Aphorism 1.
The gold standard for gout diagnosis is the finding of urate crystals in joint fluid or deposited nodules, while typical flare features, effective colchicine treatment, hyperuricemia and/or dual-energy CT and ultrasound can help in early diagnosis.
Aphorism 2.
Before gout treatment, it is necessary to understand the presence of secondary factors and to assess the severity of the disease: (1) how high the blood uric acid really is, what is the 24h uric acid excretion, etc.; (2) the presence of renal insufficiency, hematologic disorders, long-term medication history, lead poisoning, etc.; (3) the arthritic condition, the degree of pain, the number of joints involved, whether there are recurrent attacks and joint destruction; (4) the presence of visible gout stones; (5) the presence of hypertension, cardiovascular disease, diabetes mellitus and other comorbidities.
Experts have reached the following consensus: blood uric acid over 9 mg/dl (540umol/L), regardless of asymptomatic hyperuricemia or gout, and regardless of the presence of cardiovascular and cerebrovascular disease risk factors, requires uric acid-lowering therapy. The type of uric acid-lowering drug is selected based on the determination of uric acid excretion.
During an acute gout attack, 30% of patients will have normal uric acid blood due to factors such as excessive secretion of corticosteroids to promote uric acid excretion in response to stress, discontinuation of diuretics, and withdrawal of alcohol. Therefore, it is recommended to test blood uric acid during non-gout attacks.
Proverb 3.
Non-pharmacological treatment is the basis of gout treatment, including education, exercise, weight reduction, low purine diet, cessation of smoking and alcohol, and drinking more water to maintain adequate urine output. Although controlling diet can only reduce uric acid by 1mg/dl, it is still important and non-pharmacological treatment should be used throughout the gout treatment.
Foreign studies have confirmed that meat, seafood, beer, liquor and sugary drinks can raise blood uric acid, and appropriate red wine and dairy products can slightly reduce the risk of gout attacks. In addition, appropriate consumption of vegetables with high purine content will not increase the risk of gout attack.
Aphorism 4.
For acute attacks of gout, our guidelines prefer colchicine and non-steroidal anti-inflammatory drugs (NSAIDs), with colchicine to be used in small doses and NSAIDs to be used in full doses and doubled on the first day. In addition, topical glucocorticoids can be applied to the joint, and topical analgesics combined with oral analgesics are more effective. The timing is very important, the sooner the drug is used the better (within 24h), and the course of treatment is 7~10 days.
Aphorism 5.
When NSAIDs and colchicine are intolerant or contraindicated, oral, intramuscular or intravenous glucocorticoids (0.5mg/kg?d) can be chosen, and the drug can be stopped after 5~10d of full dose or gradually reduced after 3~5d of full dose and stopped after 7~10d. The duration of use should not exceed 10 days, and long-term use is not recommended.
Proverb 6.
For those with severe pain during attacks, a combination of drugs may be used, and biological agents such as interleukin 1 antagonists may be considered for refractory patients.
For severe pain (VAS score ≥7), the recommended starting combination regimen is (1) colchicine + NSAIDs; (2) colchicine + oral glucocorticoids; (3) joint cavity injection of glucocorticoids + oral hormones or colchicine or NSAIDs.
Dosage was adequate for both drugs or adequate for one + prophylactic for one. NSAIDs + hormones are not recommended.
Aphorism 7.
When colchicine is used in the treatment of acute exacerbations, a low-dose regimen is recommended: a loading dose of 1 mg at the beginning, 0.5 mg after 1 h and 0.5 mg after 12 h, bid/tid.
The results of a randomized controlled double-blind multicenter study – the AGREE study – suggest that colchicine in small doses has comparable efficacy compared to oral high doses, but with significantly fewer side effects. Therefore, colchicine should be used as recommended by EULAR or ACR guidelines, abandoning traditional dosing.
Aphorism 8.
Continuous uric acid-lowering drug therapy should be started when there is >1 gout attack or when there is renal decompensation or existing gout stone formation, and the dose should be adjusted according to the blood uric acid value.
Proverb 9.
The timing of the first addition of uric acid-lowering drugs is appropriate after the acute attack of gout has subsided, or after an adequate amount of anti-inflammatory and analgesic drugs have been given during the acute attack. Once added, gout is no longer discontinued when another attack occurs.
In this regard, the ACR guidelines differ from the consensus opinion of domestic experts. the ACR considers acute gout attacks to be treated with uric acid-lowering therapy after the start of effective anti-inflammation (Class C), based on a study with a small sample size that concluded that allopurinol application in the acute phase does not affect acute remission or increase the rate of acute recurrence.
In contrast, domestic experts believe that uric acid-lowering therapy should be started after the acute gout attack has subsided for at least 2 weeks. Because uric acid reduction is a long-term process, postponing it for 2 weeks does not affect the long-term efficacy, and most gout attacks are related to the rate of change in blood uric acid levels. Clinically, it is not uncommon that the use of anti-inflammatory and analgesic drugs + uric acid-lowering drugs during the acute attack period has resulted in untreated joint symptoms or metastatic gout.
Aphorism 10.
Allopurinol, febuxostat and benzbromarone are all commonly used uric acid-lowering drugs and should be given in small doses increasing gradually depending on the patient’s renal function, presence of gout stones and uric acid excretion.
The Chinese and Japanese guidelines recommend both production inhibitors and uric acid excretors as first-line drugs, which should be determined according to the patient’s uric acid metabolism. Patients with normal or mildly abnormal renal function, no renal stones, and poor uric acid excretion tend to prefer benzbromarone; conversely, allopurinol and febuxostat are preferred.
Proverb 11.
To prevent the development of severe hypersensitivity syndrome, it is advisable to test for the HLA-B*5801 gene before using allopurinol.
Adverse reactions to allopurinol include gastrointestinal reactions, rash, liver damage, and bone marrow suppression. The 2012 ACE guidelines recommend rapid testing for HLA-B*5801 before using allopurinol in Asians, with a positive test being contraindicated, and genetic testing before using the drug when available.
Proverb 12.
When uric acid-lowering drugs alone are not effective, they can be replaced or combined with other uric acid-lowering drugs. Inhibitors of uric acid synthesis can be combined with pro-uric acid excretory drugs, or with drugs with dual functions (e.g., both uric acid-lowering and lipid-lowering effects).
Drugs available for the three major pathways of uric acid reduction.
Refractory gout can be combined with drugs that
(1) Pro-uric acid excretory drugs + drugs that inhibit uric acid synthesis.
Allopurinol (200~600mg/d) + benzbromarone (100ng/d) / propofol (0.5g/d) / RDEA594 (200~600mg/d) > allopurinol or propofol; RDEA594 (600mg/d) + febuxostat (40~80mg/d) > febuxostat.
(2) Combinations between two drugs that inhibit uric acid synthesis.
Allopurinol (100~300mg/d) + purine adenosine phosphorylase inhibitor BCX4208 (20~80mg/d) > allopurinol.
(3) The 2011 US guidelines state that allopurinol should not be combined with febuxostat.
(4) Cloxacin, fenofibrate, halofenate and Arholofenate have both uric acid-lowering and lipid-lowering effects.
Proverbs 13.
Gout attacks should be prevented during uric acid-lowering treatment. Start uric acid-lowering with a combination of low-dose colchicine (0.5 mg, 1 to 2 times/d) or low-dose NSAIDs or low-dose glucocorticoids, with colchicine recommended in preference for 6 months.
ACR Roadmap for Gout Attack Prevention 2012.
Aphorism 14.
Sustained achievement of uric acid reduction (<360umol/L for those without gout stones and <300umol/L for those with gout stones) is the key to gout treatment. The benefits of sustained blood uric acid in the range of 200-300 umol/L are clear: reducing acute attacks, stopping joint damage, reversing the chronic course, and reducing organ damage.
Proverb 15.
The decision to lower uric acid therapy for asymptomatic hyperuricemia depends on blood uric acid levels and the presence of comorbid cardiovascular disease or cardiovascular risk factors. Initiate uric acid-lowering therapy in the following 3 conditions.
(1) blood uric acid over 9 mg/dl; (2) blood uric acid 7-9 mg/dl without cardiovascular disease or cardiovascular risk factors, with 6 months of ineffective dietary control; (3) blood uric acid over 7 mg/dl with cardiovascular disease or cardiovascular risk factors.
Although there are still many issues to be solved, such as individualized treatment of gout and genetic and hereditary research, this 15-article expert consensus standardizes the diagnosis and treatment methods, emphasizes comprehensive diagnosis and treatment, and takes into account the clinical experience of experts, so it is of great significance to the standardized treatment of gout.