Approach to Joint Pain Flashcards
What are the pathological findings of osteoarthritis?
- Destruction of articular cartilage (thinning, erosion) leads to narrowing of joint spaces
- Constant friction between 2 naked bone surfaces leads to
-> Thickening of subarticular bone
-> Eburnation (exposed bone with smooth polished surface) - Formation of subchondral cyst
- Formation of osteophytes (irregular outgrowths of bone around joint)
- Reactive thickening of synovium
- Secondary changes to surrounding tissue
What is osteoarthritis?
- most common degenerative joint disease
- chronic progressive and irreversible destruction of articular cartilage
- common in older patients and weight-bearing joints
What are the radiological features of OA?
- narrowing of joint space
- subchondral sclerosis
- subchondral cyst
- osteophytes
Drugs for OA
- Pain relief &/or anti-inflammatory:
- paracetamol, non-selective NSAID (diclofenac), cox-2 inhibitor (celecoxib) - Symptomatic slow-acting drugs for OA:
- Intra-articular hyaluronic acid
What is crystal arthropathies?
- deposition of crystals in joints and soft tissue
- acute pain, swelling, redness in joints
- clinically indistinguishable from septic joint
- joint fluid analysis (gram stain, culture, crystal analysis)
- gout or pseudogout
What is gout?
- increased serum uric acid and urate crystals deposition
- due to problems of purine metabolism, resulting in increased uric acid production as purines are precursors to uric acid and decreased uric acid excretion by kidneys
Examination of synovial fluid under polarised microscopy reveals…
strongly birefringent needle shaped crystals
What is gouty arthritis
- metabolic disorder -> hyperuricaemia
- monosodium urate crystal deposition in joint
- tophaceous growths
- men:women = 5:1
- use uricosuric drugs to inhibit URAT1 to prevent reabsorption of urate
Aim of gout treatment
decrease cytokine production
decrease adhesion and trafficking
Pathogenesis of Acute Gouty Attack
Hyperuricaemia -> precipitation of rate crystals in joints:
1) phagocytosis by monocytes -> release of IL-1, TNF, IL-6 -> release of proteases -> tissue injury and inflammation + pain
2) complement activation -> neutrophil chemotaxis -> phagocytosis of crystals by neutrophils -> lysis and activation of neutrophils -> release of lysosomal enzyme -> tissue injury and inflammation + pain
Drugs for Acute gouty arthritis Attack
- Nonselective NSAIDs (naproxen, indometacin)
- COX-2 selective NSAID (celecoxib)
for 1&2:
- anti-inflammatory and analgesic
- inhibits production of prostaglandins and urate crystal phagocytosis
- Glucocorticoids (prednisolone)
- anti-inflammatory and analgesic - Colchicine
- binds to tubulin
- prevent tubulin polymerisation into microtubules
- reduces leukocyte migration into joints -> prevent phagocytosis of crystals
- inhibits leukotriene and prostaglandin production
=> relieves pain and inflammation within 24-36 hours
=> may have side effects: diarrhoea, nausea & vomiting etc
^ helps to prevent recurrence
Drugs for Prevention of Gouty Episode
- Xanthine Oxidase Inhibitors (1st line: Allopurinol; 2nd line: Febuxostat)
- inhibit uric acid synthesis - Uricosuric Agents (Probenecid)
- inhibits proximal tubule anion transport
- inhibits uric acid reabsorption
- increase uric acid excretion
^ helps to prevent recurrence
*do NOT start during acute attacks; if not, there will be an increase of urea in the plasma, increasing the gradient btw crystals in the joint and plasma -> causing crystals to move out of the joint -> exacerbation of immune system + worsen attack
When to use xanthine oxidase inhibitors?
- debilitating gout attacks
- chronic erosive arthritis
- urate nephrolithiasis
What are the warnings of using xanthine oxidase inhibitors?
Allopurinol hypersensitivity syndrome
Severe cutaneous adverse reaction
What genotype increases the risk of AHS?
HLA-B *58:01
