childhood sle in the 21 st century the state of the art how do we get the best possible outcome...
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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
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
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
40
50
60
70
80
90
100
110
120
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
0
5
10
15
20
25
30
35
40
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-up
15 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 0.5
Hb 10.7 12.9 0.02
C3 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