PEDIATRIC

SYSTEMIC LUPUS ERYTHEMATOSUS

Department of Child Health Faculty of Medicine

Diponegoro University Kariadi Hospital
Semarang
 BACKGROUND

Systemic Lupus Erythematosus (SLE)

A rheumatic disease characterized by autoantibodies directed

against self-antigens, immune complex formation, and immune
dysregulation, resulting in damage to essentially any organ.

Kidneys, skin, blood cells, and nervous system

Flare Remission

Unpredictable many years of symptoms or with acute (life

threatening disease)
 EPIDEMIOLOGY

Incidence rates among children younger than age 15 years have

been reported to be 0.5-0.6 case per 100,000 persons.

Prevalence rates of 4-250 cases per 100,000 persons have been

reported, with greater prevalence in Native Americans, Asian
Americans, Latin Americans, and African Americans.

A female-to-male ratio of approximately 4:1 occurs before

puberty and after menopause, with a ratio of 8:1 between onset
and loss of estrogen cycles.

Uncommon in children younger than age 8 years

 Lupus in Children

Uncommon before age 4

Incidence 0.5-0.6 /100,000 per year

Females>males

Children have more organ involvement than adults

Compliance issues in adolescence dangerous

Prognosis guarded; 30% may progress to renal

insufficiency depending on treatment
 LE CELL

The LE cell is a neutrophil

that has engulfed the
antibody-coated nucleus of
another neutrophil.

LE cells may appear in

rosettes where there are
several neutrophils vying for
an individual complement
covered protein.
 PROTEAN MANIFESTATIONS

Differential Diagnosis

Fever of Unknown Origin

Arthralgia
Anemia
New Onset kidney disease
Psycosis
Fatique

Early diagnosis & careful treatment improved the prognosis

 CHARACTERISTIC

Episodic : symptoms appear intermittent (arthritis,

pleurisy, dermatitis may appear months or years

previously)

Multisystem disease : especially in children

Characterized by antinuclear antibody (especially to

dsDNA)

CHRONIC, UNPREDICTABLE, CHARACTERIZED WITH EXCACERBATIONS

& REMISSION
 ETIOLOGY

Specific cause remains undefined

 APOPTOSIS
Protease (caspase) cascade

Receptor ligation
ex: TNF, Fas

DNA fragmentation
Chromatin condensation

Cytoplasmic
blebbing
Clearance by phagocytes

Y
Apoptotic bodies
AUTOREACTIVITY Y
 PATHOPHYSIOLOGY

Autoimmune reactions directed against

constituents of cell nucleus, DNA

Antibody response related to B and

T cell hyperactivity
 MAIN PATHOLOGY

The plasma cells are producing antibodies that are specific for

self proteins, namely ds-DNA

Overactive B-cells

Suppressed regulatory function in T-cells

Lack of T-cells

Activation of the Complement system

 PATOFISIOLOGI
timbul sebagai ekspresi klinis sebab ??
Diawali :
sistem tak mampu kenali struktur
antigen diri
imun

AutoAb + AutoAg = Komplek imun

mengendap berupa depot di jaringan aktivasi mekanisme

autoimun
komplemen sehingga terjadi Rx Inflamasi
timbullah LESI !!
 Clinical Features of SLE

Constitutional symptoms
Musculoskeletal disease
Mucocutaneous involvement
Renal Disease
Central nervous system disease
Cardiopulmonary disease
Hematologic abnormalities
Gastrointestinal involvement
 SYMPTOMS

Non-specific:

Fatigue

Weight loss

Malaise = generally feeling ill

Fever

Anorexia (over time)

Arthritis

90% of patients experience arthritic symptoms

Symmetrical

Appears in hands, wrists, and knees mainly

 General symptoms
The most common symptoms listed as initial
complaints are fatigue, fever, and weight loss.

Fever: fever secondary to active disease was

recorded from 50% to 86%. No fever curve or
pattern is characteristic. It can be difficult, but very
important to distinguish the fever of SLE from that
caused by complicating infections.
 Mucocutaneous Manifestations
Frequency: 76%
Malar rash
Discoid lupus
Vasculitis (purpura, petechiae)
Raynauds phenomenon
Nail involvement
Alopecia
Periungual erythema/ Livedo reticularis
Photosensitivity
Oral/ nasal ulcers
 CLASSIC MALAR RASH

Distribution over the

cheeks and nasal bridge
Fixed erythema
Sometimes mild
induration

Butterfly Rash Nasolabial folds

Photosensitivity noted in
patients with anti-Ro
antibodies
 Vasculitic skin lesin
 Alopecia
 MUSKULOSKELETAL

Swan Neck Deformity joint and muscle pains, small

joints of hands, synovitis (pain
may appear disproportionate to
the degree of swelling), joint
erosion (unusual)

Meniscus
Cardiovascular system :

Pericarditis, pericardial effusion (10%)

Myocardial involvement conduction defect, arrhythmias, cardiac

failure

libman-sacks endocarditis (mitral valve)valvular incompetence

Respiratory system :

Pleural effusion, pleurisy, pleuritic pain

shrinking lung syndrome

Recurrent pneumonitis (may be due to immunosupresive therapy)

Renal involvement :
60% develops renal involvement
May be due from immune complex deposition
in the glomerulus
Renal biopsy : mesangial deposits of
immunoglobulin and complement (direct
immunofluorescent)
Proliferative glomerulonephritisnephrotic
syndrome, hypertension, renal failure
Mortality 60% (untreated) at 3 years
Haematological features :

Autoimmune haemolytic syndrome

Lymphopenia,neutropenia, thrombocytopenia

Normochromic anaemia of chronic disease

The anti-phospholipid syndrome :

Recurrent thrombosis (arterial or venous)

Thrombocytopenia

Recurrent fetal loss (2nd trimester)

Heart valve lesions

High-titre IgG anti-phospholipid autoantibodies and/or a

related autoantibody, the lupus anticoagulant

 Features of SLE
FEATURES %
Constitutional symptoms 50
Joints/muscles 62
Skin 50
Blood 8
Brain 15
Kidney 25
 Cumulative organ involvement in SLE patient

Organ/tissue Patient (%)

Skin 80
Joints/muscles 80
Lung/pleura 30
Blood 60
Brain 30
Kidney 40
Heart 15
 INVESTIGATION

Anti-nuclear antibodies : mostly present (anti-dsDNA

antibodies, anti-ENA)

Disease activity : measuring C3, C4

ESR elevated during acute flares

CRP normal. If CRP +, consider infection, serositis,

synovitis, vasculitis
 Autoantibodies in SLE
Antibodies to cell nucleus component
ANA, anti-dsDNA, antibodies to extracellular nuclear
antigen (ENA, anti-Sm, anti-RNP, anti-Jo1)
Antibodies to cytoplasmic antigens
anti-SSA, anti-SSB
Cell-specific autoantibodies
lymphocytotoxic antibodies, anti-neurone antibodies,
anti-erythrocyte antibodies, anti-platelet antibodies
Antibodies to serum components
antiphospholipid antibody
anticoagulants antiglobulin (rheumatoid factor)
 Diagnostic Studies
Antinuclear antibodies

ANA and other antibodies indicate autoimmune disease

Anti-DNA and anti-Smith antibody tests most specific for

SLE

LE prep can be positive with other rheumatoid diseases

ESR & CRP are indicative of inflammatory activity

 LABORATORY

Peripheral blood smear Coagulation study

VDRL
Titer IgM, IgG, IgA Combs test
Electrophoresis protein
Krioglobulin Ureum, creatinin
Prot urin ( 24 jam )
Urine and blood culture
Chest X Ray
 Diagnostic Tests
CBC for hematologic problems

UA for lupus nephritis

X-rays of affected joints

Chest x-ray for pulmonary problems

ECG for cardiac problems

 DIAGNOSIS

CLINICALLY LABORATORY

Episodic disease
Multisystem disease
Usually with ANA (antibody antinuclear)
positive

American College of Rheumatology

 CRITERIA FOR DIAGNOSING LUPUS

The diagnosis of lupus is a clinical one made by

observing symptoms. Lab tests provide only a part

of the picture. The American College of

Rheumatology has designated 11 criteria for

diagnosis. To receive the diagnosis of lupus, a

person must have 4 or more of these criteria:

 CLINICAL FEATURE
1982 American College of Rheumatology (ACR) criteria
NO CRITERIA DEFINITION
1 Malar rash Fixed erythema over the cheeks and nasal
bridge, flat or raised, butterfly rash
2 Discoid rash Erythematous raised-rimmed lesions with
keratotic scaling and follicular plugging, often
scarring
3 Photosensitivity Unusual skin reaction to light exposure
4 Oral ulcers Oral or nasopharyngeal, usuallly painless,
palate is most specific
5 Arthritis Nonerosive, two or more peripheral joints
with tenderness or swelling
6 Serositis Pleurisy, pericarditis on examination or
diagnostic ECG or imaging
7 Renal involvement Proteinuria (>0,5 g/d or 3+ on dipstick testing) or
cellular cast

8 Neurologic disorder Seizures of psychosis in the absence of other causes

9 Blood disorder Leukopenia (<4000 cells 103 /L on >1 occasion

Lymphopenia (<1500 cells/L on >1 occasion
Thrombocytopenia (<100x103L in the absence of
offending medications), hemolytic anaemia

10 Immunologic ds DNA, anti-Smith (Sm) antibodies, antiphospholipid

phenomena antibodies (anticardiolipin immunoglobulin G or
immunoglobulin M or lupus anticoagulant), biologic
false-positive serologic test results for syphilis, LE cells
(ommited in 1997)

11 ANAs Higher titesrs generally more specific (>1:160), must be

in the absence of medications associated with drug-
induced lupus
 MANAGEMENT

Individual approach

Avoidance of exposure (sunlight, drugs,

infection)

Sun-blocking creams, NSAIDs

Awareness of long-term drugs therapy

Effects of therapy for women

 1. Monitoring the lupus patients

It cannot be emphasized too strongly that lupus is a disease

requiring regular and careful follow-up.

Important initial advice should be given about avoiding UV

light, infections, extreme stress or fatigue

Laboratory testblood test, ESR, C3,IC, liver function tests

and anti-dsDNA.
 2. Grading clinical activity
The highly variable nature of the syndrome

Evaluation of lupus activity is the base or beginning of

therapy.

Non-life-threatening features such as arthralgia, skin

rash, RP, alopecia

Severe complication such as renal, cerebral and heart

involvement.
 SLE disease activity index (SLEDAI)
Clinical feature score
seizure , psychosis , organ brain syndrome 8
visual disturbance, cranial nerve disorder 8
lupus headache, cerebrovascular accidents, 8
vasculitis 8
arthritis 4
myositis 4
urinary casts, hematuria, proteinure, pyuria 4
rash, alopecia, mucosal ulcers, 2
pleurisy, pericarditis 2
low complement, increased DNA binding 2
fever 1
thrombocytopenia, leucopenia 1
 3. Clinical therapy
There are four main groups drugs useful in the
treatment of lupus: the non-steroid anti-
inflammatory drugs, anti-malarials, corticosteroid
and cytotoxic drugs.

How to treat lupus is a kind of art. Which and the

dosage of drugs will be used to treat the patient
depend on lupus activity.
 Collaborative Care
Drug therapy
NSAIDs

Antimalarial drugs

Steroid-sparing drugs

Corticosteroids

Immunosuppressive drugs
 SLE - Treatment
MILD DISEASE: Rashes, arthralgias, leukopenia,
anemia, arthritis, fever, fatigue
Treatment: NSAIDs, low dose corticosteroids (<60
mg/day), antimalarials (hydroxychloroquine), low dose
methotrexate

MODERATE DISEASE: Mild disease + mild organ

system involvement such as: mild pericarditis,
pneumonitis, hemolytic anemia,
thrombocytopenia, mild renal disease, mild CNS
disease
 SLE - Treatment
MODERATE DISEASE (cont.):
Treatment: Prednisone 1-2 mg/kg/day,
NSAIDS, Antimalarials, Low dose methotrexate,
Azathioprine, MMF

SEVERE DISEASE: Severe, life-threatening organ

system involvement
Treatment: High dose corticosteroids (2-3
mg/kg/day or pulse), Immunosuppressives (IV
pulse Cyclophosphamide), Plasmapheresis,
Anticoagulation where appropriate
 COMPLICATIONS

Hematologic abnormalities, including hemolytic anemia,

thrombocytopenia, leukopenia, or lymphopenia.

Kidneys : nephritis or nephrotic syndrome

Neurologic abnormalities, from psychosis and seizure to cognitive

disorders to peripheral neuropathies

Pulmonary disease manifests as pulmonary hemorrhage, fibrosis, or

infarct.

Various rashes, gastrointestinal (GI) manifestations, serositis,

arthritis, endocrinopathies,

Cardiac abnormalities (eg, valvulitis and carditis) are observed.

 PROGNOSIS

High risk disease with the possibility of end organ damage

Affect organ function quality of life
Potential complications from the adverse effects of steroid
Cardiovascular myocardial infarction

Survival Rate
95% rate of survival at 5 years, some reported 98-100%

Depends disease severity and compliance of therapy

Mortality rates rise over time, with the major causes of death being
infection, nephritis, central nervous system (CNS) disease, pulmonary
hemorrhage, and myocardial infarction
 Emergencies in SLE
Fever: always r/o infection
Renal disease: uremia, hypertension
Cytopenias: acute hemolytic anemia, thrombocytopenia
CNS: seizures, coma
Pleural effusion/ pneumonitis/ pulmonary hemorrhage
Pericarditis/ myocarditis
Peritonitis/ pancreatitis/ GI bleed
Raynaud's: digital necrosis
Ocular: retinal vein thrombosis, hemorrhage, edema
Thrombotic events, catastrophic antiphospholipid
antibody syndrome, microangiopathic syndromes
Lupus Crisis
 Morbidity and Mortality in SLE
Life-threatening organ system involvement:
Renal Failure (HTN, dialysis, transplant)
Cardiovascular: accelerated, premature
atherosclerotic disease (CAD, MIs),
dyslipoproteinemias
CNS: Cognitive defect
Treatment Toxicities:
Long-term steroid use: growth/ pubertal delay,
avascular necrosis of bone, osteoporosis/ fractures,
cataracts, glaucoma
Cytoxan: Fertility issues, risk of malignancy
Infectious: In immunocompromised patients- PCP,
Varicella zoster, opportunistic infections
 SPECIAL CONSIDERATIONS IN
CHILDREN AND ADOLESCENTS
Life-long burden of renal failure and (multiple)
renal transplant(s)
Steroid toxicity
Immunosuppressive toxicity
Infection risk different in children:
CMV, EBV
Bacterial infections, esp. strep
Fungal infections
Developmental age and psychosocial issues
Special treatment considerations in
children
May be approached more aggressively.
Corticosteroids in children
(prednisone, prednisolone, Medrol, SoluMedrol)
Growth effects
Body image

Cyclophosphamide
Fertility? Cancer risks?
Rituximab
Future immune function, vaccine effectiveness