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

How do we getthe best possible outcome

Thomas J. A. Lehman MDChief, Division of Pediatric rheumatologyHospital for Special Surgery, andProfessor of PediatricsCornell University Medical CollegeNew York, NY

CHILDHOOD SLE IN THE 21ST 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, atherosclerosisSuicide (overt and covert) – no self worth

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

The “standard” cyclophosphamide regimen

1 gm/M2 per dose

7 doses at monthly intervalsFollowed 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 21ST CENTURY THE STATE OF THE ART

0

10

20

30

40

50

60

initial 6 moths 12months

18months

36months

48months

60months

P<.05 at 18, 36 and 48 months

ESR

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

0.50.60.70.80.9

11.11.2

initial 6 months 12months

18months

36months

48months

60months

No statistically significant change over 5 yearspatients maintained normal renal function

Cr

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

405060708090

100110120130

initial 6 months 12months

18months

36months

48months

P<.05 at 36 months

CrCl

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

405060708090

100110120

initial 6 months 12months

18months

36months

48months

60months

P<.05 at 6, 12, 18, 36, and 48 months

C3

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

40240440640840

104012401440164018402040224024402640

initial 6 months 12months

18months

36months

48months

P<.05 at 6, 12, and 18 months

24 hr protein

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

05

10152025303540

initial 6 months 12months

18months

36months

48months

60months

P<.05 at 6, 12, 18, 36, 48 and 60 months

Prednisone dosage

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

0

2

4

6

8

10

12

activity 0 activity 36 chronicity 0 chronicity 36

P<. 05 activity decreasedP not significant

chronicity did not increase

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

10

11

12

13

14

initial 6 months 12months

18months

36months

48months

60months

P< .05 at 12, 18, 36 and 48 months

Hb

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

Eight year follow-up15 children completed 3 years of IV cyclophosphamidewith > 96 months of follow-up. 12 males/ 3 females

3 children (20%: 1 female 2 male) developed recurrent diseasewithin one year of completing the three years of treatment.

12 children (80%) remain well, without disease recurrence.

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

Laboratory findings:

Time 0 96 months Paired T

Cr. 0.76 0.73 0.5Hb 10.7 12.9 0.02C3 69 98 0.006C4 10.5 19.1 0.006

SLEDAI 19 3 0.00001

Prednisone 36 13 0.0007

CHILDHOOD SLE IN THE 21ST 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 otherlife threatening complications of SLE or therapy

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

Complications:

Two children who received 6 years of cyclophosphamide developed significant complications of therapy

1 amenorrhea1 renal papillary cell carcinoma

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

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

Current therapy for recurrent disease

Children developing active disease following treatmentreceive a 9 month course of intensive immunosuppressionCyclophosphamide 1 gm/M2

Methotrexate 300 mgs/M2

Both given IV monthlyThe MTX 4 hours afterthe cyclophosphamide

Note: Begin with 50 mgs/M2 of MTX and advance as toleratede.g. 50 then 100, then 150, then 300 mgs/M2 in successive months

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

CHILDHOOD SLE IN THE 21ST 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