Rheumatoid Arhtritis

Malikul Chair
 PENDAHULUAN
 RA  mengenai 0.5% s.d. 1% populasi di seluruh dunia
 RA terutama mengenai sendi, namun dapat juga menyebabkan manifestasi ekstra sendi:
vaskulitis, nodul, aterosklerosis dll
 Target utama penyakit RA adalah sinovium
 Merupakan penyakit autoimun  autoantibodi terhadap IgG (yaitu faktor reumatoid) dan
protein tersitrulinasi
 Tetapi ada sebagian pasien yang negatif terhadap autoantibodi tersebut
 Penyebab pasti RA belum diketahui, namun proses terjadinya RA melibatkan multifaktorial,
yang mencakup faktor genetik dan lingkungan

Kelley's textbook of rheumatology, 2013

Eular Rheumatoid Arthritis Classification Criteria, 2010
 Faktor risiko
1. Predisposisi genetik:
 STAT4 gene and CD40 locus
 human leukocyte antigen (HLA) genes  HLA‐DRB1*01 and HLA‐DRB1*04
 first-degree family members with SLE or other autoimmune diseases
2. Epigenetik  dna methylation, histone acetylation
3. Jenis kelamin  wanita 2-3x lebih tinggi
4. Merokok
5. Inhalasi debu
6. Mikrobiota:
1. Periodontal disease: oral microbiota, e.g. Porphyromonas gingivalis and
Aggregatibacter actinomycetemcomitans ;
2. Gut microbiota e.g. Prevotella copri ;
3. Virus e.g. parvovirus, EBV

Hohchberg Rheumatology; 2015

Kelley's textbook of rheumatology; 2013.
FAKTOR RISIKO

Smolen JS, et al. Lancet. 2016

 ETIOLOGI PATOGENIK
Key points

 Belum ditemukan hubungan etiologi yang pasti, namun beberapa patogen seperti virus,
bakteri, micoplasma ditemukan memiliki hubungan dengan RA
 Belum ditemukan suatu patogen RA yang tunggal dan spesifik, tetapi diketahui bahwa
mikrobiotik pada permukaan mukosa memiliki peranan penting dalam patogenesis RA

 Adanya patogen  stress inflamasi yang berulang  perubahan peptida melalui proses
sitrulinasi, kehilangan toleransi imun, dan autoimunitas.

Kelley's textbook of rheumatology; 2013.

 Patogen dapat menginisiasi penyakit RA melalui beberapa mekanisme:

1. Infeksi langsung terhadap sinovium

2. Aktivasi imunitas alami melalui pattern recognition receptor yang dapat

berikatan dengan patogen tersebut

3. Molecular mimicry yang dapat merangsang terbentuknya respon imun adaptif

Kelley's textbook of rheumatology; 2013.

Smolen, et al. Nat Rev Dis Primers. 2018 Feb 8;4:18001.
Schema of Articular Course Pattern
in RA
Clinical Manifestation: History

• Pain and stiffness in multiple joints (common)

o Initial symptoms at one location or few scattered sites in 33%
o may present with symmetric joint involvement
o multiple joints commonly involved
o morning stiffness lasting ≥ 45 minutes after initiating
movement is common
• Prodromal anorexia, weakness, or fatigue common
• Symptoms must be present ≥ 6 weeks for clear diagnosis
• Slowly progressive or variable course, flares common
Clinical Manifestation: Physical
Exam
• General physical: may have fever and weight loss
• Skin: subcutaneous (rheumatoid) nodules (30% in advanced
disease)
• Size is about 1-2 cm, usually found at pressure points -
elbow, knuckles, ischial spines, occiput, extensor
forearm, Achilles tendon
• Lungs: rales (crackles) may suggest interstitial fibrosis
• Abdomen: splenomegaly may indicate Felty syndrome
The presence of nodules  indicates seropositive and
more aggressive arthritis

Location = Flexor and extensor tendons of the hand,

sacrum, Achilles tendon, sclera, lungs and myocardium.
Clinical Manifestation: Physical Exam
Joints with highest ratio of synovium to articular cartilage most
commonly affected
• Location =
o Wrists, PIP, & MCP joints commonly affected
o DIP & Sacroiliac joints usually not affected
o Foot and ankle = MTP involvement is early sign of RA, valgus
deformities and flat-foot frequently seen in later stages
• Typically boggy, tender and warm, but usually not erythematous
• May have “puffy” hands secondary to increased blood flow to
inflamed areas
• Muscles near inflamed joints often atrophy
Clinical Manifestation

Squeeze test (compression pain in MCP and MTP joints)

 Clinical Manifestation
• Subluxation at the MCP joint
• Swan-neck deformity -- MCP
flexion, PIP hyperextension, DIP
flexion
• Boutonnière deformity -- PIP
flexion, DIP hyperextension
• Z deformity of the thumb
• Dorsal subluxation of the ulna at
the carpal joint.
Notes:
• Large joints = shoulders, elbows, hips, knees, and ankles
• Small joints = MCP joints, PIP joints, 2nd-5th MTP joints, thumb
interphalangeal joints, and wrists.
• Symmetric = bilateral involvement of at least 1 region.
• In the category “>10 joints,”  at least 1 small joint (+)
• The other joints can include any combination of large and additional small
joints, as well as other joints not specifically listed elsewhere (e.g.,
temporomandibular, acromioclavicular, sternoclavicular, etc.)
 For Prediction of Development of Rheumatoid Arthritis:
Sensitivity Specificity PPV NPV LR+ LR-

Anti-CCP antibody 83% 68% 71% 81% 2.6 0.12

Rheumatoid factor 67% 61% 60% 61% 1.7 0.54

Both (positive anti-CCP

antibody and positive 77% 84% 81% 81% 4.8 0.27
rheumatoid factor)

Abbreviations: LR+, positive likelihood ratio; LR-, negative likelihood ratio; NPV, negative predictive value; PPV, positive
predictive value.
Imaging Roles in RA?
• x-ray may be normal early in disease
• x-ray findings may include:
• marginal erosions
• joint space narrowing
• soft tissue swelling
• diffuse cartilage loss
• mild juxta-articular osteoporosis
• cortical thinning
Imaging Roles in RA?
Ultrasound  sensitive for detection of both:
• early inflammatory soft tissue lesions (such as synovitis, tenosynovitis,
and bursitis)
• early bone lesions (such as erosions) in arthritic joint diseases
• negative ultrasound findings may rule out development of
rheumatoid arthritis
Management
Goals = Disease remission (or at the very least a low
disease activity)  Treat-to-target
• normalizes physical function when achieved in early disease and
maximizes physical function in established disease;
• prevents occurrence of damage, or if joint destruction is present, its
progression
Management
• Early treat-to-target management improves disease
activity, physical function, and quality of life
• Late aggressive management is no better than
symptomatic therapy in patients with stable
rheumatoid arthritis
Nonpharmacologic management
• Patient education
• Exercise as well as physical and occupational therapies :
low impact exercise
• Cognitive therapies (may improve psychological
outcomes)
• Diet? insufficient evidence to evaluate efficacy of dietary
manipulation (including vegetarian, Mediterranean,
elemental, and elimination diets) for rheumatoid arthritis
Exercise/Physical Therapy in RA
• Physical and occupational therapies
• Maintaining joint function include:
o joint protection
o joint range of motion and strengthening exercises
o energy conservation
• Other exercise that may improve quality of life, function, and
pain:
o Aerobic exercise, resistance exercise
o Others: yoga, Tai Chi, hydrotherapy
Pharmacologic management
• DMARDS  first-line therapy
• Drugs for symptom control:
o NSAIDs
o Short-term oral corticosteroids (eg prednisone ≤ 15 mg/day)
o Intra-articular steroid injection
o Longer-term use of low-dose steroids
o Others: opioids, topical capsaicin cream, suprascapular nerve
block
DMARD Classifications for treating
RA
Non-Biologic DMARDS
1. Methotrexate 2.5-25 mg PO/IM/SC once weekly (plus folic
acid 1-4 mg/day or folinic acid 2.5-10 mg/week 24 hours
after MTX)
2. Leflunomide 10-20 mg/day PO (risk of severe liver toxicity
increased with concomitant methotrexate)
3. Sulfasalazine 2-3 g/day PO for patients with low disease
activity

Lab monitoring (CBC, liver function, serum creatinine) for leflunomide,

methotrexate, or sulfasalazine every 2-4 weeks for 3 months following dose
Non-Biologic DMARDS
Low-toxicity DMARDs used for patients with low
disease activity and without poor prognostic features
include:
1. Hydroxychloroquine 200-400 mg/day orally
Biologic DMARDS
Generally recommended after failure of nonbiologic
DMARDs, especially if moderate to high disease activity
or poor prognostic features:
1. Tumor necrosis factor (TNF) inhibitors
2. Abatacept
3. Tocilizumab
4. Anakinra
5. Rituximab
Treatment Algorithm in RA - EULAR 2016
Failure Phase I
Failure Phase II
Poor Prognostic Factors

1. Moderate (after csDMARD therapy) to high disease activity

according to composite measures
2. High acute phase reactant levels
3. High swollen joint counts
4. Presence of RF and/or ACPA, especially at high levels
5. Combinations of the above
6. Presence of early erosions
7. Failure of two or more csDMARDs
Disease activity states
1. Remission
2. Low disease activity
3. Moderate, high disease activity
Remission Criteria
• Remission is a state, not change or transition
• Absence of disease activity
• Not identical to "Cure“
• Antithetical to "Relapse", "Flare"
 Instruments to measure rheumatoid arthritis
disease activity and to define remission

Singh JA, et al. Arthritis & rheumatology. 2016 Jan 1;68(1):1-26.

RA pada kondisi tertentu
VAKSINASI

• Vaksinasi hidup tidak diperbolehkan diberikan pada pasien AR yang

mendapat terapi DMARD
• Vaksinasi yang dianjurkan sebelum pemberian DMARD adalah
influenza, pneumokokus, herpes zoster, hepatitis B dan HPV
AR PADA KEHAMILAN

• Kehamilannya harus dipersiapkan atau direncanakan, disarankan

setelah LDA atau remisi
• Obat-obatan yang digunakan harus dievaluasi keamanannya untuk
pasangan yang berencana memiliki keterunan, serta selama proses
kehamilan dan laktasi
• Aktivitas penyakit harus dievaluasi lebih ketat pada masa postpartum,
karena risiko kekambuhan yang meningkat
Manajemen Terapi pada Pasien laki-laki AR
yang Berencana Memiliki Anak

Obat Rekomendasi

Methotreksat Tunda 3 bulan sblm konsepsi : oligospermia

sulfasalazin Mengganggu kesuburan : infertilitas

azatioprin aman

leflunomid Tidak ada hasil yang merugikan

antiTNF-alfa Secara keseluruhan data : menguntungkan

rituximab Terdapat efek samping yang merugikan

abatacept Terdapat efek samping yang merugikan