Gout

The Gout by James Gillray. Source: Wikimedia Commons.

Gout is a disease caused by an excess of uric acid. Uric acid is a substance that results from the breakdown of purines (byproducts of meat that are critical components of DNA and RNA). Instead of being filtered by the kidneys, the excess uric acid in gout forms crystals which are deposited in the joints of the body. Gout is characterized by sudden, severe attacks of pain, redness and tenderness in the joints.

Other Names

• Hyperuricemia

Types

• Primary gout is inherited. It results from increased production of uric acid, reduced excretion of uric acid in the urine, or both.
• Secondary gout results when high uric acid levels are caused by medications (for example, diuretics), chronic kidney failure, or rapid destruction of cells that cause a release of the chemical precursors for uric acid (for example, during chemotherapy).

Signs and Symptoms

A toe afflicted with gout. Source: Wikimedia Commons.

Gout is a type of arthritis. Arthritis means “inflammation of the joint" and includes more than 100 different diseases that affect the joints. Gout accounts for approximately 5 percent of all cases of arthritis.

In many people, gout initially affects the joints of the big toe (a condition called podagra). But many other joints and areas around the joints can be affected in addition to or aside from the big toe. These include the ankles, heels, knees, wrists, fingers, and elbows. Uric acid deposits, also known as tophi, appear as lumps under the skin surrounding the joints. Increased uric acid levels can also appear in the urine as uric acid crystals and form into kidney stones.

The disease can progress through four stages, each of which has different symptoms:

• Asymptomatic (without symptoms) hyperuricemia – In this stage, a person has elevated levels of uric acid in the blood (hyperuricemia), but no other symptoms. Treatment is usually not required.
• Acute gout, or acute gouty arthritis – In this stage, hyperuricemia has caused the deposit of uric acid crystals in joint spaces. This leads to a sudden onset of intense pain and swelling in the joints, which also may be warm and very tender. An acute attack commonly occurs at night and can be triggered by stressful events, alcohol or drugs, or the presence of another illness. Attacks usually subside within 3 to 10 days, even without treatment, and the next attack may not occur for months or even years. Over time, however, attacks can last longer and occur more frequently.
• Interval or intercritical gout – This is the period between acute attacks. In this stage, a person does not have any symptoms.
• Chronic tophaceous gout – This is the most disabling stage of gout. It usually develops over a long period, such as 10 years. In this stage, the disease may have caused permanent damage to the affected joints and sometimes to the kidneys. With proper treatment, most people with gout do not progress to this advanced stage.

Causes

Gout occurs when the bodily waste product uric acid is deposited as needle-like crystals in the joints and/or soft tissues. In the joints, these uric acid crystals cause inflammatory arthritis, which in turn leads to intermittent swelling, redness, heat, pain, and stiffness in the joints.

Uric acid is a substance that results from the breakdown of purines. A normal part of all human tissue, purines are found in many foods. Normally, uric acid is dissolved in the blood and passed through the kidneys into the urine, where it is eliminated.

If there is an increase in the production of uric acid or if the kidneys do not eliminate enough uric acid from the body, levels of it build up in the blood (a condition called hyperuricemia). Hyperuricemia also may result when a person eats too many high-purine foods, such as liver, dried beans and peas, anchovies, or gravies. Hyperuricemia is not a disease, and by itself it is not dangerous. However, if excess uric acid crystals form as a result of hyperuricemia, gout can develop.

Diagnosis

Gout may be difficult for doctors to diagnose because the symptoms can be vague, and gout often mimics other conditions. Although most people with gout have hyperuricemia at some time during the course of their disease, it may not be present during an acute attack. In addition, having hyperuricemia alone does not mean that a person will get gout. In fact, most people with hyperuricemia do not develop the disease.

To confirm a diagnosis of gout, a doctor may insert a needle into an inflamed joint and draw a sample of synovial fluid, the substance that lubricates a joint. The joint fluid is placed on a slide and examined under a microscope for uric acid crystals. Their absence, however, does not rule out the diagnosis.

The doctor may also find it helpful to look for uric acid crystals around joints to diagnose gout. Gout attacks may mimic joint infections, and a doctor who suspects a joint infection may also culture the joint fluid to see whether bacteria are present.

Diagnostic challenges

Gout is sometimes confused with other forms of arthritis because the symptoms – acute and episodic attacks of joint warmth, pain, swelling, and stiffness – can be similar. One form of arthritis often confused with gout is called pseudogout. The pain, swelling, and redness of pseudogout can also come on suddenly and may be severe, closely resembling the symptoms of gout. However, the crystals deposited in joint are calcium phosphate crystals, not uric acid. Therefore, pseudogout is treated somewhat differently.

Treatment

With proper treatment, most people who have gout are able to control their symptoms. Gout can be treated with one or a combination of therapies. The goals of treatment are to ease the pain associated with acute attacks, to prevent future attacks, and to avoid the formation of tophi and kidney stones. Successful treatment can reduce discomfort caused by the symptoms of gout, as well as long-term damage to the affected joints. Treatment will help to prevent disability due to gout.

The most common treatments for an acute attack of gout are nonsteroidal anti-inflammatory drugs (NSAIDs) taken orally (by mouth), or corticosteroids, which are taken orally or injected into the affected joint. NSAIDs reduce the pain and inflammation caused by deposits of uric acid crystals, but have no effect on the amount of uric acid in the body. The NSAIDs most commonly prescribed for gout are indomethacin (Indocin) and naproxen (Anaprox, Naprosyn), which are taken orally every day. Corticosteroids are strong anti-inflammatory hormones. The most commonly prescribed corticosteroid is prednisone. Patients often begin to improve within a few hours of treatment with a corticosteroid, and the attack usually goes away completely within a week. Although short courses of steroids are very safe, in the long term steroid medications can have severe side effects and therefore their use is usually limited to the period immediately after a painful attack.

In severe gout attacks, when large joints are swollen and very painful, joint specialists may be involved in the care of the patient. On such occasions, as long as infection has been ruled out as a cause of the pain and inflammation, injections of steroids such as methylprednisolone and triamcinolone may be considered to reduce the inflammation inside the joint rapidly and to reduce symptoms. Since this can make infection worse, it is extremely important to rule out infection first, usually by sampling the fluid from the joint and examining it under the microscope.

When NSAIDs or corticosteroids do not control symptoms, the doctor may consider using colchicine. This drug is most effective when taken within the first 12 hours of an acute attack. Doctors may ask patients to take oral colchicine as often as every hour until joint symptoms begin to improve or side effects such as nausea, vomiting, abdominal cramps, or diarrhea make it uncomfortable to continue the drug.

Prevention

Fortunately, gout can be controlled. People with gout can decrease the severity of attacks and reduce their risk of future attacks by taking their medications as prescribed. Acute gout is best controlled if medications are taken at the first sign of pain or inflammation.

Medications

For some patients, the doctor may prescribe either NSAIDs or oral colchicine in small daily doses to prevent future attacks. The doctor also may consider prescribing medicine such as allopurinol (Zyloprim) or probenecid (Benemid) to treat hyperuricemia and reduce the frequency of sudden attacks and the development of tophi.

People who have other medical problems, such as high blood pressure or high blood triglycerides (fats) levels, may find that the drugs they take for those conditions can also be useful for gout. Both losartan (Cozaar), a blood pressure medication, and fenofibrate (Tricor), a triglyceride-lowering drug, also help reduce blood levels of uric acid.

Certain medications predispose people to gout, so patients should go over all their medications with their doctor. (See below, "Risk factors.")

Lifestyle changes

• Doctors may recommend losing weight for those who are overweight.
• Patients should drink plenty of fluids, especially water. Nonalcoholic fluids help remove uric acid from the body. They should reduce their alcohol consumption, because alcohol can raise the levels of uric acid in the blood.
• Patients should avoid low-carbohydrate diets that are designed for quick weight loss. When carbohydrate intake is insufficient, the body cannot completely burn fat. As a consequence, substances called ketones form and are released into the bloodstream, resulting in a condition called ketosis. After a short time, ketosis can increase the level of uric acid in the blood.

Foods to avoid

Patients should avoid foods that are high in purines. These include:

• Anchovies
• Asparagus
• Beef kidneys
• Brains
• Dried beans and peas
• Game meats
• Gravy
• Herring
• Liver
• Mackerel
• Mushrooms
• Sardines
• Scallops
• Sweetbreads

Chances of Developing Gout

Gout occurs in 8.4 of every 1,000 people. It is rare in children and young adults. Men, particularly those between the ages of 40 and 50, are more likely to develop gout than women, who rarely develop the disorder before menopause. People who have had an organ transplant are more susceptible to gout.

Risk factors

A number of risk factors are associated with hyperuricemia and gout. They include:

• Genetics- 20% of people have a family history of gout.
• Gender and age- It is more common in men than in women and more common in adults than in children.
• Weight- Being overweight increases the risk of developing hyperuricemia and gout because there is more tissue available for turnover or breakdown, which leads to excess uric acid production.
• Alcohol consumption- Drinking too much alcohol can lead to hyperuricemia, because alcohol interferes with the removal of uric acid from the body.
• Diet- Eating too many foods that are rich in purines can cause or aggravate gout in some people.
• Lead exposure- In some cases, exposure to lead in the environment can cause gout.
• Other health problems
  • Renal insufficiency, or the inability of the kidneys to eliminate waste products, is a common cause of gout in older people.
  • High blood pressure
  • Hypothyroidism (underactive thyroid gland)
  • Conditions that cause an excessively rapid turnover of cells, such as psoriasis, hemolytic anemia, or some cancers
  • Kelley-Seegmiller syndrome or Lesch-Nyhan syndrome, two rare conditions in which the enzyme that helps control uric acid levels either is not present or is found in insufficient quantities.
• Medications
  • Diuretics such as furosemide (Lasix), hydrochlorothiazide (Esidrix, Hydro-chlor), and metolazone (Diulo, Zaroxolyn), which are taken to eliminate excess fluid from the body in conditions like hypertension, edema, and heart disease, and which decrease the amount of uric acid passed in the urine
  • Salicylate-containing drugs such as aspirin
  • Niacin, a vitamin also known as nicotinic acid
  • Cyclosporine (Sandimmune, Neoral) which is a medication that suppresses the body’s immune system (the system that protects the body from infection and disease). This medication is used in the treatment of some autoimmune diseases, and to prevent the body’s rejection of transplanted organs.
  • Levodopa (Larodopa) is a medicine used to support communication along nerve pathways in the treatment of Parkinson’s disease.

Clinical Trials

For a list of ongoing, U.S. government-sponsored clinical trials related to gout, go to ClinicalTrials.gov.

Research

Recent discoveries

• The efficacy of Weicao Capsule (WCC), a Chinese complementary medicine, in the treatment of gout was evaluated. WCC was found to have a favorable therapeutic effect on gout. ^[1]
• Ultrasonogaphy appears to be a useful diagnostic tool for the determination of atypical gout. ^[2]
• The presence of metabolic syndrome (MS) is common with gout. A recent review is devoted to studying MS and IR in gout patients. ^[3]
• A recent study suggests that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. The study hypothesis is that uric acid has a key role in the foraging response associated with starvation and fasting. ^[4]

Current research

• A study to evaluate the efficacy of etoricoxib and indomethacin in the treatment of acute gout. ^[5]
• Two separate ongoing studies are evaluating the safety and efficacy of PEG (polyethylene glycol)-uricase in controlling the uric acid level in symptomatic gout patients with high uric acid levels who are unable to take standard gout therapies, or for whom those therapies have been unsuccessful in controlling their uric acid level. ^[6]

References

1. ↑ Song EF, Xiang Q, Rem KM. Clinical effect and action mechanism of Weicao Capsule in treating gout. Chin J Integr Med. 2008 Jun;14(2):103-6. Epub 2008 Aug 6. Abstract
2. ↑ Le Goff B, Berthelot JM, André V, Guillot P, Maugars Y. Ultrasonography for diagnosing atypical gout. Two case reports. Joint Bone Spine. 2008 Jul 30. (Epub ahead of print) Abstract
3. ↑ No authors listed. Metabolic syndrome in gout. Vestn Ross Akad Med Nauk. 2008;(6):29-32. 18652201 Abstract
4. ↑ Johnson RJ, Sautin YY, Oliver WJ, et al. Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society? J Comp Physiol [B]. 2008 Jul 23. [Epub ahead of print] Abstract
5. ↑ ClinicalTrials.gov. A Study Evaluating the Effect of Etoricoxib and Indomethacin in the Treatment of Acute Gout
6. ↑ ClinicalTrials.gov. Safety and Efficacy Study of PEG-Uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout

Links to Clinical Images

DermAtlas: Gout Images

Skinsight: Gout Images

External Links

American College of Rheumatology

Arthritis Foundation