RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS

Blondina Marpaung

Rheumatologi DivisionInterna Department

FK USU - Medan

Artritis Reumatoid :

widely spread , too all group, race, ethnic all the

world

Sistemic inflamatory autoimun deseases

Chornic inflamatory on joint

It’s a progresif poli artritis

Joint and other body organ

Symptom of chronic deseases

joint damaged deformitiy

disabilitity

Etiology sure ????

Autoimun Deseases :Autoimun Deseases :

Imune system activatedImune system activated

Attack the healty tissue Attack the healty tissue

Inflamation and tissue damage / organInflamation and tissue damage / organ

Autoimun process include :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

SinoviocyteSinoviocyte Ectopic lymphoid neogenesisEctopic lymphoid neogenesis Angiogenesis Angiogenesis HLA-class IIHLA-class II Non-MHC risk genesNon-MHC risk genes Arthritogenic antigenArthritogenic antigen Macrofag Macrofag Dendrit cellDendrit cell Blys (B-lymphocytes stimulator)Blys (B-lymphocytes stimulator) APRIL (a proliferating inducing legand)APRIL (a proliferating inducing legand) SmokingSmoking Gender Gender

EpidemiologyEpidemiology Most commonly affect ~1% from populationMost commonly affect ~1% from population

Commonly on womanCommonly on woman

Onset of disease is usually between 40 and 50 Onset of disease is usually between 40 and 50

years of age, but can start at any ageyears of age, but can start at any age

Occurs in all races and ethnic groups, but is rare in Occurs in all races and ethnic groups, but is rare in

less developed and more rural parts of the worldless developed and more rural parts of the world

Etiology/PhatogenesisEtiology/Phatogenesis

Rheumatoid arthritis (RA) is chronic, inflamatory, Rheumatoid arthritis (RA) is chronic, inflamatory,

sistemic, autoimmune disease sistemic, autoimmune disease

Commonly polyarticular disease Commonly polyarticular disease

Chronic inflamation in sinovial membran dari from Chronic inflamation in sinovial membran dari from

affected jointaffected joint

Spesific cause of RA is unknown, but immune respon Spesific cause of RA is unknown, but immune respon

is characteristic well.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 - ligament damage

- tendon damage - bone damage

proteoglycan thinning: - 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 patternClinical pattern

Lipsky (1998); Wolfe (1996)

Progressive onset (from Progressive onset (from weeks to months)weeks to months)

Pain and stiffness Pain and stiffness (synovitis)(synovitis)

Swollen jointsSwollen joints Symmetric articular patternSymmetric articular pattern Flu-like symptomsFlu-like symptoms Morning stiffnessMorning stiffness FatigueFatigue

Clinical pattern (cont’d)Clinical pattern (cont’d)

At onset, RA usually affects hands, wrists At onset, RA usually affects hands, wrists and feetand feet

Often a chronic cyclical course Often a chronic cyclical course During flare-ups, new joints are affected During flare-ups, new joints are affected

and existing lesions are worsenedand existing lesions are worsenedJoints become deformed, leading to Joints become deformed, leading to

additional disabilityadditional 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 jointsLateral 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

* Contracture flexion

* Swollen

* para-olekranon destruction

* Joint dislokation

SHOULDER

* glenohumeralis joint

* Acromioclavicularis

* Thoracoscapularis

HIPHIP

( less affected R A)( less affected R A)

* abnormal gait

* Limited joint movement

* Inguional discomfort

KNEEKNEE

( most affected.RA( most affected.RA

* Hypertrophy sinovial

* Joint effusion

* quadricep muscle atrophy

* 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 )

CERVICALCERVICAL

* 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 patternExtra-articular pattern

In some cases, RA has an extra-articular pattern In some cases, RA has an extra-articular pattern (involvement of other organ systems)(involvement of other organ systems)

Usually occurs in rheumatoid factor (RF)-positive Usually occurs in rheumatoid factor (RF)-positive patients with more severe articular diseasepatients with more severe articular disease

More common in menMore 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

LABORATORYLABORATORY

* 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

DiagnosisDiagnosisClinical patternClinical pattern

BiologyBiology

ImageryImagery

Biology Biology Elevation of common non-specific serum markers of Elevation of common non-specific serum markers of

inflammation contributes to the assessment of disease inflammation contributes to the assessment of disease activity levelactivity level

Erythrocyte sedimentation rate (ESR)Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP)C-reactive protein (CRP)

Rheumatoid factors (RF)Rheumatoid factors (RF) Usually appear in the first year of the diseaseUsually appear in the first year of the disease ~80% of RA patients are RF+ (IgM the main isotype)~80% of RA patients are RF+ (IgM the main isotype) Associated with more rapidly evolving the more erosive Associated with more rapidly evolving the more erosive

disease and a higher incidence of extra-articular disease and a higher incidence of extra-articular manifestationsmanifestations

RF can be detected in healthy patients during infections (4% RF can be detected in healthy patients during infections (4% in Caucasians)in Caucasians)

RF also associated with other chronic diseases (1)RF also associated with other chronic diseases (1)

Imagery — conventional X-rayImagery — conventional X-ray

Performed at disease onset and on a regular basisPerformed at disease onset and on a regular basis Usually hands and feet; other joints monitored Usually hands and feet; other joints monitored

according to the disease patternaccording to the disease pattern Bone erosions and joint space narrowing patterns Bone erosions and joint space narrowing patterns

notednoted Approximately 30% of patients already have bony Approximately 30% of patients already have bony

erosion at disease onset (>60% at 2 years)erosion at disease onset (>60% at 2 years)

Common X-ray featuresCommon X-ray features

CaCCCage CaCCCage damage damage int int space narrowing)space narrowing)

Bone erosionBone erosion

Ultrasounds and MRIUltrasounds and MRI

Synovitis detection is mainly assessed Synovitis detection is mainly assessed clinicallyclinically

In difficult cases, ultrasound may be useful In difficult cases, ultrasound may be useful to detect synovitis and tenosynovitisto detect synovitis and tenosynovitis

MRI is not used in routine practiceMRI is not used in routine practice

Diagnostic criteria (ACR)Diagnostic criteria (ACR)

Presence of at least 4 of the following criteria: Presence of at least 4 of the following criteria:

Morning stiffness Morning stiffness 1 hour1 hour Arthritis of Arthritis of 3 of the following joints: right or left proximal 3 of the following joints: right or left proximal

interphalangeal (PIP), metacarpophalangeal (MCP), wrist, interphalangeal (PIP), metacarpophalangeal (MCP), wrist, elbow, knee, ankle and metatarsophalangeal (MTP) jointselbow, knee, ankle and metatarsophalangeal (MTP) joints

Arthritis of wrist, MCP or PIP jointArthritis of wrist, MCP or PIP joint Symmetric involvement of jointsSymmetric involvement of joints Rheumatoid nodules over bony prominences, or extensor Rheumatoid nodules over bony prominences, or extensor

surfaces, or in juxta-articular regionssurfaces, or in juxta-articular regions Positive serum RFPositive serum RF Radiographical changes, including erosions or bony Radiographical changes, including erosions or bony

decalcification localised in — or adjacent to — the involved jointsdecalcification 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 weeks3. 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 goalsTherapeutic goals

Primary goals in the treatment of RAPrimary goals in the treatment of RAPrevention or control of structural damage to Prevention or control of structural damage to

jointsjointsPrevention or reversal of disabilityPrevention or reversal of disabilityPain reliefPain reliefTo improve quality of lifeTo improve quality of life

The ultimate goal is to achieve disease The ultimate goal is to achieve disease remissionremission

Treatment strategy approachesTreatment strategy approaches

Since the 1990sSince the 1990s Emphasis on limiting joint destructionEmphasis on limiting joint destruction Earlier use of intensive treatmentEarlier use of intensive treatment Methotrexate and sulfasalazine are considered Methotrexate and sulfasalazine are considered

first-choice DMARDsfirst-choice DMARDs Use of combination therapy including triple Use of combination therapy including triple

therapy in difficult disease (methotrexate, therapy in difficult disease (methotrexate, sulfasalazine, fractal signature analysis)sulfasalazine, fractal signature analysis)

ESTABLISHESTABLISHRA DIAGNOSISRA DIAGNOSIS EvaluateEvaluate

• Disease activity/extent of synovitisDisease activity/extent of synovitis• Structural damageStructural damage• Functional/psychosocial statusFunctional/psychosocial status

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

Assess Disease ActivityAssess Disease Activity

ACR GUIDELINES IN RA TREATMENTACR GUIDELINES IN RA TREATMENT

ACR GUIDELINES IN RA TREATMENTACR GUIDELINES IN RA TREATMENT

Remission or Satisfactory Control

Reactivation of Disease

Monitor Disease ActivityMonitor Disease ActivityPeriodicallyPeriodically

Assess Disease ActivityAssess Disease Activity

Start DMARDStart DMARDConsult RheumatologistConsult Rheumatologist

Monitor Disease ActivityMonitor Disease Activity

Revise Treatment PlanRevise Treatment Plan• Consult RheumatologistConsult Rheumatologist• Change NSAIDsChange NSAIDs• Change/add DMARDsChange/add DMARDs• Local or oral steroidsLocal or oral steroids• RehabilitationRehabilitation

Monitor Disease ActivityMonitor Disease Activity

Remission or Satisfactory Control

Spontaneous Remission (uncommon)

Persistent Active Disease

Persistent Active Disease

Reactivation of Disease

ACR GUIDELINES IN RA TREATMENTACR GUIDELINES IN RA TREATMENT

Refractory Rheumatoid ArthritisRefractory Rheumatoid ArthritisConsult RheumatologistConsult Rheumatologist• Most effective NSAIDMost effective NSAID• Most effective DMARDMost effective DMARD• Possible local or oral steroidsPossible local or oral steroids• RehabilitationRehabilitation

Persistent ActiveDisease

Monitor Disease ActivityMonitor Disease ActivityPeriodicallyPeriodically

Mechanical Joint Symptoms

Remission or Satisfactory Control

Reactivation of Disease

Surgical InterventionSurgical Intervention

Mechanical Joint Symptoms

Revise Treatment PlanRevise Treatment Plan• Consult RheumatologistConsult Rheumatologist• Change NSAIDsChange NSAIDs• Change/add DMARDsChange/add DMARDs• Local or oral steroidsLocal or oral steroids• RehabilitationRehabilitation

KlasifikasiKlasifikasiTreatment AR :Treatment AR : AnalgetikaAnalgetika Non steroidal anti inflamatory drugs (NSAID)Non steroidal anti inflamatory drugs (NSAID) Anti-rheumatic drugs Anti-rheumatic drugs

(SAARDs,DMARDs,TARTs)(SAARDs,DMARDs,TARTs) KortikosteroidKortikosteroid ImmunosuppresiveImmunosuppresive Gene therapy Gene therapy Biologicals agentBiologicals agent

• 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

SIMPTOMATIK DRUGSIMPTOMATIK DRUG : :

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

• 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

OBAT-OBAT REMITIF OBAT-OBAT REMITIF

DMADRSDMADRS

• 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 hidroksiklorokuinm1. Klorokuin or hidroksiklorokuinm2. Sulfasalazine2. Sulfasalazine3. D-penisilamin3. D-penisilamin4. Garam emas4. Garam emas5. MTX5. MTX6. Siklosporin -A6. Siklosporin -A7. Leflunomide 7. Leflunomide

Gene therapyGene therapy Biological agentBiological agent

METHOTREXATE (MTX)METHOTREXATE (MTX)

• folat acid antagonis

• Reducing activity of thymidilate synthetase inhibisi 5-

aminoimidazole-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 OFRHEUMATOID ARTHRITIS

SOME DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (DMARDs)

DMARDMethotrexate

Hydroxychloroquine

Sulfasalazine

Leflunomide

Azathioprine

Cyclosporine

Gold

MONITORINGHematologic, liver, lung

Ophthalmologic

Hematologic, GI

Hematologic, liver

Hematologic, liver

Renal, blood pressure

Hematologic, renal

BIOLOGIC AGENTBIOLOGIC 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 CAPACITYClassification 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 ClassificationPROGRESIFITY 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

4. Nodule and tenosynovitis are finding

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 .

PSIKOTHERAPIPSIKOTHERAPI

( 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 :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.

DIETDIET

• 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