• It is very rare in premenopausal women (estrogen has uricosuric effect).
• It develops as a result of the accumulation of monosodium urate (MSU) crystals in the joints.
• The most important risk factor is hyperuricemia.
• Gout; It begins as intermittent monoarthritis/oligoarthritis in the lower extremities and progresses to chronic destructive polyarthritis.
pathogenesis
• Since there is no uric acid oxidase enzyme, the end product of purine metabolism in humans is uric acid. (Allatoin is well soluble in water, uric acid is slightly soluble)
Hypoxanthine_____Xanthine_____Uric acid _____ Allantoin
• 2/3 of the daily uric acid load in the body (diet, purine catabolism) is excreted in the urine.
• The most common cause of hyperuricemia is decreased renal excretion .
Some conditions that cause hyperuricemia
Decreased uric acid excretion
clinical conditions
Decreased GFR, Hypertension, Obesity, Metabolic syndrome , Lead poisoning
Medicines
Diuretics (except spironolactone), Ethanol, Low dose salicylate, Cyclosporine and tacrolimus, Levodopa, Niacin, Ethambutol, Pyrazinamide
Increased uric acid production
clinical conditions
Myeloprol pherative-Lynphoprol erative diseases, Obesity, Psoriasis
Diet
Alcoholic beverages (especially beer), Red meat, Offal, shellfish, High fructose corn syrup
Medicines
Nicotinic acid, Cytotoxic drugs
• Formation of monosodium urate crystals and Inflammation:
o In the presence of hyperuricemia (serum uric acid > 6.8 mg/dl), uric acid precipitates on the articular cartilage and synovium and accumulates in the form of lacy crystal structures called microtofus. (asymptomatic hyperuricemia)
o Some changes (pH, temperature, increase/decrease in uric acid level, etc.) cause these lacy crystal structures to disintegrate and release large amounts of MSU crystals into the joint space.
o These crystals are phagocytosed by macrophages and acute gout attack begins.
Course of the disease and clinical findings
• Asymptomatic hyperuricemia;
o Serum uric acid level is high (> 6.8 mg/dL), but patients have not developed any symptoms yet.
• acute gouty arthritis;
o The most common early clinical manifestation is acute gout attack.
o Some factors that can trigger an acute gout attack; alcohol intake, binge eating, allopurinol therapy, infection, trauma and surgery, serious medical conditions (MI and stroke) etc.
o Classically it is monoarthritis. The most common foot. MTF joint (podagra), secondly, other joints of the foot are involved.
o Polyarthritis (hand joints, wrist and elbows) may develop in recurrent attacks.
o There is severe pain and tenderness in the joint. The joint is red and there is an increase in temperature.
o Findings resolve spontaneously within a few days, even if left untreated.
• In untreated cases, chronic gout with tophi may develop.
o There is continuous inflammation and pain in the involved joint(s).
o MSU crystals accumulated to form nodular structures called 'tophus'. It is most commonly seen in the fingers, auricle, wrist, olecranon, knee and Achilles tendon.
Laboratory findings and diagnosis
• In a gout attack, uric acid can be high, normal and low.
• Acute phase reactants and leukocyte count increase during an acute gout attack.
• Joint fluid has inflammatory character.
• Definitive diagnosis is made by demonstrating needle-shaped MSU crystals in the examination of joint fluid aspirate under polarized light microscope.
Treatment
Treatment of acute gout attack
• The aim of the treatment is to relieve the pain and end the attack as soon as possible.
• The main axis of pharmacological treatment; It forms anti-inflammatory drugs such as NSAIDs, colchicine and glucocorticoids.
• ACTH (cosyntropin) can also be preferred as an anti-inflammatory
• Anti-IL-1 agents in severe cases; Anakinra, Canakinumab, and Rilonacept can also be used
• If the patient is taking uric acid-lowering treatment during an acute gout attack, it should be continued, if not, it should not be started. Because changing (decreasing/increasing) the level of uric acid can trigger an attack and exacerbate the existing attack.
Hypouricemic treatment
• Lifestyle changes (weight loss; avoidance of offal, fructose, alcohol, red meat and shellfish, etc.)
• Uric acid-lowering drugs should be started after the attack is over and must be used with a low-dose anti-inflammatory drug (colchicine, NSAID).
• Allopurinol
It is a xanthine oxidase inhibitor.
o Side effects of allopurinol include; allergic rash, tubulointerstitial nephritis, Steven Johnson syndrome (toxic epidermal necrolysis), and vasculitis.
• Febuxostat
It is a xanthine oxidase inhibitor.
o Unlike allopurinol; No allergic side effects are expected.
Xanthine oxidase inhibitors reduce the metabolism of azathioprine and 6-mercaptopurine. If these drugs are used together with xanthine oxidase inhibitors, severe cytopenias may develop.
• Uricosuric drugs (Probenecid, Sulfinpyrazone, Benzbromarone)
o They inhibit the transporter (URAT1) that allows urate to be reabsorbed from the proximal tubules.
• Rasburicase, Pegloticase
o Recombinant uricase (uric acid oxidase) enzymes.
o Converts uric acid to allantoin, a soluble molecule.
• Other drugs with a uric acid-lowering effect; Losartan, Fenofibrate, Amlodipine.