Urinary Tract
Gout
Gout is a disease hallmarked by elevated levels of uric acid in the bloodstream. In this condition, crystals of monosodium urate (MSU) or uric acid are deposited on the articular cartilage of joints, tendons, and surrounding tissues. It is marked by transient painful attacks of acute arthritis initiated by crystallization of urates within and about the joints and can eventually lead to chronic gouty arthritis and the deposition of masses of urates in joints and other sites, sometimes creating tophi.
Historically, it was known as "The Disease of Kings" or "Rich man's disease".
Signs and symptoms
Gout is characterized by excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected foot. This occurs most commonly in men's toes but can appear in other parts of the body and affect women as well. Low-grade fever may also be present. The patient usually suffers from two sources of pain. The crystals inside the joint cause intense pain whenever the affected area is moved. The inflammation of the tissues around the joint also causes the skin to be swollen, tender and sore if it is even slightly touched. For example, a blanket or even the lightest sheet draped over the affected area can cause extreme pain.
Gout usually attacks the big toe (approximately 75 percent of first attacks); however, it also can affect other joints such as the ankle, heel, instep, knee, wrist, elbow, fingers, or spine. In some cases, the condition may appear in the joints of small toes that have become immobile due to impact injury earlier in life; the resulting poor blood circulation can lead to gout.
Patients with long-standing hyperuricemia (see below) can have uric acid crystal deposits called tophi (singular: tophus) in other tissues such as the helix of the ear. Elevated levels of uric acid in the urine can lead to uric-acid crystals precipitating in the kidneys or bladder, forming uric-acid kidney stones.
Causes
Gout may be primary (including idiopathic), or secondary to (a complication of) another condition.
Primary gout
High levels of uric acid in the blood can be caused by foods with high purine content, the body creating too much uric acid itself, or the body's inability to excrete the uric acid fast enough. Grain alcohol intake often causes acute attacks of gout in those already afflicted. A family history of gout, usually passed down through the mother, can pre-dispose individuals to high uric acid levels (see: inborn errors of purine-pyrimidine metabolism).
Gout is traditionally considered more common among affluent individuals, who may regularly drink and eat rich food and wines such as champagne, port, lobster, crab and other foods that contain the highest levels of purines, such as Foie gras. It is not rare, however, to find gout among all levels of society. Regular consumption of grain alcohol may also result in developing the disease. This is known as "poor man's gout." A sedentary lifestyle also increases the risk of developing the disease. When gout follows as a consequence of other health conditions such as renal failure, it is often regardless of the person's lifestyle.
Some studies have established a statistical connection between gout and lead poisoning, and a significant correlation between levels of lead in the body, urate excretion and gout. It is known that lead sugar was formerly used to sweeten wine. This condition is then known as saturnine gout (Saturnus being the alchemical term for metallic lead).
Diuretics (particularly thiazide diuretics) have often been blamed for precipitating attacks of gout because they compete at the same transporter, but a Dutch case-control study from 2006 appears to cast doubt on this conclusion.
About 10% of people with hyperuricemia develop gout.
Secondary gout
Secondary gout is a complication of other medical conditions. Medical conditions that commonly result in gout include:
- Metabolic syndrome (the combination of hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk)
- Leukemia
Gout also can develop as a co-morbidity of other diseases, including polycythaemia, intake of cytotoxics, obesity, diabetes, hypertension, renal disorders, and hemolytic anemia. Gout is an important complication in a minority of solid organ transplant.
Because some approved treatments for these other conditions also reduce serum uric acid, individualized treatment of gout has the potential to improve outcome.
Treatment
Treatment has three objectives: manage symptoms of acute attacks, prevent acute attacks, and reduce serum uric acid.
Patients are often started on a drug such as allopurinol, which inhibits the conversion of purine into uric acid. In this case, the purines are voided harmlessly in urine and feces.
A number of sufferers do not get relief from this class of drug, so the next class of drugs recommended are the uricosurics, which increase the excretion of uric acid from the body. This excretion is controlled by kidney hormones, which also control the reuptake of other chemicals. For this reason Probenecid may cause other drugs to be retained in the body for longer periods of time.
Because of these side effects probenecid is often reserved as the second line of defense against gout. If the patient does not obtain relief from allopurinol, though, he should be switched to probenecid promptly.
Acute attacks
The first line of treatment should be pain relief. Once the diagnosis has been confirmed, the drug options are of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and oral glucocorticoids, or intra-articular glucocorticoids administered via a joint injection.
NSAIDs such as diclofenac, etoricoxib, indomethacin, ketoprofen, naproxen or sulindac may be prescribed. For those at risk of gastric irritation from NSAIDs, an additional proton pump inhibitor may be given.
Colchicine remains a second line drug in the UK for those unable to tolerate NSAIDs, but its side effect profile has resulted in its role being relegated, at least in the US, to after that of oral glucocorticoids. It impairs the motility of granulocytes and can prevent the inflammatory phenomena that initiate an attack. Colchicine should be taken within the first 12 hours of the attack and usually relieves the pain within 48 hours, although side effects (gastrointestinal upset such as diarrhea and nausea) can complicate its use. NSAIDs are the preferred form of analgesia for patients with gout.
A randomized controlled trial found similar benefit from nonsteroidal anti-inflammatory drugs (single injection of diclofenac and then oral indomethacin) as from the oral glucocorticoid prednisolone; however, less adverse drug reactions occurred in the glucocorticoid group.
Another possibility is acetazolamide, one of the first diuretics discovered. This drug inhibits the action of carbonic anhydrase on the proximal convoluted tubules within the kidneys, which effectively inhibits reabsorption of bicarbonate, thus alkalinizing the urine. After two to three days of usage, the diuretic effects of this drug decline because of increased downstream reabsorption of ions and water by the renal tubules; however, the alkalinization of urine persists, and this basic urine attracts weak acids such as uric acid and cystine into the urine, thus increasing their urinary excretion.
Before medical help is available, some over-the-counter medications can provide temporary relief from pain and swelling. NSAIDs such as ibuprofen can reduce the pain and inflammation slightly, although aspirin should not be used as it can worsen the condition. This is because aspirin raises plasma uric acid levels even at low doses by inhibiting uric acid secretion in the renal tubules. Aspirin also reduces vasodilatation due to inhibition of prostaglandin PGE2 and PGI2 synthesis in the renal medulla and glomeruli respectively (see mechanism of action of aspirin). This may be a contra-indication for the use of aspirin for gout pain as well.
The anti-hemorrhoidal ointment Preparation H can reduce gout-induced skin swelling temporarily. Ice may be applied for 20 to 30 minutes several times a day, and a randomized controlled trial found that patients who used ice packs had better relief of pain without side effects. Since gout is caused by crystals, it has been suggested that keeping very well hydrated and heating the affected joint in hot water (rather than cooling with ice) will promote the dissolution and clearance of the urate crystals. Adequate hydration is a standard recommendation. However, a small study found that only icing, not heating, was beneficial. Keeping the affected area elevated above the level of the heart also may help. Professional medical care is needed for long-term management of gout.
Due to swelling around affected joints for prolonged periods, shedding of skin may occur. This is particularly evident when small toes are affected and may promote fungal infection in the web region if dampness occurs, and treatment is similar to that for common athlete's foot.
Some people who have gout report an aggravation of the condition in the knees and toes associated with long periods of immobility, such as when sitting at a computer desk for long hours. Individuals who notice early swelling or early pain may appear to be able to arrest the aggravation when medical treatment is applied before the condition gets worse. Where this is the case, a medically prescribed anti-inflammatory oral treatment taken with food and bed rest may provide relief within 6 to 8 hours.
Chronic joint changes
In general, gout can be controlled as long as medication begins before the tophi can be felt or seen. For extreme cases of gout (known as chronic tophaceous gout), surgery may be necessary to remove the large tophi and correct joint deformity. People whose gout has reached this stage will require continuous medication as well as lifestyle changes.
Extensive tophi that invade bone are associated with arthritis due to bone erosion.
Prevention
Prevention of chronic gout has a different objective than management of acute episodes (flareups). In an acute attack, the objective is to reduce pain and inflammation. The objective of prevention is to stop any future attacks and associated cumulative tissue damage. Prevention strategies include reducing the supply of purine, dissolving crystals of uric acid so the uric acid can return to the blood, and increasing the excretion of uric acid from the blood into the urine, without causing lithiasis there. Prevention tactics involve careful diagnosis of the factors contributing to the gout, followed by appropriate use of medication, diet, and over the counter remedies.
