1. FREEDOM FROM RHEUMATOLOGICAL DISORDERS

2. Gout
An elevated serum urate concentration
Recurrent attacks of acute arthritis in which MSU( monosodium urate) crystals are seen in synovial fluid
Aggregates of MSU crystals (tophi) are deposited in & around joints leading to deformity & crippling
Hyperuricemia
An elevated level of urate in the blood > 7mg/dl in males and >6.5mg/dl in females

3. Epidemiology
The incidence of gout varies in population with an overall prevalence of less than 1 to 15.3%
Pathophysiology
Uric acid is the end product of the degradation of purines.
The accumulation may result from either overproduction or underexecreation.

4. The purines from which uric acid is produced originate from three sources: dietary purine,conversion of tissue nucleic acid to purine nucleotides and de novo synthesis of purine bases.
Overproduction of uric acid result from:
Abnormalities in the enzyme system that regulate purine metabolism.
An increase in the activity of phosphribosyl pyrophosphate(PRPP) synthatase, a key determinant in purine synthesis and thus uric acid overproduction.

5. 3. A deficiency of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) may also result in the overproduction of uric acid.
4. Increased breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative disorders.
Drugs that decrease renal clearance:
Diuretics, salicylate<2g\d, ethanol, L-dopa, cyclosporine, ethambutol……..

6. Normal individual produce mg of uric acid daily and excrete less than 600 mg in urine. Individual who excrete more than 600 mg on a purine-free diet are considered overproducers.
Hyperuricemic individuals who excrete less than 600mg per 24 hours on purine-free diet are defined as underexcretors of uric acid.
On regular diet, excretion of >1000 mg per 24 hours reflect overproduction , less than this is probably normal.

7. Gout once called the
“Disease of Kings” is
also seen in Women,
Especially
After
Menopause

8. M:F - 7:1 to 9:1
Women before menopause- F < M
In ages younger than 65- M:F- 4:1 ratio
In the older age groups > 65- M:F-3:1 ratio
After 80 years of age-F > M

9. URIC ACID METABOLISM MEN Vs WOMEN
Estrogen have a mild uricosuric effect; therefore, gout is unusual in premenopausal women
Higher renal clearance of urate in women possibly due to their higher plasma estrogen levels
The declining use of HRT may further increase the frequency of gout in women at an earlier age

10. Pathogenesis of Gout
Hyperuricemia results from urate overproduction (10%), under excretion (90%) or often a combination of two
Gout is mediated by supersaturation and crystallization of uric acid within joints ultimately, the formation of tophi
Interactions of MSU crystals with the components of the innate immune system trigger acute gouty inflammation

11. Triggering Factors-Acute Attack
Alchol ingestion
Dietary excess of purine
Hemorrhage
Acute medical illness
Infections
Exercise
Trauma
Surgery
Drugs: cyclosporine, furosemide, ethambutol, aspirin (Low dose), pyrazinamide, thiazides, nicotinic acids etc

12. Clinical Features in Gout patient
Asymptomatic Hyperuricemia
Acute Gouty Arthritis
- Acute monoarticular arthritis
- The attacks begin abruptly and reach maximum intensity in 8-12 hours
- The joints are red, hot, and exquisitely tender
- Untreated, the first attacks resolve spontaneously in less than 2 weeks.
- Gout can initially present as a polyarticular arthritis in 10% of patients

13. Chronic tophaceous Gout
Intercritical gout
Chronic tophaceous Gout
- Attacks become more polyarticular
- Inflammation may become less intense
- Proximal and upper-extremity joints involved
- Attacks occur more frequently and last longer
- Tophi in the soft tissues (helix of the ear, fingers, toes……………)

19. Clinical Features MEN Vs WOMEN
In women, polyarticular/tophaceous disease is often the first manifestation of gout
A preceding recurrent mono-arthritis is found in joints other than the big toe
The duration of disease before tophi is shorter
The prevalence of tophi is higher and its localization different in female than in male patients

20. Tophi are usually indolent and show little surrounding inflammation
Gout in women has higher frequency of upper limb joint involvement in comparison to men
The articular features of gout are usually similar

21. Definitive diagnosis is best established by
Aspiration of joint and identification of urate crystal
The triad of acute monoarticular arthritis, hyperuricemia
and dramatic response to colchicines
Presence of 6 of the below mentioned 12 clinical,
laboratory and radiographic criteria
Criteria of Acute Gouty Arthritis
► More than one attack of arthritis
► Maximum inflammation in one day
►Monoarticular arthritis
►Joint redness
► First metatarsophalangeal joint involvement
► Unilateral attack
► Unilateral attack involving tarsal joint
► Suspected tophus
►Hyperuricemia
► Asymmetric swelling within joint (radiograph)
► Subcortical cyst without erosion (radiograph)
►Negative culture of joint fluid for microorganism

22. Co morbid Conditions Renal stones
Urate nephropathy & chronic kidney failure
Hypertension
Diabetes
Endothelial dysfunction
Obesity
Insulin resistance syndrome
Atherosclerosis
Cardiovascular disease related mortality
Cerebrovascular disease
Hypothyroidism

23. Treatment of Gout
Treat acute arthritic attack promptly
Prevent recurrence of acute gouty arthritis
Lower urate levels
Prevent or reverse complications of the disease resulting from deposition of MSU crystal in joint, kidney, or other sites
Prevent or reverse co-morbid conditions like obesity, HT & triglycerdemia & renal complications

24. Treatment of Acute Gouty Arthritis
NSAIDs are preferred in patients with uncomplicated gout
Intraarticular corticosteroid for gout affecting one or two large joints
Colchicine is preferred for patients in whom the diagnosis of gout is not confirmed
It is most effective during the first hours of an attack, effectiveness declines with the duration of inflammation

25. Long-Term or Prophylactic Therapy
Lowering uric acid with either allopurinol or probenecid can precipitate attacks of gout
NSAIDs and colchicine are frequently used as prophylaxis against recurrent acute gout
A standard practice is to use low-dose oral colchicine (0.6 mg orally twice a day in patients with intact renal function) for the first six months of antihyperuricemic therapy
Long-term use of colchicine can lead to a muscle weakness with elevated levels of creatine kinase particularly in patients with renal insufficiency
NSAIDs can be used for prophylaxis, such as indomethacin at 25 mg bid

26. Approaches to Lowering Uric Acid Levels
Asymptomatic Hyperuricemia
Rarely an indication for specific drug therapy
Symptomatic Hyperuricemia
Life long therapy with anti-hyperuricemic therapy is indicated in following situation
>2 or 3 acute attacks
Renal stones
Tophaceous gout
Chronic gouty arthritis with bony erosions.

27. Antihyperuricemic Therapy
In many cases, patients who have a first attack of gout should undergo therapy with agents that lower uric acid
Some rheumatologists advocate waiting for the second attack to begin therapy to lower uric acid levels because not all patients have a second attack
Antihyperuricemic therapy should be started a few weeks after the attack has resolved and with the institution of colchicine to prevent another attack

28. Indications for Allopurinol (Xanthine Oxidase inhibitor)
Hyperuricemia associated overproducers of uric acid
In patients at risk of tumor lysis syndrome to prevent renal
toxicity during therapy for malignancies
Uric acid excretion of 1000mg or more in 24 hours
Hyperuricemia associated with HGPRT deficiency or PRPP
synthetase over activity
Uric acid nephropathy
Nephrolithiasis
Intolerance or reduced efficacy of space uricosuric agents
Gout with renal insufficiency (GFR<60ml/min)
Allergy to uricosurics

29. Candidates for uricosuric drugs
Who is younger than 60 years of age and normal renal function (creatinine clearance greater than 80ml/min)
Uric acid excretion of less than 800 mg/24 hours on a general diet
No h/o of renal calculi

30. Probenecid
Reduce serum urate levels by enhancing the renal excretion of UA
Fewer significant adverse effects than allopurinol
Can be used in the majority of middle-aged
Maintenance dose ranges from 500 mg to 3 g per day & is administered on twice daily or thrice daily schedule
Precipitation of gout, urolithiasis, and impairment of renal function are common side effects

31. Sulfinpyrazone
Sulfinpyrazone is an alternative uricosuric agent that has antiplatelet activity but is seldom used because of the added risk of bone marrow suppression
Starting dose, 50 mg orally twice daily; gradually increased to mg daily
Precipitation of gout, urolithiasis, and impairment of renal function are common side effects

32. Dietary Management of Hyperuricemia
Alcohol consumption must be avoided
Diets like butter, red meat, pasta sweets, white rice, potatoes, white bread, wine beer, liquor, fish poultry and sea food increase the risk of gout
Higher level of consumption of dairy products is associated with a decreased risk
Moderate intake of purine-rich vegetables or protein is not associated with an increased risk of gout
Those who consumes milk 1 or more times per day have a lower serum uric acid level

33. Recent Advances in Treatment
Recombinant uricase can promote accelerated tophus dissolution
Oxipurinol is the active metabolite of allopurinol. Patients with allopurinol hypersensitivity can often tolerate oxypurinol
Febuxostat is an orally administered selective inhibitor of xanthine oxidase. It inhibits both the oxidized and reduced forms of xanthine oxidase. It is a potential alternative to allopurinol for patients with gout.
Anti-tumour necrosis factor as a new therapeutic option

34. Treatment of Co morbid conditions
The ARBs like losartan, Amlodipine & the triglyceride-lowering agent fenofibrate - Uricosuric effects
Weight loss is protective
The amelioration of insulin resistance by either a low-energy diet or troglitazone & Metformin therapy can also lower uric acid and attenuate the articular syndrome

35. Role of HRT in Gout
The effect of exogenously administered oestrogens, produce a fall in plasma uric acid concentration through a uricosuric effect
However, there is no conclusive evidence is available for the use of estrogen replacement for such cases; however it remains the potential area of research

36. Good luck