Gout is a group of clinical syndromes caused by the deposition of sodium urate from supersaturated extracellular fluid in joints, synovial membranes, other tissues or organs. It includes arthritis, gout stones, uric acid kidney stones and, less commonly, gouty nephropathy. Recent epidemiological surveys show that the prevalence of gout is increasing day by day. In addition, the age of onset of gout has become younger, and the clinical manifestations of patients are more serious. Gout, which used to be called the disease of wealth or “the disease of kings”, has now become a serious health hazard to the general public and should be given wide attention and prevention. The author would like to explain several basic clinical concepts as follows.
1.What is hyperuricemia?
Uric acid is the end product of human purine metabolism. Hyperuricemia (HUA) refers to elevated blood urate levels that exceed the solubility limit of sodium urate in the blood list (6 or 8 mg/dl at 37 degrees Celsius). Most epidemiological studies have shown that the upper limit of blood uric acid values is 7 mg/dl (417 μmol/L) in healthy men and 6 mg/dl (357 μmol/L) in women. If the blood uric acid level is >7 mg/dl, the risk of gout starts to increase.
2. Does hyperuricemia mean gout?
If the patient’s blood uric acid level is >7 mg/dl, but there is no arthritis, gout stone or urate stone, it is clinically called asymptomatic HUA, the incidence of which is 5%~7% in adult men, and has reached 16.8%~18.3% in China. However, once an asymptomatic HUA patient shows any manifestation of arthritis, gout stone or urate stone, it marks the end of asymptomatic HUA and the beginning of gout. Therefore, asymptomatic HUA is classified as the first stage of gouty arthritis.
Most people with HUA remain asymptomatic for life, but the risk of conversion to gout increases with increasing blood uric acid levels. The 5-year cumulative incidence of gout has been shown to be 0.5% in those with blood uric acid levels <6 mg/dl, 2.0% in those with blood uric acid levels between 7 and 7.9 mg/dl, and up to 30.5% in those with blood uric acid levels >10 mg/dl. Asymptomatic HUA is not gout, nor can it be transformed into gout in those with increased blood uric acid. Therefore, scholars do not advocate uric acid-lowering treatment for patients with asymptomatic HUA so far.
3.What factors increase blood uric acid level?
The increase of blood uric acid can be caused by excessive production of uric acid, such as high purine diet, alcohol abuse, reduced uric acid excretion (such as renal insufficiency) or both. In recent decades, there has been a marked increase in the number of factors contributing to HUA, such as hypertension, chronic kidney disease, obesity, metabolic syndrome, unhealthy diet and the widespread use of diuretics and low-dose aspirin. Comprehensive understanding and reduction of the above-mentioned adverse factors is beneficial to the prevention and treatment of gout.
4.What are the unique clinical manifestations of gouty arthritis?
Gouty arthritis (GA) is the first manifestation of gout, and the whole process is divided into 4 stages: asymptomatic HUA, acute GA, intermittent gout and chronic gouty stone gout. Asymptomatic HUA has been described previously. The unique presentation of acute GA is that the onset is acute, mostly in the early morning, and in 90% of patients the first presentation is in a single foot joint, with bunions predominating. Localized redness, swelling, heat and severe pain with limited mobility, with a peak period of 1 to 3 days. The blood uric acid level is not high and resolves completely on its own in about 1 week with no sequelae, but there is a tendency for recurrence.
The asymptomatic period between two episodes of arthritis is called intermittent gout. According to statistics, 62% to 89% of patients have a second attack only after an interval of 1 to 5 years. Therefore, pharmacological intervention is not advocated during the interval period. Over time, urate crystals slowly accumulate and arthritis attacks become frequent, eventually evolving from an acute, transient, non-destructive monoarthritis to a lingering, multi-joint, symmetrical, destructive arthritis of the extremities. It is also accompanied by high blood uric acid and gouty nodules, known as chronic gouty stone gout.
5.How to treat acute gouty arthritis?
The most urgent requirement for patients with acute GA is the rapid relief of joint pain and swelling. The preferred drugs are non-steroidal anti-inflammatory drugs with anti-inflammatory and analgesic effects (such as diclofenac, ibuprofen, naproxen, etoricoxib, etc.) or colchicine. Those who do not respond to the above drugs or cannot tolerate them may receive topical or systemic treatment with glucocorticoids. Treatment is usually discontinued in about 1 week when the patient’s symptoms have resolved. At present, it is a common clinical practice to treat acute GA with uric acid-lowering drugs (such as allopurinol) without anti-inflammatory and pain-relieving effects, which is a major misconception and not only ineffective, but also can aggravate the disease.
6.When should gout patients start uric acid-lowering treatment?
It has been recorded that the average interval between the first attack of arthritis and the appearance of the first gout stone in untreated patients is 11 or 7 years. Twenty years after the first symptom, 70% of patients have gout stones and 30% of patients have kidney stones. Overall, uric acid-lowering therapy is not necessary for early gout. However, in clinical practice it must be individualized depending on the patient’s condition. It is now advocated that uric acid-lowering therapy should be started in patients with one of the following conditions: (1) frequent and/or disabling acute arthritis; (2) presence of gout stones; (3) gouty urinary stones; (4) blood uric acid level >12 mg/dl (714 μmol/L) or 24h uric acid >1100 mg (6,545 mmol).
7.How to choose uric acid-lowering drugs?
Uric acid-lowering drugs can be divided into 3 major categories: pro-uric acid excretory drugs (such as propofol, benzbromarone), drugs that inhibit uric acid synthesis (such as allopurinol, febuxostat) and drugs that promote uric acid catabolism (such as labile lyase, polyethylene glycol uricase). It has also been proved that the lipid-lowering drug fenofibrate and the antihypertensive drugs amlodipine and coxsartan also have uric acid-lowering effects. The physician should choose a certain type of drug reasonably according to the patient’s condition, complications and other systemic conditions.
8.What should be the goal of uric acid-lowering treatment?
The goal of uric acid-lowering therapy is to reduce ultra-high blood uric acid levels, thereby preventing the formation of new urate crystals and promoting the dissolution of existing crystals. In short, the lower the blood uric acid level, the fewer the gout stone deposits. For this reason, the recommended target level for uric acid lowering therapy is 4-6 mg/dl, which is well below the blood uric acid saturation level and should be maintained for a long time or even for life.
Summary
Gout is a treatable and preventable disease, but do not mistake one remission of arthritis as a cure for gout; be alert to its tendency to recur. Patients who must receive uric acid-lowering therapy should be protected from inadequate doses of medication, unclear goals, inadequate courses of treatment, and lax follow-ups. In any case, long-term adherence to a low purine diet, avoidance of alcohol (especially beer), changes in unhealthy lifestyle and improved compliance with treatment are necessary for the treatment of gout.