RHEUMATOID ARTHRITIS

Blondina Marpaung
Rheumatologi Division
Interna Department
FK USU - Medan

Artritis Reumatoid :
widely spread , too all group, race, ethnic all the world
Sistemic inflamatory autoimun deseases
Chornic inflamatory on joint
Its a progresif poli artritis
Joint and other body organ
Symptom of chronic deseases
joint damaged deformitiy
disabilitity
Etiology sure ????

Autoimun Deseases :

Imune system activated

Attack the healty tissue

Inflamation and tissue damage / organ

Autoimun process include :

T

& B cell

Messenger molecules
Antibodi (RF)
Anti cyclyc citrullinated C-peptic antibody (anti-CCP-ab)
Type of cytokine
- Interleukin-1 (IL-1)
- Tumor necrosis factor (TNF- )
- Chemokin and the reseptor
Signalling and co stimulatory molecules
mast cell

Sinoviocyte
Ectopic lymphoid neogenesis
Angiogenesis
HLA-class II
Non-MHC risk genes
Arthritogenic antigen
Macrofag
Dendrit cell
Blys (B-lymphocytes stimulator)
APRIL (a proliferating inducing legand)
Smoking
Gender

Epidemiology
Most

commonly affect ~1% from population

Commonly
Onset

on woman

of disease is usually between 40 and 50

years of age, but can start at any age

Occurs

in all races and ethnic groups, but is rare in

less developed and more rural parts of the world

Etiology/Phatogenesis
Rheumatoid

arthritis (RA) is chronic, inflamatory,

sistemic, autoimmune disease

Commonly

polyarticular disease

Chronic

inflamation in sinovial membran dari from

affected joint

Spesific cause of RA is unknown, but immune respon

is characteristic well.

PATHOGENESIS ETIOLOGY
Changes are:
Microvasculer destruction, oedem on sinovial tissue, lining
proliferation cell on sinovial.
Tercell leukosit polimorfonuklear on sinovial. surface
Small vessel obliteration due to organized inflammation and
thrombus
Synovial fluid consist PMN leucocyte

Celluler Phatology
Tampak adanya :
synovial edem
Hyperplasia and hypertrophy lining cell sinovial can be
thickening due to increasing A cell (reticuloendothelial
like) and B cell
Destroy Lysosom
Kapiler obstruction
Neutrophyl infiltration to artery wall
Thrombosis area
perivaskuler haemorrhage

DEGRADATION PROCESS
- Cartilage damage
- tendon damage
proteoglycan thinning:

- ligament damage
- bone damage

- abnormal
- not shiny
- not elastic
- not strong enough
Membrane synovial proliferation
Pannus : vaskular granulation tissue insist of
proliferation fibroblast
small vessel
inflammation cell
cauesd damage

Primer synovial disease,

Scunder synovial fluid,
cartilage, paraarticuler, tendon and
vascular component changes.

Clinical pattern
Progressive

onset (from
weeks to months)
Pain and stiffness
(synovitis)
Swollen joints
Symmetric articular pattern
Flu-like symptoms
Morning stiffness
Fatigue
Lipsky (1998); Wolfe
(1996)

Clinical pattern (contd)

At

onset, RA usually affects hands, wrists

and feet
Often a chronic cyclical course
During flare-ups, new joints are affected
and existing lesions are worsened
Joints become deformed, leading to
additional disability

HANDS
spindle shape finger- shape fusiform due to PIP swollen
Swan neck deformity ( PIP hyperextention DIP flexion )
Boutonniere deformity ( PIP flexion DIP extension)
thumb :
- interphalanx joint hyperextension and MCP flexion
losss of clamp capacity thumb

Lateral deviation of the MCP joints

Slide 9

-Simetris
play roles in RA
difference from other arthritis
-DIP not include
morning stiffness can be used as disease severity

Wrist joint
( most common affected R.A)
* Boggy synovium
* ulnar swollen
* Impairment of wrist dorsoflexion
* Carpal-tunnel syndrome supressed N.Medianus tertekan)

ELBOW

SHOULDER

* Contracture flexion

* glenohumeralis joint

* Swollen

* Acromioclavicularis

* para-olekranon
destruction

* Thoracoscapularis

* Joint dislokation

HIP

KNEE

( less affected R A)

( most affected.RA
* Hypertrophy sinovial

* abnormal gait

* Joint effusion

* Limited joint movement

* quadricep muscle atrophy

* Inguional discomfort

* Baker cyst formation

(if cyst broken, signs like
thromboplebitis)
* Joint instability

LEGS AND ANKLE JOINT

Limited flexion and extention
Heel pain and bursa pain or pain in area
under bursa of tendon Achiles and plantar
pedis
Hallux valgus (deviasion lateral of thumb food
)

CERVICAL
* Cervical Pain and stiffnes
* Progressive erosion
* Sub luxatio Atlanto axial.
= Med. Spinalis compression neurologic sign
= Artery vertebralts rotation and suppresion
( sinkope can occur when down a head )
* Local pain
* Muscle spasme limited rotated movement
* occipital pain

Extra-articular pattern
In

some cases, RA has an extra-articular pattern

(involvement of other organ systems)

Usually

occurs in rheumatoid factor (RF)-positive

patients with more severe articular disease

More

common in men

 Vaskulitis
Lung disorder (Pleuritis, Pneumonitis)
Pericarditis
Nodul Rheumatic :- bursa olecranon
-upper arm external
- tendo Achilles
- ear
Neuropathy
Cornea and conjunctival lesion
Scleritis

 Lymphe hypertrophy
splenomegaly
Hyperpigmentation
Skin ulcer
Lymfphadenopathy
Anemia
Thrombocytopenia

LABORATORY
* Increase BSR
* Mild Anemia ringan
* Rheuma factor :
Rose waaler more spesific / latex more sensitive.
* Factor APF most spesific
Complete blood count, urine routin, renal and
liver function
* exudate synovial fluid

Diagnosis
Clinical

pattern

Biology
Imagery

Biology

Elevation of common non-specific serum markers of

inflammation contributes to the assessment of disease
activity level
Erythrocyte

sedimentation rate (ESR)

C-reactive protein (CRP)

Rheumatoid factors (RF)

Usually

appear in the first year of the disease

~80% of RA patients are RF+ (IgM the main isotype)
Associated with more rapidly evolving the more erosive
disease and a higher incidence of extra-articular
manifestations
RF can be detected in healthy patients during infections (4%
in Caucasians)
RF also associated with other chronic diseases (1)

Imagery conventional X-ray

Performed

at disease onset and on a regular basis

Usually hands and feet; other joints monitored
according to the disease pattern
Bone erosions and joint space narrowing patterns
noted
Approximately 30% of patients already have bony
erosion at disease onset (>60% at 2 years)

Common X-ray features

CaCCCage

damage int

space narrowing)

Bone

erosion

Ultrasounds and MRI

Synovitis

detection is mainly assessed

clinically
In

difficult cases, ultrasound may be useful

to detect synovitis and tenosynovitis

MRI

is not used in routine practice

Diagnostic criteria (ACR)

Presence of at least 4 of the following criteria:

Morning stiffness 1 hour

Arthritis of 3 of the following joints: right or left proximal
interphalangeal (PIP), metacarpophalangeal (MCP), wrist,
elbow, knee, ankle and metatarsophalangeal (MTP) joints
Arthritis of wrist, MCP or PIP joint
Symmetric involvement of joints
Rheumatoid nodules over bony prominences, or extensor
surfaces, or in juxta-articular regions
Positive serum RF
Radiographical changes, including erosions or bony
decalcification localised in or adjacent to the involved joints

Rheumatoid Arthritis ( ACR, 1987 ) :

1. Morning stiffness minimal 1 hour, minimal
for 6 weeks
2. Joint swollen in 3 or more for minimal
6 weeks
3. Swollen in wrist,
metacarpophalangeal or proximal
interphalangeal joint for 6 weeks
4. simetric joint swollen

5. Characteristic radiology for RA in hands,

includes unequivocal bone erosion and
decalsification
6. rheumatoid nodul

7. Rheumatoid positif factor ( with healthy people (+

< 5 %)
Determine Diagnosis RA if
4 kriteria or more were found

Therapeutic goals
Primary

goals in the treatment of RA

Prevention

or control of structural damage to

joints
Prevention or reversal of disability
Pain relief
To improve quality of life
The

ultimate goal is to achieve disease

remission

Treatment strategy approaches

Since the 1990s
Emphasis

on limiting joint destruction

Earlier use of intensive treatment
Methotrexate and sulfasalazine are considered
first-choice DMARDs
Use of combination therapy including triple
therapy in difficult disease (methotrexate,
sulfasalazine, fractal signature analysis)

ACR GUIDELINES IN RA TREATMENT

ESTABLISH
RA DIAGNOSIS

Evaluate
Disease activity/extent of synovitis
Structural damage
Functional/psychosocial status

Initiate Treatment
Patient education
Physical and occupational therapy, etc.
NSAIDs
Possible local or oral steroids ( 10 mg. Prednisone)

Assess Disease Activity

ACR GUIDELINES IN RA TREATMENT

Assess Disease Activity

Spontaneous Remission (uncommon)

Persistent Active Disease

Monitor Disease Activity

Start DMARD
Consult Rheumatologist
Persistent Active Disease

Reactivation of Disease
Remission or Satisfactory Control

Monitor Disease Activity

Reactivation of Disease

Revise Treatment Plan

Consult Rheumatologist Remission or Satisfactory Control
Change NSAIDs
Monitor Disease Activity
Change/add DMARDs
Periodically
Local or oral steroids
Rehabilitation

ACR GUIDELINES IN RA TREATMENT

Revise Treatment Plan
Consult Rheumatologist
Change NSAIDs
Change/add DMARDs
Local or oral steroids
Rehabilitation
Mechanical Joint Symptoms

Surgical Intervention
Mechanical Joint Symptoms

Monitor Disease Activity

Periodically
Reactivation of Disease

Persistent
Active
Disease

Refractory Rheumatoid Arthritis

Consult Rheumatologist
Most effective NSAID
Most effective DMARD
Possible local or oral steroids Remission or Satisfactory Control
Rehabilitation

Klasifikasi
Treatment AR :
Analgetika
Non

steroidal anti inflamatory drugs (NSAID)

Anti-rheumatic drugs
(SAARDs,DMARDs,TARTs)
Kortikosteroid
Immunosuppresive
Gene therapy
Biologicals agent

SIMPTOMATIK DRUG :
Journey of deseases uninfluence
Reduce pain
Using a months and waiting for remitif bioaviability
Wacth out : gastritis, nausea ect
Sistemik Steroid unrecommend to prevent
dependence and side-effect, except necesseary

1. Analgetic : - salicylate (4-6 gr/hari)

- paracetamol (1-2 gr/hari)
- codein (30 mg tiap 4 jam)
2. Anti inflamasi :
- aspirin ( 5 gr/ hari)
- indomethasin (25-150 mg/hari)
- phenylbutazone (200-400 mg/hari)
- oxyphenbutazone (200-400 mg/hari)
3. Corticosteroid :
- Given for active and progresif pain
- Minimal dose
- Prednisone 10 -15 mg/hari
- hydrocortisone asetate intra articular 20-50 mg

4. Anti inflamasi non steroid (NSAID)

- ibuprofen (600-1200 mg/hari)
- naproxen (375-750 mg/hari)
- piroxicam (10-40 mg/hari)
- profenid (100-600 mg/hari)
- ketoprofen (100-200 mg/hari)
NSAID
enzim cyclo-oxigenase supresed synthesa of
prostaglandin.
Possible stabilisation of membrane lysosomal
Inhibit release activator mediator inflammation
Inhibit cell migrasi to site of inflammation
Inhibit selular proliferasi

 Neutralize free radical

Generally potensial characteristic toxic
Side Effect at gastrointestinal ( especially if
combination with alcohol, smoking, stress, old age)
Hipersensitif reaction
Impairment liver function
Impairment renal function
Supressif of hematopoietik system

OBAT-OBAT REMITIF
DMADRS
Slow action waiting for blood level
Effec may occur 3-12 month later
Side effect and high toksicity
Expected to stop the progresifity/
become remission.

= Early joint destruction (90% RA erosion early 2 years.

= Result from worst therapy maybe because delay
DMARD

 Definite diagnose : DMARD immediately

Suspect RA, respons NSAID minimal Start DMARD
After using 3-6 month unsatisfied
Change with another DMARD
Combination

 DMARD

common use in AR Treatment

1. Klorokuin or hidroksiklorokuinm
2. Sulfasalazine
3. D-penisilamin
4. Garam emas
5. MTX
6. Siklosporin -A
7. Leflunomide
Gene therapy
Biological agent

METHOTREXATE (MTX)
folat acid antagonis
Reducing activity of thymidilate synthetase inhibisi 5aminoimidazole-carboximide-ribonucleotide transformylase
(AICAR) * IgM RF , IL-1 , IL-6
3 - 4 month action
7,5 mg per weeks (oral)
3 - 4 bulan no progress increase dose
for RA who progressive /fail with another DMARD

Side Effect MTX

susceptible with infection
nausea, vomitus, diare, stomatitis
Impair Liver fuction
alopesia
aspermia
lekopenia
-Leucovorin (folinat acid) 6 - 15 mg/m 2
6 hour during 72 hour, reduce side effect

MANAGEMENT OF
RHEUMATOID ARTHRITIS
SOME DISEASE-MODIFYING ANTI-RHEUMATIC
DRUGS (DMARDs)
DMARD
Methotrexate
Hydroxychloroquine
Sulfasalazine
Leflunomide
Azathioprine
Cyclosporine
Gold

MONITORING
Hematologic, liver, lung
Ophthalmologic
Hematologic, GI
Hematologic, liver
Hematologic, liver
Renal, blood pressure
Hematologic, renal

BIOLOGIC AGENT
= Biologic response modifiers
= Targeted therapy

Anti tumor necrosis factor alpha / anti TNF- / TNF-blocked

- ETANERCEPT (Enbrel )
anti soluble TNF receptor / sTNFR
anti cytokine therapy
- ADALIMUMAB (Humira )
- INFLIXIMAB (Renicade )
antibodi monoklonal
- RITUXIMAB (Mabthera )
depletion of B cells

Antagonis reseptor Interleukin- 1 (IL-1 ra) / blocking agent

- ANAKINRA (Kineret )

Classification FUNCTIONAL CAPACITY

(Steinbroke)
Class I : Complete Functional Capacity and able to do daily
activity with out trouble.
Class II: Functional Capacity Adequate daily activity with
dicomfort or limited movement on a joint or more
Class III: Functional Capacity for daily activity is limited.
Class IV: Nedd help with tool or person to do daily movement

PROGRESIFITY Classification
(Steinbrocker)
Stage I, Early :
1. Without destruction on X-Ray
2. Osteoporosis maybe on X-Ray

Stage II, Moderate :

1. Osteoporosis, subchondrial bone and cartilage destruction
pada rontgent
2. Disturbing joint mobility without deformity
3.Appear of muscle atrophy

Stage III, Severe :

1. Cartilage and bone destruction beside osteoporosis
finding on X-Ray
2. Deformity like subluxation , ulnar deviation,
hyperextention without fibrosis or ankylosis
3. Explicit muscle atrophy
4. Nodulus and tenosynovitis are finding

Stage IV, Terminal :

1. Presence fibrous or ankylosis
2. Stage III criteria

KRITERIA UNTUK CLINICAL REMISSION :

1. Duration of morning stiffness less than 15 minute
2. Without fatique
3. Joint pain disappear
4. Disappear of pain and rigid movement
5. Swelling of joint tissue and tendon sheath
disappear
6. BSE less than 30 mm/hour (woman), 20 mm/jam man.

IF 5 from condition direct happen in 2 month , can mention

remission reach out .

PSIKOTHERAPI
( INFORMATION , SPIRIT , FAMILY SUPPORT)
-WHAT IS RA
-(Sistemic joint deseases, chronic, deseases progresivity
unestimate)
-, can spontaneus remission and relaps, and can be
deformity)
- MENTALLY READY
- DILIGENCE TO TAKE THE THERAPY AND ECCEPT
THE TRUTH

PHYSICAL THERAPY :
Joint position at most comfortable position
Non acute process do mobilitation stage to prevent
deformity
Do not massage, symtomp will settle or increase
Deformity prevent / flexion deformity
Physiotherapy, occupational therapy, orthopedy,
phsicotherapy, social worker, phsichiatry, patient and
family cooperation
Auxillary tools : splint , stick , wheel chair,
special shoes, walking machine ect.
Surgery : synovectomia, arthrodese, total hip ect.

DIET
Well Balanced : nutritious
no specific food contra indication
If the sign occurred iron def. :
-ferros sulfat 0,2 gr, 3 x sehari /oral
-follic acid

THANK YOU

Dr. Blondina Marpaung,

SpPD - KR