Nejm 2011;364:443

Cause:Hyperuricemia, with pain due to wbc ingestion of crystals? Primary type is due to a renal tubular transferase deficiency (normally salvages urate); may be genetic, sporadic. Secondary type due to tissue breakdown or decreased renal tubular excretion of urate

Pathophys:(Ann IM 2005;143:499) In kidneys, uric acid is normally 100% filtered, 100% resorbed, 100% excreted in distal tubule but may be competitively inhibited by lactate, ETOH, ketone bodies. Podagra from traumatically increased synovial fluid from which water resorbed at night faster than urate leading to a gouty attack (Ann IM 1977;86:230, 234)

Male/female = 20:1; peak onset in males age ~30 yr and postmenopausally in women

Secondary type seen w leukemia, esp when being rx’d (hyperuricemia and urate nephropathy but not gout), polycythemia, hemolytic anemia, starvation even in obese, diuretic rx, moonshine drinkers due to lead in alcohol (Nejm 1969;280:1199), alcoholics because increased urate production and perhaps decreased excretion

Sx:Family hx (50%); podagra (inflammation/swelling of 1st mp joint of big toe) (84%) or other severely painful arthritis; low-dose ASA (<4 gm) precipitates and/or worsens

Si:Arthritis including podagra, tophi (ear > elbow > finger > foot)

Acute attacks last 1-14 d, sx free between attacks but increasing frequency over years; without rx, permanent damage ensues

DJD; no increase in pseudogout; renal stones, but the nephropathy is associated with lead-related gout (Nejm 1981;304:520) as well as other types of gout

r/o reactive (Reiter’s) arthritis; septic joint; RA; pseudogout; DJD; rare hyperuricemic X-linked recessive LESCH-NYHAN SYNDROME, characterized by choreoathetosis, dystonic spasticity and self-mutilation (Nejm 1996;334:1568); and rarely, sarcoid arthritis, which also improves with colchicine (Nejm 1971;285:1503)

Lab:

Chem:Uric acid >10 mg % (high false-pos and -neg rates with acute gout, so an elevation does not prove gout, nor does a normal value disprove it; clinical judgement like presence of podagra and course or crystals on tap make the dx)

Suppression of uric acid from uricosurics, eg, ASA, allopurinol, radiocontrast agents (Ann IM 1971;74:845); false increases from L-dopa

Joint fluid:With polarizing scope, long thin urate crystals, some inside wbc’s, negatively birefringent (yellow parallel to red filter axis, blue when perpendicular)

Urine:24-h urine acid 1 gm; urate/creat ratio >0.75;

urate_u/creat_u × creat_s/creat_u >0.7 = high excretor on am spot urine (Ann IM 1979;91:44)

Xray:Soft tissue swelling; in chronic type, DJD and punched-out areas of bone

Rx:

(Nejm 1996;334:445)

Prevention: no need to rx asx mild increases in uric acid

Diet: minimize meat and seafood (Nejm 2004;350:1095)

Meds:

• Colchicine 1-2 mg po qd
• Probenecid 1-3 gm po qd divided, start with 0.5 gm; or
• Sulfinpyrazone 800 mg po qd divided; both prevent 100% resorption, use esp if 24-h urine urate <600 mg
• Allopurinol 200-400 mg po qd if 24-h urate >600 mg, or renal disease (decrease dose to 100 mg qd in anuria to prevent rash/fever/hepatitis syndrome, or tophi; can precipitate an attack)
• Febuxostat 40 - 80 mg po qd, xanthine oxidase inhibitor, more selective than allopurinol, easier dosing, currently 2nd line (Lancet 2010, doi 10.1016 S0140-6736 10 60665-4, Nejm 2005;353:2450)
• Pegloticase (Krystexxa): IV pegylated uricase, dosing several times monthly, rapid reduction in uric acid levels, may increase gout flares because of this, danger of antibody formation with anaphylaxis in 7.3% of patients
• [Rilonacept (Arcalyst) and canakinumab (Ilaris)], antiinflammitory IL-1 inhibitors, likely will be approved for use in gout, likely for patients with contra indications to steroids or colchicine

Acute: if attack <10 d old,

• Colchicine 0.6 mg po q 1-2 h up to 3-4 doses; renal excretion, inhibits microtubular (actin) formation, hence decreases lysozymes, which cause inflammation; adverse effects: NV+D, B₁₂ malabsorption from ileum (Nejm 1968;279:845), alopecia, decreased wbc’s; myo- and neuropathies (Nejm 1987;316:1562); or
• Indomethacin 50 mg po tid-qid until relief then rapid taper over a week; beware CNS and CHF effects in elderly; or
• Steroids intra-articularly or systemically as short-tapering dose; or ACTH 80 IU im/iv, then 40 mg 12 h later (Arth Rheum 1988;31:803), esp if sx >10 d