RA Flashcards
1
Q
Rheumatoid Arthritis
A
- Patho is immune-mediated
- Autoantibodies are diagnostic markers
- General inflammation and specific inflammatory mediators are therapeutic targets
- Persistent, symmetric inflammation of multiple peripheral joints
- Chronic inflammatory proliferation of synovial lining
- Cartilage destruction, bony erosions
- High disability rate and shortened life expectancy of 5-7 years
2
Q
RA Etiology
A
- Results from genetic and possibly environment exposures
- Genetic: majority of patient have HLA-DR4, HLA-DR1, or both antigens in MHCII region
3
Q
RA Clinical Features
A
- Sudden onset in multiple joints
- Symmetric
- Preceded by fever, fatigue, anorexia, weight loss, myalgia, malaise
- Morning stiffness and gelling after inactivity (>1 hour)
- Stiff, painful, swollen joints
- “Boggy” or “spongy” joints
- Fluid wave or liquid composition
- Affected joints are warmer
- Disease activity fluctuates
- Structural damage is cumulative and irreversible
4
Q
RA Hand/Wrist Clinical Features
A
- Grip weakness, instability, subluxation (partial joint dislocation)
- Muscle atrophy, carpal tunnel syndrome
- Ulnar deviation of fingers
- Swan neck deformity: hyperextension of PIP and flexion of DIP
- Boutonniere deformity: flexion of PIP and hyperextension of DIP
5
Q
RA Feet Clinical Features
A
- Subluxation of MP joint (“cock-up” or “hammer” toe)
- Lateral deviations of toes (“hallux valgus”)
6
Q
RA Pathophysiology
A
- Systemic autoimmune disease featuring abnormal activation of B and T cells
- Most inflammation is in joint synovium
- ~3x expansion of lining layer composed of activated cells
- Highly inflammatory interstitium
- Cytokine, TNF, drives much of the inflammation
- IL-1, IL-6, and GM-CSF can also affect inflammation
7
Q
RA Pathophysiological Changes
A
- Fatigue
- Multiple joint involvement with symmetric distribution
- Joint become demineralized
- Joint inflammation: pain, swelling, warmth, morning stiffness
- Inflamed synovial tissue invades and destroys adjacent cartilage and bone
8
Q
RA Extra-articular Involvement
A
- Anemia of chronic disease and hemolytic anemia
- Vasculitis: infarcts near end of digits
- Pulmonary complications: pleural effusions, interstitial pneumonitis
- Cardiac: artherosclerotic CAD (low dose aspirin)
- Ocular complications: Sjogren’s syndrome (decreased tears)
- Felty’s syndrome: splenomegaly, neutropenia, and thrombocytopenia
9
Q
RA Laboratory Diagnostics
A
- ESR > 40
- RF Titer > 1:40
- Anti-cyclic citrullinated peptide (CCP) antibodies (ACPA)
- Elevated C-Reactive Protein (CRP)
- Inflammatory synovial fluid
10
Q
RF
A
- Rheumatoid factor
- Antibody produced against Fc-portion of human IgG
- Crosslinking leads to formation of immune complexes (aggregates)
11
Q
RA Treatment Goal
A
- Prevent or control joint damage
- Prevent loss of function
- Decrease pain
- Aggressive treatment early in disease course
- Target immune system to slow or reverse progression of arthritis
12
Q
RA Non-pharm
A
- Rest, OT, PT, assistive devices
- Weight reduction or management
- Splinting, joint protection
13
Q
RA Treatment - DMARDs
A
- Should be started within 3 months
- Select based on patient’s severity, comorbid diseases, adherence habits, convenience, monitoring requirements, costs, AE
14
Q
Why use mAbs?
A
- Bind to soluble inflammatory cytokines
- Block cell surface receptors
- Target specific cells for clearance (ADCC and CDCC)
- VERY specific but also VERY expensive
15
Q
mAb MoA
A
- Alters intracellular signaling
- Inhibition of function of growth factor receptors
- Inhibition of function of adhersion molecules
