Gout (also known as podagra when it involves the big toe) is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected (approximately 50% of cases). It may also present as tophi, kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in the blood. The uric acid crystallizes, and the crystals deposit in joints, tendons, and surrounding tissues.
SIGNS AND SYMPTOMS
The signs and symptoms of gout almost always occur suddenly — often at night — and without warning. They include:
Intense joint pain. Gout usually affects the large joint of your big toe, but it can occur in your feet, ankles, knees, hands and wrists. The pain is likely to be most severe within the first four to 12 hours after it begins.
Lingering discomfort. After the most severe pain subsides, some joint discomfort may last from a few days to a few weeks. Later attacks are likely to last longer and affect more joints.
Inflammation and redness. The affected joint or joints become swollen, tender, warm and red.
Limited range of motion. Decreased joint mobility may occur as gout progresses
RISK FACTORS
You're more likely to develop gout if you have high levels of uric acid in your body. Factors that increase the uric acid level in your body include:
Diet. Eating a diet that's high in meat and seafood and high in beverages sweetened with fruit sugar (fructose) promotes higher levels of uric acid, which increases your risk of gout. Alcohol consumption, especially of beer, also increases the risk of gout.
Obesity. If you are overweight, your body produces more uric acid and your kidneys have a more difficult time eliminating uric acid, which greatly increases your risk of gout.
Medical conditions. Certain diseases and conditions make it more likely that you'll develop gout. These include untreated high blood pressure and chronic conditions such as diabetes, metabolic syndrome, and heart and kidney diseases.
Certain medications. The use of thiazide diuretics — commonly used to treat hypertension — and low-dose aspirin also can increase uric acid levels. So can the use of anti-rejection drugs prescribed for people who have undergone an organ transplant.
Family history of gout. If other members of your family have had gout, you're more likely to develop the disease.
Age and sex. Gout occurs more often in men, primarily because women tend to have lower uric acid levels. After menopause, however, women's uric acid levels approach those of men. Men also are more likely to develop gout earlier — usually between the ages of 30 and 50 — whereas women generally develop signs and symptoms after menopause.
Recent surgery or trauma. Experiencing recent surgery or trauma has been associated with an increased risk of developing gout
PATHOPHYSIOLOGY
Gout is a disorder of purine metabolism, and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues. Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells, and therefore avoids inflammation. Naked crystals may break out of walled-off tophi due to minor physical trauma to the joint, medical or surgical stress, or rapid changes in uric acid levels.When they breach the tophi, they trigger a local immune-mediated inflammatory reaction, with one of the key proteins in the inflammatory cascade being interleukin 1β An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common.
The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase.Other factors believed important in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate.The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to a number of factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol.Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension
TESTS AND MEDICAL EXAMS
Exams and tests that may help with diagnosis and treatment of gout include:
1. A joint fluid analysis (arthrocentesis) to see whether uric acid crystals are present. This is the only certain way to diagnose gout.
2. A medical history and physical exam.
3. A test to measure levels of uric acid in blood. This may be done if your doctor cannot safely get fluid from the affected joint.
4. A test to measure levels of uric acid in urine.
5. While X-rays of extremities (hands and feet) are sometimes useful in the late stages of the disease, X-rays aren't usually helpful in the early diagnosis. Pain often causes people to seek medical attention before any long-term changes can be seen camera.gif on an X-ray. But X-rays may help to rule out other causes of arthritis.
Your doctor may evaluate you for lead poisoning if you have been exposed to lead in your job or through hobbies
TREATMENTS
The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by different drugs used to reduce the serum uric acid levels. Tentative evidence support the application of ice for 20 to 30 minutes several times a day to decrease pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and steroids, while options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease. Treatment of associated health problems is also important. Lifestyle interventions have been poorly studied. It is unclear if dietary supplements have an effect in people with gout.
NSAIDs
NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly more or less effective than any other. Improvement may be seen within four hours, and treatment is recommended for one to two weeks. They are not recommended, however, in those with certain other health problems, such as gastrointestinal bleeding, renal failure, or heart failure.While indomethacin has historically been the most commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.
Colchicine
Colchicine is an alternative for those unable to tolerate NSAIDs. At high doses, side effects (primarily gastrointestinal upset) limit its usage. At lower doses, which are still effective, it is well tolerated. Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.
Steroids
Glucocorticoids have been found as effective as NSAIDs and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into the joint; a joint infection must be excluded, however, as steroids worsens this condition.
Pegloticase
Pegloticase was approved in the USA to treat gout in 2010. It is an option for the 3% of people who are intolerant to other medications. Pegloticase is administered as an intravenous infusion every two weeks and has been found to reduce uric acid levels in this population It is likely useful for tophi but has a high rate of side effects.
Prophylaxis
A number of medications are useful for preventing further episodes of gout, including xanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics (including probenecid and sulfinpyrazone). They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack, and are often used in combination with either an NSAID or colchicine for the first three to six months. They are not recommended until a person has had two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist, as medications have not been found cost-effective until this point. Urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/l (5.0–6.0 mg/dl), and are continued indefinitely. If these medications are being used chronically at the time of an attack, discontinuation is recommended. If levels cannot be brought below 6.0 mg/dl and there are recurrent attacks, this is deemed treatment failure or refractory gout. Overall, probenecid appears less effective than allopurinol.
Uricosuric medications are typically preferred if undersecretion of uric acid, as indicated by a 24-hour collection of urine results in a uric acid amount of less than 800 mg, is found. They are, however, not recommended if a person has a history of kidney stones. In a 24-hour urine excretion of more than 800 mg, which indicates overproduction, a xanthine oxidase inhibitor is preferred.
Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acid production, and long-term therapy is safe and well tolerated, and can be used in people with renal impairment or urate stones, although allopurinol has caused hypersensitivity in a small number of individuals. In such cases, the alternative drug, febuxostat, has been recommended.
PROGNOSIS
Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease, and thus are at increased risk of death.This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.
Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi. These tophi occur in 30% of those who are untreated for five years, often in the helix of the ear, over the olecranon processes, or on the Achilles tendons. With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH promoting the precipitation of uric acid. Other forms of chronic renal dysfunction may occur.
The signs and symptoms of gout almost always occur suddenly — often at night — and without warning. They include:
Intense joint pain. Gout usually affects the large joint of your big toe, but it can occur in your feet, ankles, knees, hands and wrists. The pain is likely to be most severe within the first four to 12 hours after it begins.
Lingering discomfort. After the most severe pain subsides, some joint discomfort may last from a few days to a few weeks. Later attacks are likely to last longer and affect more joints.
Inflammation and redness. The affected joint or joints become swollen, tender, warm and red.
Limited range of motion. Decreased joint mobility may occur as gout progresses
RISK FACTORS
You're more likely to develop gout if you have high levels of uric acid in your body. Factors that increase the uric acid level in your body include:
Diet. Eating a diet that's high in meat and seafood and high in beverages sweetened with fruit sugar (fructose) promotes higher levels of uric acid, which increases your risk of gout. Alcohol consumption, especially of beer, also increases the risk of gout.
Obesity. If you are overweight, your body produces more uric acid and your kidneys have a more difficult time eliminating uric acid, which greatly increases your risk of gout.
Medical conditions. Certain diseases and conditions make it more likely that you'll develop gout. These include untreated high blood pressure and chronic conditions such as diabetes, metabolic syndrome, and heart and kidney diseases.
Certain medications. The use of thiazide diuretics — commonly used to treat hypertension — and low-dose aspirin also can increase uric acid levels. So can the use of anti-rejection drugs prescribed for people who have undergone an organ transplant.
Family history of gout. If other members of your family have had gout, you're more likely to develop the disease.
Age and sex. Gout occurs more often in men, primarily because women tend to have lower uric acid levels. After menopause, however, women's uric acid levels approach those of men. Men also are more likely to develop gout earlier — usually between the ages of 30 and 50 — whereas women generally develop signs and symptoms after menopause.
Recent surgery or trauma. Experiencing recent surgery or trauma has been associated with an increased risk of developing gout
PATHOPHYSIOLOGY
Gout is a disorder of purine metabolism, and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues. Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells, and therefore avoids inflammation. Naked crystals may break out of walled-off tophi due to minor physical trauma to the joint, medical or surgical stress, or rapid changes in uric acid levels.When they breach the tophi, they trigger a local immune-mediated inflammatory reaction, with one of the key proteins in the inflammatory cascade being interleukin 1β An evolutionary loss of urate oxidase (uricase), which breaks down uric acid, in humans and higher primates has made this condition common.
The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase.Other factors believed important in triggering an acute episode of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate.The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to a number of factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol.Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension
TESTS AND MEDICAL EXAMS
Exams and tests that may help with diagnosis and treatment of gout include:
1. A joint fluid analysis (arthrocentesis) to see whether uric acid crystals are present. This is the only certain way to diagnose gout.
2. A medical history and physical exam.
3. A test to measure levels of uric acid in blood. This may be done if your doctor cannot safely get fluid from the affected joint.
4. A test to measure levels of uric acid in urine.
5. While X-rays of extremities (hands and feet) are sometimes useful in the late stages of the disease, X-rays aren't usually helpful in the early diagnosis. Pain often causes people to seek medical attention before any long-term changes can be seen camera.gif on an X-ray. But X-rays may help to rule out other causes of arthritis.
Your doctor may evaluate you for lead poisoning if you have been exposed to lead in your job or through hobbies
TREATMENTS
The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by different drugs used to reduce the serum uric acid levels. Tentative evidence support the application of ice for 20 to 30 minutes several times a day to decrease pain. Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and steroids, while options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease. Treatment of associated health problems is also important. Lifestyle interventions have been poorly studied. It is unclear if dietary supplements have an effect in people with gout.
NSAIDs
NSAIDs are the usual first-line treatment for gout, and no specific agent is significantly more or less effective than any other. Improvement may be seen within four hours, and treatment is recommended for one to two weeks. They are not recommended, however, in those with certain other health problems, such as gastrointestinal bleeding, renal failure, or heart failure.While indomethacin has historically been the most commonly used NSAID, an alternative, such as ibuprofen, may be preferred due to its better side effect profile in the absence of superior effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor may be given.
Colchicine
Colchicine is an alternative for those unable to tolerate NSAIDs. At high doses, side effects (primarily gastrointestinal upset) limit its usage. At lower doses, which are still effective, it is well tolerated. Colchicine may interact with other commonly prescribed drugs, such as atorvastatin and erythromycin, among others.
Steroids
Glucocorticoids have been found as effective as NSAIDs and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into the joint; a joint infection must be excluded, however, as steroids worsens this condition.
Pegloticase
Pegloticase was approved in the USA to treat gout in 2010. It is an option for the 3% of people who are intolerant to other medications. Pegloticase is administered as an intravenous infusion every two weeks and has been found to reduce uric acid levels in this population It is likely useful for tophi but has a high rate of side effects.
Prophylaxis
A number of medications are useful for preventing further episodes of gout, including xanthine oxidase inhibitor (including allopurinol and febuxostat) and uricosurics (including probenecid and sulfinpyrazone). They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack, and are often used in combination with either an NSAID or colchicine for the first three to six months. They are not recommended until a person has had two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist, as medications have not been found cost-effective until this point. Urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/l (5.0–6.0 mg/dl), and are continued indefinitely. If these medications are being used chronically at the time of an attack, discontinuation is recommended. If levels cannot be brought below 6.0 mg/dl and there are recurrent attacks, this is deemed treatment failure or refractory gout. Overall, probenecid appears less effective than allopurinol.
Uricosuric medications are typically preferred if undersecretion of uric acid, as indicated by a 24-hour collection of urine results in a uric acid amount of less than 800 mg, is found. They are, however, not recommended if a person has a history of kidney stones. In a 24-hour urine excretion of more than 800 mg, which indicates overproduction, a xanthine oxidase inhibitor is preferred.
Xanthine oxidase inhibitors (including allopurinol and febuxostat) block uric acid production, and long-term therapy is safe and well tolerated, and can be used in people with renal impairment or urate stones, although allopurinol has caused hypersensitivity in a small number of individuals. In such cases, the alternative drug, febuxostat, has been recommended.
PROGNOSIS
Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular disease, and thus are at increased risk of death.This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.
Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi. These tophi occur in 30% of those who are untreated for five years, often in the helix of the ear, over the olecranon processes, or on the Achilles tendons. With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH promoting the precipitation of uric acid. Other forms of chronic renal dysfunction may occur.
