Rheumatology

Question 1

Osteoarthritis joints

Answer 1

DIP (Herberden's)
PIP (Bouchard's)
1st CMC
Hips and knees
Spine
First MTP

Question 2

OA mechanism

Answer 2

No systemic features
MMP breakdown of type II collagen in cartiladge:
increased chondrocytes
increased MMP
increased water content
decreased proteoglycan
decreased TIMP

Question 3

OA synovial fluid

Answer 3

noninflammatory

type I fluid (200-2,000 WBCs)

Question 4

OA cytokine factors and MMP effects

Answer 4

IL-1: stimulates MMPs and NO, PG, IL-6 production
NO: increases MMPs and inhibits proteoglycan/chondro
Prostaglandins: produce and activate MMPs

Question 5

OA radiographs

Answer 5

joint space loss
sclerosis
osteophytes

Question 6

RA joints

Answer 6

Non-symmetric, inflammatory joints
Spare DIP
Medium/large joints can be involved

Question 7

RA genetics

Answer 7

shared epitope QKRAA with HLA-DR4/HLA-DR1

damage mediated by RF-IgG immune complexes (rheumatoid nodules)

Question 8

RA markers

Answer 8

RF (IgM) not specific
Anti-CCP more specific
Both = very specific
Anti-CCP corresponds well with shared epitope

Question 9

RA mechanism (intra and extra articular)

Answer 9

Inflammed synovium
Pannus invasion and damage
Cytokine release -> B cell -> RF, Anti-CCP release
Immune complexes, complement activation
MMP stimulation and damage
Extra-articular: RF-IgG complex=vasculitis, rheum nodules

Question 10

RA cell types

Answer 10

CD4 - modulate/amplify local response via antigen recognition
Th17
B cells and plasma cells (RF, anti-CCP)

Question 11

Gout joints

Answer 11

1st MTP (podagra)
Cool, peripheral joints

Question 12

Gout hyperuricemia causes

Answer 12

Over-production (Xlinked): PRPP synthease overactivity, HGPRT deficiency
Under-excretor: 90%

Question 13

Gout mechanism

Answer 13

Purine metabolism byproduct, humans lack uricase
MSU recognized by TLR2/TLR4
NLRP3 Inflammasome activation resulting in caspase-1 pathway and IL-1ß production

Question 14

Gout synovial fluid

Answer 14

Dx by arthrocentesis

MSU crystals - needle shaped, negatively birefrigent

Question 15

Gout self limiting treatment

Answer 15

Protein coat: IgG or Apolipoprotein B
More phagocytosis = less concentration
Inflammatory heat
ACTH secretion suppresses inflammation

Question 16

Calcium Pyrophosphate Dihydrate Deposition Disease mechanism and crystal formation

Answer 16

Abnormal PPi metabolism
ANK gene mutation resulting in excess PPi leaking from chondrocytes
PPi precipitate with Ca2+ = CPPD crystals
Shedding, enzymatic strip mining
CPPD crystals: rhomboid, positively birefrigent

Question 17

Spondyloarthropathies joints and signs/symptoms

Answer 17

Spine and SI joints
Small and large peripheral joints
Enthesitis
Mucocutaneous lesion, rash, conjuctivitis
Anterior uveitis

Question 18

SAP genetics

Answer 18

HLA-B27

Negative RF and ANA

Question 19

Ankylosing Spondylitis chance of development

Answer 19

2% if HLA-B27 positive

20% if HLA-B27 and first degree relative affected

Question 20

Other HLA-B27 risks

Answer 20

Skin, nail, genital tract involvement
IBD
Heart involvement

Question 21

Reactive Arthritis joints and signs/symptoms

Answer 21

Asymmetric, oligo, lower extremity arthritis
Dactylitis - sausage digits
Can’t pee, can’t see, can’t climb tree

Question 22

ReactA mechanisms

Answer 22

molecular mimicry
Arthrogentic peptide: processed HLA-B27
HLA-B27 heavy chain, NK activation
***Unfolded protein - ER stress, Th17 activation***
Th2 response

Question 23

Systemic Lupus Erythematous defect

Answer 23

autoimmune (foreign as self)
T and B cell process
antigen driven (CD4+ T cells)
Loss of T cell tolerance allowing autoreactive B cell

Question 24

SLE pathogenesis

Answer 24

dsDNA as foreign

Ex. PMN death, DNA release to kill bacteria

Question 25

SLE genetics

Answer 25

Polygenic
HLA-DR3
C4A null allele (greatest risk)

Question 26

SLE markers and antibody targets (with pathology)

Answer 26

ANA positive (not specific, could be other CTD)
anti-dsDNA (renal disease)
anti-histone (SLE and drug induced lupus)
other (SSA, SSB, Smith, Ribonuclear protein)

Question 27

SLE Immune type disease

Answer 27

Type II
(anti-RBC/WBC, anti-phospholipid - block prothrombin, increased clotting)
Type III
(lumpy bumpy)

Question 28

Vasculitis cellular characteristics

Answer 28

Infiltrating of every immune cell (all)
Granulomas/giant cells in vessel wall (some)
Fibrinoid necrosis secondary to complexes (some)
Focal and segmental of vascular lesions (all)

Question 29

Vasculitis mechanisms

Answer 29

Immune complexes -> increased permeability -> deposition-> palpable purpura
ANCA
Anti-endothelial antibodies
T-cell dependent endothelial injury (HLA-DR4, not shared epitope)

Question 30

SLE sources for antigen

Answer 30

Bugs
Drugs
CTD
Malignancy

Question 31

ANCA mediated vasculitis

Answer 31

cytoplasmic ANCA = proteinase 3 in PMN granules
cANCA = GPA
perinuclear ANCA = MPO in PMN granules
pANCA = microscopic polyangitis (MPA)

Question 32

Polymyositis/Dermatomyositis clinical signs

Answer 32

Proximal muscle weakness
idiopathic or overlap with CTD
Grotton's papules
Helitrope rash
Vsign/shawl sign
Mechanics hands
Periungual changes

Question 33

PM/DM Anti-synthetase syndrome:
Diseases
2 antibodies

Answer 33

Top presenting disease = interstitial lung disease (60%)
Anti-aminoacyl tRNA synthetase (cytoplasm)
Anti-jo1 = anti-histadyl-tRNA synthetase
Not pathologic/myotoxic antibodies

Question 34

PM/DM staining patterns

Answer 34

PM: CD8+ T cells surrounding and invading fibers (direct damage mediated)
DM: CD4+ T cells perivascular/perifascicular (complex mediated)

Question 35

PM/DM etiology

Answer 35

Possible viral etiology
NO live virus cultured, but particles and RNA detected
Juvenile DM: increased ab to coxsackie B
Seasonal patterns (anti-jo)
DM: mRNA profiling with interferon response (viral)