B6.002 Rheumatoid Arthritis - Big Case

Question 1

what is considered polyarticular?

Answer 1

> 5 joint affected

Question 2

viral etiologies that can cause polyarticular joint pain

Answer 2

hep B
hep C
parvovirus B19
rubella
HIV
dengue
chikungunya

Question 3

bacterial etiologies that can cause polyarticular joint pain

Answer 3

lyme
endocarditis
rheumatic fever
reactive arthritis

Question 4

systematic rheumatological etiologies of polyarticular joint pain

Answer 4

RA
psoriatic arthritis
IBD
SLE
sarcoidosis
ANCA vasculitis
scleroderma

Question 5

miscellaneous etiologies of polyarticular joint pain

Answer 5

malignancy

familial Mediterranean fever

Question 6

clinical manifestation of RA

Answer 6

symmetric polyarthritis
morning stiffness > 1 hour
spares DIPs and lumbar spine

Question 7

pulmonary manifestations of RA

Answer 7

interstitial lung disease (SOB, cough, crackles)
pulmonary nodules
pleural effusion
pleurisy

Question 8

cardiac manifestations of RA

Answer 8

accelerated cardio disease
pericarditis, pericardial effusion
myocarditis
nodules

Question 9

hematologic manifestations of RA

Answer 9

Felty’s syndrome

anemia of chronic disease

Question 10

what is Felty’s syndrome triad

Answer 10

neutropenia
splenomegaly
recurrent infections

Question 11

skin manifestations of RA

Answer 11

rheumatoid nodules

Question 12

neurologic manifestations of RA

Answer 12

C1-C2 atlantoaxial instability

peripheral neuropathy

Question 13

ocular manifestation of RA

Answer 13

dry eyes/ mouth
secondary Sjogren’s syndrome
episcleritis
corneal melt

Question 14

diagnosis tests for RA

Answer 14

rheumatoid factor (RF)
anti-citrullinated protein antibodies (ACPA) (CCP)

Question 15

tests that assist with RA disease activity

Answer 15

ESR

CRP

Question 16

evaluations for alternative explanations of arthritic pain

Answer 16

anti nuclear antibodies (ANA)
hep B,C
HIV
parvovirus IgM

Question 17

what is seropositive RA

Answer 17

rheumatoid factor and/or CCP positive

80%

Question 18

what is seronegative RA

Answer 18

rheumatoid factor and/or CCP negative

20%

Question 19

what is RF?

Answer 19

autoantibody

IgM against the Fc (constant) portion of IgG

Question 20

causes of elevated RF

Answer 20

RA (nonspecific)
infection
antibody production

Question 21

what are ACPAs?

Answer 21

anti-citrullinated protein antibodies
70% sensitive for RA
95% specificity for RA

Question 22

describe the process of citrullination

Answer 22

post translational modification to arginine
performed by peptidylarginine deiminase (PAD)
forms citrulline

Question 23

is imaging used in diagnosis of RA?

Answer 23

not required for diagnosis
used more to evaluate prognosis/progression
patients with erosions at initial presentation do worse overall

Question 24

what imagine modalities are most common in RA diagnosis/management

Answer 24

Xrays of hands and feet

Question 25

what might an Xray of an first time RA patient look like?

Answer 25

periarticular osteopenia is earliest change
ulnar styloid and 5th metatarsal are first locations of erosions
symmetric joint space narrowing
absence of osteophytes

Question 26

how is a synovial fluid evaluation helpful in diagnosing arthritic pain?

Answer 26

noninflammatory processes have WBC <2000
inflammatory processes have WBC >2000
infectious processes have WBC >100000

Question 27

give a brief description of the pathogenesis of RA

Answer 27

1. P. gingivalis bacteria is present in the gingiva of teeth
2. PPAD enzyme (bacterial PAD) citrullinates human and bacterial proteins
3. citrullinated antigens taken up by APCs
4. certain individuals are predisposed to presenting these antigens and activating T cells in response
5. T cell activation leads to B cell activation
6. B cell activation leads to production of ACPAs against citrullinated proteins
7. immune complexes form and can deposit in joints where citrullinated proteins are common
8. joint inflammation is exacerbated by joint injury

Question 28

what 2 factors work together in the pathogenesis of RA

Answer 28

genes (specifically HLA-DRB1 shared epitope)

environment (specifically smoking)

Question 29

what mediated tissue damage in RA

Answer 29

immune complexes lead to activation of:
osteoblasts
neutrophils
synovial fibroblasts

Question 30

RA epidemiology

Answer 30

1% prevalence- increased in some native populations
15-30% identical twin risk
5% first degree relative risk
2-3x more likely in women
peak onset 50-75

Question 31

what is the shared epitope?

Answer 31

highly similar AA sequence in alleles in HLA-DRB1 locus

strongest genetic link to RA

Question 32

what is the function of the shared epitope

Answer 32

involved in MHC molecule based antigen presentation and responsible for self-peptide selection and T cell repertoire
-particularly effective at presenting citrullinated peptides

Question 33

what is the treatment approach in RA?

Answer 33

goal is clinical remission

stepwise approach of escalation of therapy until goal is reached

Question 34

first line RA drug

Answer 34

methotrexate

Question 35

special considerations of methotrexate

Answer 35

ethanol use

pregnancy

Question 36

what is the step after methotrexate

Answer 36

ADD
1. sulfasalazine + hydroxychloroquine (triple therapy)
OR
2. TNF inhibitor (etanercept, adalimumab, infliximab, certolizumab, golimumab)
AND THEN ADD
3. others: abatacept, rituximab, tocilizumab, anakinra, tofacitinib