Gout is a disorder of purine metabolism, mainly manifested as acute arthritis, gout stones, interstitial nephritis due to hyperuricemia and urate crystallization and deposition, and in severe cases, joint deformity and functional impairment. It is often accompanied by uric acid urinary tract stones. Its prevalence is gradually increasing with the change of lifestyle and the improvement of economic level.
Classification of gout
I. Primary gout
Primary gout is associated with genetic factors, and more and more studies have shown that primary gout is closely related to obesity, primary hypertension, dyslipidemia, diabetes, and insulin resistance.
Secondary gout
It is mainly caused by diseases such as kidney disease, blood disease, or drugs, high purine food, etc.
1.Enzyme and metabolic defects: myogenic hyperuricemia.
2, excessive cell destruction: hemolysis, burns, trauma, chemotherapy, radiotherapy, excessive exercise.
3, cell proliferation: leukemia, lymphoma, myeloma, erythrocytosis.
4, dietary factors: high purine diet, such as beans, seafood, beef and mutton, excessive alcohol consumption, etc.
5, reduced renal clearance: renal failure, ketoacidosis, gestational hypertensive syndrome, drugs, toxins.
6.Decreased amount of extracellular fluid : dehydration, uremia.
The pathogenesis of gout Gout should depend on the concentration of blood uric acid and its solubility in body fluids.
I. Mechanism of hyperuricemia
The balance of blood uric acid depends on the absorption and production versus breakdown and excretion of purines.
1. Absorption: 20% of uric acid in the body comes from the intake of purine-rich foods, and excessive intake can induce gout attacks, but is not the cause of hyperuricemia.
2, decomposition: uric acid is the end product of purine metabolism, about 1/3 of uric acid in normal people is processed by bacterial degradation in the intestine, about 2/3 is excreted by the renal prototype, humans lack uric acid enzymes, so uric acid decomposition is reduced as a mechanism of hyperuricemia has been excluded.
3.Production: 80% of uric acid in the body comes from purine biosynthesis in the body. In the process of purine metabolism, there are enzymes involved in the regulation of each link. Once the regulation of enzymes is abnormal, the increase or decrease of blood uric acid will occur. 0 4. Excretion: In primary gout, 80% to 90% of the direct mechanism of pathogenesis is a decrease in renal tubular clearance of urate, and the main link to increased blood uric acid is thought to be a decrease in renal tubular secretion, which also includes elevated reabsorption. Decreased uric acid excretion is often accompanied by increased production.
Second, the mechanism of gout
Uric acid is supersaturated in body fluids. The normal range of blood uric acid has a certain span, and generally the blood uric acid concentration leading to supersaturation is more than 7.0 mg/d1. There are some factors that also affect the solubility of uric acid, such as estrogen, temperature, H+ concentration, etc. can promote uric acid free. In hyperuricemia, even in combination with uric acid stones, it is not called gout. Gout occurs in only 10%-20% of cases of hyperuricemia.
The clinical features of gout are long-term history of hyperuricemia, mostly in middle-aged and elderly men with obesity and post-menopausal women, and 5% to 25% may have a family history of gout.
I. Acute arthritis
Acute arthritis is the first symptom of gout, which is an inflammatory reaction caused by urate crystallization and deposition.
The onset of the disease is rapid, typically starting at midnight, with severe pain and awakening. 90% of the joints are single, occasionally bilateral or multiple joints are involved at the same time or successively, showing redness, swelling, heat and pain, and there may be joint cavity fluid, but also with fever, leukocytosis and other systemic symptoms. The attacks are often self-limiting and resolve spontaneously within hours, days, or weeks, with local flaking and pruritus characteristic of the disease. The remission period can last for months, years or even a lifetime. However, most of the attacks are recurrent, even to the stage of chronic arthritis. In some patients, there is no remission period until the chronic arthritis stage. The pain is usually pronounced, but a few have mild symptoms. Alcohol consumption, high protein diet and foot sprain are important triggers, as well as wearing tight shoes, walking more often, cold, strain, infection and surgery are also common triggers.
Second, gout stone and chronic arthritis
Gout stone is a chronic foreign body-like reaction caused by the precipitation of fine needle-like crystals of monosodium urate, surrounded by mononuclear cells, epithelial cells, and giant cells forming foreign body nodules, causing a mild chronic inflammatory reaction. Gout stones can involve any part of the body except the central nervous system, most commonly in and near the joints and the otoconia. They appear as yellowish-white elevations of varying sizes, as small as sesame seeds or as large as eggs; they are soft at first and become hard as stones as fibers proliferate, which is characteristic of gout damage. The nodules are easy to wear and tear near the joints, and the nodule elevation makes the epidermis thin and easy to break down into fistulae, with white paste discharge, and the tissue around the fistulae is chronic granuloma that does not heal easily, but rarely secondary infection and poor recoverability. The damage to the subcutaneous tissue, synovial bursa, cartilage, bone, resulting in tissue fracture and fibrous degeneration, cartilage, bone destruction is the most significant, involving more joints, even to the spine, jaw and other joints, cartilage presents degenerative changes, formation of vascular opacities, bursal thickening, bone erosion defects and even fractures, coupled with the increase in gout stones, resulting in joint stiffness, breakdown, deformity.
Third, gouty nephropathy
The clinical manifestations are proteinuria, hematuria, isotonic urine, and then hypertension, azotemia and other renal insufficiency manifestations. Gout patients die from uremia in 17-25%, but it is rarely caused by gout alone and is often associated with a combination of factors such as advanced age, hypertension, atherosclerosis, renal calculi or infection.
Acute obstructive nephropathy, also known as hyperuricemic nephropathy, is mainly seen in patients with acute and marked increase in blood uric acid due to radiotherapy and chemotherapy, resulting in acute, massive and extensive uric acid crystalline obstruction of the renal tubules – acute renal failure. Pathological studies have confirmed that 90% to 100% of patients with gout have kidney damage.
IV. Uric acid urinary tract stones
Stones can appear during the hyperuricemic phase, accounting for 40% of hyperuricemia and 25% of gout patients. The vast majority of them are pure uric acid stones, characterized by non-visible X-rays, partly mixed with calcium oxalate and calcium phosphate, which can be visible on X-rays.
V. Gout and metabolic syndrome
Metabolic syndrome is often accompanied by gout, characterized by obesity, primary hypertension, hyperlipidemia, type 2 diabetes mellitus, hypercoagulability, hyperinsulinemia, accounting for the majority of obese middle-aged and elderly people, with a trend of younger onset in recent years.
Diagnosis
1, combined with family history, clinical manifestations of metabolic syndrome, middle-aged and elderly men, with onset triggers, sudden midnight arthritis attacks or the appearance of uric acid stones, and increased blood uric acid levels, the diagnosis of gout can be considered.
2, conditions for joint cavity aspiration, gout stone biopsy, X-ray examination, arthroscopy, etc. can assist in the diagnosis.
3.Difficult to diagnose can be diagnostic treatment with colchicine, if the treatment is rapidly effective, it has characteristic diagnostic value.
Differential diagnosis
Some cases have atypical performance and need to be differentiated from other diseases.
1, acute arthritis: ① rheumatoid arthritis: mostly seen in adolescents, mainly knee arthritis, often with annular erythema, etc.; ② rheumatoid arthritis: mostly seen in young and middle-aged women, mostly small joints, pyknotic swelling, high rheumatoid factor titer; ③ traumatic arthritis: because gout often attacks after trauma, it is easy to misdiagnose, and it is important that the gout condition and the degree of trauma are not parallel; ④ septic arthritis: systemic (4) septic arthritis: severe symptoms of systemic toxicity without uric acid crystals in the bursal fluid; (5) pseudoarthritis: rare, elderly knee arthritis, calcium pyrophosphate crystals can be seen in the bursal fluid.
2, urinary tract stones: calcium oxalate, calcium phosphate, calcium carbonate stones x-ray visualization, easily confused with mixed uric acid stones, but gouty stones have hyperuricemia and corresponding gout manifestations. Cystine stones do not show up on X-ray, but the blood uric acid is not high.
3, chronic arthritis ① rheumatoid arthritis: chronic stiff deformity of the joint, mostly in young and middle-aged women, blood uric acid does not increase, X-ray lack of chisel-like characteristic defects; ② psoriatic arthritis: about 20% with hyperuricemia, showing asymmetric toe (finger) end joint destruction and bone resorption, X-ray end toe (finger) in the shape of a pencil cap; ③ bone tumor: multiple chisel-like destruction resulting in fracture, deformity and misdiagnosed as Bone tumor.
The principle of treatment is early, rapid and effective pain relief, complete termination of acute arthritis and prevention of chronic arthritis. Bed rest should be provided and the affected joint should be placed in the most comfortable position.
I. Acute treatment
Colchicine: It can reduce or terminate the chemotactic factors secreted by leukocytes and synovial endothelial cells that phagocytose uric acid salts. Note: Colchicine has great side effects and toxicity, nausea and vomiting, diarrhea, liver cell injury, bone marrow suppression, hair loss, respiratory depression, etc. Therefore, those with bone marrow suppression, hepatic and renal insufficiency, and leukopenia are prohibited, and those whose treatment is ineffective should no longer be used, and should be replaced by NSAIDs.
2, NSAIDs: indomethacin (anti-inflammatory pain) 25-50mg once, 3 times a day; diclofenac, ibuprofen, ketoprofen, aminoprofen, acemetacin, nimesulide, sulforaphane, naproxen, meloxicam, piroxicam and other NSAIDs can be used as appropriate, and reduce the dosage after the symptoms are controlled. It should be noted that non-steroidal anti-inflammatory drugs also have more digestive system, blood system, kidney and other side effects.
3, glucocorticoid treatment: when the above two types of drugs are ineffective or contraindicated, prednisone 30mg/day, generally in 24 to 36 hours relief. Glucocorticosteroids also have obvious side effects and need to follow medical advice when there are contraindications.
4.Promote uric acid excretion and inhibit uric acid synthesis during acute attack can be suspended.
II. Intermittent and chronic treatment
Control the blood uric acid at normal level, prevent and protect the function of damaged organs.
1.Promote uric acid excretion drugs: Reduced uric acid excretion is the main cause of primary gout, this drug is suitable for the period of hyperuricemia and intermittent and chronic period.
Commonly used drugs are: (1) propofol (carbenzenesulfonamide), 0.25g, twice a day at first, increasing to 0.5g within two weeks; (2) sulfopirone (benzosulfone), stronger than propofol, 50mg, twice a day, gradually increasing to 100mg, three times a day; (3) benzbromarone, stronger, 25-100mg, once a day; often with rash, fever, gastrointestinal irritation, stimulation of acute attacks and other side effects. Side effects such as rash, fever, gastrointestinal irritation, and acute seizures. Drink more water and take alkaline drugs such as sodium bicarbonate 3-6g per day during the medication.
2. Inhibition of uric acid synthesis: The mechanism is to inhibit xanthine oxidase and block the conversion of xanthine into uric acid. It is suitable for those who produce too much uric acid or those who are not suitable to use drugs that promote uric acid excretion.
Prevention of primary gout is a chronic and lifelong disease, which cannot be cured yet.
1. Prevention and control objectives.
①Control hyperuricemia and prevent the occurrence of supersaturated urate deposits.
② Rapidly terminate acute arthritic attacks.
③ deal with gout stone disease, treatment of the original disease, improve the quality of life.
2.Preventive measures.
①Examine suspected patients and their families for early detection of hyperuricemia.
②Reduce exogenous purine sources, avoid diets containing high purine such as animal offal, fish, shrimp, clams, crabs and other seafood, meat, soy products, etc.
③Adjust the diet structure, actively reduce body weight, control protein diet at lg/kg per day, carbohydrates account for 50%-60% of total calories, and eat less candy, etc.
④Increase uric acid excretion: drink more water, do not use drugs that inhibit uric acid excretion, diuretics, aspirin, etc.
⑤ Avoid triggers that promote the formation of urate crystals: get cold, overwork, stress, wear comfortable shoes, don’t make joints injured, quit drinking, take alkaline drugs, such as adding acetazolamide 0.25g at night to keep urine alkaline and prevent stone formation.
(6) In case of hyperuricemia without gout, use uric acid synthesis inhibitors or/and uric acid excretion promoters as appropriate according to the type of occurrence.