Rheumatoid Arthritis Pathology - Rheumatic Disorders & Tendinitis

Pathology

Underlying process is Immune Complex Depositions
Causing uncontrolled & ongoing inflammatory response
Rheumatoid Factor » Antibodies formed to IgG Fc portion
Three parts
- Synovitis
- Vasculitis
- Secondary changes » mechanical & enzymatic destruction with resultant deformity

Synovitis

Synovial Reaction
Non-suppurative chronic inflammation of the synovium
Angiogenesis
- 1st stage
- Due to vascular budding & synovial invasion
- Result of some vasculoproliferative factor released by activated cells
Inflammatory Infiltrate
- Lymphocytes adhere to & migrate through walls of newly formed vessels
  - T Cells > B Cells
  - Enhanced by growth factor
- Helper T Cells activate B Cells » transformation into Plasma Cells
  - Contain Russell Bodies (inclusions of Ig complexes)
Hyperplasia
- Increase in cell number (A & B synovial cells)
  - Intima hypertrophies from 1-2 cells thick to 10 cells thick
  - Papillary pattern
- Forms frond-like villi
  - 1cm high & 2mm thick
  - Increase in surface area
Articular cartilage destruction
- Enzymes
  - Released into joint by
    - Inflamed synovium
    - Activated chondrocytes
    - Dead PMN
  - These include
    - Hydrolytic enzymes & Metalloproteases
    - Oxygen radicals
    - Prostaglandins & Interleukins
  - Enzymatic degradation of cartilage
    - Initiated by Metalloproteases
    - Propagated by removal of enzyme inhibitors
  - Followed by Collagen degradation
    - Proteases destroy X links
    - Collagen then soluble & digested by Collagenases
  - Osteoclasts activated by PG ‘s
- Mechanical
  - Pannus
  - Mal-alignment
- Avascularity & Nutrition
  - Pannus
  - Capillary Damage
  - Raised Joint Pressure
Pannus
- Proliferating synovium penetrates synovial-cartilage junction
- Consists of
  - Vascular granulation tissue
  - Proliferating fibroblasts
  - Inflammatory cells
- Produces angular erosion
  - Undermines cartilage & lifts it
  - Bone then excavated
- Pannus also spreads over surface of cartilage
  - Destruction of cartilage
    - Interruption of chondrocyte nutrition
    - Enzymatic degradation of matrix with collagenases
- Response
  - Mechanical properties of cartilage lost
  - Surface fragmentation
  - Extends into deeper layers
  - Articular cartilage replaced by fibrocartilage & fibrous tissue
- Subchondral Bone
  - Inflammatory changes occur
  - Hyperaemia of bone leads to
    - Periarticular osteopaenia
    - Epiphyseal hypertrophy
    - Early physeal closure
  - Periosteal hyperaemia leads to
    - Cortical thickening adjacent to joint
    - Periostitis
- Leads to subsequent bony or fibrous ankylosis
- Also invades the surrounding capsule & supporting / stabilising ligaments leading to
  - Instability
  - Deformity
Synovial Fluid
- Exudate of fluid that produces effusion
  - Turbid
  - Thin with low viscosity
  - WCC of 20-50 000 x10e6/L (20-50 000 cells/mm3)
    - » 50% PMN
  - Immune complexes present
  - Hyaluronate depolymerized
    - Lower viscosity
  - Copious amounts of fibrinoid material
    - ‘Rice Bodies’
Raised Intra-articular Pressure
- Normal pressure is negative
- Raised due to
  - Effusion
  - Thick stiff capsule
  - Pressure ↑ with exercise
- This has effect on tissues
- Bone
  - Subarticular cyst due to fluid forced through cartilage
  - Increased pressure » Enlarges
- Soft Tissue
  - Fluid forced into periarticular soft tissue
  - Soft tissue cyst
  - Most common is Popliteal Cyst
- Capillary
  - Joint Pressure may be > Capillary blood pressure
  - Leads to intra-articular anoxia
Tenosynovitis
- Similar synovitis occurs in tendon sheaths
- Becomes thickened
  - Impaired motion
- Adhesions between synovial layers or tendons
- Tendon rupture secondary to
  - Inflammatory invasion by synovium
  - Vasculitis
  - Mechanical wear
  - ? Nodules

Vasculitis

Three forms
- Necrotising Arteritis
  - Luminal thrombosis & adventitial infiltrate
  - Small & Medium arteries
  - May cause
    - Neuropathies
    - Especially Mononeuritis
    - GIT infarction
    - Parenchymal lung changes
- Subacute Arteritis
  - Blood vessels surrounded by lymphocytes
  - Fibrosis occurs
  - Nodule
  - Flow unimpaired so few side effects
- Fibromuscular Hyperplasia
  - Fibrosis & proliferation of intima
  - Gradual occlusion of lumen
  - Thrombosis can then occur
  - Causes digital arteritis

Skin lesions seen as brown spots in nail folds & digital pulp
Larger ischaemic ulceration can be seen distally particularly around the malleoli
Fatal intestinal & MI reported
Secondary changes
- See above

Rheumatoid Nodules

25% of patients
Most prominent feature of vasculitis
Initiated by pressure or trauma
Cell-mediated Type III Hypersensitivity reaction
- Immune complexes deposited on blood vessel wall
- Chemotactic effect attracts PMN
- Inflammation augmented & vasculitis produced
- Intense fibrous reaction around blood vessels
- Necrosis occurs in centre of nodule
May appear prior to any signs of the disease itself
Characterised histologically by
- Irregular shape
- Central fibrinoid necrosis
- Palisading array of histiocytes & giant cells
- Outer zone of chronic inflammatory cells & fibrous tissue
Occur in
- Skin » Extensor surfaces of the elbow & forearm
- Heart
- Lungs
- Synovium

Parenchymal Changes

Lung & Heart Lesions
- Granulomas
- Fibrosis
- Pleural/ Pericardial Effusions
- Valve nodules
- Heart lesions rarely cause problems but lung disease may lead to Pulmonary Failure

Kidney Lesions
- Nonspecific
  - Amyloidosis + CRF
- Papillary necrosis from NSAID
Sjogren’s Syndrome / SICCA Syndrome
- Dry eyes, mouth, nose, ears
- Due to infiltration of secretory glands & surfaces by lymphocytes