Systemic Lupus Erythematosus :

War against “self”

Dr. Wistiani, SpAK, MSi Med
 Genetic & epidemiologic factors

• Ratio female : male = 5 : 1 to 9 : 1

What factors ?

• Hormones
• X chromosome

Chronic inflammation
 Epidemiology

• Incidence in children 15-17%

• Rarely happens at less than 5 years old

• Prevalence is higher in black race

compare to white

• Prevalence 1/2000
 Characteristics

• 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)
• Drugs: GENETIC :
- procainamide • Monozygotic twins 25%
• Dizygotic twins 2%
- hydralazine
- quinidine

• Female >
• Viral : EBV
• Ultraviolet
radiation

LES
 PATHOGENESIS OF SLE

Mok CC, Lau CS. J Clin Pathol 2003;56

PATHOGENESIS
PATHOGENESIS
PATHOGENESIS (2)
PATHOGENESIS (3)
SLE
impaired clearance of apoptotic cells

Early apoptotic cell Secondary necrotic cell

In SLE

clearance by phagocytes
no necrosis
no danger signals
no immune response
impaired clearance
secondary necrotic cells
danger signals
inflammation
exposure of autoantigens
autoimmune reaction > ANA
 Systemic lupus erythematosus
Presentation
90% tired, arthritis, arthralgia
80% fever
70% hair loss, anemia, swollen lymph nodes
60% weight loss, malar rash
50% pleuritis, pericarditis, nephritis
40% sun light sensitivity

SLE : 4 out of 11 ARA criteria (1982 / 1997)

1 Malar rash
2 Discoid lupus
3 Photosensitivity
4 Oral ulcers
5 Arthritis
6 Serositis (pleuritis or pericarditis)
7 Renal disorders (proteinuria or cellular casts)
8 Seizures or psychosis
9 Hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia
10 Anti-DNA antibody, anti-Sm antibody or antiphospholipid antibody positive
11 Positive antinuclear antibody test (positive ANA)
 Clinical features
Systemic form : common initial symptoms are fatigue,
fever, weigh loss, joint pains and skin rash
Musculoskeletal : - joint and muscle pains,
small joints of hands, synovitis (pain may appear
disproportionate to the degree of swelling),
joint erosion (unusual)

Menisc
us
Cutaneous features : classical rash,
sun-exposed areas, “butterfly rash”,
alopecia.
“Photosensitivity” noted in patients
with anti-Ro antibodies.

Biopsy shows immunoglobulin and

complement deposits at the dermal-
epidermal junction

Mucous ulceration
 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)
Neurological features :
• Neuropsychiatric symptoms
• No specific test to predict nor confirm
• Disordered mental ability, seizures
• Cranial nerve palsy, headache, tremor, etc
• May be due to small-vessel vasculitis or
specific anti-neuronal immunological activity
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 glomerulonephritisnephrotic
syndrome, hypertension, renal failure
• Mortality 60% (untreated) at 3 years
Haematological features :
• Autoimmune haemolytic syndrome
• Lymphopenia, neutropenia,
thrombocytopenia
• Normochromic anaemia of chronic
disease
 DIAGNOSIS
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 /µL on >1 occasion

Lymphopenia (<1500 cells/µL 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
SLE
pathogenesis and therapy

Abundant antibodies to nuclear epitopes (ANA)

Epitope spreading
Antibodies to DNA
Antibodies to cell wall constituents (eg thrombocytes)
Immune complex formation
Complement activation
Lupus nephritis due to IgG and C3 deposits

Therapy
Immunosuppressive (steroids, CY, azathioprine, MMF)
Anti-CD20 ?
Autologous stem-cell transplantation ?
 PATHOGENESIS (4)

Target of management
 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
 MANAGEMENT

• Individual approach
• Avoidance of exposure (sunlight, drugs,
infection)
• Sun-blocking creams, NSAIDs
• Awareness of long-term drugs therapy
• Effects of therapy for women
 References
1. Chapel H, Haeney M, Misbah S, Snowden N. In : Essentials of Clinical
Immunology. Massachusetts, Blackwell Publishing,2006
2. Akib AAP, Munasir Z, Kurniati N. Buku Ajar Alergi-Imunologi Anak.
Jakarta : BP IDAI, 2007
3. Gorczynski R, Stanley J. Problem-Based Immunology. Philadelphia :
Elsevier Inc, 2006
 HIDDEN MESSAGE

Diverse presentation of lupus :

• Range from rash and arthritis, through
anemia and thrombocytopenia to serositis,
nephritis, seizures, and psychosis, so LUPUS
should be part of the differential diagnosis in
any patient presenting with one of these
clinical problems, especially in female patients
between 15 and 50 years of age