Overview: Gout is a crystal-associated arthropathy caused by monosodium urate deposition, which is directly related to hyperuricemia due to disorders of purine metabolism and/or reduced uric acid excretion, and belongs to the category of rheumatic diseases. Gout refers specifically to acute gouty arthritis and chronic gouty stone disease, which can be complicated by renal lesions, joint destruction and renal function impairment in severe cases, often accompanied by hyperlipidemia, hypertension, diabetes, atherosclerosis and coronary heart disease. Its incidence is increasing year by year.
The complete diagnosis of gout: including the following
I. Gout diagnosis.
Criterion I: Mostly using the 1977 ACR classification criteria for acute gouty arthritis
1977 ACR classification criteria for acute gouty arthritis
1. Specific uric acid crystals in the joint fluid
2. The presence of urate crystals in the gouty stones was confirmed by chemical methods or polarized light microscopy
3.With 6 of the following 12 items (clinical, laboratory and X-ray manifestations)
(1) Acute arthritis attack > 1 time
(2) Inflammatory response peaks within 1 d
(3) Single arthritis attack
(4) Redness of the joint is visible
(5) Pain or swelling of the first metatarsophalangeal joint
(6) Unilateral involvement of the first metatarsophalangeal joint
(7) Unilateral tarsal joint involvement
(8) Suspected gout stone
(9) Hyperuricemia
(10) Asymmetric intra-articular swelling (confirmed by x-ray)
(11) Subcortical cysts without bone erosion (confirmed by x-ray)
(12) Negative microbiological culture of joint fluid at the onset of arthritis
Criterion 2: New gout classification criteria jointly introduced by NIH and Arthritis Foundation, and ACR and EULAR in 2014.
Diagnostic steps.
1. At least one of the symptoms of peripheral joint or bursa swelling, pain or pressure is present before being considered for the classification criteria.
2. Sufficient condition: Gout crystals are detected in symptomatic joints/bursae (e.g. synovial fluid) or gout nodules. The diagnosis can be confirmed directly without the following classification criteria.
3.Do not have the above sufficient conditions, the following criteria assessment, ≥ 8 points can be diagnosed.
II. gout staging: acute gouty arthritis; intermittent gout; chronic stage (gout stone) gout.
Third, biochemical typing: excessive uric acid production type; reduced uric acid excretion type; mixed type.
IV. Gouty renal lesions: chronic uric acid nephropathy, uric acid urinary stones, acute uric acid nephropathy.
V. Concomitant diseases: hyperlipidemia, hypertension, diabetes, atherosclerosis and coronary heart disease, chronic kidney disease (CKD), etc.
1. Differential diagnosis.
(1) Acute phase: cellulitis, dengue, infectious septic arthritis, traumatic arthritis, reactive arthritis, pseudogout, etc.
(2) Chronic phase: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, osteoarthritis, bone tumors, etc.
2.Checkup items: choose according to the situation.
(1) blood uric acid, 24h uric acid quantification (daily diet normal range 300-750mg), uric uric acid/urine creatinine (>1.0 for overproduction type; <0.5< excretion reduction type), blood uric acid/blood creatinine (>2.5 chronic uric acid nephropathy; <2.5< chronic kidney disease secondary to hyperuricemia) (all of the above in mg/dl)
(2) X-ray or CT or MRI examination of joints, ultrasonography of joints and urinary tract
(3) Blood and urine routine, blood sedimentation, liver and kidney function, blood lipid, blood sugar.
(4) HLA-B5801.
(5) Uric acid crystals examination.
(6) CRP, rheumatoid factor, HLA-B27, anti-CCP antibody if necessary
VI. Treatment.
Objective: Rapid and effective relief and elimination of acute attack symptoms; prevention of recurrence of acute arthritis; correction of hyperuricemia, dissolution of urate crystals, prevention of new crystals formation, reversal and cure of gout; treatment of concomitant other diseases.
Methods: Comprehensive standardized treatment
1.Non-pharmacological treatment of gout.
(1) Patient education, adjustment of lifestyle and diet structure. Control your mouth, open your legs, control your weight and drink more water.
(2) Alkalization of urine, alkalization of urine can dissolve uric acid stones, maintain urine pH at about 6.5 is most appropriate. Commonly used alkalizing urine drug is sodium bicarbonate.
(3) Actively treat metabolic risk factors associated with elevated blood uric acid, including active control of hyperlipidemia, hypertension, hyperglycemia, obesity and smoking cessation. The antihypertensive drug coxsartan and the lipid-lowering drug fenofibrate have the effect of promoting uric acid excretion and are preferred when combined with hypertension and hyperlipidemia.
(4) Avoid drugs that raise blood uric acid, such as aspirin (weigh the pros and cons when anticoagulation), diuretics, cyclosporine, tacrolimus, nicotine, alcohol, levodopa, pyrazinamide, ethambutol, etc., which can cause blood uric acid to rise and should be avoided. For patients who need to take diuretics and have combined hyperuricemia, avoid thiazide diuretics and strong diuretics such as furosemide and diuretic acid.
(5) Instruct patients in self-management and regular review: Patients should be informed about the pathogenesis, process and treatment of gout and understand their comprehensive treatment plan, measures, goals and prognosis. Prevent and monitor possible adverse drug reactions and various acute and chronic complications, relax, and reasonably adjust the diet structure. Regular review, during the process of adjusting uric acid-lowering drugs, measure blood uric acid every 2-5 weeks, review blood routine, urine routine, kidney function once in 3-6 months. review liver function, blood sugar, blood pressure, ultrasound of digestive system and ultrasound of urinary system once in 6-12 months.
2. pharmacological treatment for acute attack control: the principle of stratified treatment should be used to control acute gout attacks. firstly, patients should be evaluated for their condition, and indicators include the number of joints involved and pain VAS score. vas score: ≤4: mild; 5-6: moderate; ≥7: severe. Number of joints involved: 1 or a few small joints; 1 or 2 large joints; polyarticular involvement (3 or more large joints, or 4 or more joints and greater than 1 joint area). For pain VAS scores greater than or equal to 7, especially in multiple joints, the recommended starting treatment is combination therapy, otherwise starting monotherapy can be given. The first-line drugs for seizure control are colchicine, NSAIDS-like drugs, and glucocorticoids. There is no priority recommendation for all three, and clinical selection should be based on patient preference, contraindications, and prior treatment response.
(1) Colchicine: used in small doses, high doses are not recommended. Colchicine treatment may be chosen if the patient is not on colchicine prophylaxis at the time of the gout attack, or if, although on colchicine prophylaxis, a loading dose of colchicine is not used for acute gouty arthritis within 14 d. The loading dose is 1.2 mg (0.6 mg per tablet) or 1.0 mg (0.5 mg per tablet), followed by 0.6 mg (or 0.5 mg) after 1 h. After 12 h, follow 0.5 mg-0.6 mg, taken l to 2 times a day, or 0.5 mg, maintained 3 times a day until complete remission of gout. If a patient is treated prophylactically with colchicine and a loading dose of colchicine is used within 14d, colchicine is no longer chosen for this attack, but NSAIDs or glucocorticoids.
(2) NSAIDs: Treatment emphasizes adequate dosage and full course (until acute gouty arthritis is completely relieved), with reduced dosage for patients with comorbidities and hepatic and renal impairment, paying attention to digestive system adverse effects and adding gastroprotective agents if necessary.
(3) Glucocorticoids: can be used systemically or locally, it is recommended to first assess the number of affected joints, oral prednisone dose of 0.5mg/Kg?d, a course of 5-10d, direct discontinuation, or 0.5mg/Kg?d, 2-5d, then gradually reduce the dose, 7-10d discontinuation; can also choose methylprednisolone, intramuscular or intravenous injection, the starting dose of 0.5-2mg/ If one or two large joints are involved, glucocorticoid joint cavity injection can also be chosen, with the dose decided according to the size of the involved joints, and combined with oral glucocorticoids or NSAIDs or colchicine.
(4) Combination therapy: Combination therapy is recommended for patients with severe acute gout attacks.
Combination therapy regimen.
(1) colchicine + NSAIDS.
(2) Oral hormones + colchicine.
(3) Intra-articular injection of hormone + oral hormone/colchicine/NSAIDS. combination of NSAIDS and hormone is not recommended. Dose of combination therapy: adequate dose of both drugs or adequate dose of one drug and preventive dose of the other drug.
(4) For acute gout attack with poor effect of first treatment (poor is defined as improvement of VAS score <20% within 24h of drug treatment, or improvement of VAS score <50% for ≥24h of treatment) the diagnosis of gout needs to be reconsidered, and treatment should first consider switching to another first-line drug treatment, or adding another first-line drug combination treatment. For patients who remain ineffective, interleukin 1 receptor antagonists, such as anakinra 100 mg, subcutaneously, once daily for 3 d, or canakinumab 150 mg, subcutaneously, or Rilonacept (Linacip) weekly subcutaneously, may be considered. Biological agents have not been fully entered into the clinic in China yet.
3.Uric acid-lowering drug therapy: firstly, the indications for uric acid-lowering drug therapy are clearly defined: acute gout recurrence (or greater than or equal to 2 times/year), polyarticular involvement, gout stone, chronic gouty stone arthritis, uric acid kidney stone, radiological changes, kidney disease (CKD grade 2 and above). Correct timing of uric acid-lowering therapy: start uric acid-lowering therapy after acute gout attack is controlled for at least 2 weeks; or during acute gout attack, uric acid-lowering therapy can also be started after effective anti-inflammatory therapy is started; if uric acid-lowering drugs have been used and another attack occurs, continue with uric acid-lowering drugs instead of stopping uric acid-lowering drugs; for chronic gouty stone gout attack without obvious interval, add uric acid-lowering drugs at the same time as applying NSAIDA or colchicine The choice of uric acid-lowering drugs
The choice of uric acid-lowering drugs: there are three categories: drugs to inhibit uric acid production, including allopurinol and febuxostat; drugs to promote uric acid excretion, such as propofol and benzbromarone; and drugs to promote uric acid decomposition, such as uricase. At present, the first 2 kinds of uric acid-lowering drugs are mainly used in China, either alone or in combination.
(1) Allopurinol and febuxostat are the first-line uric acid-lowering drugs: the initial dose of allopurinol is 50-100mg/d, and the dose is gradually increased for 2-5 weeks to a maximum of <800mg/d. The dose is reduced in case of renal insufficiency, and 24hCcr<15ml/min is prohibited. Allopurinol allergy syndrome is a serious and fatal side effect with an incidence of 0.1-0.4% and a mortality rate of 25-30%, mainly seen in high-risk groups such as Han Chinese, Thais, and Koreans with CKD stage 3 or higher. Hypersensitivity reactions can be treated with desensitization therapy (50ug/d, doubled for three days, only for mild allergy). Febuxostat has the advantages of being potent, safe, and does not require dose adjustment in mild to moderate renal insufficiency. The dose is 20-40mg/d, doubled and tapered to the target dose in 1-2 weeks.
(2) Benzbromarone and propofol: If allopurinol and febuxostat are not effective or cannot be tolerated, uric acid excretory drugs can be used, propofol is preferred abroad, and benzbromarone is prohibited due to the side effect of liver failure. It is contraindicated in patients with increased urinary uric acid excretion, urinary tract stones, and chronic uric acid nephropathy. The application requires alkalinization of the urine.
(3) Uric acid oxidase Prevacid is an intravenous application of uric acid-lowering drugs, which has the outstanding advantage of rapidly depleting the uric acid pool and making the gout stones disappear quickly. However, its infusion reactions are serious, and moderate to severe infusion reactions (facial flushing, urticaria and hypotension) may occur in 8% to 11% of patients, followed by more acute gout attacks after drug administration, which may be frequent in the first few months (nearly 80%), and other side effects include fever, anemia, allergy (2% to 5%), gastrointestinal discomfort, non-cardiogenic chest pain or muscle cramps, so it is currently used only for traditional uric acid-lowering therapy Therefore, it is currently only used for adults with refractory gout who have failed to respond to conventional uric acid-lowering therapy.
4.Target of uric acid reduction: the ideal target value of blood uric acid for patients without gout stones is <360umol/L; for those with gout stones, the target is <300umol/L, which can reduce and disappear gout stones and prevent joint destruction and kidney damage; for chronic refractory gout with a large number of gout stones, the target is <240umol/L.
5, prophylactic treatment of acute gout attack: treatment for attack prevention should be given when starting uric acid-lowering therapy, and attack prevention drugs should be started 2 weeks before or at the same time of uric acid-lowering therapy, with preference for low-dose colchicine, 0.5 mgbid or tid; or low-dose NSAIDs, and when intolerant or contraindicated, small-dose glucocorticoids (prednisone ≤10 mg/d) can also be used as second-line prophylactic drugs. Prophylactic regimen: For those with gout symptoms (within 3 months of acute gout attack, presence of gout stones, chronic gout arthritis), continuous prophylactic treatment is recommended; for those without the above gout symptoms, prophylactic treatment is recommended for at least 6 months; or for those without gout stones, treatment is required until 3 months after blood uric acid levels reach the standard; for those with gout stones at baseline, treatment is still required for 6 months after blood uric acid reaches the standard.
6. Asymptomatic hyperuricemia: non-pharmacological treatment is the mainstay, and uric acid-lowering drugs are generally not recommended. Patients with cardiovascular risk factors or comorbidities should be treated with uric acid-lowering drugs if their blood uric acid level is greater than 8mg/dl, and patients with hyperuricemia whose blood uric acid level is less than 8mg/dl should be treated with additional uric acid-lowering drugs if it is still higher than normal after 6 months of life guidance; patients without cardiovascular risk factors or comorbidities should be treated with uric acid-lowering drugs if their blood uric acid level is greater than 9mg/dl. Patients without cardiovascular risk factors or comorbidities should be treated with uric acid-lowering drugs if their blood uric acid level is greater than 9 mg/dl. Cardiovascular comorbidities or risk factors include: hypertension, abnormal glucose tolerance or diabetes mellitus, hyperlipidemia, coronary heart disease, stroke, heart failure or renal abnormalities.