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Indian Pediatr 2009;46: 711-715 |
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Clinical Features and Outcome of Systemic
Lupus Erythematosus |
Indira Agarwal, T Sathish Kumar, Kala Ranjini, Chellam Kirubakaran and *Debashish
Danda
From the Departments of Child Health and *Medicine,Christian
Medical College, Vellore, Tamil Nadu, India.
Correspondence to: Dr Indira Agarwal, Department of Child
Health, Christian Medical College, Vellore 632 004,
Tamil Nadu, India.
Email: [email protected]
Manuscript received: April 3, 2007;
Initial review : May 16, 2007;
Accepted: July 29, 2008.
Published online 2009 Jan 1: PII: S001960610700225-2
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Abstract
We report the clinical profile, treatment and outcome
of systemic lupus erythematosus in 70 patients between the age of 4-15
years. Fever (94.2%), arthritis (65.7%) and malar rash (57.1%) were the
chief extra-renal manifestations. The ESR was raised in 98.5% patients,
anemia was seen in 60% and direct Coombs test was positive in 58.3%.
Antinuclear antibody was positive in all; anti-double stranded DNA
antibody and low C3 levels were seen in 77.1% and 80%, respectively.
Renal involvement was noted in 77.1% and included proteinuria (53%),
hematuria (42.8%), hypertension (18.5%) and elevated serum creatinine
(8.6%). Renal histology showed class I nephritis in 3.7%, class II in
44.4%, class III in 4.3%, class IV in 44.4% and class V in 1.8%. On
follow up 18.8 months later, 70% patients were in remission, 7.5% had
active disease and 7.5% died. The characteristics of childhood lupus
erytematosus were similar to those previously reported. The outcome was
favorable in most cases.
Keywords: Systemic lupus erythematosus, Lupus nephritis, India.
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Systemic lupus erythematosus (SLE) is a
disorder with varied clinical manifestations. Although most common in
women of childbearing age, nearly 15% cases present in children younger
than 16 years(1). Rates of organ involvement are higher in children.
Lupus nephritis is one of the main clinical
presentations determining the course and outcome in patients with
SLE(1,2). Clinically overt nephropathy is more often a presenting clinical
manifestation of SLE in children than adults. Patients with severe
histological forms of nephritis have more severe renal
manifestations(2,3). Although the results of several studies regarding
factors affecting outcome are controversial, male sex, black race, onset
before puberty, persistent hypertension, impaired renal function,
nephrotic syndrome, anemia, class IV nephritis and increased histological
index scores are identified as prognostic parameters(4-8). This
retrospective study aimed to describe the profile of children at our
center.
Methods
Case records of children who presented to the
Department of Child Health between May 1987 and May 2006 and were
diagnosed to have SLE by the Revised American Rheumatism Association
Criteria(9) were reviewed. Patients with drug-induced lupus, discoid
lupus, or mixed connective tissue disease were excluded. Clinical and
laboratory features at the time of presentation were recorded.
Lupus nephritis was considered in patients showing
hypertension, abnormal urinalysis or serum creatinine >1 mg/dL.
Hypertension was defined as systolic and/or diastolic blood pressure above
the 95th percentile for gender, age and height centile. Urinalysis was
considered abnormal in the presence of >5 red blood cells per high power
field of centrifuged specimen, urine protein >1 + or presence of red cell
casts. Nephrotic range proteinuria was considered in patients showing
>1g/m 2/day protein excretion or
first morning urine protein to creatinine ratio >3.0.
Renal biopsy was performed in all children with SLE.
Light microscopy and immunoflourescence was done for categorization as per
WHO criteria for lupus nephritis(10). Patients with class I lupus
nephritis were treated for extra renal manifestations of SLE. Patients
with class II lupus nephritis who had proteinuria <1 g/day and normal
renal function were treated with oral prednisolone at an initial dose of
1-2 mg/kg per day (maximum 80 mg/day) which was tapered over the next 3-4
months to a maintenance dose of 0.5-0.75 mg/kg on alternate day for a
minimum of 3 years or more. In those with proteinuria >1 g/day or with
serum creatinine >1 mg/dL, azathioprine at a dose of 2-3 mg/kg per day was
added to prednisolone. Patients with WHO class III or IV lupus nephritis
were treated with cyclophosphamide as infusion at a dose of 1 g/m 2
monthly for 6 months followed by every 3 months for next 24-30 months.
Patients with class V nephritis received prednisolone along with
azathioprine (2-3 mg/kg/day) or cyclosporine (3-6 mg/kg/day).
Drug doses were adjusted according to clinical response
or to maintain blood levels of C3 and anti-double stranded DNA antibody as
near to normal as possible. Discontinuation of treatment was attempted
when there was stable renal function, proteinuria less than 0.5 g/day and
normal immunological tests for at least 3 yr. Aspirin, at a dose of 3
mg/kg/day, was given to patients with positive anticardiolipin antibody or
lupus anticoagulant. All patients were initially monitored monthly for 6
months and then quarterly. Complete blood count, ESR, C reactive protein
and blood levels of creatinine, transaminases, C3 and anti-double stranded
DNA antibody were tested.
The duration of follow up was calculated from the time
of diagnosis until the last clinic visit. The outcome was classified as: (i)
remission (normal urinalysis, blood pressure and serum creatinine; no
extra renal symptoms) (ii) active disease (proteinuria > 0.5g/day,
microscopic hematuria >5 red cells per high power field, hypertension,
extra renal manifestations), (iii) death or (iv) lost to
follow-up. Data were analyzed by SPSS version 11.
Results
Of 70 patients, 60 were girls (female: male ratio 6:1).
The mean age at diagnosis of SLE was 10.5 yr (range 4-15 yr). Majority of
children were referred from north east states of India (48.6%) followed by
Tamil Nadu (38.6%), Andhra Pradesh (7.1%) and Kerala (5.7%).
TABLE I
Patient Characteristics at Presentation
Feature |
Number (%) |
(n=70) |
Fever |
66 |
(94.2%) |
Renal involvement |
54 |
(77.1%) |
Arthritis/arthralgia |
46 |
(65.7%) |
Malar rash |
40 |
(57.1%) |
Photosensitivity |
36 |
(51.4%) |
Lymphadenopathy |
33 |
(47.1%) |
Alopecia |
32 |
(45.7%) |
Hepatosplenomegaly |
30 |
(42.8%) |
Weight loss |
21 |
(30.0%) |
Neurological involvement |
15 |
(21.4%) |
Pleural effusion |
2 |
(2.8%) |
Pericardial effusion |
2 |
(2.8%) |
Table I shows that the most common extra-renal
manifestation was fever (94.2%), followed by joint involvement (65.7%).
The hematological and immunological characteristics are shown in
Table II. 77.1% of patients had renal involvement. Class II
(mesangioproliferative GN) and class IV (diffuse segmental proliferative
GN), 44.4% each were the most frequent histopathological findings followed
by class III (focal proliferative GN) in 4.3%, class I (mild mesangial
change) in 3.7% and class V (membranous nephropathy) in 1.8%. Presence of
proteinuria, hematuria, hypertension and raised creatinine indicated the
severity of renal presentation and were associated with Class IV disease
(Table III). Three children had autoimmune
hypothyroidism, two had central nervous system lupus with progressive
renal dysfunction and one developed steroid induced diabetes mellitus. No
severe complications of intra-venous cyclophosphamide therapy were
observed. Major infections were observed only in 3 patients though minor
infections were seen in a few.
TABLE II
Hematological and Immunological Findings at Presentation
Laboratory data |
Number (%) |
Increased ESR |
69/70 |
(98.5) |
Low C3, C4 |
56/70 |
(80.0) |
Elevated anti-double stranded DNA antibody |
54/70 |
(77.1) |
Anemia (hemoglobin <10 g/dL) |
42/70 |
(60.0) |
Positive Coombs test |
28/48 |
(58.3) |
Thrombocytopenia |
17/70 |
(24.2) |
Anti-cardiolipin antibody |
14/39 |
(35.8) |
Lupus anticoagulant |
6/38 |
(15.7) |
Renal disease was in remission in 38/54 (70.3%)
patients (Table III). Three patients with class IV nephritis
and one with class III had active disease. Eight children were lost to
follow-up. Four children (7.5%) died, 2 each in class II and class IV. One
patient with Class IV disease died of ESRD while one patient each died due
to septicemia, pulmonary hemorrhage and multiorgan dysfunction.
TABLE III
Correlation of Histology With Clinical Features and Outcome
|
Class I
n=2 |
Class II
n=24 |
Class III
n=3 |
Class IV
n=24 |
Class V
n=1 |
Hypertension |
|
1(7.7%) |
4(30.8%) |
8(61.5%) |
|
Proteinuria |
|
10(32.2%) |
2(6.5%) |
18 (58.1%) |
1
(3.2%) |
Nephrotic
range* |
1(14.2%) |
|
5 (71.4%) |
1 (14.2%) |
|
Hematuria |
|
5 (16.6%) |
4(13.3%) |
20 (66.6%) |
1
(3.3%) |
Microscopic |
|
5 (22.7%) |
2 (9.1%) |
14 (63.6%) |
1
(4.5%) |
Macroscopic |
|
2 (25.0%) |
6 (75.0%) |
|
|
Serum
creatinine >1 mg/dL |
|
|
1 (16.6%) |
5 (83.3%) |
|
Remission
|
1 (50.0%) |
18 (75.0%) |
2 (66.6%) |
16 (66.0%) |
1
(100%) |
Active
disease |
|
|
1 (33.3%) |
3 (12.5%) |
|
Death
|
|
2 (8.3%) |
|
2 (8.3%) |
|
Lost to
follow up |
1 (50.0%) |
4 (16.6%) |
|
3 (12.5%) |
|
*Two children with
nephrotic range proteinuria did not have a renal biopsy. |
The mean survival since onset of illness was 18.8
months (range 1-96 months). There was no correlation between gender, age
below 10 years, presence of hypertension, impaired renal function or
anemia with renal histopathology. Gross hematuria was significantly
associated with more severe renal histopathology (P=0.03).
Nephrotic syndrome at presentation was not significantly associated with
adverse outcome (P=0.4).
Discussion
The clinical characteristics of 70 children with SLE
were compared with other Indian and western studies. Age at presentation
was comparable with other studies(11-13). Female predominance (ratio 6:1)
was comparable to a previous study(12) but higher than others(11,13). The
clinical presentation was similar to Chandrasekaran, et al.(13) and
Singh, et al.(12). Bone marrow suppression is reported as a usual
feature in SLE, which differentiates it from other collagen vascular
disorders. The occurrence of anemia and leukopenia in our series was
similar, while thrombocytopenia was higher than that reported in earlier
Indian studies(11-13). Direct Coombs test positivity was higher than other
Indian studies(12,13).
Renal involvement is more common in children. The
histological changes may precede the appearance of clinical symptoms of
renal involvement; hence early screening for management is required. Renal
involvement in developed countries is seen in 30-70% of patients(5) while
our study reported 77.1 %. Ali, et al. and Singh, et al.
reported it in 75% and 56%, respectively(11,12). Proteinuria and
microscopic hematuria were the commonest symptoms.
Class II and IV lupus nephritis were the commonest
lesions, similar to previous reports(12, 13). However western studies
observed more of class III and IV(6,8). The low proportion of patients
with class III LN in our study (5%) in contrast to the 15-25% reported in
other series is not explainable(6-8). It is known that prior steroid
therapy may decrease immune deposits in the kidney and the degree of
necrosis and proliferation(16), and might have influenced the
histopathological findings.
Treatment options have been studied in several centers
with varied success. High-dose and long-term steroids, cyclophosphamide
and other immunomodulators used in the treatment of SLE carry the risk of
growth retardation, and severe infectious complications. In this study,
steroids were used in all children with lupus nephritis along with
intermittent intravenous pulse cyclophosphamide. Mycophenolate mofetil is
a promising option in moderate to severe forms of renal disease but was
used only in one child.
In the last decade the prognosis of pediatric SLE has
improved dramatically(6,7). It is known that renal disease and its
treatment remain the main cause of morbidity and mortality; 94.3% of our
children are alive and doing well at the end of 18.8 months. There were
only 4 deaths which is lower than data from studies in the previous
decade(12,13). Early diagnosis, better treatment protocols and aggressive
management of infections all contribute to the improved outcome in this
severe disease.
Contributors: IA, SK and CK conceived and
supervised the study and were involved in data acquisition, analysis and
writing the manuscript. KE and DD were involved in data acquisition
Funding: None.
Competing Interests: None stated.
What This Study Adds?
Renal disease remains the main cause of
morbidity and mortality in SLE in India.
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