-10	Mten.
-10-
-9	274.0 274.1 274.8 274.9
-9-	, ,
OMIM	138900
DiseasesDB	29031
MedlinePlus
eMedicine	emerg/221 med / 924 med / 1112 oph / 506 orthoped / 124 radio / 313
MeSH	D006073

́ (.-. ποδάγρα,  — ; πούς, . . ποδός — ἄγρα — , )^[3] — , . , ().  — . . , , . , , .

. 2600  . .^{[4] [4]}. V  . . «», , ^[5][6]. ^[7]. 150 , «, »^[8].

XVII - , 30 , « » (. «Tractatus de podagra et hydrope»). « » , , « »^[9]. 1679 ^[5].

1848 (Alfred Baring Garrod, 1819—1906) , , , ^[10][11][12].

: « » (. Les altérations des cartilages dans la gouite, 1858), « () » (Les concrétions tophacées de l’oreille externe chez les goutteux, 1860), « » (Les altérations du rein chez les goutteux, 1864), « » (Les rapports de la goutte et de l’intoxication saturnine, 1864).

In 1899, the presence of urate crystals in the joint fluid was discovered during an attack of gouty arthritis. In 1961, MacCarty and Hollander revealed the role of urate crystals in the onset and development of gouty inflammation ^[13] .

Historically, from the Middle Ages to the 20th century, mainly rich and noble people suffered gout, in connection with which it was called “the disease of the kings” ^{[4] [14]} , “the disease of the rich” and “the disease of the aristocrats” ^[4] . It was believed that it was associated with overweight, overeating (especially the abuse of meat) and excessive consumption of alcoholic beverages. For example, in 1739, the Frenchman Eugene Mushron ( fr.  Eugene Moucheron) published a pamphlet entitled “On Noble Gout and the Virtues Accompanying It,” in which he praised gout and noted that it was a disease of kings, princes, prominent commanders, intelligent and gifted people, and also cited examples of crowned persons, politicians, and artists, suffering from gout ^[15] . A new outburst of interest in gout arose at the beginning of the 20th century, when Havelock Ellis ( Eng.  Henry Havelock Ellis , 1859-1939) published in 1927 a book called The History of English Genius. In it, the author dealt with the topic of gout and cited as an example 55 well-known prominent English people who suffer from it ^[16] . In 1955, the work of Egon Orowan, “ The origin of man, ” published in the journal “Nature ”, in which he described the increased incidence of gout infections among geniuses and explained that uric acid is structurally very similar to methylated purines: caffeine , theophylline and theobromine , which are stimulants of mental activity that have a stimulating effect on higher brain functions, in particular , attention span and ability to concentrate. Orovan pointed out that uric acid in all developed mammals , with the exception of anthropoid apes and humans, is broken down by the action of the uricase enzyme produced in the liver to allantoin, in primates, due to the lack of uricase, it remains in the blood ^[16]

Epidemiology

Hyperuricemia is detected in 4-12% of the population, 0.1% of the Russian population suffers from gout ^[17] . In the United States and Europe, 2% of people suffer from gout, among men aged 55–65 years, 4–6% suffer from gout.

The ratio of men to women is from 7: 1 to 19: 1. The peak incidence occurs in 40-50 years in men, 60 years and older in women. Before menopause, women rarely get sick, probably due to the effect of estrogen on uric acid excretion ^[17] .

The frequency of gouty arthritis in different populations varies from 5 to 50 per 1000 men and 1-9 per 1000 women, and the number of new cases per year is 1–3 per 1000 in men and 0.2 per 1000 in women ^[17] . Over the last decade^{[ when? ] the} incidence of gout has increased ^[18] .

An acute attack of gout in adolescents and young people is rarely observed, usually it is mediated by a primary or secondary defect in the synthesis of uric acid ^[17] .

Etiology

Disease development factors

There are a number of risk factors that contribute to the occurrence and development of gout in certain individuals.

Risk factors for gout include arterial hypertension , hyperlipidemia , and also:

• increased intake of purine bases in the body , for example, when consuming a large amount of red meat (especially offal), some varieties of fish, cocoa, tea, chocolate, peas, lentils, fructose, alcohol (especially beer, which contains a lot of guanosine and xanthine - precursors of uric acid );
• an increase in the number of purine nucleotides with general catabolism (for example, with antitumor therapy; massive apoptosis in people with autoimmune diseases);
• inhibition of uric acid excretion in urine (for example, with renal failure);
• increased synthesis of uric acid while reducing its excretion from the body (for example, with alcohol abuse, shock conditions, glycogenesis with glucose-6-phosphatase deficiency);
• hereditary predisposition (the nature of inheritance is still not completely clarified).

Pathogenesis

The pathogenesis of the disease is based on an increase in the level of uric acid in the blood. But this symptom is not a synonym for the disease, since hyperuricemia is also observed in other diseases (blood diseases, tumors, kidney diseases, etc.), extremely high physical overload and eating fatty foods.

There are at least three main elements of the occurrence of gout:

• accumulation of uric acid compounds in the body;
• deposition of these compounds in organs and tissues;
• the development of acute attacks of inflammation in these lesions, the formation of gouty granulomas and gouty "cones" - tofuses, usually around the joints.

Symptoms and course of the disease

The complete natural evolution of gout goes through four stages:

• asymptomatic hyperuricemia;
• acute gouty arthritis ;
• intercritical period;
• chronic gouty deposits in the joints.

Nephrolithiasis can develop at any stage except the first. There is a constantly increased concentration of uric acid in blood plasma and in urine; joint inflammation of the type of monoarthritis, which is accompanied by severe pain and fever; urolithiasis and recurrent pyelonephritis, resulting in nephrosclerosis and renal failure.

Diagnostics

The diagnosis of gouty arthritis can be made on the basis of the epidemiological diagnostic criteria adopted at the third international symposium on the study of rheumatic diseases, New York , 1966 .

1. With chemical or microscopic detection of uric acid crystals in the synovial fluid or deposition of urate in the tissues.

2. If there are two or more of these criteria:

• a clear history and / or observation of at least two attacks of pain swelling of the joints of the extremities (attacks, at least in the early stages, should begin suddenly with severe pain; complete clinical remission should occur within 1-2 weeks );
• a clear history and / or observation of a gouty attack (see above) with damage to the big toe;
• clinically proven tofus; a clear history and / or observation of a quick reaction to colchicine , that is, a decrease in objective signs of inflammation within 48 hours after the start of therapy.

An X-ray study is not included in the list of required diagnostic tests, but it may show tofus deposits of crystals and damage to bone tissue as a result of repeated inflammations. An x-ray may also be useful for monitoring the effects of chronic gout on joints.

Detection of hyperuricemia is not enough to establish a diagnosis, since only 10% of people with hyperuricemia suffer from gout ^[17] .

Diagnostic criteria for gout (WHO 2000)

I. The presence of characteristic crystalline urates in the joint fluid.

II. The presence of tofuses (proven) containing crystalline urates, confirmed chemically or by polarization microscopy.

III. The presence of at least 6 of the 12 signs below:

• more than one acute history of arthritis attack;
• maximum inflammation of the joint in the first day;
• monoarticular nature of arthritis;
• hyperemia of the skin over the affected joint;
• swelling or pain localized in the I metatarsophalangeal joint;
• unilateral damage to the joints of the arch of the foot;
• nodular formations resembling tofus ;
• hyperuricemia
• unilateral lesion of the I metatarsophalangeal joint;
• asymmetric swelling of the affected joint;
• detection on radiographs of subcortical cysts without erosion;
• lack of flora in the joint fluid.

The most reliable signs are acute or, less commonly, subacute arthritis, the detection of crystalline urates in the synovial fluid, and the presence of proven tofuses. Urate crystals look like sticks or thin needles with broken or rounded ends about 10 microns long. Microcrystals of urates in the synovial fluid are found both freely lying and in neutrophils .

Differential Diagnostics

Gout is differentiated with sepsis , which can occur in parallel with it, as well as with other microcrystalline arthritis (crystal-associated synovitis, primarily with chondrocalcinosis (primarily with deposition of calcium pyrophosphate  - especially in the elderly); reactive , psoriatic and rheumatoid arthritis .

Treatment

Patients with gout, first detected or during an exacerbation of the disease, are subject to inpatient treatment in specialized rheumatology departments of regional or city hospitals. Patients with gout during the period of remission of the disease, provided that adequate therapy is prescribed, can be supervised by a rheumatologist , nephrologist at the place of residence in district clinics. The approximate duration of treatment in stationary conditions (specialized rheumatology departments) is 7-14 days, subject to the selection of adequate effective therapy, improvement of clinical and laboratory signs of the disease.

To date, modern pharmacology has not been able to present a single drug that would be universal at the same time, and could really solve the issue of treating gout.

Treatment for gout involves:

1. if possible, quick and careful relief of an acute attack;
2. prevention of relapse of acute gouty arthritis;
3. prevention or regression of complications of the disease caused by the deposition of crystals of monosubstituted sodium urate in joints, kidneys and other tissues;
4. prevention or regression of concomitant symptoms such as obesity , hypertriglyceridemia, or hypertension ;
5. prevention of the formation of uric acid kidney stones.

Treatment for an acute attack of gout

In acute gouty arthritis, anti-inflammatory treatment is performed. Most commonly used colchicine. It is prescribed for oral administration, usually at a dose of 0.5 mg every hour or 1 mg every 2 hours, and treatment is continued until: 1) there is a relief of the patient's condition; 2) there will be no adverse reactions from the gastrointestinal tract or 3) the total dose of the drug will not reach 6 mg against the background of no effect. Colchicine is most effective if treatment is started shortly after the onset of symptoms. In the first 12 hours of treatment, the condition improves significantly in more than 75% of patients. However, in 80% of patients, the drug causes adverse reactions from the gastrointestinal tract, which may occur earlier or simultaneously with a clinical improvement. When ingested, the maximum level of colchicine in plasma is reached after about 2 hours. Therefore, we can assume that its intake is 1,0 mg every 2 hours is less likely to cause the accumulation of a toxic dose until a therapeutic effect occurs. Since, however, the therapeutic effect is associated with the level of colchicine in leukocytes, and not in plasma, the effectiveness of the treatment regimen requires further evaluation.

With the intravenous administration of colchicine, side effects from the gastrointestinal tract do not occur, and the patient's condition improves faster. After a single injection, the level of the drug in leukocytes rises, remaining constant for 24 hours, and can be determined even after 10 days. As an initial dose, 2 mg should be administered intravenously, and then, if necessary, repeat the administration of 1 mg twice with an interval of 6 hours. Special precautions should be taken with the administration of colchicine. It is irritating and, if it enters the surrounding tissue, can cause severe pain and necrosis.. It is important to remember that the intravenous route of administration requires accuracy and that the drug should be diluted in 5-10 volumes of normal saline, and the infusion should be continued for at least 5 minutes. With both oral and parenteral administration, colchicine can inhibit bone marrow function and cause alopecia, liver cell failure, mental depression, convulsions, ascending paralysis, respiratory depression, and death. Toxic effects are more likely in patients with pathology of the liver, bone marrow or kidneys, as well as those receiving maintenance doses of colchicine. In all cases, the dose should be reduced. It should not be prescribed to patients with neutropenia.

In acute gouty arthritis, other anti-inflammatory drugs are also effective, including indomethacin , phenylbutazone , naproxen , etoricoxib, etc.

Indomethacin can be prescribed for oral administration at a dose of 75 mg, after which every 6 hours the patient should receive 50 mg; treatment with these doses continues on the next day after the symptoms disappear, then the dose is reduced to 50 mg every 8 hours (three times) and to 25 mg every 8 hours (also three times). Side effects of indomethacin include gastrointestinal upsets, sodium retention, and symptoms from the central nervous system. Despite the fact that these doses can cause side effects in almost 60% of patients, indomethacin is usually more easily tolerated than colchicine and is probably the treatment of choice for acute gouty arthritis. Uric Acid Excretion Drugs and Allopurinolwith an acute attack, gout is ineffective. In acute gout, especially with contraindications or ineffectiveness of colchicine and non-steroidal anti-inflammatory drugs, systemic or local (i.e. intraarticular) administration of glucocorticoids is beneficial. For systemic administration, whether oral or intravenous, moderate doses should be prescribed for several days, since the concentration of glucocorticoids decreases rapidly and their action ceases. Intra-articular administration of a long-acting steroid drug (for example , triamcinolone hexacetonide at a dose of 15-30 mg) can stop an attack of monoarthritis or bursitis within 24-36 hours. This treatment is especially advisable if you cannot use the standard dosage regimen.

Diet

The traditional dietary guidelines are to limit your intake of purines and alcohol. High purine foods include meat and fish products, as well as tea, cocoa and coffee. Recently, it was also shown that weight loss achieved by a moderate restriction of carbohydrates and high-calorie foods, combined with a proportional increase in protein and unsaturated fatty acids, in gout patients led to a significant decrease in uric acid levels and dyslipidemia ^[19] .

See also

• Microcrystalline Arthritis
• Chondrocalcinosis
• Urata
• Uric acid
• Tofus

Notes

Links

• Uric acid hits your head // Around the world