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2. 2 CLINICAL MANIFESTATION & TREATMENT OF GOUT Azami Ahad.MD. Rheumathologist1392,9,8

3. Classic stages of Gout I.Asymptomatic hyperuricemia II.Acute Intermittent Gout (Gouty Arthritis) with Intercritical Gout III.Chronic Tophaceous Gout 3

4. Asymptomatic hyperuricemia:  Very common biochemical abnormality  Defined as 2 SD above mean value  Majority of people with hyperuricemia never develop symptoms of uric acid excess 4

5. ACUTE GOUTY ARTHRITIS Flare: classic descriptionFlare: classic description Sydenham, 1683 Sydenham, 1683 5

6. ACUTE GOUTY ARTHRITIS Explosive suddenness & commonly begins at night.Explosive suddenness & commonly begins at night. The affected part becomes: Hot, dusky red,swollen & extremely tender Hot, dusky red,swollen & extremely tender Monoarticular (85%-90%)Monoarticular (85%-90%) Polyarticular (3%-14%)Polyarticular (3%-14%) 6

7. ACUTE GOUT 7 Systemic: patients may have fever, chills and malaiseSystemic: patients may have fever, chills and malaise Desquamation Desquamation

8. Common Sites of Acute Flares Midfoot Gout can occur in bursas, tendons, and joints Olecranon Bursa Elbow Wrist Knee Ankle Subtalar 1st MTP (eventually affected in ~90% of individuals with gout) Fingers 8

9. intercritical or interval gout ? intercritical or interval gout ? intervals between acute gout flares 9

10. Intervals Between 1 st & 2 nd Acute Flares Majority experience second acute flare within 1 year of first gout flare Yu et al. Ann Int Med. 1961;55:179-192 10

11. Clinical Course of Classic Gout 11

12. Chronic gouty arthritis Chronic polyarticular gout confused with other conditionsChronic polyarticular gout confused with other conditions 3-42 yrs (11.6 yrs) after 1 st attack3-42 yrs (11.6 yrs) after 1 st attack Urate crystals deposition in cartilage, synovial membranes,tendons,soft tissues,Urate crystals deposition in cartilage, synovial membranes,tendons,soft tissues, tophustophus 12

13. Chronic tophaceous gout Tophus : localized deposit of monosodium urate crystals 13

14. Chronic tophaceous arthritis Tophus: Tophus: Hands and feetHands and feet & knees & knees Olecranon bursaOlecranon bursa HelixHelix Achilles tendonsAchilles tendons 14

15. Chronic tophaceous arthritis Tophus: Tophus: Hands and feet & kneesHands and feet & knees Olecranon bursaOlecranon bursa HelixHelix Achilles tendonsAchilles tendons 15

16. Chronic tophaceous arthritis Tophus: Tophus: Hands and feet & kneesHands and feet & knees Olecranon bursaOlecranon bursa HelixHelix Achilles tendonsAchilles tendons 16

17. Diagnostic Studies Uric AcidUric Acid 24hr urine uric acid24hr urine uric acid CBCCBC ESRESR AST, ALTAST, ALT LipidsLipids creatininecreatinine

18. SYNOVIAL FLUID ANALYSIS The Gold standardThe Gold standard Crystals intracellular during attacksCrystals intracellular during attacks Needle & rod shapesNeedle & rod shapes Strong negative birefringenceStrong negative birefringence 18

19. A-birefringent MSU crystal perpendicular to orienting line of compensator B-same crystal extinct on the axis of the polarizer or analyzer C-birefringent MSU crystal parallel to orienting line of compensator 19

20. Gout: Imaging Soft tissue swelling Soft tissue swelling Asymmetric changes Asymmetric changes Erosive lesions (overhanging edge) Erosive lesions (overhanging edge) Preserved joint space until late Preserved joint space until late Juxta articular osteoporosis minimal or absent Juxta articular osteoporosis minimal or absent 20 Erosion with overhanging edge

21. 21 joint destruction & erosions joint destruction & erosions cysts joint destruction destruction destruction Gout - X-ray changes

22. Differential diagnosisAcute:  Septic arthritis  Bursitis, cellulitis, tenosynovitis  Other crystal  Traumatic arthritis  Hemoarthrosis  Sarcoid arthritis  palindromic rheumatim  ReA  AS with peripheral involvement  PsA  Rheumatic fever 22

23. Differential diagnosis 23 Chronic:  Nodular RA  PsA  OA( with Heberden ’ s & Bouchard ’ s nodes)  Sarcoid arthritis  Xanthomatosis

24. 24 TREATMENT OF TREATMENT OF GOUT GOUT Aims of therapy? Aims of therapy?

25. TREATMENT OF GOUT Asymptomatic hyperuricemia  Associated factors : Obesity, hyperlipidemia, alcoholism,& HTN Obesity, hyperlipidemia, alcoholism,& HTN Hypertriglyceridemia fenofibrate Hypertriglyceridemia fenofibrate HTN losartan HTN losartan Diets? Diets? 25

26. TREATMENT OF GOUT Acute Gouty Arthritis RestingResting Colchicine, NSAIDs, Corticosteroids, ACTHColchicine, NSAIDs, Corticosteroids, ACTH The timing of therapy initiation? The timing of therapy initiation? Ice pack? Ice pack? 26

27. TREATMENT OF GOUT Acute Gouty Arthritis  Colchicine:  Po or iv  Dose:1pill/2-6h  Low therapeutic index  Side effects? In severe renal insufficency should be started at 0.3 mg/ day. 27 Colchicum automnale

28. TREATMENT OF GOUT Acute Gouty Arthritis NSAIDs : In established diagnosis In established diagnosis Indomethacin (traditional choice) Indomethacin (traditional choice) Initial dose: 50-75mg Followed by 50mg/6-8h(for 48h) taper Initial dose: 50-75mg Followed by 50mg/6-8h(for 48h) taper to 50mg for the next 2day to 50mg for the next 2day Max dose in 1 st 24h:200mg Max dose in 1 st 24h:200mg Other NSAIDs: Other NSAIDs: Naproxen,fenoprofen,ibuprofen,sulindac,piroxicam,ketoprofen & Naproxen,fenoprofen,ibuprofen,sulindac,piroxicam,ketoprofen & cox2 inhibitors cox2 inhibitors 28

29. TREATMENT OF GOUT Acute Gouty Arthritis Corticosteroids: Triamcinolone: 10-40 mg Intra-articular to a single joint Intra-articular to a single joint Injection to bursa methylprednisolone:25-50mg Injection to bursa methylprednisolone:25-50mg Oral, IM & IV Oral, IM & IVIndications: 1) Intolerance of colchicine or NSAIDs 2) Medical condition such as: PUD & renal disease  Oral : High doses are needed (prednisone 20 to 60 mg/day for 3-5 days then taper 1-2 weeks ) (prednisone 20 to 60 mg/day for 3-5 days then taper 1-2 weeks )  Improvement seen in 12-24 hr 29

30. TREATMENT OF GOUT Acute Gouty Arthritis Adrenocorticotropic Hormone (ACTH): Single inj of IM ACTH gel (25 to 80 IU) Single inj of IM ACTH gel (25 to 80 IU) Repeat if required q 24-72 h Repeat if required q 24-72 h  Is effective postoperatively  may be more effective than GCs.  Mechanism: stimulating of GCs production activation of melanocortin R-3 activation of melanocortin R-3 30

31. Acute Gouty Arthritis prophylaxis Only indicated when patient uses urate lowering Rx Only indicated when patient uses urate lowering Rx Colchicine: 0.6 mg, 1-3 times /day Colchicine: 0.6 mg, 1-3 times /day  85% effective  Axonal neuromyopathy : prximal muscle weakness painful paresthesia & CPK prximal muscle weakness painful paresthesia & CPK  Rhabdomyolysis OR OR NSAIDs: indomethacin 25 mg- BID OR NSAIDs: indomethacin 25 mg- BID OR naproxen 250 mg/day naproxen 250 mg/day Continue still serum urate levels stabilize and no attacks for 3–6 moths. Continue still serum urate levels stabilize and no attacks for 3–6 moths. 31

32. TREATMENT OF GOUT CONTROL OF HYPERURICEMIA  Lifelong treatment  2 weeks after acute gout subsides  Concomitantly to colchicine Goal:Goal: Urate level<6.8mg/dl (preferably 5 to 6 mg/dL)Urate level<6.8mg/dl (preferably 5 to 6 mg/dL) 32

33. TREATMENT OF GOUT CONTROL OF HYPERURICEMIA Indications:Indications: >2-3 acute attacks>2-3 acute attacks Renal stones (urate or calcium)Renal stones (urate or calcium) Tophaceous goutTophaceous gout Chronic gouty arthritis with bony erosionsChronic gouty arthritis with bony erosions Asymptomatic hyperuricemia with serum uric acid >12 mg/dL or 24-hr urinary excretion >1100 mg ?Asymptomatic hyperuricemia with serum uric acid >12 mg/dL or 24-hr urinary excretion >1100 mg ? 33

34. Urate-lowering drugs 34 net reduction in total body pool of uric acid block production block production enhance excretion

35. CONTROL OF HYPERURICEMIA xanthine oxidase inhibitors Indications:  large quantity of U.A in urine  renal calculi  tophus  RF due to U.A 35 Allopurinol – oxypurinol - febuxostat

36. CONTROL OF HYPERURICEMIA xanthine oxidase inhibitors Allopurinol:Allopurinol:  Dose  Side effects  Drug interactions 36

37. CONTROL OF HYPERURICEMIA xanthine oxidase inhibitors Oxypurinol:Oxypurinol: Allopurinol active metabolitesAllopurinol active metabolites In pats sensitive to allopurinolIn pats sensitive to allopurinol FDAFDA Febuxostat (Uloric)Febuxostat (Uloric) Potent xanthine oxidase inhibitorsPotent xanthine oxidase inhibitors Excellent alternativeExcellent alternative In the United States: 40 or 80 mg a dayIn the United States: 40 or 80 mg a day In Europe: 80 and 120 mg a dayIn Europe: 80 and 120 mg a day 37

38. Febuxostat  No adjuste in mild to moderate renal insufficiency  Cardiovascular events 38

39. Febuxostat Phase III Clinical Trial Results Febuxostat 80 mg Febuxostat 120 mg Allopurinol 300 mg Last 3 sUA <6.0 mg/dL 53% (136/255)* 62% (154/250)* 21% (53/251) Wk 52 sUA <6.0 mg/dL 81% (129/159)* 82% (119/145)* 39% (70/178) 39 Compared to allopurinol, significantly more patients on either dose of febuxostat were able to achieve mean serum urate concentrations less than 6.0 mg/dL *p<0.05 for each febuxostat group vs. allopurinol group Proportion of Subjects with sUA <6.0 mg/dL (ITT Subjects) Becker et al. ACR/ARHP Program Book Supplement. 2004;L18.

40. Uricosuric Agents  Renal U.A excretion  Indications: age<60 yrage<60 yr C.C>80ml/minC.C>80ml/min uric acid excretion<800mg/24huric acid excretion<800mg/24h no history of renal calculino history of renal calculi Probencid 500mg - 3g/dayProbencid 500mg - 3g/day renal calculi renal calculi 40 Probencid – sulfinpyrazone - benzbromarone

41. Uricosuric Agents  Sulfinpyrazone:  Initiate: 50mg/day 300-400mg/day (in divided dose)  full dose: 800mg/day  Benzbromarone:  100 -200 mg/day  More potent than probencid & sulfinpyrazone  Well tolerated  Effective in cyclosporine-treated patients Can be used in moderate renal dysfunction (creatinine clearance approximately 25 mL/min).Can be used in moderate renal dysfunction (creatinine clearance approximately 25 mL/min).  losartan 41

42. UricasesUricases Pegloticase is a pegylated mammalian (porcine-like) recombinant uricasePegloticase is a pegylated mammalian (porcine-like) recombinant uricase Approved by the FDAApproved by the FDA 8 mg iV/ 2 wk s in severe tophaceous gout8 mg iV/ 2 wk s in severe tophaceous gout 42

43. Complication of gout  Joint: destruction  Soft tissue  nerve entrapment syndrome: CTS, tarsal tunnel syndromes  kidney: uric acid calculi(10-15%), chronic urate nephropathy, and acute uric acid nephropathy  Heart: ischemic heart disease 43

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