Interactive Lecture of Clinical Immune Disorder

Rheumatoid Arthrirtis &

Systemic Lupus
Erythematosus

Tjokorda Raka Putra

Divisi of Reumathology -Alergy
Dept of Internal Medicine, Medical Faculty
Udayana University/ Sanglah Hospital
Denpasar
2012

Refrences
1. Harrisons Principle of Internal Medicine
2. Buku Ajar Ilmu Penyakit dalam PAPDI
3. Primer on Rheumatic Diseases, Arthritis
Foundation
4. Pedoman Diagnosis dan Terapi Penyakit
Dalam, RSUP Denpasar

The Goal
Able to diagnose and manage
SLE and RA
Strategy : Must know
the anatomy and physiology of joints
the etiophatogenesis
the phatology of Ds

Anatomy of joint

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

Rheumatoid Arthritis ( RA)

RA is an autoimune and systemic
inflamatooory diseases, that affect
spredominantly the joints.
Etiologic factor : no clear
Genetic factor (HLA-DR4)
Athritogenic agents (bakteri, virus)
Pathologic : erocive synovitis, periferal joints ,
simetry dan chronic
Extra articular patholologic : rare

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

Etiologic Factors
No clear
Sugested :
Genetic factor,
HLA DR-4

Enviroment
Infection : bacteri, virus

Etiologic factor
Genetic
factors
(HLA)

Arthritogenic
(Bacteri, virus)

Autoimmune
Humoral immunity (RF)
Cellular immunity
Inflamatory mediators, cytokines

SYNOVITIS

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

Rheumatoid Factor (RF)

Is an auto antibodi to antibody
An Ab that bind to Fc portin of IgG
molecule
75-80 % in RA
High titer in severe case of RA
May be present in other disesas
3% in normal population

Pathogenesis of Rheumatoid Arthritis

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

Phatologic inflamation of RA

Pathologic
Synovium inflammation (sinovitis) with
hypertopic, and villi proliferation
tumor-like proliferation (pannus)
to damage cartilage and bone, tendon

Damage of bone in AR

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

Arthritis in small pheripheral joints

Early sign : tenderness and
swelling monoarticular and
asymetris
Within a week or few month
symetrical arthritis (warm, pain,
tender, without local heat)
Joints : wrist, MCP, PIP,
small joint s of the feet, etc
Late stage : joint deformity
Swan neck deformity

Rheumatoid Arthritis of hand

Early onset of RA

Late stage of RA

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 indication of inflamation
lymphocyteosis
Rhumatoid Factor positip (85%)
Elektrophoresis (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

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)

Terapi Medisinal :
Simptomatis
NSAID

Kortikosteroid
Efek antiinflamasi dan imunosupresi
Tanpa efek disease modication

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, Metrotreksat,
Sulfasalazine, Klorokiun, etc
Starat 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
Erytemathosus
(SLE)

Selft Assesment
To make the diagnosis dan its
managements

To explain the difinition

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

 Epidemiology
Sex : female- to female ratio 9 : 1,
Age : at any age group
Usually in scond and fourth decade

Ethnic distribution :
All race, Family distributions

Etiologic factors of SLE

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

The Pathogenese 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
Glomerulunephritis (membraneus, mesangial, [proliferative,
etc)

CNS
Multifocal cerebral microinfark

Clinical Manifestation of SLE

A multisyatem disease
Manifestation of extra articular more dominnat
General manifestation : fever, fatique, anorexia

Cutaneous
Facial erythema (Butterfly eruption), Fotosensitive
chronic discoid lessiondiskoid with central
atropy, depigmentation, alopecia with or without
sicatric (lupus hair).
Ulcer on skin or mucous membrane, purpura and
ecchymosis
Raynauds phenomenome
Echymosis and peringual eritheme ,Livido
retikularis, the form of slight vaskulitis

 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.

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

 Lung :
Pleuritis with or without effusion
pneumonitis
Pulmonary Hemorrhage - Hemoptisis

Other organ :
Non specific abdominal pain, steril
peritonitis (serositis), pancreatitis,
hepatomegalim, splenomegali.
Lymphadenopathy
Conyungtivitis, episcleritis, retinal vasculitis

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.

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

Management
Individual response
Depend on the severity of disease and organ
damage.
Active form , depend on :
Aktivitas penyakit ditentukan adanya :
Pathologic figure of organ :
Nephritis, cardiopulmoner pathologic, Skin rash ,
serositis , hematologic abnormality
Sign of systemic inflamation
fever, fatique and decreasing of BW
Immunologic abnormality positive of
ANA , Ab Anti-DNA , decreasing of complement.

Management
Education
Prevent from exposure of sun light.
The use of drug , be carefull- allergic.
Plan the time of Gravid and contraseption pill (use
the non hormonal contraception).
Live stile and psycologis
Prevent the infektion
Diet, ?
Monitor and controle regularly

Phyisical activity and excercise .

Medicine
NSAIDs
Indications for fever, joint pain, maucle pain.
Aspirin 500mg, po 3 x/d or
other NSAIDs

Cortikosteroid : the most important.

Antimalaria
Imunosupresant

Indicationns of cortikosteroid drug

Dermal efflorecense steroid topical

Atritis, that fails with NSAIDs, prednison 10-20 mg perhari
Serositis (al. perikarditis) Prednison 20mg 3x/d.
Fulminant pnemonitis : high dose cortikossteroid
Haemolitic Aenemia Prednison 40-60mg/d.
Immune Thrombocytopenia = haemolitic aenemia.
Vasculitis
Small vessel (hand): small dose of prednison (20mg/d).
Medium or Large vessel : prednison 60mg/d
Cerebrall lupus Prednison 20 mg 3 x/d.
Peripheral nerve abn. : prednison 20 mg 3 x/d
Lupus Nefritis)
prednison 60 mg/d

Thank you