Rheumatoid Arthritis

Question 1

Epidemiology of RA

Answer 1

• Most common type of polyarthritis. 3x more common in women. 1% total population.
• Peak onset in 3rd to 5th decade

Question 2

2 risk factors for RA

Answer 2

Tobacco and HLA-DRB1 (shared epitope)

Question 3

Pathogenesis of RA

Answer 3

Synovial membrane cells proliferate into a pannus rich w/ macrophages, fibroblasts, PMNs, B cells, plasma cells, and T cells. Vascular proliferation permits increased cell trafficking. Cytokines are released, MMPs break down bone / cartilage

Question 4

5 diagnostic criteria for RA

Answer 4

• Must have synovitis w/o other cause
• Multiple joints
• RF / CCP (more specific). High titer is >3xULN.
• Increased ESR / CRP
• > 6 weeks

Question 5

What joints are usually involved in RA? Which are not involved?

Answer 5

Usually involves PIPs, MCP, wrist, and MTP.

Usually does NOT involve hips, DIPs, and lumbar spine.

Question 6

ESR vs CRP

Answer 6

ESR reflects 1 month, CRP reflects days.

Question 7

Extra-articular / systemic manifestations of RA
Mild
Moderate / severe

Answer 7

• Mild: rheumatoid nodules, nail fold infarcts, iron deficiency anemia, Raynauds, Sjogrens
• Moderate / severe: scleritis, interstitial lung disease, pericarditis, pleuritis, vasculitis (may cause ulcers), Felty syndrome (neutropenia + splenomegaly), nerve impingement from cervical spine disease, premature CVD (due to systemic inflammation)

Question 8

Treating acute RA (3)

Answer 8

• NSAIDs – naproxen is good to start with.
• Prednisone – use while DMARDs kick in. Good for flares. Extra-articular disease requires higher dose.
• Steroid injections if only a few joints are involved.

Question 9

4 DMARDs

What does DMARDs stand for?

Answer 9

Disease modifying anti rheumatic drugs

Methotrexate, leflunomide, Sulfasalazine, and hydroxchloroquine.

Question 10

Methotrexate
Mechanism
Toxicity
Requirements

Answer 10

• Mechanism – inhibition of dihydrofolate reductase blocks purine synthesis. Blocks cells w/ high turnover.
• Toxicity – TERATOGEN, CIRRHOSIS (esp w/ ETOH), oral ulcers, GI, cytopenias, cough / SOB (lung hypersensitivity), infection
• Requires daily folic acid. Monitor CBC, liver, kidney. Get baseline LFTs, Hep B / C, and CXR.

Question 11

Leflunomide
Mechanism
Toxicity
Requirements
How is drug eliminated quickly?

Answer 11

• Mechanism – inhibits dihydroorotate dehydrogenase → stops pyrimidine / purine synthesis → stops proliferation of T cells.
• Toxicity – Teratogen, GI, alopecia, HTN, cytopenias, liver toxicity (esp w/ alcohol), infection
• Requirements: Monitor CBC, liver, kidney. Get baseline Hep B / C and CXR.
• Give cholestyramine in hospital for px w/ infection to get rid of drug quickly

Question 12

Sulfasalazine
Mechanism
Toxicity
Safe with what?
Requirements

Answer 12

• Mechanism – AB and anti-inflammatory
• Toxicity – GI, liver toxicity, aplastic anemia, nephritis syndrome, pancreatitis, headache. Contraindicated w/ sulfa allergy.
• Safe w/ pregnancy and alcohol.
• Monitor CBC, liver, and screen for G6PDH

Question 13

Hydroxychloroquine
Use
Mechanism
Toxicity
Requirement

Answer 13

• Use – Mainstay for lupus. Used for very mild RA.
• Mechanism – mild antimalarial that stablizes lysosomes, inhibits DNA polymerase, decreases fibronectin / platelet aggregation / histamine / IL1 cellular inflammation and destruction. Does NOT cause immunosuppression.
• Toxicity – retinal toxicity, pigment, neuromyopathy
• Monitor visual field testing every 1-5 years

Question 14

Triple therapy

Works as well as what?

Answer 14

Mtx, Ssz, Hcq.

Works as well as TNF-inhibitor

Question 15

TNFa Inhibitors
4 monoclonal Abs
1 soluble receptor drug

Answer 15

• Monoclonal Abs: infliximab, adalimumab, golimumab, certolizumab
• Etancercept is soluble receptor

Question 16

4 risks of TNFa Inhibitors

Answer 16

• Infection – may not mount high fever, atypical / fungal infection, disseminated TB (TB test should be done before starting anti-TNF)
• Heart failure
• Demyelination
• Malignancy – nonmelanoma skin cancer, lymphoma

Question 17

4 non-TNF biologics

Answer 17

Abatacept, rituximab, tocilizumab, tofacitinib

Question 18

Abatacept
Mechanism
Pro / con

Answer 18

CTLA4 blocks T cell co-stimulation.

Lower infection risk than anti-TNF, but takes 4 months to work

Question 19

Rituximab
Mechanism
Risk factors

Answer 19

Anti-CD20 Ab depletes naïve B cells.

Risk of Hep B reactivation and progressive multifocal leukoencephalopathy (PML, brain infection)

Question 20

Tocilizumab mechanism

Answer 20

Anti-IL6, which normally triggers cartilage destruction

Question 21

Tofacitinib
Mechanism
Risk

Answer 21

JAK kinase inhibitor.

Risk of EBV-related malignancy

Question 22

4 general risks of biologics

Answer 22

• Injection / infusion rxns due to being foreign molecules
• Predisposition to infection. Avoid live vaccinations. Evaluate fever / monoarthritis.
• Non-melanoma skin cancer
• Biologics should not be combined. May be used w/ DMARDs.

Question 23

Fibromyalgia
Gender / age
Sxs
Management

Answer 23

• 2x more common in women. Mean onset is 45 y/o. 2-5% of adults.
• Sxs: Diffuse chronic pain is hallmark. May have migrating burning, tender skin, flares, fatigue / sleep disruption, cognitive problems (“fibro fog”), headache, IBS, TMJ
• Management – sleep regulation, gentle exercise, non-narcotic pain meds; NO steroids b/c not inflammatory.