Rheumatoid Arthritis

Question 1

Patients with Arthritis usually also have what…?

Answer 1

Normochromic and Normocytic anaemia: reduced numbers of normal-sized erythrocytes with normal Hb content associated with chronic disease

Raised inflammatory markers (ESR and CRP)

Question 2

What is Rheuatoid Arthritis and who does it afffect?

Answer 2

Common systemic autoimmune disorder affecting 1% of UK population

Pre-menopause, women 3 times more like to be affected than men (1:1 after menopause)

Can present at any age but peak prevalence between 30-50 years

Gradual onset of symptoms most common

Question 3

The cause of rheumatoid arthritis is unknown but describe the proposed mechanism

Answer 3

Generalised non-specific inflammatory response, localised tissue damage and release of neo-autoantigens leading to activation of synovial T cells (initiating event)
B-cells activated and produce autoantibodies and rheumatoid factors which form immune complexes, bind to complement, and stimulate neutrophils to produce pro-inflammatory cytokines (IL-1 and TNF-alpha) and chemokines

Question 4

Describe the immune response in RA?

Answer 4

(1) Non-specific inflammation
(2) Synovial T cell activation

(3) B cell activation, auto-
antigen antibodies and rheumatoid factors

(4) Production of pro-inflammatory cytokines (IL-1 and TNF-alpha) & chemokines

Chronic inflammation is maintained by rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines

Question 5

What is RA characterised by?

Answer 5

Chronic synovitis - inflammation of the synovial lining of joints, tendons sheaths or bursae

Question 6

Describe the pathology of RA?

Answer 6

New synovial blood vessels, induced by angiogenic cytokines, and endothelial cell activation expedites leucocyte extravasion into the synovium

Synovium proliferates, growing out over cartilage surface, and forms a pannus.

Pannus destroys articular cartilage and subchondral bone, producing bony erosions

Subcutaneous rheumatoid nodules form

Question 7

What are some of the symptoms of RA? (5)

Answer 7

Swelling of small joints
Morning stiffness
Joint capsules are weakened leading to instability
Joint effusions 
Muscle Wasting

Question 8

What are the Periarticular features of RA? (4)

Answer 8

Bursitis
Tenosynovitis
Muscle wasting
Subcutaneous nodules (20% cases)

Question 9

What are the Extra-articular features of RA? (5)

Answer 9

Fever
Fatigue
Anaemia
Sjörgens syndrome (dry eyes and mouth due to destruction of epithelial exocrine glands)
Carpal tunnel syndrome (pressure on median nerve)

Question 10

what are the diagnostic features of RA?

Answer 10

1. Blood count
   Anaemia (normochromic and normocytic)
   Thrombocytosis (over production of platelets)
   Raised ESR (Erythrocyte sedimentation rate) & CRP (C-reactive protein) - both in response to inflammation
2. Serum Autoantibodies
   Rheumatoid factor present in 70-80% RA cases (but not only in RA)
   Antinuclear factor present in 30% RA cases
   Anti-citrulline-containing peptide (CCP) in 50-60% early RA cases and in erosive disease
3. Radiology
   Soft tissue swelling, erosion at joint
4. Sterile synovial fluid with high neutrophil count

Question 11

As there is no available cure, what management options are there for RA?

Answer 11

1. NSAIDs
2. DMARDs (Disease modifying anti-rheumatic drugs)
3. Corticosteroids

Question 12

Give examples of Disease modifying anti-rheumatic drugs? (6)

Answer 12

Penicillamine
Gold salts
Antimalarials (chloroquine, hydrochloroquine)
Sulfasalazine
Methotrexate
Cytokine inhibitors (adalimumab, anakinra, etanercept, infliximab)

Question 13

How do NSAIDs work for RA?

Answer 13

Relieve pain ONLY. do not slow progression
Pain relief takes about 1 week
Anti-inflammatory effect takes up to 3 weeks

Start with low dose of least gastric toxic NSAID (i.e. ibuprofen 200-400mg tbs)

Gastric protection is recommended (PPIs etc)

Question 14

When would corticosteroids be used in RA patients?

Answer 14

Disease flares, pulse with high dose corticosteroids until other drugs take effect

If patient shows no response to other drug therapies

Intra-articular injections to relieve symptoms in 1-2 joints
Limit number of injections into each joint to no more than 3 per year

Question 15

When should DMARDs be used?

Answer 15

Only under consultant supervision
Started early in disease (3-6months)

Used in combination with methotrexate. Or alone if combination can not be tolerated

Question 16

What is the first choice of DMARDs monotherapy for RA?

Answer 16

Sulfasalazine - effective in 70% of patients after 1 year

Question 17

What dose regime of Sulfasalazine is required for RA?

Answer 17

Initially 500mg daily by mouth, increased by 500mg at intervals of 1 week to max of 2-3g daily in divided doses

Question 18

What are some side effects of Sulfasalazine?

Answer 18

GI disturbances, malaise and headache, rashes, blood disorders (in first 3-6 months)

Question 19

What needs to be monitored with Sulfasalazine and when?

Answer 19

Blood counts and liver function tests required initially and then monthly for first 3-6 months

Question 20

What supplement is usually given with Sulfasalazine?

Answer 20

Folic acid to counteract impaired folic acid absorption

Question 21

Antimalarials can be used as treatment as they can be better tolerated than gold or penicillin but why should they be used with caution?

Answer 21

may cause ocular toxicity/progressive loss of vision on long term treatment

Risk of ocular toxicity increases with abnormal liver or kidney function, after cumulative dose of 800g, or in patients >70 years

Question 22

Which antimalarials can be used?

Answer 22

Hydroxychloroquine is used to treat moderate active RA

Chloroquine is less commonly used and should only be used if all other drugs have failed

Question 23

What monitoring is recommended for hydroxychloroquine use?

Answer 23

Pre-treatment assess renal and liver function, ask about visual impairment and get optometrist assessment if present, record visual acuity.
If no abnormality, initiate treatment
During treatment, assess visual symptoms and acuity annually, refer to ophalmologist if changes/blurring of vision (discontinue treatment)

Question 24

What dose of Hydroxychloroquine is used for RA?

Answer 24

400mg daily in divided doses, then 200-400mg daily for maintenance

Question 25

What cautions and side effects of hydroxychloroquine?

Answer 25

VERY TOXIC in over dose - max dose of 6.5mg/kg daily (but not exceeding 400mg)

Side effects:
Common - GI disturbances, headache

Less common: ocular toxicity, hair loss, discolouration of hair, skin/nails

Question 26

What is the mechanism of action of methotrexate?

Answer 26

A “folic acid antagonist”, inhibits dihydrofolate reductase, reducing availability of tetrahydrofolic acid (required for purine production and DNA synthesis), which suppresses cell division in immune cells, suppressing cell-mediated immunity.

Question 27

How long until a response is seen with methotrexate?

Answer 27

4-6 weeks

Question 28

What monitoring is required with Methotrexate?

Answer 28

Careful monitoring is required to detect/prevent occurrence of serious adverse effects such as blood disorders (some fatal), renal impairment, liver cirrhosis, pulmonary fibrosis
FBC, renal and liver function tests prior to, repeated weekly until therapy is stabilised and then every 2-3 months thereafter

Question 29

Which drug class does methotrexate belong to?

Answer 29

An anti-metabolite drug; used at low dose as a disease modifying anti-rheumatic drug (DMARD)

Question 30

What dose is recommended of methotrexate for moderate to severe RA?

Answer 30

Moderate to severe RA, by mouth, adult over 18yrs, 7.5mg once weekly, adjusted according to response to max. weekly dose of 20mg)

Question 31

What dose is recommended of methotrexate for severe active RA?

Answer 31

Severe active RA, by SC, IM or IV injection, adult over 18yrs, 7.5mg once weekly, adjusted by 2.5mg according to response to max. weekly dose of 25mg

Question 32

Which OTC medications should patients avoid with methotrexate?

Answer 32

Aspirin or Ibuprofen

Question 33

How is Penicillamine thought to work

Answer 33

Reduction in joint swelling and nodules, ESR rate and RhF titre decrease
effective in 60% of patients within 8-12 weeks
70% within 6 months

Question 34

What dose of Penicillamine should be used?

Answer 34

Start with 125-250mg daily orally with food, increasing after 4-6 weeks to 500-750mg daily (Max dose 1.5g daily (1g in elderly))