Gout: a modern view of a literary disease

Pathogenesis of the disease

It is known that purine bases in the human body are broken down into uric acid and then excreted by the kidneys. When the concentration of uric acid in the blood exceeds, its crystals are deposited in the form of monosodium urate in the joints, kidneys, and soft tissues. As a result, arthritis occurs, formations appear on the flexor surfaces of the joints, ears (tophi), kidney damage develops in the form of urate nephropathy, and stones form in the kidneys.

Most often, men aged 30-60 years suffer from gout; in women, the disease develops less frequently, more often in the postmenopausal period.

Scenario from life

The following scenario is common in most cases: a person diagnoses himself with “gout” and prescribes treatment in the format “that’s what our grandmothers did and what age they lived up to!” What does this include? All kinds of lotions, ointments, applications. Of course, dietary restrictions. For example, for some reason all patients are sure that if you have gout you can’t eat…tomatoes! And they don’t eat. The most amazing thing is that the pain attack completely disappears after 2-3 days. And the person is absolutely sure that he has recovered, he has cured himself and outsmarted everyone.

The further course of the disease manifests itself on an individual basis, but the general outline is as follows: nothing bothers us for about a year, and then attacks are repeated more often, become more protracted, other joints are damaged, the patient begins to take analgesics, but they help less and less... The pain becomes unbearable . And at about this stage we meet our lyrical hero. He finally arrives at the clinic.

When such a patient comes to a rheumatologist, then, as a rule, according to his scenario still working in his head, there is certainly a pill that will cure him once and for all, but he himself did not get to it, since his knowledge in medicine, although extensive, is still they have limits.

After the examination, it turns out that in addition to a high level of uric acid in a person, most often there is arterial hypertension, kidney stones, and the kidneys themselves are already working at half their capacity. According to statistics, 50-75% of patients at the stage of chronic gouty inflammation in the joints have kidney damage!

Causes of gout

• Taking medications:
  thiazide diuretics, aspirin (2 g per day), cyclosporines.
• Diseases leading to the appearance of gout symptoms:
  coronary heart disease (CHD), arterial hypertension, metabolic syndrome, chronic renal failure, psoriasis, some blood diseases. The development of gout can also be promoted by organ transplantation and the introduction of a contrast agent during X-ray examinations.
• Abuse of foods rich in purine bases can provoke and aggravate the development of this disease:
  fatty meats and fish, alcohol, carbonated drinks, legumes, eggs, chocolate, mushrooms.

Diagnostics

For an accurate diagnosis, the patient must undergo a complete examination. First, arthrocentesis (synovial fluid sample) is performed to detect the crystalline form of sodium urate. At the same time, a biochemical blood test is performed. If the content of the end product of purine metabolism is excessive, the presence of a disease can be assumed. But the results of the study do not allow a clear diagnosis. The presence of a crystallized form of urate in the joint fluid may indicate a change in purine metabolism. If the disease is chronic, the doctor may prescribe an x-ray. The picture will show changes in diarthrosis.

Signs and symptoms of gout

This is an acute attack of arthritis, usually of one joint, most often the first metatarsophalangeal, ankle or knee. Typically, an attack of arthritis develops in the early morning or at night, in the midst of complete health. It manifests itself in the form of severe pressing pain in one or another joint. The affected joint swells, the temperature in the joint area rises, the skin turns red and begins to become shiny. Usually the pain becomes less during the day, but by night it gets worse again. The duration of a gout attack lasts from two to three days to a week, sometimes more. With a repeated attack, other joints may be involved in such inflammation. With a long course of gout, tophi form on the flexor surfaces of the joints, which can open with the release of uric acid crystals. At this moment, the patient experiences quite intense pain.

Acute gouty arthritis

Acute gouty arthritis occurs as a consequence of hyperuricemia, which is asymptomatic. At the same time, kidney stones may occur. If left untreated, this condition can lead to frequent pyelonephritis, nephrosclerosis and renal failure within 3-4 years. Symptoms of this pathological condition include:

• fever, which is accompanied by severe pain and inflammation in the joints;
• The 1st day of pain is the most painful;
• the skin over the sore joint turns red and becomes hot;
• the joint of the big toe (first metatarsophalangeal) is swollen and very painful;
• asymmetric swelling of the joints.

Symptoms and treatment of acute gouty arthritis should be determined by a doctor by palpation, radiography and culture of synovial fluid.

Criteria for the diagnosis of gout

Example of using diagnostic criteria:

• Attack of arthritis of the first metatarsophalangeal joint - +2 points
• Characteristics of the episode: erythema over the joint, inability to tolerate touch/pressure, great difficulty walking/inability to use the affected joint +3 points
• More than 1 “typical episode of arthritis” – +2 points
• Hyperuricemia (548 µmol/l) – +3 points

Diet

Regardless of the damage to the joints of the hands, feet or knees, the recommendations of a nutritionist cannot be ignored for successful therapy. For a year, jellied meat, veal, liver, lungs, lamb, meat broths, sardines and herring are excluded from the diet. The consumption of ham, liver, game, beans, legumes, radishes, sorrel, sprat, sprat, beer and coffee should be limited.

• Gouty arthritis: forms of the disease and its treatment

Treatment methods for gout

Treatment of gout consists of both pharmacological and non-pharmacological methods, and should take into account the following factors:

• uric acid concentration, number of previous arthritis attacks,
• stage of the disease (asymptomatic increase in uric acid, interictal period, acute or intermittent arthritis, chronic tophi gout,
• age, gender, obesity, hyperuricemic drugs, polypharmacy.

It should be remembered that asymptomatic hyperuricemia does not equate to gout. Currently, there is no data proving the need for drug therapy to maintain normouricemia in such patients; the main method of therapy in this case is the treatment of comorbid diseases, dietary correction and lifestyle modification.

In the treatment of gout, a combination of non-pharmacological and pharmacological treatments is more effective than monotherapy. When treating, it is necessary to take into account the phase of the disease: acute attack of arthritis, inter-attack period, chronic form, tophi form, serum uric acid concentration, number of arthritis attacks, the presence of comorbid conditions such as diabetes mellitus (DM), arterial hypertension, coronary artery disease, and risk factors for hyperuricemia.

The main aspect of therapy is teaching the patient a healthy lifestyle, weight loss, diet, and reducing alcohol intake, especially beer. Dietary restriction of purine-rich animal products and weight loss help reduce serum uric acid levels.

One of the mandatory conditions for the treatment of gout is the control of comorbid diseases - dyslipidemia, alternative hypertension, diabetes mellitus, as well as weight loss and smoking cessation.

Treatment of an acute attack of gouty arthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine (when taken orally) are used to treat an acute attack of gout. One effective treatment is removal of synovial fluid and intra-articular injection of long-acting steroids. This treatment method is effective and safe.

Publications in the media

Gout is a disease associated with a disorder of purine metabolism, characterized by an increase in uric acid in the blood (hyperuricemia) and the deposition of urate in articular and/or periarticular tissues. Detection of hyperuricemia is not enough to establish a diagnosis, because only 10% of people with hyperuricemia have gout. The most common causes are decreased excretion or increased production of uric acid. Chronic gout is characterized by the formation of tophi. Statistical data . Hyperuricemia is detected in 4–12% of the population, gout affects 0.1% of the population. The majority of patients (80–90%) are middle-aged or older with a history of asymptomatic hyperuricemia for 20–30 years. Men are more often affected (20:1). Before menopause, women rarely become ill, possibly due to the effect of estrogen on uric acid excretion. An acute attack of gout is rarely observed in adolescents and young adults and is usually mediated by a primary or secondary defect in uric acid synthesis. The predominant age is over 45 years. Etiology • Overproduction of uric acid with a normal level of excretion is noted in 10% of patients •• Primary overproduction is associated with •• defects in the enzymatic system for the synthesis of uric acid •• increased activity of 5-phosphoribosyl-1-synthetase •• deficiency of hypoxanthine-guanine phosphoribosyl transferase •• with glycogen storage diseases (types 1, 3, 5, 7) •• Secondary hyperproduction is caused by •• increased cell breakdown during alcoholism, myeloproliferative diseases, chronic hemolysis, psoriasis or antitumor chemotherapy •• increased purine catabolism during alcoholism, tissue hypoxia, excessive physical loads •• exposure to drugs: cytostatic immunosuppressants, cyanocobalamin, fructose. • Impaired uric acid excretion (uric acid excretion less than 700 mg/day) is observed in 90% of patients. May be associated with •• diseases leading to a decrease in urate clearance: renal failure, dehydration, acidosis, hyperparathyroidism, hypothyroidism, hyperaldosteronism, eclampsia, hypoestrogenemia •• the action of drugs: diuretics, alcohol, small doses of acetylsalicylic acid, caffeine, diazepam, diphenhydramine, ascorbic acid, lead.

Genetic aspects . The activity of phosphoribosyl pyrophosphate synthetase 1 (311850, PRPS1 gene, Xq22 q24) is controlled by the X chromosome, so only males are affected. Pathogenesis of a gout attack. As a result of prolonged hyperuricemia, microtophi (clusters of crystals) are formed in the synovial membrane and cartilage. Due to injury, increased temperature in the joint, or changes in the concentration of uric acid in the blood or synovial fluid, the microtophi are destroyed and the crystals are released into the joint cavity. Synovial cells produce IL-1, IL-6, IL-8, which act as chemoattractants for neutrophils. Immunoglobulins and complement components opsonize (envelop) urates, stimulating the phagocytic activity of neutrophils. The phagosomes of neutrophils that have absorbed the crystals merge with lysosomes, and lysosomal enzymes destroy the protein shell of the crystals. The crystals damage neutrophils, and lysosomal enzymes released into the synovial cavity trigger inflammation.

Clinical presentation (by stage of progression) • Asymptomatic hyperuricemia - elevated levels of uric acid in the blood in the absence of clinical signs of crystal deposition (ie, no arthritis, tophi, nephropathy or urate stones). • Acute gouty arthritis - the second stage and the first manifest form of gout - sudden onset arthritis with severe pain. A typical attack most often affects one joint on the legs, and in 50% of patients the first metatarsophalangeal joint is affected. Most gout attacks occur at night and occur with a rapid increase in erythema and temperature around the joint, swelling and pain. Inflammation can spread to soft tissues, forming the clinical picture of cellulite or phlebitis. Severe cases are accompanied by an increase in body temperature. The usual duration of an attack is several days, less often several weeks. After an attack, the joint returns to its normal shape. In some cases, a polyarticular variant is also possible. • Interictal period - the third stage of gout - occurs after the end of the first attack and can be interrupted by the next acute attack •• Repeated monoarticular attacks. In 7% of patients, after the first episode of gout, no repeated attacks are noted. However, in 62%, repeated attacks occur during the first year of illness. In typical cases, during the interictal period, patients do not complain, but if the patient does not receive treatment, then each subsequent attack is more severe and the interictal period is shortened • Progression of the disease. Over time, the attacks become more severe and take on the character of polyarthritis. Some patients quickly develop chronic gouty arthritis, with virtually no remissions; in such cases, differential diagnosis is made with rheumatoid arthritis. • Chronic gouty arthritis (chronic tophi gout) occurs in the absence of treatment; it is considered the final stage of gout. Tophus form clusters of urate crystals surrounded by inflammatory cells and fibrous masses. Tophi are dense, mobile, cream or yellowish in color with the release of chalky contents when ulcerated. Typical localization of tophi: auricle; over the affected joints; subchondral parts of the articular surfaces; on the extensor surface of the forearm; in the elbow area; over the Achilles and hamstring tendons. • Kidney damage: nephrolithiasis, tubulointerstitial nephritis. Laboratory data • Leukocytosis in the blood with a shift to the left and acceleration of ESR during acute attacks • Increased uric acid in the blood. In 10% of cases, the concentration of uric acid in the blood is within normal limits • In the synovial fluid, leukocytes are 10–60109/l, predominantly neutrophils. Of diagnostic importance are the determination of needle-shaped urate crystals located intracellularly and birefringent light when examined under a polarizing microscope • In the aspirate of the tophi contents there are crystals of uric acid • The study of daily excretion of uric acid is carried out after a 3-day diet excluding purines. Instrumental data • On the radiograph - pronounced erosions (a “puncture” symptom) in the subchondral zone of the bone, most often in the first metatarsophalangeal joint and in the phalanges of the fingers, but possibly in other joints • Periarticular osteoporosis is not typical. Diagnostic criteria • Presence of characteristic crystalline urates in the joint fluid and/or • Tophi (proven) containing crystalline urates, confirmed chemically or by polarization microscopy • Presence of 6 of the 12 features listed below: •• History of more than one attack of acute arthritis •• Joint inflammation reaches its maximum on the first day of the disease •• Monoarthritis •• Hyperemia of the skin over the affected joint •• Swelling and pain in the first metatarsophalangeal joint •• Unilateral damage to the first metatarsophalangeal joint •• Unilateral damage to the joints of the foot •• Suspicion of tophi •• Hyperuricemia •• Asymmetric swelling of the joints (radiography) •• Subcortical cysts without erosion (radiography) •• Negative results on bacteriological examination of synovial fluid. Differential diagnosis • Infectious arthritis • Pyrophosphate arthropathy • Hydroxyapatite arthropathy • Osteoarthritis • Amyloidosis • Hyperparathyroidism • Rheumatoid arthritis.

TREATMENT General tactics • Prescribe diet No. 6. Treatment with anti-gout drugs is carried out for life in case of primary gout; in case of secondary gout, it is carried out depending on the reversibility of the situation that provokes the development of gout. Regimen • In the acute period - rest. Diet • Products, the consumption of which must be excluded •• alcoholic beverages (especially beer) •• parenchymal organs of animals (liver, kidneys) •Food products, the consumption of which should be limited •• fish (caviar, Baltic herring, sardines, etc.; in the diet larger fish are acceptable), crustaceans •• meat (veal, pork, poultry, broths) •• some vegetables (peas, beans, mushrooms, cauliflower, asparagus, spinach) •Food products that can be consumed without restrictions •• grains ( bread, cereals, bran) •• dairy products (milk, sour cream, cheese) •• all fruits and fruit juices •• fats (butter, margarine, cooking oil) •• coffee, tea, chocolate • most vegetables (potatoes, lettuce, cabbage, tomatoes, cucumbers, pumpkin, onions, carrots, beets, radishes, celery) •• sugar (but: causes weight gain!) •• spices.

Drug treatment • Tactics for asymptomatic hyperuricemia are mainly observational. The level of uric acid excretion is examined. If it is within the normal range, it is rational to limit yourself to dietary recommendations. According to some researchers, when the normal excretion of uric acid is exceeded, it is necessary to prescribe allopurinol, but the advantage of using this drug over non-drug management of the patient has not been shown (due to the possibility of side effects from treatment, as well as its high cost). • In the treatment of acute gouty arthritis, rest and cool wraps are very important • Colchicine plays an important role, prescribed 0.5 mg every hour until the arthritis subsides, or until side effects (vomiting, diarrhea) appear, but not less than 6–8 mg/ days To treat an acute attack of gout, colchicine is used for no more than a day. • NSAIDs (indomethacin, ibuprofen, naproxen, piroxicam, but not salicylates) are usually used in large doses and for a short course (2-3 days). Particular caution should be exercised in case of concomitant diseases of the liver and kidneys, especially in elderly patients. • The introduction of GC into the joint cavity in acute gouty arthritis is dangerous due to the possible presence of unrecognized septic arthritis, which debuted under the guise of gout or against its background. In addition, extreme pain in the joint due to gout makes any manipulation difficult. • Uricostatic and uricosuric drugs are not used during an acute attack, since any fluctuations in the concentration of urates in the blood can prolong an attack of gout. • With reduced urate excretion, preserved renal function and the absence of urinary stones, it is possible to use both uricosuric and uricostatic agents. These properties are combined by allopurinol + benzbromarone, taken 1 tablet 1 time per day. Probenecid, proposed in foreign guidelines for uricostatic purposes, is not registered in the Russian Federation. Allopurinol is considered a generally accepted uricostatic (i.e., blocking urate production) drug. Allopurinol is prescribed at a starting dose of 100 mg/day, followed by a gradual increase in the dose to 300 mg/day over 3–4 weeks. If the GFR is reduced to 30–60 ml/min, the dose of allopurinol should not exceed 100 mg/day, and if the GFR is 60–90 ml/min, it should not exceed 200 mg/day. • In cases of increased uric acid excretion in urine and/or gouty kidney damage, allopurinol is preferred. In the first weeks of allopurinol therapy in such patients, the use of agents that increase the solubility of uric acid in urine is indicated. • In case of secondary gout against the background of hematological, oncological diseases during the period of cytotoxic or radiation therapy, allopurinol remains the treatment of choice. The prognosis is favorable with early recognition and adequate treatment. Prognostically unfavorable factors: development of the disease before the age of 30 years, persistent hyperuricemia over 0.6 mmol/l, persistent hyperuricosuria over 1100 mg/day, the presence of urolithiasis in combination with a urinary tract infection, progressive nephropathy, especially in combination with diabetes and arterial hypertension hypertension. Hyperuricemia is a predictor of MI and death in patients with hypertension and congestive heart failure. Age characteristics • Children and adolescents: the onset of the disease in this age group indicates the presence of inborn errors of metabolism • Elderly people: gout is usually associated with taking drugs. Premenopausal women rarely get sick.

ICD-10 • M10 Gout

Application. Familial calcium gout exists in two forms (*118600, 5p, CCAL1 gene, ; chondrocalcinosis with early manifestation of osteoarthritis, *600668, 8q, CCAL2 gene, ). Clinically: arthropathy, acute intermittent arthritis, ankylosis of joints, chondrocalcinosis. Laboratory findings: calcium pyrophosphate crystals in the synovial fluid with normal serum calcium levels, decreased pyrophosphohydrolase activity in the synovial fluid. Synonyms: limited calcinosis, calcium pyrophosphate storage disease, familial articular chondrocalcinosis.

ICD-10. M11.1 Hereditary chondrocalcinosis.

Recommendations for antihyperuricemic therapy

The goal of antihyperuricemic therapy is to prevent the formation and dissolution of existing monosodium urate crystals by maintaining uric acid (UA) levels below 360 µmol/L.

• Allopurinol

  – promotes adequate long-term antihyperuricemic therapy. The drug is recommended at a dose of 100 mg daily, if necessary, the dose is increased by 100 mg every two to four weeks. Patients with renal failure require dose adjustment of this drug.

• Uricosuric agents

  (probenecid, sulfinpyrazone) are used as an alternative to allopurinol in patients with normal renal function. These drugs are relatively contraindicated in patients with urolithiasis.

• Benzbromarone

  - powerful uricozourik; the drug is more effective than allopurinol. It is used for moderately reduced renal function, but requires monitoring due to hepatotoxicity.

• Colchicine

  can be used as a prophylaxis for joint attacks during the first month of antihyperuricemic therapy (0.5-1.0 grams per day) and/or NSAIDs.

It is worth noting that in patients with gout, diuretics should be discontinued if possible (except for cases where diuretics are prescribed for health reasons).

• Losartan and fenofibrate
  have a moderate uricosuric effect. These drugs are recommended for use in patients who are resistant to or intolerant of allopurinol or other uricosurics, in the presence of hypertension or metabolic syndrome. However, the clinical significance of such therapy and its cost-effectiveness are still unknown.

At the Clinic of High Medical Technologies named after. N.I. Pirogov patients will be able to determine the serum level of uric acid and other important biochemical blood parameters, as well as undergo clinical blood and urine tests, and receive qualified advice from a rheumatologist on treatment both during the interictal period of the disease and during the attack of an acute gouty arthritis.

Symptoms of gouty arthritis

Symptoms and treatment of gouty arthritis may vary depending on the period of the gout disease - latent, acute or chronic. And if during the latent stage only a biochemical test of blood or urine helps to reveal the disease, then an acute gouty attack cannot be missed. The attacks occur irregularly, the intervals between them vary from a couple of weeks to a year or more. Gout is characterized by pain when moving and pressing on the tissue around the affected joint: negative symptoms usually increase at night.

The disease usually affects the small joints of the extremities; in 9 out of 10 cases, the big toe is the first to be affected.

The clinical picture of gouty arthritis in the chronic stage (when pain lasts 3 months or more) implies the presence of exacerbations and remissions. In later stages, deformation of the affected joints and limbs is observed.

By the way, the level of urate in the blood can remain low even despite solid deposits in the joints, ears and adjacent tissues.

Important: arthritis and osteoarthritis contribute to the localization of gouty joint lesions in the affected areas. In this case, differential diagnosis of the two diseases, which can only be carried out by a doctor, is especially important.