Rheumatoid arthritis

Question 1

Define Rheumatoid arthritis (RA)

Answer 1

systemic inflammatory, autoimmune disorder resulting in synovitis leading to cartilage and bone destruction and joint deformities.

Question 2

What joints are involved in RA?

Answer 2

mostly peripheral synovial joints in a symmetric pattern(particulatly the small joints of hands and feet), DIP often spared, Cervical spine common (C1-C2), Other synovial joints (cricoarytenoid, ossicles of inner ear, and TMJ)

Question 3

common symptoms of RA?

Answer 3

morning stiffness, soft tissue swelling around joints, pain, deformities and loss of function

Question 4

common signs of RA

Answer 4

Joint warmth and swelling, tenderness to palpation with limitation of motion, possible deformities

Question 5

T or F: Rheumatoid factor (RF) is a common finding in RA

Answer 5

TRUE; seen in 85% of patients

Question 6

T or F: ESR and C-reactive protein are often normal in RA

Answer 6

FALSE: they are elevated

Question 7

T or F: Citrullinated proteins can be found in many sites of inflammation in RA

Answer 7

TRUE

Question 8

T or F: Anti-cyclic citrullinated peptide (Anti-CCP) antibodies are not commonly found in RA

Answer 8

FALSE: they are present in 70% of cases and are highly specific for RA

Question 9

How do peptides contain citrulline?

Answer 9

Enzyme peptidyl arginine deiminase (PAD) modifies an arginine residue

Question 10

What does the synovial fluid analysis look like in RA?

Answer 10

inflammatory (>2000 WBC/uL) with predominant neutrophils, complement and glucose levels usually low

Question 11

What are some common radiographic findings in RA? (4 things)

Answer 11

1) soft tissue swelling, 2) Juxta-articular osteopenia, 3) Symmetric loss of joint space, 4) Erosions in marginal distributions

Question 12

Extra-articular manifestations of RA

Answer 12

Fatigue, malaise, anorexia, weight loss, low-grade fever, Rheumatoid nodules on extensor surfaces and tendon sheaths and internal organs (ie lungs)

Question 13

What organs can be involved in RA

Answer 13

Numerous organ systems in ~20% of pts, including eyes (scleritis), lungs (fibrosis or nodules), peripheral nerves (neuropathy), vasculitis, or granulomatous infiltration

Question 14

What is the ratio of RA in females compared to males?

Answer 14

~2.5:1

Question 15

Are there any genetic factors involved in RA?

Answer 15

YES! Concordance rate of monozygotic twins is ~30% and HLA-DR4 in present in 50% or more of cases

Question 16

T or F: RA is primarily a synovial-based with secondary affects on articular cartilage and junta-articular bone

Answer 16

TRUE

Question 17

Early events in the synovial tissue in RA are characterized by what?

Answer 17

microvascular injury and edema

Question 18

what cell changes occur in RA synovial tissue early on

Answer 18

synovial lining cell hyperplasia and infiltration of the sunlining region with CD4+ Tcells, B cells, plasma cells, monocytes/macrophages, and fibroblasts.

Question 19

T or F: Neutrophils are distinctly rare in early events of RA

Answer 19

TRUE

Question 20

What events can help lead to chronic phase of RA

Answer 20

genetic susceptibility (shared epitope), T and B cell function, and activation of MACs and fibroblasts

Question 21

What is the chronic stage distinguished by?

Answer 21

neutrophilic infiltration of synovial fluid

Question 22

T or F: Rheumatoid factor (RF) is produced locally by plasma cells and binds IgG in synovial fluid

Answer 22

TRUE

Question 23

What can help cause the neutrophil chemotaxis?

Answer 23

IL-8 and RF activation of complement

Question 24

How do MACs contribute to cartilage and bone damage?

Answer 24

IL-1, TNF-alpha, IL-6, etc. release stimulates production of MMPs

Question 25

What inflammatory agents may induce catabolic function of chondrocytes and osteoclasts?

Answer 25

prostaglandin E2, and IL-1. leads to juxta articular osteopenia and loss of cartilage

Question 26

How do neutrophils fuck the shit?

Answer 26

ROS, proinflammatory eicosanoids, and shear numbers overwhelming proteinase inhibitors

Question 27

how do TNFalpha, IL-1, and IL-17 induce bone reabsorption?

Answer 27

induce osteocyte expression of RANKL, which binds RANK receptor on osteoclast precursors, thus activating reabsorption.

Question 28

what does osteoprotegerin (OPG) do?

Answer 28

competitively binds RANKL and modulates its activity

Question 29

T or F: bony reabsorption in RA is due to RANKL:OPG ratio

Answer 29

TRUE

Question 30

What are some treatment options to prevent bone resorption?

Answer 30

anti-TNF therapies and monoclonal antibody against RANKL (denosumab)

Question 31

What drugs are given early on in RA to relieve symptoms and prevent further tissue destruction

Answer 31

NSAIDs AND disease-modifying anti-rheumatic drugs (DMARDs)

Question 32

What drugs are DMARDs and what do they do?

Answer 32

hydroxycloroquine, sulfasalazine, leflunomide, and methotrexate. Primarily inhibit MACs and lymphocytes

Question 33

What do newer therapeutic agents target for RA?

Answer 33

IL-1, TNF-alpha, IL-6, T-cells inactivation, deplete B-cells, and JAK inhibitors

Question 34

What is the significance QKRAA sequence in the HLA-DRB1 class II MHC?

Answer 34

hypervariable portion of DRB1 that surrounds antigen-binding groove and may interact with side chains of bound antigen and with T cell receptor. It determines susceptibility and severity of disease. Enhance binding of citrullinated proteins and is sen with anti-CCP antibodies

Question 35

T or F: Pannus can be seen in RA

Answer 35

TRUE. It?s the spongey material that forms in joint from infiltrating cells and hyperplasia of synovial cells