1. Gout extra Q’s

2. After giving Marilyn analgesia you arrange an ultrasound and guided aspiration of Marilyn's first metatarsophalangeal joint. The initial report comments that the fluid appears inflammatory. What other investigations maybe of use? What information do you expect to specifically be of use?

3. Hyperuricemia remains the cardinal feature of gout – limited usefullness in gout diagnosis since levels may fall within the normal range on occasion, even during acute attacks; although most patients with gout will have an elevated serum urate (greater than 7.0 mg/dL).The greatest utility of measuring serum urate is in monitoring the effects of urate-lowering therapy FBC may show a leukocytosis with increased neutrophils CRP and ESR During an acute attack, the synovial fluid findings are consistent with moderate to severe inflammation. The leukocyte count usually ranges between 5 and 80,000 cells/L with an average between 15,000 and 20,000 cells/L. The cells are predominantly neutrophils. The definitive diagnosis of gout is made by examination of synovial fluid or tophaceous material with compensated polarized light microscopy and identifying the characteristic monosodium urate crystals. When these crystals are perpendicular to that axis, they are blue. Crystals are usually intracellular and needle-shaped during acute attacks but may be small, blunted, and extracellular as the attack subsides or during intercritical periods. The 24-hour urine uric acid measurement is not required in all patients with gout but is useful for determining potential causes of hyperuricemia as well as determining whether uricosuric therapy can be effective, since this form of therapy is effective only in underexcreters. Patients with gout often suffer from hyperlipidemia, glucose intolerance, hypertension, coronary artery disease, and obesity. Accordingly, it is appropriate to measure serum lipids and fasting blood sugars in patients with gout. Because renal dysfunction develops in many patients with hypertension and gout, it is appropriate to monitor serum creatinine levels as well. Transmission electron microscopy and x-ray powder diffraction to look for other crystalline arthritides — Arthritis or periarthritis 2ndry to deposition of calcium phosphate crystals. X-Ray showing bone erosions due to tophi may have characteristic delicate "overhanging" edges. MRI of tophi is useful (T1, T2 and gadolinium weighted) for tophus sizing. Dual energy CT to quantify tophi. Ultrasound examination directed to joints or soft tissue deposits is an increasingly promising modality for the early detection and monitoring of therapy for gout.

4. What acute pharmacology options for treatment are available? Acutely NSAIDs first line Tx, usually indomethacin (50mg tds) or naproxen (500mg bd). Avoid Aspirin due to paradoxical effect on serum urate levels Colchicine dose – An initial dose of 1.8 mg (3 tabs) over one hour followed by 0.6 mg (1 tab) for five additional hours (maximum total dose 4.8 mg to try to mitigate GIT effects) Corticosteroids – Predisone/ prednisolone in doses of 30 to 50 mg/day for one to two days, then tapered over seven to ten days, However, rebound attacks are relatively common once glucocorticoids are withdrawn In patients who cannot take oral medications, intravenous glucocorticoids or subcutaneous adrenocorticotropic hormone (ACTH) are options. Intra-articular steroid injection – methylprednisolone IL-1 inhibition – Anakinra and Canakinumab (not currently in use)

5. What is clinical course of gout? Course — Prior to the availability of effective urate-lowering treatment, it took about 12 years from the first acute gout to the onset of chronic arthritis or detectable tophi. Currently, arthritis/ tophi onset intervals range from less than 5 years to 40 years in individual patients. In the era preceding the availability of effective urate-lowering treatment, duration of gout and degree of hyperuricemia were correlated with the rate and extent of tophus formation. After 20 years of untreated gout, almost 75 percent of patients were affected with tophi formation, with the highest prevalence in patients with the highest serum urate concentrations. In contrast to the classic presentation, a number of reports have described patients with tophaceous deposits in the absence of, or prior to, gouty arthritis, a presentation thought only due to myeloproliferative disorders or hereditary enzyme defects. These patients are more likely to be women, to have predominant involvement of the fingers, have chronic kidney disease, and to be treated with a diuretic or antiinflammatory drug. Urate-lowering treatment of gout with uricosuric agents and allopurinol initially led to a dramatic reduction in chronic gouty arthritis and tophaceous gout, with a prevalence of less than 5 percent reported in some studies. However, these progressive forms of gout are being seen more frequently once again the following groups of patients: Men who have excess EtOH, diuretics and suboptimal management/ compliance Women who have renal insufficiency, nodal OA, and diuretic induced Organ transplant recipients treated with cyclosporine, which impairs urate excretion, are at increased risk for the accelerated development of chronic tophaceous gout.

6. What are the non joint complications which may arise? Nephrolithiasis — Uric acid stones are a major component of the morbidity suffered by patients with gout There are three major risk factors for uric acid nephrolithiasis: Increased uric acid excretion Reduced urine volume Low urine pH, Chronic urate nephropathy — Renal impairment is common among patients with gout, but usually reflects the coexistence of other disorders such as hypertension, diabetes mellitus, obesity, atherosclerosis. Extra articular tophi formation in soft tissue - painless

7. What preventative measures/ treatments/lifestyle changes may be implemented? Risk reduction: Wt EtOH Fructose-containing beverages HTN Diuretics Tx of recurrent gout attacks: Probenecid is a uricosuric drug that is a weak organic acids and promotes renal clearance of uric acid by inhibiting urate-anion exchangers in the proximal tubule that mediates urate reabsorption. angiotensin II receptor antagonist, Losartan, has a modest uricosuric effect that appears to plateau at a dose 50 mg/day Fenofibrate, a fibric acid derivative used for the treatment of hyperlipidemia, also has uricosuric activity. Vitamin C may have a mild but persistent urate-lowering effect. Allopurinol - In contrast to probenecid, which is primarily indicated only in patients who have impaired renal excretion of uric acid, xanthine oxidase inhibitors are likely to be effective in virtually all circumstances warranting urate-lowering therapy for gout. However, safety considerations limit their use in some patients. MOA inhibition of uric acid production is in large part due to inhibition of xanthine oxidase (xanthine dehydrogenase) by both the native drug and the active metabolite oxypurinol. Urate production falls but hypoxanthine and xanthine accumulate in body fluids, producing a state of pharmacologic xanthinuria.