DR MD REZAULKARIM DR MD REZAULKARIM
PROFESSOR PROFESSOR
Department of Biochemistry and Department of Biochemistry and
molecular Biology molecular Biology
Rheumatoid Arthritis
Rheumatoid Arthritis
Arthritis Arthritis
“arthro” = joint
“itis” = inflammation
“Arthritis can affect babies and children, as well as people in the prime of their lives”
• Rheumatoid arthritis is an autoimmune disease in which the normal immune response is directed against an individual's own tissue, including the joints, tendons, and bones, resulting in
inflammation and destruction of these tissues.
• Commonest inflammatory joint disease seen in clinical practice affecting approx 1% of population.
• Characterized by persistent inflammatory synovitis leading to cartilage damage, bone erosions, joint deformity and disability.
Anatomy of the Joint
Articular/hyaline cartilage -acts as a shock absorber
- allows for friction-free movement - not innervated!
Synovial membrane/synovium -secretes synovial fluid
-nourishes cartilage -cushions the bones
Overview Overview
Age: Any age, commonly 3Age: Any age, commonly 3rdrd to 6 to 6thth decade decade
Female: male 3:1Female: male 3:1
pattern of joint involvement could be:-pattern of joint involvement could be:-
1)1) Polyarticular : most commonPolyarticular : most common
2)2) OligoarticularOligoarticular
3)
3) MonoarticularMonoarticular
Morning joint stiffness > 1 hour Morning joint stiffness > 1 hour and easing with physical activity is and easing with physical activity is characteristic.
characteristic.
Small joints of hand and feet Small joints of hand and feet are typically involved.are typically involved.
Clinical Manifestations Clinical Manifestations
Articular Articular
Extra-articular Extra-articular
Articular manifestation Articular manifestation
Pain and swelling in Pain and swelling in affected joint
affected joint aggravated by aggravated by
movement is the most movement is the most
common symptom.
common symptom.
Morning stiffness ≥1 Morning stiffness ≥1 hr hr
Joints involved - Joints involved -
Joints involved in RA Joints involved in RA
Don’t forget the Don’t forget the cervical spine cervical spine !! !!
Instability at cervical spine can lead to Instability at cervical spine can lead to
impingement of the spinal cord.
impingement of the spinal cord.
Thoracolumbar, sacroiliac, and distal Thoracolumbar, sacroiliac, and distal
interphalangeal joints (DIP)of the hand are
interphalangeal joints (DIP)of the hand are
NOT NOT involved. involved.
PIP Swelling
PIP Swelling
Ulnar Deviation, MCP Swelling, Ulnar Deviation, MCP Swelling,
Left Wrist Swelling
Left Wrist Swelling
Extra-articular Extra-articular
manifestations manifestations
Present in 30-40% Present in 30-40%
May occur prior to arthritisMay occur prior to arthritis
Patients that are more likely to get are:Patients that are more likely to get are:
High titres of RF/ anti-CCPHigh titres of RF/ anti-CCP
HLA DR4+HLA DR4+
Male Male
Early onset disabilityEarly onset disability
History of smokingHistory of smoking
Constitutional symptoms Constitutional symptoms ( most ( most common)
common)
Rheumatoid nodules Rheumatoid nodules (30%) (30%)
Hematological Hematological - -
normocytic normochromic anemia normocytic normochromic anemia
leucocytosis /leucopenia leucocytosis /leucopenia
thrombocytosis thrombocytosis
Felty’s syndrome- Felty’s syndrome-
Chronic nodular Rheumatoid Arthritis Chronic nodular Rheumatoid Arthritis
Spleenomegaly Spleenomegaly
Neutropenia Neutropenia
Extraarticular Extraarticular
Involvement
Involvement
Respiratory Respiratory - pleural effusion, pneumonitis , - pleural effusion, pneumonitis , pleuro-pulmonary nodules, ILD
pleuro-pulmonary nodules, ILD
CVS CVS -asymptomatic pericarditis , pericardial -asymptomatic pericarditis , pericardial effusion, cardiomyopathy
effusion, cardiomyopathy
Rheumatoid vasculitis Rheumatoid vasculitis - mononeuritis - mononeuritis multiplex, cutaneous ulceration, digital multiplex, cutaneous ulceration, digital
gangrene, visceral infarction gangrene, visceral infarction
CNS CNS - peripheral neuropathy, cord- - peripheral neuropathy, cord-
compression from atlantoaxial/midcervical compression from atlantoaxial/midcervical
spine subluxation, entrapment neuropathies spine subluxation, entrapment neuropathies
EYE EYE - kerato-conjunctivitis sicca, episcleritis, - kerato-conjunctivitis sicca, episcleritis, scleritis
scleritis
Rheumatoid nodule Rheumatoid nodule
•These are small subcutaneous nodules present at the extensor surfaces of hand, wrist, elbow and back in rheumatoid
arthritis patients.
•Characteristics feature of rheumatoid arthritis
•A marker of disease activity
•Can be present even if other features of rheumatoid Arthritis are absent
Laboratory investigations Laboratory investigations
in RA in RA
CBC- TLC, DLC, Hb, ESR & GBP CBC- TLC, DLC, Hb, ESR & GBP
Acute phase reactants Acute phase reactants
Rheumatoid Factor (RF) Rheumatoid Factor (RF)
Anti- CCP antibodies Anti- CCP antibodies
Rheumatoid Factor (RF) Rheumatoid Factor (RF)
Antibodies that recognize Fc portion of IgGAntibodies that recognize Fc portion of IgG
Can be IgM , IgG , IgACan be IgM , IgG , IgA
85% of patients with RA over the first 2 years become RF+85% of patients with RA over the first 2 years become RF+
• A negative RF may be repeated 4-6 monthly for the first two year of A negative RF may be repeated 4-6 monthly for the first two year of disease, since some patients may take 18-24 months to become disease, since some patients may take 18-24 months to become
seropositive.
seropositive.
• PROGNISTIC VALUEPROGNISTIC VALUE- Patients with high titres of RF, in general, - Patients with high titres of RF, in general, tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR tend to have POOR PROGNOSIS, MORE EXTRA ARTICULAR
MANIFESTATION.
MANIFESTATION.
Anti-CCP Anti-CCP
IgG against synovial membrane IgG against synovial membrane
peptides damaged via inflammation peptides damaged via inflammation
Sensitivity (65%) & Specificity (95%) Sensitivity (65%) & Specificity (95%)
Both diagnostic & prognostic Both diagnostic & prognostic value
value
Predictive of Erosive Disease Predictive of Erosive Disease
Disease severity Disease severity
Radiologic progression Radiologic progression
Poor functional outcomes Poor functional outcomes
Elevated APRs( ESR, CRP ) Elevated APRs( ESR, CRP )
Thrombocytosis Thrombocytosis
Leukocytosis Leukocytosis
ANA ANA
30-40% 30-40%
Inflammatory synovial fluid Inflammatory synovial fluid
Hypoalbuminemia Hypoalbuminemia
Radiographic Features Radiographic Features
Peri-articular osteopeniaPeri-articular osteopenia
Uniform symmetric joint space narrowingUniform symmetric joint space narrowing
Marginal subchondral erosionsMarginal subchondral erosions
Joint Subluxations Joint Subluxations
Joint destructionJoint destruction
CollapseCollapse
Ultrasound Ultrasound detects early soft tissue lesions.detects early soft tissue lesions.
MRI MRI has greatest sensitivity to detect synovitis and has greatest sensitivity to detect synovitis and marrow changes.
marrow changes.
ACR Diagnostic Criteria (1987) ACR Diagnostic Criteria (1987)
Description Description
Morning stiffness Morning stiffness
Arthritis of 3 or more joints Arthritis of 3 or more joints
Arthritis of hand joints Arthritis of hand joints
Symmetric arthritis Symmetric arthritis
Rheumatoid nodules Rheumatoid nodules
Serum rheumatoid factor Serum rheumatoid factor
Radiographic changes Radiographic changes
A person shall be said to have rheumatoid A person shall be said to have rheumatoid
arthritis if he or she has satisfied 4 of 7 criteria, arthritis if he or she has satisfied 4 of 7 criteria,
with criteria 1-4 present for at least 6 weeks
with criteria 1-4 present for at least 6 weeks . .
Goals of management Goals of management
Focused on relieving pain Focused on relieving pain
Preventing damage/disability Preventing damage/disability
Patient education about the disease Patient education about the disease
Physical Therapy for stretching and range of motion Physical Therapy for stretching and range of motion exercises
exercises
Occupational Therapy for splints and adaptive devices Occupational Therapy for splints and adaptive devices
Treatment should be started early and Treatment should be started early and should be individualised .
should be individualised .
EARLY AGGRESSIVE TREATEMNT EARLY AGGRESSIVE TREATEMNT
Treatment modalities Treatment modalities
for RA for RA
NSAIDS NSAIDS
Steroids Steroids
DMARDs DMARDs
Immunosuppressive therapy Immunosuppressive therapy
Biological therapies Biological therapies
Surgery Surgery
NSAIDS NSAIDS
Non-Steroidal anti-inflammatories Non-Steroidal anti-inflammatories
(NSAIDS) / Coxibs for symptom control (NSAIDS) / Coxibs for symptom control
1)1)
Reduce pain and swelling by inhibiting COX Reduce pain and swelling by inhibiting COX
2)2)
Do not alter course of the disease. Do not alter course of the disease.
3)3)
Chronic use should be minimised. Chronic use should be minimised.
4)4)
Most common side effect related to GI tract. Most common side effect related to GI tract.
Corticosteroids in Corticosteroids in
RA RA
Corticosteroids , both systemic and intra- Corticosteroids , both systemic and intra- articular are important adjuncts in
articular are important adjuncts in management of RA.
management of RA.
Indications for systemic steroids are:- Indications for systemic steroids are:-
1.1.
For treatment of rheumatoid flares. For treatment of rheumatoid flares.
2.2.
For extra-articular RA like rheumatoid For extra-articular RA like rheumatoid vasculitis and interstitial lung disease.
vasculitis and interstitial lung disease.
3.3.
As As bridge therapy bridge therapy for 6-8 weeks before the for 6-8 weeks before the action of DMARDs begin.
action of DMARDs begin.
4.4.
Maintainence dose of 10mg or less of Maintainence dose of 10mg or less of
predinisolone daily in patients with active RA.
predinisolone daily in patients with active RA.
5.5.
Sometimes in pregnancy when other DMARDs Sometimes in pregnancy when other DMARDs cannot be used.
cannot be used.
Disease Modifying Anti-rheumatic Agents Disease Modifying Anti-rheumatic Agents
Drugs that actually alter the disease course . Drugs that actually alter the disease course .
Should be used as soon as diagnosis is made. Should be used as soon as diagnosis is made.
Appearance of benefit delayed for weeks to Appearance of benefit delayed for weeks to months.
months.
NSAIDS must be continued with them until true NSAIDS must be continued with them until true remission is achieved .
remission is achieved .
Induction of true remission is unusual . Induction of true remission is unusual .
DMARDs DMARDs
Commonly used Less commonly used
Methotrexate Chloroquine
Hydroxychloroquine Gold(parenteral &oral) Sulphasalazine CyclosporineA
Leflunomide D-
penicillamine/bucillamine Minocycline/Doxycycline Levamisole
Azathioprine,cyclophosph amide, chlorambucil
Immunosuppresive
Immunosuppresive therapy therapy
Agent Usual dose/route Side effects
Azathioprine 50-150 mg orally GI side effects , myelosuppression, infection,
Cyclosporin A 3-5 mg/kg/day Nephrotoxic , hypertension , hyperkalemia Cyclophosphamid
e
50 -150 mg orally Myelosuppression , gonadal toxicity
,hemorrhagic cystitis , bladder cancer
. .
Surgical Surgical Approaches Approaches
Synovectomy is ordinarily not recommended for Synovectomy is ordinarily not recommended for
patients with rheumatoid arthritis, primarily because patients with rheumatoid arthritis, primarily because
relief is only transient.
relief is only transient.
However, an exception is synovectomy of the wrist, However, an exception is synovectomy of the wrist,
which is recommended if intense synovitis is persistent which is recommended if intense synovitis is persistent
despite medical treatment over 6 to 12 months.
despite medical treatment over 6 to 12 months.
Persistent synovitis involving the dorsal compartments Persistent synovitis involving the dorsal compartments of the wrist can lead to extensor tendon sheath rupture of the wrist can lead to extensor tendon sheath rupture
resulting in severe disability of hand function.
resulting in severe disability of hand function.
Total joint arthroplasties , particularly of the knee, hip, Total joint arthroplasties , particularly of the knee, hip, wrist, and elbow, are highly successful.
wrist, and elbow, are highly successful.
Other operations include release of nerve entrapments Other operations include release of nerve entrapments (e.g., carpal tunnel syndrome), arthroscopic
(e.g., carpal tunnel syndrome), arthroscopic
procedures, and, occasionally, removal of a symptomatic procedures, and, occasionally, removal of a symptomatic
rheumatoid nodule.
rheumatoid nodule.
Thank
you.
