Gout

Gout

• It is an inflammatory response to monosodium urate (MSU) monohydrate crystal deposition in the joints due to alteration in body urate metabolism. • Gout is the most common crystal arthropathy occurring in men above 40 years of age. • It results from an increased body pool of urate with hyperuricemia. It typically is characterized by episodic acute and chronic arthritis caused by deposition of MSU crystals in joints and connective tissue tophi and the risk for deposition in kidney interstitium or uric acid nephrolithiasis.

Clinical Features Gout usually has three distinct stages: (1) acute gouty arthritis, (2) intercritical gout (asymptomatic phases between acute gouty flares which may last several months to years) and (3) chronic tophaceous gout • Most cases of gout are characterized by the sudden onset of severe acute monoarthritis in a peripheral joint, mostly in the lower limb • The metatarsophalangeal joint of the first toe often is involved, but tarsal joints, ankles, and knees also are affected commonly. • The arthritis remits completely within few days with or without therapy and then recurs with increasing frequency in coming days. Recovery is typically associated with desquamation of the skin overlying the joint • Several events may precipitate acute gouty arthritis: dietary excess, trauma, surgery, excessive ethanol ingestion, hypouricemic therapy, and serious medical illnesses such as myocardial infarction and stroke • After approximately 10 years of recurrent gouty arthritis, patient develops into chronic gout with appearance of tophi. • Chronic gouty arthritis is usually polyarticular with deposition of MSU crystals on tendons (e.g. tendo Achilles), ligaments, bursae, tibial tuberosity, and it may have concomitant tophi formation in fingers, toes, ears or upper part of forearm

Laboratory Investigations

• Gold standard for the diagnosis of acute gout is the demonstration of strongly negative birefringent needle- and rod-shaped crystals of MSU in the synovial fluid under compensated polarizing light microscopy • Synovial fluid leukocyte counts are elevated from 2000 to 60,000/L. Effusions appear cloudy due to the increased numbers of leukocytes. • Serum UA is usually raised (> 10 mg/dL) but up to 40% patients may have normal or low SUA level during the acute attack (stress-induced liberation of adrenocorticotropic hormone (ACTH) and disease-induced secretion of cytokines are uricosuric) • A 24-h urine collection for uric acid can, in some cases, be useful in assessing the risk of stones, elucidating overproduction or underexcretion of uric acid. Excretion of >800 mg of uric acid per 24 h on a regular diet suggests that causes of overproduction of purine should be considered • Serum urea and creatinine should be monitored for signs of renal impairment Radiology • Cystic changes, well-defined erosions with sclerotic margins (often with overhanging bony edges), and soft tissue masses are characteristic features of advanced chronic tophaceous gout. • Ultrasound, CT and MRI are being studied and are likely to become more sensitive for early changes. Differential Diagnosis • Septic arthritis, • Cellulitis, • Pseudogout, • Hemarthrosis and • Palindromic rheumatoid arthritis.

Treatment Acute Gout Relief of pain and inflammation is the primary aim of treatment in acute gout and this is achieved by • Nonsteroidal anti-inflammatory drugs: o Drugs like coxibs, naproxen, diclofenac, ibuprofen, piroxicam or indomethacin may be used. o Indomethacin is regarded as “gold standard” NSAID for acute gout by some clinicians though its side effects are unacceptably high. o NSAIDs are used most often in individuals without complicating comorbid conditions o effective in 90% of patients, and the resolution of signs and symptoms usually occurs in 5–8 days • Colchicine: o If NSAIDs are contraindicated, oral colchicine may be started with 0.5–0.6 mg, three to four times per day to control acute flare. o colchicine interferes with phagocytosis of neutrophils and chemotaxis, and its efficacy progressively declines with delay in initiation of treatment. o Common side effects are nausea, vomiting and diarrhea. The drug must be stopped promptly at the first sign of loose stools • Glucocorticoids: o Intramuscular or intra-articular (for single joint affection) methylprednisolone depot preparation 40–120 mg is useful. o oral prednisolone, starting with doses of 20–40 mg/day, tapered over 2 weeks are often very effective and dramatic in relief of pain. The time of initiation of treatment is more important than the choice of the drug. The sooner the drug is started, the more rapidly a complete response is attained. Generally, NSAIDs are preferred when the diagnosis is confirmed 

Hypouricemic Therapy • Ultimate control of gout requires correction of the basic underlying defect: the hyperuricemia. Attempts to normalize serum uric acid to 5.0–6.0 mg/dL to prevent recurrent gouty attacks and eliminate tophaceous deposits entail a commitment to long-term hypouricemic regimens and medications that generally are required for life

• Indication of hyperuricemia cannot be corrected by simple means o after two attacks of acute gout o serum uric acid levels >9.0 mg/dL o presence of uric acid stones o tophi or chronic gouty arthritis

• Lifestyle Measures : control of body weight, o low-purine diet, o increase in liquid intake, o limitation of ethanol use, o decreased use of fructose-containing foods and beverages o avoidance of diuretics

• Pharmacotherapy

• Uricosuric Agents o Probenecid and benzbromarone increase urate excretion by inhibiting URAT1 and other organic acid transporter family. o Probenecid can be started at a dose of 250 mg twice daily and increased gradually as needed up to 3 g per day to maintain a serum uric acid level 6 mg/dL. o Probenecid is generally not effective in patients with serum creatinine levels 2 mg/dL. These patients may require allopurinol or benzbromarone o Benzbromarone is another uricosuric drug that is more effective in patients with renal failure

• Xanthine Oxidase Inhibitors o Allopurinol-  best drug to lower serum urate in overproducers, urate stone formers, and patients with renal disease.  It can be given in a single morning dose, 100–300 mg initially and increasing up to 800 mg if needed  side effects include life-threatening toxic epidermal necrolysis, systemic vasculitis, bone marrow suppression, granulomatous hepatitis, and renal failure  Requires dose adjustment in renal failure o Febuxostat is approved at 40 or 80 mg once a day and does not require dose adjustment in mild to moderate renal disease o Pegloticase is a new urate-lowering biologic agent that can be effective in patients allergic to or failing xanthine oxidase inhibitors