RHEUMATOID ARTHRITIS Patgen,Patfis,Gejala,Diagnosis

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


• 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


• 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


• 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


• Synovial fluid in RA:– Leakage from the synovial microvasculature ↑

volume of synovial fluid ↑– There are neutrophils (predominant ),

lymphocytes, macrophages, NK cells, and fibroblasts


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


• 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


• 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


• ECM damage :– Bone destruction :• Cytokine expression of RANKL on T cells & FLS ↑

paired with RANK in osteoclast maturation & activation of osteocalast ↑ bone resorption ↑

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

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

GAMBARAN KLINIS

• Rheumatoid Factor (RF) positif (pada 70% kasus)

• Kelainan hematologi: anemia, trombositopenia, leukopenia/neutropenia, laju endap darah (LED) ↑

LABORATORIUM

• Cairan Sinovial• Warna: kuning sampai putih• Mucin clot• Leukosit 5.000-50.000/mm3,didominasi

neutrofil (65%) • Glukosa : normal atau rendah

LABORATORIUM

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

LABORATORIUM

• Darah Tepi• Leukosit: normal atau meningkat

(<12.000/mm3), menurun jika ada splenomegali (Felty’s syndrome)

• Anemia normositer atau mikrositer

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 ↑

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

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

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

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

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

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

DIAGNOSIS

RHEUMATOID ARTHRITIS Patgen,Patfis,Gejala,Diagnosis

Documents

Transcript of RHEUMATOID ARTHRITIS Patgen,Patfis,Gejala,Diagnosis