Tophi Gout: Causes, Symptoms, Treatments, Preventions

Tophi gout is a disease in which urate crystals produced by uric acid concentration in the blood increase in the tissues such as cartilage and tendons in joints. Settled crystals cause inflammation of the joints and are accompanied by excruciating pain.

Tophi gout is a relatively common disease with a prevalence of about 1% in Western society. The incidence of gout varies from 0.20 to 0.35 per 1,000 population, and the overall prevalence ranges from 1.6 to 13.6 per 1,000, depending on the population. The prevalence increases with age and with higher serum uric acid levels.

Hyperuricemia refers to an increase in blood uric acid concentration of 7.0 mg/dL or more. The level of uric acid in the blood varies with age and gender. The normal level for adults is 3-6 m/dL for men and 2-5 mg/dL for women. Children have a high rate of uric acid excretion from the kidneys, so they normally maintain uric acid levels of 3-4 mg/dL. After puberty, it is 1-2 mg/dL higher in men than in women. In women, hyperuricemia rarely occurs before menopause because the ability to remove uric acid is maintained under the influence of female hormones.


As the last metabolite of purine, uric acid is synthesized in the liver and small intestine, which has an enzyme called xantine oxidase, and exists as monosodium urate, an ionized form in plasma, body fluids, and joint fluids. Two-thirds to three-quarters of these urates are excreted through the kidneys and the rest is excreted through the intestines. Thus, hyperuricemia occurs when the production of serum uric acid increases, uric acid excretion decreases, or both mechanisms exist together.

1. Excess production of uric acid

Excessive production of uric acid is caused by dysfunction of enzymes involved in the metabolism of purine, hemolytic disease, lymphoproliferative disease, myeloproliferative disease, erythropoiesis, psoriasis, Paget’s disease, rhabdomyolysis, excessive exercise, excessive drinking, obesity, and excessive purine intake. Can occur.

2. Decreased excretion of uric acid

The production of uric acid is normal, but uric acid excretion is reduced. In some cases, kidney dysfunction, diabetes insipidus, hypertension, polycystic kidney disease, acidemia, ketonemia, starvation, sarcoidosis, lead poisoning, hyperparathyroidism, hypothyroidism, pregnancy And addiction. Low-dose aspirin, diuretics, alcohol, and ethambutol, an anti-tuberculosis drug. It can also occur if you are taking drugs such as pyrazinamide.

3. Reduced uric acid excretion and overproduction of uric acid

Both mechanisms of uric acid overproduction and reduced excretion can cause hyperuricemia, such as alcohol and shock.


γ€ˆ4 stages of the natural process of tophi gout〉

  1. Asymptomatic hyperuricemia
  2. Acute gouty arthritis
  3. Intermittent gout
  4. Chronic tophi gout

1. Asymptomatic hyperuricemia

Asymptomatic hyperuricemia is a condition in which the uric acid concentration in the blood is increased, but the symptoms of gout have not yet been observed. 95% of patients with asymptomatic hyperuricemia are asymptomatic for almost life. However, even hyperuricemia without symptoms may accompany hyperlipidemia, high blood pressure, and arteriosclerosis, so careful observation is required.

2. Acute gouty arthritis

Acute gout tends to develop when uric acid levels in the blood increase rapidly. It usually first occurs between the 30s and 50s. If you develop an onset before age 30, you should consider the possibility of an enzyme disorder related to purine metabolism with an atypical form of gout. In 85-90%, it occurs in one joint and the first toe is the most common. However, it can also occur on the back, ankles, heels, knees, wrists, fingers, and elbows.

The first seizure of most acute gouts occurs suddenly and usually begins at night when the patient is asleep in comfort. The affected joint within a few hours becomes hot, red, swollen, and very painful. The course of untreated acute gout varies widely. Mild seizures go away within a few hours or last one to two days, while severe seizures last from days to weeks.

3. Intermittent gout

Intermittent gout is the asymptomatic period between acute gout attacks. Most often, a second seizure occurs between 6 months and 2 years. It occurs between 60% and 80% within 2 years, and some may not have a second seizure. The frequency of gout seizures increases over time in untreated patients. Later, seizures appear slowly rather than acutely, invade several passes, and tend to be more severe and lasting.

Diagnosis of gout may be difficult if an acute attack of one arthritis improves in people with hyperuricemia and is in the intermittent stage. Even in the case of these intermittent gout patients, urate crystals can be found in the joint fluid in 12-58%, so even in the asymptomatic period by puncturing the joint to prove uric acid crystals, it can be diagnosed as gout.

4. Chronic tophi gout

If not treated consistently, gout progresses to a chronic tophi gout through a painless intermittent period. Chronic tophi gout can be easily confused with other types of arthritis. The time to first gout attack and chronic tophi gout in untreated patients varies widely (years to decades), and the average duration is known to be over 10 years.

The most important factor in the formation of gout tophi and the progression to chronic tophi gout is the severity and duration of hyperuricemia, especially serum uric acid levels. Another important cause of uric acid tophi formation is related to the severity of kidney disease. However, as treatments for hyperuricemia are developed, the incidence of tophi is decreasing.

Chronic tophi gout is caused by the accumulation of uric acid in the body because it is not excreted as long as it produces uric acid chronically. Deposits of uric acid crystals appear in various areas such as cartilage, synovium, ligaments, and soft tissues. Tophi is commonly found in the auricle, and in addition, it forms irregular, asymmetric, and bumpy lumps on the fingers, hands, knees, and feet, making it impossible to wear gloves or shoes. The deposition process of gout tophi proceeds slowly, and although the tophi itself is relatively less painful, it may cause progressive stiffness and persistent pain in the affected joint.

Eventually, extensive damage to the joints and large tophis under the skin can cause deformities and progressive disability. The swollen, thinner skin that covers the tophi can ulcer and cause infection by releasing a white, chalky or toothpaste-like substance composed of tiny needle-shaped crystals.

5. Tophi gout related diseases

Gout patients are twice as likely to have metabolic syndrome compared to the general population, and it is known that more than 70% of those with uric acid levels of 10 mg/dL or more have metabolic syndrome.

1) Obesity

Blood uric acid levels and body weight are closely related.

2) Hyperlipidemia (hypertriglyceridemia)

About 80% of gout patients are high in triglycerides.

3) High blood pressure

High blood pressure is present in 25 to 50% of gout patients.

4) Kidney disease

(1) Urolithiasis

The risk of urolithiasis is associated with a sharp increase in serum uric acid levels and an increase in uric acid excretion. In other words, high serum uric acid and high uric acid excretion also increase the prevalence of urolithiasis. About 80% of urinary tract stones in gout patients are uric acid stones.

(2) Urate nephropathy

Uric acid nephropathy is a disease in which urate crystals accumulate in the kidney’s stroma, causing a chronic inflammatory reaction. Eventually, it causes chronic kidney failure. In this case, there are often no symptoms, proteinuria occurs in the urine, and high blood pressure and renal dysfunction gradually occur.

(3) Acute renal failure due to uric acid accumulation

When a large amount of uric acid is produced suddenly, a large amount of uric acid can deposit in the kidneys, blocking the urinary tract, leading to acute kidney failure.


1. History taking

The overall contents such as the time and site of symptom onset, severity and duration, past medical history, various medications, and deteriorating factors are checked. If it is difficult to collect joint fluid, there is no way to confirm it, but if three things are satisfied: acute arthritis of a single site, hyperuricemia, and a dramatic response to colchicine treatment, gout can be clinically suspected.

2. Physical examination

Most acute gout arthritis causes sudden pain in a single joint area, such as the big toe, and the affected joint turns red and is accompanied by severe tenderness. It occurs over hours and can be accompanied by fever. Over several days, the inflammation can improve on its own, and the skin at the inflamed area begins to fall off. In case of chronic gout, uric acid tophi is observed in certain areas.

3. Blood test

1) Uric acid in the blood

Hyperuricemia is not enough to diagnose gout. Even without hyperuricemia, it can lead to joint symptoms. However, hyperuricemia is the most commonly observed blood abnormality, which is an important test finding to diagnose gout and predict future gout seizures.

2) Other blood tests

During acute gout, neutrophils are increased, accompanied by an increase in erythrocyte sedimentation rate and C-reactive protein related to inflammation. Chronic gout may be accompanied by anemia associated with a persistent inflammatory response. There are many abnormalities in plasma lipids, especially hypertriglyceridemia.

4. Joint fluid collection and polarization microscope inspection

Gout can be confirmed by puncturing a joint or soft tissue to prove a needle-like characteristic form of uric acid crystals in the joint fluid or tissue. The crystal is observed with a polarizing microscope and negative double refraction can be seen. If you do not have a polarizing microscope, observations of an optical microscope can help to some extent.

5. Radiation examination

In acute gout, swelling of the soft tissue is characteristic, and in chronic gout, a characteristic radiographic change may result in osteo erosion around the tophi with clear boundaries and overhanging edges. These findings are difficult to distinguish from rheumatoid arthritis, but the presence of a thin overhanging edge can be attributed to gout. Recently, ultrasound or CT is in the spotlight as a very important radiographic examination method to diagnose gout.

6. Differential diagnosis

Diseases to be diagnosed differently from gout include calcium crystal arthritis (pseudo-gout), bacterial arthritis, soft tissueitis, arthritis with tophi erythema, trauma, recurrent rheumatism, reactive arthritis, psoriatic arthritis, and rheumatoid arthritis.


γ€ˆThe therapeutic purposes of tophi gout〉

  • Reduction of pain and inflammation in acute gout arthritis
  • Prevention of recurrence of acute gout
  • Prevents damage to organs by uric acid by reducing serum uric acid levels to an appropriate level
  • Integrated management of diseases associated with gout

1. Drug treatment of gout in acute phase

  • Acute gout seizures are more effective the sooner they are treated.
  • Treatment with a nonsteroidal anti-inflammatory drug, glucocorticoid, and colchicine, which is the most suitable for individual patients.
  • Changes in blood uric acid concentration lead to prolonged or worsening joint pain.

The three drugs used in the treatment of acute gouty arthritis are nonsteroidal anti-inflammatory drugs, glucocorticoids, and colchicine. Which drug is not more effective, the drug is selected according to the patient’s condition or concomitant disease, and the sooner you treat all of the drugs, the more effectively you can control the pain. Unless contraindicated, nonsteroidal anti-inflammatory drugs are generally recommended, and glucocorticoids or colchicine are recommended in cases of peptic ulcer, renal dysfunction, etc., where the use of nonsteroidal anti-inflammatory drugs is restricted. Limited narcotic pain relievers may also be used early in the outbreak.

During an acute attack, it is a rule not to administer a new drug for lowering uric acid in principle, and you must not stop taking drugs for lowering uric acid. This is because changing uric acid levels during inflammation can intensify the inflammation, leading to prolongation or worsening of joint pain.

1) Nonsteroidal anti-inflammatory drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs are the most commonly used drugs for the treatment of acute gout with a certain diagnosis and show similar effects regardless of the type. Depending on the symptoms, the maximum dose is initially administered, and after the symptoms of acute attack have completely disappeared, the dose is reduced to about half, and then stopped.

There is insufficient research on whether COX-2 (cyclooxygenase-2) selective inhibitors are effective in gout, but some studies suggest that they may be as effective as non-selective nonsteroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs should be used with caution in cases of renal impairment and gastrointestinal bleeding, and COX-2 selective inhibitors should be used with caution in case of cardiovascular disease.

2) Colchicine

It inhibits the activation and migration of inflammatory cells, and although it is a traditionally used drug, its serious side effects can occur when used in high doses. In addition, the use of nonsteroidal anti-inflammatory drugs is expected to have comparable effects, so colchicine can be used with limited use in the following two cases in acute gout seizures. First, if the diagnosis is uncertain, it can be helpful in differential diagnosis by administering colchicine to see the reaction. Second, it can be useful in cases where nonsteroidal anti-inflammatory drugs cannot be used.

Most of the acute seizures disappear within 24 hours when colchicine is administered at a sufficient dose. If administered within a few hours after the onset of pain, this response rate is 90%, but after 12 hours, the response rate drops to 70%. So, if there is no response after taking a sufficient amount of colchicine relatively early, it is necessary to confirm that the diagnosis is correct. In the case of poor kidney or liver function, the dose should be reduced, and the dose should be reduced even in mild acute gouty arthritis, elderly patients, and patients who have been using colchicine before.

3) Glucocorticoid

Steroids are useful in cases where nonsteroidal anti-inflammatory drugs or colchicine are not available, and can be administered jointly, orally, intravenously, and intramuscularly. Intra-articular steroid injections can be used for 1 to 2 joints or for joints with insufficient response to oral medications for multiple gout arthritis. However, steroids have the disadvantage that they cannot be used if they are accompanied by infectious arthritis, or if high blood sugar is severe or uncontrolled.

2. Treatment of chronic gout

  • Correction of causative factors of hyperuricemia with proper diet
  • Uric acid lowering drugs are taken regularly and permanently
  • Prophylactic use of small amounts of colchicine between acute gout attacks

1) Use of uric acid lowering agents

γ€ˆConditions requiring long-term uric acid lowering drugs〉
  • Recurrent gout seizures (2 or more)
  • Uric acid stones
  • Chronic tophi gout
  • Damage to bone and cartilage on radiographs
  • Accompanied by kidney complications such as urate nephropathy

There is some controversy over when uric acid-lowering drugs will be administered as a treatment for gout, but it is recommended to administer uric acid-lowering drugs when you have two or more acute gout attacks. This means that the probability of having a second seizure after the first seizure is 62% within 1 year, 16% in 1-2 years, 11% in 2-5 years, 6% in 5-10 years, and recurrence for more than 10 years in 7%. This is because the probability of having a third seizure after the second seizure exceeds 90%. In general, it is appropriate to keep the uric acid concentration in the blood below 6 mg/dL, but if you have gouttophi, you may need to keep the lower concentration below 4-5 mg/dL for several years to expect the loss of tophi.

In uric acid lowering drugs, uric acid production inhibitors and uric acid excretion promoters are mainly used, and uric acid decomposing agents are being developed recently. In theory, allopurinol, an inhibitor of uric acid production, should be used in the uric acid overproduction group, and uric acid excretion promoter should be used in the low excretion group. In many cases, it is determined according to the side effects of drugs or diseases associated with individual patients. In particular, it is important to note that uric acid-lowering drugs of any type should be taken regularly and permanently.

(1) Uric acid production inhibitor

If renal function is normal and uric acid excretion is less than 800 mg per day, both uric acid excretion stimulators and production inhibitors have similar effects. Except for drug sensitization, allopurinol, an inhibitor of uric acid production, is generally preferred over uric acid excretion promoters in terms of efficacy and compliance. Allopurinol is an inhibitor of xanthine oxidase, which mediates purine metabolism. The half-life is relatively short, so it is about 40 minutes, but the active metabolite, oxypurinol, has a long half-life of 14-28 hours, so once a day is sufficient.

The initial dose of allopurinol starts with a single dose of 100-300 mg per day, but it is recommended to start with 50-100 mg in case of impaired renal function or elderly patients because it is metabolized to oxypurinol and excreted into the kidney. While testing the blood uric acid level, it can be gradually increased up to 600 mg over 2-4 weeks. After administration, the effect of lowering uric acid occurs within 4-14 days, and in most cases, normal blood uric acid concentration can be maintained at 300 mg per day. .

γ€ˆConditions to use allopurinol rather than uric acid excretion accelerators〉
  • There is a new absence in any form
  • Renal dysfunction
  • When urine volume is less than 1,400 mL/24h
  • If the patient is over 60 years of age
  • When uric acid excretion is normal
  • If there are side effects of uric acid excretion promoters

If uric acid excretion is normal or gouttophi is involved, allopurinol is recommended. About 20% of patients taking allopurinol experience side effects, including gastrointestinal disorders, myelosuppression, and skin rash, and allopurinol hypersensitivity syndrome is the most severe reaction. There is. In the case of allopurinol hypersensitivity, it is suggested that you can continue taking allopurinol by attempting a desensitization regimen that starts at 50 ΞΌg per day and increases by 2 times over 3 days and increases to 100 mg per day. You can try using oxypurinol instead, but care should be taken in this case, as about 40% of oxypurinol may also cause an allergic reaction.

Febuxostat, which has recently proven its effectiveness, is attracting attention as a new uric acid production inhibitor that can be used in patients with side effects of allopurinol. Since Febuksostat is mainly metabolized in the liver, it can be used without dose adjustment even in cases of renal dysfunction. Although side effects such as hepatotoxicity and diarrhea have been reported, it is relatively safer and more effective than allopurinol. However, there is a disadvantage that the price is high.

Uric acid oxidase (uricase) is an enzyme that works when uric acid is converted into water-soluble allantoin and excreted by the kidneys. Primates lack these enzymes, which can cause gout. In contrast to allopurinol, which blocks uric acid production, it is a drug that can be used to control hyperuricemia as it has the ability to break down uric acid that has already been produced.

(2) uric acid excretion accelerator

The uric acid excretion stimulator acts on the proximal tubule of the kidney and inhibits the reabsorption of uric acid after excretion, thereby promoting uric acid excretion into the urine. This drug can only be used under the age of 60, where it has been proven that the cause of elevated uric acid in the blood is lack of excretion and the kidneys are functioning normally and there are no kidney stones. When using this drug, uric acid crystals may be deposited in the renal tubules or uric acid stones may form, so it is necessary to intake sufficient fluids and maintain the amount of urine (more than 1.5 L/day). For the first few weeks when uric acid excretion is used or the dose is increased, the urine should be alkalized by taking sodium bicarbonate (0.5 g, 4 times a day).

Probenecid (0.5 g 1 to 3 times a day) and benzbromarone (50 mg 1 to 2 times a day) are mainly used, but also start with a low dose to reduce the occurrence of acute gout seizures and side effects. It must be gradually increased over the period. Benzbromarone is advantageous compared to probenecid in that it has few side effects and works even when renal function is bad, but caution should be exercised as it may have hepatotoxicity. In addition, fenofibrate, an ACE antagonist, used as a lipid-lowering agent, and losartan, an angiotensin II receptor antagonist, are known to promote uric acid excretion.

2) Colchicine prophylaxis

Most of the time colchicine is only known as a treatment for acute gout seizures, but since acute seizures can develop within the first few months of starting uric acid-lowering treatment, a low dose of colchicine can be used to prevent this. In general, if there are no symptoms of acute gout and uric acid is maintained at a normal level, it is used in combination with uric acid-lowering drugs for about 6 months and then stopped. In some cases, gout patients less than 10 years of age may maintain a low dose of colchicine for 1 year, as uric acid-lowering drugs for about 1 year will almost eliminate gout tophi in the body’s joints. In general, the first dose of colchicine is 0.6 mg twice a day and then reduced to once a day, and this preventive treatment for colchicine effectively prevents gout seizures in about 82-94%. Low doses of nonsteroidal anti-inflammatory drugs may be added or replaced if colchicine alone cannot prevent seizures or if colchicine cannot be used.

3. Treatment of comorbid diseases

People with gout or hyperuricemia are often accompanied by high blood pressure or hyperlipidemia. Diuretics, used to treat high blood pressure, are known to increase uric acid and are a common cause of gout. On the other hand, losartan or a calcium channel blocker, amlodipine, is known to have uric acid excretion effects, so it can be advantageously used for gout patients. And among the treatments for hyperlipidemia, there are drugs that have been reported to excrete uric acid. Therefore, if you are controlling hyperuricemia, it is necessary to consider these factors when choosing antihypertensive drugs or antihyperlipidemia drugs. In addition, drugs that inhibit uric acid excretion (cyclosporine, diuretics, ethambutol, pyrazinamide, low-dose aspirin) should be avoided in gout patients as much as possible.


1. Diets

With the development of several different uric acid lowering drugs, the importance of a strict diet is relatively diminishing. Because gout is a metabolic disorder, it can be affected by diet. Also, considering that gout is often associated with other metabolic syndromes, it is necessary to control your weight through proper diet or exercise. Therefore, it has traditionally been recommended to avoid foods high in purines and eat foods low in protein. However, this diet can only reduce the blood uric acid concentration of 1.0 mg/dL, and it is practically very difficult to continue this diet for a long time, and it is currently not recommended to gout patients.

On the other hand, a recent study reported that when a diet with moderately low calorie and increased protein content was administered, the average uric acid concentration decreased by 18% and the frequency of gout seizures decreased by 67% after 4 months. And in other studies, dairy intake has been reported to be associated with a reduced risk of gout by lowering uric acid.

In addition, many fructose in soda and corn syrup have attracted attention as the cause of more than doubling of gout over the past decades in the United States, and the link between hyperuricemia and insulin resistance has been known. So, the following is recommended to gout patients.

  • Diet to avoid overeating and lose weight
  • Lowering overall calories, reducing carbohydrate content, increasing protein content somewhat, and containing unsaturated fats.
  • Diet that is beneficial to diabetes (diabetic diet), hyperlipidemia (low fat), cardiovascular disease (low salt diet) as a concomitant disease

2. Sobriety

It is known that about half of gout patients drink too much. Alcohol reduces the excretion of uric acid from the kidneys, stimulates purine synthesis and increases uric acid synthesis, leading to hyperuricemia. If you drink an appropriate amount of beer regularly, the occurrence of gout increases in proportion to the amount you drink, but if you drink an appropriate amount of wine, it is known that the risk of gout is not high, and it is estimated that the risk of gout may differ depending on the type of alcohol. However, it is recommended that patients who have already developed gout should severely limit their intake of all types of alcohol.

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