Management of Acute Gout,John J. Cush, MD Presbyterian Hospital of Dallas,江西不孕不育医院 ,Who Manages Acute Gout,Rheumatologists:musculoskeletal medicine specialists Tends to see minority of Gout patients, often those with severe, recalcitrant, chronic disease Compared with RA (similar prevalence), far fewer gout patients are seen/followed by rheumatologists Rheum referral more accurate dx, shorter Sx duration (3.1day), shorter hospitalization (7.4 days), lower hospitalization costs ($5995 less). Solomon DH. Ann Int Med 12:52, 1997 Primary Care and Emergency Dept Physicians First line for acute gouty attacks Education is needed to optimize outcomes and limit toxicity Survey in Mexico shows significant drug misuse by non-rheumatologists (GP,IntMed,Ortho) Rev Invest Clin 55:621,2003 Survey of N.Zealand Rheums and GPs: differences in NSAID, colchicine, allopurinol use. Stuart RD N Z Med J 104:115,1991,Gout,Disorder of urate metabolism, results in deposition of monosodium urate (MSU) crystals in joints and soft tissues. 1st described 5th century BC Hippocrates described gout as “the king of diseases and the disease of kings” Burden: In 1981, 37 million lost work days in US* 2003 Kim et al estimates the annaul cost of Acute Gout is $27,378,494 in the USA (underestimate: women excluded & not all indirect and intangible costs included),* Roubenoff et al,National Health Intv Survey (&PE) = 17,030 men/women,(2.7%),(5.6%),NHANES III 1988-94,Prevalence of Gout,NHANES III 1988-94,Gout,Acute: intermittent/recurrent, LE, ascending, inflammatory mono/oligoarthritis, “Podagra” Intercritical gout: between attacks Tophaceous gout: chronic, accumulation of MSU crystals as “tophi” (may look like RA) Asymptomatic hyperuricema: elevated uric acid without evidence of gout, nephrolithiasis. Higher levels increase risk of these diseases Renal: nephrolithiasis, gouty nephropathy, uric acid nephropathy,Acute (Classic) Gout,Acute, severe onset of pain, warmth, inflammation, Limited motion cant walk, cant put sheet on it. Podagra (50-90%): pain, swelling warmth in 1st MTP Joints: MTP, tarsus, ankle, knee Associated with fever, leukocytosis, high ESR or C-reactive protein levels. Initially monarthritis (80-90%) and with repeated attacks ascends from the lower extremity (initial polyarthritis in elderly, women, myeloproliferative disorders, CyA) Precipitants: stress, trauma, excess alcohol, infection, surgery, drugs Chronology: untreated attacks last 7-14 days. Acute gout risk of repeat attack estimated to be 78% w/in 2 yrs,Natural Hx of Acute Attack Bellamy N, et al. Br J Clin Pharmacol 24:33-6, 1987,11 volunteers with acute podagra studied 2 withdrew on day 4 for severe pain 9 remaining showed improvement Pain by day 5 Swelling by day 7 Tenderness improved in 7/9 by day 7 (2 persisted) But only 3 noted resolution of pain during 7d study Implications for clinical trial endpoints? Pain improvement/resolution by day 3-5 Resolution of symptoms, return to normal activity,Acute Gout,Laboratory Findings 40-49% will have normal uric acid levels Leukocytosis common ESR and CRP elevated No indices of chronic inflammatory disease (alb, Hgb) Measureable elevations in IL-6 and IL-1 Radiographic findings Soft tissue swelling (Opacities = tophi) Normal Joint space and Normal ossification Erosions: nonarticular, punched out, Sclerotic margins, overhanging edge,Gouty Tophi,Incidence has decreased over last few decades Seen in 25-50% of untreated patients (after 10-20yrs) Location: Olecranon, bursae, digits, helix of ear Damages bone, periarticular structures and soft tissues Palpable measure of total body urate load Other Extraarticular Complications Renal Uric acid calculi (seen in10-15% of gout pts) Chronic urate nephropathy (in those with tophi) Acute uric acid nephropathy (in pts undergoing chemotherapy) Hypertensive Renal disease is the most common cause of renal disease in gout,Uric Acid,Random hyperuricemia gout (likely CRI, diuretic use) Acute attack: Urate levels may be normal, low or high 40-49% of acute gouty attacks normouricemic Mechanism: increased excretion of uric acid Probably mediated by IL-6, inflammation Urano W, et al. J Rheumatol 29:1950-3, 2002 Schlesinger N, et al. J Rheumatol 24: 2265-6, 1997 Negative association between Gout RA Few reports of both coexisting in literature RF preferentially binds MSU coated with IgG and inhibited neutrophil chemiluminescence (RF may block interaction of crystal bound IgG and Fc recpt),Diagnosis of Gout,1977 ARA criteria: Urate crystals*: IA or Tophus Any 6 of following: 1 attack acute arthritis; Max. inflammation w/in 1day; Erythema over joint; Podagra; hx podagra; Unilateral tarsal involvement; Tophus; Hyperuricemia; Asymmetric swelling on xray; subcortical cyst w/o erosion; c/s neg. inflam arthritis Practical Approach: Acute or recurrent inflammatory monarthritis/oligoarthritis With evidence of MSU crystal identification OR One of the following: History of recurrent, intermittent similar at