Osteoarthritis and spondylarthropathies

Question 1

1) what is Osteoarthritis?

2) who is affected by this disease?

Answer 1

1) Disease of synovial joints where articular cartilage loss leads to and accompanying periarticular bone response
- Major cause of locomotor disability
2) Most common form of arthritis, twice as common in women than men
3) recognised as a metabolically active disease process that affects whole joint (cartilage, bone, capsule, muscle)

Question 2

summarise the disease Progression of osteoarthritis?

Answer 2

1) Initial Repair: Proliferation of chrondrocytes synthesising extracellular matrix (ECM) of bone
2) Early stage OA: Degradation of ECM exceeds chrondrocyte activity resulting in net breakdown and loss of articular cartilage in joint
3) Intermediate stage OA: Failure of ECM synthesis and increased breakdown of cartilage
4) Late-stage OA: Extreme or complete loss of cartilage with joint space narrowing
- Bony outgrowths appear at joint margins (osteophytes)
- General bone sclerosis

Question 3

outline the risk factors of osteoarthritis

Answer 3

1) Increasing age: OA is uncommon in people < 45 years (2%) but in people >65 years prevalence is 68% in women and 58% in men
2) Gender: <45 yrs more common in men
- 55-70yrs more common in women
3) Race: Hip OA is less common in Chinese, Afro-caribbeans and Asians than Europeans
4) Genetic predisposition (inherited)
5) Obesity (63% OA can be attributed to obesity)
(Physical and occupational factors (i.e. Farmers)
Trauma)

Question 4

what are the symptoms of Osteoarthritis?

Answer 4

1) Joint pain: Commonly affected joints are weight bearing joints. Asymmetry of joints affected is common
Pain is worse with movement, no pain at rest
- Morning stiffness in joint lasts for <30 minutes
2) Synovial thickening
3) Deformity of joint
4) Bony swellings (Heberden’s or Bouchard’s nodes)
5) Joint Effusion
6) Muscle weakening or wasting
7) Crepitus

Question 5

Outline the diagnosis of Osteoarthritis

Answer 5

1) Primarily based on clinical presentation: Location of affected joints Pain on movement, not at rest
2) X-ray: Narrowing of joint space, Bony protrusions (osteophytes), Bone sclerosis (abnormal bone density)
3) Arthroscopy: Yellowing, irregular, ulcerated cartilage often present

Question 6

summarise the treatment goals of ostheoarthritis

Answer 6

1) Reduce Pain: In most cases pain is due to damage to bone and cartilage, not inflammation, so analgesia and joint protection often are all that is required
2) Increase mobility
3) Physical therapy, exercise regime etc
4) Reduce disability
5) Minimise disease progression: Joint protection

Question 7

Many OA patients (60%) report benefiting from non-drug treatments and/or complementary medicine. Discuss the Non-drug treatments for osteoarthritis

Answer 7

1) Exercise builds up muscle strength and improve range of joint movement
2) Weight loss, if necessary, helps protect affected weight-bearing joints
3) Physical therapy (ie. heat, cold, ultrasound, TENS etc)
40 Education (i.e. OA is a chronic but not necessarily progressive disease) can alleviate psychological factors - depression/anxiety, improve pain

Question 8

list the Complementary therapies for OA

Answer 8

1) Nutriceuticals (i.e. glucosamine, chondroitin)
- Not recommended by NICE
2) Acupuncture
- Not electro-acupuncture (NICE guidelines)
3) Magnets, copper bracelets

Question 9

outline the pharmacological management of OA

Answer 9

1) Paracetamol, up to 4g daily, or a paracetamol/opiate combination (if required) should be first choice
2) Topical preparations of NSAIDs, can provide pain relief with less risk of GI effects (recommended)
3) Low dose oral NSAIDS (with PPI) and COX2 inhibitors can be used if pain is not controlled adequately (ideally intermittent use)
4) Intra-articular corticosteroid injections (moderate to severe pain). Temporary benefit of reduced pain, increased mobility.
5) Surgery may be necessary, if physical therapy and drug treatment fail

Question 10

Intra-articular injection of hyaluronic acid derivatives can be given to those with OA. how is it believed to work?

Answer 10

1) Thought to supplement natural hyaluronic acid in synovial fluid and return its elasticity and viscosity to normal
2) Not recommended by NICE

Question 11

A rubefacient is a substance for topical application that produces redness of the skin e.g. by causing dilation of the capillaries and an increase in blood circulation. are these recommended in OA?

Answer 11

1) Rubefacients (counter-irritants) are not recommended by NICE (adjunct)
2) Example: Capsaicin (0.025%) is licensed for the symptomatic relief of osteoarthritis. Might take 1-2 weeks of use before pain relief is achieved

Question 12

list some Nutriceuticals that can be used for OA. are they recommended by NICE?

Answer 12

1) Glucosamine, Chondroitin, fish oils, cod liver oil etc
2) Controversial whether glucosamine modifies OA progression
3) Not recommended by NICE

Question 13

Spondylarthropathies refers to any joint disease of the vertebral column. list some Inflammatory rheumatic diseases that are part of this family.

Answer 13

1) Ankylosing spondylitis
2) Psoriatic arthritis
3) Reactive arthritis
4) Enteropathic arthritis (Arthritis associated with 5) inflammatory bowel disease)

Question 14

what is Ankylosing spondylitis and who commonly gets it?

Answer 14

1) Ankylosing spondylitis (AS) is a long-term (chronic) condition in which the spine and other areas of the body become inflamed.
2) Relatively common condition . More common in men
3) 95% patients are HLAB27 antigen positive

Question 15

what are the symptoms of Ankylosing spondylitis and what can the progression of the disease lead to?

Answer 15

1) Typically presents as morning back stiffness/pain (> 30mins) in young man (late teens-20s). Pain improves with exercise but not at rest.
- Inflammation of sacroiliac joint moves up the spine leading to symptoms
2) Progression of disease leads to spinal fusion (ankylosis) that decreases spinal movement and can lead to spinal kyphosis, sacroiliac joint fusion, neck hyper-extension and rotation

Question 16

According to the modified New York criteria, a definite diagnosis of ankylosing spondylitis requires the radiological criterion and at least one clinical criterion. list the radiological and clinical criteria

Answer 16

1) Radiological criterion:
- Sacroilitis at least grade 2 bilaterally or grade 3 or 4 unilaterally
2) Clinical criteria
- Low back pain and stiffness for more than 3 months that improves with exercise but is not relieved by rest
- Limitation of motion of the lumbar spine in both the sagittal and frontal planes
- Limitation of chest expansion relative to normal values for age and sex

Question 17

The Bath AS disease activity index (BASDAI) is used to assess ankylosing spondylitis. describe the BASDAI state what the different scores indicate.

Answer 17

consists of 10cm visual analog scales used to answer 6 questions pertaining to the 5 major symptoms of AS

1) Fatigue (How tired?)
2) Spinal pain (How painful?)
3) Joint pain / swelling (How painful?)
4) Areas of localized tenderness (Any tenderness?)
5) Morning stiffness (Present? Duration?)
- the BASDAI score is between 0-10, where mild AS is 1-3, Moderate AS is 4-7, Severe AS is 8-10

Question 18

Exercising (twice daily) is essential during the treatment of AS as it helps maintain posture and mobility. outline the pharmacological treatment for AS

Answer 18

1) Slow-release NSAIDs taken at night relieves night pain and morning stiffness (i.e. ibuprofen modified release or diclofenac sodium, modified release)
2) Sulfasazaline or methotrexate might help peripheral arthritis but no evidence that they control the spinal disease
3) Cytokine modulators are recommended by NICE for patients with active disease and failed to respond to 2 NSAIDS at max. tolerated dose for 4 weeks (cost effectiveness still being debated!)

Question 19

below is a list of some Cytokine modulators, for each one state their MOA.

1) Adalimumab -
2) Etanercept
3) Infliximab
4) Golimumab

Answer 19

1) Adalimumab - Antibody that binds to TNF-alpha blocking its interaction with receptors
2) Etanercept - TNF-alpha receptor fusion protein that inhibits TNF-alpha activity
3) Infliximab - Antibody that binds to TNF-alpha and neutralises its activity
4) Golimumab- Anti-TNF drug

Question 20

what is the MOA of Diclofenac sodium and what dose should be given in AS?

Answer 20

1) Non-selective cyclooxygenase (COX) inhibitor; Inhibits COX enzymes leading to inhibition of prostaglandin synthesis and anti-inflammatory actions
2) Pain and inflammation in rheumatic disease 75mg-150mg daily in 1-2 times daily, modified release for AS

Question 21

What is the MOA of ibuprofen and what dose should be given in AS?

Answer 21

1) Non-selective cyclooxygenase (COX) inhibitor; Inhibits COX enzymes leading to inhibition of prostaglandin synthesis and anti-inflammatory actions
2) 300-400mg 3-4 times daily, increased if necessary to max dose of 2.4g

Question 22

what is Psoriatic arthritis?

Answer 22

1) Psoriatic arthritis is a type of arthritis that develops in some people with the skin condition psoriasis
- Asymmetrical arthritis in small joints of hand
- Rheumatoid-like symmetrical seronegative poly-arthritis

Question 23

what is the Treatment of Psoriatic arthritis?

Answer 23

1) Analgesia and NSAIDs
2) DMARDs :
- Methotrexate (unlicensed indication), azathioprine (unlicensed indication) sulfasalazine, leflunomide (licensed indication) and ciclosporin
3) Cytokine modulators are licensed by NICE for patients with severe active psoriatic arthritis in patients who have failed to respond to DMARDs

Question 24

Leflunomide (DMARD) is licensed for active psoriatic arthritis (as well as rheumatoid arthritis). what is its MOA?

Answer 24

1) Potent inhibitor of pyrimidine synthesis that affects T cell proliferation and, thus, is immunomodulatory
- Active metabolite of leflunomide persists for a long time which can be a concern if serious adverse effects are experienced (Washout procedure)

Question 25

1) what are the side effects of Leflunomide?

2) what should be excluded before taking Leflunomide?

Answer 25

1) Severe adverse effects include bone marrow toxicity, life-threatening hepatotoxicity, infection and malignancy
- Other side effects: GI disturbance, hypertension, headache, dizziness, eczema, dry skin, rash
2) Pregnancy must be excluded before treatment and effective contraception must be used during and for at least 2 years after treatment in women or 3 months in men.

Question 26

what should be monitored when taking Leflunomide?

Answer 26

Patients must be monitored; Blood counts and liver function

Question 27

what is Reactive arthritis

Answer 27

1) a painful form of inflammatory arthritis . It occurs following an infection:
- GI infection (Shigella, Salmonella, Campylobacter etc)
- Sexually-acquired infection (i.e. Chlamydia)
2) Persistent bacterial antigens in inflammed but sterile synovium of affected joints drive inflammation reaction

Question 28

how does reactive arthritis present?

Answer 28

Presents as acute arthritis (knees, ankles, feet) occurring within 4 weeks of an enteric or venereal infection; skin lesions resembling psoriasis

Question 29

what is the treatment for reactive arthritis?

Answer 29

1) Treat infections with antibiotics and acute inflammation with NSAIDs, local joint aspiration and corticosteroid injections
2) Treat chronic condition with DMARDs (i.e. sulfasalzine)
- Acute condition resolves in a few months but 50% patients go on to develop recurrent arthritis

Question 30

what is Enteropathic arthritis?

Answer 30

1) Arthritis is linked to inflammatory bowel disease
- 10-15% patients with ulcerative colitis or Crohn’s disease have arthritis
2) Arthritis often parallels activity of the bowel condition, improving as bowel symptoms improve.

Question 31

how is Enteropathic arthritis treated?

Answer 31

1) Very difficult to treat/manage

2) NSAIDs improve joint pain but aggravate bowel condition