Disajikan pada tanggal 19 Juli 2018

A 15 Years Old Girl with Lupus Nephritis, Chronic Kidney Disease, Organic
Mental Disorder and Short Stature

CASE REPORT II

Nanda Juwita

Tutors :

Dr. dr. Krisni Subandiyah, Sp.A (C)

Department of Child Health

Brawijaya University Medical Faculty
Saiful Anwar General Hospital
Malang
2018
 LIST OF CONTENT

ABREVETIATION……………………………………………………………………..4

INTRODUCTION………………………………………………………………………5
CASE REPORT………………………………………………………………………..7
DISCUSSION…………………………………………………………………………17
SUMMARY……………………………………………………………………………29
REFERENCE…………………………………………………………………………30

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3
 ABREVETIATION

SLE Systemic Lupus Erythematosus

LN Lupus Nephritis

CKD Chronic Kidney Disease

OMD Organic Mental Disorder

MMF Mycophenolate Mofetil

DM Diabetes Mellitus

ARV Anti Retro Viral

BUN Blood Urea Nitrogen

ESRD End stage renal disease

CPA Cyclophosphamide

CAPD Continuous ambulatory peritoneal dialysis

PPDGJ Pedoman Penggolongan Diagnosis Gangguan Jiwa

4
INTRODUCTION

Lupus nephritis is kidney disease due to autoimmun condition. This

situation related to error of body immune system in detecting antigen inside the
human body. Lupus nephritic has strong associated with disease called SLE
(Systemic Lupus Erythematosus). Lupus nephritis (LN) is one of many serious
manifestations due to Systemic Lupus Erythematosus (SLE) which ussually
appears five years after diagnosed1. Increased quantity of patients and the long
time that needed for treatment augment morbidity and mortality in society.
SLE is a chronic inflammatory disease that affects the kidneys in about
50% of patients. Lupus Nephritis is a major risk factor for overall morbidity and
mortality in SLE, and despite potent anti-inflammatory and immunosuppressive
therapies still ends in CKD or ESRD for too many patients2. While the patients fell
into CKD or even ESRD state, the burden in morbidity and mortality would
increase. SLE is a disease that can affect any organ, but very often injures the
kidney. It can manifest as neuropsychiatric problems too. SLE is more prevalent
in women than men across all age groups and populations. It has no different
prevalence in white and non-white patient from lower socioeconomic groups3.
The female-to-male ratio is highest at reproductive age, ranging between 8:1 and
4,5,6
15:1, and is lowest in prepubertal children at about 4:3 . It suggests that the
disease has some correlation with hormonal activity.
Childhood-onset systemic lupus erythematosus (cSLE) is a rare but
severe autoimmune disease with multisystem involvement, the incidence is
0.3/100000-0.9/100000 children per year with a prevalence of 3.3/100000-
8.8/100000 children7. A higher frequency of cSLE is reported in Asians, African
Americans, Hispanics, and native Americans8. Median age of onset of cSLE is
between 11 and 12 years (rare below 5 years), and 80% of patients are female 9.
cSLE follows a more severe disease course than adult-onset SLE, with higher
morbidity and lower survival rates10. SLE can also manifest with neuropsychiatric
disorder. Neuropsychiatric lupus is the least understood yet perhaps the most
prevalent manifestations of lupus. It affects 14% to over 80% in adults and 22%
to 95% in children11,12 and can occur independently of active systemic disease
and without serologic activity13 .
Prevalence data in each countries are different. A study in Pacific Asia
reveals that the incident figures in the amount of 0.9-3.1 people per 100.000

5
population/year. On the other hand, the crude prevalence is about among 4.3-
45.3 per 100.000 population. In America, The Lupus Foundation of America
estimates around sixteen thousands new cases that have been found every year,
by means of total prevalence around 1.5 million cases. The definite sufferer of
lupus in Indonesia still unknown appropiately. Prevalence study held by Prof.
Handono Kalim, and friends in Malang reveals number of 0.5% towards total
population14.
Clinical manifestation of patient with lupus nephritic very varied, starting
from asymptomatis, proteinuria only, mild hematuria, until severe clinical
manifestation which is nephrotic syndrome or glomerulonephritis accompanied by
decreased of progressive renal function15. The goal therapy for LN are to
normalize renal function or else inhibit progressivity of renal destruction (CKD).
Application of immunosuppresan therapy and supportive therapy shall be able to
improve renal functino and patient’s life expectancy16. Some needs to undergo
renal replacement therapy (dialysis or renal transplantation) to save their life.
Even after going hemodialysis or CAPD, one still needs to consume many
medications for their lifetime. Therefore, clinicians should focus on preventing
CKD and ESRD for lupus nephritic patients.
Lupus Nephritis, SLE, and CKD bring many burden for nations. Many
patients have to do lifetime treatment; some others couldn’t even be treated.
Neuropsychiatric manifestations including psychosis and personality disorder
may also occur. No single objective test for the presence of CNS-SLE is accurate
in childhood. The diagnosis of cerebral SLE, even in adults, is easily overlooked
in the absence of more widespread systemic involvement by the disease. In
children there is an even greater likelihood of misdiagnosis because of the rarity
of the disorder in this age group
The purpose of this paper is to report a 15 Years Old Girl with Lupus
Nephritis, Chronic Kidney Disease, Organic Mental Disorder and Short Stature
The best approach to patients with central nervous system (CNS) SLE surrounds
the diagnostic difficulties.

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CASE REPORT
A fifteen year old girl was hospitalized in Department of Pediatric Saiful
Anwar Hospital on May 7th 2018 with main complaint of pale and behavioral
disorder. Patient looked pale since 2 weeks before admission. According to her
mother, the patients had behavioral changes a few days before admitted. She
looked confused, just sitting without doing anything and did not pay attention to
others. She did not want to sleep and often scream loud without any purpose. At
the time she still recognize her parents, but later becoming less speech even
don't know her parents.
She had been diagnosed lupus nephritis since four months ago. The
diagnosis was based on malar rash, oral ulcers, hematological disorder, positive
anti ds- DNA, positive ANA test, C3 complement did not perform. Her urinary
tests showed hematuria +2 and proteinuria +2. A kidney biopsy not yet perform.
She had been treated with metilprednisolon pulse 500 mg/m2 for 2 cycles. From
abdomen ultrasonography found bilateral chronic lupus nephritis suggesting SLE
appearance. She had been diagnosed with chronic kidney disease stage V since
4 months ago, level of ureum 128.60 mg/dL and creatinine 4.63 mg/dL with
estimated glomerular filtration rate (eGFR) 17,2 and BUN/creatinine 13,8 and
oliguria developed. Patient has been used CAPD since February 2018. Result
from renal Doppler examination is bilateral parenchymatous renal disease.
The antenatal care from gestational history was normal with no history of
maternal infection, teratogenic drugs consumption or antiepileptic drugs, no
smoking, no herbal medications consumption, no traumatic injury, bleeding or
severe illness. Her mother was on healthy condition, no history and sign of
diabetic mellitus, congenital heart disease, hypothyroid and hyperthyroid. She
was delivered spontaneously at full term by a doctor. She cried immediately after
birth, no cyanotic and her birth weight was 2800 grams, length 48 centimeters.
She had been fed with breast milk until 4 months old. Milk formula and
rice porridge was introduced at the 5th month. She had no difficulty in feeding and
gained weight normally. In the last 6 months, she has low appetite. Her brother
reported that her weight seems to be a bit decreased.
The patient growth and development: the patient could turn over at 3
months old. The patient can be roll over at 3 months old, sit with no support at 7
month old. Patient's speech and language development was normal. Although
her brother forgot about it, she said that her immunization was complete.

7
 The patient is the 5th child from her parents’ first marriage. She lives with
her mother and second older sister. Her mother is a 50 years old housewife and
her father passed away 2 years ago at 54 years old. She didn’t know what
disease that her father had. Her mother is in healthy condition now. Brother and
sisters are on healthy condition. Now the patient is in 3rd grade junior high school.
She was having a bit stressed because she has to move to high school. Their
house floor was tiled and the water for cooking and bathing derived from public
water installation. Their family doesn’t have any pets.

Physical Examination
Physical examination on admission revealed an alert girl but irritable with
body weight 34 kg, body height 145 cms (< P3) ~ 11 years old, arm
circumference in 20 cms (P10 – P25) and ideal body weight 36 kgs (94%). The
blood pressure 80/50 mmHg, pulse rate 98 x/minute, respiratory rate 22 x/minute,
and the temperature 36,6 C. She looked anemic. Neither jaundice nor cyanosis
was noted. There was not found sub costal retraction on the chest, auscultation
on heart and lung were normal. No enlargement of liver and spleen. Other
abnormality on her abdomen was not found. Her peripheral perfusion was good.
The meningeal signs or pathologic reflexes were not found. Laboratory
examinations revealed: hemoglobin 4,9g/dL, hematocrite 13,80%, WBC
9.390/mm3, platelet 203.000/mm3, blood glucose 114, BUN 72, creatinine serum
9,85, eGFR 8, albumin 3,67, sodium 129 and potassium 3.44. There were +1
protein on urine examination. Chest X-ray showed within normal limit (figure 1).

The patient was diagnosed as lupus nephritis, chronic kidney disease on

CAPD, suspicious of cerebral lupus and short stature. She was treated with oral
methylprednisolone 2mg/kg/day, oral MMF 2 x 500mg, chloroquine 1 x 100mg,
packed red cell transfusion, planning methylprednisolone pulses 30 mg/kg/day for
3 days and regularly CAPD. The patient was planned to perform head CT-scan,
repeat complete blood count, and also consulted to psychiatric department.
On the 3rd day of hospitalization, she was getting better. The result from blood
examination revealed hemoglobin 6,8 g/dL, WBC 5.990/mm3, platelet 136.000
/µL, sodium 133. The treatment was continued. Assessment from Psychiatric
department was an organic mental disorder, she was given oral risperidone
0.5mg/kg/day.

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 Figure 3. Chest X- ray within normai limit

On the 4th day of hospitalization, the patient was getting better, but still
irritable and sometimes still talking unmeaning words. CT-scan examination
showed no pathologic lesion found in brain parenchymal (Figure 2).

Figure 2. Head CT Scan no pathologic lesion found in brain parenchymal

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 On the 10th day of hospitalization, the patient was given the third
methylprednisolone pulses 30 mg/kg/day for 3 days. Laboratory examinations on
the 10th day of hospitalization revealed hemoglobin 8.1 g/dL, WBC 5.710/mm3,
platelet 171.000/µL. In general the patient looked well, but her hands became
tremor even when she was resting. She walked around the room without right
purpose. Psychiatric department assumed that the organic mental disorder was
because SLE itself. The patient was discharge from hospital after 15 days
hospitalization

Anthropometric Measurement

From anthropometric chart :

body weight : 34 kgs (<P3)
body height : 145 cms (< P3) ~ 11 years old
arm circumference : 20 cms (P10 – P25)
ideal body weight : 36 kgs (94%)

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Figure 1. CDC chart showing weight for age was abnormal (below percentil 5
standart deviation), short stature (same as 11 years old), and ideal body
weight is 36 kgs.

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Laboratory Findings
The laboratory examinations were checked several times, including
hematology, urinalysis, electrolyte serum, and liver and kidney function.

Table 1. The laboratory test result in Saiful Anwar Hospital 7th May 2018
Laboratory Value Normal range
Hematology
Hb 4.9 g/dL 11.4-15.1
RBC 1.9x106/µL 4.0-5.0
WBC 9.39x103/µL 4.7-11.3
Hct 13.80 % 38-42
PLT 203.000/µL 142-424
MCV 72.60 fL 80-93
MCH 25.80 pg 27-31
MCHC 35.50 g/dL 32-36
RDW 13.20 11.5-14.5
Diff count:
Eosinofil 0.0 % 0-4
Basofil 0.0 % 0-1
Neutrofil 92.6 % 51-67
Lymphocyte 5.9 % 25-33
Monocyte 1.5 % 2-5
SGOT 11 U/L 0-32
SGPT 5 U/L 0-33
Albumin 3.67 g/dL 3.5-5.5
RBG 109 mg/dL <200
Ureum 145.90 mg/dL 16.6-48.5
Creatinine 9.85 mg/dL <1.2
Uric acid 10.4 mg/Dl 2.4-5.7

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Table 2. The laboratory test result in Saiful Anwar Hospital 9th May 2018

Laboratory Value Normal range

Hematology
Hb 6.8 g/dL 11.4-15.1
RBC 2.76x106/µL 4.0-5.0
WBC 5.99x103/µL 4.7-11.3
Hct 20.70 % 38-42
PLT 136.000/µL 142-424
MCV 75.00 fL 80-93
MCH 24.60 pg 27-31
MCHC 32.90 g/dL 32-36
RDW 10.20 11.5-14.5
Diff count:
Eosinofil 0.0 % 0-4
Basofil 0.0 % 0-1
Neutrofil 71.0 % 51-67
Lymphocyte 21.2 % 25-33
Monocyte 7.8 % 2-5

Serum Electrolite
Natrium (Na) (mg/dL) 133 136-145
Kalium (K) (mg/dL) 3.13 3.5-5.0
Chlorida (Cl) (mg/dL) 104 98-106
Calcium (Ca) (mg/dL) 7.8 mg/dL 7.6-11.0
Phospor (mg/dL) 4.7 mg/Dl 2.7-4.5

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Table 3. The laboratory test result in Saiful Anwar Hospital 10th May 2018
Laboratory Value Normal range
Hematology
Hb 8.7 g/dL 11.4-15.1
6
RBC 3.42x10 /µL 4.0-5.0
WBC 7.76x103/µL 4.7-11.3
Hct 24.50 % 38-42
PLT 178.000/µL 142-424
MCV 71.60 fL 80-93
MCH 25.40 pg 27-31
MCHC 35.50 g/dL 32-36
RDW 14.70 11.5-14.5
Diff count:
Eosinofil 0.0 % 0-4
Basofil 0.0 % 0-1
Neutrofil 80.3 % 51-67
Lymphocyte 13.5 % 25-33
Monocyte 6.2 % 2-5

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Table 4. The laboratory test result in Saiful Anwar Hospital 10th May 2018

Urinalyisis
Turbidity Clear
Colour Yellow
pH 5.5 4.5-8.0
Specific Gravity 1.025 1.005-1.030
Glucose Negative Negative
Protein +1 Negative
Keton Negative Negative
Bilirubin Negative Negative
Urobilinogen Negative Negative
Nitrit Negative Negative
Leukocyte Negative Negative
Blood Trace-lysed Negative
10x
Epithel 7.8/SVF ≤3
Cillinder Negative/SVF
40x
Eritrocyte 1.2/LVF ≤3
Eumorphic -%
Dysmorphic -%
Leukocyte 32.0/LVF ≤5
Crystal - LVF
Bacteria 1678.5.0 x 103 / Ml ≤ 93 x 103 / mL

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Table 5. The laboratory test result in Saiful Anwar Hospital 16th May 2018

Laboratory Value Normal range

Elecrolyte Serum
Natrium (Na) (mmol/L) 135 136-145
Kalium (K) (mmol/L) 2.96 3.5-5.0
Chlorida (Cl) (mmol/L) 105 98-106
Calcium (Ca) (mmol/L) 8.1 mg/dL 7.6-11.0
Phospor 4.2 mg/dL 2.7-4.5

Hematology
Hb 8.10 g/dL 11.4-15.1
RBC 3.19x106/µL 4.0-5.0
WBC 5.71x103/µL 4.7-11.3
Hct 23.60 % 38-42
PLT 171.000/µL 142-424
MCV 74.0 fL 80-93
MCH 25.40 pg 27-31
MCHC 34.30 g/dL 32-36
RDW 14.90% 11.5-14.5
Diff count:
Eosinofil 0.0 % 0-4
Basofil 0.0 % 0-1
Neutrofil 6.0 % 51-67
Lymphocyte 8.0 % 25-33
Monocyte 3.9 % 2-5
RBG 194 mg/dL <200
Ureum 158.5 mg/dL 16.6-48.5
Creatinine 8.07 mg/Dl <1.2

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DISCUSSION

Lupus nephritis is kidney inflammation caused by systemic lupus

erythematosus. SLE is an autoimmune disease, disorder in which the body’s
immune system attacks the body’s own cells and organs. Up to 60 percent of
people with SLE are diagnosed with lupus nephritis, which can lead to significant
illness and even death.1
Systemic lupus erythematosus (SLE) is a rheumatic disease
characterized by autoantibody directed against self-antigens, immune complex
formation, and immune deregulation, resulting in damage to essentially any
organ. Childhood SLE generally presents between the ages of 4 and 15 years,
with girls out numbering boys 4:117. In 10-20% of SLE patients, the diagnosis is
made for the first time in childhood18,19. SLE development is triggered by genetic,
20,21
environmental, infectious, and hormonal factors .Women are more frequently
affected than men (incidence ratio: 8-13 : 1)20,22,23 .SLE onset before puberty and
in the elderly is uncommon The incidence in children was estimated at 0.36-
0.9/100,000 children/year, morbidity: 3.3-24/100,000 children/year24. The onset of
SLE is rare before the age of 5 years25.
The patient presented in this paper is 15 years old. But the very first time
she was diagnosed SLE is about a half year earlier. A study conducted in Poland
by Grzelak et al described the mean age for the lupus nephritis is 14.4 years
old26. While another study in Libya said the mean age was 9 years old27.
Although many studies were done in countries, and the mean age is still variable,
people agree that SLE generally presents between the ages of 4 and 15 years17.
And as many epidemiologic studies say, SLE is more favorable at girl. Maybe it is
enhanced by the hormonal activity in woman. These mean that this patient match
the expectation.
The disease can affect any organ but the most frequent are the kidneys,
skin, blood vessels and cells, joints, heart and SLE nervous system The patients
may present with many years of symptoms or with acute history of life-
threatening disease. Nephropathy, fever, and arthralgia and anorexia were the
most common in pediatric patients as presenting clinical manifestations27. A study
shows high percentage of renal involvement (84%) in SLE but lupus nephritis is
probably present to some degree in all children with SLE and is a major
determinant of a long term outcome28,29,30. SLE can also manifest as

17
neuropsychiatric disorder. It’s the least understood yet perhaps the most
prevalent manifestations of lupus which affects 22-95% children with SLE11,12.
Systemic lupus erythematosus arises in individuals with an appropriate
genetic background exposed to certain environmental triggers. Several genes
have been associated with SLE susceptibility, most prominently in the human
HLA loci. A meta-analysis of HLA-DRB1 alleles in SLE concluded that carriers of
HLA-DR4 and DR11 were protected against SLE30. Conversely HLA-DR3 and
DR15 conferred an increased risk of SLE. The mechanisms of HLA-based
disease susceptibility and protection remain unknown. It has been suggested that
this may be related to the degree of stability of the interaction between self-
peptide and its HLA binding partner31,32.
Lupus nephritis (LN) develops in approx. 50-70% adults with SLE and 37-
82% of children22,23. At the early stages of SLE the clinical signs of LN occur only
in 25-40% of patients and may present as minor abnormalities in the urine
(microhaematuria and/or proteinuria and/or leukocyturia) or as nephrotic
syndrome, nephritic syndrome, hypertension, or renal failure20,21,22,23.
No genetic backgrounds can be found in this patient, although SLE
correlates with genetic predisposition. Maybe her family got the SLE history, but
they weren’t aware of this. Genes test could be done, but it costs very much. The
symptom which dominated her disease was pale and lethargy. While on the
urinalysis, proteinuria could be found. Proteinuria was present because of renal
destruction by lupus nephritis.
Until now, there are lot theories about pathogenesis of Systemic Lupus
Erythematosus (SLE). In SLE, a generalized autoimmunity is present with
autoantibodies directed against a variety of self components46, and the role of the
autoantibodies in generating the organ damage is unclear. This contrasts with
organ-specific autoimmunity such as that found in myasthenia gravis or anti-
glomerular basement membrane nephritis, in which clearly pathogenic
autoantibodies are directed against a single self-epitope. Genetic factors, sex,
medicine, and infective agents are important factor in development of SLE47.
Lupus is defined by its clinical picture, together with antibodies directed against
one or more nuclear components, particularly anti-double stranded DNA
(dsDNA)48. Typically, there are multiple autoantibodies in lupus directed against
nucleic acids and proteins concerned with intracellular transcriptional and
translational machinery, the main targets are nucleosomes (DNA-histone) or

18
even quaternary antigens on the chromatin itself, small nuclear
ribonucleoproteins and small cytoplasmic ribonucleoproteins. Patients with lupus
nephritis usually show antibodies directed against dsDNA, Sm, and C1q47.
Systemic lupus erythematosus often manifest in renal complication as
lupus nephritis. This is because antibodies that attack renal cell. Those with
nephritis usually have antibodies directed against dsDNA as well as single-
stranded DNA, and have at most low titers of anti-Ro and anti-La antibody. They
also have high avidity anti-DNA antibodies that activate complement strongly.
Higher avidity anti-DNA antibodies also occur in proliferative more than
membranous lupus nephritis, and cationic antibodies appear to be more
pathogenic. Antibodies directed against C1q are more frequent in those with
nephritis also. Immune aggregates are present at sites of injury in glomeruli, and
in the tubules also in about two-thirds of renal biopsies, as are complement
components. These aggregates will also disturb renal function and caused lupus
nephritis47. There is no evidence that the effector mechanisms of renal damage
(complement, polymorphs, monocytes, cytokines, eicosanoids, etc.) are different
in lupus from primary glomerulonephritis, but the interstitial cellular infiltrates in
lupus often show an excess of CD81 cytotoxic T lymphocytes over CD41,
compared with the usual majority of CD41 T-helper lymphocytes and monocytes
seen in primary glomerulonephritis47.
Lupus nephritis is a common and serious manifestation of systemic lupus
erythematosus (SLE). More than half of all patients with SLE develop nephritis
during their course of illness, and in 10–25% of these the kidney disorder
progresses to endstage renal disease (ESRD)49. ESRD condition is due to
immune aggregate collected in renal and injury of glomeruli and tubules which
will cause renal failure and ESRD. Proteinuria is the dominant feature of Lupus
Nephritis that presents in almost every patient and commonly leading to the
nephrotic syndrome. Microscopic hematuria is almost always present, but never
in isolation, while macroscopic hematuria is rare. Hypertension is not overall
more common, but those with more severe nephritis are more commonly
hypertensive. About half will show a reduced GFR, and occasional patients
present with acute renal failure. If the progression couldn’t be halted, the patient
will finally fall in CKD and ESRD state. Delay onset of renal biopsy increased risk
of ESRD from lupus nephritis. Elevated s-creatinine at the time of renal biopsy
was also identified as a strong predictor of ESRD. Hypercreatininemia in the

19
setting of lupus nephritis may reflect either reversible inflammatory changes
within the renal parenchyma, irreversible chronic lesions, or a combination of
acute and chronic alterations50.
The pathogenesis of neuropsychiatry disorders in SLE is multifactorial and
can involve various inflammatory cytokines, autoantibodies, and immune
complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated
neuronal injury. The most common microscopic brain finding in SLE seems to be
microvasculopathy although not specific, which may due to complement
activation and antiphospholipid antibodies33. Post mortem histopathologic studies
in people with SLE have demonstrated an array of pathologies including
multifocal micro infarcts, gross infarcts, hemorrhage, cortical atrophy, ischemic
demyelination, and patchy multiple sclerosis–like demyelination34.
A positive ANA test result is present in 95-99% of individuals with SLE.
This test has poor specificity for SLE, as up to 20% of healthy individuals also
have a positive ANA test result, making the ANA a poor screening test for SLE.
ANA titers are not reflective of disease activity; therefore, repeating ANA titers is
not helpful in disease management. Antibodies to double-stranded DNA are more
specific for SLE, and in some individuals, anti–double-stranded DNA levels
correlate with disease activity, particularly those with significant nephritis. Anti-
Smith antibody, although found specifically in patients with SLE, does not
correlate with disease activity. Serum levels of total hemolytic complement
(CH50), C3, and C4 are typically decreased in active disease and often improve
with treatment. Inflammatory markers, particularly erythrocyte sedimentation rate,
are often elevated in active disease. C-reactive protein (CRP) correlates less well
with disease activity and acutely elevated CRP values may reflect infection, while
chronic mild elevation of CRP may indicate increased cardiovascular risk.
Antiphospholipid antibodies, which increase clotting risk, can be found in up to
66% of children and adolescents with SLE.35.
The diagnosis of SLE requires a comprehensive clinical and laboratory
assessment revealing characteristic multisystem disease and excluding other
etiologies, including infection and malignancy. Presence of 4 of the 11 American
College of Rheumatology (ACR) 1997 Revised Classification Criteria for SLE
simultaneously or cumulatively over time establishes the diagnosis of SLE36. Of
note, although a positive antinuclear antibody (ANA) test result is not required for
the diagnosis of SLE, ANA-negative lupus is extremely rare. Although ANA is

20
very sensitive for SLE (95-99%), it is not very specific (~50%). Antibodies against
double-stranded DNA and anti-Smith are specific for SLE (~98%) but not as
sensitive (40-65%). Another way to diagnose SLE is the updated criteria
validated by the Systemic Lupus International Collaborating Clinics (SLICC) in
201237.
This patient was diagnosed as SLE based on anamnesis, physical
examination, and laboratory examinations. Then ACR criteria were used to judge
the data. If 4 of 11 criteria were present, the patient could be diagnosed as SLE.
The patient said that her cheeks turn red at sunlight exposure. Originally, this was
called malar rash, one of many symptoms that frequently manifested in SLE.
Then she also had ulcer in her mouth, it’s another criteria for SLE. Next, joint
pains or arthritis were also present. Then lab results showed a hematologic
disorder of anemia and renal disorder as hypercreatininemia. It was 5 of 11.
Besides, after diagnosed as SLE, she also developed neuropsychiatric problem
marked by personality changes. This was the reason why she was diagnosed as
SLE.
Cerebral lupus may present as seizure, psychosis, myelopathy, or stroke
in a patient with SLE. A neurological disorder may occur as an isolated event or
in association with other systemic signs of SLE or even precede the onset of
systemic disease. The duration of CNS involvement may vary from a few minutes
to years. Neurological signs of cerebral are categorized into focal, non-specific,
and neuropsychiatric35

21
 Precise diagnosis of cerebral lupus is extremely difficult. In children there
is an even greater likelihood misdiagnosis because of the rarity of the disorder in
this age group37. There is no single diagnostic gold standard. Most of all
recommended that diagnosis should be based on both clinical assessment as
well as the presence of antibodies in the serum and CSF. A diagnosis of cerebral
lupus cannot be made from radiologic finding alone, because true vasculitis is
rarely seen radiologically. Various imaging studies that aid in diagnosing cerebral
lupus have been reported such as computed tomography, magnetic resonance
imaging, electroencephalography, cerebral blood flow, positron emission
tomography/single photon emission computed tomography, transcranial doppler,
and cerebral angiogram36
Neuron reactive autoantibodies are considered a much better marker for CNS
involvement, with levels significantly higher in cerebral lupus. Specifically, lympho-
cytotoxic antibodies (LCAs) are seen in 80% of patients. Assessments of
complement components (C3 and C4), which are part of the coagulation cascade,
show low serum and CSF concentration. We not performed complement component
(C3) on this case. The exact pathophysiologic process of CNS involvement in SLE is
unknown. The proposed mechanisms that are likely due to the assault of several
autoimmune system changes include circulating immune complexes, anti-neuronal
antibodies, antiphospholipid antibodies, and cytokine release. No one clear
mechanism appears to cause cerebral lupus. All mechanism may present or act
independently32,34,33.
The immune complexes, which consist of DNA and anti-DNA, cause an
inflammatory response as well as a disruption of the blood brain barrier. These
circulating complexes have been found trapped in the highly vascular choroids
plexus of SLE patients upon autopsy36.
The three identified anti-neuronal antibodies postulated in CNS involvement
are the lympho-cytotoxic antibodies (LCAs), which somehow react with brain tissue
and interfere with the neuron's ability to respond. These antibodies also correlate with
cognitive and visual spatial defects. Second, the anti-neuronal membrane antibodies
are targeted directly to neuronal antigens. And third, the intracytoplasmic antibodies
target the constituents of the neuron cells. They are also called anti-SSA or anti-SSB
antibodies. These antibodies are seen in 99% of SLE patients with psychosis. Those
antibodies mentioned above are found in CSF and serum patients with
cerebritis35,36,37

22
 The final mechanism of cerebral lupus involves the cytokines. The
cytokines trigger oedema, endothelial thickening, and infiltration of neutrophils in
brain tissue. Two cytokines, interferon alpha and interleukin-6, have been found
in the CSF of SLE patients with psychosis34. We did not perform any specific
antibodies examination to both cases; therefore, we could not be sure the
proposed mechanism to cause cerebral lupus in these cases35
Body measurement data that were taken from this patient showed that
she had short stature. Measurement data were input into the CDC chart, and the
result showed her height is below P3 (3rd percentile). Compared with a well-
nourished, genetically relevant population, short stature is defined as a standing
height more than 2 standard deviations (SDs) below the mean (or below the 2.5
percentile) for sex55. The causes of short stature can be divided into 3 broad
categories: chronic disease (including undernutrition genetic disorders), familial
short stature, and constitutional delay of growth and development. SLE is a
chronic disease which can interfere with children growth. A study conducted by
Bekenstein et al. showed that cSLE is associated with shorter-than-expected final
height. Onset of SLE in the pubertal period, near the time of maximum linear
growth, may have a particularly significant impact on final height 56. These effects
may rise due to disease activity, side effects of drug treatments, and/or the
presence of diseases other than lupus. Although she was diagnosed as SLE in
about these 3 months, it’s very possible to guess the cause of her short stature
was the chronic disease (SLE). Further investigation is still needed though.
Treatment of SLE is depended on the individual and based on their
specific disease manifestations. Their tolerability for the medications is one that
should be judged. For all patients, avoidance to long direct sun exposure is
advised. Hydroxychloroquine (5-7 mg/kg/day) with maximal dose 400 mg/day, is
recommended for all patients if it can be well tolerated. NSAID agents are useful
for management of arthralgia and arthritis. Corticosteroids are the mainstay
treatment for SLE because it works quickly to improve patients’ acute condition.
The optimal dosing of corticosteroid in SLE child remains unknown. Some severe
diseases are often treated with high dose of intravenous methylprednisolone (30
mg/kg/day for 3 days, followed by weekly pulses) or high doses of oral
prednisone (1-2 mg/kg/day). As the symptoms decreasing, the dosages are
gradually tapered off. Immunosuppressive agents often used in the treatment of

23
pediatric SLE include methotrexate, leflunomide, azathioprine, and
cyclophosphamide35.
Currently, only three medications are FDA-approved for treatment of SLE
in the United States: glucocorticoids, aspirin, and hydroxychloroquine. Treatment
choices tend to vary and are tailored to individual patient’s clinical presentation,
disease severity, and potential pathogenic mechanism. Mild neuropsychiatric
may only need symptomatic treatment. Treatment strategies should include
identification and treatment of any secondary causes of CNS dysfunction such as
infection, increased intracranial pressure, medication side effects, or primary
psychiatric disorders. Immunosuppressive agent with better side effect profile,
such as mycophenolate mofetil (MMF), have been used frequently for
maintenance and even initial treatment of SLE with psychiatric manifestations.
Intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been
used in central nervous system manifestations unresponsive to glucocorticoid
therapy and/or cytotoxic therapy41. Nonpharmacological approaches, like
cognitive rehabilitation programs or psychological group intervention may be
important in SLE patients with psychiatric disorders such as depression, anxiety
or cognitive dysfunction with impaired attention, concentration and memory42.
Psychotropic medications (antidepressants, anxiolytics, and atypical
antipsychotics) may have an important adjunctive role in SLE patients with
affective disorder or psychosis. There is no standardized treatment in lupus
psychosis. The treatment for acute psychosis includes a combination of
antipsychotic medications as symptomatic treatment and glucocorticoids to
control underlying disease activity43,44.
Diseases of the brain are frequently manifested by psychiatric
symptomatology, a condition conventionally termed Organic Mental Disorder or
Organic Brain Syndrome. It is a form of decreased mental function due to a
medical or physical disease, rather than a psychiatric illness. There exist a
number of different and distinct organic brain syndromes seem more likely. OBS
is not a specific neurological diagnosis although it remains a standard diagnostic
category. It should be stressed that OBS are defined in psychiatric terms and not
in neurologic terms. They are purely descriptive and carry no specific etiologic
implications38. According PPDGJ III, Indonesia’s most used guidelines in clinical
psychiatry, Organic Mental Disorders (OMD) include many psychiatric disorders
which divided based on causes and can be proved. It can be divided by the

24
symptoms to delirium, dementia, and amnestic. The primary causes are disease,
trauma or brain injury, which effects directly on brain dysfunction. The secondary
causes are systemic diseases and disorders that harm human’s brain39. The
treatment depends on which disorder is involved. If psychosis symptoms are
present, neuroleptics should be given. There are two generations of neuroleptics.
The first generation (typical) antipsychotics have many side effects rather than
the second generation (atypical). Risperidone, Olanzapine, and Clozapine are the
atypical antipsychotics. The dose is up-titrated until the pharmacologic effects are
acquired40.
This patient was given nifedipine, valsartan, methylprednisolone pulse,
oral corticosteroid while monitoring the vital signs and fluid status, high dose of
intravenous methylprednisolone (10-30 mg/kg/day) was given for 3 days. Oral
prednisone is also given with the dosage of 2 mg/kg/day. After the session
finished, she still looked a bit pale but the laboratory results are better than the
first time. From blood analysis, hemoglobin level raised to 8.7 g/dL from the first
day 4.9 g/dL.
Oral corticosteroids in high doses (starting with 60 mg/24 h) carry a heavy
penalty in terms of side effects. Thus, today many clinicians believe pulse
intravenous methylprednisolone, together with low-dose oral prednisolone (10 to
20 mg daily), can reduce the incidence of these side effects, particularly on facial
appearance. This is of course provided that treatment is limited to a maximum
two courses of 3 days’ intravenous 0.5 to 1 g methylprednisolone. Side effects
described after intravenous injection of high doses of corticosteroids include
unpleasant flushing sensations, acute hypertension, gastric pain, and
occasionally acute psychosis47. This patient was given Nifedipine and Valsartan
as anti-hypertension drugs. Aspilet is given to reduced SLE symptoms as joint
paint and reduced high dosed corticosteroid side effect like flushing. Sucralfate
was used to prevent gastric ulcer as high dosed corticosteroid was given.
Chloroquine is an anti-malaria drug. Together with corticosteroid, they prevent
flares in SLE and reducing their severity and duration when it occurs47.
Cyclophosphamide (CPA) is still used as a cytotoxic agent in the acute
phases of severe lupus nephritis51, and this behavior is supported by meta-
analyses of controlled trial52,53. Cyclophosphamide has the advantage in the
induction phase that it is a much more powerful inhibitor of B cells than
azathioprine, and the resynthesizes of autoantibodies is reduced to normal levels

25
rapidly and efficiently. Therefore, most physicians prefer it for induction therapy.
Also, the drug has to be extensively metabolized before it is active, so that (unlike
methylprednisolone) there is no immediate effect. Since the patient is usually in
the hospital at this point, compliance should not be an issue. MMF
(mycophenolate) is also used as immunosuppressive drug and commonly used
as initial treatment to SLE with psychiatric problems.
Risperidone also given for her anti-psychotic drug to overcame the
patient’s psychosis symptoms. The advantage of this atypical anti-psychotic is
the long half-life, so it can be given once daily with dosage 0.5-1 mg/day. Another
advantage of the atypical anti-psychotic is the fewer side effects than typical anti-
psychotic. It was known that anti-psychotics have extrapyramidal syndrome as
side effects and happened frequently at children41. So the second generation
anti-psychotic is more preferable in children. This patient was given Risperidone
1 mg once daily. The extrapyramidal side-effects still need to be considered and
monitored though.
Chronic kidney disease (CKD) is determined by the presence of kidney
damage and level of kidney function (GFR), irrespective of diagnosis. The stage
of the CKD is assigned based on the level of kidney function. It has many
etiologies, acquired or even inherited disorders. For children above 5 years old,
acquired disease, including lupus nephritis, dominate the etiology. There are
many pathogenesis in chronic kidney disease despite removing the original insult.
Progressive injury and renal structural destruction or even metabolic genetic
diseases are frequently found below it. Then proteinuria, uncontrolled
hypertension, and hyperphosphatemia can contribute to renal function decline
and harm renal blood vessels45.
Laboratory findings can include elevations in blood urea nitrogen and
serum creatinine and can reveal hyperkalemia, hyponatremia (if volume
overloaded), hypernatremia (loss of free water), acidosis, hypocalcemia,
hyperphosphatemia, and an elevation in uric acid. Patients with heavy proteinuria
can have hypoalbuminemia. A complete blood cell count may show a
normochromic, normocytic anemia. Serum cholesterol and triglyceride levels are
often elevated. Inulin clearance is the gold standard to determine GFR, but it is
not easy to measure. Endogenous creatinine clearance is the most widely used
marker of GFR, but creatinine secretion falsely elevates the calculated GFR45.

26
 Chronic kidney disease is defined as either kidney damage or decreased
kidney function (decreased GFR) for 3 or more month. Kidney disease can be
diagnosed without knowledge of its cause. Although in this patient, the cause was
most likely the Lupus Nephritis. Persistent proteinuria is the principal marker of
kidney damage. The first time she came to Saiful Anwar General Hospital, her
urinalysis showed +3 for protein. Then from blood test, her ureum was 344.9 and
creatinine was 10.82. Glomerular filtration rate is the best measure of overall
kidney function in health and disease. A GFR level less than 60 mL/min per 1.73
m2 represents loss of half or more of the adult level of normal kidney function.
Below this level, the prevalence of complications of chronic kidney disease
increases. The guidelines defined kidney failure as either GFR less than 15
mL/min per 1.73 m2, which is accompanied in most cases by signs and
symptoms of uremia, or a need to start kidney replacement therapy (dialysis or
transplantation). The estimated GFR for this patient when she first came to
hospital was 6.67 mL/min. According to guideline, this number is categorized as
Stage 5 CKD and needs kidney replacement if uremia presents54.
The treatment of CKD is aimed at replacing absent or diminished renal
functions, which progressively deteriorate in parallel with the progressive loss of
GFR, and slowing the progression of renal dysfunction. Children with CKD should
be treated at a pediatric center capable of supplying multidisciplinary services.
The management of CKD requires close monitoring of a patient’s clinical and
laboratory status. Blood studies to be followed routinely include serum
electrolytes, blood urea nitrogen, creatinine, calcium, phosphorus, albumin,
alkaline phosphatase, and hemoglobin levels45.
If the disease progression reach ESRD (end stage renal disease), renal
replacement therapy becomes necessary. It could be done by dialysis or renal
transplantation. The selection of dialysis modality must be individualized to fit the
needs of each child. Children and adolescents typically have 3 hemodialysis
treatments (3-4 hour each) per week during which fluid and solute wastes are
removed. But peritoneal dialysis is not as efficient as hemodialysis, it must be
performed daily rather than 3 times a week34. Renal transplantation is the
ultimate goal of these patients, however there are so many things need to be
considered to do this. Despite having many advantages, the preparation and the
maintenance is somewhat difficult.

27
 This patient fell into ESRD and had to do renal replacement therapy. She
had CAPD access since 3 months ago. Treatment by CAPD was chosen
because she was still in school age, and continuous hemodialysis would interrupt
with her study. Thus, she can keep studying at school and doing CAPD at home.
But the next month, she had 3 sessions of hemodialysis at Saiful Anwar General
Hospital after fainted two times. She fainted because of uremic encephalopathy.
It’s a state that happens because urea level in the blood is too high and harms
brain function. Seems like CAPD treatment wasn’t enough for her condition, so
she had to go down with hemodialysis. There was still no plan to do renal
transplantation.

28
SUMMARY

A case of lupus nephritis with clinical manifestation neuropsychiatric and

chronic kidney disease has been reported. The case was present predominantly
neuropsychiatry manifestations such as personality disorders, irritability, anxiety,
depression, crying, apathy, poor eye contact, difficulty concentrating and
speaking, and movement disorder. Proposed mechanism of CNS involvement in
SLE is circulating immune complexes, anti-neuronal antibodies, antiphospholipid
antibodies, and cytokine release. We do not know exactly about the proposed
mechanism to cause cerebral lupus in our cases. No one diagnostic test is
conclusive of the CNS involvement in SLE; however clinical manifestations
support diagnosis. This patient was diagnosed organic mental disorder made
based on clinical manifestations, laboratory and radiographic findings.
Treatment in our cases included corticosteroids immunosuppressive therapy and
anti-psychotic drug

29
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