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Tuesday, July 27, 2021
Gout And Pseudogout Treatment & Management
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A published in vitro human liver microsome study showed that about 16% of colchicine is metabolized to 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) by CYP3A4. Glucuronidation is also believed to be a metabolic pathway for colchicine. Advise the patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine.
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It was unclear from these studies if the reported adverse events were directly attributed to the colchicine use. A total of 2325 studies of colchicine use were identified, as summarised in a PRISMA flowchart of the literature search , and a final total of 49 studies were eligible for data extraction . Twenty of these 49 studies, which were mostly case series or case reports, described the efficacy and/or safety outcomes of colchicine use stratified by renal function, as summarised in Tables2 and 3, respectively . The remaining 29 studies reported efficacy and/or safety outcomes of colchicine use without renal function stratification, as summarised in Supplementary Table2 and Supplementary Table3, respectively .
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After six weeks, all the groups showed lower levels of uric acid. The studies concluded that lemons and lemon juice might be a useful remedy to help treat gout along with medications and other dietary changes. Lemon juice may also help prevent gout in people with high uric acid levels.
These medications decrease the total amount of uric acid in the body and lower the serum uric acid level. For most patients, the goal of uric-acid-lowering medication is to achieve a serum uric acid level of less than 6 mg/dl. These medications also are effective treatments to decrease the size of tophi, with the ultimate goal of eradicating them. Uric-acid-lowering medications include allopurinol , febuxostat , probenecid, and pegloticase .
Clinical Pearls
Rheumatologists often adjust allopurinol doses higher than 300mg when needed to reach uric acid goal, although the literature on higher doses of allopurinol is limited. If an attack seems to be coming on in the lower extremity, patients are well-advised to try to get off their feet, since impact seems to worsen gout attacks. Clues to an attack of gout coming on include local swelling, heat, redness, and tenderness in a joint, especially in the foot, ankle, or knee. Some patients have fever and chills as the first warning that an attack of gout is coming on. Corticosteroids, such as prednisone and methylprednisolone (Medrol®), are anti-inflammatory agents that are quite effective against gout attacks. Anti-inflammatory steroids are very different in action and side-effects as compared to male hormone steroids.
A daily subcutaneous injection of anakinra was compared with oral treatments administered according to the standard of care, using optimal dosages as recommended in gout guidelines. As far as we know, this is the first double-blind, randomized controlled trial to evaluate the use of anakinra in an acute gouty arthritis population. Pegloticase is appropriate for patients with tophaceous gout with persistent gout attacks or damaging arthropathy who have failed or are intolerant of conventional therapy . Presumably, many such patients will now be eligible for and respond to febuxostat, but others will not and may receive pegloticase.
Prophylaxis Against Acute Attacks
Cardiovascular disease risk has been shown to increase with the use of COX-2 inhibitors. Current FDA labeling suggests limiting NSAID and COX-2 inhibitor use in patients with a history of myocardial infarction , congestive heart failure, or stroke. Given the potential impact on cardiovascular risk factors, including hypertension, T2DM, and hyperlipidemia, glucocorticoids may not be ideal for patients with known CVD or those at high risk. Hypertension is one of the most common comorbidities among patients with gout.
The remaining 18 studies reported efficacy and/or safety outcomes of IL-1 inhibitor use without renal function stratification, as summarised in Supplementary Table2 and Supplementary Table3 respectively . Overall, there were 17 studies of anakinra use, 7 studies of canakinumab use, and 2 studies of rilonacept use. For the safety outcome, all studies reported varying level of transient change in renal function during colchicine use as well as after drug cessation. Fifteen studies reported colchicine-induced neuromyopathy and rhabdomyolysis . Nine studies reported colchicine toxicity secondary to drug-drug interaction with statin, cyclosporin, clarithromycin, and hepatitis C treatments (i.e. sofosbuvir/ledipasvir) .
In many cases, lowering uric acid levels to less than 5 mg/dL is necessary to improve the signs and symptoms of gout. ACR guidelines recommend that once palpable tophi and all acute and chronic gout symptoms have resolved, urate-lowering therapy should be continued indefinitely, if it is well-tolerated and not burdensome. Gout, also known as acute gouty arthritis, is a chronic, inflammatory form of arthritis that is increasing in prevalence. It has been reported to affect 3 to 6 million adults in the United States. The first gout attack (also referred to as a “flare”) usually occurs in men between the ages of 40 and 60 years, and in women after the age of 60. A single joint is usually involved; the most commonly affected joint is the big toe.
Reduce dose of pravastatin, atorvastatin, and simvastatin when prescribed concomitantly. Reduce dose and monitor closely when prescribed in patients with hepatic impairment or mild-moderate CKD. Consider initiating urate-lowering therapy in select patients (see “Indications” in “Urate-lowering therapy” for details). There is a lack of consensus regarding strict diagnostic criteria for gout in clinical settings.
Urate
No new onset of attacks has developed for more than 18 months, and our patient remains free of corticosteroids and using benzbromarone twice daily. Patients are important partners in long-term gout management, experts said. They need to understand the difference between an acute attack and treatment of the underlying problem.
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Gout remedies: Ice or heat
For some people, holding an ice pack or a bag of frozen peas on the painful joint for 15-20 minutes may relieve pain. “But for [others], it makes pain worse,” Wei says. In that case, try a moist heating pad, which might keep painful crystals from forming, he suggests.
"In contrast to glucocorticoids and/or NSAIDs, anakinra has not been reported to exacerbate diabetes, or promote hypertension, renal failure, sodium retention, gastric ulcerogenesis, or myocardial infarction," they noted. In addition, colchicine requires careful dosing in certain patients, such as those with kidney disease. The interleukin -1 receptor antagonist anakinra was not superior to triamcinolone for relieving gout flares, but had similar effects for pain reduction as the glucocorticoid, a randomized phase II study found.
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Reviewer specialties include internal medicine, gastroenterology, oncology, orthopedic surgery and psychiatry. You have several attacks during the same year or your attacks are quite severe. Pain is often severe, described as throbbing, crushing, or excruciating. You are encouraged to report negative side effects of prescription drugs to the FDA.
Differences Between The American College Of Physicians Acp And Rheumatology Guidelines For Gout Management Table
Purines are also found in certain foods, including red meat and organ meats, such as liver. Purine-rich seafood includes anchovies, sardines, mussels, scallops, trout and tuna. Alcoholic beverages, especially beer, and drinks sweetened with fruit sugar promote higher levels of uric acid.
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This uricosuric agent is usually prescribed once daily because its metabolites have a half-life of 17–20 h . However, the peak action of this medication occurs within 4 hours following intake. Patients with gout should avoid excess ingestion of alcoholic drinks, particularly beer, because alcohol use elevates uric acid levels and thus can precipitate attacks of gout. Indeed, heavy drinkers are much more likely to have recurrent gout attacks, even with allopurinol therapy. Moderate wine intake is not associated with increased development of incident gout, but excesses of any form of alcohol in gout patients are associated with acute gout flares.
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