pathophysiology and therapeutics of gouty arthritis

1. GOUTY ARTHRITIS

2. INTRODUCTION
• Chronic heterogeneous disorder of urate metabolism.
• Results in deposition of monosodium urate crystals in the joints and
soft tissues, with accompanying inflammation and degenerative
consequences.
• Most common form of inflammatory joint disease in men aged ≥40
years.
• Gout has been referred to as the “disease of kings” since it has often
been associated with affluent societies since ancient times.

3. EPIDEMIOLOGY
• Gout is one of the oldest recognized diseases and was identified by Egyptians in
2460BC.
• Due to an ageing population and rising obesity, the burden of gout is increasing
around the world, especially in high income countries.
• The reported prevalence worldwide ranges from 0.1% to approximately 10%.
• In the USA, gout has overtaken rheumatoid arthritis to become the most common
inflammatory arthritis.
• Worldwide, the prevalence of gout is significantly higher in men than women
(about 3:1).

4. RISK FACTORS
• Excessive consumption of red meat
• Obesity
• Excessive consumption of alcohol
• Drugs – Loop diuretics, NSAIDs, cytotoxic therapy,
salicylates
• Trauma
• Other disease –renal failure,etc

5. PATHOPHYSIOLOGY
• Hyperuricaemia results in the crystallization of monosodium urate in the
synovial fluid.
• This triggers an inflammatory cascade.
• Crystal deposits on cartilage surface lead to the cartilage damage.
• Deposition around joints lead to joint destruction
• Long standing gout joint erosions occur.
• Urate deposition occurs in peripheral joints where temperatures are lower
than the core body temperature.

6. MONOSODIUM URATE CRYSTALS

7. Uric acid metabolism
cell breakdown
dietary intake purine bases
hypoxanthine
xanthine
uric acid
xanthine oxidase
catalyzes
hypoxanthine to
xanthine &
xanthine to uric
acid

9. MANIFESTATION OF GOUT
• Asymptomatic hyperuricaemia
• Acute gout
• Chronic gout
• Chronic tophaceous gout
• Gouty nephropathy

10. CLINICAL FEATURES
• Acute gout is a painful condition that typically affects only
one or a few joints.
• The big toe, knee, or ankle joints are most often affected.
• Throbbing, crushing, or excruciating pain.
• Joint appears warm and red. Fever may be present.

11. CLINICAL FEATURES
• Chronic gout
• Acute episodes occur with increasing
frequency
• Tophus formation
• Permanent joint damage
• Renal damage increases with time

15. LABORATORY INVESTIGATIONS
• Plain radiographs – X-Ray
• Serum Uric acid
• 4.0 to 8.6 mg/dl in men
• 3.0 to 5.9 mg/dl in women.
• Synovial fluid analysis (shows uric acid crystals)
• BUN (blood urea nitrogen), Serum Creatinine
• Synovial biopsy
• Uric acid – urine

16. MANAGEMENT
Aim
• Prompt relief of pain in acute attack
• Eliminate secondary causes
• Prevent recurrence and complications (eg renal stones,
joint damage)

17. DRUGS USED IN TREATMENT
• NSAIDs
• Colchicine
• Uricosuric agents
• Allopurinol/ Febuxstat

18. PHARMACOLOGICAL MANAGEMENT
Pain and inflammation relief
• NSAIDs – choice - indomethacin 75mg stat, then 50mg 6-8 hrly
(days 1 & 2), 25 mg 4hr (day 3), then taper slowly over 10-14 days.
• Alternatives- naproxen, aceclofenac, diclofenac
• Cox 2 inhibitors -etoricoxib

19. PHARMACOLOGICAL MANAGEMENT
Colchicine
• Produces its anti-inflammatory effects by binding to the intracellular
protein tubulin, preventing its polymerization leading to the inhibition of
leukocyte migration into affected area.
• Inhibits the synthesis & release of leukotrienes.
• If NSAIDs are contra-indicated use colchicine.
• Initial dose is 1mg, then 0.5 mg every 4 hrs (total of 6mg/course)
• Colchicine is more toxic than NSAIDs

20. PHARMACOLOGICAL MANAGEMENT
Uricosuric agents
• Probenecid & Sulfinpyrazone
• They are weak organic acids .
• Sulfinpyrazone is a metabolite of phenylbutazone.
• Increase the excretion of Uric acid.

21. PHARMACOLOGICAL MANAGEMENT
Allopurinol
• Inhibits synthesis of uric acid by inhibiting xanthine oxidase enzyme.
• It is the prophylactic drug of choice in the management of recurrent gout.
• Initial dose is 100mg daily and could be increased to 900mg daily in patients with
normal renal function.

23. NON-PHARMACOLOGICAL MANAGEMENT
• Acute attack
• Rest the affected joint
• Maintain high fluid intake
• Chronic gout
• Maintain high fluid intake
• Lose weight if obese
• Provide dietary advice
• Avoid alcohol
• Avoid red meat and foods rich in purines (offal, shell fish, spinach)