Rheumatoid Arthritis

Question 1

RA basic

Answer 1

Most common chronic inflammatory arthritis, and is characterized by autoantidobidy production, synovial inflmmation, and bony destruction

Question 2

Genetic and environemtn of RA

Answer 2

Genetic and environmental

Most genetic related to MHC class 2

May have abnormal DNA methylation in MNC and synovial cells

Smoking, viral infections, periodontitis, steessful life events

Question 3

Patho of RA

Answer 3

INnate immune activated

Neoantigen generation also relevant

Induction of PAD in macrophages, converting arginiine to citruklline…increased citrullination of different matrix proteins creates neoantigens recognized by imimune system

APCs with neoantigens migrate to lymphid and interact with T cells…increases Th1 and Th17 and diminish Th2 and T regs

Th1 activate B cells and rpdocue ACPA and anti-IgG antibodies (RF)

Question 4

Witihin joints, RA

Answer 4

Activated Th1 cells stimulate macrophages and fibroblast-like synoviocytes to generate proinflam mediators and proteases

B cells produce ACPA(inflammatory process) and RF (immune complexes)

Question 5

Cytokines and RA

Answer 5

TNFalpha, IL6, IL1

TnF alpha - activating other cytokines and endothelial cell adhesion molecules and suppresses T regs

IL6- pleotropic effect by influencing hematopoiesis and other immune cells…endothelial activation and bone erosions…also induces acute phase protein production (CRP)

IL1 - activates leukocytes, endothelial cells ,and osteoclasts

Question 6

Net effect of RA

Answer 6

Immune system activation and cytokine production alters function of fibroblast-like synoviocytes within the joint

Increase in population of synoviocytes os tissue proliferation

Synoviocytes release matrix metalloproteases resulting in local destruction

Production of MCSF and RANKL promotr osteoclast

Question 7

Epidemiology of RA

Answer 7

Females more common

50-75 is peak onset

Question 8

CM of RA

Answer 8

Polyarticular dz of graudal onset but may have acute presentation

Classic - insidious onset of pain, morning stiffness, and swelling of multiple joints

small joints - MCP, PIP, wrists, MTP

Large - elbows, shoulders, ankles, and knees

Morning lasts ore than 1 hr

May have systemic sx

Question 9

PE of CM

Answer 9

Pain and swelling of involved joints

Local pressure on joint or passive movement may provoke pain

Boggy feel to a swollen joint bc of synovial hypertrophy

Question 10

Hematologic

Skin comps

Answer 10

ANemia of chronic d, reactive thrombocytosis, Felty’s syndrome ,diffuse large B cell lymphoma

Reumatoid nodules, pyoderma gangrenosum

Question 11

Pullm and skeltal RA

Answer 11

Intertstitial lung dz, plueirtis and pleural effusiom lung nodules

Osteoporosis

Question 12

Cardiac, ocular, AI comps

Answer 12

Pericarditis, ischemic heart dz

Epicleritis, slecereits

Sjorgerns syndrome

Question 13

Rheumatoid ndoules

Answer 13

Adherent to periosteum or tendons

Typically firm, nontender, and located on forearm or achilles tendon

Question 14

Deformities

Answer 14

Due to bone erosions

Can lead to vertebral malalignment

Question 15

Boutonniere and swan neck deformity

Answer 15

Bout - relaation of the PIP joint causing flexion of the PIP joint with hyperextension of DIP

Swan neck causes hyperextension of PIP joint with flexion of the DIP joint

Question 16

RA diagnosis

Answer 16

May need CBC, ESR, and CRP to confirm inflam arthrtitis

RG and anti-CCP should also be persormed

Joint involvemtn - up to 5 points
Serology - Low ACPA or RF
Acute-phase reactants - CRP or EST
Duration of sx - more than 6 weeks

over 6 is definite RA

Question 17

Other dx of RA

Answer 17

Arthrocentesis WBC betwen 5 and 50000 and glucose is low

Xray shows joint space narrowing and bny erosions of hands and feet

Question 18

Methotrexate MOA and adverse effects

Answer 18

Folate antimetabolite interfering with DNA synthesis and producing anti-inflamm effect

Liver, BM, dyspepsia, N/V

Question 19

Sulfasalazine MOA and SE

Answer 19

Unclear but modulates cytokine mediators of inflamm response

N/V, skin rash and photosensitivity, HA

Question 20

Hydroxychloroquine MOA and SE

Answer 20

Block stimulation of the B cell receptors through inhibition of TLRs

N/V, skin rash, HA, corneal desposits and retinopathy

Question 21

Leflunomide MOA and SE

Answer 21

Inhibiyion of pyrimidine synthesis, resultiing in anti-inflamm effects

HTN, N/V
Alopecia

Question 22

TNF-alpha inhibitor function

Answer 22

Blocks potent proinflammatory and immunoregulatory mediator

Question 23

TNF alpha inhibitor structures

Answer 23

Monoclonal - adalimummab, golimumab, infliimab

TNF-alpha receptor-Fc fusion protein - Etanercept
Fab’ fragement of TNF-alpha - certolizumab

Question 24

CD20 function, structure, drug

Answer 24

Loss of CD20 in pre-B cells depletes B cells

Monoclonal AB - rituximab

Question 25

CD80/86

Answer 25

Blockade of costim of T cells

CTLA4 IgG fusion protein

Abatacept

Question 26

IL-1

Answer 26

Inhibits production of prostaglangdss and matri metalloproteinase by synovial cells

Receptor antagonist
Anakinra

Question 27

IL-6 R

Answer 27

Inhibition of cytokine activation of T, B, macro, osteoclasts

Monoclonal Ab - tocilizumab

Question 28

Janus Kinase

Answer 28

Inference of cytokine and GF singlaing pathways

Small molecular inhibitor

Tofacitinib

Question 29

Prognosis of RA

Answer 29

Most get flucutations but progression

Joint erosions are detectable within 1st 2 years if no managmenrt

Life span shorten from pensity to develop CV dz (chonic inflamm) and infection (drugs)