1. Management

2. Main Diagnosis Acute gouty arthritis on top of chronic tophaceous gout
Ruptured tophi with secondary bacterial infection of the foot with osteomyelitis
Anemia secondary to occult GI bleeding probably due to NSAID gastropathy
Chronic kidney disease secondary to gout

3. Panel B: Acute Gouty Arthritis Y N Y N
Patient with ACUTE GOUT ARTHRITIS
Panel B:
Acute Gouty Arthritis
Identify and treat precipitants of gout flare*
Do NOT start Allopurinol
If the patient is already taking allopurinol, do not change its dose.
Ice compress (20 min x 4x/day up to one week)
Any contraindications to colchicine/ NSAID/ COX-2 selective inhibitor Y
REFER TO RHEUMATOLOGIST
Start Prednisone 30 mg single dose on day 1, reduce dose by 5 mg daily and discontinue by day 7
Intravenous or intramuscular steroids are options N
Colchicine 0.5 mg/tab 1 tab TID-QID ± NSAID/ COX-2 selective inhibitor ± analgesic
On day 7, is the arthritis RESOLVING Y
Discontinue NSAID/ COX-2 inhibitor/ Steroids
Start or adjust Colchicine 0.5 mg/tab 1 tab BID
Go to Panel C
(Intercritical and Chronic Gout N
Review adherence to meds
Recheck if precipitants have been adequately treated
REFER TO RHEUMATOLOGIST
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

4. Known precipitants of gout flares
Stress
Hospital admission or surgery
Infection
Dehydration
Drugs/ Medication (aspirin <1g/day, pyrazinamide, ethambutol, diuretics, etc)
Irregular intake of urate lowering medications
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

5. Intercritical and Chronic Gouty Arthritis
Panel C:
Intercritical and Chronic Gouty Arthritis
Patient with INTERCRITICAL/ CHRONIC GOUT
Start Colchicine 0.5 mg/tab 1 tablet BID
Prescribe lifestyle modifications*
Correct modifiable risk factors
REFER TO RHEUMATOLOGIST/ NEPHROLOGIST
Is there an INDICATION to start Allopurinol?
Is crea clearance <80 mL/min? Y Y N N
Instruct patient on colchicine use to avert flare
Monitor/ observe for indications to start allopurinol
Baseline crea, uric acid every 1-3 months & ALT every 6 months
Start Allopurinol at mg once daily, to be titrated by mg every 2-4 weeks
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

6. Y Y N N Y N Maintain on allopurinol and colchicine Check lifestyle
Check adherence to medications
REFER TO RHEUMATOLOGIST
On periodic monitoring, is SUA <6mg/dL?
Any flare in between visits? Y Y N N
Maintain allopurinol
May discontinue colchicine
Continue periodic monitoring of SUA, crea
Has allopurinol 300 mg/day been used? Y
Review the diagnosis of GOUT
REFER TO RHEUMATOLOGIST N
Continue titration of allopurinol
Maintain colchicine
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

7. Lifestyle modifications that should be prescribed to all patients with gout
Low to moderate purine diet
Intake of more fluid (at least 2 L/day if without contraindication)
Avoidance of alcoholic beverages
Maintenance of appropriate body mass index
Engagement in low-to-moderate aerobic exercises at least 45 minutes per day 4 times a week

8. Indications for starting urate lowering therapy
Recurrent arthritis, at least 2 episodes
Presence of tophaceous deposits
Radiographic evidence of chronic gout
Recurrent uric acid nephrolithiases

9. Febuxostat
inhibitor of xanthine oxidase, it is structurally different from allopurinol
has an alternate mechanism of enzyme inhibition, and is more potent
Love, BL et al. (2010). Urate-lowering therapy for gout: focus on febuxostat. Pharmacotherapy 30(6):

10. Febuxostat
Unlike allopurinol, which undergoes oxidation to the active metabolite oxypurinol and interacts chemically with the molybdenum center of xanthine oxidase
febuxostat remains unchanged and inhibits xanthine oxidase by binding in a narrow channel leading to the molybdenum center of the enzyme.
By this mechanism, febuxostat is able to inhibit both the reduced and oxidized form of xanthine oxidase to produce sustained reductions in sUA levels.
XOR is synthesized as XDH, which in mammals can easily be converted to XO by oxidation of sulfhydryl residues or by proteolysis
Love, BL et al. (2010). Urate-lowering therapy for gout: focus on febuxostat. Pharmacotherapy 30(6):

11. Gaffo, AL and Saag KG. (2009). Febuxostat: the evidence for its use in the treatment of hyperuricemia and gout. Core Evid 4:25-36

12. Rilonacept
Being evaluated as a therapeutic drug candidate for the prevention of gout flares in patients who are initiating uric acid- lowering therapy
Fusion protein designed to attach to and neutralize IL-1 before IL-1 can bind to cell surface receptors and generate signals that trigger inflammation
In patients with frequent gout attacks who have elevated blood levels of uric acid, chronic treatment with uric acid-lowering medicines, such as allopurinol, may be prescribed to eliminate the uric acid crystals and prevent reformation. During the first months of uric acid-lowering drug therapy, while uric acid blood levels are being reduced, the break up of the uric acid crystals, previously deposited in joints, can result in release of IL-1, causing acute flares of joint pain and inflammation.
IL-1 is a protein secreted by infection-fighting cells in the blood and tissues. It normally acts as a messenger to regulate inflammatory responses by attaching to surface receptors on cells that participate in the body’s immune system.2 In gout and certain other diseases, infection-fighting cells can generate excess levels of IL-1, transforming this normally helpful molecule into a key driver of inflammatory disease.3 12

13. Rilonacept
Currently indicated in the U.S. for the treatment of Cryopyrin-Associated Periodic Syndroms (CAPS), including Familial Cold Auto-inflammatory Syndroms (FCAS) and Muckle-Wells Syndroms (MWS) in adults and children 12 and older
IL-1 blockade may interfere with immune response to infections. Serious, life-threatening infections have been reported in patients taking rilonacept. Rilonacept should be discontinued if a patient develops a serious infection. Taking rilonacept with tumor necrosis factor inhibitors is not recommended because this may increase the risk of serious infections. Treatment with rilonacept should not be initiated in patients with active or chronic infections. Patients should not receive a live vaccine while taking rilonacept. It is recommended that patients receive all recommended vaccinations prior to initiation of treatment with rilonacept. Patients should be monitored for changes in their lipid profiles and provided with medical treatment if warranted. Hypersensitivity reactions associated with rilonacept administration have been rare. 13

14. PRE-SURGE
PREventive Study against URate-lowering drug-induced Gout Exacerbations 1 and 2
Evaluating the mean number of gout flares per patient over the first 16 weeks of initiation og allopurinol therapy.
Approximately 240 patients are being randomized on a 1:1:1 basis in each study to receive one of the following regimens:
Rilonacept 160mg as an initial loading dose, followed by weekly 80mg subcutaneous injections
Rilonacept 320mg as an initial loading dose, followed bu weekly 160mg subcutaneous injections
Weekly placebo injections

15. Preliminary results of PRE-SURGE 1
Patients who received rilonacept at a weekly dose of 160mg had an 80% decrease in mean number of gout flares compared to the placebo group over the 16 week treatment period (0.21 flares vs 1.06 flares, p<0.0001)
Patients who received rilonacept at a weekly dose of 80mg had a 73% decrease compared to the placebo group (0.29 flares vs 1.06 flares, p<0.0001)
Released on june 9, 2010 15

16. Preliminary results of PRE-SURGE 1
Adverse events that occurred at a frequency of at least 5% in any study group were:
Injection site reaction
Upper respiratory tract infection
Lower respiratory tract infection
Musculoskeletal pain/discomfort
headache

17. Global RE-SURGE
REview of Safety Using Rilonacept in preventing Gout Exacerbations study
Evaluating the safety of rilonacept vs placebo over 16 weeks in 1,200 patients at risk for gout flares from uric-acid lowering treatment, including allopurinol, febuxostat, probenecid, or sulfinpyrizone
About 300 patients receive placebo, 900 patients receive rilonacept as an initial 320mg loading dose, followed by weekly 160mg subcutaneous injections
Data expected in first half of 2011 17

18. Rilonacept with NSAIDs
Compared to indomethacin, there was no significant benefit from combining indomethacin with rilonacept
Measured by the primary endpoint of the average intensity of gout pain from hours after initiation of treatment. 18

19. Wound Management
Debridement may be accomplished by sharp, mechanical, enzymatic, and/or autolytic measures.
Wounds should be cleaned initially and each dressing changed by a nontraumatic technique.
Use normal saline
Selection of a dressing should ensure that the ulcer tissue remains moist and the surrounding skin dry.
Give tetanus prophylaxis
James, WD, et al. (2006). Andrews’ Diseases of the skin: Clinical Dermatology, 10th ed.

20. Cellulitis
Initial empiric therapy should cover both staphylococci and streptococci.
Intravenous penicillinase-resistant penicillins or a first-generation cephalosporin are usually effective
James, WD, et al. (2006). Andrews’ Diseases of the skin: Clinical Dermatology, 10th ed.

21. Osteomyelitis
Empiric therapy guided by findings on Gram’s stain or chosen to cover the most likely pathogens
Should include agent active against anaerobes in the setting of a decubitus ulcer or diabetic foot infection
Fauci, AS, et al. (2008). Harrison’s Principles of Internal Medicine, 17th ed

22. Fauci, AS, et al. (2008). Harrison’s Principles of Internal Medicine, 17th ed

23. ceftriaxone or cefotaxime
initial empiric therapy to cover gonococci, S. aureus, and streptococci, pending culture results
ceftriaxone or cefotaxime
Cef… 3rd gen expanded g- coverage.
Ciprofloxacin
Second Generation (fluorinated) Quinolones
These drugs are synthetic fluorinated analogues of nalidixic acid and are highly
potent bactericidal agents that alter the structure and function of bacterial DNA by
interfering with DNA gyrase. These drugs have a broad spectrum of activity against
gram-negative bacilli including H. influenzae, Enterobacteriaceae, Pseudomonas
aeruginosa, some gram-positive cocci, gram-negative cocci and various species
of mycobacteria. They have limited activity against Streptococci, Corynebacterium
spp. but with moderate activity against Staphylococci and virtually no activity
against anaerobes
Firestein, GS, et al. (2008). Kelley’s Textbook of Rheumatology, 8th ed
PNDF Vol II, 3rd ed (2006)

24. 3rd gen cephalosporins
more stable to hydrolysis by beta-lactamases than 2nd generation cephalosporins.
wider spectrum and greater potency against gram-negative organisms especially for Enterobacteriaceae
treating serious gram-negative bacillary infections including sepsis and meningitis when microorganisms are resistant to customarily used drugs or when aminoglycosides are contraindicated
cefotaxime and ceftriaxone - gram-positive organisms and beta-lactamase producing Proteus, Klebsiella, Serratia, H. influenzae, Enterobacter, N. gonorrheae and S. typhi
PNDF Vol II, 3rd ed (2006)

25. GI bleeding
Feldman, M et al. (2006). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.

26. GI Bleeding
Treatment of patients with fecal occult blood depends on the underlying disorder.
NSAIDs should be discontinued if possible
PPIs are more effective than H2 receptor antagonists and misoprostol
Feldman, M et al. (2006). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.

27. Anemia Blood transfusion
normal daily blood loss of 0.5 to 1.5 mL/day, a stool weight of 150 g, and a circulating hemoglobin level of 15 g/dL, the usual stool hemoglobin concentration is 0.5 to 1.5 mg/g of stool.
under normal circumstances, a total of 0.25 to 0.75 mg of elemental iron is lost because of gastrointestinal bleeding daily.
A small amount of iron is also lost in sloughed intestinal cells and from minute amounts of bleeding, making the average daily iron loss approximately 1 mg
The absorptive capacity of the small intestine for iron can increase dramatically in response to iron depletion but normally is limited.
Feldman, M et al. (2006). Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.

28. iron deficiency results only when iron loss exceeds absorption, usually when blood loss exceeds 5 to 10 mL/day over many weeks.
When diagnosis of iron deficiency anemia is established
iron therapy should be instituted
Ferrous sulfate, 325 mg orally two to three times daily, is recommended

29. Hypertension Diuretics – contraindicated in hyperuricemia, gout
Anti-adrenergics
Alpha Adrenoceptor Blockers - salt and/or water depleted may exhibit a sudden, drastic drop in standing BP after the first dose
Beta Adrenoceptor Blockers – relative contraindication insulin-requiring diabetes; renal failure; lipid disorders
Adrenergic Neuron Blockers – contraindicated in patient with PUD
Centrally Acting Anti-hypertensives – 2nd or 3rd line with multiple drug regimen
Fauci, AS, et al. (2008). Harrison’s Principles of Internal Medicine, 17th ed
PNDF Vol II, 3rd ed (2006)

30. Hypertension
Direct Vasodilators – precaution in renal or hepatic impairment
Calcium Channel Blockers
Angiotensin Converting Enzyme (ACE) Inhibitors – contraindicated in renal failure
Angiotensin 2 Receptor Blockers (ARB) – precaution in renal insufficiency
Fauci, AS, et al. (2008). Harrison’s Principles of Internal Medicine, 17th ed
PNDF Vol II, 3rd ed (2006)

31. Calcium Channel Blockers
Reduce vascular resistance through L-channel blockade, which reduces intracellular calcium and blunts vasoconstriction
NIFEDIPINE 5-10 mg q8h,
Amlodipine 5-10 mg daily
Felodipine Initially, 5 mg once daily, PO; titrated slowly to 10 mg once daily.
Nicardipine Start with 10 mg 3x/d PO
Nimodipine PO 60 mg q4h.
Fauci, AS, et al. (2008). Harrison’s Principles of Internal Medicine, 17th ed
PNDF Vol II, 3rd ed (2006)

32. Thank you!!!

33. Jordan, KM, et al. (2007). Guideline for Management of Gout
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

34. Ice compress 20 min x 4x/day up to one week
In the absence of contraindications
0.5 mg/tab TID-QID
initially at 30 mg and rapidly tapered over 6 days can be given as alternative
Allopurinol started at 100 mg/day 2 weeks after the pain and swelling has subsided.
Dose is titrated by mg/day every 2 to 4 weeks to achieve SUA <6 mg/dL.
The maximum dose of allopurinol is 300 mg/day.
SUA and serum creatinine should be periodically monitored.
NOTE: Those in pink boxes are from the PHILIPPINE cpg… just to jive the figure with PHIL guidelines…
Colchicine 500mcg tablets 0.5mg
Allopurinol toxicity – skin rash to toxic epidermal necrolysis, systemic vasculitis, bone marrow suppression, granulomatous hepatitis, renal failure
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

35. Jordan, KM, et al. (2007). Guideline for Management of Gout
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

36. Absence of response after a week should prompt re-evaluation of the diagnosis and referral to a rheumatologist
URICOSURICS
Drug Saf. 2008;31(8):
A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?
Standard dosages of benzbromarone (100 mg/day) tend to produce greater hypouricaemic effects than standard doses of allopourinol (300 mg/day) or probenecid (1000 mg/day) It is effective in patients with moderate renal impairment. Even assuming a causal relationship between benzbromarone and hepatotoxicity in the identified cases, benefit-risk assessment based on total exposure to the drug does not support the decision by the drug company to withdraw benzbromarone from the market given the paucity of alternative options. It is likely that the risks of hepatotoxicity could be ameliorated by employing a graded dosage increase, together with regular monitoring of liver function.
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

37. In the absence of contraindications, i. e
In the absence of contraindications, i.e.. renal impairment or gastrointestinal ulcers, the use of colchicines, traditional non-steroidal anti-inflammatory drugs (NSAIDs), OR selective cyclo-oxygenase 2 (COX-2) inhibitors is recommended for the treatment of acute gouty arthritis.
The expert panel recommends that colchicines (500 mcg tab) should not exceed 4 tablets in divided doses per day.
Prednisone, initially at 30 mg and rapidly tapered over 6 days can be given as alternative if colchicines, traditional NSAIDs or COX-2 inhibitors are contraindicated or not tolerated by the patient
Absence of response after a week should prompt re-evaluation of the diagnosis and referral to a rheumatologist
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

38. Ice compress is recommended in combination with pharmacologic agents for relief of joint pain and swelling of acute gouty arthritis
Serum uric acid (SUA) level should be reduced to and maintained at <6 mg/dL (0.36 mmol/L)
Continuous long term therapy with allopurinol is advised to achieve a target SUA level of <6 mg/dL
Allopurinol should be started at 100 mg/day 2 weeks after the pain and swelling of gouty arthritis has subsided. The dose is titrated by mg/day every 2 to 4 weeks to achieve SUA <6 mg/dL. The maximum dose of allopurinol is 300 mg/day. SUA and serum creatinine should be periodically monitored.
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

39. A referral to an internist or rheumatologist is recommended if SUA persistently remains > 6 mg/dL despite maximum dose.
Colchicine should be used at 0.5 mg/tab OD BID to prevent gout flares when initiating urate-lowering therapy with allopurinol. This should be maintained for 3-6 months from the last occurrence of gout flare and after the optimal SUA target is achieved. In the event that adverse events like diarrhea occur, a lower dose of colchicines should be used. NSAIDs should not be used for prevention of gout flares.
Dietary modification (to promote weight loss) and avoidance of alcohol should be prescribed.
Low impact exercises (walking, biking, swimming, ballroom dancing) may also be advised.
Li-Yu J, et al. (2008) Philippine Clinical Practice Guidelines for Management of Gout. Phil. J. Internal Medicine, 46:

40. Management of acute gout
(1) Affected joints should be rested and analgesic, anti-inflammatory drug therapy commenced immediately, and continued for 1–2 weeks.
(2) Fast-acting oral NSAIDs at maximum doses are the drugs of choice when there are no contraindication.
(3) In patients with increased risk of peptic ulcers, bleeds or perforations, co-prescription of gastro-protective agents should follow standard guidelines for the use of NSAIDs and Coxibs.
(4) Colchicine can be an effective alternative but is slower to work than NSAIDs. In order to diminish the risks of adverse effects (especially diarrhea) it should be used in doses of 500g bd–qds.
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

41. (6) Opiate analgesics can be used as adjuncts.
(5) Allopurinol should not be commenced during an acute attack but in patients already established on allopurinol, it should be continued and the acute attack should be treated conventionally.
(6) Opiate analgesics can be used as adjuncts.
(7) Intra-articular corticosteroids are highly effective in acute gouty monoarthritis and i.a., oral, i.m or i.v corticosteroids can be effective in patients unable to tolerate NSAIDs, and in patients refractory to other treatments.
(8) If diuretic drugs are being used to treat hypertension, an alternative antihypertensive agent should be considered, but in patients with heart failure, diuretic therapy should not be discontinued.
Jordan, KM, et al. (2007). Guideline for Management of Gout. British Society for Rheumatology

42. Given in ward Omeprazole 40 mg tab OD Amlodipine 10 mg tab OD
Clindamycin 300 mg cap q 6
Ciprofloxacin 250 mg tab BID
Given Colchicine as follows to treat acute gout: 2 tabs now then 1 tablet after 6 hours
Cold compress x mins TID on inflamed joints
AMLODIPINE - This drug acts primarily on peripheral vascular beds and have little effect on
cardiac muscle contraction or AV conduction. Pharmacokinetics: Bioavailability of
60-65%; plasma protein binding of 97.5%; terminal plasma half-life of h;
metabolized in the liver. Not dialyzable.
Clindamycin
It is a semisynthetic derivative of lincomycin and is effective for susceptible
streptococci, S. aureus, and Bacteroides spp.
Calcium channel blockers are a group of drugs that block the voltage dependent
calcium channel inhibiting the availability of intracellular calcium to interact with the
myosin complex of smooth muscles. This action leads to relaxation of the smooth
muscle allowing a decrease in peripheral resistance which leads to BP lowering.

43. COLCHICINE Oral: 500 mcg tablet NSAIDs For chronic gout
ANTIGOUT
For acute gout
COLCHICINE Oral: 500 mcg tablet
NSAIDs
For chronic gout
ALLOPURINOL Oral: 100 mg and 300 mg tablet
Colchicine is a mild anti-inflammatory drug with no analgesic effects. It acts
by inhibiting microtubule polymerization by binding microtubule protein subunits
and preventing their aggregation, thus disrupting membrane-dependent functions
as chemotaxis and phagocytosis, which are cardinal events in the inflammatory
response to precipitated crystals. It has no effect on the serum uric acid levels or
its renal excretion.
Pain relief after an oral dose occurs in less than 12 h. It concentrates in the
leucocytes, kidney, spleen and liver and does not distribute to the brain, heart or
skeletal muscles. It is partly deacetylated in the liver. Its protein binding is 10-31%;
half-life, min, and is prolonged to 45 min among patients with end-stage
renal disease. It achieves a peak serum concentraton of h after an oral dose
then declines for about 2 h prior to increasing again due to significant enterohepatic
cycling. It is eliminated both in the feces and the urine.
Acute attack: 500 mcg tab taken orally hourly until pain and inflammation
subside, to a maximum cumulative dose of 6.0 mg, or until GI
symptoms occur (reduce dose by 50% if CrCl is < 10 mL/min).
ADVERSE REACTIONS:
GIT: nausea, vomiting, diarrhea and abdominal pain in up to 80% of patients
undergoing rapid colchinization; hepatotoxicity, hemorrhagic colitis with overdose
or with liver or renal disease.; HEMATOLOGIC: aplastic anemia, bone marrow
suppression (specially with overdose or liver or renal disease); CNS: peripheral
neuritis; colchicine induced-myopathy and polyneuropathy with prolonged use;
DERMATOLOGIC: alopecia, rash; OTHERS: anorexia, azoospermia, renal
dysfunction with overdose or with liver or renal disease.
PNDF Vol. I, 7th ed. (2007)

44. 2.4 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
2.4.1 Non-selective COX inhibitors
IBUPROFEN
NAPROXEN
diclofenac
indometacin
ketoprofen
mefenamic acid
2.4.2 Selective COX 2 inhibitor
CELECOXIB
PNDF Vol. I, 7th ed. (2007)