Gout is a group of diseases caused by disorders of purine metabolism and/or decreased uric acid excretion. Clinical features are hyperuricemia, recurrent acute monoarthritis, gouty stone deposits formed by sodium urate, and gouty chronic arthritis, which usually eventually progresses to gouty nephropathy if not properly treated.
Hyperuricemia is the heaviest biochemical basis of gout, but is not synonymous with gout. Caiyue Bian, Department of Rheumatology and Immunology, Xinxiang Central Hospital, Henan Province, China
Primary gout occurs 90% of the time in middle-aged men, especially in those aged 40-50 who are fat. The ratio of male to female is about 9:1, and the incidence of postmenopausal women is slightly higher than that of premenopausal women. The incidence is rare in children and the elderly, and is mostly secondary.
I. Etiology and classification of hyperuricemia
1. Increased endogenous biosynthesis
Increased exogenous intake Excessive intake of purine-rich foods such as sardines, clams, crabs, animal offal, etc., and heavy alcohol consumption can increase uric acid synthesis.
3. Decreased renal excretion or increased reabsorption Renal lesions, acidosis and the use of acidic drugs can decrease the excretion of uric acid from the kidneys; dehydration, uremia or the use of diuretics can increase the reabsorption of uric acid from the proximal tubules.
All these factors can cause an increase in blood uric acid level. In addition, estrogen has the effect of promoting the excretion of uric acid by the kidneys, which is related to the increase of uric acid in women after menopause.
2. Promoting factors of gout
1. Blood uric acid concentration A sudden increase in blood uric acid level can cause crystallization of supersaturated uric acid in tissue fluid and synovial fluid; and when blood uric acid value suddenly decreases, it can lead to dissolution of gout stones on the joint surface, and crystallization can also be precipitated.
2. Urine pH Uric acid crystals are easily deposited in the kidneys and even form stones, which are influenced by urine pH in addition to the kidneys being the channel of excretion. When urine pH is low, the solubility of uric acid decreases, and both simple uric acid crystals and monohydrate sodium urate crystals can precipitate, causing uric acid nephropathy. The higher concentration of medullary sodium makes it more likely to be deposited. 3.
3. temperature The solubility of uric acid decreases with lower temperature. The higher deposition of uric acid crystals in the terminal joints of the limbs and the earwires, as well as the tendency of gout symptoms to flare up in the cold and at night, are presumed to be related to the decrease in temperature.
The gout occurs in 75% of the metatarsophalangeal joints of the [toes], which is associated with repeated abrasion and trauma.
Clinical manifestations
Clinical manifestations of gout can be seen in four categories: ① asymptomatic hyperuricemia; ② acute gouty arthritis; ③ chronic gouty arthritis and gouty stone formation; ④ gouty nephropathy. Patients may present with one of these categories, or several of them may be present simultaneously or sequentially.
Acute gouty arthritis 80% of patients have precipitating factors, such as: eating too much purine-rich food, drinking a lot of alcohol, excessive fatigue, localized joint injury, cold stimulation, application of diuretics, receiving chemotherapy, etc. In nearly 2/3 of patients, the first metatarsophalangeal joint is involved, with acute localized redness, swelling, heat, pain, and limitation of motion. This is followed by the tarsometatarsal joints, ankle and heel. Finger, wrist and elbow joints are uncommonly involved. The distribution of joints is asymmetrical, with more lower extremities than upper extremities, and involvement of the medial joints is rare. The onset of symptoms is usually at midnight, with a rapid onset and progression, and the pain peaks within a few hours. Patients often have difficulty sleeping because of the severe pain, tossing and turning, and cannot even tolerate the shaking of the sheets or the surrounding area. Some patients may have systemic symptoms, such as fever, headache and general discomfort. Physical examination may reveal localized swelling, redness, high skin temperature and restricted movement of the joint.
Acute arthritis lasts for a few days to a few weeks and often resolves on its own, but most patients have intermittent reoccurrences, which are gradually more frequent and increase the number of joints involved, becoming chronic arthropathy, but the interval between attacks can be several years.
(C) Chronic gouty arthritis and gouty stone formation With the increased deposition of uric acid in the joint cavity and surrounding tissues, recurrent episodes of arthritis, local fibrous tissue hyperplasia, and gouty stone formation. The disease gradually develops, eventually causing stiffness and deformity of the joints and functional impairment. The progression from acute gout to chronic gout takes about 10 years or more. Factors associated with the formation of gout stones include: long-lasting and severe elevated blood uric acid, early onset of gout, long-term active but untreated gout, and a tendency for upper extremity and multi-joint involvement. In this case, there is persistent discomfort and swelling in the involved joints, but the intensity of symptoms is significantly reduced.
Bone and joint imaging of gout The X-ray examination of gout is characteristic. Early acute attacks show only soft tissue swelling, and after repeated attacks become chronic, local joint surfaces are seen to be unsmooth, with chisel-like or worm-like defects in the subchondral bone and bone marrow with clear borders. In gout, the bony erosion is slightly distant from the joint, whereas in rheumatoid arthritis, the erosion is proximal to the joint surface, with a raised and prominent border visible under the edge of the area of destruction, which may have hyperplastic calcification. Characteristically, gout has a “prominent rim” caused by both atrophy and hypertrophy. The joint space only narrows in advanced stages.
Diagnosis
The diagnosis is based on the presence of typical acute monoarticular inflammation, elevated blood uric acid, uric acid crystals in the joint fluid or synovial membrane, and effective treatment with colchicine in middle-aged and elderly men, combined with radiographic changes.
In 1977, the American Rheumatism Association proposed its classification criteria as follows.
1. specific urate crystals are examined in the synovial fluid; or
2. Gout stones with sodium urate crystals confirmed by chemical methods or polarized light microscopy; or
3. with 6 of the following 12 clinical, laboratory and X-ray signs.
(1) More than 1 episode of acute arthritis.
(2) Inflammatory manifestations peaking within 1 day.
(3) Single episode of arthritis.
(4) Dark red color of the skin of the affected joint.
(5) Pain or swelling of the first metatarsophalangeal joint.
(6) Unilateral attacks involving the first metatarsophalangeal joint.
(7) Unilateral attacks involving the tarsal joint.
(8) Suspected gout stones.
(9) Hyperuricemia.
(10) X-rays show asymmetric swelling of the joint.
(11) Radiographs show subcortical cysts without bone erosion.
(12) Negative microbiological culture of joint fluid during the inflammatory episode of the joint.
V. Treatment
(a) Dietary control Strictly restrict the intake of high purine food, but since uric acid is mainly synthesized endogenously in the body, the problem of high uric acid cannot be solved fundamentally. These patients often have hyperlipidemia, hypertension, diabetes and obesity. It is still necessary to appropriately limit the intake of high purine and high calorie foods, such as avoiding animal offal, sardines, oysters, crabs and clams. Strict abstinence from alcohol is required to prevent acute attacks. Advocate drinking more water to keep the daily urine volume above 2000ml.
(B) Avoid attack triggers Exertion, mental stress, dampness and cold, trauma, etc. should be avoided. Drugs that inhibit uric acid excretion, such as diuretics, aspirin, etc., should not be used.
(C) Drug treatment
1. Acute phase The purpose of treatment is to rapidly control the symptoms of acute arthritis and actively remove the triggering factors. Patients should rest in bed and elevate the affected limbs.
(1) Colchicine is the drug of choice in the acute phase and should be used as early as possible. The first dose should be 0.5-1.Omg, followed by 0.5mg every hour until one of the following three criteria is met: (1) significant improvement in pain and inflammation; (2) severe gastrointestinal reactions such as diarrhea; (3) a total of 6.0mg of colchicine in 24 hours with normal renal and hepatic function, after which the dose is changed to 0.5mg once to three times daily. Most patients’ symptoms are relieved within 24-48 hours of taking the drug. Patients with gastrointestinal bleeding or ulcer disease can be administered intravenously by slowly pushing 2mg of colchicine into 20ml of saline, with the total amount not exceeding 4mg for repeated injections. common side effects include gastrointestinal reactions, leukopenia, bone marrow suppression, and abnormal liver function.
(2) Non-steroidal anti-inflammatory drugs For colchicine treatment is contraindicated, ineffective or intolerable, or for gout that has been attacked for several days, these drugs can be used. For example, 25~75mg of anti-inflammatory pain, once every 6~8 hours, not more than 200mg per day, after the symptoms are reduced, 25mg per day, 3~4 times for 2~3 days, then gradually reduce the dose. Fotalin 25~50mg 2~3 times daily. The side effects should be noted in patients with renal insufficiency.
(3) Adrenal glucocorticoids or ACTH can be used for a short period of time when the above drugs are not effective or cannot be tolerated or when there are severe recurrent attacks. Prednisone lOmg three times a day; or hydrocortisone succinate 200-300mg intravenous drip once a day is commonly used. It is also recommended to use ACTH 25mg in glucose intravenously or 40~80mg intramuscularly.
2. Chronic phase The main treatment in this period is to lower the blood uric acid value to maintain it in the normal range. There are two types of drugs to promote uric acid excretion and inhibit uric acid production, which can be used alone or in combination. To prevent acute attacks caused by a sudden drop in uric acid levels, colchicine or non-steroidal anti-inflammatory drugs should be added at the beginning.
(1) Uric acid-removing drugs Mainly inhibit the reabsorption of uric acid in the proximal renal tubules and promote its excretion. In order to avoid the sudden passage of large amounts of uric acid through the kidneys and to prevent acute attacks of gout, these drugs should be started in small doses and gradually increased. Commonly used ①Probenzenesulfonamide (probe- necid): start at 0.25 twice daily, increase to 0.5 three times daily after 2 weeks, not more than 2 g/d. Contraindicated in patients with allergy to sulfonamides. Side effects include gastrointestinal reactions, rash, fever, etc. ②Benzenesulfonazolone (sulfinpyrozone): Start at 50mg twice daily, gradually increase to lOOmg three times daily, the maximum daily dose is 600mg, synergistic with probenecid. This drug has less side effects than probenecid. (3) Benzbromarone: such as gout lixian (narcaricin): strong effect of uric acid excretion, the initial dose of 25mg, once a day, gradually increased to lOOmg per day. light toxicity, no effect on liver and kidney function, gastrointestinal reactions, gout acute attack, renal colic, rash, fever and other side effects.
(2) Inhibition of uric acid production Currently, only allopurinol is widely used, which inhibits the activity of xanthine oxidase by competing with hypoxanthine to reduce uric acid synthesis. It is suitable for those who have uric acid excretion of more than 600mg in 24 hours, or those who have uric acid nephropathy, or those who cannot take uric acid excreting drugs. It is also commonly used before radiotherapy or chemotherapy. The initial dose is 50mg, 2-3 times daily, and then it is increased by lOOmg per week to 200-600mg per day, divided into 2-3 oral doses. A few patients showed drug rash, gastrointestinal reactions, leukopenia, bone marrow suppression, xanthine stones, liver damage, etc.
3. Intermittent period Drink more water and take alkaline drugs to avoid acidic urine. 1g of sodium bicarbonate is commonly used 3 to 4 times a day, especially important for those with renal changes. To keep the blood uric acid within the normal range, take uric acid-removing drugs or drugs to inhibit uric acid production. Colchicine 0.5mg, 1 to 3 times daily, is needed prophylactically for frequent attacks.
4. Asymptomatic hyperuricemia If uric acid >535.5μmol/L (9mg/dl), or uric acid >1100 mg/24h, or if there is a family history of gout, allopurinol can be given as treatment.