Interactive Lecture of Clinical

Immune Disorder

Autoimmunity in
Rheumatology

RA & SLE
Dr. Gede Kambayana SpPD-KR
Reumathology-Immunology Division, Dept of Internal Medicine,
Medical Faculty Udayana University/ Sanglah Hospital Denpasar
2014

Rheumatology ??

Anatomy of joint

RHEUMATIC CASES

Disabilities caused by rheumatic diseases

Rheumatoid Arthritis

Selft Assesment
To make the diagnosis dan its managements

To explain the difinitionn

To explain the Etiopathogenecis
To explain the pathologic abnormality
To inform the clinical symptoms and signs
To plan the supporting data
To explain the criteria of diagnosis
To perform the general management

Epidemiology
Age :
Mostly in 30-40 yrs
Increasing in older patients
US Health Examination (1960-62)
0.3% age< 35 th
10.0% age> 60 th
Sex :
Women : Man (2,5 :1)
Another factors :
Social status, education, & Psycho-stress

Etiopathogenesis of RA

Rheumatoid Factor

Humoral Immunity (RF) in AR

Antigen

Limfosit B
Sinovium

Produksi Ig G
Abnormal

Ab 1 / Ag 2

Produksi FR

Ab 2

Ag 1

(Ag2 + Ab2)

Kompleks Imun
Aktivasi Komplemen

Artritis

Keradangan Sinovium

Pathogenesis of Rheumatoid Arthritis

(Choy EHN, Panayi GS. N Engl J Med. 2001)

Phatologic inflammation of RA

Clinical Manifestations of RA
History : pain, swelling and morning
stiffness of small peripheral joint
Often with general symptom ,(general
fatigue,
Simetrical arthritis in small peripheral
joint
Extra articular manifetation : rare

Reumatoid atritis

Arthritis in small pheripheral joints

Early sign : tenderness and
swelling monoarticular and
asymetris
Within a week or few month
symetrical arthritis (warm,
pain, tender Joints : wrist,
MCP, PIP, small joint s of the
feet, etc
Late stage : joint deformity
Swan neck deformity

Extra articular manifestation of RA

Skin
Rheumathoid nodul in pressure areas (rare in Indonesia)
Vasculitis (purpura, echimosis, necrosis of nail, ulcer, atau
gangren)

Eye
Kerato-conjungtivitis sicca (Sjogrens Syndrome)
Scleritis, episcleritis

Lung
Instertitial Pnemonitis
Pleural effusions, fibrosis

Cardiovascular
- Pericarditis , myocarditis
Nodul reumathoid in myocard atau palve

Hematology
Mild Anaemia (on chronic disease)
Feltys Syndrome (granulocytopenia,splenomegaly & recurrent
infection)

Rheumatoid Nodules

Diagnostic Investigations
Laboratory Test
Anemia (nn)
ESR or CRP
Good indicator of inflammation
lymphocytosis
Rhumatoid Factor positive (85%)
Electrophoresis (increasing of Ig )

Diagnostic Investigations
Imaging / X Ray

Normal (in early onset)

Soft tissue swelling
Periarticular osteopenia
Marginal or central erossion and cysts

CRITERIA of RHEUMATOID ARTHRITIS

(The American Rheumatism Associations, 1987 revised criteria)

1. Morning stiffness ( 1 jam)

2. Arthritis of 3 joints or more
3. Arthritis of hand joints
4. Symetrical Arthritis
5. Rhematoid nodule
6. Serum Rheumatoid Factor
7. Typical radiologic changes of RA
Artritis Rematoid: 4 criterias or more,
Note : Criteria 1 through 4 must have been present for at least 6 weeks

ALETAHA ET AL ,ARTHRITIS & RHEUMATISM, Vol. 62, No. 9, September

ALETAHA ET AL ,ARTHRITIS & RHEUMATISM, Vol. 62, No. 9, September

Clinical pattern of disease in RA

Management of AR
Early Diagnosis and early treatment
The goal : to achive the remission
Patient Education and motivation
To suppress the inflamations
To perform maximal joint function
To protect joint damage
The tool :
Education
Physical rehabilitation
Medications
Surgical therapy
Other : alternatif treatmant
By the teams (Ruematologist/Internist, Orthopedist,
Physioterapist, Psychiater, Social worker and Family)

Medical Therapy :
Symptomatic
NSAID

Corticosteroid
Antiinflammation and immunosuppresion
without disease modification effect

DMARD
(Disease Modified Anti Rheumatic Drug)
Biologic response modifiers
TNF alfa-antagonist, IL1-Ra

The choice of DMARDs

Traditional methode (Pyramida sytem)
Combination of Multidrug: Step-down Bridge
Start with multidrugs, Oral Steroid, Metrotrexate,
Sulfasalazine, Klorokuin, etc
Start with multiple drug, step by step stop the most
dangerous drug and the last, Klorokiun.
Continuous until several month- years.

The Sawtooth Strategy

DMARD UNTUK TERAPI ARTRITIS REMATOID

Drug

ONSET

DoSe

Hidroksiklorokuin

2-4 mont

200 mg;
2x/day

Rash, diare, toksissitas retina

Sulfasalasin

1-2 mont

1000 mg;
2-3x/day

Rash, mielosupresi, intoleransi GI

Metotreksat

1-2 mont

7,5-17,5
mg/wk

Gejala GI, stomatitis, rash, alopesia,

mielosupresi, kelainan hati dan
paru

Asztioprin

2-3 mont

50-150
mg/day

Mielosupresi, gangguan hati, flu-like

illness, gejala GI, peningkatan
TFH

D-penisilamin

3-6 mont

250-750
mg/hr

Mielosupresi. stomatitis, dysgeusia,

proteinuri, , kelainan autoimun,
rash

Leflunomidfe

6-12
mont

100mg/day
(3days)
20mg/day

Side effects

Liver side effect

SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)
LUPUS

dr. Gede Kambayana, SpPD-KR

IKATAN REUMATOLOGI INDONESIA

CABANG BALI

Selft Assesment
To make the diagnosis dan its
managements

To explain the definition

To explain the Etiopathogenecis
To inform the clinical symptoms and signs
To plan the supporting data
To explain the criteria of diagnosis
To perform the general management

SLE is a chronicprogressive systemic

and multisystem
disease, that
indentification and
characterization of an
abnormal
autoantobodies

LUPUS = PENYAKIT SERIBU WAJAH

HISTORY
HIPOCCRATES (460-370 BC) :
Lupus/Herpes Esthiomenhos
Amatus lusitonus (1510 1568) : Herpes
ulcerosus
Sennert, Bateman, Biett, Hebra (1611) :
Lupus (Butterfly rash)
Cavenaze (1851 1852 ) : SLE

Epidemiologi

Wanita > laki-laki

Mengenai semua usia terutama dekade ke-2 dan 4

(masa reproduksi)
>> wanita ( wanita : pria 9 : 1)
Semua ras dapat terkena. ( >> negroid)
Prevalensi USA 14,6 50,8 per 100.000 pddk

Etiologic factors of SLE

No clear
Suggested :
Genetic factor,
HLA DR-2 or HLA DR-3
Difficiency of complement (C2, C3, and C$)
Environment
Infection : Slow virus as trigger
Hormonal
Abnormality in metabolism of estrogen and
hyperprolaktinemia.
Other factors
Exposure of ultraviolet, drugs, stress, etc

The Pathogeneses of SLE

Genetik

T Helper

Faktor Penyebab

Limfosit B

Antibodi terhadap DNA

Nukleoprotein
Histon
Nuclear Ribonucleoprotein
Lain-lain dari bahan inti sel

Virus ?

T Supressor

Komplek imun di
seluruh organ

Pathology of SLE
No histologic feature is pathognomonic in SLE
The general features :
Fibrinoid necrosis of blood vessels and connective tissue
The hematoxylin body (LE cell) phenomenon

Skin
Epidermal thikening , lequefactive degr. Of basal layer,
infiltration lymphocyte

Synovium of joint
Fibrinous villous synovitis

Kidney
Glomerulonephritis (membranous, mesangial, proliferative,
etc)

CNS
Multifocal cerebral microinfark

SYMPTOMS :
no spesific symptoms
EARLY : usualy not recognized as LUPUS
because its manifestations dont occur at
the same time
General symptoms
Fever
Weakness, tiredness
Decrease of body weight.

Clinical Features of SLE

Lymphadenopathy
Lymphadenopathy weakness
weakness
12-50%
90%
12-50%
90%
CNS
CNS
20%
20%
Prolonged
Prolonged fever
fever
80-82%
80-82%
Hepatomegaly/
Hepatomegaly/
Splenomegaly
Splenomegaly
20%
20%
GI
GI tract
tract
18%
18%

Decrease
Decrease body
body weight
weight
60%
60%

SLE

Arthritis/Arthralgia
Arthritis/Arthralgia
90%
90%
skin
skin
50-58%
50-58%

lung
lung
38%
38%
Hematology
Hematology
50%
50%

Heart
Heart
48%

Vaculitis
Vaculitis

kidney
kidney
50%
50%

Clinical Features

Erythematous Rash

Oral Ulcers

Photosensitivity

Discoid Lupus

Discoid Lupus

Small Vessel
Vasculitis

 Joint :
Arthritis (pain and inflammation in joints)
joints>> : hand, knee, wrist, elbow and ankle

Clinical Features

HEART AND LUNG

ABNORMALITY
Pleural Effusion
Pericardial Effusion

 Musculoskletal system
Slight arthritis in small or large joint, asymetris
The joints : proximal interphalangeal
joint,knee,wrist, elbow, etacarpophalangeal joint,
feet.

Inflamatory myositis
Osteonecrosis

 Kidney :
Glomerulonephritis
(Nefritis Lupoid) - biopsi
Clinical : proteinuria, hematuria,
silinderuria
Sindrom Nefrotik Renal Failure.

CNS :
Seizure, Psychosis ,
Cranial or pheriphreal nerve disorder.

Cardiovasculer :
Atherosclerotic cardio-vascular ds
Pericarditis with or without effusion
(serositis)
Myocarditis
Endokarditis verucosa.
Peripheral vascular manivestation
Vaskulitis on small arteries,
capiller on the skin

Diagnostic Investigations
Laboratory Tests
Anemia, in aktive phase
Coombs test positive (haemolitic anemia ).
Leucopenia in active phase, limpofenia (e.c.
Antilymphocyte Ab).
Thrombocytopenia
ESR or CRP is elevated
False positive reaction to VDRL (test for
syphilis)
Hypergammaglobulinemia
Urinalysis and Kidney fuction

 Autoantibody test.
ANA (Antinuclear Antibody) antibody to
nuclear component.
Anti-ds-DNA, spesific for LES ( 40-50% )
For diagnositic and aktivities of diseases
LE cell
Complement, decrease in active phase

 Imaging Studies
To support the clinnical assesment
Chest X-ray
Joint X-ray
Body Scan
Ensefalogram,
etc.

Citeria of DIAGNOSE
Criteria of ARA (American Rheumatism Association) revised in
1982.
1. Erytema on face (Butterfly Rash)
2. Discoid Lupus
3. Fotosensitivitas
4. Ulcer on mouth or nasopharing.
5. Non Erosive Arthritis
6. Kidney abnormality: Proteinuria > 0,5 gm/24 jam, Sylinderuria
7. Pleuritis atau Pericarditis
8. Psychosis, seizure
9. Haematologic abnomelity : Haemolitic Aenemia, Lecopenia,
Limphonemia, Trombocytopenia
10.Immunologic abn : LE cell positive, Ab Anti-DNA, Ab Anti-Sm,
11.False positive VDRL tes.
12.ANA test is positip
Diagnose of SLE : 4 or more of that criterias.

DISEASE ACTIVITY
LUPUS
DISEASE ACTIVITY

REMISI
- Total (without
drugs)
- Partial, drugs minmax

RELAPS/FL
ARE
- DRUGS
STOPPED
- ACTIVITY >>
- stress
- Infection
- PREGNANCY
www.themegallery.com

SLE activity monitoring : Mex-SLEDAI

Live threatening lupus

THERAPY

LUPUS NEPHRITIS

62

Live threatening lupus

PROGNOSE
5 ysr : 90%.
Depend on the abnormal of organs
(Kidney or CNS)

tiredness

Sun exposure

Diet

Weather

General Management

smoking
oral contraception

Stress and
physical
trauma

NON FARMACOLOGY
Education
Social Support
Rest
Avoid sun exposure
Pregnancy planning and contraception
methods choosing
Infection Management
Tight Monitoring

EDUCATION
Chronic disease
Patient : must have enough konowledge
about lupus, not misguided
Knowledge about frequent symptoms
Knowledge about medication, effects and
side effects
Diet : enough nutrition, healthy diet, avoid
allergen, no spesific prohibition

SOCIAL SUPPORT
Psychological support from family
Family knows about emergency signs in
lupus

FORMS ASSOCIATION
YAYASAN
MASYARAKAT PEDULI LUPUS
ETC

ENOUGH REST
Frequently with weakness and tiredness
Sports, adjust with conditions

SUN EXPOSURE
Avoide
Sun block: SPF > 30, 30 - 60 before
exposure, repeat @ 4 6 hous for face

INFECTION CONTROL

Frequently as disease trigger

Frequently happens in lupus
Be alert with fever without clear cause
Careful with drugs easily alergic

MONITOR
Very important
Do it regularly

Medications
NSAID
Corticosteroid
very important drugs,
not all SLE need corticosteroid.
Antimalarial agent
Immunosuppresan
Biologic agent

Thank
you