RHEUMATOID

ARTHRITIS

Hermansyah
Bagian Ilmu Penyakit Dalam
FK UNSRI / RSMH Palembang
INTRODUCTION
 RHEUMATOID ARTHRITIS (RA)
• A chronic, systemic, inflammatory
autoimmune disease
• Primary target the synovial tissues
• Peripheral joints, symmetrical
• Marked morning stiffness
• Extra-articular manifestations (nodules,
pulmonary fibrosis, serositis, vasculitis, eye
inflammation)
Scott DL, et al. Lancet 1987;1:1108-1111
Gabriel SE. Rheum Dis Clin North Am 2001;27:269-281
Lipsky, PE. In: Harrison's Principles of Internal Medicine.2005,p.1968-77
RHEUMATOID ARTHRITIS (RA)
• Affects approximately 0.8 percent of adults
worldwide (0,3 – 1,2%)
• More common in women (by a ratio of 3 to 1)
• 80% in range 35-50 years-old
• Monozygotic twins : 2-15%
• Dizygotic twins : 5%

Scott DL, et al. Lancet 1987;1:1108-1111

Gabriel SE. Rheum Dis Clin North Am 2001;27:269-281
Lipsky, PE. In: Harrison's Principles of Internal Medicine.2005,p.1968-77
 The Burden of RA
 Chronic polyarthritis lead to joint
erosions are the most prominent clinical
manifestations.
 RA over time leading to premature
mortality, decrease in quality of life and
work disability.
 Prevention of joint erosions in RA is still
challenging.
 Work disability of RA

l 10% of patients with RA stop working

within 1 year of diagnosis
l 50% stop working within 10 years of
diagnosis
l 60% stop working within 15 years of
diagnosis

l 90% leave work within 30 years of diagnosis

Yalin E .t &, Arthritis Rheum 30:507–512, 1987

PATOGENESIS
Immunopathogenesis

not fully understood Genetic

Auto
immune
T
disease

DC
Imune
Regulation Environment
 CAUSES OF RA
• Heterogenous disease of variable severity, and
unpredictable response to therapy
• Genetic and environmental factors are clearly
implicated in its etiology and pathogenesis
• Environmental factors :
– Cigarrete (risk of developing anti-CCP (+))
– Silica dust
– Infection : bacterial (bacterial DNA,
peptidoglycans, LPS) and viral (EBV)

Klareskog L, et al In: Rheumatoid Arthritis. 2009,p. 28-34.

 CAUSES OF RA
• Genetic factors :
– Overall heritability about 50-60% (twin study)
– Genome study:
 HLA gen : HLA DR4, HLA DRB1
 non-HLA gen : cytotoxic-T-lymphocyte-
associated protein 4 (CTLA-4) gen, protein
tirosin phosfatase (PTPN22), specific signal
transducers and activators of transcription-4
(STAT4)

Weyand CM, et al. Med Clin North Am 1997;81(1):29-55

Plenge RM. In: Rheumatoid Arthritis. 2009,p.23-7
HLA-DR4
HLA-DRB1
CIGARETTE
SILICA DUST
PATHOGENESIS
non-HLA INFECTION OF RA
AUTOAg
 Articular effects of IL-6 in RA
B-cell
Antibody Synoviocytes
production

VEGF
Macrophage IL-6 Endothelial cells
Pannus formation

MMPs1
T-cell RANKL
Neutrophil
Joint destruction
Mediation of chronic Osteoclast activation
inflammation Bone resorption

VEGF = vascular endothelial growth factor; Dayer JM, et al. Rheumatology 2010; 49:1524
MMPs = matrix metalloproteinases. Smolen J, et al. Nat Rev Drug Disc 2003; 2:473488
 Systemic effects of IL-6 in RA
Acute-phase The acute-phase
proteins (e.g. CRP) response

IL-6
Hepcidin production
Alterations in iron homeostasis Anaemia

Inflammation Thrombocytosis

Hypothalamic- Systemic osteoporosis

Increased pituitary-adrenal
(HPA) axis
cardiovascular risk Fatigue and mood

CRP = C-reactive protein. Dayer J-M & Choy E. Rheumatology 2010; 49:1524
 Normal

The normal synovial membrane is a thin, glistening tissue that lines the diarthrodial
joints

The membrane normally consists of a lining layer that is only a few cells thick and a
sublining layer that consists of loose connective tissue

The lining layer contains fibroblast-like synoviocytes and macrophages, and

it produces extracellular-matrix molecules and synovial fluid
 RA

In rheumatoid arthritis, there is a dramatic increase in the number of cells in the

lining layer, and the sublining layer becomes infiltrated with inflammatory cells,
including lymphocytes, macrophages, and mast cells

These cells produce cytokines that, together with locally produced autoantibodies,
are thought to drive the chronic inflammatory process
 Stage of RA
1 month 6 months 2 years
DIAGNOSIS
 }

Classical appearance
Rare finding
Not always positive
Late finding
bvghtyy yyyyy

Aletaha et al.
Arthritis Rheuma
2010, 62: 2569–81
Aletaha et al.
Arthritis Rheuma
2010, 62: 2569–81
 Importance of Early Right Treatment of
RA
Radiographic evidence of
damage often established
within 1 to 2 years

Premature death
Disease onset

Early Established End stage

Window of opportunity
for disease control

Green M, et al. Arthritis Rheum. 1999;42:2184-2188.

Types of RA therapy currently available
Disease-modifying
Terapi simtomatik
therapies
• NSAIDs • Traditional DMARDs
• (COX-2) inhibitors • Biological agents
• Corticosteroids

Sifat Sifat

Tidak
menghentikan Mengurangi Mencegah Safety
Mengurangi Mengatasi
progresivitas progresivitas kerusakan
nyeri peradangan
dan kerusakan penyakit sendi lanjut issues
sendi

Gaffo A, et al. Am J Health Syst Pharm 2006; 63:2451–2465.

 Kenali segera dan obati segera
Deteksi dini Obati segera : agresif

• Deteksi dini menentukan • Pengobatan dini menentukan

keberhasilan pengobatan tercapainya remisi
• Memperbesar peluang • Hasil pengobatan klinik
untuk terhindar dari optimal
kerusakan sendi yang berat • Mencegah kerusakan sendi,
• Mencegah kecacatan,
• Memperbaiki kualitas hidup
• “Cost effective”
 RA dapat dikontrol dengan
CERMATI AR :
- Perhatikan gejala awal :
1. Tanda peradangan : merah, bengkak, hangat. CEk
2. > 3 sendi yang bengkak
3. Kaku sendi > 30 menit
4. Gejala > 6 minggu
- Tes Remas : remas sendi tangan / kaki.

Bila ada peradangan dan nyeri sendi , Terkontrol

segeralah berkonsultasi ke dokter ahli PeRiksa
rematologi.

Setelah mendapatkan pengobatan, amati

perjalanan penyakit. AMAti
Keuntungan mengamati pengobatan RA

Pilihan terapi
paling tepat

Meminimal-
Cost kan
effective progresivitas
penyakit

Personalized
treatment
pada RA

Melindungi
Efek samping sendi,
minimal mempertahan
kan fungsi

Memperbaiki
kualitas hidup

Isaacs J & Ferraccioli G. Ann Rheum Dis 2011;70:4–7.