rheumatoid arthritis patgen,patfis,gejala,diagnosis ary
TRANSCRIPT
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RHEUMATOID ARTHRITIS
Patogenesis, Patofisiologi, Gambaran Klinis, Diagnosis
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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
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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, fibronectin, hyaluronic acid, and other molecules facilitate the lubrication and function of cartilage surfaces
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PATOGENESIS & PATOFISIOLOGI
• The synovium in RA:– Synoviocytes ↑ lining layer ↑ (the lining is the
primary source of inflammatory cytokines and proteases, both ↑), 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
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PATOGENESIS & PATOFISIOLOGI
• In the synovial sublining region:– Edema, blood vessel proliferation, and increased
cellularity tissue volume ↑– T and B lymphocytes, plasma cells, interdigitating
and follicular dendritic cells (IDC and FDC), and natural killer cells (NK cells) accumulate in rheumatoid synovium
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PATOGENESIS & PATOFISIOLOGI
• Synovial fluid in RA:– Leakage from the synovial microvasculature ↑
volume of synovial fluid ↑– There are neutrophils (predominant ),
lymphocytes, macrophages, NK cells, and fibroblasts
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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
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PATOGENESIS & PATOFISIOLOGI
• Mechanism of Joint Destruction• Angiogenesis & cell migration:– Tissue ↑ > angiogenesis hypoxia (it is a potent
stimulus for angiogenesis in the synovium) VEGF, IL-8, Angiopoietin-1 are expressed angiogenesis ↑
– Proinflammatory cytokines migration of leukocytes to the synovium
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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 , cytokine-activated chondrocytes , PMNs destructive enzymes (MMP, serine protease, cathepsin)↑ loss of proteoglycan & cleavage of native type II collagen
• Protease inhibitors : serine protease inhibitors, tissue inhibitors of metalloproteinase (TIMPs)
• The relative balance between MMPs and TIMPs is unfavorable in RA compared with osteoarthritis
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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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GAMBARAN KLINIS
• Gejala bervariasi, bisa muncul sewaktu-waktu atau menetap, dapat mengalami eksaserbasi dan remisi.
• Nyeri dan bengkak pada sendi perifer simetris, khususnya jari-jari tangan
• Kelainan bentuk: deviasi ulnar, boutonniere, swan neck, Lanois, mutilasi sendi
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GAMBARAN KLINIS
• Demam ringan, lelah, berat badan kurang, nyeri otot, pembesaran KGB
• Bersifat sistemik, manifestasi di mata, kulit, susunan syaraf, paru, hati, ginjal, jantung, limfa, usus, otot
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GAMBARAN KLINIS
• Rheumatoid Factor (RF) positif (pada 70% kasus)
• Kelainan hematologi: anemia, trombositopenia, leukopenia/neutropenia, laju endap darah (LED) ↑
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LABORATORIUM
• Cairan Sinovial• Warna: kuning sampai putih• Mucin clot• Leukosit 5.000-50.000/mm3,didominasi
neutrofil (65%) • Glukosa : normal atau rendah
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LABORATORIUM
• Cairan Sinovial• RF positif• Komplemen ↓• IgG dan kompleks imun ↑• Fagosit
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LABORATORIUM
• Darah Tepi• Leukosit: normal atau meningkat
(<12.000/mm3), menurun jika ada splenomegali (Felty’s syndrome)
• Anemia normositer atau mikrositer
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LABORATORIUM
• Pemeriksaan Sero-imunologi• RF + IgM : pada 75% penderita. 95% pada
penderita dengan nodul subkutan• Anti CCP antibodies (+)• Antinuclear antibodies (+) (10-50% penderita)• Anti-DNA antibodies (-)• CRP, fibrinogen, dan LED ↑
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LABORATORIUM
• Pemeriksaan Sero-imunologi• Alpha 1 dan alpha 2 – globulin ↑, sebagai
acute phase reactant• γ-globulin ↑ • Kadar komplemen serum normal, bisa turun
pada gejala ekstra artikuler yang berat seperti vaskulitis
• Adanya circulating immune complexes
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GAMBARAN RADIOLOGIS
• Perubahan awal umumnya pda jari-jari tangan dan kaki
• Distribusinya bilateral dan simetris• Pembengkakan jaringan lunak periartikular,
osteoporosis jukstaartikular, melebarnya permukaan sendi, memadatnya jukstaartikular atau periostitis, erosi marginal dan pembentukan kista, kerusakan seluruh permukaan sendi
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GAMBARAN RADIOLOGIS
• Perubahan bentuk berupa subluksasi, dislokasi, kerusakan tulang artikular, fusi tulang, dan kerusakan total kavum artikular
• MCP dan PIP: deviasi ulnar, boutonniere, swan neck deformities, spindle digit
• Pergelangan tangan: erosi pada stiloid ulnar, erosi multipel sendi karpal (spotty carpal sign), ankilosis tulang, zig-zag deformity
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GAMBARAN RADIOLOGIS
• Kaki: perubahan awal pada MTP 4 dan 5. Gambarannya paralel dan identik dengan yang terjadi di tangan. Perubahan bentuk Lanois – dorsal subluxation dari sendi MTP, deviasi fibular
• Vertebra servikal: paling sering terkena (70% pasien RA), peningkatan celah atlantodental >3mm (pada posisi fleksi), erosi odontoid, subluksasi sendi (C3, C4, C5), kadang pada sendi torakolumbal
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GAMBARAN RADIOLOGIS
• Coxae: kerusakan menyeluruh permukaan sendi, erosi marginal (migrasi axial), erosi minimal, protrusio acetabulae bilateral
• Genu: kerusakan seluruh permukaan sendi, erosi marginal (pada kondilus os tibial), osteoporosis
• Bahu: kerusakan sendi glenohumeral, erosi marginal humerus, subluksasi superior, penonjolan klavikula
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GAMBARAN RADIOLOGIS
• Sakroiliaka: biasanya unilateral, mengenai 2/3 bagian bawah, tampak erosi tapi tidak sklerosis, dan jarang ankilosis
• Thorax: efusi pleura minimal. Kadang ditemukan nodul rematoid yang menyerupai neoplasma dengan pembentukan kavitas (necrobiotic nodules). Fibrosis interstisial difus atau basilar dengan gambaran siluet jantung iregular, honeycomb lung
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DIAGNOSIS
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