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Flashcards in RHEUMATOLOGY REVIEW Deck (91):
1

Degeneration of articular cartilage with hypertrophy of contiguous bone:

DX: joint space loss, subchondral cysts, sclerosis, osteophytes

Osteoarthritis (OA)

2

OA: Predisposing Factors (primary)

Age
Obesity
Occupational risks:
Miners: OA hips, knees, shoulders
Weavers: OA hands
Trauma

3

Osteoarthritis (OA) Joint Involvement:

DIP (Heberden’s), PIP (Bouchard’s), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP

4

Osteoarthritis (OA) DX:

joint space loss, subchondral cysts, sclerosis, osteophytes

5

OA: Predisposing Factors secondary

Secondary OA:
Inflammatory
Metabolic: hemochromatosis, Wilson’s disease, ochronosis

Sports: in general, no increased risk; exercise may be protective

6

****Sports: in general, no increased risk for OA; exercise may be _______

protective

7

Collagen: predominantly type II

Proteoglycans (chondroitin and keratin sulfate) linked to hyaluronic acid

Matrix proteins
~Metalloproteinases (MMPs): collagenase, gelatinase, stromelysin
~Tissue inhibitors of metalloproteinases (TIMPS)

Chondrocytes

Water

Cartilage components (avascular, no nerves)

8

In OA, the big problem is

cartilage tries to repair itself unsuccessfully

9

Cartilage in early Osteoarthritis

↑ inc chondrocytes
↑ inc metalloproteinases
↑ inc water content

dec TIMP
dec proteoglycan

cartilage changes from a spounge into a dish rag

10

OA Characteristics

Lacks systemic features
Synovial fluid: noninflammatory, type I fluid (200-2000 WBC/mm3)

11

__________ stimulates MMP production, PGE2, nitric oxide (NO), IL-6 in OA

Interleukin-1:

12

___________: increases MMP production, inhibits proteoglycan synthesis, induces chondrocyte apoptosis in OA

Nitric oxide

13

__________: ↑ production and activation of MMPs in OA

Prostaglandins

14

Complement activation
Adipokines
Interleukin-1:
Nitric oxide
Prostaglandins

present in?

OA

15

Adipokines

fat cells may produce IL-6

16

OA: Knees

Joint space loss
Sclerosis
Subchondral cysts
Osteophytes

17

A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, symmetric synovitis which can result in cartilage and bone destruction

Joint involvement:
Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

X-rays: marginal joint erosions and deformities

Rheumatoid Arthritis (RA)

18

Rheumatoid Arthritis (RA): A systemic, inflammatory, autoimmune disorder of unknown etiology that results predominantly in a peripheral, ________________ which can result in cartilage and bone destruction

symmetric synovitis

19

Rheumatoid Arthritis (RA) Joint involvement:

Bilateral, symmetric - small joints hands + feet sparing the DIPs
Medium and large joints can be involved

20

Rheumatoid Arthritis (RA) Disease susceptibility and severity associated with shared epitope (QKRAA; in antigen binding groove) in subtypes of _____________ other genes are also involved

**HLA-DR4 and HLA-DR1

21

Antibody directed against the Fc portion of IgG; RF usually IgM, can be IgG or IgA
RF present in 85% of patients with RA
Not specific for RA or CTDs
Produced locally in the synovial tissue

RF-IgG immune complexes are pathogenic

Rheumatoid factor (RF):

22

RF-IgG immune complexes are _______

pathogenic

Rheumatoid factor (RF):
Can cause vasculitis or nodules

23

Rheumatoid factor (RF) ispresent in

many disease
ex
ra
sjordons
sle

24

Anti-CCP
Anti-Cyclic Citrullinated Peptide Antibodies

RF not very specific for RA

reactive with synthetic peptides containing the unusual amino acid citrulline (modified arginine residue) are specifically present in the sera of RA patients:


Anti-CCP abs occur more frequently in individuals with the shared epitope; citrullination of peptides enhances binding

25

Inflammed tissue of macs, t cells, plasma cells

Pannus

in RA

26

Synovial fluid major cell in RA?

neutrophils

27

Production of metalloproteinases and other effector molecules
Migration of polymorphonuclear cells
Erosion of ____________ in RA

bone and cartilage

28

CD4+ memory T cells related to RA

modulation and amplification of local immune response through antigen recognition (query altered proteoglycans or collagen; citrullinated peptides)

unknown antigen sparks RA, by RA start disease is cleared but RA goes on

29

Extra-articular manifestations in RA

RF-IgG immune complex-induced vasculitis
Rheumatoid nodule formation in tissues/organs

30

The result of tissue deposition of monosodium urate (MSU) crystals due to hyperuricemia (MSU supersaturation of extracellular fluids)

Gout

31

Gout Joint Involvement:

1st MTP (podagra)GRaet Toe

Cool, peripheral joints of lower and upper extremities

32

Gout Hyperuricemia: over-production or under-excretion of uric acid; _______ (90%) most cases

underexcretors

33

Uric acid is a product of ______ metabolism

purine

34

Humans lack ______ which oxidizes uric acid into allantoin (more soluble compound)

uricase

35

___________of uric acid (X-linked):
PRPP synthetase overactivity
HGPRT deficiency (complete: Lesch-Nyhan)

Overproduction

36

Crystal arthritis is ________________ and crystal identification by polarized microscopy (MSU crystals: needle-shaped, negatively birefringent)

diagnosed by arthrocentesis

37

X-linked inborn errors of Gout

inc PRPP synthetase
dec HGPRT

38

_______ inhibited by allopurinol and febuxostat, can treat gout

Xanthine oxidase

39

Overproduction of uric acid (X-linked):
__________overactivity
HGPRT deficiency (complete: Lesch-Nyhan)

PRPP synthetase

40

IgG-coating promotes phagocytosis by PMNs
IgG: not specific anti-crystal antibodies

(Proteins coating the crystals modulate the cellular response)

These are NOT ANTI CRYSTAL AB

41

Apolipoprotein B-coating____________phagocytosis

inhibits

(Proteins coating the crystals modulate the cellular response)

42

Overproduction of uric acid (X-linked):
PRPP synthetase overactivity
__________(complete: Lesch-Nyhan)

HGPRT deficiency

43

___________ includes ligamentous-, tendinous-, fibrous-osseous junctions

Enthesitis

(Seronegative Spondyloarthropathies)

44

Phagocytosis of crystals ___________concentration

decrease

45

Local heat of inflammation __________MSU solubility

increase

46

Calcium Pyrophosphate Dihydrate Deposition Disease

Abnormal pyrophosphate (PPi) metabolism

"pseudogout"

47

PPi precipitates with calcium forming CPPD crystals in mid-zonal cartilage layers. Crystal release into the joint space. On xray?

Chondrocalcinosis

48

CPPD crystals:

rhomboid, positively birefringent

49

Seronegative Spondyloarthropathies hallmark

SI joints (sacroiliitis); morning (am) stiffness

50

Seronegative Spondyloarthropathies affect

Enthesitis:
ligamentous-, tendinous-, fibrous-osseous junctions

51

Seronegative Spondyloarthropathies Synovium:

Synovium: increased expression of TNF

52

HLA-B27 and Ankylosing Spondylitis (AS) Chance of developing AS

2% if HLA-B27 positive
20% if HLA-B27 positive with a first-degree relative with AS

53

HLA B27 + has a ___ chance of AS

2%

54

HLA B27 + w/ AS FDR has a ___ chance of AS

20%

55

Reactive Arthritis

Asymmetric, oligoarticular, lower ext arthritis

56

Dactylitis are?

sausage digits?

57

Reactive Arthritis Unfolded protein hypothesis: ER stress response

in ER HLA b27 misfolds and cannot be released
builds up in ER
stress response to cell
ER stress makes Il-23--> Th17 --> inflammation

58

Reiter’s syndrome: clinical triad of conjunctivitis, urethritis, arthritis

Former name of Reactive Arthritis

59

Reiter’s syndrome: clinical triad of ___________

conjunctivitis, urethritis, arthritis

60

Systemic Lupus Erythematosus (SLE)

A chronic, systemic autoimmune disease which affects multiple organ systems including the skin, joints, serosal surfaces, lungs, kidneys, CNS, and hematologic system

61

SLE - Fundamental defect is the ________________, resulting in an autoimmune process; T cell and B cell process

misdirected recognition of self as foreign

62

SLE is a?

T AND B CELL PROCESS

63

SLE Antibody responses toward autoantigens are antigen-driven and require ____________

CD4+ T cells

64

SLE Loss of T cell tolerance permitting autoreactive B cell stimulation: ? central or peripheral abnormality in_____________ lymphocyte deletion or anergy

self-reactive

65

Association with HLA-DR3 and C4A null allele (greatest risk)

SLE

66

SLE Association with HLA-DR3 and _________ (greatest risk)

C4A null allele

67

SLE- Loss of T cell tolerance permitting ___________: ? central or peripheral abnormality in self-reactive lymphocyte deletion or anergy

autoreactive B cell stimulation

68

Antinuclear Antibodies (ANA)

SLE: > 95% patients have + ANAs
Not specific for SLE
Antibodies are directed to multiple nuclear antigens
CD4 directed

69

Systemic Lupus Erythematosus (SLE)

Genetics (polygenic):
C4A null allele (greatest risk)

70

ANA specific for SLE?

NOPE

71

Anti-dsDNA antibodies:

renal disease

72

Anti-histone antibodies:

SLE and drug-induced lupus

73

Anti-phospholipid antibodies: block prothrombin activation in the clotting cascade; associated with increased _______ ? neutralize anticoagulant effect of 2 GP1; do not cause a vasculitis

clotting


Specific antibody-mediated disease (Type II):

74

Inflammation within or through the vessel wall resulting in damage to vessel integrity/flow

Vasculitis

75

Vasculitis Pathology


Varying degree of infiltrating lymphs, monocytes, histiocytes, eosinophils, and PMNs
Granulomas and/or giant cells in vessel wall in some types of vasculitis
Fibrinoid necrosis of vessel wall secondary to immune complex deposition
Focal and segmental nature of vascular lesions common to all types of vasculitis

76

Vasculitis Pathology

Immune complexes: inflamm→ PAFs→ ↑vascular permeability→ IC deposition; __________

palpable purpura

77

Vasculitis Pathology- Pathophysiology:

Immune complexes: inflamm→ PAFs→ ↑___________→ IC deposition; palpable purpura

vascular permeability

78

Vasculitis Pathology- Pathophysiology:

T cell dependent-mediated endothelial cell injury: (HLA-DR4 and giant cell arteritis; suggests ___________ vascular inflammation)

antigen-driven

79

HLADR4 in Vasculitis is not related to?

RA HLADR4

80

Vasculitis- Sources of antigen for immune complexes:

Drugs
Bugs: infectious agents
Connective tissue disease: autoimmune process
Malignancy

81

ANCA Vasculitis

Antineutrophil Cytoplasmic Antibodies. Seperates small Vasculitis

82

*Cytoplasmic ANCA (c-ANCA):

Proteinase-3 (PR3) in primary granules of PMNs
Associated with generalized GPA (Wegener’s)

83

*Perinuclear ANCA (p-ANCA):

Myeloperoxidase (MPO) in primary granules of PMNs
Associated with microscopic polyangiitis (MPA)

84

Inflammatory myopathies are characterized by:
Muscle weakness (proximal) and low endurance
Usually idiopathic but may occur in association with neoplastic diseases or in “overlap” with CTDs

Polymyositis / Dermatomyositis (PM/DM)

85

-DM presents with typical skin rashes:

Gottron’s papules
Heliotrope rash
V-sign and shawl-sign
Mechanic’s hands
Periungual changes/erythema

86

*Anti-synthetase Syndrome

PM or DM presenting with:
Interstitial lung disease (ILD): 60%*****


Anti-synthetase antibodies:
Anti-aminoacyl-tRNA synthetases (cytoplasm)
Anti-Jo-1 = anti-histadyl-tRNA synthetase
Not pathologic or myotoxic antibodies

87

Anti-synthetase antibodies:
Anti-aminoacyl-tRNA synthetases (cytoplasm)
Anti-Jo-1 = ______________
Not pathologic or myotoxic antibodies

anti-histadyl-tRNA synthetase (antiJo1)

Not pathologic or myotoxic antibodies- IT IS A MARKER OF DISEASE

88

Endomysial distribution of inflammatory cells (CD8+ T cells) surrounding and invading muscle fibers

Polymyositis

89

Perivascular (CD4+ T cells) and perifascicular inflammatory infiltrate

Dermatomyositis

Around vasical

90

Polymyositis / Dermatomyositis Evidence suggesting a _________ etiology:

viral

Viral particles by EM and viral RNA detected in muscle from PM/DM patients. *NO* live virus has been cultured from muscle

91

Osteoarthritis (OA) Joint Involvement:

Joint Involvement:
DIP (Heberden’s), PIP (Bouchard’s), 1st CMC
Hips and knees
Spine: cervical and lumbar
First MTP