For an expanded article on the subject of gout, with extensive diagrams and radiographic images, read Dr. Fields' piece entitled Gout: Risk Factors, Diagnosis, and Treatment.
Definition of Gout
Gout is a form of arthritis caused by needle-like crystals of uric acid in the joints. It leads to sudden, severe attacks of pain and inflammation in joints. Gout usually affects only one joint at a time, most commonly the joint at the base of the big toe. But other joints - especially the ankles, hands, wrists, and elbows - may be affected.
Gout can occur alone, in which case it is called primary gout. It is called secondary gout when the problem occurs in conjunction with other diseases (such as psoriasis or lymphoma) or in association with excessive alcohol consumption.
Pathogenesis: Origins in Disordered Metabolism Purines
Pathogenesis refers to the origin and development of a disease. Gout is caused by disordered metabolism of purines. You largely get purines from food, and they are essential to the working of the body. Excess purines are normally eliminated in the urine. But sometimes an excess can lead to high levels of urate - a breakdown product of purines - in the blood, a condition called hyperuricemia. This can lead to the deposition of needle-like urate crystals in joints. Think of how small amounts of salt remain dissolved in water but, if too much salt is in the water, it break out into crystals; that same type of thing happens when too much uric acid is in the body, leading to crystal formation in the joints.
In most cases, high urate levels arise because the kidneys don't eliminate enough through the urine. However, high urate levels also can arise from its over-production. It is also possible that a combination of both processes may be at work. While these mechanisms can be inherited, they can also be affected by other diseases, medications, and alcohol.
Gout is inherited in most cases and affects mostly men (90%). It most commonly occurs between the ages of 40 and 60 in men and after menopause in women. It also occurs more frequently in those who are obese, and those who have hypertension, high cholesterol, and diabetes.
Other factors that may precipitate the development of gout are:
- chronic kidney disease, which impairs the kidney's ability to dispose of excess urate properly;
- lead poisoning, which also reduces the kidneys ability to clear urate;
- use of certain medications that may affect kidney function, including some types of diuretics (water pills), daily aspirin therapy, and cyclosporine;
- alcohol abuse;
- any type of stress to body, including sudden weight loss or gain, recent surgery, or infections.
Clinical Presentation: Your Symptoms, Your Age, Your Family History
The types of symptoms you have, your medical history, your age, and family history define the clinical presentation that your doctor observes.A. Acute gout
In about 70% of acute gout attacks, one joint becomes suddenly affected with excruciating pain, exquisite tenderness, and the three key signs of inflammation - heat, redness, and swelling. This most often begins at night and may last hours and may be accompanied by chills and a low fever. If untreated, the attack usually peaks after 24 to 48 hours and then gradually subsides within 7 to 10 days. Most people get acute attacks again, usually within 2 years; 62% have a second attack within a year - and 90% within 10 years. But, clearly 10% never experience an attack again. However, the greater the number of such acute attacks, the more likely you are to get further attacks.
The metatarso-phalangeal (MTP) joints - those where the arch of the foot meets the toes - are most likely to be hit, especially the joint at the base of the big toe. The ankles, hands, wrists, or elbows also may be affected. It is extremely rare for gout to affect the shoulders or hips.B. Chronic Gout
After multiple gouty attacks, some permanent changes may occur in the joint, including joint damage and tophi (the plural of tophus). A tophus is a local deposit of uric acid that, externally, looks like a chalk-colored nodule. Such tophi indicate that you need to be treated with one of the long-term uric-acid lowering drugs.
In addition, long term elevated uric acid in the urine can lead to the development of kidney stones.
Laboratory Findings: Testing an Inflamed Joint
Your doctor will likely do blood and urine tests to check for high levels of urate. To confirm the diagnosis, a needle can be inserted into the joint to withdraw some fluid. Examination of this fluid under the microscope will reveal urate crystals in the great majority of cases. It is easier for the physician to get fluid from a joint when it is inflamed and swollen, but crystals can be found even in joints which are not apparently inflamed at the moment.
You may be asked to collect your urine for 24 hours and bring it in for laboratory evaluation. This helps in deciding whether you are making too much uric acid - and therefore have a lot in the urine - or whether you make a normal amounts but just can't put enough out in the urine. If you have high uric acid in the urine - and therefore are producing too much - you are at risk for kidney stones in addition to gout. People on a standard diet who excrete more than 800 mg. per day of uric acid are over-excreting it and are most likely to benefit from allopurinol. This can help prevent kidney stones as well as prevent gout attacks.
Differential Diagnosis: Finding the Source of Your Joint Pain
Many different diseases cause joint pain. Gout that doesn't follow the classical pattern might even look like osteoarthritis or rheumatoid arthritis at its outset; people who already have these types of arthritis might also develop gout. Differential diagnosis is the process by which the physician figures out which disease is causing your problems. This is important because other types of arthritis are treated with very different drugs from those used to treat gout - and other types have a very different prognosis.
Finding urate crystals in the joint or in a tophus makes the diagnosis. But if urate crystals cannot be found, your doctor may make the diagnosis if six of the 12 following criteria are present:
- more than one discrete arthritis attack;
- maximal inflammation within 24 hours;
- an episode of arthritis in just one joint;
- redness over the joint;
- swollen or painful first MTP joint;
- inflammation of an MTP joint on just one side of the body (unilateral);
- inflammation of a tarsal (ankle) joint on just one side of the body;
- possible tophus;
- asymmetric swelling in a joint on X-ray;
- X-ray showing joint cysts without the erosions characteristic of rheumatoid arthritis;
- a culture from an inflamed joint that does not reveal any bacteria.
In particular, it is important to differentiate true gout from pseudogout; while the initial symptoms may be similar, treatment is very different. The key way to differentiate the two is by examination of the joint fluid. While gout is caused by uric acid crystals, pseudogout is the result of crystals formed from calcium pyrophosphate dihydrate (CPPD). Another name for pseudogout is calcium pyrophosphate deposition disease.
Initial Treatment for Gout, a Highly Treatable Type of Arthritis
The good news is that gout is one of the most treatable types of arthritis. Effective therapies are available and the outlook is generally quite good. The therapy your physician prescribes will depend on whether you are in the midst of an acute attack, are in between acute attacks, or have developed chronic gout, with or without tophi.A. Medications
It has been suggested by Dr. Robert L. Wortmann that crystals of uric acid be thought of as if they were matches (See annotated references at the end of this article). Left untreated, the matches can inflame, causing a gout attack.
One group of drugs can "put out the fire" - and treat an attack of gout - but do nothing to lower the uric acid level or to prevent a future attack. This group includes non-steroidal, anti-inflammatory agents, local or systemic corticosteroids, and high doses of colchicine.
A second group of drugs can "make the matches damp" - a way of saying that they reduce the likelihood of the crystals causing inflammation. The crystals (or "matches") are still there, just less likely to be "lit." This involves the use of low doses of colchicine on an ongoing basis.
A third group of drugs "removes the matches from the body" - or lowers the amount of uric acid in the body. This includes drugs like allopurinol and probenecid. These drugs can prevent future attacks by lowering the level of urate crystal "matches" to levels where attacks ("flames") do not occur.
B. Lifestyle Management
- Non-steroidal Anti-Inflammatory Drugs (NSAIDs) have long been the mainstay of treatment for putting out the fire of acute gout. They decrease the swelling and the inflammatory process within the joint. This group includes: indomethacin (brand named Indocin), sulindac (Clinoril) and naproxen (Naprosyn). If you have a history of gastrointestinal problems when taking NSAIDs, or are at high risk for such problems, your physician may prescribe a special class of NSAIDs called COX-2 inhibitors, which are less likely to cause such difficulty. This group includes: celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra).
- Corticosteroids, like prednisone, can be helpful in reducing inflammation during a gout attack - dousing the flames. Your physician may prescribe systemic corticosteroids (taken by pill) or may use a needle to remove fluid from the inflamed joint and then inject the corticosteroid (such as methylprednisolone) locally into the joint. Such local injections are extremely effective in treating acute gout, especially when only one joint is involved. Oral corticosteroids may be recommended when multiple joints are involved and NSAIDs don't quell the inflammation quickly - or if you can't take NSAIDs.
- Colchicine inhibits factors contributing to gouty inflammation in the joint. It is used in two ways:
- High doses of oral colchicine can relieve the pain and inflammation of acute gout attack. This is not commonly used now because such high doses often cause diarrhea at the same time or even before the benefit comes. Colchicine can also be given intravenously, but this is also given rather rarely now, due to possible side-effects. One reason why colchicine could still be used for an attack of gout is when the diagnosis is in question because colchicine quells the flames of gout so dramatically - but usually does not help most other forms of arthritis. So if colchicine works, that helps confirm the diagnosis. In occasional cases, the types of medical problems a patient has (in addition to the gout) make oral or intravenous colchicine their safest option.
Although we have used colchicine for many years, it was only officially approved by the FDA in July of 2009. Included in the approval was a recommended dosing of allopurinol for acute gout that is lower than many rheumatologists have been using. This dosing regimen was based on a study by Terkeltaub et al, which showed that giving 2 colchicine tabs (total of 1.2mg) followed by 0.6mg an hour later gave as good results at 24 hours as the "old" regimen of one 0.6mg tab every hour until improvement or diarrhea (whichever came first). This new regimen will hopefully reduce the GI morbidity commonly seen with colchicine treatment for acute gout, with equal effectiveness.
- Low doses of colchicine may be prescribed for long-term use to help lower the risk of future attacks, and it has been used this way for many years. It can "make the matches damp," decreasing the risk of subsequent attacks. If this therapy is prescribed for you, take the medicine regularly as directed, even if you feel well. If you miss a dose, take it as soon as possible, but if it is almost time for your next dose, skip the missed dose. If you have a gout attack, do not take extra colchicine; rather, call your physician, who may prescribe NSAIDs or other medications for immediate treatment.
- Potential bone marrow toxicity limits the use of intravenous colchicine for acute gout. However, it may be prescribed for patients who have contraindications for both NSAIDs and corticosteroids.
- Uricosurics, like Probenecid (brand named Benemid and SK-Probenecid) and Sulfinpyrazone, are used to prevent gout attacks in patients who are found not to be at risk of kidney stones. (This will require collecting the urine for 24 hours and testing for uric acid). Because of their relative safety, uricosuric drugs are good choices for patients with recurrent gouty attacks despite colchicine prophylaxis in patients who have a creatinine clearance greater than 80 mL/m (meaning essentially normal kidney function). Probenecid prevents reabsorption of uric acid by the kidney and thus leads to more excretion of uric acid. Probenecid also retards the excretion of penicillin in the urine, so you might need lower doses if you were prescribed penicillin. Sulfinpyrazone, another drug that increases the excretion of uric acid, seems to cause more side effects than probenecid. If you are taking one of these drugs, you must drink sufficient water to reduce the risk of kidney stones; drink at least 4 to 5 glasses of water daily.
A new uricosuric agent, presently known only as RDEA 594, is currently under investigation. This agent can be used once a day, rather than the twice-daily probenecid, and has other features that might make it easier to use than probenecid.
- Xanthine oxidase inhibitors include allopurinol and febuxostat (trade name Uloric®). These agents are prescribed in chronic gout to lower serum uric acid levels to prevent future gout attacks. They do this by inhibiting xanthine oxidase activity, which decreased the body's production of uric acid. However, they will not relieve an attack that has already started, and may actually worsen an attack that is already in progress. Thus, the time for allopurinol or febuxostat is after a gouty flare has calmed down; it should not be started for two to three weeks after symptoms have resolved. Allopurinol is called for when you have had more than one attack of gout in a year, when you have hyperuricemia with kidney stones associated with your gout, when uricosurics (see above) have failed to maintain appropriate serum urate levels, when you are allergic or intolerant of uricosuric agents, when you have tophaceous gout, or as prophylaxis against kidney damage from uric acid crystals in patients on cancer chemotherapy.
Because its action causes a reduction in both blood and urine levels of uric acid, allopurinol is used in the treatment of gout when the patient has had kidney stones related to uric acid, or when tophi are present. Febuxostat, working in a similar way to allopurinol, is approved by the FDA to treat patients with hyperuricema and gout. Only 3% of febuxostat is removed from the body by the kidney, while 90% of allopurinol is removed by the kidney. This is a potential advantage of febuxostat in patients who have mild to moderate abnormality of kidney function (which is fairly common in gout).
If allopurinol or febuxostat is prescribed for you, take it regularly, even if you are taking another medicine for attacks.
- Uricase: For patients where the above long-term uric acid lowering agents don't help or aren't tolerated, in late 2010 the FDA approved the intravenous drug pegloticase (Krystexxa®). This agent is very effective in lowering uric acid and shrinking tophi. It is reserved for patients not appropriate for other agents because pegloticase needs to be given intravenously and can cause reactions during the infusion, including drops in blood pressure. Infusion Units are well-aware of how to manage such reactions, but because these occur it is required that patients for pegloticase therapy be carefully selected.
- Medications under study for gout: as mentioned under "Uricosurics" above, a new agent that works by increasing the excretion of uric acid is under study. This agent, RDEA594, has shown some early promise that it may be easier and possibly safer to use than probenecid, the agent currently used in the U.S. to increase uric acid excretion.
- Diet can play an important role in reducing your risk of gout attacks. The key is to limit your intake of purines. Unfortunately, in patients with very high levels of uric acid, watching your diet is helpful but often not sufficient to prevent attacks - although it may decrease them. (See recommended diet books in Annotated References for recipes.)
- Avoid foods with very high purine content such as organ meats (liver, kidney, hearts, sweetbreads [thymus and pancreas]), also known as offal, anchovies, salmon, sardines, meat extracts, and meat gravies.
- Red meat and shellfish should also be reduced in the diet.
- Recent data suggests that vegetables are not a major issue in causing the onset of a gout attack.
- Low-fat dairy products have been shown to have a degree of preventive effect in gout onset.
- Alcohol of any kind can increase the risk of gout, but beer and ale are especially problematic. Patients with gout should try to eliminate beer from their diet if at all possible.
- Drink fluids (At least 4-5 cups a day) to prevent kidney stones and to help eliminate uric acid.
- Exercise: Obesity is associated with gout, but not proven to cause gout, although often obesity is associated with eating or drinking the kinds of things that cause gout. Patients with gout should exercise regularly in view of the many known benefits. However, relatively mild injuries can set off gout attacks, especially in the feet. It is important to remember that gout attacks can resolve very quickly (within hours) if treatment is started very early after onset. If you feel an attack coming on after exercise, or at any other time, early treatment is often advisable. Work out a plan with your physician as to what type of pills you should carry around with you, especially on vacation, to use if you develop a gout attack.
C. Doctor - Patient Communication
Because of the complexity of the short- and long-term approaches to gout therapy, it is important to maintain a good communication with your physician. Knowing which medication needs to be taken for a sudden attack, which needs to be taken to prevent attacks, and how your uric acid levels will be followed are all issues that you need to have clarified by your physician. You need to understand the overall principles of gout therapy and how they may be applied to at any point in your disease. This becomes even more important as you move into long-term management of the disease.
Long-term Management Issues
Problems seen with long-standing gout include:
- Joint damage after multiple gouty attacks. We can't do a lot to take away prior damage, but treatment, as with allopurinol, can be extremely effective in preventing any further damage.
- Development of tophi (local deposits of uric acid - often on the elbows, or on the ears, hands or other locations)-These can be prevented with allopurinol, and will often gradually shrink and ultimately disappear on allopurinol therapy.
- Kidney stones due to elevated uric acid in the urine - These can be very effectively prevented with allopurinol.
- Hypertension, which is often associated with recurrent gout, should be monitored by your physician. It may even be wise for you to have a blood pressure monitoring machine at home. Medication may be prescribed because chronic hypertension can also damage the kidney. Treating the hypertension won't improve the gout, but when a physician sees a patient with gout, it makes it more important to look for hypertension, since the two conditions often appear in the same patient.
- Alternative medicine - When gout becomes an ongoing presence in your life, the temptation exists to look around for "something better" in alternative medicine. However, we urge you resist the siren songs of their pitchmen. Despite the promises of some websites and other sources marketing "cures" for gout, there is no cure (although medications like allopurinol can provide lifelong relief for most patients - as long as they continue the medication). None of the herbs, serums, and other dietary supplements marketed on the Internet will help your gout. And the very limited diets some sites prescribe will not give you the adequate nutrition you need to stay healthy, especially in the presence of a chronic disease. Working together, the physician and patient can develop a regimen that can markedly decrease attacks - and usually fully banish them over time. But the medications must be taken forever or the gout is likely to return. If by chance you have seen or heard of something in the world of alternative medicine that you think you would like to try, please be sure to discuss it with your doctor first. You would not want to try something that could actually make your gout worse - or worsen some other health problem you might have.
Prognosis: The Long-term Outlook for Patients with Gout
What is the long-term outlook for patients with gout? Given the available medications to control gout, the long-term outlook is excellent. However, patients often have increased attacks of gout in the early phases of allopurinol therapy and require treatment for such attacks. This should not discourage patients from continuing on allopurinol. Patients successfully treated for gout generally require lifelong therapy to prevent the attacks from returning.
When to seek referral to a specialist
A primary care physician or internist often works in partnership with a rheumatologist in the care of people with gout. You may wish to seek referral to a rheumatologist for a second opinion or ongoing care in the following situations:
- When the diagnosis is in question;
- At the start of therapy, in order to craft the optimal medication regimen;
- During the course of gout if the prescribed regimen is not preventing recurrences;
- When symptoms that may be medication side-effects occur;
- The presence of fever, marked fatigue, or weight loss;
- Prior to orthopaedic or other surgery (since it is not rare for surgery to set off a gout attack).
- Gout is a free pamphlet offered by the Arthritis Foundation. Visit their website to order your copy.
- Wortmann RL. Effective Management of Gout: An Analogy. Am J Med. 1998 Dec;105(6):513-4. This is a valuable review article.
- Terkeltaub R, et al: Low Dose (1.8 mg) vs High Dose (4.8 mg) Oral Colchicine Regimens in Patients with Acute Gout Flare in a Large, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, Arthritis & Rheumatism, Abstract #1944, Supplement, September 2008.
- Emmerson B, Emmerson BT. Getting Rid of Gout: A Guide to Management and Prevention. (Oxford University Press;1996) A leading authority on nephrology, who specializes in gout, provides a complete background for understanding the disease, which is so important for treatment and prevention of attacks.
- The 2002 Official Patient's SourceBook on Gout. James N. Parker (Editor) Phillip M. Parker (Editor).
- Porter R, Rousseau GS. Gout: The Patrician Malady. (Yale Univ Press; 2000) This is a socio-medical history of the disease.
- Schneiter J. Gout Hater's Cookbook: Recipes Lower in Purines and Lower in Fat. (Reachment Publications; 2000) In addition to comprehensive lists of foods lower, relatively high and highest in purines, this book offers nearly 100 low-purine recipes.
- Schneiter J. Gout Hater's Cookbook II: The Low Purine Diet Cookbook. (Reachment Publications: 2001) More recipes from the same author.