Rheumatoid Arthritis

CLINICAL MANIFESTATION AND MANAGEMENT OF

RHEUMATOID ARTHRITISI Gede PalgunadiSMF Penyakit DalamRSUP NTB/FK UNRAM

RHEUMATOID ARTHRITISChronic erosive sinovitis Poliartritis, potentially disablingMore frequent in female Extra articular manifestation considered to be a systemic autoimmune disease

NORMAL SYNOVIUM vs RANormalRheumatoid synovitisbursitistendinitissynovitisbonecartilageHyperplasiaof Lyning cellpannusPolimorf exudation

fibrosismonocyteMononuclear infiltration

THE CLINICAL PROGRESS OFRHEUMATOID ARTHRITIS

TREATMENTANALGESICANTI-INFLAMMATORY* STEROID* NON STEROIDDISEASES MODIFYING ANTI RHEUMATIC DRUGOCCUPATIONAL THERAPYPHYSIOTHERAPHYPSYCHOTERAPHYCOMPLEMENTARYSURGERY

Common X-ray features

Cartilage damage (joint space narrowing)

Bone erosion

AFirst exposure to antigen (sensitizing dose)AntigenSelection of specific lymphocytesB lymphocytesPrimary transformationImmune responsePlasma cellsHumoral immune responseProduction of specific antibody *IgG, IgM, rarely IgA)Second (or prolonged) exposure to antigen (challenge dose)BAntigenSecondary immune responseSpecific antibodyAntigen antibody complexes (immune complexes) circulate in blood (systemic) or form at site of antigen entry (local)Immune complex deposition in tissues Complement activationAcute inflammation mediated by C3a, C5a; Necrosis (tissue damage) mediated by C67891 + weeks

Potential Roles of B Cells in the Immunopathogenesis of RA

NSAID adjuvant analgesic weak opioid(codeine)paracetamolor NSAID adjuvant analgesicchronic painpain persists or increasesStrong opioid NSAID adjuvant analgesicacute painpain decreases or goes awayMILDMODERATESEVERE

Rasio Selektivitas Cox2/Cox1DrugRasio Cox2/Cox1Piroxicam250Acetylsalicylic acid175Indomethacin 60Ibuprofen 15Paracetamol 7.4Sodium salicylate 2.8Carprofen 1Meloxicam 0.8Diclofenac 0.7Naproxen 0.6Nimesulide 0.1Celecoxibe 0.05

Selektif Cox 2 Selektif Cox 1Adapted from Vane, J.R. IC50 Value (mol/L) of NSAIDs on COX-2 or COX-1 activity in intact cells

SOME DISEASE-MODIFYING ANTI-RHEUMATIC DRUGs (DMARDs) DMARDsMethotrexateHydroxychloroquineSulphasalazineLeflunomideAzathioprineCyclosporineGoldAnti TNF-, IL-1CellceptAnti B cellsSHOULD BE MONITOREDHaematologic, liver, lungOfthalmologicHaematologic, GI Haematologic, liverHaematologic, liverKidney, Blood pressureHaematologic, kidneyInfectionKidney, neutrophil countBlood presure, Temp, Resp

ACR GUIDELINE FOR THE TREATMENT OF AR

ACR GUIDELINE FOR THE TREATMENT OF AR

Remission or under controlledDisease reactivationRemission or under controlledSpontaneous remission (uncommon)Active persistant diseaseActive persistant diseaseDisease reactivation

MATUR SUKSME

*Rheumatoid arthritis (RA) is a chronic inflammatory, erosive, and potentially disabling polyarthritis, usually occurring in females. This is considered to be a systemic autoimmune disease.*In contrast to OA (which starts off as a cartilage problem), RA is predominantly a synovitis, with the participation of several inflammatory cells and mediators such as cytokines, forming a sheet of inflammatory reaction with fibrosis, called pannus.*The clinical course of RA varies among individuals even with the same diagnosis.*This shows stage 4 or burnt-out RA , with the classical chronic hand deformities including joint subluxation.**References:Drner T, Burmester GR. The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol 2003;15:246252.Edwards JC, Cambridge G, Abrahams VM. Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology 1999;97:18896.Gause A, Berek C. The role of B cells in the pathogenesis of rheumatoid arthritis: potential implications for treatment. BioDrugs 2001;15:7379.Shaw T, Quan J, Totoritis MC. B-cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis 2003;62(Suppl. 2);559. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B-cell dependent. J Immunol 2001;167:47104718. Zhang Z, Bridges SL. Pathogenesis of rheumatoid arthritis. Role of B lymphocytes. Rheum Dis Clin North Am 2001;27:335-53.

*Disease-modifying anti-rheumatic drugs or DMARDs are a mainstay in the management of RA. These are primarily instituted by a specialist. The role of the primary care physician is to monitor and recognize side effects of the individual drugs.*American College of Rheumatology guidelines in RA treatment I. It is fundamental to establish the diagnosis of RA. NSAIDs constitute the first line of therapy, and can be given while observing the patient during the 6 weeks of symptoms required for RA diagnosis. Patient education and physical therapy are important adjuncts in the treatment.*American College of Rheumatology guidelines in RA treatment II. Patients with persistent active disease should be referred to the rheumatologist, who will reassess the patient and likely start a DMARD or a combination of DMARDs. The patient may be referred back to the primary care physician (usually for proximity reasons) for monitoring of response to, and any adverse effects of, therapy.