Hyperuricemia and gouty arthritis have become a common disease in China. Gout patients account for 95% of men, and the peak age of onset is 40-45 years old, and is mostly associated with abdominal obesity, hyperlipidemia, hypertension and diabetes mellitus, and is prone to cardiovascular and cerebrovascular disease.
The typical gout is divided into four stages.
1. Asymptomatic hyperuricemia phase
The symptomatic hyperuricemia phase occurs when the blood uric acid value is greater than 416umol/l. This period can last for many years, but the incidence of gout increases with the course of the disease and the increase in uric acid value.
2.Acute attack period
Acute gouty arthritis occurs in 80% of cases with causative factors, such as consumption of high purine foods (seafood and animal offal), alcoholism, fatigue, localized joint injury, cold stimulation, diuretics, chemotherapy drugs. 2/3 of gouty arthritis starts with the first toe and metatarsal joint, with acute localized redness, swelling, heat and pain, and limited activity, mostly at night, with rapid onset and severe pain, which can be relieved by itself in a few days or weeks.
3.Intermittent period without symptoms
After repeated gouty arthritis, gouty stones can be formed, typically at the olecranon, but also commonly in the first toe and plantar, gouty stones are characteristic lesions of gout, when a large number of gouty stones deposited in the joint can cause bone erosion defects, surrounding soft tissue fibrosis, joint stiffness and deformity.
4.Chronic phase
Forty percent of chronic gout patients have renal damage, manifesting as chronic uric acid nephropathy, urinary stones, and also acute uric acid nephropathy under triggers, which can rapidly occur as renal failure. Uric acid stones do not show up on X-rays and can be detected during ultrasound examinations. In chronic uric acid nephropathy, tubular lesions appear early, manifested by increased nocturia, low specific gravity urine, and in some patients, progressive renal failure.
Diagnostic criteria for gouty arthritis (American Rheumatism Association diagnostic criteria)
1.Uric acid crystals are detected in synovial fluid.
2.Gouty stone confirmed by chemical test.
3. Those with 6 of the following 12 conditions.
(1) Acute arthritis attack > 1 time;
(2) Maximum joint inflammation within 1 day;
(3) Monoarthritis ;
(4) Redness of joints;
(5) Pain or swelling of the metatarsophalangeal joint of the bunion;
(6) Unilateral [toe joint;
(7) Unilateral tarsometatarsal joint;
(8) Suspected gout stone;
(9) High blood uric acid;
(10) Asymmetric swelling of one joint (radiograph);
(11) Subcortical cysts without broken rings (radiographs);
(12) Negative synovial fluid culture at the onset of arthritis.
A diagnosis of gouty arthritis can be made if any one of the above three is present.
Principles of gout treatment
Goal: To control blood uric acid level to 357 μmol/L (6
mg/dl) or less to dissolve formed urate crystals and to prevent new crystal formation. Treatment of acute gouty arthritis; prevention of acute gout attacks; correction of hyperuricemia and prevention of urate deposition in joints, kidneys and other tissues; treatment of chronic complications.
Acute gouty arthritis drug treatment
Objective: To rapidly control inflammation, relieve symptoms and restore function.
Types of drugs: NSAIDs, glucocorticoids and colchicine. The choice of uric acid-lowering drugs in the acute phase is not only ineffective, but also aggravates or prolongs the course of the disease in the acute phase. And patients who are receiving uric acid-lowering drugs can continue to use uric acid-lowering drugs when acute attacks of gouty arthritis occur during treatment, and anti-inflammatory painkillers should be added promptly.
Non-steroidal anti-inflammatory drugs (NSAIDs)
Have anti-inflammatory, analgesic and antipyretic effects, and can work quickly. They are becoming the first choice for the treatment of gouty arthritis, and the earlier they are used, the better the anti-inflammatory and pain-relieving effects and the shorter the duration of treatment required. NSAIDs increase the risk of gastrointestinal bleeding, but the use of selective inhibitors of cyclooxygenase-2 (COX2) has minimal adverse gastrointestinal effects.
Glucocorticoids
can be effective in treating acute attacks of gout. Glucocorticosteroids are not recommended as systemic therapy except for a short period of time when the patient has failed to respond to all other drugs, or when the adverse effects are not tolerated, or in patients with hepatic or renal insufficiency. When patients with renal insufficiency (blood creatinine level >2mg/L or 177.4μmol/L) have an acute gout attack, glucocorticoids should be used orally for a short period of time.
Colchicine
Colchicine has a therapeutic and diagnostic effect on acute gouty arthritis, and has been used in the past: colchicine 0.5mg or 0.6mg/2h until the joint swelling and pain are controlled, but the maximum daily dose does not exceed 6mg. only 75% of the patients get results in 12-18h, but the number of adverse drug reactions is as high as 50%-80%. The drug has been gradually relegated to the second line both at home and abroad, and is no longer the drug of choice for the treatment of acute attacks of gouty arthritis.
Strategies for uric acid-lowering therapy
Timing of treatment
Frequent acute arthritis with more than 2-3 episodes per year; presence of gouty stones or gouty urinary stones or chronic gouty nephropathy; blood uric acid >536μmol/L (9mg/dl) despite dietary control; bone destruction of joints on x-ray.
Goals of uric acid reduction therapy
Blood uric acid level below 357µmol/L.
Selection of appropriate uric acid-lowering drugs
Uric acid excretory agents include benzbromarone, probenecid and benzosulfone; inhibitors of uric acid synthesis: allopurinol and the newer febuxostat; agents that promote uric acid catabolism: labrynase and polyethylene glycol uricase.
Drug selection according to renal function, total 24-hour uric acid excretion and gout stone formation
Traditional inhibitors of uric acid production, allopurinol: the most commonly used uric acid-lowering drug, economical and convenient, in small increments. Dose adjusted according to renal function. Allergic reactions: 2% incidence, with rare occurrence of hypersensitivity syndrome (rash, hematocrit). Ineffective treatment:Even with >600mg/d, blood uric acid cannot be reduced to the target value.
Drugs to increase uric acid excretion
Benzbromarone: The requirement for renal function can be relaxed to creatinine clearance >25 ml/min. The uric acid-lowering effect is stronger than that of allopurinol. Hepatotoxicity has been observed in a small number of patients.
Selection of drugs according to comorbidities
To achieve the dual purpose. Clozaril: suitable for gout patients with hypertension and insignificant increase in uric acid, without increasing the formation of urinary crystals. Fenofibrate: While lowering blood lipids, blood uric acid is reduced by 23% after 160mg/d treatment for 2 months, and rapid reduction of uric acid does not cause acute attacks of gout, which may be related to its anti-inflammatory properties. Atorvastatin: It has both uric acid-lowering and blood cholesterol-lowering effects. Amlodipine: while lowering blood pressure, 5-10mg/d significantly reduced uric acid levels in cyclosporine A-induced hyperuricemia after renal transplantation.