4/3/18 Disclosures None Resolving Controversies in Gout - PDF document

4/3/18 Disclosures • None Resolving Controversies in Gout Management Andrew J. Gross, MD Rheumatology Clinic Chief Clinical Professor University of California, San Francisco Teaching Objectives • Understand management of acute gout • Understand the management of chronic gout and the approaches to uric acid lowering therapy. Acute Gout Management 1

4/3/18 75 y.o. man with DM, CKD with 1 day acutely swollen Acute Gout - Case 1 & warm ankle with low-grade fever. Synovial fluid A 75 year old man with a history of diabetes, CKD, and gout is shows negatively birefringent crystals & WBC 85,000. admitted with 1 day of acute swelling and pain in the right ankle. What do you do next: His temp is 99.4. The ankle is warm and swollen. The other joints seem unremarkable. Arthrocentesis in the ED demonstrates negatively birefringent crystals. Cell count 85,000 WBC – 91% PMNs. A. Hold allopurinol & wait What do you do next: for GS & Cx A. Hold allopurinol & wait for cultures B. Inject corticosteroid B. Inject corticosteroids into the joint C. Prednisone taper C. Prescribe a prednisone taper D. Naproxen 500 mg BID D. Prescribe naproxen 500 mg BID E. IV antibiotics and wait E. Prescribe IV antibiotics & wait for for GS & Cx the results of the gram stain & Cx 5 Acute Gout - Case 1 Differential Diagnosis of monoarticular arthritis A 75 year old man with a history of diabetes, CKD, and gout is admitted with 1 day of acute swelling and pain in the right ankle. • Septic Arthritis • Trauma His temp is 99.4. The ankle is warm and swollen. The other joints – Gram Positive cocci • Exacerbation of seem unremarkable. Arthrocentesis in the ED demonstrates Osteoarthritis – Gram Negative Rods negatively birefringent crystals. Cell count 85,000 WBC – 91% PMNs. – Lyme disease What do you do next: – Tb/Fungal • Crystal Arthritis A. Hold allopurinol & wait for cultures 1-5% of patients with crystal – Gout arthritis will also have septic B. Inject corticosteroids into the joint – Pseudogout arthritis of the same joint C. Prescribe a prednisone taper • Spondyloarthritis (e.g. Papanicolas et al, J Rheumatol 2012; D. Prescribe naproxen 500 mg BID Reactive Arthritis) Shah K, et al, J Emerg Med 2007 • Vasculitis E. Prescribe IV antibiotics and wait for • Palindromic Rheumatism the results of the gram stain & Cx 2

4/3/18 Acute Gouty Arthritis • Provocation: trauma, ethanol, exercise, new medication What can help us feel more confident • First Attack: this is a gout attack and not infection – fourth to sixth decade of life – 90% Monoarticular without waiting for the cultures? – 50% Podagra • Sites: – 1st MTP – Instep, mid-foot, ankle, knee – wrist, fingers, elbow Septic Arthritis most commonly affects large joints http://images.rheumatology.org/image_dir/album75676/md_99-14-0009.tif.jpg The Value of a Careful Joint Exam Acute Gout - Case 2 Tip: A 53 year old man with HTN, nephrolithiasis, In a patient with a history of many and a history of “crystal proven gout” comes to attacks of gout, attacks tend to be see you for acute foot pain. oligoarticular or polyarticular. This His first attack of gout came in his 1 st toe about can be appreciated by doing a very 2 years ago with a sudden onset of intense pain careful joint examination. that gradually improved over 2 weeks. Since then he has had 2 more attacks in both feet. Negatively birefringent crystals were seen in joint fluid aspirated from his ankle. The most recent attack started 3 days ago in his 1 st toe and instep. On examination there is marked swelling, erythema and tenderness over the 1 st MTP bursa as well as the 1 st metatarsal-tarsal joint. http://www.eorthopod.com/public/patient_education/6588/gout.html 3

4/3/18 All of the following are reasonable treatments Test Your Knowledge… for acute gout EXCEPT: All of the following are reasonable treatments for A. NSAIDS acute gout EXCEPT: B. Prednisone Taper a) NSAIDS (naproxen 500mg 2x/d, indomethacin 50mg 3x/d) C. IM Triamcinolone b) Prednisone 20-60 mg/d, tapered over 6-18 days D. Intra-Articular c) Intra-muscular corticosteroid injection. (Triamcinolone 60- 80 mg IM; may need to repeat in a couple of days) Triamcinolone d) Intra-articular steroid injection (Triamcinolone 20-40 mg) E. Colchicine every hour e) Colchicine 0.6 mg every hour for 6 doses 5 Test Your Knowledge… Update : Low dose Colchicine is effective for acute gout Diarrhea “low-dose” colchicine (1.2 mg followed 26%, 0% by 0.6 mg in 1 hour [1.8 mg total]) All of the following are reasonable treatments for 77%, 19% acute gout EXCEPT: “high-dose” colchicine (1.2 mg followed by 0.6 mg every hour for 6 hours [4.8 mg total]) any, severe a) NSAIDS (naproxen 500mg 2x/d, indomethacin 50mg 3x/d) % of patients improved b) Prednisone 20-60 mg/d, tapered over 6-18 days c) Intra-muscular corticosteroid injection. (Triamcinolone 60- 80 mg IM; may need to repeat in a couple of days) d) Intra-articular steroid injection (Triamcinolone 20-40 mg) e) Colchicine 0.6 mg every hour 1.2 mg then 0.6 mg 1 hour later. (Do not repeat for 2 weeks if patient has CKD.) % improvement Terkeltaub RA, et al, Arthritis Rheum 2010, PMID 20131255 4

4/3/18 Efficacy of NSAIDs & Corticosteroids for Treatment of Acute Gout Acute Gout • NSAIDS (naproxen 500mg BID, indocin 50mg TID, diclofenac 50 mg BID) NSAIDs are problematic in patients with CKD • Prednisone: 60mg qd, taper over 6-18 days NSAIDs use was associated with increased risk of CKD in patients with hyperuricemia or gout (matched case-control study) [Risk of CKD] Naproxen Prednisone Henry D, et al, Br J Pharmacol 1997, Withdrawal of NSAIDs for 1 year (along with control of hyperuricemia) resulted in improved renal function in patients. Perez-Ruiz F, et al, Nephron 2000, PMID 11096285 Janssens H, et al, Lancet 2008, PMID 18514729 also see Rainer TH, et al, Ann Intern Med 2016, PMID 26903390 Update: Targeting Inflammatory Pathways to Update: Targeting Inflammatory Pathways to treat acute gout treat acute gout Mechanisms of Inflammation • All patients received anakinra (IL-1 receptor antagonist) in Gout • Treated with 100 mg SQ injection daily for 3 days ($50-100/injection) All 10 patients with acute gout responded rapidly to anakinra. • • 9/10 had complete resolution of gout symptoms in 3 days • No adverse effects were observed. Similar Results reported by Chen K et al, Semin Arthritis Rheum 2010 • ASGARD Study in process comparing anakinra vs. solumedrol in CKD • Burns CM, Wortmann RL, Lancet, 2011, PMID 20719377 5

4/3/18 Chronic Gout - Case 3 The same 53 year old man with HTN, nephrolithiasis and gout returns 9 months later complaining of another flare of joint pain in his feet (now 4 total in 3 years). His medications Chronic Gout Management include ASA, HCTZ, lisinopril, and ibuprofen for the joint pain. He asks what can be done to prevent future attacks. Choose the most correct answer: A. Modify his diet to avoid foods with moderate-high purine content B. Stop the thiazide C. Stop the ACE inhibitor D. Treat with probenecid E. Treat with colchicine 53 y.o. man with HTN and nephrolithiasis with 4 gout Case 3 (continued) attacks over 3 years asks what can be done to prevent future attacks. Choose most correct answer: The same 53 year old man with HTN and nephrolithiasis returns 9 months later complaining of another flare of joint A. Avoid moderate-high pain in his feet (now 4 total in 3 years). His medications purine foods include ASA, HCTZ, lisinopril, and ibuprofen for the joint pain. He asks what can be done to prevent future attacks. B. Stop thiazide Choose the most correct answer: C. Stop ACE inhibitor A. Modify diet to avoid foods with mod-high purine content D. Treat with probenecid B. Stop the thiazide E. Treat with colchicine C. Stop the ACE inhibitor D. Treat with probenecid E. Treat with colchicine 5 6

4/3/18 Non-Pharmacologic Uric Uric Acid homeostasis Acid Lowering Therapy Treatment Approaches: Treatment Approaches: • Reduce Intake • Reduce Intake • Reduce Production • Reduce Production • (Increase Metabolism) • (Increase Metabolism) • Increase Excretion • Increase Excretion Neogi T, N Engl J Med, 2011, PMID 21288096 Update : Not all high purine foods Treating Gout: Diet & Meds contribute to development of gout Diet and Risk of Gout in Men Relative Risk of Developing Gout Foods Moderately to Very Medications that inhibit uric 1.6 High in Purines acid secretion Higher risk 1.4 • Hearts, sweetbreads, liver, • Thiazide diuretics 1.2 Kidney, Herring, smelt, • Aspirin (< 1 gm/d) 1 sardines, mussels, anchovies, Lower risk 0.8 Yeast • Grouse, Turkey, Partridge, 0.6 Goose, Pheasant, Mutton, Veal, 0.4 Beverages associated with Bacon hyperuricemia 0.2 Salmon, Trout, Haddock, • 0 Scallops • Beer Total Meat Seafood Purine-rich Total Dairy • High fructose drinks Vegetables Men in the top quintile of intake compared with those in the lowest quintile (multivariate analysis) Johns Hopkins: Diet and Gout Adapted from Choi HK, et al, New Engl J Med 2004, PMID 15014182 http://www.johnshopkinshealthalerts.com/reports/arthritis/460-1.html 7