RA and Systemic Sclerosis Flashcards
What is Rheumatoid Arthritis?
Autoimune disease (Collagen-vascular type)
- Chronic, non-supperative, synovitis (“pannus”) with joint and bone destruction
- -> Autoimmune attack on the synovium that leads the synovitis
- Extra-articular features
What are the stages of RA?
Stage 1:
Gradual onset fatigue, weight loss, weakness, and vague musculoskelatal discomfort
Stage 2:
Small joints of hand and feet, symmetrical
Stage 3:
Wrists, ankles, elbows, knees, cervical spine
*Pain, tenderness, and swelling of joints
What is shown on Xray of RA?
Juxta-articular osteopenia
Bone erosions
Narrowed joint space from cartilage loss
What is are clinical signs of RA destruction?
Destruction of tendons, ligaments, joint capsule
- Deformities (late):
Radial deviation of wrist
Ulnar deviation and flexion-hyperextension of fingers
Ankylosis (bony fusion)
What is Pannus?
Term for Inflammed synovium
Acute and chronic inflammation with synovial cell hyperplasia
- Neutrophils in synovial fluid
- Spread of pannus into cartilage and bone
- Fibrous then bony anylosis
- Deformed joint; loss of function
What is the current theory on RA pathogenesis?
- Arthritogenic microbial antigen/genetic background leads to RA susceptibility
- *CD4+ T cell activation and release of cytokines leads to:**
- Induing macrophages/synovial lining cells to release IL-1 and TNF-a
- Upregulation of endothelial adhesion molecules –> inflammatory cell influx into synovium
- Promotion of B cell hyperactivity (CD4+ Tcell dependent) production of Rheumatoid factor
What is rheumatoid factor?
Auto Ab to the Fc protion of IgG
- Creates immune complexes in sera, synovial fluid, and membrane
- Augment joint inflammation, induce vasculitis
- High titer-associated with severe disease
- Not specific; other CVDs, even healthy ppl can be RF+
- For RA:
RF+ = poor Px
RF- = good Px
What causes the joint destruction of RA?
- Neutrophils and synoviocytes release protease and elastase
- Macrophage and synoviocytes release IL-1 and TNF-a which induce:
Collagenase (break down substrate of cartilage and bone)
Osteoclast activating factor (bone resorption)
Endothelial cell adhesion molecules - Pannus invasion isn’t directly needed for destruction, but it doesn’t help
What are rheumatoid nodules?
- Firm, moveable, non-tender, round to oval noduels present on RA patients
- Generally found on pressure regions:
ulnar aspect of forearm
elbows
Occipu
Lumbosacral area - Central fibrinoid necrosis surrounded by epithelioid histiocytes, lymphs, and plasma cells (granuloma)
Can be found in more dangerous areas:
- Cardiac- Bundle of His –> arrythmia
- *Lung** - Fibrosis, respiratory failure
Other than RA, when can rheumatoid nodules be found?
SLE
Rheumatic fever
What is rheumatoid vasculitis?
Associated with severe disease, rheumatoid nodules, and high RF titers
- Small to medium arteries affected
- -> potentially catastrophic if in a vital organ
- Digital arteries affected
- -> peripheral neuropathy, ulcers, gangrene
- *- Leukocytoclastic venulitis** affected
- -> purpura, skin ulcers, nail bed infarction
What are the main causes of death in RA?
Amyloidosis
Vasculitis
GI bleed (NSAID and Aspirin use)
Infections (chronic steroids, anti-TNF-a Ab, underlying disease)
Heart and lung nodules
Cervical spine subluxation (if affected by disease)
What is Systemic Sclerosis?
- Chronic disease (Collagen vascular disease type)
- Evidence of immune-mediated vascular injury (mechanism unclear)
- Vascular instability, narrowing, ischemia in multiple organs
- Excessive collagen in skin due to fibroblast activation
What is diffuse scleroderma?
- *Widespread skin involvement**
- involvement skin areas extend proximal to elbows and knees
- *Severe multiple organ involvement**
- and decreased survival
Anti-topoisomerase Antibody often present
What is limited Scleroderma?
Skin involvement is confined to fingers, forearms, and face
Visceral involvement limited and late
Better prognosis than diffuse scleroderma
Subgroup = CREST
(anti-centromere antibody)
