RA

Question 1

Rheumatoid Arthritis

Answer 1

• 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

Question 2

RA Etiology

Answer 2

• Results from genetic and possibly environment exposures

- Genetic: majority of patient have HLA-DR4, HLA-DR1, or both antigens in MHCII region

Question 3

RA Clinical Features

Answer 3

• 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

Question 4

RA Hand/Wrist Clinical Features

Answer 4

• 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

Question 5

RA Feet Clinical Features

Answer 5

• Subluxation of MP joint (“cock-up” or “hammer” toe)

- Lateral deviations of toes (“hallux valgus”)

Question 6

RA Pathophysiology

Answer 6

• 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

Question 7

RA Pathophysiological Changes

Answer 7

• 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

Question 8

RA Extra-articular Involvement

Answer 8

• 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

Question 9

RA Laboratory Diagnostics

Answer 9

• ESR > 40
• RF Titer > 1:40
• Anti-cyclic citrullinated peptide (CCP) antibodies (ACPA)
• Elevated C-Reactive Protein (CRP)
• Inflammatory synovial fluid

Question 10

RF

Answer 10

• Rheumatoid factor
• Antibody produced against Fc-portion of human IgG
• Crosslinking leads to formation of immune complexes (aggregates)

Question 11

RA Treatment Goal

Answer 11

• 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

Question 12

RA Non-pharm

Answer 12

• Rest, OT, PT, assistive devices
• Weight reduction or management
• Splinting, joint protection

Question 13

RA Treatment - DMARDs

Answer 13

• Should be started within 3 months
• Select based on patient’s severity, comorbid diseases, adherence habits, convenience, monitoring requirements, costs, AE

Question 14

Why use mAbs?

Answer 14

• Bind to soluble inflammatory cytokines
• Block cell surface receptors
• Target specific cells for clearance (ADCC and CDCC)
• VERY specific but also VERY expensive

Question 15

mAb MoA

Answer 15

• Alters intracellular signaling
• Inhibition of function of growth factor receptors
• Inhibition of function of adhersion molecules

Question 16

Suffix + % Human

Answer 16

• omab: 0%
• ximab: 65%
• zumab: >90%
• umab: 100%

Chances for immunogenicity lowers as the percentage of human increases

Question 17

TNF-alpha

Answer 17

• Chronic systemic inflammation
• T-cell proliferation
• B-cell proliferation and differentiation
• Immune cell trafficking
• Bone destruction: increased osteoclasts, decreased osteoblasts

Question 18

IL-1

Answer 18

• Increases immune cell trafficking
• Induces the release of inflammatory mediators (PGE2)
• Bone and joint destruction: inhibits collagen production and stimulates osteoclast maturation

Question 19

IL-6

Answer 19

• B-cell differentiation into plasma cells
• T-cell proliferation and differentiation into helper cells that produce IL-17
• IL-17 recruits immune cells which damage tissue
• Mediates systemic effects of RA including CRP expression

Question 20

RA Treatment based on…

Answer 20

• Disease duration: less or more than 6 months

- Disease activity: low, moderate, or high (measured at least annually)

Question 21

RA + Vaccinations

Answer 21

• Prior to starting any DMARD or biologic get all killed, recombinant, and live attenuated vaccines
• If already taking a DMARD or biologic received killed pneumonia, flu, or Hep B vaccines and a recombinant HPV

Question 22

RA + Surgery

Answer 22

• Utilized when pain is unacceptable for symptom relief

- Can also be utilized when having unacceptable ROM or function