Rheumatoid Arthritis

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• Rheumatoid Arthritis
• (RA)
• I. General Considerations
• Systemic autoimmune disease
• Chronic poly-arthritis, usually symmetric
• Mainly involve peripheral joints

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II. Etiology

• Genetic Background
• HLA-DR
• Infections Agents
• especially Epstein-Barr Virus

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III. Pathogenesis

• Activation of both B and T lymphocytes

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IV. Pathology

• Synovitis
• Infiltrates of inflammatory cells
• Angiogenesis
• Synovial cell proliferations

• Formation of Pannus
• Destruction of cartilage and Subchondral bone
• ?
• Narrowing of joint space and bone erosion

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Pathology

• IV. Pathology

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V. Clinical Features of RA
1. Articular Manifestations a. polyarthritis
(1)symmetrical (2)6 weeks
(3)wrists, hand joints, knee, feet joints
commonly affected (4)erosive
(5)deformity b. motion of joints limited
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Frequently involved joints

• PIP
• proximal interphalangeal joint
• DIP
• Distant Interphalangeal joint
• MCP
• Metacarpophalangeal joint
• Wrist
• MTP
• Metatarsophalangeal joint

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Spindle finger

• Swollen of the PIP joints makes the finger
  spindle shape

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Common deformities

• Swan-neck deformity Hyperextension of the PIP
  in conjunction with flexion of DIP joint .

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Boutonniere deformity Flexion of PIP joints
and extension of the DIP joints.
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ulnar deviation

• frequently accompanied
• by palmar subluxation of
• the proximal phalanges.

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Ulnar deviation with muscle atrophy
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2. Extra-articular Manifestations
Skin (1) Subcutaneous nodules
(2) Vasculitis
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• Subcutaneous nodules with muscle atrophy

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ulnar deviation with the vasculitis-induced
finger necrosis after surgical resection
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ischemic necrosis due to vasculitis
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• Cardiac Manifestations
• (1)Pericarditis
• (2)myocarditis
• (3)valvular insufficiency

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Pulmonary Manifestations 1. Rheumatoid pleural
disease pleural effusion exudative,
low glucose, LDH elevated, Low
complement, RF Multiple subpleural
nodules. 2. Nodular change Rheumatoid nodule in
the lung. 3. Diffuse interstitial fibrosis
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• Neurologic Manifestations
• (1) Mononeuritis Multiplex
• Sensory loss, foot, wrist drop
• (2) Carpal tunnel Syndrome
• Ocular Manifestations
• Sjogren Syndrome Causing corneal and
• conjunctival lesions along with
• dryness of the eyes.
• episcleritis, scleritis

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• Felty Syndrome
• Splenomegaly, lymphadenopathy,
• anemia, Bpc ? WBC ? , RF positive

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VI. Lab Findings in RA Test
Characteristic Results Blood
Elements Moderate normochromic, normocytic
anemia Erythrocytes Low plasma iron,
decreased total iron binding
Capacity Leukocytes Normal or
slightly elevated
Leukopenia rare ( Felty Syn. ) Acute-phase
Reactants and immunoglobulin ESR
Increased C-Reactive Protein (CRP)
positive Ig. IgG
increased, IgA, M increased Immune Factors
ANA Present in 15 RF
Present in 70 Complement
Normal or slightly elevated
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Rheumatoid Factors
RF are now defined as antibodies
specific to antigenic determinants on the Fc
fragments of human or animal immunoglobulin.
Seropositivity of patients with RA or with
other disease is usually defined by the latex
fixation test or red cell agglutination
tests. These assays reflect the presence of
IgM Rheumatoid factors (IgM-RFs). The presence
of RF is not unique to RA, and a positive RF
should not be used as the sole criterion for
the diagnosis of RA.
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Occurrence of RF in various Dis IgM-RF
Negative Rheumatoid Arthritis
Osteoarthritis Other rheumatic
Diseases Ankylosing Spondylitis
Sjogrens Syn SLE, PSS, PM
Gout Infections Diseases
Psoriatic arthritis SBE TB Non-infections
Disease Normal individuals (Aged) Chronic
active hepatitis Diffuse Interstitial
pulmonary fibrosis
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• Radiological Examination
• S-soft tissue
• A-alignment
• B-bone
• C-cartilage

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erosion
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Classification of Progression of RA Stage 1,
Early 1. No destructive changes on X-ray
film 2. Radiological evidence of
osteoporosis Stage II, moderate Osteoporosis
with Slight Subchondral bone destruction, No
joint deformities Stage III, Severe 1.
Radiological evidence of cartilage and
bone destruction 2. Joint deformity without
ankylosis Stage IV 1. Fibrous or bony
ankylosis 2. Criteria of Stage III.
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VII. Proposed 1987 Revised ARA criteria for
RA 1. Morning stiffness for at least one hour
and Present for at least six weeks 2.
Swelling of three or more joint6 weeks 3.
Swelling of wrist, MCP or PIP joints6 weeks 4.
Symmetric Joint swelling 5. Hand X-ray changes
typical of RA that must include erosions or
unequivocal bony decalcification 6. Rheumatoid
nodules 7. Serum RF positive Four or more
criteria must be present to diagnose RA
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Differential Diagnosis
Rheumatic Fever Osteoarthritis SLE Ankylosing
Spondylitis ( AS )
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The Hand in Rheumatoid Arthritis
and in Osteoarthritis Criter
ia Rheumatoid Arthritis
Osteoarthritis Character of Swelling Synovial,
Capsular, Bony with
Soft-tissue, bony
irregular
only in late stages Spurs Tenderness
Usual
None or mild

except during

occasional
acute
onset DIP involvement Not usual,
except Characteristic
thumb PIP involvement
Characteristic Frequent MCP
involvement Characteristic
Rare Wrist involvement Usual or common
Rare, except

base of thumb
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Clinical Course of RA Progressive
Chronic disease with remission
and exacerbations but continuing
disease activity
(70) Intermittent Brief attacks with
intermittent remissions
with no disease activity
(25) Malignant Severe disease with
extra-articular
manifestations, especially vasculitis
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VIII. Treatment
Objective of treatment

• 1. relief of pain
• 2. reduction or suppression of inflammation
• 3. minimizing undesirable effects
• 4. preservation of muscle and joint function
• 5. return to a desirable and productive life

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Drug Therapy

• 1. Non-steroid Anti-inflammatory
• Drugs ( NSAIDs )
• a. Analgesic
• b. Anti-inflammatory
• c. Anti-pyrexia

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Processes influenced by NSAIDs
Prostaglandin Production Leukotriene
Synthesis Superoxide
Generation Lysosomal enzyme release
Neutrophil aggregation
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Adverse effects of NSAIDs

• a. Gastrointestinal effects
• b. Hepatic effects
• c. Renal effects
• d. others skin rash

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COX-1/COX-2 Theory

• COX-1
• Constitutive
• Homeostatic functions
• GI tract
• Renal function
• Platelet function

• COX-2
• Regulated
• Inflammation

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• The advantage of selective COX-2 inhibition
• NSAIDs with a good GI side effect profile
  have been
• shown to have lower ratios of COX-2/COX-1
  inhibition
• Newly designed selective COX-2
  inhibitors have
• significantly fewer GI side effects compared
  with traditional
• NSAIDs

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• 2. Disease - Modifying Anti-rheumatic
• Drugs ( DMARDs)
• Features of DMARDs
• a. Modifying the progression of RA
• b. Slow acting
• c. More adverse effects

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Disease-Modified Anti-rheumatic Drugs (
DMARDs) Drug
Major adverse
reaction Methotrexate (MTX) Hepatic
fibrosis, Nausea, Cytopenia
Anti-malanial (CQ
HCQ) Visual disturbance Leflunomide
(LEF) Hepatic
damage Sulfasalazine (SASP)
GI irritation, rashes
D-penicillamine (D-PA) Rashes,
Proteinuria, Cytopenia,
Taste disturbance
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Principles for DMARDs therapy

• 1. early use
• 2. combination therapy

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Common combination therapy

• MTXCQ(HCQ)
• MTXSASP
• MTXLEF

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3. Corticosteroids usually low dose
(below 10mg/day) combined with DMARDs
Indications for Large doses
Rheumatoid vasculitis Felty Syn
High fever (Systemic Onset)
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Biological agents

• Anti-TNFa preparations
• Infleximab and Etanercept

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Surgical treatment

1. Synovectomy
2. Joint replacement

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Comprehension questions

• female, 30 years old , joint pain with low fever
  for two months, RF ()
• diagnosis RA ?
• Choice yes ,no, uncertain

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• Thank you