* - GOUT IS OFTEN CLUSTERED WITH INSULIN RESISTANCE SYNDROME KNOWN AS METABOLIC SYNDROME OR SYNDROME X, DIABETES MELLITUS, HYPERTENSION, HYPERTRIGLYCERIDEMIA, ABDOMINAL OBESITY & LOW HDL WHICH MAY INCREASE CHANCES OF CORONARY ARTRY DISEASE, WHICH ALREADY IS MORE COMMON IN GOUT.
* - PODAGRA ( INFLAMMATION OF FIRST METATARSOPHALANGEAL JOINT ) IS ALSO SEEN IN PSEUDOGOUT, SARCOIDOSIS, GONOCOCCAL ARTHRITIS, PSORIATIC ARTHRITIS & REACTIVE ARTHRITIS.
* - ATTACKS OF GOUT MAY PRECIPITATE DUE TO INFECTION, ALCOHOL INTAKE(INCLUDING BEAR), DRUGS LIKE THIAZIDE DIURETICS, ANTICANCER DRUGS, CERTAIN FOODS, TRAUMA, HAEMORRHAGE.
* - GOUT PATIENTS MAY HAVE HIGHER INCIDENCE OF RENAL STONES.
Medical Care: There are 3 stages in the management of gout: (1) treating the acute attack, (2) providing prophylaxis to prevent acute flares, and (3) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of uric crystals.
" Management of acute gout: Options for treatment of acute gout include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine (a classic treatment but now rarely indicated). The choice is based primarily on the patient's other health problems, such as renal insufficiency and peptic ulcer disease.
o Nonsteroidal anti-inflammatory drugs
" NSAIDs are the drugs of choice in most patients without underlying health problems.
" Indomethacin is the traditional choice unless the patient is elderly, because of the potential for adverse CNS effects in this age group. However, most NSAIDs can be used. Select an agent with a quick onset of action, but do not use aspirin because it can alter uric acid levels and potentially prolong and intensify an acute attack. Cyclooxygenase-2 (COX-2) inhibitors have been used with success.
" Start with the highest dose for 2-3 days and taper down over approximately 2 weeks. Patients should be asymptomatic for at least 2 days before discontinuing the NSAID.
" Avoid NSAIDs in patients who have a history of peptic ulcer disease or GI bleeding, patients with renal insufficiency, patients with abnormal hepatic function, patients taking coumadin (selective COX-2 inhibitors can be used), and patients in the intensive care unit who are predisposed to gastritis.
o Corticosteroids
" Corticosteroids can be given to those patients who cannot use NSAIDs or colchicine. Some rheumatologists recommend corticosteroids over NSAIDs as the preferred choice for treatment of acute gout. Steroids can be given orally, intravenously, intramuscularly, intra-articularly, or indirectly via adrenocorticotropic hormone (ACTH).
" Prednisone can be given at a dose of approximately 40 mg for 1-3 days and then tapered over approximately 2 weeks. Tapering more rapidly can result in a rebound flare.
" Using parenteral corticosteroids confers no advantage unless the patient cannot take oral medications.
" Intra-articular corticosteroids are particularly useful in patients with a monoarticular flare to help reduce the systemic effect of oral steroids. Ensuring that the joint is not infected prior to injecting intra-articular corticosteroids is particularly important.
" ACTH at 40 IU IM can be given to induce corticosteroid production by the patient's own adrenal glands. Such a regimen does not depend on the patient to taper prednisone properly.
o Colchicine
" Colchicine is the classic medication for gout but is not the preferred medication for the treatment of acute gout. It is most effective during the first 12-24 hours of an attack, but its effectiveness declines with the duration of inflammation. Moreover, when used to treat an acute attack, colchicine causes adverse GI effects, particularly diarrhea and vomiting, in 80% of patients.
" To treat an acute attack colchicine is given orally at 0.5-0.6 mg every hour until the patient has relief, has adverse GI effects, or takes 6 mg (ten 0.6-mg tabs). The total dose and the frequency need to be reduced in patients with renal or hepatic insufficiency, and colchicine generally is not recommended in these situations.
" Patients may be able to abort an attack by taking a single colchicine tablet at the first twinge of an attack.
" Colchicine should not be used if the glomerular filtration rate (GFR) is less than 10 mL/min, and the dose should be decreased by at least half if the GFR is less than 50 mL/min.
" Colchicine also should be avoided in patients with hepatic dysfunction, biliary obstruction, or an inability to tolerate diarrhea.
" A clinical response to colchicine is not pathognomonic for gout and can be seen with pseudogout, sarcoid arthropathy, psoriatic arthritis, and calcific tendonitis.
" Colchicine also can be administered intravenously. While this route of therapy can quickly abort an attack of gout, it should be employed only in unusual circumstances because it is potentially toxic. Indeed, this therapy is banned in some countries due to a 2% fatality rate. IV colchicine should be used cautiously, if at all, in patients with renal insufficiency or hepatic dysfunction.
" When given intravenously, 1 mg of colchicine is diluted in 20 mL of isotonic sodium chloride solution without glucose and pushed over 10-20 minutes in a secure IV line. A maximum of 4 mg is given over 24 hours, and no further colchicine should be given for the next week.
" If the medication extravasates, it can cause tissue necrosis. Within the vessels, it also can cause thrombophlebitis.
" Granulocytopenia is a prime complication of IV colchicine. The WBC count should be measured before infusion.
" Other complications include disseminated intravascular coagulopathy, renal failure, hepatocellular toxicity, seizures, and shock.
" Prophylaxis to prevent acute flares
o Lowering uric acid with either allopurinol or probenecid can precipitate attacks of gout. When used prophylactically, colchicine can reduce such flares by 85%.
o The standard dose for prophylaxis is colchicine at 0.6 mg bid. In patients with renal insufficiency, this dose may need to be decreased to daily or every-other-day administration.
o Compared with the 80% risk of adverse GI effects in patients using colchicine for the treatment of acute gout, the prophylactic dose of colchicine induces adverse GI effects in only 4% of patients.
o Long-term use of colchicine can lead to a muscle weakness associated with elevated levels of creatine kinase due to a drug-induced neuromyopathy, particularly in patients with renal insufficiency.
o In patients who cannot take colchicine, NSAIDs can be used for prophylaxis, such as indomethacin at 25 mg bid.
o Prophylaxis with colchicine can be started during the acute attack.
" Lowering uric acid levels
o In many cases, patients who have a first attack of gout should undergo therapy with agents that lower uric acid, given the high risk for further inflammatory attacks and the potential for destructive tophaceous deposition in the bone and synovium, even without episodes of acute inflammation.
o Some rheumatologists advocate waiting for the second attack to begin therapy to lower uric acid levels because not all patients have a second attack and because some patients may need to be convinced they need life-long therapy. This decision is partly dependent on the baseline serum uric acid levels (a level >9 mg/dL denoting higher risk for recurrent gouty arthritis and tophi).
o In all cases, the risks and benefits need to be judged based on the individual patient. For instance, in an elderly patient with multiple medical problems and renal insufficiency, the risks of therapy to lower uric acid levels may outweigh the benefits.
o The goal of therapy is to lower serum uric acid levels to approximately 5-6 mg/dL.
o The risk of a second attack of gout after the first attack is 62% after 1 year, 78% after 2 years, and 93% after 10 years.
o Treating patients with colchicine alone may help prevent flares of inflammatory arthritis but does not prevent the accumulation of uric acid in the joints, which can lead to further joint destruction.
o While using agents that lower uric acid is important, they should not be started during an acute attack. This may lead to a more intense and prolonged attack. Typically, they should be started a few weeks after the attack has resolved and with the protection of colchicine to prevent another attack.
o If the patient develops a flare of gout when starting on agents that lower uric acid, do not discontinue the agent because this will only cause another flux in the uric acid level that may prolong and intensify the attack.
o Probenecid
" Some rheumatologists prefer probenecid whenever possible because it has fewer significant adverse effects than allopurinol. Probenecid can be used in the majority of middle-aged, otherwise healthy men with gout.
" Indications for the use of allopurinol instead of probenecid include renal insufficiency (GFR <50 mL/min), renal stones, use of aspirin (blocks the effect of probenecid), overproduction of uric acid, and unresponsiveness to probenecid.
" Drug interactions may occur with probenecid.
" Patients using probenecid need to drink 2 L of fluid daily at the inception of therapy to ensure adequate diuresis to decrease the risk of renal stones.
o Sulfinpyrazone: Sulfinpyrazone is an alternative uricosuric agent that has antiplatelet activity but is seldom used because of the added risk of bone marrow suppression.
o Allopurinol
" Allopurinol blocks xanthine oxidase and thus reduces the generation of uric acid. Therefore, it should be used in patients who are overproducers of uric acid and in patients at risk of tumor lysis syndrome to prevent renal toxicity during therapy for malignancies. It is the most effective agent to lower serum uric acid levels. However, alcohol can interfere with the effectiveness of allopurinol.
" Approximately 3-10% of patients taking allopurinol develop dyspepsia, headache, diarrhea, or pruritic maculopapular rash. More infrequently, patients can develop allopurinol hypersensitivity, which has a mortality rate of 20-30%. Features of allopurinol hypersensitivity include fever, toxic epidermal necrolysis, bone marrow suppression, eosinophilia, leukocytosis, renal failure, hepatic failure, and vasculitis. Corticosteroids often are used to treat allopurinol hypersensitivity. Allopurinol hypersensitivity is more likely to occur in patients with renal insufficiency, patients who are taking a diuretic, and patients begun on 300 mg of allopurinol.
" Allopurinol should be discontinued in patients who develop a rash. In patients with a history of drug eruptions due to allopurinol, both an oral (Fam, 2001) and IV (Walz-LeBlanc, 1991) desensitization regimen are available that can be considered.
" In most patients, start at 100 mg per day and adjust the dose monthly according to the uric acid level until the goal of a uric acid level of 5-6 mg/dL is achieved.
" Beware of drug interactions. For example, allopurinol prolongs the half-life of azathioprine and 6-mercaptopurine. It enhances the toxicity of cyclophosphamide. Patients taking concomitant ampicillin have an increased incidence of rash.
" Once the target level is achieved and maintained for 6 months, discontinue colchicine prophylaxis.
" Avoiding the use of medications that elevate uric acid in patients with gout is prudent. Thus, other agents are preferable to a thiazide diuretic to treat hypertension. However, if such a medication is needed, it can be used with appropriate adjustments of allopurinol or probenecid.
" Allopurinol can be used in combination with probenecid. However, note that allopurinol increases the half-life of probenecid, whereas probenecid increases the excretion of allopurinol.
o Other potential therapeutic options include the following:
" Nonrecombinant urate-oxidase (uricase) is used in Europe to prevent severe hyperuricemia induced by chemotherapy in malignant patients, as well as for selected patients with treatment-refractory gout. Recently, the Food and Drug Administration (FDA) approved recombinant Aspergillus flavus uricase for the prevention of tumor lysis syndrome. However, it is highly immunogenic and may cause anaphylaxis.
" Patients with allopurinol hypersensitivity can often tolerate oxypurinol, which is a metabolite of allopurinol.
" Benzbromarone is an effective uricosuric agent that may eventually become available. However, it can cause fulminant hepatotoxicity.
" Febuxostat, a nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with gout. It is orally administered and metabolized mainly in the liver. In contrast, allopurinol and its metabolites are excreted primarily by the kidney. Therefore, febuxostat can be administered in patents with renal insufficiency, with no dosage adjustment. Its efficacy and side-effect profile otherwise appears similar to that of allopurinol.
" The angiotensin receptor blocker losartan and the triglyceride-lowering agent micronized fenofibrate have moderately potent uricosuric effects. They should therefore be considered in patients with gout who also require treatment for hypertension and hypertriglyceridemia.
" Vitamin C, with its uricosuric effect, may reduce the serum concentration of uric acid.
Surgical Care:
" If diagnosed and treated early, patients should not need orthopedic surgery. In patients who are untreated or in those who are treated late in the course of their disease, orthopedic repair may be necessary.
" Tophi should not be surgically removed unless they are in a critical location or drain chronically.
" In patients undergoing arthroscopy, the presence of white lesions, sometimes on an erythematous base, should prompt consideration for gout.
Diet:
" Diet modifications can only improve the serum uric acid levels by 1 mg/dL and rarely are able to lower uric acid levels sufficiently to prevent further attacks and accumulation of uric acid.
" Patients should avoid alcohol because it elevates levels of uric acid and therefore can precipitate attacks of gout. Indeed, heavy drinkers are much more likely to have recurrent gout attacks, even with allopurinol therapy.
" Particularly because of the association of gout with atherosclerosis, the diagnosis of gout may be a good time to advise a low-cholesterol, low-fat diet if otherwise appropriate for the patient. While such a diet may help uric acid levels, such advice should be given primarily to help prevent atherosclerosis.
" Weight reduction in patients who are obese can improve hyperuricemia.
Activity: Patients should avoid using the inflamed joint during the acute attack. Otherwise, they should be active.