Professional Documents
Culture Documents
Primordial
Autoimmne
Genetically Response
Susceptible
Individual
Healthy
Cross
Autoimmunity Reaction (s)
Organ/ Epitope
Spreading to
Tissue Pathogenic
Damage AutoAbs
Harley JB, Harley ITW, Guthridge JM and James JA. The curiously suspicious: a role for Epstein-Barr virus in Lupus
Looking for environmental factors
at the right time
Multiple environmental
exposures
Genetically Disease
susceptible
individual
Clinical disease
Early life infectious exposure may Threshold
programme a plastic immune system
Edwards CJ and Cooper C. Early environmental exposure and the development of lupus. Lupus 2006 ; 15 :
814-819.
Autoimmune pathogenesis paradigm. APC, antigen-
presenting cell; MHC, major histocompability complex
EVOLVING
AUTOIMMUNE AUTOIMMUNITY
SPECTRUM OF
*DIATHESIS* WITHOUT DISEASE
AUTOIMMUNE
DISEASE
Genetic Risk Factors :
Autoreactive
- MHC
Lymphocytes
- Other
Autoreactive Autoreactive
Lymphocytes Lymphocytes
Modulating and Perpetuating Factors acting at multiple levels: e.g. UV radiation, hormones, drugs,
Reeves G.E.M. Update on the immunology, diagnosis and management of systemic lupus erythematosus. Internal Medicine Journal 2004;34:338-347
Therapy
Induction
Maintenance
Some AutoAb
before Dx: 80%
Sal cerna
SLE Artritis/Artralgia
90%
18%
Kulit
Paru 50-58%
38% Ginjal
Hematologi 50%
Jantung Vaskulitis
50%
48%
Trigger/Eksaserbation
Procainamid
Drugs: Hidralazin UV radiance
Metildopa
CPZ
(320-400 nm)
Abortion Infection
SLE
Pregnancy Surgery
Erythematous Rash
Small Vessel
Vasculitis
Discoid Lupus
Discoid Lupus
Photosensitivity
Oral Ulcers
The 1997 Revised Criteria for
the Classification of SLE
(MD SOAP BRAIN)
1. Malar rash
2. Discoid rash
3. Serositis
a. Pericarditis
b. Pleuritis
4. Oral ulcer
5. Arthritis
6. Photosensitivity
The 1997 Revised Criteria for
the Classification of SLE
7. Blood / Hematologic disorder
a. Hemolytic anemia OR
b. Leukopenia (< 4000/ ml) OR
c. Lymphopenia (<1500/ ml) OR
d. Thrombocytopenia (<100.000)
8. Renal disorder
a. Persistent Proteinuria (>0.5 gr/d)
b. Cellular cast or any tipe
9. ANA
10. Immunologic disorder
a. Anti ds DNA OR
b. Anti Sm OR
c. Antiphospholipid ab
11. Neurological disorder
CURRENT TREATMENT
OF SYSTEMIC LUPUS
ERYTHEMATOSUS
Principles of therapy
1. Remission
2. Organ/ Renal
Survival
3. Patient Survival
4. Complication/
Comorbid
5. Quality of Life
(Cost)
Introduction
Anti-inflammatory drugs
Cortocosteroids
Anti-malarials
Cytotoxic, or immunosuppressive, drugd
Investigational (research) drugs:
Hormone modifications
More selective immunosuppressive
Biologic agents
Klippel John H, et.all. Medications. Lupus Fondation of Amerika
Anti Inflammatory Drugs
Anti-inflammatory medication are the most
commonly used drugs for lupus treatment,
particularly for symptoms such as:
o Fever
o Arthritis, or
o Pleurisy
Improvement in symptoms is generally noted
within several days of beginning treatment
In the majority of people with lupus, anti-
inflammatory drugs are the only medication
that is ever required to control their lupus
Types of anti malarials
Hydroxychloroquine (Plaquenil)
Chloroquine (aralen)
Quinacrine (atabrine)
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition,
Lippincot Williams & Wilkins 2007
Which Medication are Right for My Lupus
Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
Immunosuppressive effects
1. Lymphopenia
2. Inhibition of signal transduction events critical
for T-cell activation
3. Inhibition of IL2 synthesis and signaling
4. Downregulation of cell surface molecules
important for full T-cell activation and function
5. Inhibition of antigen-presenting cell function.
Depletion of plasmacytoid dendritic cells and
production of interferon-alpha
6. Deviation of immune responses towards a Th2-
type cytokine formation
7. Induction of T-cell apoptosis
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition, Lippincot
Williams & Wilkins 2007
Prednisone
It may be givens as often as four times each day,
as frequently as once every other day, or at any
frequency
Dose Miligrams
Low Less than 10 mg daily
Moderate 11 to 40 mg daily
High 41 to 100 mg daily
Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
1 gr/IV 3 hari berturut-turut
Katz R.S. Steroids In The Treatment of Lupus. Lupus Foundation of America, 2001
Retinal damage that is caused
by Plaquenil is sometimes
reversible if it is detected early.
However, damage due to the
use of chloroquine (Aralen) is
irreversible
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
IMURAN
Prolong life
Preserve kidney function
Reduce disease symptoms
Reduce damage to vital organs, such
as the kidney and lungs
Sometimes even serve to put the
disease info remission
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
Cytoxan (Cyclophosphamide)
An increasing risk of developing malignancies, including
leukimia and bladder cancer, with long-term Cytoxan
use
Temporary or permanent sterility in both women and
men
Leading to damage of a developing fetus if a woman gets
pregnant while being treated with the drug
Bleeding from the bladder-this usually can be prevented
by drinking large amounts of water
Causing a prediposition to develop shingles
Hair loss
Like Imuran, causing a prediposition to develop unusual
infections, particularly when given in combination with
high doses of steroids
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
Immunosuppressive Side Effects
The drugs have a major effect on cells produced by the
bone marrow, including:
o White blood cells
o Red blood cells
o Platelets
Thus, people treated with cytotoxic drugs must have
regular complete blood counts (CBCs) to make certain
that levels of these cells do not become too low
In addition, cytotoxic drugs reduce a persons ability to
fight off infections
Those receiving cytotoxic drugs are more likely to
contract viral infections such as shingles (herpes zoster)
Katz. R.S. Immune Suppressants and Related Drugs Used for Lupus
Possible Risk Cytotoxic Drugs
The immune system may be suppressed too
much, which causes an increased susceptibility
to infection, particularly shingles (a painful,
blistering skin condition) and pneumonia
The bone marrow can be suppressed as well,
which results in reduction in red blood cells,
white blood cells, or clot-forming platelets
Suppression of hair cell growth may lead to
overall lost of hair
The cytotoxic effects on gonadal cells can lead
sterility
New Treatment in SLE
(cell surface molecules)
Treatment Mode of action Status
Anti CD20 (Rituximab) B cell depletion Phase II/III trial in
patients SLE is
ongoing
Anti CD22 Modulation of B cell Safe in phase I. Phase
(Epratuzumab) signaling II it is on going
Very High Dose GC (VHDGC): > 100 Life or organ-threatening complications (as
mg PD Neq/d, IV/PO (Start with for PGC)**
divided doses)
DPGN or severe FPGN (for less than 6-8
High Dose GC (HDGC): >30 mg and weeks)
100 mg PDNeq/d, IV/PO Thrombocytopenia/hemolytic anemia
Acute lupus pneumonitis; Lupus crisis
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition, Lippincot
Williams & Wilkins 2007
Usual Regimens of Systemic Glucocorticoid
Therapy in SLE*
GC Regimen Representative Indications
Low Dose GC (MDGC): Arthritis, mild constitutional
7.5 mg PDNeq/d, PO symptoms (unresponsive to
analgesics/NSAID/AM).
Generalized LN
Maintenance therapy
Alternate Day GC (ADGC) Membranous nephritis with
nephrotic syndrome (120 mg
PDNeq)
During tapering GC dose
Maintenance therapy (i.e., 15
mg PDNeq for GN)
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition,
Lippincot Williams & Wilkins 2007
Recommended Therapy for Lupus Nephritis
Disease severity Induction Therapy Maintenance Therapy
Boumpas T Dimitrios, Sidropoulus Prodromos, Bertsias George Bertsias, Optimum therapeutic approaches for lupus
nephritis: what therapy and for whom?, Nature publishing group, 2005
Recommended Therapy for Lupus Nephritis
Click to
view
Halloran PF. N Engl J Med 2004; 351; 2715-2729 reference
Prognosis in SLE
I. Disease manifestation
SUPPORT
CARE TREATMENT
MONITORING
Thank You
Sinar matahari
Kelelahan
Diet
Cuaca
Penatalaksanaan
Umum
Merokok
Kontrasepsi oral Stres dan
trauma fisik
Pengobatan muskuloskeletal
pada LES
NSAID + + - (+)
Anti malaria + + - -
Steroid (+) (+) + -
Imunosupresan - - (+) -
Analgesik - - - +
Clinical Monitoring1
Hematologic abnormalities (Cytopenia)
Anemia
Leukopenia
Lymphocytopenia
Thrombocytopenia
Active SLE
Secondary to drug
Sepsis associated with SLE
4 / 11 ARA 3 / 11
WHO LLD
LES
Kerusakan
Organ
Multiple environmental
exposures
Genetically Disease
susceptible
individual
Clinical disease
Early life infectious exposure may Threshold
programme a plastic immune system
Edwards CJ and Cooper C. Early environmental exposure and the development of lupus. Lupus 2006 ; 15 :
814-819.
Autoimmune pathogenesis paradigm. APC, antigen-
presenting cell; MHC, major histocompability complex
EVOLVING
AUTOIMMUNE AUTOIMMUNITY
SPECTRUM OF
*DIATHESIS* WITHOUT DISEASE
AUTOIMMUNE
DISEASE
Genetic Risk Factors :
Autoreactive
- MHC
Lymphocytes
- Other
Autoreactive Autoreactive
Lymphocytes Lymphocytes
Modulating and Perpetuating Factors acting at multiple levels: e.g. UV radiation, hormones, drugs,
Reeves G.E.M. Update on the immunology, diagnosis and management of systemic lupus erythematosus. Internal Medicine Journal 2004;34:338-347
Therapy
Induction
Maintenance
Primordial
Autoimmne
Genetically Response
Susceptible
Individual
Healthy
Cross
Autoimmunity Reaction (s)
Organ/ Epitope
Spreading to
Tissue Pathogenic
Damage AutoAbs
Harley JB, Harley ITW, Guthridge JM and James JA. The curiously suspicious: a role for Epstein-Barr virus in Lupus
Looking for environmental factors
at the right time
Multiple environmental
exposures
Genetically Disease
susceptible
individual
Clinical disease
Early life infectious exposure may Threshold
programme a plastic immune system
Edwards CJ and Cooper C. Early environmental exposure and the development of lupus. Lupus 2006 ; 15 :
814-819.
Neuropsychiatric syndromes
associated with SLE
Central nervous system Peripheral nervous system
Click to
view
Halloran PF. N Engl J Med 2004; 351; 2715-2729 reference
Global measures of disease
activity
LACC (Lupus Activity Criteria Count)
SLAM (The systemic Lupus Activity Measure)
clinical features
BILAG (The british Isles Lupus Activity Group)
intent to treat approach
SLEDAI (The systemic Lupus Disease Activity Index)
- prognostic studies severity (Toronto 1985) / clinical &
laboratory
ECLAM (European Consensus Lupus Activity
Measurement) ~ SLEDAI
Global measures of damage
SLE
Other techniques
Immunoadsorption
AntiC5a
T cell vaccination
chain transfection
Peptide therapies: edratide targeting antiDNA
idiotypes
DCruz P David, Khamashta A Munther, Hughes RV Graham, Systemic lupus erythematosus,
Lancet 2007; 369:587-96
L : Leukopenia, anemia,
thrombocytopenia
U : Urine abnormality as
proteinuria
Imunopatogenesis dan Penatalaksanaan
Nanang Sukmana
Subbagian Alergi - Imunologi Klinik
Bag. Ilmu Penyakit Dalam FKUI / RSCM - Jakarta
Anti-DNA antibodies
dsDNA antibodies are associated with systemic lupus and nephritis,
but not subacute cutaneous lupus or discoid lupus.
Frequency of serological positivity in SLE
Autoantibody % Positive at any Possible clinical association
target stage of disease (see text)
(any assay)
dsDNA 30-70 Nephritis, disease activity
Sm 20-40 Rarely seen outside SLE
RNP 40-60 MCTD/overlap features
Ribosomal P0, 10-15 Sjorgrens/skin invovement/congenital
P1, P2 heart block
Histone 5-10 Neuropsychiatric SLE, disease activity
ACA 30 Drug induced SLE, idiopathic SLE,
disease activity
40-50 Risk of thrombotic complications/fetal
loss/ITP
Egner William. The Use of Laboratory tests in the diagnosis of SLE. J Clin Pathol 2000;53:424-432
Common antinuclear antibody (ANA) HEp-2
patterns and their clinical use in SLE
DCruz P David, Khamashta A Munther, Hughes RV Graham, Systemic lupus erythematosus, Lancet 2007;
369:587-96
LES MEDICATION
Anti malaria
Hydrockcycloroquin
Cloroquin
Cortikosteroide
Prednisone
Metilprednosolone
Immunosupresif
Azathioprine
MMF
Cyclophospamide
Plasmapheresis
Usual Regimens of Systemic Glucocorticoid Therapy in SLE*
GC Regimen Representative Indications
Pulse GC (PGC): 250 mg Life or organ-threatening complications
PDNeq /d x 1-5 days. Typically 0.5- (i.e.,RPGN, myelopathy, severe acute
1 g MP/d IV x 1-3 d, monthly as confusional state, alveolar hemorrhage,
indicated. Usually with oral GC (30- vasculitis, optic neuritis)**
60 mg PDNeq/d) HDGC-refactory Disease
DPGN or severe FPGN
Very High Dose GC (VHDGC): > 100 Life or organ-threatening complications (as
mg PD Neq/d, IV/PO (Start with for PGC)**
divided doses)
DPGN or severe FPGN (for less than 6-8
High Dose GC (HDGC): >30 mg and weeks)
100 mg PDNeq/d, IV/PO Thrombocytopenia/hemolytic anemia
Acute lupus pneumonitis; Lupus crisis
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition, Lippincot
Williams & Wilkins 2007
Usual Regimens of Systemic Glucocorticoid
Therapy in SLE*
GC Regimen Representative Indications
Low Dose GC (MDGC): Arthritis, mild constitutional
7.5 mg PDNeq/d, PO symptoms (unresponsive to
analgesics/NSAID/AM).
Generalized LN
Maintenance therapy
Alternate Day GC (ADGC) Membranous nephritis with
nephrotic syndrome (120 mg
PDNeq)
During tapering GC dose
Maintenance therapy (i.e., 15
mg PDNeq for GN)
Wallace J Daniel & Hahn Hannahs Bevra : Dubois lupus Erythematosus, Seventh Edition,
Lippincot Williams & Wilkins 2007
Recommended Therapy for Lupus Nephritis
Disease severity Induction Therapy Maintenance Therapy
Boumpas T Dimitrios, Sidropoulus Prodromos, Bertsias George Bertsias, Optimum therapeutic approaches for lupus
nephritis: what therapy and for whom?, Nature publishing group, 2005
Recommended Therapy for Lupus Nephritis
Autoreactive Autoreactive
Lymphocytes Lymphocytes
Modulating and Perpetuating Factors acting at multiple levels: e.g. UV radiation, hormones, drugs,
Reeves G.E.M. Update on the immunology, diagnosis and management of systemic lupus erythematosus. Internal Medicine Journal 2004;34:338-347