CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART How do we get the best possible outcome Thomas J. A. Lehman MD Chief, Division of Pediatric rheumatology Hospital for Special Surgery, and Professor of Pediatrics Cornell University Medical College New York, NY

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART The rationale for immunosuppressive therapy: Prolonged corticosteroid therapy (In excess of 0.25 mg/kg/day) Is associated with an unacceptable frequency of complications AVN, Cushingoid facies, atherosclerosis Suicide (overt and covert) – no self worth

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART The “standard” cyclophosphamide regimen 1 gm/M 2 per dose 7 doses at monthly intervals Followed by 10 doses at 3 month intervals Treat persistent leukopenia with bolus IV solumedrol Discontinue therapy if Cr > 4.0 after six months of therapy ALL DOSES GIVEN ON INPATIENT UNIT!!!

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 18, 36 and 48 months ESR

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART No statistically significant change over 5 years patients maintained normal renal function Cr

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 36 months CrCl

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 6, 12, 18, 36, and 48 months C3

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 6, 12, and 18 months 24 hr protein

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 6, 12, 18, 36, 48 and 60 months Prednisone dosage

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<. 05 activity decreased P not significant chronicity did not increase

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART P<.05 at 12, 18, 36 and 48 months Hb

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Eight year follow-up 15 children completed 3 years of IV cyclophosphamide with > 96 months of follow-up. 12 males/ 3 females 3 children (20%: 1 female 2 male) developed recurrent disease within one year of completing the three years of treatment. 12 children (80%) remain well, without disease recurrence.

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Laboratory findings: Time 096 monthsPaired T Cr Hb C C SLEDAI Prednisone

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Complications SLE complications 1 patient developed a cavernous sinus thrombosis treated with anticoagulants No patient developed renal failure, sepsis, or other life threatening complications of SLE or therapy

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Complications: Two children who received 6 years of cyclophosphamide developed significant complications of therapy 1 amenorrhea 1 renal papillary cell carcinoma

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Current therapy for recurrent disease Children developing active disease following treatment receive a 9 month course of intensive immunosuppression Cyclophosphamide 1 gm/M 2 Methotrexate 300 mgs/M 2 Both given IV monthly The MTX 4 hours after the cyclophosphamide Note: Begin with 50 mgs/M 2 of MTX and advance as tolerated e.g. 50 then 100, then 150, then 300 mgs/M 2 in successive months

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART

CHILDHOOD SLE IN THE 21 ST CENTURY THE STATE OF THE ART Major needs at present: Standardized criteria for the initiation of therapy Early intervention PREVENTS BOTH CORTICOSTEROID AND DISEASE RELATED COMPLICATIONS