

27. FUTURE STUDY • Are difference in clinical manifestations related to genetic and environmental factors? • SLERI project – DNA for genetic • Looking for risk factors for worse outcome

28. SLE- acknowledgements • Moshe Rubinstein – website Data collection and analysis • Pediatric rheumatology study group of Israel • SLERI

29. Thank You!