Rheumatoid Arthritis (RA) :Chronic, systemic, inflammatory autoimmune Primary target : synovial tissues Symmetric polyarthritis It leads to substansial disability & premature deathEarly detectionEarly treatment*

Mortality of RA 2-3 times than normal populationCause of death : Infection and gastrointestinal disordersPrognostic factors: Socio-demografic Clinical feature Laboratory findings Radiographic changes *

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Immunopathogenesis of RA not fully understood Genetic Environment Infection Molecular mimicry Rheumatoid Arthritis *

In 1995, what data provided clues to pathogenesis in rheumatoid arthritis?

Immune complexes HLA-DR4 genetic risk Benefit of TNF-blockade

Sinovial hyperplasia Villi hypertrophy >> A and B synoviocyteInflammatory cells infiltrationNeovascularizationThe worst : cartilage-pannus junctionLate stage periarticular damage & bone erosion*

Histology of rheumatoid synovitis. A. The characteristic features of rheumatoid inflammation with hyperplasia of the lining layer (arrow) and mononuclear infiltrates in the sublining layer (double arrow). B. A higher magnification of the largely CD4+ T cell infiltrate around postcapillary venules (arrow).*

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sinovial : dikenali sebagai antigen spesifik oleh sel T inflamasi bahan bahan inflamasi IL-1,TNF,IFN,IL-10 Kronik progresive sinovial inflamasi & destruksi sendi hiperplasi sinovia ke kartilago & tulang panus

Poliartritis simetris sendi kecil, kaku sendi Gejala sistemik: Demam,Malaise,AnemiaPemeriksaan fisik sendi bengkak (sinovitis) tanda radang/inflamasiStadium lanjut deformitas Swan neck*

Erosion of Joint can occur early in the course of the disease maximal rate at 2 years course the diseases

Fatigue Loss of appetite, weight loss, flu-like symptoms, depression, anemia

Inflamed joints that are warm, tender, swollen, often red and painful, and difficult to move

Poliartritis simetris sendi kecil, kaku sendi Gejala sistemik: Demam,Malaise,Anemia

Pemeriksaan fisik sendi bengkak (sinovitis) tanda radang/inflamasiStadium lanjut deformitas Swan neck

Gejala klinik

simetric Poliarthritis Late phase Early phase

Rheumatoid nodules ,Vasculitis ,Sicca or Sjgrens syndrome Episcleritis, peripheral neuropathy, palmary erythema, Digital necrosis Raynould fenomenaSubcutan noduleInflammation surrounding heart and lungsleg ulcersFELTY SYNDROME

Permasalahan Keterlambatan Diagnosis sering terjadi Most GP refer new arthritis patients to a rheumatologist more than 3-6 months80 % pasien RA dapat terdiagnosis rheumatologist dalam waktu 2 minggu pada gejala awal It can be difficult, particularly in the early stage of the disease, No definite test

Kaku pagi > 1 jamArtritis pada 3 sendi atau lebihArtritis pada sendi-sendi tangan & pergelangan tanganArtritis simetrisNodul subkutanReumatoid faktor yang positifPerubahan radiografis

Gambaran klinis :nyeri sendiKaku pagi hari > 1 jam Pada pemeriksaan fisik : sendi bengkak,( sinovitis) disertai tanda radang , stadium lanjut deformitasSwan neck Sendi : MCP,PIP.DIP,pergelangan tangan ,siku bahu ,pergelangan kaki, lutut dan pingulKriteria diagnosis ARA 1987Gambaran radiologis : Awal osteoporosis periartikuler, erosi sendi (mice bite),penyempitan ruang antar sendi, ankilosingLaboratorium : anemia, LED/CRP

Kulit : nodul rheumatoidMata : keratokonjuctivitis siccaParu : intersisial lung diseases,pleuritisJantung : pericarditis, myocarditisGinjal : amiloidosisCNS : C1-C2 subluxasi cervical myelopatiHematologi : anemia , felty syndrome

1990--> aggressive therapy has been shown in improve out come surogate marker of damage CRP Early initiation of treatment with DMARD can reserve morbidity, as measured by disability and radiographic progressionGreatest potential for limiting the disability resulting from RA lies in identifying and treating the diseases in its earlist phases beforeDamage has been done

Prediction of diseases severity :Large joint involmenthigher overall joint countupper extremities diseasesfemaleRF +CRP/ESRHLA DRB1malaise/weakness

Menekan proses inflamasiMengurangi rasa nyeri Mencegah deformitas Memelihara produktivitas dan aktivitas sehari-hari

Anti inflamasi non steroid (NSAID) menekan keradangan dan rasa nyeriKortikosteroid efek anti inflamasi dan imunosupresif sebagai bridging therapy dlm mengatasi gejala sinovitisDisease modifying anti rheumatic drugs (DMARD):PenicillamineGaram emas oral/intra muscularSulphazalazine Antimalaria (choroquine & hydroxychloroquine)Methotrexate AzathioprineCyclosporineLeflunomideDigunakan sedini mungkin mencegah kerusakan sendi

Traditional paradigma pyramid approach that NSAID, aspirin are the initial drugs administered to control inflamation and pain DMARD traditionally more toxic added relatively late in the course of the diseases pyramid approach was base on @ RA is benign, non life threatening diseases@ aspirin & NSAID are benign therapies@ DMARD are too toxic for routine use

Over the last decade thre has been a stady accumaltion of evidence suggessting thal all of these assumption are in correctNSAID are not benign therapiesMany DMARD are not more toxic than NSAIDEficacy Of DMARDs in the treatment Of RA1.effect on the rate of joint destruction in RA :there is good evidence that DMARDs can reduce the rate of joint destruction that occur in RA2.effect on pain and disability

MethotrexateLeflunomide (Arava)SulfasalazineAzathioprineMycophenolate MofetilCorticosteroidsHydroxychloroquineMinocycline

Early initiation and titration of DMARDIf incomplete response to DMARD alone, after reasonable titration, addition of biologic recommended

What is meant by the term Biologic Therapy? Double meaning:Organic compounds made by living cellsAs opposed to products from a chemistry labModify biologic responsesAntibody-antigen interactionsCytokine-receptor interactions (both ends)Cell signaling proteins, inhibitors, or ligands

Anti-Tnf medications Etanercept (cytokine receptor fusion protein)Infliximab (anti-cytokine antibody)Adalimumab (anti-cytokine antibody)B-cell depleting agents (monoclonal antibody)RituximabT-cell costimulation inhibitors (receptor-ligand )AbataceptIl-1 Inhibitors (Il-1 cytokine receptor decoy)Anakinra

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