Rheumatoid arthritis

Question 1

List the extra-articular features of RA (six systems)

Answer 1

Eyes: sicca, scleritis
Skin: rheumatoid nodules- ONLY in RF positive patients
Vasculitic: ischaemia, digital gangrene
Neurologic: compressive neuropathy eg carpal tunnel, cervival cord compression, mononeuritis multiplex
Lung: pleural effusions, nodules, ILD
Haem: B cell lymphomas 2-3 x increased

Question 2

What is Felty’s syndrome

Answer 2

In RA, the triad of:
Splenomegaly
Neutropaenia below 2
Low platelets

More often seen in people with extra-articular features (nodules, hepatomegaly, leg ulcers.

Bone marrow shows maturation arrest

Increased susceptibility to infection and risk of lymphoproliferative disorders

Tx: RA aggressively, G-CSF or GM-CSF

Question 3

What is special about RA-related pleural effusion?

Answer 3

One of the few causes of pH less than 7.2 (along with empyema and oesophageal rupture)

White cells often high but less than 10 000
Low complement
Glucose low
Exudate

Question 4

What are the cell count findings in aspiration of an RA joint?

Answer 4

WCC per microlitre 2 to 10 thousand, over 50% polys
A septic joint is over 50-70 thousand with more than 75% polys
Non inflammatory like OA is 2 hundred to 2 thousand

Question 5

Rheumatoid factor titre has what implications for disease

Answer 5

More severe joint involvement and radiographic progression
Extra-articular features- ILD, vasculitis
increased likelihood of response to B cell depletion (ritux)
Titre may derease with effective treatment especially DMARDs

Question 6

What are the non RA causes of increased RF

Answer 6

If VERY high think cryoglobulins and primary Sjogren's syndrome
Age
Chronic infection
Malignancy
Other CTD like lupus

Question 7

Compared with rheumatoid factor, what is the significance of elevated anti -citrullinated protein antibody? (ACPA)

Answer 7

More aggressive disease
More specific a test
Better predictor of errosive disease
Not associated with extra-articular features
Associated with shared epitope
If active smoker and ACPA postitive–>VERY high risk of going on to develop RA

Question 8

Poor prognostic markers in RA

Answer 8

Chronically elevated synovial and systemic inflammation eg CRP
RF and/or ACPA titre
HLADRB1*04 homozygosity
Smoking
Poor education, low SES
RADIOGRAPHIC ERROSIONS AT BASELINE (STRONGEST MARKER)

Question 9

Radiographic features RA (7)

Answer 9

Periarticular soft tissue swelling
Juxta-articular osteoporosis
Marginal erosions
Joint space narrowing
symmetric involvement
Deformities in advanced disease 
Erosion of the ulnar styloid

Question 10

What blood test in RA at baseline predicts subsequent risk of death from CV disease?

Answer 10

CRP

Overall fourfold increase in rate of incident CV events

Question 11

Which HLA is associated with RA?

Answer 11

HLA-DRB1*04

Question 12

What is RANK-ligand and what happens to levels in RA?

Answer 12

promotes osteoclast formation, activation, and survival
Increased in RA, especially active disease
Predicts bone errosions
Decreases in TNF blockers

Question 13

Name the non-biologic DMARDS used in RA

Answer 13

Glucocorticoids
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide

Question 14

When on methotrexate, avoid coadministration of which folate depleting drugs?

Answer 14

bactrim
trimethoprim
probenecid

Question 15

Side effects of methotrexate?

Answer 15

Oral ulcers
nausea/GI
hair loss

Question 16

When might you choose to use sulfasalazine in RA and what are the potential side effects?

Answer 16

If regular alcohol intake or another contraindication to methotrexate.
Rash
headache
GI
idiopathic- skin, hepatitis, pneumonitis, agranulocytosis, aplastic anaemia, haemolytic anaemia

Question 17

Which is the best tolerated DMARD?

Answer 17

Hydroxychloroquine (but modest clinical benefit)

First line treatment for palindromic rheumatism.

Question 18

What review is needed when using hydroxychloroquine?

Answer 18

Retinal toxicity

Question 19

leflunomide MOA?

Answer 19

Inhibits key enzyme in de-novo pyrimidine synthesis (dihydro-orotate dehydrogenase)
Pyrimidines needed for T cell proliferation and activation

Question 20

Side effects of leflunomide?

Answer 20

diarrhoea
peripheral neuropathy
ILD
elevated LFTs

Question 21

Biologic DMARDs- list with mechanisms

Answer 21

TNF blockers

• ertanacept
• infliximab
• adalimumab
• golimumab
• certolizumab

IL-6 antagonists
-Tocilizumab

Costimulatory molecule blocker (CTLA-4 agonist)
-Abataept

B cell depleter
-Rituximab

Kinase inhibitors
-Tofacitinib

Question 22

True or false, TNF inhibitors more effective when combined with methotrexate?

Answer 22

true

Question 23

Adverse effects of TNF inhibitors?

Answer 23

Skin site reaction
TB reactivation (more likely extrapulmonary, often disseminated)
Infection- skin, chest, sinus
Demyelinating disease (low risk)
Autoimmunity (ANA 11%, SLE 3%)
Cancer- skin cancers

Question 24

Which RA drugs are okay in pregnancy?

Answer 24

NSAIDS- avoid or use in lower doses, stop 6-8 weeks before delivery
Corticosteroids- probably increase risk of cleft lip
AZA, hydroxychloroquine, sulfasalazine probably safe
Need a cholestyramine washout if want to get pregnant within two years of leflunomide

Question 25

How does Sulfasalazine work in RA?

Answer 25

Cleaved in colon by bacterial enzymes to release acetylsalycilic acid and sulfapyridine - possibly inhibits transcription of inflammatory mediators

Question 26

Hydroxychloroquine MOA?

Answer 26

Increases pH within macrophage phagolysosomes so that this interferes with Ag presentation.

Question 27

type of vasculitis in RA

Answer 27

medium vessel

Question 28

PTH acts on…

Answer 28

osteoBLASTS to increase RANKL expression

Question 29

If GI side effects on MTx, do what

Answer 29

change to subcut

Question 30

Why would you give folic acid in mtx

Answer 30

reduce Gi side effects and hepatotox

mainly to reduce MOUTH ULCERS

Question 31

DIP are spared in

Answer 31

RA, SLE