RHEUMATOID ARTHRITIS

RHEUMATOID ARTHRITIS

Definiton
Chronic systemic inflammatory disease mainly affecting the joints.

Etiology

• Genetic susceptibility
• Gender: women before menopause are affected 3 times more than
men
• Familial: Increase incidence in those with a family history of RA
• Immunological reaction possibly involving a foreign body mainly on
the synovial tissue
• Inflammatory reaction in joints and tendon sheaths
• Appearance of rheumatoid factors ( RF) and anti-citrullinated
antibodies ( anti-CCP)
• Perpetuation of inflammatory process
Pathology

Stage 1 : Pre-clinical

• Raised in ESR, C-reactive protein and RF may be detectable years

before diagnosis.

Stage 2: Synovitis

• Vascular congestion with new blood vessel formation ( early changes)

• Proliferation of synoviocytes
• Infiltration of subsynovial layers by polymorphs, lymphocytes and
plasma cells
• Thickening of capsular structures, villous formations and cell-rich
effusion into joints and tendons
• Structures are still intact and mobile ( potentially reversible)
Stage 3: Destruction

• Persistent inflammation causes destruction of joints and tendons

• Articular cartilage is eroded partly by proteolytic enzymes, some by
vascular tissue, direct invasion of the cartilage by pannus of granulation
tissue creeping over the articular surface)
• Bone is eroded by tissue invasion and osteoclastic resorption.
• Rupture of tendons
• Synovial effusion, often containing copious amount of fibrinoid material ,
produces swelling of joints, tendons and bursae.

Stage 4: Deformity

• Combination of articular destruction, capsular stretching and tendon

rupture leads to progressive instability and deformity of the joints
• Inflammatory process continues but mechanical and functional effects of
joints and tendon now become vital.
Clinical features

Early stage

• Early morning stiffness ( lasting more than 30 mins)

• Onset of pain
• Symmetrical distributed swelling and tenderness at the
metacarpophalangeal joints and proximal interphalangeal joints and
wrist
• Loss of mobility in the proximal joints of fingers
Later stage

• Joint deformity becomes increasingly apparent

• Acute pain replaced with more constant ache cause by progressive joint
destruction
• Joint instability
• Tendon rupture
• Ulnar deviation of fingers, radial displacement of wrists
• Valgus knees,feet and clawed toes
• Restricted movements of joint
• Swan-neck deformities
Non-articular features

• Systemic : Fever, fatigue

• Neurological : Carpal tunnel syndrome, cord compression
• Haematological: Lymphadenopathy, Felty’s syndrome( RA,
splenomegaly, neutropenia), anemia
• Vasculitis : Leg ulcer, gangerene
Investigations

Imaging

1. X-rays
• Earlier stage,shows features of synovitis ( soft tissue swelling and peri-
articular osteoporosis)
• Appearance of marginal bony erosions and narrowing or articular
space at the later stage. Mostly within 2 years.
• In advanced disease, articular destruction and joint deformity are
obvious.

2. Ultrasound scanning and MRI

• Soft tissue changes and early erosions within the joints.
Blood investigations
• Raised in ESR and C-reactive protein
• Serological test for RF are positive in 80% of patient and antinuclear factors in 30%

Diagnosis of RA
• For 6 weeks or more
• -morning stiffness >30mins
-Arthritis of three or more joints
• Symmentrical arthritis
• Subcutaneous nodules
• A positive serum RF
• Typical radiological changes( erosions and, or periarticular osteopenia)
 TREATMENT AND
MANAGEMENT OF RHEUMATOID
ARTHRITIS
PRINCIPLES OF THERAPY
Goals of Early Treatment
• To achieve clinical and radiological remission of disease
• Low disease activity is a treatment goal alternative in long standing disease
• To reduce functional limitations and permanent joint damage

Treat-to-target (T2T) treatment strategy, formulated in 2010, has resulted in

better disease outcomes. It includes:
• a defined treatment target (clinical remission or at least low disease activity)
• shared decision making
• assessment of disease activity
• regular adjustment of treatment
 PHARMACOLOGICAL TREATMENT
• should be initiated as soon as RA diagnosis is made
• Goals: reduce pain, swelling, stiffness, prevent articular damage and bone
erosions, prevent deformities & preserve joint function

 Disease Modifying Anti-Rheumatoid Drugs*

 conventional synthetic DMARDs (csDMARDs)
 targeted synthetic DMARDs (tsDMARDs)
 biologic DMARDs (bDMARDs)

 Adjuvant therapy
 Analgesics
 Corticosteroids
 NSAIDs
Conventional Synthetic DMARDs
• methotrexate, sulfasalazine , hydroxychloroquine and leflunomide
• slow the disease course and prevent further damage to the joints
• American College of Rheumatology
• DMARDs to be initiated within 3 months of diagnosis

Methotrexate
• Recommended as the first choice of DMARDs at doses of 10–25 mg/week
• Folic acid antagonist with cytotoxic & immunosuppressant activity with potent
anti-rheumatoid action at a low dose
• Preferred DMARD for both early and established rheumatoid arthritis
• Combination therapy may be required (MTX + Leflunomide/ Etanercept)
• Contraindicated in pregnancy, lactating mothers, liver disease
Leflunomide
• Recommended as part of the initial treatment strategy in patients with
contraindication to or intolerance of Methotrexate
• Inhibits proliferation of stimulated lymphocytes in patients with active RA
• Inhibits the enzyme dihydroorotate dehydrogenase, necessary for pyrimidine
synthesis
• slows the progression of structural damage by inhibiting osteoclast production

Sulfasalazine
• Recommended as part of the initial treatment strategy in patients with
contraindication to or intolerance to Methotrexate
• One of the most active compounds in terms of frequency of remissions and time to
onset of action
Hydroxychloroquine
• Is the same as the other DMARDs on its slow onset action
• As monotherapy or in combination therapy
• treatment option for patients with early or established rheumatoid arthritis if
Methotrexate is unavailable or with intolerance

Gold Salts (Parenteral)

• Recommended as part of the early treatment strategy in patients with
contraindication to or intolerance of Methotrexate
• Patients shows improvements from disappearance of rheumatoid nodules,
reduction of joint swelling and a fall with C-reactive protein (CRP) levels
Targeted Synthetic DMARDs
• Eg Baricitinib, Tofacitinib
• Janus kinase (Jak) inhibitors are recommended for patients with treatment failure
after biologic DMARDs
• May also be considered as initial therapy in DMARD-naive patients
Biologic DMARDs
• agents designed to specifically target immune cells involved in the pathogenesis of RA
• Expensive, reserve drugs

 TNF Inhibitors: Etanercept (Modified TNF receptor), Infliximab, Adalimumab(monoclonal

antibody)

 Recommended for the following:

o Early rheumatoid arthritis patients with high disease activity (with or without Methotrexate)
o Established RA patients with low disease activity where DMARD monotherapy with added Methotrexate,
Hydroxychloroquine and Leflunomide have failed
o Established RA patients where 1st TNF inhibitor regimen has failed (ACR recommends switching to another
TNF inhibitor or replacing the TNF inhibitor with Abatacept, Rituximab or Tocilizumab)
o Adalimumab, Etanercept and Certolizumab may be given as monotherapy in patients with intolerance of
Methotrexate or if treatment with Methotrexate is considered to be inadequate
o Certolizumab in combination with Methotrexate is indicated for the treatment of moderate-severe rheumatoid
arthritis in patients whose response to conventional synthetic DMARDs including Methotrexate, has been
inadequate
 Increased risk for infections: fungal opportunistic infections, and pancytopenia, risk of
lymphomas

 Interleukin-6 (IL-6) receptor blocker: tocilizumab (TCZ)

 Anti-B cell agent: Rituximab
Monitoring Treatment With DMARDs
• These drugs need frequent monitoring
• Blood, liver, lung, and kidney are frequent sites of adverse effects
• Interval of laboratory testing varies with the drug
• 4- to 8-week intervals are commonly needed
• Most patients need to be seen 3 to 6 times a year
Adjunctive Therapy
Analgesics
• Eg Paracetamol, Aspirin
Corticosteroids
• Low-dose prednisone (10 mg qd)
o can be used in combination with DMARD therapy for short term relief of signs and symptoms,
and in the medium to long term to minimize radiological damage
• Therapies:
o bridging therapy*
o continuous low-dose therapy
o short-term high-dose bursts to control flares
• Intra-articular corticosteroids are used to provide rapid, symptomatic relief in the
target joints
• May be administered to any joint not >3-4x/year
• If used long term, consider prophylactic treatment for osteoporosis
o Oral supplementation with daily calcium (Ca) (1000-1200 mg) and vitamin D (600-800 IU) should
be given to limit bone demineralization
o Fracture risk assessment
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Symptomatic relief, improved function but no change in disease
progression
• Interferes with prostaglandin synthesis through inhibition of the
enzyme cyclo-oxygenase
• Screen for risk factors for NSAID-induced ulcers before prescribing:
o Age > 60yrs
o Past H/O peptic ulcer
o Concomitant corticosteroid use
o High dose/ multiple NSAIDs
• Start with lowest dose of an agent with established safety
• Avoid prescribing two NSAIDs at the same time
• Allow a 2-3 weeks trial to assess the efficacy
SURGICAL INTERVENTION
• Surgical referral should be done before damage or deformity becomes irreversible in the following cases:
 Actual or imminent tendon rupture
 Nerve compression (eg Carpal tunnel syndrome)
 Stress fractures

• Indications
• Unacceptable levels of pain
• Persistent localized synovitis
• Worsening joint function (ie. instability or severe loss of range of joint motion)
• Progressive deformity

• Benefits
• Deformity prevention
• Joint function improvement and/or prevention of further deterioration
• Pain relief
SURGICAL PROCEDURES
Arthrodesis
• Advantage: Provides stability and relief from pain
• Indication: Young, active patients with severe
unilateral joint involvement
• Contraindication: Involvement of contralateral hip

First Metatarsalphalangeal joint

arthrodesis

Fusion at the IP joint with an iliac bone grafting

Arthroplasty
• Total knee arthroplasty is the surgical treatment of choice
in most patients with rheumatoid arthritis affecting the
knees
• Relieves pain and may increase range of motion in patients with
advanced RA who did not benefit from synovectomy
• Indication:
 Patients with rheumatoid arthritis class III or class IV without
multiple joint, ipsilateral hip or ankle or contralateral or both
knee involvement
• Complications:
• Deep wound infection
• Involves multiple joints limiting rehabilitation
• Poor tissue healing
• Severe flexion contracture, joint laxity and osteopenia

Total Knee Arthroplasty

Synovectomy
• Indicated in cases of inappropriate response to
pharmacologic management after 6 months
• Disease should be limited to synovial membrane
but may involve little cartilage or bone or if any
narrowing of joint space as seen on radiograph
• Arthroscopic knee synovectomy controls synovitis,
improvement in pain and preserves existing range
of motion
Other Procedures
• Finger small joints fusion/arthroplasty
• Joint replacement
• Tendon reconstruction
• Tendon transfers
• Total joint arthroplasty
• Tenosynovectomy
REFERENCES
• Apley’s System of Orthopaedics and Fractures
• CPG Management of Rheumatoid Arthritis
• MIMS Rheumatoid Arthritis Treatment