Clinical features of RA and an approach to therapeutics

Question 1

Define Rheumatoid Arthritis

Answer 1

chronic, autoimmune, systemic illness characterised by a symmetrical peripheral polyarthritis and other systemic features.

Question 2

outline the 1987 ARA criteria for classification of RA

Answer 2

morning stiffness, arthritis of more than 3 joint areas, hand joints, systemic arthritis, rheumatoid nodules, serum rheumatoid factors, radiographic changes

Question 3

outline the 2010 EULAR/ACR criteria for classification of RA

Answer 3

Question 4

what is the epidemiology and aetiology for RA?

Answer 4

1% of pop, female 3:1,

overall incidence of RA rises to 4% in siblings and 15% in monozygotic twins, genetic contribution is said to be 50-66%.

Closest association with a specific amino acid sequences at positions 70-74 of DRbeta1. cigarette smoking and chronic infection (e.g.peridontal disease)

Question 5

aetiology and pathogenesis of RA…

Answer 5

women before menopause are effected three times more than men.

Fhx.

HLA-DR4, HLA-DRB1 confer susceptibility to RA. Smoking is also an environmental risk.

The triggering antigen in RA is not known but factors produced by activated T cells (interferon, IL-2 and IL-4), macrophages (IL-1, IL-8, TNF-α, macrophage inflammatory protein), mast cells (histamine and TNF-α) and fibroblasts (IL-6, vascular cell adhesion molecule, delay accelerating factor) contribute to the ongoing synovial inflammation.

Local production of rheumatoid factor (autoantibodies directed against the Fc portion of immunoglobulin [Ig]) by B cells and formation of immune complexes with complement activation also maintain the chronic inflammation.

Question 6

Pathogenesis of RA

Answer 6

there is synovitis = villous hyperplasia, infiltration od t cells, b cells, macrophages and plasma cells. Intimal cell proliferation (fibriblasts), production of cytokines and proteases, increased vascularity. Self amplyfying process.

Erosion of the corner of the joint, inflamed synovium spreading across the surface of the joint, thinning of the cartilage, inflamed tendon sheath and inflamed joint capsule.

RA is characterized by synovitis (inflammation of the synovial lining of joints, tendon sheaths or bursae) with thickening of the synovial lining and infiltration by inflammatory cells.

Generation of new synovial blood vessels.

The synovium proliferates and grows out over the surface of cartilage, producing a tumour-like mass called ‘pannus’. Pannus destroys the articular cartilage and subchondral bone, producing bony erosions. This early damage justifies the use of disease-modifying drugs within 3 months of onset of the arthritis to try and induce disease remission.

Question 7

Clincial features of RA

Answer 7

Pain, early morning stiffness, rheumatoid nodules,

ulnar deviation of the fingers,

radial deviation of thhe wrist.

synovitis of the MCP and PIP joints,

wasting of hand muscles, fixed deformity of the hands and wrists, symmetrical swelling in small proximal joints of the hands and feet,

Z shaped thumb, ulnar deviaiton,

Swan-neck deformity,

Boutonnière deformity.

There is spindling of the fingers caused by swelling of the PIPJs but not DIPJs.

The metacarpophalangeal and wrist joints are also swollen. instability, subluxation (partial dislocation) and deformity.

systemic symptoms, symptoms get better thorughh the day. tenderness, limitation of movement, redness, heat.

Question 8

Systemic features of RA

Answer 8

fatigue, weight loss, anaemia, vasculitic rash eyes - scleritis,

Sjogren’s syndrome (dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), parotid gland enlargement)

lungs - pleural effusion, lung fibrosis, rheumatoid nodules

Haematological - Felty’s syndrome (RA, splenomegaly and neutropenia),

Lymphadenopathy.

neurological - carpal tunnel syndrome, cord compression

CVS - perdicarditis, pericardial effusion, Raynaud’s syndrome.

Kidneys - amyloidosis

Vasculitis - leg ulcers, nail fold infarcts, gangrene

Question 9

Ix for RA - long version

Answer 9

Basically look at acute phase reactants first so…ESR, CRP, also give a cheeky FBC to look for anaemia and to check on those u’s and e’s.

The main test for RA is ANTI-CCP! - this is specific to RA. (Serum antibodies (ACPA), anti cyclic citrullinated abx (anti-CCP) found).

Rheumatoid factor - you can do this but its not always specific - REMEMBER it’s only found in 70-90% of patients with RA.

Of course you can bang an MRI, USS and Xray

Question 10

Ix of RA - short version

Answer 10

Basically - ESR, CRP, FBC, UandE’s

ANTI-CCP!

Rheumatoid factor

MRI, USS, XRAY

Question 11

DDX for RA

Answer 11

Septic arthritis,

Reactive arthritis,

Reiters syndrome,

Psoratic arthritis

(SLE)

(Gout)

Question 12

assessment of RA

Answer 12

Disease assessment score

less than 2.4 represents clinical remission,

more than 5.1 represents eligibility for biologic therapy.

Question 13

prognosis

Answer 13

not v good - 50% disabled within 20 yrs of diagnosis,

50% out of workplace in 2 yrs of diagnosis.

Shortens life expectancy by 7 yrs.

Question 14

therapeutic mx

Answer 14

Education,

physio,

DMARDS,

NSAIDS (give with PPI cover)

CORTICOSTERIOD INJECTIONS,

ANALGESIA,

Biologics - anti-b cell agents,

community support,

surgical intervention

Question 15

what are the 4 tx options for RA?

Answer 15

NSAID’s,

Disease modifying anti rheumatic drugs (DMARD),

biologics,

corticosteroids.

Question 16

name 4 DMARD’s

Answer 16

methotrexate, sulfasalazine, hydroxychloroquine, leflunomide.

( DON’T USE gold salts, penicillamine) some have been toxic and had adverse feects.

Question 17

why is methotrexate preferred?

Answer 17

effective, well tolerated and cheap, not as toxic, cornerstone of tx. People stay on it.

Question 18

name biologics used

Answer 18

sulfasalazine, etanercept, adalinumab. TNFalpha inhibitors, IL-1 inhibitors (Anakinra), Anti B Cell therapies (CD20, rituximab), Anti T Cell therapies (Abatacept), IL-6 inhibitors (tocilizumab)

STARE

Question 19

SE’s of Sulfasalazine?

Answer 19

mouth ulcers, hepatitis, male infertility.

Question 20

SE’s of Methotrexate?

Answer 20

mouth ulcers and diarrhhoea, liver fibrosis, pulmonary fibrosis, renal impairment.

Don’t use in pregnancy - use sulfasalazine instead

Question 21

what are the issues with biologics?

Answer 21

better when coprescribed with methotrexate, minor toxicity, can be costly.

Question 22

tx strategies

Answer 22

sequential monotherapy,

combination (step up, down, parallel),

treat to target.