Treatment of Gouty Arthritis
|Substance/group||Proposed therapy||Adverse drug effects||Major
|Nonsteroidal antiinflammatory drugs (NSAIDs) PO||Maximum dose; 5 to 10 days or until symptoms resolve||Renal dysfunction||Renal failure||(A) Cochrane review: NSAID treatment option for acute gout flare [Rx]||Early start of treatment more important than the choice of NSAID|
|Corticosteroids PO||30 to 35 mg prednisolone PO for 5 days||Overproduction of stomach acid, Cushing’s syndrome, metabolism disorder, hypertension/hypotension||– Infection in particular
– Poorly managed diabetes mellitus or arterial hypertension
– Ulcerating wound(s)
|(A) RCT: Corticosteroids have no disadvantages versus NSAIDs [Rx]|
|Colchicine PO||Low-dose therapy:
2 × 0.5 mg initially, then single administration 0.5 mg after 1 hour
|Gastrointestinal effects in particular||Reduced creatinine clearance or liver failure; concomitant administration of CYP3A4 inhibitors, e.g. statins [Rx]||(A) RCT: Low-dose therapy has the same clinical effect as higher dose and fewer adverse effects [Rx]||If gout flare was no longer than 24 hours ago|
|Cortisone IA or IM||Overproduction of stomach acid, Cushing’s syndrome, metabolism disorder, hypertension/hypotension||(B) Cochrane review: no evidence to date of clinically significant superiority over oral corticosteroid therapy [Rx]||IM or IA corticosteroid injection possible in exceptional cases|
|Single administration (150 mg SC), repeat administration after no less than 12 weeks [Rx]||Infections (e.g. urinary tract infections, airway infections); local skin reactions at the site of injection||If active infections present||(B) Cochrane review: more effective than 40 mg triamcinolone IM [Rx]||If all 3 standard treatment options contrain‧dicated/not tolerated|
IA: Intra-articular; IM: Intramuscular; NSAID: Nonsteroidal anti-inflammatory drug; PO: Per os; SC: subcutaneous; RCT: a Randomized controlled trial
The immediate goals for treating a gout flare-up are to reduce intense pain, swelling, warmth, and redness. With proper treatment, gout pain and other symptoms can be under control within 24 hours and completely gone within a matter of days.
- Ice – A soft cool compress applied to the affected joint can help relieve discomfort.
- Avoid pressure – Avoid contact with anything. Anything that touches the affected joint may cause a sharp increase in pain.
- Rest – It is usually painful to use the affected joint, and resting it will help alleviate pain, swelling, and other symptoms.
- Elevation – Elevate the affected limb to help reduce swelling. If the foot is affected, sit down with the foot resting on a footstool or lie down with the foot propped up on a pillow.
- Patient education – As already emphasized above, patient education is key to gout management success, as shown by a preliminary study that explored the effect of a predominantly nurse-delivered education program. Following this program, 98 of 103 included patients had their uricemia at a target after one year of allopurinol treatment, in sharp contrast with what is usually observed [Rx]. Information should be given on the pathophysiology of the disease, its relationship with uricemia, its curable nature, uricemia targets to be reached, the life-long nature of urate-lowering treatment, the importance to treat flares early, the mechanisms of ULD-induced flares and ways to prevent them. Patient education takes time and must frequently be repeated, but it is a mandatory tool to achieve success in long-term gout management.
- Over-the-counter medication – Over-the-counter anti-inflammatory medications, such as ibuprofen and naproxen, can relieve pain, particularly if pills are taken as soon as the patient perceives the gout attack coming on. A doctor should be consulted regarding the adequate dosage. Aspirin should be avoided, since it can impair the kidneys’ ability to filter out uric acid, making gout symptoms worse.
- Prescription pain relievers – When over-the-counter pain relievers are not sufficient, prescription painkillers such as codeine, hydrocodone, and oxycodone may be prescribed for short-term relief of acute pain.
- Colchicine – A prescription drug called colchicine is very effective at stopping an acute gout attack. Evidence shows that gout pain, swelling, and inflammation decrease when colchicine is taken within the first 12 to 24 hours of an attack, along with a second, smaller dose an hour or two later. When taken within 12 h after flare onset, 1.8 mg (1.2 mg than 0.6 mg one hour later) of colchicine has been shown to be as effective as the traditional higher doses [Rx]. In clinical practice, this drug appears as much less efficient when given long after the flare onset. The EULAR and American College of Rheumatology (ACR) have restricted the use of colchicine to patients presenting within 12 and 24 h of flare onset respectively. Colchicine should be taken only as directed. Many people taking colchicine to experience gastrointestinal side effects, such as vomiting or diarrhea.
- Corticosteroids injections – A doctor may inject the inflamed joint with steroids to relieve the pain. This treatment is particularly useful for people with sensitivities to certain medications. Repeated corticosteroid injections, however, can have side effects. Up until recently, colchicine was the treatment of choice for acute gout. However, due to recent safety concerns, colchicine is now only recommended if NSAIDs or corticosteroids are inappropriate. High dose colchicine therapy is no longer recommended because of its toxicity.
- NSAIDS – NSAIDs (non-steroidal anti-inflammatory drugs) – These are generally the medicines of choice for most patients who do not have underlying health problems. Aspirin should be avoided as it can alter urate levels and worsen the attack. NSAIDs or COXIBs are used at the maximum authorized dose, with proton inhibitors when indicated. Their efficacy is largely accepted, even though no placebo-controlled trial has been performed. Early prescription allows reducing administered doses.
- Steroids – Oral prednisone, at a daily dose of 30 mg/d for 7 days has been shown to be effective [Rx] and is recommended by the ACR and EULAR panels as potential first-line therapy in the management of gout flares [Rx]. However, steroids can worsen hypertension and diabetes [Rx] and are, in our view, best indicated in patients contraindicated for NSAIDs or colchicine (i.e. CKD patients). Co-prescription of a small dose (0.5–1 mg/d) of colchicine, when not contraindicated, may avoid rare inflammation relapses after steroid cessation. Open studies also suggest that ACTH can relieve gouty inflammation [Rx].
- Intra-articular steroid injections – appear as very efficient and are recommended by both the ACR and the EULAR in the management of mono or pauciarticular flares, despite the lack of randomized clinical trials (RCT).
- IL-1 blockers – Open studies of the IL-1 receptor antagonist anakinra [Rx], [Rx] support its off-label use in patients resistant or contraindicated to NSAIDs, colchicine, and steroids. Canakinumab, a long-lasting antibody to IL-1 beta, has been approved by the European Medical Agency, following 2 RCT trials against intramuscular triamcinolone acetonide [Rx]. The EULAR recommends considering IL-1 blockers for the management of gout flares in patients with frequent flares contraindicated to NSAIDs, colchicine, and steroids (oral or injectable). Current infection is a contraindication [Rx].
|Substance/group||Proposed therapy||Adverse drug effects||Major contraindications||Recommendation grade||Comments|
|Xanthine oxidase inhibitor: allopurinol||Initially 50 to 100 mg/day; increase to max. 800 mg/day||Diarrhea, nausea, vomiting, increased liver enzymes, skin reactions (2%), hypersensitivity syndrome (0.1%) [Rx]||Known hypersensitivity to allopurinol||(A) Cochrane review: target serum uric acid levels achieved more frequently with allopurinol than with placebo [Rx]||Adjust dose in cases of known renal failure (table) Monitor liver and kidney enzyme levels|
|Xanthine oxidase inhibitor: febuxostat||Initially 80 mg/day, increase to 120 mg/day if necessary||Liver dysfunction, diarrhea, nausea, headache, skin rash||Ischemic heart disease <12 months or decompensated heart failure [Rx]||(A) Cochrane review: lowers uric acid levels more effectively than allopurinol [Rx]||If allopurinol not toler‧ated, in cases of renal failure, or if target uric acid level not achieved despite increased allopurinol dose (A)|
|Uricosuric agent: probenecid||Probenecid can be combined with allopurinol if allopurinol alone is insufficiently effective [Rx]||Irritation of gastrointestinal tract, skin reactions, anorexia||Urolithiasis, advanced renal failure (creatinine clearance <50 ml/min), or increased uric acid production (e.g. during chemotherapy)||(B) There are no placebo-controlled trials of uricosuric agents. RCT [Rx]: probenecid less effective than allopurinol||Take with sufficient fluids to prevent kidney stone formation|
|Selective inhibitor of URAT1 transporter: leisure||Authorized in combination with xanthine oxidase inhibitor for treatment-refractory cases since February 2016 [Rx]||A headache, influenza-like symptoms increased creatinine levels, gastroesophageal reflux||Severe renal failure, tumor lysis syndrome, Lesch–Nyhan syndrome||(B) RCT: lowers uric acid levels more effectively in combination with allopurinol [Rx]||Further studies required on cardiovascular safety according to the European Medicines Agency (EMA) [Rx]. Therefore not currently recommended by these authors for patients with cardiovascular events <12 months (c).|
|Uricosuric agent: benzbromarone||Not recommended by these authors due to liver toxicity [Rx] (C)|
|Uricase: pegloticase||Taken off the market in July 2016 [Rx]||Uric acid levels reduced due to the breakdown of uric acid into allantoin, which is eliminated in the urine. Adverse drug effects: infusion issues, anaphylaxis, antibody formation.|
RCT: Randomized controlled trial
Medicines to Reduce Uric Acid
Long-term management of gout focuses on lowering urate levels, aiming for levels under 0.36 mmol/L, or better still, under 0.30 mmol/L. These medicines can prevent attacks of gouty arthritis and prevent MSU crystals from being deposited in the tissues. Medicines that lower urate levels should not be started during an acute attack of gout; instead they should be started a few weeks after the attack has resolved.
- Allopurinol – Allopurinol is an effective uric-acid lowering therapy, but it has a number of side effects and interactions with other medicines. Dermatological side effects of allopurinol range from a mild morbilliform eruption (measles-like rash, which resolves when the drug is discontinued) to Stevens-Johnson syndrome / toxic epidermal necrolysis and drug hypersensitivity syndrome. Drug hypersensitivity syndrome is rare but potentially very severe. It usually occurs within the first 6 weeks of therapy but some cases have been reported up to 12 weeks after starting allopurinol.
- Febuxostat – Febuxostat is a new medication for gout that may be used to reduce urate levels in patients with poor kidney function or intolerant of allopurinol. Phase III clinical trials have reported febuxostat to be more effective than allopurinol at a dose of 300mg.
- Probenecid – Probenecid is an alternative uric acid lowering medicine with fewer significant side effects than allopurinol. It is important to drink plenty of fluids while on probenecid, to flush out the uric acid and prevent crystals forming within the kidneys or urinary tract. The starting dose of probenecid is usually 250 mg twice daily but it may need to be increased to up to 1 g twice daily.
- Benzbromarone – Benzbromarone is a new medication for gout that may be used to reduce urate levels where allopurinol and/or probenecid are contraindicated, not tolerated, or are ineffective. A liver function must be monitored on benzbromarone, as it is reported to cause hepatic toxicity. ACR considers febuxostat as a first line ULD [Rx], whereas for EULAR, the drug is indicated in patients intolerant or refractory to allopurinol. Dose titration is recommended to reduce ULD-induced flares, even though there is no evidence that this improves febuxostat tolerance [Rx].
- Uricosurics – Uricosurics lower uricemia by increasing uric acid output in the urine. Therefore they expose the patients to the risk of uric acid stone, which is worse at the onset of treatment. When uricemia has decreased, urticaria and the risk become lower, as urticaria also decreases. They should not be administered as a monotherapy in patients with a history of uric acid stone or hyperuricuria and should be taken with abundant water intake; the urinary pH should also be checked and kept above 6 to decrease the concentration of uric acid in urine, which governs the risk of lithiasis. Except for lesinurad, uricosurics can be used alone; they are now most often used in combination with xanthine oxidase inhibitors when these fail to obtain the uricemia targets.
- Probenecid – has been the first commercialized ULD [Rx] and was at first a very popular drug. When allopurinol became available, probenecid was much less used because it had to be given in divided doses and required high fluid intakes and adjustment of the urine pH. In addition, probenecid, which was first developed to decrease the renal excretion of penicillin, could interfere with the excretion of other organic acid drugs and gastrointestinal or cutaneous intolerance were fairly common. It has been recently confirmed to be a decent ULD, including those patients with moderate kidney involvement and remains one of the therapeutic options in patients intolerant or refractory to allopurinol [Rx]. The initial dose is 250 mg twice daily, which can be weekly increased up to 1 g twice daily. Larger doses expose to major central nervous system toxicity.
- Sulfinpyrazone – is not universally available. This uricosuric drug is usually given twice daily at the total daily doses of 200–400 mg, progressively attained. Side effects include gastrointestinal intolerance, skin rashes, platelet aggregation impairment, and rare bone marrow toxicity.
- Benzbromarone – is a powerful uricosuric drug, which is used once a day at a dose of 100–200 mg/d. [Rx]. Following reports of severe liver toxicity, the drug has been retrieved from Europe, where it can still be prescribed on a named patient basis, but is still largely used in Asia. The uricosuric property is largely retained in renal failure patients [Rx].
- Lesinurad – is selective URAT1 inhibitor which has been recently approved at the dose of 200 mg/d in the USA and Europe, as an add-on therapy to xanthine oxidase inhibitors when these failed to lower uricemia down to the suitable target [Rx]. Serum creatinine elevations have been observed, which although most often transient, require renal function monitoring.
- Fenofibrate – atorvastatin and losartan are non-licensed uricosurics which can be used to treat gout comorbidities or in association with xanthine oxidase inhibitors [Rx].
- Urate oxidases – Rasburicase is a short-life IV uricase, which is approved for the management of tumor lysis syndrome. Its non-licensed use has been reported in tophaceous gout [Rx]. Pegloticase is a PEGylated uricase which has been approved, in the USA and Europe, for the management of severe gout, refractory to oral ULDs and is commercially available in the USA. The drug is administered by IV infusions of 8 mg every 2 weeks and has been shown to be very effective [Rx]. Antibodies develop at high titers in about half of the patients, leading to loss of uricemia response and to an increased risk of serious infusion reactions. It is therefore recommended to measure uricemia in the 24 h preceding every planned reinfusion and to stop the drug if uricemia is not decreased. No other ULD should be prescribed concomitantly to keep this warning signal.
- Canakinumab –Canakinumab, a monoclonal antibody, neutralizes IL-1β to suppress inflammation. Canakinumab is a US Food and Drug Administration (FDA)-approved for cryopyrin-associated periodic fever syndromes, Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and systemic idiopathic juvenile arthritis. Phase 3 trials of canakinumab by Schlesinger et al. demonstrated its efficacy in acute gout and for prophylaxis during a-lowering therapy (ULT) Rx, . The FDA declined to approve canakinumab for acute gout therapy, citing concerns about the use of a long-acting immunosuppressant for an ostensibly short-term condition. In contrast, the European Medicines Agency approved canakinumab for the same indication.
- Anakinra –Anakinra is a recombinant human IL-1β receptor antagonist that is FDA-approved for rheumatoid arthritis and neonatal-onset multisystem inflammatory disease. To date, randomized controlled trials assessing anakinra’s efficacy in the management of gout are lacking Rx, but case series and uncontrolled trials support its efficacy Rx. In practice, anakinra has been the preferred off-label anti-IL-1β strategy among experienced “goutologists”, based on its relatively short half-life and lower cost compared with canakinumab.
- Pegloticase – Pegloticase is a recombinant, pegylated uricase that degrades uric acid Rx. Approved by the FDA in 2010, pegloticase is indicated for the treatment of hyperuricemia in adults with chronic or tophaceous gout refractory to conventional ULT. Pegloticase is administered intravenously every 2 weeks. Studies confirm the ability of pegloticase to rapidly and dramatically lower sUA and to promote the often-dramatic resolution of tophi Rx.
- Lesinurad – Lesinurad is a selective, highly potent uric acid reabsorption inhibitor. Lesinurad reduces sUA by inhibiting both the sUA-anion exchanger transporter 1 (URAT1) and the organic anion transporter 4 (OAT4), which are involved in the reabsorption of sUA across the renal proximal tubule Rx. In contrast to the older uricosuric probenecid, lesinurad is more potent and remains effective even in moderate renal insufficiency. In 2015, lesinurad gained FDA approval as a second-line treatment for gout patients who have failed to meet target sUA despite treatment with a traditional XOI ULT (that is, allopurinol or febuxostat).
- Arhalofenate – Arhalofenate is a pipeline drug with a dual mechanism of action. Patients initiating ULT are routinely prescribed concurrent anti-inflammatory prophylaxis to reduce the risk of gout attacks precipitated by the sUA-lowering process itself. Historically, all gout medications have been either anti-inflammatory or sUA-lowering. In contrast, arhalofenate, a peroxisome proliferator-activated receptor gamma (PPAR-γ) partial agonist, demonstrates dual ULT and anti-inflammatory effects. Specifically, arhalofenate inhibits expression of IL-1β while inhibiting renal reabsorption of uric acid at the URAT1, OAT4, and OAT10 transporters Rx.
- Allgemeinmedizin – recommends that uric acid levels should be maintained below 6.5 mg . The EULAR advises uric acid levels of less than 6 mg/dL, and even as low as <5 mg/dL in patients with severe gout (B). Lifelong therapy is recommended. A prospective cohort study has shown that withdrawal can be attempted after uric acid levels have successfully been maintained at a low level for more than 5 years [Rx] (B).
- Complementary and Alternative Therapies – A combination of therapies can be very effective at reducing both the length and frequency of attacks. When choosing complementary and alternative therapies (CAM) for gout treatment, it is best to work with a knowledgeable provider. Herbs and supplements that may be beneficial for some people, may be harmful to others. If you are pregnant or thinking about becoming pregnant, do not use any CAM therapies unless directed to do so by your physician.
Nutrition and Supplements
These nutritional tips may help reduce symptoms:
- Eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may test for food sensitivities.
- Eat antioxidant-rich foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers). Some nutrition-minded doctors promote a low fructose diet to treat gout. Another theory states that one-half pound of cherries per day (fresh or frozen) for 2 weeks lowers uric acid and prevents attacks. Cherry juice (8 to 16 oz. per day) is also helpful.
- Eat more high fiber foods, including oats, root vegetables (such as potatoes and yams), and psyllium seed.
- Avoid refined foods, such as white bread, pasta, and sugar.
- Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy) or beans for protein.
- Cut down on foods containing oxalates, such as spinach, rhubarb, beets, nuts, chocolate, black tea, wheat bran, strawberries, and beans.
- Include foods rich in magnesium and low in calcium, such as barley, bran, corn, rye, oats, soy, brown rice, avocado, banana, and potato.
- Restrict purines in your diet. Foods with high purine content include beef, goose, organ meats, sweetbreads, mussels, anchovies, herring, mackerel, and yeast. Foods with a moderate amount of purines include meats, poultry, fish, and shellfish not listed above. Spinach, asparagus, beans, lentils, mushrooms, and dried peas also contain moderate amounts of purines.
- Use healthy cooking oils, such as olive oil or coconut oil.
- Reduce or eliminate trans fatty acids, found in commercially baked goods, such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
- Avoid alcohol and tobacco.
- Drink 6 to 8 glasses of filtered water daily to help flush uric acid from the body. Dehydration often triggers a gout attack.
- Exercise at least 30 minutes daily, 5 days a week.
- Avoid sugar-sweetened soft drinks. Diet soft drinks have not been associated with the risk of gout.
- Preliminary studies suggest moderate coffee consumption may help alleviate symptoms.
You may address nutritional deficiencies with the following supplements:
- A daily multivitamin, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals, such as magnesium, calcium, zinc, and selenium.
- Omega-3 fatty acids, such as fish oil, to help reduce inflammation and promote general health. Cold-water fish, such as salmon or halibut, are good sources. Talk to your provider before taking omega-3 supplements if you are taking blood-thinning medications, such as aspirin or warfarin (Coumadin).
- Inositol hexophosphonate (IP-6). Check with your alternative health care provider for proper dosing.
Caution – May increase the blood-thinning effects of anti-clotting medications, such as warfarin and others. IP-6 may lower iron and calcium in the body.
- N-acetyl cysteine, for antioxidant effects.
- Vitamin C, as an antioxidant. In one study, higher vitamin C intake was independently associated with a lower risk of gout.
- Acidophilus (Lactobacillus acidophilus). When needed to maintain gastrointestinal and immune health. Some acidophilus products may need refrigeration. Although acidophilus is good for the immune system, people with severely compromised immune systems should check with their physicians before starting a probiotic supplement. Check the labels carefully.
- Methylsulfonylmethane (MSM), to help reduce inflammation.
Avoid taking extra niacin and vitamin A. Both may play a role in gout.
Herbs are generally a safe way to strengthen and tone the body’s systems. As with any therapy, you should work with your provider before starting any treatment. You may use herbs as dried extracts (capsules, powders, or teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, make teas with 1 tsp. herb per cup of hot water. Steep covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes for roots. Drink 2 to 4 cups per day. You may use tinctures alone, or in combination, as noted.
- Cranberry (Vaccinium macrocarpon). For kidney health. You may also take 8 to 16 ounces of unsweetened cranberry juice daily.
- Green tea (Camellia Sinensis). For antioxidant and immune effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
- Devil’s claw (Harpagophytum procumbens). For pain and inflammation. Devil’s claw may increase the blood-thinning effect of certain medications, such as aspirin and warfarin (Coumadin). Devil’s claw should never be used during pregnancy, or while breastfeeding. It can potentially affect blood sugar levels, as well as blood pressure, and can interact with many medications.
- Cat’s claw (Uncaria tomentosa) standardized extract. For inflammation, immune, and antibacterial/antifungal activity. Cat’s claw may worsen certain conditions, such as leukemia or some autoimmune disorders. Cat’s claw may also interact with many different medications. Talk to your doctor.
- Bromelain (Ananas comosus). For pain and inflammation. Bromelain can increase the blood-thinning effect of certain medications, such as aspirin and warfarin (Coumadin).
- Turmeric (Curcuma longa). For inflammation. Tumeric may increase the blood-thinning effect of certain medications, such as aspirin and warfarin (Coumadin).
Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of gout symptoms (such as pain and inflammation) based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account your constitutional type, includes your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for you individually.
Some of the most common remedies used for gout are listed below. A common dose is 3 to 5 pellets of a 12X – 30C remedy every 1 to 4 hours until your symptoms improve.
- Aconite – For the sudden onset of burning pain, anxiety, restlessness, and attacks that come after a shock or injury. Also, take if your joints are swollen and painful.
- Belladonna – For intense pain that may be throbbing, if motion worsens pain and pressure improves it, or if the joint is very hot.
- Berberis vulgaris – For spasms of pain in joints or twinges made worse by walking. There may be back pain and a tendency to develop kidney stones.
- Bryonia –For pain that worsens with motion, or if the pain is better with pressure and with heat.
- Colchicum –For pains made worse by motion and weather changes, especially if there is any nausea associated with the attacks.
- Ledum -When joints become mottled, purple, and swollen, or if the pain is much better with cold applications and is worse when overheated.
- Rhus Toxicodendron – For stiff, swollen joints that are hot and painful, or if the pain is worse with cold applications and better with heat.