I. Basic concepts and principles
*Gout is a group of diseases caused by disorders of purine metabolism and/or reduced uric acid excretion
*When blood uric acid concentration is persistently high or fluctuates sharply, urate crystallizes and deposits in the tissues, causing the signs and symptoms of gout
*Acute gouty arthritis is not difficult to diagnose clinically, and the presence of uric acid crystals in synovial fluid or gout stones is the “gold standard” for diagnosis.
*Intermittent periods may be asymptomatic. Gout stone formation is a sign that the disease has entered the chronic phase, during which destruction of articular cartilage and bone erosion may occur.
*Gout patients may have kidney lesions such as uric acid nephropathy and uric acid urinary tract stones.
*Patients with gout should control their diet
* Colchicine, non-steroidal anti-inflammatory drugs or glucocorticoids can be used in the acute phase to rapidly control symptoms
* Intermittent period and chronic period should be long-term use of uric acid-lowering drugs to control blood uric acid at normal level
(Hyperuricemia is defined as serum uric acid greater than 417μmol/L in men and 357μmol/L in women)
Second, the characteristics of each stage and diagnosis and treatment
(A) Acute gouty arthritis
Acute attacks often have the following triggers present.
(1) Heavy alcohol consumption or consumption of purine-rich foods;
(2) Overexertion or joint strain;
(3) Emotional excitement or mental stimulation;
(4) exposure to cold and moisture; (5) surgery or trauma;
(6) Drug induced, such as the application of diuretics;
(7) Chemotherapy or radiation therapy for cancer.
The first attack usually starts in the early morning and usually involves only the peripheral individual joints. The first metatarsophalangeal joint is the first joint in about 50% of cases. Throughout the course of the disease, more than 90% of patients have involvement of the first metatarsophalangeal joint. The joints are painful, flushed and even shiny, sometimes with dilated veins and petechiae, and limited motion. The local symptoms worsen rapidly and can reach a peak within a few hours, making the patient’s tossing and turning unbearable. It is often accompanied by general discomfort, even chills and shivers, and elevated body temperature.
In cases of high fever, the temperature can be 39°C or higher, with tachycardia, so it is often misdiagnosed as an infectious disease such as dengue. After the initial attack, the milder cases resolve on their own within a few hours or 1 to 2 days, while the more severe cases last for several days or weeks and then subside. After the inflammation subsides, the local skin is dark red and slightly purple, with skin wrinkling, accompanied by flaking and mild scratching, and then gradually recovers.
Except for the toe joints, all joints of the extremities can be involved, but most of them are the joints of the lower extremities, and the more distal the joints of the extremities are damaged, the more typical the symptoms are. The distribution of joint involvement and its composition ratio, 879 cases were reported in China in the order of first toe (58.7%), toe (11.7%), metacarpophalangeal, interphalangeal (8.9%), ankle (8.7%), knee (3.9%), wrist (2.8%), and other joints were rare.
After remission of acute gouty arthritis, recurrence often occurs within 1 year. The frequency of recurrence varies greatly among individuals. According to the results of the analysis of 1289 cases, 62% of recurrences occurred within 1 year, 16% within 1 to 2 years, 11% within 2 to 5 years, 4% within 10 years, and 7% without recurrence.
Treatment of acute gouty arthritis: bed rest, elevation of the affected limb, avoid weight bearing. Withhold the use of uric acid-lowering drugs to avoid causing fluctuations in blood uric acid, prolonging attacks or causing metastatic gout.
(1) Colchicine: It can inhibit inflammatory cell chemistry and is effective in stopping inflammation and relieving pain. It should be used early, and most patients can have significant pain relief within 24 hours after drug administration, with oral administration of 0.5mg/h or 1mg/2h until one of the three discontinuation indicators occurs.
(1) Significant relief of pain and inflammation;
② nausea and vomiting, diarrhea, etc.;
If colchicine is not tolerated by the digestive tract, it can also be administered intravenously by diluting colchicine 1mg with 0.9% sodium chloride solution to 20ml for slow injection (>2~5 minutes). In addition to gastrointestinal reactions, there may be leukopenia, aplastic anemia, hepatocyte damage, hair loss, etc. Use with caution if you have renal insufficiency.
(2) Non-steroidal anti-inflammatory drugs (NSAIDs): Used more often than colchicine for acute attacks, usually start with a full dose and reduce it after the symptoms have subsided. Indomethacin, diclofenac, etc. may be used. The most common side effects are gastrointestinal symptoms, which may also aggravate renal insufficiency and affect platelet function, etc. It is contraindicated in active peptic ulcers. Those with stomach problems can use nabumetone dispersible tablets (less irritating to the stomach)
(3) Glucocorticoids: usually used for those who are ineffective or intolerant to colchicine and NSAIDs. ACTH 25μ intravenous drip or 40~80μ intramuscular injection, repeat if necessary; or oral prednisone 20-30mg daily, gradually reduce and stop after 3-4 days. The newer domestic marketed ones are betamethasone sodium phosphate injection.
(B) Gout interval
After the acute attack of gout is relieved, there are usually no obvious sequelae, sometimes only the skin pigmentation of the attack site deepens, dark red or purplish red, flaking and itching, which is called asymptomatic intermittent period. Most patients experience a longer interval after the initial attack, which can last 6 months-2 years (a few 5-10 years), but the length of the interval varies widely.
Although there are usually no obvious symptoms during this period, the blood uric acid level often increases. If no attention is paid to controlling blood uric acid, subsequent attacks will become more frequent, several times a year, with prolonged duration of symptoms so that they cannot be completely relieved, and more joints are involved, and a few patients may have sacroiliac, thoracic lock or cervical spine involvement. Even the bursa around the joint, tendons, tendon sheaths and other places urate deposits, symptoms gradually atypical, and gradually into the chronic phase. It is very important to drink a lot of water and alkaline soda, and to review blood uric acid regularly and control it in the normal range.
(C) Chronic gout stone stage
Gout stones appear 10 years after the onset of the disease and are a sign that the disease has entered the chronic phase. They can be found in joints, peri-articular areas, subcutaneous tissue and internal organs. They appear as uric acid stones in the kidneys and uric acid deposits in the joint capsules throughout the body (see figure). Chronic arthritic phase: Repeated deposits of urate cause a chronic foreign body-like reaction in local tissues, and the deposits are surrounded by monocytes, epithelial cells, and macrophages, and fibrous tissue proliferates to form nodules, called gout stones.
They are typically found in the auricle, but also around the joints of the toes, fingers, wrists, ankles, elbows, etc. They are elevated under the skin and appear as yellowish-white sesame-sized to egg-sized nodules with a thin surface, and when they break down, they discharge a white powder or paste that does not heal over time but is rarely secondary to infection. When gouty stone occurs in the joint, it can cause joint cartilage and bone erosion and destruction, reactive hyperplasia, periarticular tissue fibrosis, persistent joint pain, swelling, ankylosis, deformity, and even fracture, called gouty stone chronic arthritis.
Uric acid nephropathy: deposition of urate crystals in renal tissue, especially in the renal medulla and conus, can lead to chronic interstitial nephritis, which deforms, atrophies, fibrosis and sclerosis of the renal tubules, and then involves the glomerular vascular bed. It manifests as decreased renal tubular concentration function, increased nocturia, low specific gravity urine, hematuria, proteinuria, back pain, edema, hypertension, and advanced renal insufficiency.
It is worth noting that renal pathology is almost always damaged in gout patients, and about 1/3 of patients clinically present with renal symptoms, which can be seen at any period of the gout disease course. In addition to renal damage caused by chronic precipitation of uric acid salts, acute hyperuricemic nephropathy is worthy of attention: it is mostly seen in secondary hyperuricemia, mainly after tumor radiotherapy and chemotherapy, with a sudden and significant increase in blood and uric acid, and a large number of uric acid crystals deposited in renal tubules, collecting ducts, renal pelvis and ureter, causing extensive and severe urinary tract obstruction, manifested as oliguria, anuria and acute renal failure, with a large number of uric acid crystals visible in urine and red blood cells.
(iv) Treatment of intermittent and chronic phases.
The aim is to control blood uric acid at normal levels. Uric acid-lowering drugs are divided into two categories, one is pro-uric acid excretory drugs and the other is inhibitory drugs for uric acid production, both of which have positive efficacy. In order to prevent acute arthritis induced by rapid decrease of blood uric acid after medication, we should start with small dose, gradually increase to therapeutic amount, and then change to maintenance amount after it takes effect, so that blood uric acid can be maintained below 327µmol/l (5.5mg/dl) for a long time.
Uric acid excretory drugs: Inhibit the reabsorption of uric acid in the proximal renal tubules to facilitate uric acid excretion. Since most gout patients belong to the type with reduced uric acid excretion, this class of drugs can be preferred for patients with normal or mildly abnormal renal function (invalid when endogenous creatinine clearance <30ml/min), no urinary stones and uric acid nephropathy. Take alkaline medication such as sodium bicarbonate 1~2g 3 times daily or alkaline combination 10ml 3 times daily to keep urine pH around 6.5 (but not too alkaline to prevent calcium stone formation), and drink plenty of water to maintain urine output.
Benzbromarone is a new type of uric acid excretory drug. 50mg once daily, gradually increase to 100mg once daily. Main side effects: Gastrointestinal reactions such as diarrhea, occasionally rash, allergic conjunctivitis and granulocytopenia.
Inhibitors of uric acid production: Inhibits xanthine oxidase, blocks the conversion of xanthine into uric acid, and reduces uric acid production. It is used for hyperuricemia with excessive production of uric acid, or for those who are not suitable to use uric acid excretory drugs, and also for secondary gout. The representative drug is Allopurinol 100mg once a day, gradually increasing to 100mg-200mg three times a day. 300mg or less can be taken once a day, more than 300mg can be taken orally in divided doses.
Main side effects: gastrointestinal reactions, rash, drug fever, bone marrow suppression, hepatic and renal impairment, and occasionally serious toxic reactions. For those with renal insufficiency, the dosage should be reduced. Liver and kidney function, blood and urine routine should be checked regularly.
Relatively speaking, the side effects of drugs that promote uric acid excretion are significantly less than those of drugs that inhibit uric acid production, and to a lesser extent, so drugs that inhibit uric acid production are the second most important drugs to consider.
(E) Treatment of kidney damage
Treatment of renal lesions: In addition to actively controlling the blood uric acid level, it is very important to alkalize the urine and drink more and urinate more. For gouty nephropathy, thiazide diuretics, tachyphylaxis, and diuretic acid, which affect uric acid excretion, should be avoided when using diuretics, and spironolactone (Amphotericin) can be chosen. The carbonic anhydrase inhibitor acetazolamide, which has both diuretic and alkalizing effects on urine, can also be used. The use of angiotensin-converting enzyme inhibitors to lower blood pressure, avoiding the use of beta-blockers and calcium antagonists that reduce renal blood flow; other treatments are the same as those for chronic kidney damage caused by various causes.
For uric acid urinary tract stones, most of them can be dissolved and excreted by themselves, while large and fixed ones can be treated by extracorporeal lithotripsy or surgery. For acute uric acid nephropathy, in addition to the use of allopurinol to actively reduce blood uric acid, it should be treated as acute renal failure. For chronic renal insufficiency, the treatment is the same as other end-stage renal disease.
Misdiagnosis and omission of gout
In foreign countries, because gout is more common, physicians often diagnose non-gout diseases as gout. In China, because gout is relatively rare, it is often easy to diagnose gout as a non-gout disease. Gouty arthritis is most often misdiagnosed as rheumatoid arthritis in the acute phase, and rheumatoid arthritis is common in the interictal phase.
Surgeons often misdiagnose gout as dengue, cellulitis, septic arthritis, traumatic arthritis, etc. The key is the effective application of penicillin treatment, which is an important cause of long-term misdiagnosis. For uric acid urinary tract stones combined with gout, because stone disease can be the first symptom of gout, it is easy to misdiagnose as simple urinary tract stones and miss the diagnosis of gout. If a gouty nodule breaks down and exudes chalky material, it will be misdiagnosed as osteomyelitis or tuberculous abscess.
IV. Schedule.
Table of purine content of common foods
Classification
Food category
Examples of foods
High purine food
(150-1000 mg/100g)
Animal meat
Liver, intestine, pancreas, heart, stomach, kidney and other animal organs, thick soup
Aquatic products
Fish (sardines, anchovies, mackerel, shark, sea eel, scallops, pomfret and other sea fish, fish skin, fish eggs, dried fish, etc.), shellfish (har gow, tamari, dried shellfish, etc.), shrimp (sea shrimp, shrimp, sea cucumber, etc.)
Legumes and algae
Soybeans, lentils, nori, shiitake mushrooms, etc.
Others
Yeast powder, etc.
Medium purine foods
(25-150 mg/100g)
Livestock meat
Pork, beef, sheep, dog and other livestock meat, chicken, duck, goose, pigeon, quail and other poultry meat
Aquatic products
Fish (grass carp, carp, cod, flounder, perch, swordfish, eel, river eel, etc.) and their products (fish balls, shark fins, etc.), crab, snail
Beans and their products
Dried beans (mung beans, red beans, black beans, broad beans, etc.), bean products (tofu, dried tofu, curd, soy milk, soy milk, soybean milk, bean seedlings, bean sprouts, etc.)
Vegetables
Spinach, bamboo shoots (asparagus, dried bamboo shoots, etc.), asparagus, fresh beans (string beans, fava beans, broad beans, rainbow beans, peas), seaweed, golden needles, silver fungus, cauliflower, lobster, mushrooms, etc.
Others
Peanuts, cashew nuts, almonds, sesame seeds, chestnuts, lotus seeds, etc.
Low purine food
(<25 mg/100g)
Staple foods
Fine rice flour and its products (bread, pastries, cookies, etc.), various starches
Milk and eggs
Milk and its products (fresh milk, cheese, yogurt, milk powder, etc.), eggs and their products (eggs, duck eggs, quail eggs, etc.)
Vegetables
Bok choy, chickpea, cabbage, cabbage, lettuce, amaranth, chrysanthemum, celery, mustard, leek, chives, tomatoes, eggplant, melons (cucumber, winter squash, loofah, pumpkin, bonito, zucchini, bitter melon, etc.), radish (white radish, carrot, etc.), potato, taro, sweet potato, water chestnut, kale, olive, persimmon, pepper, onion, garlic, onion, ginger, fungus, etc.
Fruits
Various kinds of fresh and dried fruits, jams, fruit juices
Beverages
Light tea, carbonated drinks (soda, soft drinks, cola, etc.), mineral water, etc.
Others
Various fats and sugars (which do not contain purines, but should be used in moderation)