Systemic Lupus Erythematosus

& Rheumatoid Arthritis

Hildebrand Hanoch Victor

Departemen Ilmu Penyakit Dalam
FK UKI
2014
SYSTEMIC
LUPUS
ERYTHEMATOSUS
(SLE)
 Self Assessment
Making diagnosis & management of SLE

• Determine of Etiopathogenesis
• List of clinical symptoms
• Proposed supporting examination
• Make of List of diagnosis criteria
• Performe management
• DEFINITION OF SLE
– Systemic Lupus Erytemathosus (SLE) is a
chronic-progressive systemic disease
– Autoimmune disease that marked with
antibody to nuclear cell
• Epidemiology
– Mostly in female ( female : male = 9 : 1),
occurred in all age especially on 2nd – 4th
decade (reproductive period).
– Affect all race.
There is familial tendency
 ETIOLOGY OF SLE
• Etiology of SLE still unknown
approximately interaction of genetic, environment, hormonal
and social factors.
– Genetic
approximately on HLA-DR2 or DR3,
there were C2, C3, and C4 complement deficiency
– Environment
approximately slow viral possible retroviral as a trigger
– Hormonal
Disorder of estrogen metabolism and hyperprolactinemia
– Other factors
Sun exposure (ultraviolet), drugs, stress, nutritional
imbalance and smoking, etc.
 SLE Pathogenesis
Etiology
Genetic Virus ?
Factor

B Lym- T
T Helper phocyte Supressor

Antibody to DNA
•Nucleoprotein Immune
•Histon complex in
•Nuclear Ribonucleoprotein
•Others from nuclear whole organs
Clinical point of SLE
• Autoimmune and systemic
disease
• Systemic disorder (extra articular) :
dominants
• Articular disorder : rarely
Clinical symptoms
• Great a many variations,
there is no specific abnormality
• First stage  usually unknown,
manifestation is not simultaneously
• Caustitutional symptoms:
– Febrile
– Anorexia
– Weakness or decreased body weight
 Clinical Symptoms
• Skin:
– Facial Erythema (“butterfly rash”)
– Dermatitis caused by sensitive of sunshine
(photosensitive)
– Bulosa lesion.
– Annular and papulosquamouse lesion on
subacute condition
– Chronic condition: Discoid with central
atrophy, depigmentation or alopecia with or
without scar tissue (hair lupus)
– Ulcer could occurred on finger
– Raynaud complaint caused by
“acroscllerosis”.
 Clinical symtoms :
• skin (cont) :
– Purpura or echymosis can occurred caused
by its’ disease or side effect of corticosteroid
– In mucous can occurred ulcer on pallatum or
perforation of septum nasalis
– Skin vasculitis can cause ulceration small to
big formed
– Bleeding and periungual erythema, livido
reticularis are mild vasculitis form which very
usual found
• Joints:
– Arthralgia, arthritis, rarely to make deformity or
myositis
– The most involved joint that affect are
interphalangeal joint, knee, wrist,
metacarpophalangeal, interphalangeal proximal
Cardiovascular :
Pericarditis
Coronary heart diseases due to artherosclerosis
Verucosa endocarditis.

Periphery blood vessel

Vasculitis, involved small artery to skin capilary
• Lung:
– Pleuritis with pleural effusion and pneumonitis
– Hemoptisis, a seriously abnormality
• Gastrointestinal :
– Gastrointestinal manifestation
not specific
– Abdominal pain often complained caused by
abdominal distress due to disease or drugs
– Can occurred sterile peritonitis, intestinal
perforation, pancreatitis and hepatomegaly
• Kidney:
– Lupus nephritis
– Clinic: proteinuria, hematuria
– Cylinderuria
– Nephrotic syndrome or kidney failure
• Nerve system :
– Seizure
– Psychosis and peripheral neuropathy
 Diagnostic Examination
• Routine Laboratory Examination
– Anemia : active phase
Positive Coombs Test (hemolytic anemia).
Chronic stage : anemia normochrome-
normocyter
– Leucopenia : active phase
Can occurred lymphopenia due to
Antilymphocyte
– Could: decrease of number T-helper
lymphocyte and T-supressor lymphocyte
during active phase of disease
– Thrombocytopenia
• Immunology Examination
– Autoantibody examination
– ANA (Antinuclear Antibody) antibody to all nuclear
component
– Anti-Sm, antibody to Acidic Nucleoprotein, with high
spesivity
– others Ab. Anti-ds-DNA specific for SLE but only
found 40-50% patients
– Positive result for this test is a important diagnostic
and used as disease activity reference if high titer
– LE cell examination
– Number of complement examination
– False Positive for Syphilis Test due to Ab
Anticoagulant and Ab Anticardiolipin
LE cell
 Diagnostic Support
• Biochemistry examination
– Hypergamaglobulinemia.
– Renal function test
• Other examination depend on organ
manifestation involved
– Chest X-Ray
– Body Scan
– Eencephalogram, etc.
 Diagnostic Support
• Routine laboratory examination
– Thrombocytopenia, due to antibody to thrombocyte,
with Direct Coombs-like Test
– Prolonged Partial Thromboplastin Time test
due to antibody to clothing factor (F.VIII,IX,XII).
– Increase ESR,
but not always to reflect disease activity
– Proteinuria, hematuria, atau silinderuria, if renal
disorder occurred
 DIAGNOSIS
• Diagnosis of SLE established on ARA criteria (American
Rheumatism Association) that improved on 1982.
these criteria are:
1. Facial erythema (Butterfly Rash)
2. Discoid Lupus
3. Photosensitivity
4. Ulcer on mouth or nasopharynx
5. non erosive Arthritis
6. Renal disorders : Proteinuria > 0,5 gm/24H, Siilinderuria
7. Pleuritis atau Pericarditis
8. Psychosis, convulsion
9. Hematologic disorders : Hemolytic Anemia, Leucopenia,
Lymphonemia, Thrombocytopenia
10.Immunology disorders : Positive LE cell, Ab Anti-DNA, Ab Anti-
Sm, False positive of syphilis test
11.ANA positive
• Diagnosis of SLE established if there are 4 or more criteria above
PROGNOSIS

• 5 years survival could reached 90%.

• Depend on affected organ (kidney or
CNS)
MANAGEMENT
• Very individual, drug selection depend of
kind and severity of organ damage .
• Treatment especially on active phase disease
• Disease activity is determinated by :
– Organ pathology disorders as:
Nephritis, cardiopulmonary disorder, skin rash and
serositis
– Non specific systemic inflammation sign 
fever, general weakness and decreased of body
weight
– Presence of Immunologic reaction 
positive ANA, positive Ab Anti-DNA, or decrease
of complement
• Education
Avoid of sunshine
Be careful to drugs – drug allergic
Pregnancy and contraception
SLE influence pregnancy or on the contrary
Used non hormonal contraception
Require to pay attention to the good attitude to life and
keep patient psychology
Infection controlled
Regularly disease monitoring

• Physical therapy, rheumatic sport

Drug treatment

• NSAID
• Corticosteroid
the very important drugs,
not all SLE need corticosteroid
• Antimalaria
• Other Immunosuppressants
 Indication for Corticosteroid :

• Skin abnormality  topical corticosteroid or intra lesi

• Arthritis fail with NSAID  Prednisone po 10-20 mg OD
• Serositis (ia. pericarditis)  Prednisone 20mg TID
• Pnemonitis This condition often temporarily, self limiting
– On fulminant pneumonitis with bleeding, need high dose
corticosteroid  Prednisone 20mg TID, often combined with
other Immunosuppressant
• Severe Anemia hemolytic and symptomatic  Prednisone
40-60mg daily, in 2-3 doses  as soon as possible
decreased after good Hb level
• Immune Thrombocytopenia due to SLE  Dose as
hemolytic anemia .
– If not yet have effect in several weeks, could combine with
intravenous gamma globulin
• Vasculitis
– Vasculitis of small skin vessel on finger or hand need small
dose prednisone, 20mg OD.
– Vasculitis of moderate or big vessel need prednisone 60mg
OD, divided dose
• Brain parenchyma disorder Prednisone 20 mg
TID till improved.
• Peripheral neurologic disorder
– Eg mononeuritis due to vasculitis could give prednisone 20
mg TID  if not improved could combine with azathioprine
or cyclophosphamide
• Renal disorder (Nephritis Lupus)
– Active renal disorder (proteinuria, silinduria decreased
of renal function)  prednisone 60 mg daily till
improved and dose could decreased
Antimalaria Drug
• Indication :
– Skin abnormality
• Often combined with topical corticosteroid.
• Hidroxychloroquine, 200 mg BID, atau Quinacrine
100 mg
• Could apply on arthritis.
• Control to ophthalmologist every 3-6 month for toxic effect
like macular degeneration
 Other Immunosuppressant Drugs
• Azathioprine and cyclophosphamide
– Giving along with steroid
– Indication :
• Malignant Pneumonitis with bleeding
• Immune Thrombocytopenia on SLE with
corticosteroid resistant
• Neuritis that corticosteroid resistant
• Nephritis Lupus that corticosteroid resistant or not
hold up to side effect of corticosteroid
– Doses, Azathioprine 1-3 mg/kg/day, or
cyclophosphamide pulse iv 0,3-1,0 mg/mm2 skin surface
wide with interval 1-3 month.
Other drugs :
• Anticovulsions (Phenitoin, Phenobarbital)
• Mayor tranquilizer
• Others measure
– Whole lymphoid tissue Iradiation  decreased T4
number
– Plasmapharesis  decreased intravascular
antibody concentration, immune complex and
other inflamation mediators in the circulation
RHEUMATOID ARTHRITIS
 Selft Assesment
Making diagnosis and management of
RA
• Determine of Etiopathogenesis
• List of clinical symptom
• Proposed supporting examination
• List of diagnosis criteria
• Performed management
RHEUMATOID ARTHRITIS (RA)

• Systemic autoimmunne disease

• Unknown cause
• Genetic predisposition (HLA-DR4)
• Atritogenic agents (viral, bacterial)
• Abnormalities: symetrical and chronic
peripheral joint erosive sinovitis,
• Extraarticular abnormalities
 Epidemiology
• Age :
– 30-40 years old predominant
– Increasing on elderly
US Health Examination (1960-62)
0.3% < 35 YO
10% > 60 YO
• Sex :
– Female prepoderance (2,5 :1)
• Dependent to many factors :
– Socioeconomic, education, & physical stress
 Etiology
• Still unclear
• Suspecion :
– Genetic factor
– HLA DR-4
– Environment
– Bacterial/viral infections
 Etiology of RA
Genetic Artritogenic agent
(HLA) (Bacterial, viral)

Autoimunne Process
humoral immunity (FR)
seluler immunity
mediator of inflammation
sitocynes

SYNOVITIS
Pathogenesis
• Autoimmune process,
• Viral infection is suspected as a
precipitating factor  malfunction of T
Lymphosit  producing abnormal Ab
against the body itself (nuclear).
• immuneComplex in circulation is
suspected causing local and systemic
pathological abnormalities.
 Trimolecular complex
(HLA molc.,peptide Ag, T cell receptor)

APC

HLA class II molecule

Peptide antigen

CD4  T cell receptor

CD4 T cell
 The inflammation products on RA after trimolecdular
complex (TMC)

Keadaan
Awal

TNF-a IL-2
IL-1 IFN-g
Regulasi IL-6 TNF-b
IL-8 IL-4
IL-10 INOS
Inflamasi /
TGF-b
Kerusakan Sendi
Sel B Synoviocyte Aktivasi Adhesion

Immunoglobulin Limfosit, PMN,

Metalloproteinase
Rheumatoid factor Makrofag
 Rheumatoid Factor (RF) :
• Is an auto antibody
• This Ig make a complex with Fc of Ig
mol
• Found 3% of healthy people
• Commonly positive in RA
 Role of Humoral Immunity on RA
Limfosit B Produksi Ig G
Antigen Ab 1 / Ag 2
Sinovium Abnormal
Ag 1
Produksi FR Ab 2

(Ag2 + Ab2) Kompleks Imun

Aktivasi Komplemen

Artritis Keradangan Sinovium

figure 2. cytokine signaling on RA
(Choy EHN, Panayi GS. N Engl J Med. 2001)
Figure 2. Pathogenesis of Reumatoid artritis
(Choy EHN, Panayi GS. N Engl J Med. 2001)
The changes of synovitis on RA
Joint inflammation
(RheumatoidArtritis)
 Pathology
• Synovium :
– Hypertrophy, swelling
– Vili development
• Stromal connective tissue:
– Performing tumor-
like proliferation
destroying the cartylago
and bones around synovium
– Pannus destro the sourronding tissue
The changes of joint in RA
 Clinical Apperance of RA

• Autoimmune & systemic disease

• Joint abnormalities (mostly)
• Extraarticular abnormalities (rarely)
 Clinical appearance of the joint
• Joint abnormality
– Early symptoms :
• Gradually Poliartritis (weeks)
Mostly on peripheral joint
– Joint abnormality cause by :
• Synovitis process (reversible)
• Joint structure damage (irreversible)
– Stiffening of the joint in the morning, at least 1 hour
– Joint inflammation
– Spasm of muscle & tendon
– Joint deformity
 The frequent affected joint :
• Hand :
– Espescially MCP, PIP and wrist (rarely PID)
– Swan neck deformity (contracture flexion),
hiperektensi PIP, fleksi DIP)
– Boutonniere ( PIP flexion and DIP hyperextention)
– Carpal tunnel syndrome (compression of
n.medianus)
– Compression of n.ulnarir in the Guyon canal.
• Other joint :
– vertebra servikal, shoulder, elbow, hip ,
knee, foot and ankle.
The frequent
affected joint
Rheumatoid Arthritis of the hands
 Extraarticular abnormalities
• Skin
– Rheumatoid Nodul (rarely in Indonesia)
– Vasculitis (purpura, ekhimosis, nail necrosis, ulcer, or
gangren)
• Eyes
– Kerato-konjungtivitis sicca (Sindr.Sjogren)
– Skelritis, episkleritis
• Lung
– Pnemonitis instertisial
– Pleural effussion or lung fibrosis
• Cardiovascular
Perikarditis
– Rheumatoid Nodul on myocard or valve
• Hematology
– Mild Anemia (a.on chronic disease)
– Sindr.Felty (AR, limfadenopati, leukopenia and foot ulcer
• Kidney and GI tract : rarely
• Mostly cause by NSAID side effect
Rheumatoid Nodul
Supporting test for diagnosis
• Laboratory
– CBC
• Hb (nn)
• ESR increasing
• Limfositosis
– Immunologis
• FR positive (85%)
• CRP increasing
• Elektroporesis (Ig increasing)
– Joint fluid aspiration
• Inflammatory appearance
Still’s Syndrome
 Supporting test for diagnosis

• Radiology
– Early stadium : normal
– Soft tissue sweling
– Periartikular osteopenia
– Marginal erosion
• Astroscopy
– See directly macroscopis
– Biopsy – PA
RA Diagosis
CRITERIA OF RA
1. Morning Stiffeness of the hand joints  1 jam
2. Arthritis  3 joint
3. Arthritis joint of the hands
4. Symetrical Artritis
5. Rhuematoid Nodule
6. Rheumatoid Factor positive
7. Typical imaging picture
Artritis Rematoid:  4 criteria above;
criteria 1-4  6 weeks
RA PROGRESSION
 Management of RA
• Goals :
– Education & Motivation
– Reducing inflammation
– Keeping joint function
– Correcting joint damage
– By :
• Education
• Physical treatment
• Medication treatment
• Surgery
• Others : alternatif
• Do by team (Ruematologist/Internist, Ortopedist,
Fisioterapist, Psikiater, Sosial worker and family)
Medical treatment :
• Symptomatic
– NSAID
• Cortikosteroid
– Antiinflammatory and Immunosupresant efect
– Without disease modication efect
• DMARD
(Disease Modified Anti Rheumatic Drug)
/Remitive drug
• Biologic response modifiers
– Beyond treatment
 How to choose DMARD
• Traditional way (Pyramida system)
– Early step– QAINS
– 1 - 3 months no response/ more progresif
– add OR (eq klorokuin, garam emas, or sulfasalasin)
combination of Steroid oral or intra-artikuler.
• Multidrug combination: “ Step-down Bridge”
– Some OR together (Steroid oral, garam Emas,
Metrotreksat dan Klorokiun)
– Step by step stopping, begin from the most toxic OR
then OR that most mild toxicity effect (Klorokiun)
– Continou for few months or years.
• The Sawtooth Strategy
– Multidrug serial combination that given since the early
then switch to other serial combination if there is no
response therapy.
 THE CHOICE OF DMARD
• Traditional way
(Pyramidal system)

• Multidrugs Combination :
“ Step-down Bridge”

• The Sawtooth Strategy

 DMARD :
• Chloroquin
– Decrease of releasing of unsaturated fatty acid (precursor mediator of
inflammation
– Dose of chloroquin 250 mg or Hidroksi Klorokuin 400 mg po, OD,at
least 6 months.
– If good effication continou for few years

• Sulfazalasin.
– Devide into 2 components in the gut,  Sulfanamid (Sulfapiridin )
that has antiinflammatory effect.
– Dose Sulfazalasin 0,5 g a day and titrate 0,5 every week untill maximal
dose 2 g a day.
– If still no good response can increase 3 g a day after 3 month
– Response therapy shown in 1 - 2 months.
– If in 3 months there is no response therapy  stop the medication.
– Maintance dose 1 g a day (maximal 2 g).
• Metrotrexat.
– Is an imunosupresant drug that starting wide using in RA treatment
– Unclearly therapeutic effect mechanism.
DMARD FOR RA TREATMENT
DRUGS ONSET DOSE TOXICITY

Hidroksiklorokuin 2-4 bulan 200 mg;

Rash, diare, toksissitas retina
2x/hr
Sulfasalasin 1-2 bulan 1000 mg;
2-3x/hr Rash, mielosupresi, intoleransi GI

Metotreksat 1-2 bulan 7,5-17,5 Gejala GI, stomatitis, rash, alopesia,

mg/mgg mielosupresi, kelainan hati dan
paru
Garam emas i.m. 3-6 bulan 25-50 mg; Stomatitis, mielosupresi, proteinuri
@2-4 mgg trombositopeni, rash
Garam emas oral 4-6 bulan 3 mg; 1- Sama seperti garam emas i.m. tetapi
2x/hr lebih jarang, diare
Asatioprin 2-3 bulan 50-150 Mielosupresi, gangguan hati, flu-like
mg/hr illness, gejala GI, peningkatan
TFH
D-penisilamin 3-6 bulan 250-750 Mielosupresi. stomatitis, dysgeusia,
mg/hr proteinuri, , kelainan autoimun,
rash