RHEUMATOID ARTHRITIS

Patogenesis, Patofisiologi, Gambaran Klinis, Diagnosis

PATOGENESIS & PATOFISIOLOGI
Synovial Pathology • The synovium is the primary site of inflammation in rheumatoid arthritis (RA) • The normal synovium consists of:
– An intimal lining layer – The sublining below the intima contains blood vessels, lymphatics, nerves, and adipocytes distributed within a less cellular, fibrous matrix

fibronectin. and other molecules  facilitate the lubrication and function of cartilage surfaces . hyaluronic acid.PATOGENESIS & PATOFISIOLOGI • The intimal lining layer comprises of two different cell types : – Macrophage-like synoviocytes or type A synoviocytes – Fibroblast-like synoviocytes (FLS) or type B synoviocytes  synthesis of extracellular matrix (ECM) proteins including collagen.

both ↑).PATOGENESIS & PATOFISIOLOGI • The synovium in RA: – Synoviocytes ↑  lining layer ↑ (the lining is the primary source of inflammatory cytokines and proteases. in concert with activated chodrocytes and osteoclasts  joint destruction – Villous projections protrude into the joint cavity. invading the underlying cartilage and bone where the proliferating tissue is called pannus .

blood vessel proliferation. interdigitating and follicular dendritic cells (IDC and FDC). and natural killer cells (NK cells) accumulate in rheumatoid synovium . plasma cells.PATOGENESIS & PATOFISIOLOGI • In the synovial sublining region: – Edema. and increased cellularity  tissue volume ↑ – T and B lymphocytes.

lymphocytes. and fibroblasts .PATOGENESIS & PATOFISIOLOGI • Synovial fluid in RA: – Leakage from the synovial microvasculature ↑  volume of synovial fluid ↑ – There are neutrophils (predominant ). macrophages. NK cells.

PATOGENESIS & PATOFISIOLOGI Autoimmunity & Autoantibodies in RA • Autoantibodies : – Rheumatoid Factor (RF) – Anti-Cyclic Citrullinated Peptide Antibodies (ACCP) – Others: Antitype II collagen antibodies • T cells have been implicated in RA due to their presence in the synovium and the class II MHC association .

IL-8.PATOGENESIS & PATOFISIOLOGI • Mechanism of Joint Destruction • Angiogenesis & cell migration: – Tissue ↑ > angiogenesis  hypoxia (it is a potent stimulus for angiogenesis in the synovium)  VEGF. Angiopoietin-1 are expressed  angiogenesis ↑ – Proinflammatory cytokines  migration of leukocytes to the synovium .

tissue inhibitors of metalloproteinase (TIMPs) • The relative balance between MMPs and TIMPs is unfavorable in RA compared with osteoarthritis . serine protease. PMNs  destructive enzymes (MMP.PATOGENESIS & PATOFISIOLOGI • Role of FLS : Activated type-B synoviocytes are a major source of inflammatory mediators and metalloproteinases in RA • ECM damage : – Cartilage destruction : • Aggressive synoviocytes . cathepsin)↑  loss of proteoglycan & cleavage of native type II collagen • Protease inhibitors : serine protease inhibitors. cytokine-activated chondrocytes .

PATOGENESIS & PATOFISIOLOGI • ECM damage : – Bone destruction : • Cytokine  expression of RANKL on T cells & FLS ↑  paired with RANK in osteoclast  maturation & activation of osteocalast ↑  bone resorption ↑ .

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mutilasi sendi . khususnya jari-jari tangan • Kelainan bentuk: deviasi ulnar. bisa muncul sewaktu-waktu atau menetap. • Nyeri dan bengkak pada sendi perifer simetris. dapat mengalami eksaserbasi dan remisi. boutonniere. swan neck.GAMBARAN KLINIS • Gejala bervariasi. Lanois.

nyeri otot. pembesaran KGB • Bersifat sistemik. paru. berat badan kurang. kulit. susunan syaraf. manifestasi di mata. lelah. hati. jantung.GAMBARAN KLINIS • Demam ringan. ginjal. limfa. usus. otot .

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laju endap darah (LED) ↑ . leukopenia/neutropenia.GAMBARAN KLINIS • Rheumatoid Factor (RF) positif (pada 70% kasus) • Kelainan hematologi: anemia. trombositopenia.

didominasi neutrofil (65%) • Glukosa : normal atau rendah .LABORATORIUM • • • • Cairan Sinovial Warna: kuning sampai putih Mucin clot Leukosit 5.000/mm3.000-50.

LABORATORIUM • • • • • Cairan Sinovial RF positif Komplemen ↓ IgG dan kompleks imun ↑ Fagosit .

menurun jika ada splenomegali (Felty’s syndrome) • Anemia normositer atau mikrositer .LABORATORIUM • Darah Tepi • Leukosit: normal atau meningkat (<12.000/mm3).

fibrinogen. 95% pada penderita dengan nodul subkutan • Anti CCP antibodies (+) • Antinuclear antibodies (+) (10-50% penderita) • Anti-DNA antibodies (-) • CRP.LABORATORIUM • Pemeriksaan Sero-imunologi • RF + IgM : pada 75% penderita. dan LED ↑ .

LABORATORIUM • Pemeriksaan Sero-imunologi • Alpha 1 dan alpha 2 – globulin ↑. bisa turun pada gejala ekstra artikuler yang berat seperti vaskulitis • Adanya circulating immune complexes . sebagai acute phase reactant • γ-globulin ↑ • Kadar komplemen serum normal.

memadatnya jukstaartikular atau periostitis. melebarnya permukaan sendi. kerusakan seluruh permukaan sendi .GAMBARAN RADIOLOGIS • Perubahan awal umumnya pda jari-jari tangan dan kaki • Distribusinya bilateral dan simetris • Pembengkakan jaringan lunak periartikular. erosi marginal dan pembentukan kista. osteoporosis jukstaartikular.

zig-zag deformity . spindle digit • Pergelangan tangan: erosi pada stiloid ulnar. erosi multipel sendi karpal (spotty carpal sign). kerusakan tulang artikular. dan kerusakan total kavum artikular • MCP dan PIP: deviasi ulnar. swan neck deformities. ankilosis tulang.GAMBARAN RADIOLOGIS • Perubahan bentuk berupa subluksasi. boutonniere. fusi tulang. dislokasi.

C4. erosi odontoid. kadang pada sendi torakolumbal . deviasi fibular • Vertebra servikal: paling sering terkena (70% pasien RA). subluksasi sendi (C3. C5). peningkatan celah atlantodental >3mm (pada posisi fleksi). Gambarannya paralel dan identik dengan yang terjadi di tangan. Perubahan bentuk Lanois – dorsal subluxation dari sendi MTP.GAMBARAN RADIOLOGIS • Kaki: perubahan awal pada MTP 4 dan 5.

protrusio acetabulae bilateral • Genu: kerusakan seluruh permukaan sendi. erosi marginal humerus. penonjolan klavikula . erosi marginal (migrasi axial). subluksasi superior. erosi minimal. osteoporosis • Bahu: kerusakan sendi glenohumeral.GAMBARAN RADIOLOGIS • Coxae: kerusakan menyeluruh permukaan sendi. erosi marginal (pada kondilus os tibial).

dan jarang ankilosis • Thorax: efusi pleura minimal. Fibrosis interstisial difus atau basilar dengan gambaran siluet jantung iregular.GAMBARAN RADIOLOGIS • Sakroiliaka: biasanya unilateral. mengenai 2/3 bagian bawah. tampak erosi tapi tidak sklerosis. Kadang ditemukan nodul rematoid yang menyerupai neoplasma dengan pembentukan kavitas (necrobiotic nodules). honeycomb lung .

DIAGNOSIS .

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