090514 gout, rheumatold arth, osteoarth

Question 1

synovial membrane is not present over what?

Answer 1

articular cartilage

Question 2

patterns of arthritis

Answer 2

inflam or non-inflam

monoarthritis or polyarthritis

Question 3

what are some causes of inflammatory monoarthritis?

Answer 3

trauma
crystals (monosodium urate, calcium pyrophosphate)
septic joint
other

Question 4

how can you tell if the arthritis is inflammatory (vs non inflammatory)?

Answer 4

morning stiffness of longer than 1 hr

PE: erythema and warmth, synovitis (thickening of synovium around joints, tenderness upon palpation)

lab: ESR and CRP, peripheral blood leukocytosis, joint fluid analysis
radiography: XR (erosions of bone at joint margins)

Question 5

WBCs would be elevated in synovial fluid for what types of arthritis?

Answer 5

inflammatory (septic would have an extraoridinarily high WBC count)

Question 6

90% of gout occurs due to?

Answer 6

underexcretion

Question 7

where does uric acid in gout come from?

Answer 7

1/3 from dietary nucleotides and nucleoproteins

2/3 from cellular nucleotides and nucleoproteins

Question 8

how is uric acid usually excreted?

Answer 8

1/3 through the gut (bacterial degradation)

2/3 through renal excretion

Question 9

how much is usually excreted of uric acid of the filtered load?

Answer 9

10%

Question 10

how would does overproduction-induced hyperuricemia occur?

Answer 10

enzymatic abnormalities
increased cell turnover
diet
ethanol

Question 11

how would underexcretion-induced hyperuricemia occur?

Answer 11

metabolic syndrome
renal disease
drugs like diuretics, cyclosporine
ethanol

Question 12

what is the onset of gout in men related to?

Answer 12

uric acid level

Question 13

what test supports gout?

Answer 13

yellow, parallel crystals of monosodium urate (mneunomic is yellow, parallel, allopurinol–all double L’s)

uric acid level–if higher, higher chance of gout happening

swelling, warmth, tenderness

Question 14

tophaceous gout

Answer 14

large deposits of uric acid crystals

can get secondary calcification of tophi

Question 15

what can precipitate a gout attack?

Answer 15

elevation of uric acid

reduction of uric acid (see third point here)

release of crystals from pre-formed deposits

Question 16

inflammatory cascade of gout

Answer 16

MSU crystals are phagocytosed by monocyte, you get inflammasome activation, then monocyte release IL-1, which then activates the endothelium, get pro-inflammatory mediators and neutrophil recruitment

Question 17

CPPD deposition disease occurs in whom?

Answer 17

12% of elderly

Question 18

what is the cause of CPPD deposition disease

Answer 18

unknown but most cases are related to overproduction of PPi

Question 19

what is CPPD

Answer 19

calcium pyrophosphate dihydrate, formed from pyrophosphate and calcium coming together to make the crystal

Question 20

in pts less than 60, CPPD can occur how?

Answer 20

secondary to problems like hemochromatosis, hypophosphatasia, hypomagnesemia, hyperparathyroidism

Question 21

how is psuedogout diff from gout

Answer 21

acute arthritis like gout, but in usually larger joints (knee, wrist, shoulder)

Diagnosed from thromboidal shaped, positively birefringent cyrstals in joint fluid

XR: diagnosis may be supported by chondrocalcinosis but not seen always

Question 22

CPPD arthritis signs

Answer 22

commonly asymptomatic

or pseudogout - acute inflam of 1 or 2 joints

or osteoarthritis (but may be associated with osteoarthritis in atypical joints)

or like rheumatoid arthritis (MCP involvement)

Question 23

how should NSAIDs be used to treat gout

Answer 23

within first 24 hrs

indomethacin, naproxen

never use aspirin (aspirin inhibits uric acid secretion)

for the inflammation in gout

Question 24

how are steroids used to treat gout

Answer 24

symptomatic relief for pts that can’t take NSAIDs

used short term

Question 25

MOA of colchicine in treating gout

Answer 25

antimitotic interferes with microtubule formation, inhibits neutrophil activation and migration

Question 26

route of administration of colchicine for gout

Answer 26

oral

Question 27

what is notable about colchicine for gout

Answer 27

CYP450 metabolism substrate for P-glycoprotein significant adverse effects (narrow therpeutic toxicity window, GI) ---therefore use is limited contraindicated for hepatic or renal disease pts, elderly, CYP3A4 and P glyprotein drug taking pts

Question 28

for multiple acute gout attacks, drug therapies to prevent gout flare and destruction on joint snad kidneys?

Answer 28

allopurinol febuxostat probenecid pegloticase

Question 29

allopurinol MOA

Answer 29

blocks xanthine oxidase, inhibiting terminal steps in uric acid biosynthesis converted to oxypurinol, which is the active compound (hypoxanthine normally is converted to xantine; allonpurinol is a structural analog of hypoxanthine)

Question 30

adverse effects of allopurinol

Answer 30

hypersensitivity | acute gout attack (give drug w/ colchicine or NSAID)

Question 31

use of allopurinol

Answer 31

prevention of primary hyperurecemia of chronic gout prophylactic treatment in secondary forms of hyperurecemia

Question 32

febuxostat MOA

Answer 32

non-purine xanthine oxidase inhibitor (not a structural analog for binding to xanthine oxidase) forms stable complex with both reduced and oxidized xanthine oxidase and inhibits catalytic fxn in both states

Question 33

compare fubuxostat vs allopurinol in treating gout

Answer 33

febuxostat is more potent incidence of adverse events like dizziness, diarrhea, headache and nausea was similar in both drugs incidence of CV side effects higher in febuxostat

Question 34

MOA of pegloticase

Answer 34

PEGylated-polyethylene glycol covalently linked to the molecule the molecule is a recombinant form of urate oxidase enzyme (uricase, an enzyme usually not in humans) uricase will convert uric acid to allantoin

Question 35

side effects of pegloticase

Answer 35

infusion site rxns (must be given IV) gout flare immune response (at PEG portion of molecule)

Question 36

uses of colchicine

Answer 36

acute gout attacks (within hours) | prophylactically in pts with chronic gout

Question 37

use of pegloticase

Answer 37

refractory chronic gout

Question 38

probenecid MOA

Answer 38

increases uric acid exretion by competing with renal tubular acid transcrporter (OAT/URAT1) so that less urate is reabsorbed

Question 39

route of administration of probenecid

Answer 39

oral

Question 40

what is notable about probenecid

Answer 40

dose-dependent half life (second order kinetics) plasma protein binding

Question 41

side effects of probenecid

Answer 41

GI ineffective in pts with renal insufficiency contraindicated in pt with uric acid kidney stones

Question 42

Rheumatoid arthritis involves what cells of immune system

Answer 42

T cell disease with significant B cell contribution

Question 43

what factors predispose someone to getting rheumatoid arthritis

Answer 43

``` genetic (HLA-DR) hormonal (females more than males) environmental (smoking) infections stress ```

Question 44

what do you see in rheumatoid arthritis with regards to the synovrium

Answer 44

invasion by immune lineage cells with recruitment of local cells (synovial fibroblasts) get proliferation of synovium (synovitis) with characteristics of a benign locally invasive tumor

Question 45

pathology of rheumatoid arthritis

Answer 45

chronic papillary synovitis: chronic inflammation of synovium (frequently formed lymphoid follicles) accompanied by synovial cell hyperplasia--resulting in papillary like pattern on surface of synovium hyperplastic inflammed synovium extends over articular surface forming pannus which fills joint space (gradually, articular cartilage is destroyed; increased osteoclast activity in underlying bone; end result may be joint fusion (ankylosis) due to fibrosis and ossification)

Question 46

diff btwn rheumatoid arthritis and osteoarthritis

Answer 46

ostephytes and new bone formation are not prominent in RA

Question 47

rheumatoid nodules

Answer 47

occur in 25% (usually in severe disease) central zone of fibrinoid necrosis surrounded by rim of epithelioid histiocytes and then lymphocytes and plasma cells caused by necrosis secondary to vascular damage possibly secondary to vasculitis develop commonly on skin subcutaneously in areas exposed to pressure (extensor surfaces of forearm and elbow)

Question 48

Hx of RA

Answer 48

gradual onset of joint pain, swelling, inflammation inflam present for greater than 6 weeks in 3 or more joints symmetrical in nature morning stiffness lasting more than 1 hour for >6 wks difficulty opening jars, etc, pain in the ball of foot upon arising from bed

Question 49

what is RF?

Answer 49

IgM binding to IgG however, not positive in all RA pts

Question 50

anti-cyclic citrullinated peptide (CCP)

Answer 50

may be seen in early RA positive in some cases of RF negative RA same sensitivity as RF; more specific than RF correlates with overall disease activity

Question 51

clinical presentation of RA

Answer 51

affects usually small joints of hands and feet usually not DIPs; PIPs and MCPs are common tends to be in rows can see swan neck deformity (hyperflexion of DIP, hyperextension of PIP); Boutiniere deformity (PIP flexion, DIP hyperextension)

Question 52

criteria for classification of RA

Answer 52

4 out of the 7 below for greater than 6 weeks: ``` AM stiffness greater than 1 hr symmetrical arthritis at least three swollen joints wrist, MCP, PIP involvement rheumatoid nodules positive RF XR change typical of RA in hand ```

Question 53

how is RA systemic?

Answer 53

``` can have: Sjogren's CV disease (similar to diabetes) lung involvement GI (b/c of NSAIDs or other med side effects) neurology (hand numbness, neuropathy) ```

Question 54

pulmonary involvement of RA

Answer 54

rheumatoid pleuritis with exudate that is low in glucose interstitial fibrosis nodules Caplan's syndrome (rheumatoid pneumoconiosis) medication related (unusual chronic infections)

Question 55

for RA, etanercept MOA

Answer 55

inhibits the ability of soluble TNF-alpha to bind to its receptor is a recombinant fusion protein

Question 56

onset of action of etanercept

Answer 56

1-2 weeks

Question 57

adverse effects of etanercept

Answer 57

injection site rxns increased risk of infections lymphomas in children

Question 58

etanercept is used for

Answer 58

initially just used for moderate to severe RA, but now used for early stage

Question 59

adalimumab MOA

Answer 59

IgG monoclonal antibody binds to soluble and transmembrane forms of TNF-alpha

Question 60

adverse effects of adalimumab

Answer 60

same as for etanercept

Question 61

tocilizumab MOA

Answer 61

humanized antibody that binds to soluble and membrane bound IL-6 receptors, inhibiting IL-6 signanling

Question 62

adverse effects of tocilizumab

Answer 62

injection site rxns increased risk of infec alterations in lipid profile

Question 63

uses of tocilizumab

Answer 63

adults pts with moderately to severely active RA who haven't had a good response to TNF antagonists

Question 64

tofacitinib MOA

Answer 64

JAK inhibitor, inhibiting cytokine or growth factor mediated gene expression and intracellular activity of immune cells

Question 65

what is notable about tofacitinib

Answer 65

it is administered orally (as opposed to tocilizumab and TNF inhibitors) CYP3A4 metabolism

Question 66

adverse effects of tofacitinib

Answer 66

increased risk of infec | increase in cholesterol

Question 67

uses of tofacitinib

Answer 67

moderately to severely active RA in pts who have had inadquate response to methotrexate

Question 68

biologic DMARDs

Answer 68

proteins designed mostly to target cyokines and cell-surface molecules

Question 69

osteoarthritis

Answer 69

progressive disorder of the joints caused by gradual loss of cartilage bony spurs and cysts develop at margins of joints

Question 70

risk factors for osteoarthritis

Answer 70

``` female gender (particularly knee and hand) increasing age race or ethnicity genetics obesity trauma ```

Question 71

pathology of osteoarthritis

Answer 71

early changes-superficial layers of cartilage are destroyed (limited chondrocyte proliferation and new matrix formation)

Question 72

eburnation

Answer 72

advanced osteoarthritis-you see eburnation, which means polished, in the exposed bone

Question 73

advance osteoarthritis-appearance?

Answer 73

EBURNATION SUBCHONDRAL SCLEROSIS-more dense bone develops underneath the areas where cartilage is gone--in these areas, in addition, you can get micro fractures and then cysts--(called SUBCHONDRAL CYSTS, where you have break in the cartilage and then the bone and then fluid goes in) OSTEOPHYTE FORMATION

Question 74

osteophyte formation

Answer 74

bony outgrowths developed at margins of articular surface - cause increase in joint size

Question 75

pathogenesis of OA?

Answer 75

imbalance in cytokine and growth factor activity resulting in matrix loss and degradation etiology is likely multiple: wear and tear theory is not sufficient to explain risk factors

Question 76

which joints are affected in OA

Answer 76

for women-small joints in hands (DIPs PIPs NOT MCPs) hips knees bunions in the feet

Question 77

PE findings for OA

Answer 77

mild to moderate FIRM swelling around joint line (b/c of formation of chondrophytes or osteophytes at margin) crepitus restricted ROM limited by pain weakness and wasting of muscles acting on joint periarticular tenderness deformities Heberden's and Bouchard's nodes hallux valgus (bunion) genu varus (bow legs) genu valgus (knock knees0

Question 78

diagnosis of OA

Answer 78

blood tests usually not helpful imaging synovial fluid aspiration typically viscous and translucent-non inflam WBC count <2000

Question 79

infliximab MOA

Answer 79

chimeric IgG monoclonal antibody that binds to both soluble and transmembrane forms of TNF-alpha

Question 80

abatacept MOA

Answer 80

costimulation modulator inhibits T cell activation by binding to CD80 and CD86 on APC and blocking then the required interaction with CD28

Question 81

adverse effects of abatacept

Answer 81

headache hypersensitivity increased risk of infec should NOT be used in combo with anakinra or TNF-inhibitors

Question 82

rituximab MOA

Answer 82

monoclonal Ig directed against CD20 antigen on B lymphocytes; this activates complement dependent B-cell cytotoxicity and antibody dependent cellular toxicity

Question 83

side effects of rituximab

Answer 83

tumor lysis syndrome leading to acute renal failure

Question 84

anakinra MOA

Answer 84

antagonist of IL-1 receptor

Question 85

azathioprine MOA

Answer 85

purine antimetabolite that inhibits purine biosynthesis, inhibiting DNA synthesis

Question 86

hydroxychloroquine MOA

Answer 86

not understood useful for early, mild disease in RA

Question 87

side effects of hydroxychloroquine

Answer 87

retinal damage

Question 88

lefluonomide MOA

Answer 88

immunomodulatory agent in RA; inhibits dihydroorotate dehydrogenase, which is involved in production of uridine monophosphate

Question 89

side effects of lefluonomide

Answer 89

diarrhea, rash, alopecia, elevated liver fxn tests