I. What is hyperuricemia and gout?
Hyperuricemia refers to an abnormally high level of uric acid in the blood. When the concentration of uric acid (salt) in the blood is too high, it can precipitate and form crystals in joints, soft tissues, cartilage and kidneys, causing pain and dysfunction, which is called gout.
The clinical characteristics of gout are hyperuricemia, recurrent episodes of characteristic acute arthritis, sodium urate crystals in the synovial fluid, and gout stone formation. In severe cases, it can lead to joint mobility disorders and deformities, urinary stones and gouty nephropathy. Gout or hyperuricemia is clinically classified as primary or secondary depending on the cause. Primary gout is caused by enzyme defects in about 1% to 2%, and most of the causes have not been elucidated; secondary gout can be caused by kidney disease, blood disease and drugs.
At present, the incidence of hyperuricemia in some areas of China has reached 13.3%, and the age of onset is mostly seen in men over 40 years old, while female patients usually develop the disease after menopause, and the incidence increases with age.
Second, what are the triggers of hyperuricemia and gout attack?
Triggers include poor dietary habits (e.g. alcohol abuse, eating a high purine diet, etc.), family history, obesity, drug triggers (e.g. taking thiazide diuretics, vitamin B1, insulin, penicillin and cyclosporine, etc.), trauma and surgery, radiation therapy, acute infections, and mental stress.
Hyperuricemia is often associated with a variety of diseases, such as hyperlipidemia, hypertension, coronary heart disease, cerebral infarction, diabetes mellitus, obesity and fatty liver, called metabolic syndrome.
What is gout stone?
Gout stone is a chronic foreign body-like reaction caused by the precipitation of uric acid crystals, and sodium urate can be deposited in any part or tissue. The most common sites of deposition are in and around joints, such as cartilage, bone, synovium, joint capsule and subcutaneous tissue. Typically, gout stones occur around the olecranon, opposite olecranon, and first metatarsophalangeal joint. They can affect any joint, mainly the distal joints of the lower extremities, the peripatellar joint, the infrapatellar bursa, and often form a tubercular or cystic shape along the ulnar surface of the forearm in the hawk’s-eye region, or expand in a pike or tuberculocystic shape toward the heel bone. Occasionally, it may develop subcutaneously along the surface of the tibia.
IV. Does asymptomatic hyperuricemia require treatment?
When blood uric acid is higher than 535mmol/L (9mg/dl), urate crystals will form and precipitate in the tissues and joint cavities causing gout. However, the majority of patients with hyperuricemia do not develop gout throughout their lives, and only 5-12% of patients can develop gout. Uric acid crystals can precipitate in the renal pelvis, ureter or in the renal tubules and interstitium, forming kidney stones and causing kidney damage.
It is generally believed that when the blood uric acid level is lower than 8-9mg/dl, no drug treatment is needed, but obesity, high purine and high calorie diet, alcoholism, overwork, trauma, cold and wet and mental stress should be avoided as triggering factors. If the blood uric acid level is too high, medication to reduce uric acid should be used. For those who have complications or concomitant diseases such as hypertension, coronary heart disease, obesity, urinary tract infection, renal failure, etc., timely symptomatic treatment should be given according to the etiology.
If there are the following conditions.
1. those with a family history of gout, uric acid kidney stones and reduced urinary output
2. those with blood uric acid higher than 535 mmol/L (9.0 mg/dl) after removal of the causative factor
3, those with uric acid excretion >5.948mmol (1000mg) per 24 hours
4, those with uric acid kidney stones or acute uric acid nephropathy
5, those with clinical symptoms of gout.
6, for those with hypertension, coronary artery disease, diabetes mellitus. All the above cases should be given treatment, and patients should have regular checkups or consider treatment with uric acid-lowering drugs.
V. How should gout patients control their diet?
In general, patients with acute gouty arthritis should strictly limit the intake of purine in the diet, choosing foods with low purine content and avoiding high purine foods as much as possible. However, recent studies have shown that even a strict diet restriction can only reduce blood uric acid levels by 15%. Improving the body’s sensitivity to insulin is beneficial to the excretion of uric acid, and weight reduction and low protein diet can help increase the body’s sensitivity to insulin.
The diet of gout patients should be controlled at about 80% to 90% of the normal diet. By limiting carbohydrates and increasing protein and unsaturated fatty acids in the diet, the body weight can be reduced and the sensitivity of insulin can be increased, thus facilitating the excretion of uric acid. Protein intake should be mainly vegetable protein, animal protein can be used milk, eggs, etc. Vitamin C has a significant pro-uric acid excretion effect and has a competitive inhibition of uric acid reabsorption effect.
Vegetables and fruits are mostly alkaline foods, which can increase the body’s alkaline reserves and raise the pH of body fluids. When the pH of joint fluid rises above 6, uric acid is mostly free and rarely forms urate crystals. The increase of urine pH can prevent the formation of uric acid crystals and promote their dissolution, increase the amount of uric acid excretion, prevent the formation of stones or dissolve the formed stones. Moreover, vegetables and fruits are mostly rich in potassium, which can promote the excretion of uric acid from the kidneys and reduce urine salt deposition.
Patients should ensure that the fluid intake is maintained at more than 2000 ml per day to keep the daily urine volume at 2000-3000 ml to promote the excretion of uric acid.
The main component of alcohol is ethanol, and large intake can lead to the aggregation of lactic acid and ketone bodies in the body, thus inhibiting the excretion of uric acid; ethanol can also promote the conversion of adenine nucleotides, which increases the synthesis of uric acid, causing a significant increase in blood uric acid and inducing acute gouty arthritis. The correlation between alcohol consumption and high uric acid as well as the development of gout is well established, with blood uric acid values being positively correlated with total alcohol intake, with a 1.17-fold increase in the risk of gout for every 10 grams of increased daily alcohol intake, with beer having the most significant correlation. However, wine was not significantly associated with high uric acid and did not increase the risk of gout. Studies have also shown that daily wine consumption can keep uric acid levels low.
Milk, especially low-fat milk, can lower blood uric acid. The mechanism may be that the casein and whey proteins in milk increase the excretion of uric acid and thus lower blood uric acid. Therefore, low-fat milk has a protective effect against gout. However, yogurt contains more lactic acid, which competes with uric acid for excretion and is not good for gout patients, so it should not be consumed.
How to treat the acute stage of gouty arthritis?
The purpose of treatment is to quickly control the symptoms of acute arthritis and remove the triggering factors. The acute phase should be treated as early as possible to bring about rapid relief of symptoms and to prevent prolongation. Patients should rest in bed to relieve pain caused by exercise, elevate the affected limb to improve blood circulation in the limb and promote recovery from inflammation, and resume activities only after 72 hours of pain relief. The following drugs are available for the treatment of gouty arthritis.
1, non-steroidal anti-inflammatory drugs: acute gouty arthritis should be given immediately after the diagnosis of anti-inflammatory and analgesic treatment, drugs including non-steroidal anti-inflammatory drugs, colchicine, analgesics and glucocorticoids, while the affected joints should be cold compresses and avoid activities. The above treatment process usually lasts about 1~2 weeks. In terms of drug selection, NSAIDs should be preferred because of their fast onset of action and low side effects, while patients with peptic ulcer and bleeding risk are recommended to be given COX2 selective inhibitors, but patients with combined ischemic heart disease should use COX2 selective inhibitors with caution.
Colchicine is an effective drug for the treatment of acute gouty arthritis, but the onset of action is slower than NSAIDs, and there are serious side effects such as diarrhea and bone marrow suppression, which are more prominent in elderly patients. It is recommended that colchicine be given at 0.5 mg/dose, 2-4 times a day, and patients should be closely observed for side effects.
3. Glucocorticoids can be used for patients with acute gouty arthritis who cannot tolerate colchicine or NSAIDs, as well as for patients with poor efficacy of the above drugs, and intra-articular injection can be used for acute monoarthritis with large joint involvement. For patients with small or multiple joint involvement, glucocorticoids can be administered orally, intramuscularly or intravenously.
4. Patients in the acute phase are generally not advocated to use uric acid-lowering drugs such as allopurinol to avoid aggravating arthritis symptoms and prolonging gouty arthritis attacks. However, patients who have applied allopurinol before the onset of arthritis can continue to use it during the acute attack. Opioid analgesics can be used in patients with acute attacks where conventional treatment is not effective, to supplement other drugs to relieve the patient’s pain.
How to treat intermittent and chronic gouty arthritis?
1. The number of attacks can be reduced in some patients by changing bad habits and stopping the use of drugs that can cause hyperuricemia. Patients with gout stones, patients with combined renal insufficiency, patients with uric acid stones, patients with recurrent gout attacks, and patients who must continue to use diuretics should be given uric acid-lowering drugs. For patients without comorbidities, if arthritis flares up again within 1 year, uric acid-lowering drugs may be given. Uric acid-lowering drugs are usually started after 1~2 weeks of acute inflammation control, and blood uric acid should be maintained at ≤ 360μmol /L.
2. Regarding the choice of uric acid-lowering drugs, it is generally believed that allopurinol therapy is preferred for patients without comorbidities. The starting dose of this drug should be low (e.g., 50-100 mg/day) and can be increased by 50-100 mg every 2-4 weeks until the blood uric acid is reduced to the desired level. Benzbromarone can be used in patients with gout who have mild to moderate renal insufficiency, patients with impaired uric acid excretion, patients who cannot tolerate allopurinol or patients with poor efficacy of allopurinol.
3.For patients with hypertension and hyperlipidemia, cloxacin and fenofibrate should be considered respectively, the above drugs have the effect of lowering blood uric acid at the same time.
4.Small dose aspirin (75-150mg/day) used to prevent and control cardiovascular diseases does not affect blood uric acid level, while high dose aspirin (600-2400mg/day) used for analgesia inhibits uric acid excretion, therefore, it should be avoided for gout patients.
5. New uric acid-lowering drugs such as febuxostat have started to be used clinically and have achieved good efficacy. In view of the low side effects of this drug, it is likely to become an ideal choice for the treatment of hyperuricemia.