Systemic lupus erythematosus in children

Josua Sitorus and Sri Wulandari

Medical Faculty University of Sumatera Utara/ Haji Adam Malik General
Hospital

Supervisor:
dr.
Selvi
(Ped),SpA(K)

Nafianti

M.Ked

Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a complex, multisystem
autoimmune

disease

which

results

from

the

interplay

environmental, hormonal and genetic factors.

Lupus can be a mild disease, a severe and life-threatening illness,
or anything in between

of

Introduction
The diversity of clinical symptoms in SLE is great, and all organ
systems are vulnerable

Widespread inflammation of vessels and connective tissues

Presence of antinuclear antibodies

Epidemiology
Pediatric SLE represent 15-20% of all SLE
Prevalence: 2140/100,000 worldwide but as high as
207/100,000
Incidence: 110/100,000 worldwide
Population at highest risk:
Female:male ratio is approximately 9:1
Variation in race/ethnicity:
More common in Black (36x),
Hispanic and Native American (23x), and
Asian (2x) populations

Etiology

Environmen
t

Antigen
Hormones (estrogen)
Infections
Toxins
Medications
Sun exposure

Infection

Gene

Hormone
s

Etiology is Unknown

Genetic SusceptibilityClinical Studies

Rate of SLE concordance in monozygotic twins is 24%35%; in

dizygotic twins is 2%5%
10%12% of SLE patients have 1st- or 2nd-degree relatives
with SLE compared with <1% in healthy individuals
SLE patients may have family members with other
autoimmune diseases

Etiology

Pathogenesis

From Bertsias GK, Salmon JE, Boumpas DT. Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospect
for the new decade. Ann Rheum Dis 2010;69:160311.

Examples of Immune Dysregulation

in Lupus
B-cells
Defective selection/signaling
Autoantibody production
T-cells
Increased numbers of Th17 and Th2 cells and decreased numbers of Tregs
T-cells are less susceptible to activation-induced cell death
Plasmacytoid dendritic cells
Produce large amounts of interferon
Plasmacytoid dendritic cells: Stimulate activation and
proliferation of autoreactive T- and B-cells

Pathogenesis of Lupus Important

Concepts
Autoimmunity is an altered immune homeostasis that leads to
autoreactivity, immunodeficiency, and malignancy

Immune dysregulation leading to autoreactivity and

autoantibodies in SLE occurs in different phases and likely
represents the untoward effects of environmental triggers on the
genetically susceptible host

ACR (Revised) Criteria for

Classification
Hematologic
disorder:
Malar rash
4/11= 95% Specificity;
85%
Immune-mediated
Discoid rash
Sensitivity
hemolytic anemia,

Photosensitivity
Oral ulcers
Arthritis
Serositis
Glomerulonephritis
Neurologic disorder:
Seizures and/or psychosis

leukopenia,
lymphopenia,
thrombocytopenia

Antinuclear antibodies
(ANA)

Immunologic disorder:
anti-DNA antibody, antiSm
antibody, or

Tan EM, Cohen AS, Fries JF, et al. Arthritis Rheum. 1982;25:1271-1277. Hochberg MC. Arthritis Rheum. 1997;40:1725. [

Examples of Organs Involved, Signs,

and Symptoms

Medical Illustration Copyright 2012. Nucleus Medical Media. All rights

reserved

Lupus on the Outside

Synovitis

Subacute
cutaneous lupus
erythematosus

Malar
Rash

Vasculit
is

Discoid rash

Lupus profundus

Oral
ulcer

Jaccouds
arthropathy

Systemic Lupus Erythematosus Overview Dr. Graciela Alarcn The University of Alabama at Birmingham

Lupus on the Inside

Serositi
s

Pericardial
effusion

Cerebral infarct

Brain atroph

Spherocytes

Spherocytes

Glomerulonep
hritis

Systemic Lupus Erythematosus Overview Dr. Graciela Alarcn The University of Alabama at Birmingham

Diagnosis and
Diagnostic Tests

ANA

Autoantibodies against various components of the cell nucleus

Present in many autoimmune disorders as well as some healthy subjects
Sensitive (not specific for SLE)

ANA

Because of low specificity, ANA usefulness increases if the pretest

probability for lupus is high; ie, the patient has symptoms and signs that
can be attributed to SLE

Because of the high sensitivity of the ANA, a patient with negative ANA is
unlikely to have lupus even when her/his clinical presentation is suggestive
of lupus

Incidence of Positive
ANA
Normal subjects 3%4%
SLE 95%99%
Scleroderma 95%
Hashimotos thyroiditis 50%
Idiopathic pulmonary fibrosis 50%
Incidence increases with age, chronic infections, and other
chronic conditions

Autoantibodies
in SLE
Antibodies

Lupus
Specificity

Clinical Associations

ANA

Low

Nonspecific

Anti-dsDNA

High

Nephritis

Anti-Sm

High

Nonspecific

Anti-RNP

Low

Arthritis,
disease

Anti-SSA

Low

Dry eyes/mouth, subacute

cutaneous
lupus
erythematosus
(SCLE),
neonatal
lupus,
photosensitivity

Anti-SSB

Low

Same as above

Antiphospholi
pid

Intermediate

myositis,

Clotting diathesis

lung

Predictors of flare (in some but not all cases)

New evidence of complement consumption
Rising anti-dsDNA titers
Increased ESR
New lymphopenia

Differential Diagnosis
Polyarticular diseases

Rheumatoid arthritis
Stills disease

Undifferentiated connective tissue

disease

Sjgrens syndrome,
Antiphospholipid syndrome,
Fibromyalgia with positive ANA,
Idiopathic thrombocytopenic purpura,
Drug induced lupus

Glomerulonephritis
Fever or splenomegaly/lymphadenopathy
Pulmonaryrenal syndrome

Post-infectious glomerulonephritis
(streptococcal, staphylococcal)
Membranoproliferative
glomerulonephriti
Infectious diseases or lymphoma
Goodpastures syndrome, or
antineutrophil
Cytoplasmic antibody (ANCA) associated
vasculitis

Prognosis
Characterized by
Abrupt onset of symptoms
Increased renal, neurologic, hematologic, and serosal
involvement
Rapid accrual of damage (irreversible organ injury)
Factors contributing to increased mortality
-Disease duration; increased mortality early on
-High disease severity at diagnosis
-Younger age at diagnosis
-Ethnicity: Black, Hispanic, Asian, and Native American
populations are at greater risk
-Male gender
-Low socioeconomic status
-Poor patient adherence*
-Inadequate patient support system*
-Limited patient education*
Bernatsky S, Boivin JF, Joseph L, et al. Arthritis Rheum. 2006;54:2550-2557.

Therapeutic Principles

Goals of therapy
Stop and reverse ongoing organ inflammation
Prevent or limit irreversible end-organ damage
Potential toxicities of immunosuppressive therapies demand
vigilant management

Current Therapy for SLE

Corticosteroids
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
Azathioprine
Hydroxychloroquine
Belimumab

New Therapeutic Strategies

Targeted Immunotherapy
Immune targeted therapy
B-cell directed
Cytokine inhibitors
Costimulation blockade
Peptide inhibitors
Kinase inhibitors
T regulatory cells
Stem cell transplant

Yildirim-Toruner C, Diamond B. J Allergy Clin Immunol. 2011;127:303-312.

Current TherapyLimitations
Immunosuppressive drugs confer an
increased risk for
Infection
Cancer
Infertility
Common side effects of corticosteroids
Diabetes
Infections
Cushingoid appearance

Osteoporosis

Mood disturbances

Hypertension

Osteonecrosis

Lipid abnormalities

Therapeutic combinations aimed at

induction of remission, maintenance
therapy, and supportive therapy

Case
Presentation

RN, a 14-year-old girl presented to pediatric division, adam malik hospital with a
complaint continue chemotherapy.
The patient has been enrolled in the division of allergy immunology Adam Malik
hospital with the diagnosis of Systemic lupus ertematosus.
History of previous illness : Patients come first in September 2015 with a history of
joint pain and swelling in the hands, knees, and ankles .pain was felt already for 1
week. Joints pain getting worse in the morning, especially on waking.
Reddish rash experienced by the patient in simultaneously with pain. The rash felt
heat and itching. The rash initially patchy reddish spots alone and increasingly
spread on both sides of the cheeks. Rash worsens when exposed to sunlight.

Patients experienced hair loss since 2 weeks.

Urination abnormality denied.
Complaints of pale and yellow body denied.
Present seizures denied.
Previous history of seizures experienced by patients until there is a decrease

History of disease: Gland TBC, Systemic lupus

History
of medication :Methylprednisolone injection, CPA injection,
erythematosus
methylprednisolone tablet
History of family : None
History of parents medication : None
History of pregnancy: 9 months in the age
History
of birth: assited by midwife, birth spontaneous, cried immediately after birth,
29
BW and BL unclear.
History of feeding: in normal feeding per category of year.
History of immunization : Unclear
History of growth and development: normal

Head:
Hair and scalp

: alopesia

Face

: edema (-), malar rash (+), discoid rash (+)

Eye

: endofthalmus (-), exofthalmus (-), light reflex (+/+),

isochoric pupil, palpebral conjunctiva pale (-/-),scleraikerik (-/-),

normal vision
Ears

: both ear lobe in normal morphologic, ear discharge (-/-), inflammation

(-/-), impurities
Nose

(-/-), dirt (-/-),

: septum deviation (-), polyp(-/-), impurities (-/-) secret (-/-), nasal

canule (+), pinkish

Mouth :

cyanosis on lips (-), pinkish oral mucose, pseudomembrane (-),

detritus (-), secret (-),

measurement T1

choncae
tongue measurement normoglosia, tonsil

Neck

: Bullneck (-), tyroidmeasurement(-), Lymph node enlargement (-),

neck stiffness (-), JVP (-)

Thorax :
Inspection : Barrel chest (-), Pigeon chest (-), Funnel chest(-),
Symmetrical fusiform, retraction (-)
Palpation

stem fremitus left=right, normal condition within both

lungs.
Percussion :
Lungs : sonor on both lungs.
Heart : Upper barrier : ICS III sinistra
Right barrier : ICS V LPSD dextra
Left barrier; ICS V 1 cm medial LMCS
Auscultaion:
Lungs : Breathing sound :vesikuler, Additional sound:ronki(-/-), wheezing
(-/-)
Heart : S1,S2 (+), S3(-), S4 (-), murmur (-)

 Abdomen

Inspection : Simetris, ascites (-)

Palpation : Soepel, liver unpalpable, kidney unpalpable spleen unpalpable, tumor
unpalpable
Percussion: Shifting dullness (-), costovertebral pain (-),
Auscultation: Normoperisaltik, double sound (-)

Extremities : Pulse 80bpm, regular,adequate p/v, felt warm, CRT < 3, pitting
oedema (-/-), muscle
Anogenital : Female

rigidity (-)

Differential diagnosis:

Systemic lupus

erithematosus
Drug induced lupus
Rheumatoid arthritis
Fibromyalgia with
positive ANA

Working diagnosis : Systemic lupus

erithematosus

Test

Complete blood
analysis
Result11 January 2016
Unit

References

Hemoglobin

11,50

g%

11.3-14.1

Erythrocyte

3.65

106/mm3

4.40-4.48

Leucocyte

4,27

103/mm3

6.0-17.5

Thrombocyte

189

103/mm3

217-497

Hematocrite

33.00

37-41

Eosinophil

8,20

1-6

Basophil

0.900

0-1

Neutrophil

50.60

37-80

Lymphocyte

25,50

20-40

Monocyte

14,80

2-8

MCV

90.40

fL

81-95

MCH

31.50

Pg

25-29

MCHC

34.80

g%

29-31

Carbohydrate Metabolism
Blood Glucose

85.50

mg/dL

< 200

Ureum

10.80

mg/dL

< 50

Creatinine

0.45

mg/dL

0.24-0.41

Calcium (Ca)

8.9

mEq/L

9.2-11.0

Natrium

143

mEq/L

135-155

Potassium

3.9

mEq/L

3.6-5.5

Chloride

109

mEq/L

96106

Renal Function

Electrolyte

Lab Result on
September 2015
Liver
Total Bilirubin

0.31

mg/dL

<1

Direct Bilirubin

0.15

mg/dL

0-0.2

AlkaliPosfatase(ALP)

144

U/L

<187

AST/SGOT

178

U/L

<32

ALT/SGPT

70

U/L

<31

Albumin

2.6

g/dl

3.2-4.5

Imunoserology
ANA Test

149

<20

Anti ds-DNA

862.0

0-200

CRP Kuantitatif

<0.7

mg/dL

3.6-5.5

THERAPY

Normal diet 1800kcal with 72mg protein

Inj. Methylprednisolone 1000 mg in 100cc NaCl 0.9%
finish in 1 hour.
Inj. CPA 840mg (20/m2) mix with Mesna 500 mg
Methyl prednisolone tab 3-3-3

Follow Up
12 January 2016

P
Normal diet
1800kcal with 72mg
protein
Inj.

Fever (-)
Cough (-)
Vomiting (-)
Continuous
Malar
Rash Chemotheraphy
(+)
Alloplesia (+)

Methylprednisolone
1000 mg in 100cc

SLE

NaCl 0.9% finish in 1

hour.
Inj. CPA 840mg
(20/m2) mix with
Mesna 500 mg
Methyl
prednisolone tab 33-3

Follow Up
13-14 January 2016

P
Normal diet 1800kcal with
72mg protein

Fever (-)
Cough (-)
Vomiting (-)
Continuous
Malar
Rash Chemotheraphy
(+)
Alloplesia (+)

Inj. Methylprednisolone 1000

mg in 100cc NaCl 0.9% finish in
1 hour.

SLE

Inj. CPA 840mg (20/m2) mix

with Mesna 500 mg
Methyl prednisolone tab 3-3-3

/P: Consult gastro-- recheck Liver

Function

Follow Up
15 January 2016

Continuous
Fever (-)
Chemotheraphy
Cough (-)
Vomiting (-)
Lab Results:
Malar
Rash SGOT/AST: 88 U/L
(+)
SGPT/ALT : 86 U/L
Alloplesia (+)

P
Normal diet 1800kcal with
72mg protein
Inj. Methylprednisolone 1000

SLE

mg in 100cc

NaCl 0.9% finish

in 1 hour.
Inj. CPA 840mg (20/m2) mix
with Mesna 500 mg
Methyl prednisolone tab 3-3-3

Discussion

THEORY

CASE

EPIDEMIOLOGY : Pediatric SLE (pSLE) represents approximately

15-20 % of all SLE patients. It is more common in females than in

A girl 14 years old An asian

males, with a female to male ratio varying from 2.3:1 to 9:1,

depending on the study. The incidence of the disease varies
according to different ethnic groups. SLE is more common in
African-American females.
ETIOLOGY :
Idiopatic Genetic factorEpigenetic effectHormonal factorDrug.
Induced Lupus ErythematousNeonatal Lupus Erythematous

Idiopatic

CLINICAL MANIFESTATION / CLASIFICATION ACR :

Malar rash
Discoid rash
Photosensitivity
Oral ulcers

Malar rash
Photosensitivity
Arthritis,

Arthritis

Abnormality antinuclear antibodies

Serositis

ANA test & ds-DNA

Glomerulonephritis
Neurologic disorder: Seizures and/or psychosis
Hematologic disorder:Immune-mediated
hemolyticanemia, l eukopenia,
lymphopenia,Thrombocytopenia
Antinuclear antibodies (ANA)
Immunologic disorder:anti-DNA antibody, antiSmantibody, or antiphospholipidantibodies

LAB DIAGNOSTIC:
Cytopenias (anemia, thrombocytopenia, leukopenia)
Elevated ESR,

Elevated ESR

CRP, Immunoglobulins
Hypoalbuminemia

AST/ALT : 145/126
Decreased cratinine

Proteinuria; RBCs, casts in urine

ANA test +

Decreased creatinine clearance

ds-DNA +

Low complement levels (C3/ C4)

Autoantibodies (ANA, APL, Coombs, anti-platelet Ab,
rheumotoid factor, etc.)
TREATMENT:
Corticosteroids
Methotrexate
Azathioprine

Cyclophosphamide
Mycophenolate mofetil
Hydroxychloroquine Rituximab

Corticosteroid: Methylprednisolone
Cyclophosphamide

Conclusion:

RN, a 14 years old girl, with 36 kg of body weight and 155 cm of body
height, came to RSUP Haji Adam Malik Medan on January, 11 2016. His main
complaint is to continue the chemotherapy. Patient was registered as
allergic and immunologic divisions patient in Adam Malik Hospital
diagnosed with Systemic Lupus Erythematosus. She was primarily
diagnosed with Systemic Lupus Erythematosus and treated with Inj.
Methylprednisolone 1000 mg in 100cc NaCl 0.9% finish in 1 hour, Inj. CPA
840mg (20/m3 mix with Mesna 500mg, Methyl prednisolone tab 3-3-3.

Thank You