Rheumatoid Arthritis

Question 1

Prevalence of RA

Answer 1

0.5-1%

Question 2

Age and gender of RA

Answer 2

30-60 years, female

Question 3

What is the reduced life expectancy of RA?

Answer 3

7-10 years

Question 4

Which environmental factors lead to the progression of RA?

Answer 4

smoking, periodontitis, gut microbiome

Question 5

What is the shared epitope of RA?

Answer 5

The amino acid motif QKRAA in the HLA-DRB1 region

Question 6

Which bacteria in periodontal disease is an environmental factor in RA?

Answer 6

prophyromonas gingivalis

Question 7

When do anti CCP antibodies peak?

Answer 7

disease onset to first year of symptoms

Question 8

What are the autoantibodies in RA?

Answer 8

RF, ACPA, anti-PAD4, AntiCarP, Anti-MDA, Anti-MMA

Question 9

What are RF antibodies directed against?

Answer 9

Fc portion of human IgG

Question 10

What percentage of patients with RA will have positive RF?

Answer 10

75%

Question 11

Who has more severe disease seropositive or seronegaitve patients?

Answer 11

seropositive

Question 12

Which other autoimmune diseases may have positive RF?

Answer 12

sjogrens, cryoglobulinaemia, SLE

Question 13

Which non autoimmune diseases may have positive RF?

Answer 13

chronic infection (hep B, hep C), cancer

Question 14

What is citrullination?

Answer 14

the post translational conversion of peptidylarginine to peptidylcitrulline

Question 15

What are ACPAs associated with?

Answer 15

more severe disease, RA related lung disease, cardiovascular disease

Question 16

What are the key cytokines in RA?

Answer 16

TNF, IL-17A, IL-17F, IL-1alpha, IL-1beta, IL-6

Question 17

Which joints are spared in RA?

Answer 17

DIP

Question 18

What is RS3PE syndrome?

Answer 18

Remitting, seronegative, symmetric synovitis with pitting edema syndrome:

• oedema of dorsum of hand or foot
• tenosynovitis
• seronegative for RF and ACPA
• responds well to glucocorticoids
• can be paraneoplastic

Question 19

Which direction does the wrist deviate?

Answer 19

radial

Question 20

Which direction do the fingers deviate at the MCP?

Answer 20

ulnar

Question 21

What are the dermatologic manifestations of RA?

Answer 21

rheumatoid nodules, vasculitis, ulcers, neutrophilic dermatoses, treatment related rashes

Question 22

What are the opthalmologic manifestations of RA?

Answer 22

episcleritis, scleritis, perilimbic ischaemic ulcers, secondary sjogren’s syndrome

Question 23

What are the pulmonary manifestations of RA?

Answer 23

pleural effusions, nodules, cricoaretynoid arthritis, interstitial lung disease, bronchiectasis, cryptogenic organising pneumonia

Question 24

What are the cardiovascular manifestations of RA?

Answer 24

premature atherosclerosis, pericarditis, pericardial effusion, arrhythmias, myocarditis, heart failure, cardiac nodules

Question 25

What are the GI manifestations of RA?

Answer 25

xerostomia, gastritis (from NSAIDs), stomatitis, mucositis (from methotrexate)

Question 26

What are the renal manifestations of RA?

Answer 26

glomerulonephritis, proteinuria, treatment related kidney injury

Question 27

What are the hepatic manifestations of RA?

Answer 27

nodular regenerative hyperplasia, portal fibrosis, treatment related hepatitis/cirrhosis

Question 28

What are the haematological manifestations of RA?

Answer 28

lymphadenopathy, felty syndrome, lymphoma, amyloidosis, cryoglobulinaemia, large granular lymphocyte syndrome

Question 29

What are the radiographic characteristics of RA?

Answer 29

``` Periarticular soft tissue swelling (joint effusion, tenosynovitis) Juxta-articular osteoporosis Marginal erosions Joint space narrowing Symmetric involvement Deformities in advanced disease ```

Question 30

Which is the most important DMARD?

Answer 30

methotrexate

Question 31

What is the dose of methotrexate?

Answer 31

15-25mg weekly

Question 32

What are the adverse effects of methotrexate?

Answer 32

nausea, hair loss, stomatitis, hepatotoxicity, cytopaenias, pneumonitis, teratogenecity

Question 33

What is the efficacy (ACR70 response rate) of methotrexate?

Answer 33

20-40%

Question 34

How is methotrexate excreted?

Answer 34

renally

Question 35

What is the dose of sulfasalazine?

Answer 35

2-4g daily

Question 36

What is the efficacy (ACR70 response rate) of sulfasalazine?

Answer 36

8% at 2g/d

Question 37

What are the adverse effects of sulfasalazine?

Answer 37

hypersensitivity reactions, nausea, diarrhoea, agranulocytosis, drug induced lupus, azoospermia

Question 38

What are the adverse effects of hydroxychloroquine?

Answer 38

hyperpigmentation, retinopathy, myopathy, cardiomyopathy

Question 39

What is the mechanism of action of leflunomide?

Answer 39

inhibition of DHODH (dihydrooratedehydrogenase), an enzyme in de novo pyrimidine synthesis (required for T-cell activation)

Question 40

What is the dose of leflunomide?

Answer 40

10-20mg daily

Question 41

What are the adverse effects of leflunomide?

Answer 41

``` Diarrhoea(~25%) Hypertension Hypersensitivity reactions LFTs and pneumonitis (esp. if combined with methotrexate and b/g ILD) Leukocytopenia Teratogenicity Peripheral neuropathy ```

Question 42

What are the different types of biologic DMARDs?

Answer 42

TNF inhibitors, Anti-CD20, IL-6R inhibitor, Jak inhibitors, T cell costimulation inhibitors

Question 43

What are the contraindications for TNF inhibitors?

Answer 43

``` SLE Demyelinating disorders Current, active, serious infection Recurrent or chronic infection Untreated latent or active mycobacterial infection Hepatitis B infection Congestive heart failure Pregnancy ```

Question 44

What are the adverse effects of TNF inhibitors?

Answer 44

``` Infections (including serious infections) Opportunistic infections (e.g., tuberculosis) Malignancies (skin cancer, lymphoma [?]) Demyelinating conditions Autoantibodies (ANA, anti–ds DNA) Hepatotoxicity Dermatologic reactions Lupus-like syndromes ```

Question 45

What is abatacept?

Answer 45

A T-cell costimulation inhibitor

Question 46

What is tocilizumab?

Answer 46

An IL-6 receptor inhibitor

Question 47

Why can't CRP be used as a measure of infection in patients on tocilizumab?

Answer 47

Because IL-6 is a driver of inflammation so CRP may be normal

Question 48

What are the adverse effects of tocilizumab?

Answer 48

``` Infections Deranged LFTs Thrombocytopaenia Neutropaenia GI perforation Anaphylaxis ```

Question 49

What is rituximab?

Answer 49

An anti CD-20 antibody that depletes B cells but spares plasma cells

Question 50

What are the adverse effects of rituximab?

Answer 50

Infections, infusion reactions, diminished response to vaccination, reactivation of hepatitis B, rarely: progressive multifocal leukoencephalopathy

Question 51

What are the adverse effects of jak inhibitors?

Answer 51

infections herpes zoster cytopaenias hyperlipidaemia

Question 52

What is the standard strategy for RA treatment?

Answer 52

first line: start methotrexate plus short term glucocorticoids second line: add a biologic DMARD or targeted synthetic DMARD third line: use a different biologic or targeted synthetic when in remission phase taper doses or increase time between treatment

Question 53

How should you manage cardiovascular risk in patients with RA?

Answer 53

measure lipids while in remission or low disease activity