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▎Gout, edited by WuXi AppTec's content team, is a common chronic disease.
Research data from Asia, Europe and North America show that the adult prevalence is between 0.
68% and 3.
90%.
Gout is more common among men, and Asian studies show that the ratio of male to female is about 8:1.
However, the treatment of gout is generally unsatisfactory.
Many patients have repeated attacks and have not received standard uric acid-lowering treatment.
Elevated serum urate concentration is the most important risk factor for the development of gout.
Long-term reduction of uric acid levels to reverse hyperuricemia is also the main strategy for effective management of gout.
How to deal with gout attacks, what are the precautions for long-term management, and how to prevent it? Recently, "The Lancet" published a review article comprehensively summarizing the latest developments in the clinical features, pathophysiology and treatment of gout.
Screenshot source: The Lancet Four pathophysiological stages: high uric acid ≠ gout Hyperuricemia and the progression of gout have four pathophysiological stages: development of hyperuricemia, deposition of urate crystals, and acute inflammation due to deposited crystals Sexual reaction causes gout attacks, and advanced disease characterized by tophi.
Some patients may not have experienced an attack of gout, and they may have advanced to the advanced stage.
Hyperuricemia is the "only way" for the development of gout.
Urate is the final product of the degradation of purine nucleotides.
High-purine diets or other dietary factors (such as alcohol and fructose intake) that cause degradation of purine nucleotides can increase serum urate levels and the risk of gout.
Diseases such as psoriasis and myelodysplasia can also lead to increased serum urate levels.
Urate excretion is regulated by the kidneys and intestines.
Insufficient urate excretion will increase serum urate concentration.
Elevated circulating insulin concentration (in the case of high body mass index and metabolic syndrome) and diuretics also reduce renal excretion of urate.
Most patients with hyperuricemia are asymptomatic and will not develop gout.
Even among people with severe hyperuricemia (≥600 µmol/L; about 10 mg/dL), less than half of them will develop gout in 15 years.
The deposition of urate crystals in patients with hyperuricemia is considered to be an important node in the occurrence and development of gout.
Approximately 25% of patients with hyperuricemia have urate crystal deposits, which can be confirmed by imaging studies.
The activation of NLRP3 inflammasomes in macrophages and monocytes by urate crystals is particularly relevant to gout attacks.
The activation of NLRP3 inflammasomes depends on two signaling systems.
The inflammatory response caused by urate crystals is only one step, which is why there may be no obvious clinical inflammation in the early stage of urate deposition.
Tophi is a chronic, foreign-body granulomatous (foreign-body granulomatous) inflammatory response of the body to urate crystals.
Clinical manifestations are more than just gout attacks.
The typical first symptom of gout is a gout attack—a severely painful acute inflammatory arthritis that mainly affects the joints of the lower limbs (foot, ankle and knee).
Gout attacks can also occur in the elbow, wrist, and hand joints, but upper limb involvement usually only occurs in long-term, poorly controlled patients.
Gout attacks are usually single-joint attacks; multi-joint attacks usually occur in patients with poor disease control, and can be accompanied by obvious systemic symptoms, including fever, chills, and even delirium.
▲Gout attacks mainly affect the joints of the lower extremities (picture source: 123RF) The time from the onset of gout to the peak of pain is usually less than 12 hours, accompanied by varying degrees of redness and swelling, which may lead to limited mobility and difficulty walking.
Without treatment, the gout attack usually resolves on its own within 7-14 days, and after a period of painless period, the attack occurs again.
The recurrence of gout is usually difficult to predict, but it is related to the severity of hyperuricemia.
The triggers for gout attacks include high purines, alcohol intake, joint trauma, and acute illness.
Most patients will have recurrent attacks, and with continuous exposure to higher levels of serum urate, the burden of urate continues to increase, and each gout attack may last longer.
Over time, some people with persistent hyperuricemia can also develop tophi, chronic gouty arthritis, and joint structural damage.
Typical locations where tophus appears include joints, ears, bursa, fingertips, and tendons.
The size of tophi may vary greatly.
Tophi is usually hard, but it may soften during the treatment of urate-lowering.
Depending on the location, tophi may restrict joint movement.
Gout is also often associated with a variety of diseases, including hypertension, obesity, cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease, and kidney stones.
These comorbid diseases will complicate the treatment of gout and increase the risk of premature death.
.
Gout attacks: early anti-inflammatory treatment.
For asymptomatic hyperuricemia patients, the prevention of gout should be considered, such as dietary adjustments and weight loss.
At present, it is not recommended to prevent gout through urate-lowering drugs or anti-inflammatory drugs.
Once an acute attack of gout occurs, anti-inflammatory treatment is recommended as soon as possible.
The focus of treatment is to control pain and suppress joint inflammation.
First-line treatments include oral corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or colchicine.
The choice of specific drugs depends on the patient's personal factors, including comorbidities, concomitant medications, and the efficacy and side effects of previous medications.
Accompanied by kidney disease, heart disease, peptic ulcer disease or taking anticoagulant drugs, non-steroidal anti-inflammatory drugs should be avoided.
In cases of infection, fluid retention, or diabetes, high-dose oral prednisone should be avoided.
In patients with severe kidney disease, severe liver disease, and the simultaneous use of ABCB1 inhibitors and CYP3A4 inhibitors (such as cyclosporine, ketoconazole, clarithromycin, and verapamil), colchicine may be toxic.
In addition, clinical trials have shown that oral prednisolone, non-steroidal anti-inflammatory drugs (including non-selective or COX-2 selective drugs), and low-dose colchicine are equally effective in treating gout attacks.
However, oral corticosteroids may have better safety than non-steroidal anti-inflammatory drugs, and non-steroidal anti-inflammatory drugs have fewer side effects than low-dose colchicine.
A small dose of colchicine (1.
0-1.
2 mg immediately followed by 0.
5-0.
6 mg one hour later) is as effective as a high-dose colchicine (4.
8 mg taken within 6 hours), but with fewer side effects, so high doses are not recommended Colchicine.
For patients with gout attacks who cannot take oral medications, intra-articular, intramuscular, or intravenous corticosteroids are also an option.
IL-1 inhibitors are only used in patients who cannot tolerate or have contraindications to first-line anti-inflammatory therapy.
Non-drug therapy (such as ice compress) has a certain analgesic effect.
Supportive therapy includes rest, mobility assistance, and adequate nutrition and hydration.
At the same time, all patients with gout attacks need to understand long-term effective urate-lowering therapy to prevent recurrence and joint damage.
Gout requires long-term continuous treatment to reduce and maintain the level of uric acid to reach the standard.
The main strategy for long-term gout management is to achieve standard treatment of serum urate.
Continuously reduce urate through treatment to dissolve urate crystals.
Clinical trials have shown that, in the long run, this treatment strategy can reduce gout attacks, subside tophi and prevent joint damage.
For most patients with gout, the target serum urate level should be less than 360 µmol/L.
For those with a high uric acid load (for example, tophi has occurred), the target serum uric acid level should be more stringent, ≤300 µmol/L.
Image source: Under what circumstances should 123RF lower uric acid? Urate-lowering therapy is usually recommended for the following patients: appearance of tophi, imaging evidence of joint damage caused by gout, frequent attacks of gout (≥2 times within a year) and urinary tract stones; high serum uric acid concentration (> 480 µmol/L) ) Or young patients (<40 years old) with comorbid diseases (kidney or heart disease).
Uric acid-lowering therapy can be initiated during a gout attack, and the dose should be adjusted gradually from a low dose.
During this period, low-dose anti-inflammatory drugs can also be used to prevent gout attacks (such as 250 mg naproxen per day or 0.
6 mg colchicine per day for 3-6 months).
Uric acid-lowering drug choice For most gout patients, allopurinol is the first-line uric acid-lowering therapy.
Most patients with gout can achieve serum urate levels by monotherapy with allopurinol.
Allopurinol is generally well tolerated, with a rash in 1%-2% of patients and the need to stop treatment.
Carriers of the HLA-B*5801 gene (some Asians and African Americans) are prone to allopurinol hypersensitivity syndrome, which can be avoided by screening the gene in advance.
Febuxostat is recommended as a second-line uric acid-lowering therapy.
The effect of febuxostat on cardiovascular risk has not yet reached a consistent conclusion in different large-scale trials.
For patients who do not respond well to or intolerance to allopurinol treatment, doctors can recommend febuxostat and pay attention to the patient’s heart.
Vascular risk.
In addition, urological drugs such as probenecid and benzbromarone can promote the excretion of urate, and can also be used as a monotherapy or in combination with allopurinol.
But the potential side effect is the risk of urinary stones.
Pegloticase can metabolize urate, and clinical trials have shown that it can improve symptoms such as gout attacks and tophi.
Long-term management of gout: It is also very important to focus on the management of comorbidities and dietary comorbid diseases, such as body mass index, blood pressure, creatinine, and glycosylated hemoglobin.
Some other therapeutic drugs for comorbid diseases, such as the antihypertensive drug Losartan, and the SGLT-2 inhibitor antidiabetic drug fenofibrate, also have certain characteristics of lowering urate.
Dietary adjustments through the DASH diet and weight loss can help achieve a moderate reduction in serum uric acid levels.
DASH diet: advocate low fat, low salt, low sugar, and provide balanced nutrition.
Use refined meat, poultry, and fish as the main protein sources, and a balanced intake of fruits and vegetables, dairy products, grains, soy products, nuts, a small amount of fat and sweets; at the same time reduce the intake of salt and saturated fat, such as drinking low-fat milk , Do not eat or eat less fat.
At the same time, sugary drinks and excessive alcohol (especially purine-rich beer) should be avoided.
Purine-rich foods such as red meat and seafood can also increase the concentration of serum urate and the risk of gout.
Patients can pay attention to identifying specific foods that trigger gout attacks, and avoiding these dietary triggers may help.
However, most patients with gout cannot achieve the standard of serum uric acid only by diet management.
Summary Gout is common but treatable.
In particular, long-term lowering of urate through allopurinol and other drugs can prevent gout and improve the quality of life of patients.
By standardizing the initiation and durability of uric acid-lowering therapy, high-quality gout management can help improve patient prognosis.
Research data from Asia, Europe and North America show that the adult prevalence is between 0.
68% and 3.
90%.
Gout is more common among men, and Asian studies show that the ratio of male to female is about 8:1.
However, the treatment of gout is generally unsatisfactory.
Many patients have repeated attacks and have not received standard uric acid-lowering treatment.
Elevated serum urate concentration is the most important risk factor for the development of gout.
Long-term reduction of uric acid levels to reverse hyperuricemia is also the main strategy for effective management of gout.
How to deal with gout attacks, what are the precautions for long-term management, and how to prevent it? Recently, "The Lancet" published a review article comprehensively summarizing the latest developments in the clinical features, pathophysiology and treatment of gout.
Screenshot source: The Lancet Four pathophysiological stages: high uric acid ≠ gout Hyperuricemia and the progression of gout have four pathophysiological stages: development of hyperuricemia, deposition of urate crystals, and acute inflammation due to deposited crystals Sexual reaction causes gout attacks, and advanced disease characterized by tophi.
Some patients may not have experienced an attack of gout, and they may have advanced to the advanced stage.
Hyperuricemia is the "only way" for the development of gout.
Urate is the final product of the degradation of purine nucleotides.
High-purine diets or other dietary factors (such as alcohol and fructose intake) that cause degradation of purine nucleotides can increase serum urate levels and the risk of gout.
Diseases such as psoriasis and myelodysplasia can also lead to increased serum urate levels.
Urate excretion is regulated by the kidneys and intestines.
Insufficient urate excretion will increase serum urate concentration.
Elevated circulating insulin concentration (in the case of high body mass index and metabolic syndrome) and diuretics also reduce renal excretion of urate.
Most patients with hyperuricemia are asymptomatic and will not develop gout.
Even among people with severe hyperuricemia (≥600 µmol/L; about 10 mg/dL), less than half of them will develop gout in 15 years.
The deposition of urate crystals in patients with hyperuricemia is considered to be an important node in the occurrence and development of gout.
Approximately 25% of patients with hyperuricemia have urate crystal deposits, which can be confirmed by imaging studies.
The activation of NLRP3 inflammasomes in macrophages and monocytes by urate crystals is particularly relevant to gout attacks.
The activation of NLRP3 inflammasomes depends on two signaling systems.
The inflammatory response caused by urate crystals is only one step, which is why there may be no obvious clinical inflammation in the early stage of urate deposition.
Tophi is a chronic, foreign-body granulomatous (foreign-body granulomatous) inflammatory response of the body to urate crystals.
Clinical manifestations are more than just gout attacks.
The typical first symptom of gout is a gout attack—a severely painful acute inflammatory arthritis that mainly affects the joints of the lower limbs (foot, ankle and knee).
Gout attacks can also occur in the elbow, wrist, and hand joints, but upper limb involvement usually only occurs in long-term, poorly controlled patients.
Gout attacks are usually single-joint attacks; multi-joint attacks usually occur in patients with poor disease control, and can be accompanied by obvious systemic symptoms, including fever, chills, and even delirium.
▲Gout attacks mainly affect the joints of the lower extremities (picture source: 123RF) The time from the onset of gout to the peak of pain is usually less than 12 hours, accompanied by varying degrees of redness and swelling, which may lead to limited mobility and difficulty walking.
Without treatment, the gout attack usually resolves on its own within 7-14 days, and after a period of painless period, the attack occurs again.
The recurrence of gout is usually difficult to predict, but it is related to the severity of hyperuricemia.
The triggers for gout attacks include high purines, alcohol intake, joint trauma, and acute illness.
Most patients will have recurrent attacks, and with continuous exposure to higher levels of serum urate, the burden of urate continues to increase, and each gout attack may last longer.
Over time, some people with persistent hyperuricemia can also develop tophi, chronic gouty arthritis, and joint structural damage.
Typical locations where tophus appears include joints, ears, bursa, fingertips, and tendons.
The size of tophi may vary greatly.
Tophi is usually hard, but it may soften during the treatment of urate-lowering.
Depending on the location, tophi may restrict joint movement.
Gout is also often associated with a variety of diseases, including hypertension, obesity, cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease, and kidney stones.
These comorbid diseases will complicate the treatment of gout and increase the risk of premature death.
.
Gout attacks: early anti-inflammatory treatment.
For asymptomatic hyperuricemia patients, the prevention of gout should be considered, such as dietary adjustments and weight loss.
At present, it is not recommended to prevent gout through urate-lowering drugs or anti-inflammatory drugs.
Once an acute attack of gout occurs, anti-inflammatory treatment is recommended as soon as possible.
The focus of treatment is to control pain and suppress joint inflammation.
First-line treatments include oral corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), or colchicine.
The choice of specific drugs depends on the patient's personal factors, including comorbidities, concomitant medications, and the efficacy and side effects of previous medications.
Accompanied by kidney disease, heart disease, peptic ulcer disease or taking anticoagulant drugs, non-steroidal anti-inflammatory drugs should be avoided.
In cases of infection, fluid retention, or diabetes, high-dose oral prednisone should be avoided.
In patients with severe kidney disease, severe liver disease, and the simultaneous use of ABCB1 inhibitors and CYP3A4 inhibitors (such as cyclosporine, ketoconazole, clarithromycin, and verapamil), colchicine may be toxic.
In addition, clinical trials have shown that oral prednisolone, non-steroidal anti-inflammatory drugs (including non-selective or COX-2 selective drugs), and low-dose colchicine are equally effective in treating gout attacks.
However, oral corticosteroids may have better safety than non-steroidal anti-inflammatory drugs, and non-steroidal anti-inflammatory drugs have fewer side effects than low-dose colchicine.
A small dose of colchicine (1.
0-1.
2 mg immediately followed by 0.
5-0.
6 mg one hour later) is as effective as a high-dose colchicine (4.
8 mg taken within 6 hours), but with fewer side effects, so high doses are not recommended Colchicine.
For patients with gout attacks who cannot take oral medications, intra-articular, intramuscular, or intravenous corticosteroids are also an option.
IL-1 inhibitors are only used in patients who cannot tolerate or have contraindications to first-line anti-inflammatory therapy.
Non-drug therapy (such as ice compress) has a certain analgesic effect.
Supportive therapy includes rest, mobility assistance, and adequate nutrition and hydration.
At the same time, all patients with gout attacks need to understand long-term effective urate-lowering therapy to prevent recurrence and joint damage.
Gout requires long-term continuous treatment to reduce and maintain the level of uric acid to reach the standard.
The main strategy for long-term gout management is to achieve standard treatment of serum urate.
Continuously reduce urate through treatment to dissolve urate crystals.
Clinical trials have shown that, in the long run, this treatment strategy can reduce gout attacks, subside tophi and prevent joint damage.
For most patients with gout, the target serum urate level should be less than 360 µmol/L.
For those with a high uric acid load (for example, tophi has occurred), the target serum uric acid level should be more stringent, ≤300 µmol/L.
Image source: Under what circumstances should 123RF lower uric acid? Urate-lowering therapy is usually recommended for the following patients: appearance of tophi, imaging evidence of joint damage caused by gout, frequent attacks of gout (≥2 times within a year) and urinary tract stones; high serum uric acid concentration (> 480 µmol/L) ) Or young patients (<40 years old) with comorbid diseases (kidney or heart disease).
Uric acid-lowering therapy can be initiated during a gout attack, and the dose should be adjusted gradually from a low dose.
During this period, low-dose anti-inflammatory drugs can also be used to prevent gout attacks (such as 250 mg naproxen per day or 0.
6 mg colchicine per day for 3-6 months).
Uric acid-lowering drug choice For most gout patients, allopurinol is the first-line uric acid-lowering therapy.
Most patients with gout can achieve serum urate levels by monotherapy with allopurinol.
Allopurinol is generally well tolerated, with a rash in 1%-2% of patients and the need to stop treatment.
Carriers of the HLA-B*5801 gene (some Asians and African Americans) are prone to allopurinol hypersensitivity syndrome, which can be avoided by screening the gene in advance.
Febuxostat is recommended as a second-line uric acid-lowering therapy.
The effect of febuxostat on cardiovascular risk has not yet reached a consistent conclusion in different large-scale trials.
For patients who do not respond well to or intolerance to allopurinol treatment, doctors can recommend febuxostat and pay attention to the patient’s heart.
Vascular risk.
In addition, urological drugs such as probenecid and benzbromarone can promote the excretion of urate, and can also be used as a monotherapy or in combination with allopurinol.
But the potential side effect is the risk of urinary stones.
Pegloticase can metabolize urate, and clinical trials have shown that it can improve symptoms such as gout attacks and tophi.
Long-term management of gout: It is also very important to focus on the management of comorbidities and dietary comorbid diseases, such as body mass index, blood pressure, creatinine, and glycosylated hemoglobin.
Some other therapeutic drugs for comorbid diseases, such as the antihypertensive drug Losartan, and the SGLT-2 inhibitor antidiabetic drug fenofibrate, also have certain characteristics of lowering urate.
Dietary adjustments through the DASH diet and weight loss can help achieve a moderate reduction in serum uric acid levels.
DASH diet: advocate low fat, low salt, low sugar, and provide balanced nutrition.
Use refined meat, poultry, and fish as the main protein sources, and a balanced intake of fruits and vegetables, dairy products, grains, soy products, nuts, a small amount of fat and sweets; at the same time reduce the intake of salt and saturated fat, such as drinking low-fat milk , Do not eat or eat less fat.
At the same time, sugary drinks and excessive alcohol (especially purine-rich beer) should be avoided.
Purine-rich foods such as red meat and seafood can also increase the concentration of serum urate and the risk of gout.
Patients can pay attention to identifying specific foods that trigger gout attacks, and avoiding these dietary triggers may help.
However, most patients with gout cannot achieve the standard of serum uric acid only by diet management.
Summary Gout is common but treatable.
In particular, long-term lowering of urate through allopurinol and other drugs can prevent gout and improve the quality of life of patients.
By standardizing the initiation and durability of uric acid-lowering therapy, high-quality gout management can help improve patient prognosis.
