1. Gout Disease of Kings
Dr.Fakhir Yousif

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

3. Gout: foot
Gout: foot
This patient presented with acute pain, redness, swelling of the left second toe. Tophaceous material drained from the distal toe following needle aspiration. Note the adjacent skin inflammation resembling cellulitis. #

4. Gout: tophus, hand Gout: tophus, hand
This patient with gout has a large tophaceous deposit over the MCP joints of the long and index fingers of the left hand. #

5. Gout: tophi of the pinna, ear
The decrease in solubility of monosodium urate with cooler temperatures may explain the predilection for tophi to form in the external ear, fingers, toes, and olecranon bursae. #

6. GOUT
Gout is a true crystal deposition disease. It can be defined as the pathological reaction of the joint or periarticular tissues to the presence of monosodium urate monohydrate (MSUM) crystals.
Urate : end product of purine metabolism
Hyperuricemia : serum urate > urate solubility)
6.8 mg/dl

7. The prevalence of gout varies between populations but is around 1% with a strong male predominance (> 10:1). Prevalence increases with age and increasing serum uric acid concentration. 'Primary' gout is almost exclusively a male disease and the most common cause of inflammatory arthritis in men over the age of 40..

8. HYPERURICEMIA & GOUT Hyperuricemia caused by Overproduction 10%
Underexcretion %

10. Classification of Hyperuricemia
Overproduction (10%)
Ethanol
HGPRT deficiency
(hypoxanthine-guanine phosphoribosyl transferase)
PRPP synthetase overactivity
(phosphribosyl pyrophosphate synthetase)
Myeloproliferative disorders
Cytotoxic chemotherapy
Underexcretion (90%)
Renal insufficiency
Drugs and toxins
Diuretics
Ethanol
Cyclosporine A
Pyrazinamide
Lead nephropathy
Low-dose aspirin
Ketosis
Hyperuricemia #

11. 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

12. Pathogenesis of Gouty Inflammation
Urate crystals stimulate the release of numerous inflammatory mediators in synovial cells and phagocytes The influx of neutrophils is an important event for developing acute crystal induced synovitis

13. GOUT RISK FACTORS Male Postmenopausal female Hypertension
Pharmaceuticals:
Diuretics, ASA, cyclosporine
Alcohol intake
Highest with beer
High BMI (obesity)
Diet high in meat & seafood

14. Clinical features
1- Acute gouty arthritis
extremely rapid onset, reaching maximum severity in just 2-6 hours, often waking the patient in the early morning
severe pain, often described as the 'worst pain ever'
extreme tenderness-the patient is unable to wear a sock or to let bedding rest on the joint
marked swelling with overlying red, shiny skin .

15. During the attack the joint shows signs of marked synovitis but also periarticular swelling and erythema. There may be accompanying fever, malaise and even confusion, especially if a large joint such as the knee is involved. As the attack subsides, pruritus and desquamation of overlying skin are common. The main differential diagnosis is septic arthritis, infective cellulitis or another crystal disease.

16. After an acute attack some people never have a second episode; in others the next episode occurs after years. In most, however, a second attack occurs within 1 year and the frequency of attacks gradually increases with time. Later attacks are more likely to involve several joints and to be more severe

17. 2-Chronic tophaceous gout
Large MSUM crystal deposits produce irregular firm nodules ('tophi') at the usual sites for nodules around extensor surfaces of fingers, hands, forearm, elbows, Achilles tendons and sometimes the helix of the ear. The white colour of MSUM crystals may be evident and permits distinction from rheumatoid nodules.

18. TOPHI
Solid urate deposits in tissues
Irregular & destructive

19. Gout: tophi, hands Gout: tophi, hands
There are multiple large tophi affecting the wrists and several finger joints, consistent with advanced tophaceous gout. #

20. 3- Progressive renal disease
an important complication confined to untreated severe chronic tophaceous gout. This results from MSUM crystal deposition in the interstitium of the medulla and pyramids with consequent chronic inflammation, giant-cell reaction, fibrosis, glomerulosclerosis and secondary pyelonephritis…Renal stone ..

21. Investigations
Definitive diagnosis requires identification of MSUM crystals in the aspirate from a joint, bursa or tophus. In acute gout synovial fluid shows increased turbidity due to the greatly elevated cell count (> 90% neutrophils..)

23. Assessment of renal function (serum creatinine, urine testing), hypertension, blood glucose and serum lipid profile should be undertaken. An FBC and ESR should detect myeloproliferative disorders during remission of acute gout. During an attack a marked acute phase response (elevated CRP, neutrophilia) is usual; the ESR is often modestly raised in tophaceous gout

24. X-rays can assess the degree of joint damage
X-rays can assess the degree of joint damage. In early disease they are usually normal, but narrowing of joint space, sclerosis, cysts and osteophyte (changes of OA) may develop in affected joints with time, or be present as a predisposing factor in secondary gout. Gouty 'erosions' (bony tophi) are a less common but more specific feature occurring as para-articular 'punched-out' defects with well-delineated borders and retained bone density. Tophi may also be visible as eccentric soft tissue swellings..

25. Management
The acute attack A fast-acting oral NSAID (. Indomethacin 50 mg 4hourly. naproxen, diclofenac,) can give effective pain relief and is the standard treatment. Patients can keep a supply of an NSAID with which they are familiar and take it as soon as the first symptoms are noticed, continuing for the duration of the attack.

26. . Oral colchicine (a potent inhibitor of neutrophil microtubular assembly) can be very effective, but unfortunately often causes vomiting and severe diarrhoea at the doses needed for rapid relief (1 mg loading dose, then 0.5 mg 6-hourly until symptoms abate). The compromise is to try lower doses (0.5 mg 8-12-hourly) for a slower onset of benefit. Aspiration of the joint will give instant relief and, when combined with an intra-articular corticosteroid injection to prevent fluid reaccumulation, often effectively aborts the attack

27. Correction of any predisposing factors
should always be attempted. Lifestyle alteration to correct obesity and reduce excess beer consumption may significantly reduce hyperuricaemia. Diuretics should be stopped if possible. Although a very high purine diet (large amounts of seafood, red meat and offal) should be tempered, there is no need for a specific highly restrictive diet. and trigger acute attacks.. .

28. HYPOURICAEMIC DRUGS INDICATIONS FOR HYPOURICAEMIC DRUGS
1-Recurrent attacks of acute gout
Tophi
2-Evidence of bone or joint damage
3-Associated renal disease
4-Gout with greatly elevated serum uric acid

29. ALLOPURINOL Allopurinol: blocks conversion
of xanthine to uric acid. Works
for underexcretors and overproducers
The aim of treatment is to bring the serum uric acid level into the lower half of the normal range to ensure dissolution of crystals and to prevent new ones forming. The serum uric acid should therefore be measured every 3-4 weeks and the dose of allopurinol increased in 100 mg increments until this is achieved (maximum 900 mg daily).