Rheumatoid Arthritis

Front 1

Describe the genetic and epidemiological distribution of RA.

Back 1

Rheumatoid Arthritis – 80% HLA DRB1 positive but accounts for approximately 30% of total genetic component and 3 times more likely in women. Affects 1% of population and is rare in Asians and Africans but common (5%) in American Indians

Front 2

What is the ACR classification of RA?

Back 2

• 4/7 criteria must be satisfied for RA – RA RA RSM
o Rheumatoid nodules
o Arthritis in 3 or more areas (>6 weeks)
o Radiographic changes
o Arthritis of hand joints (wrist, MCP, PIP – not usually DIP  OA) (>6 weeks)
o Rheumatoid factor
o Symmetric involvement (>6 weeks)
o Morning stiffness of joints >1 hour (>6 weeks)

Front 3

Describe the distribution of joint involvement in RA.

Back 3

o 90% Metacarpo-phalangeal and PIP joints and Metatarso-phalangeal joints – DIP joints spared
o 80% - Wrist and Knee and ankle
o 50% - shoulder, elbow, hip and AC joints
o 30-40% - cervical spine and tempero-mandibular joints

Front 4

Name at least 5 extraarticular manifestations of RA.

Back 4

o Cardiac
 Pericarditis
 Endocarditis
o Haematological
 Anaemia of chronic disease
 Thrombocytosis
o Pulmonary
 Pleural effusions

Front 5

What is the pathophysiology of RA?

Back 5

As usual Tc activation in LN trigerred by unknown stimulus in periphery which is picked up by APC.
Key cytokines: IL-1, IL-6, TNF-α

Front 6

Describe the 2 autoantibodies present in RA.

Back 6

o Rheumatoid factor
 Antibody to Fcportion of IgG
 Present in ~75% of patients with RA
 Not specific for RA
 IgG, IgM and IgA RFs are present in RA
 IgM RF correlates best with disease activity and severity (including extra- articularmanifestations)
o Anti-cyclic citrullinatedpeptide antibodies (anti-CCP)
 More specific for RA than RF
 Not more sensitive than RF
 Citrullineis a modified version of amino acid arginine
 Citrullination (by peptidylargininedeiminase) is more common in RA
o ANA is not definitive (+/-)

Front 7

Describe the formation of pannus in joint affected by RA.

Back 7

Early RA: thickened synovial membrane because of hyperplasia and hypertrophy of synovial lining cells
↓
Angiogenesis of synovium
↓
Infiltration of the synovial membrane by Tc (predominantly CD4Tc) and Bc and neutrophils
↓
Established RA: synovial membrane transformed to form pannus which invades and destroy the adjacent cartilage and bone

Front 8

Name at least 5 conventional DMARDs (Disease Modifying Anti Rheumatic Drugs) and associated toxicities.

Back 8

MTX - GI upset, hepatotoxicity, blood dyscrasia
Hydroxychloroquine - eyes (corneal deposits, loss of accommodation
Sulfasalazine - GI upset, liver toxicities
Leflunomide - GI upset, liver toxicity
Cyclosporin - GI upset, alopecia
Azathioprine -
Penicillamine - Rash and renal toxicity
Gold - highly toxic, rash and renal toxicity

Front 9

Name the biological DMARDs.

Back 9

TNF Inhibitor
• Etanercept (Enbrel)
• Infliximab (Remicade)
• Adalimumab (Humira)
IL-1 inhibitor - Anakinra (Kineret)
IL-6 inhibitor - Tocilizumab(Actrema)
Tc costimulation interference - Abatacept (Orencia)
Bc depletion - Rituximab (Mabthera)

Front 10

What are the 4 goals of treatment in RA?

Back 10

o Symptom relief
o Preservation of normal function
o Preservation of structural damage and deformity
o Achieve remission with DMARDs (esp. if early)

Front 11

What are the indicators of poor prognosis to treatment? (at least 5)

Back 11

o High RF titre
o Anti-CCP (Cyclic citrullinated) Ab +ve
o Structural damage/deformity (bone erosion on Xrays)
o Nodules, vasculitis and other extra-articular disease
o Polyarthritis
o Young age, female
o Low education, poverty and psychosocial problems
o Uncontrolled inflammation (high CRP and ESR)
o Functional disability
o Genetic components (PTPN22 polymorphisms, GSTase)

Front 12

State the MOA of: aspirin, non-selective NSAIDs, COX-2 selective inhibitor, paracetamol

Back 12

Aspirin - irreversible inhibitor of both COX 1 and 2
NSAIDs - competitive inhibition of both COX 1& 2
COX -2 selective inhibitor
Paracetamol - reduced oxidised form of COX OR inhibit COX 3

Front 13

State the location by which COX-1 can be located

Back 13

Ubiquitous: platelet, gastric mucosa, vascular endothelium and renal.

Front 14

Where can you find COX-2?

Back 14

expresesed under basal condition in brain and renal.
It is normally undetectable in most tissues but is induced during pathophysiological process.

Front 15

Why is COX-2 inhibitor associated with increased cardiovascular risk?

Back 15

COX-1 synthesises thromboxane A2 which main function is to promote vasoconstriction and platelet aggregation. This action is normally balanced by prostacyclin synthesised by COX-2, it is a vasodilator and inhibit platelet aggregation. With inhibition of COX-2, the action of Thromboxane A2 is unopposed -> increased cardiovascular risk (thrombosis, atherosclerosis, HTN)