Gout ( ) is a form of
inflammatory arthritis Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE).
...
characterized by recurrent attacks of a red, tender, hot and
swollen joint,
caused by deposition of monosodium
urate
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown o ...
monohydrate crystals. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours.
The
joint at the base of the big toe is affected in about half of cases.
It may also result in
tophi
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
,
kidney stone
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
s, or
kidney damage
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...
.
Gout is due to persistently elevated levels of
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
in the blood.
[ This occurs from a combination of diet, other health problems, and genetic factors.][ At high levels, uric acid crystallizes and the crystals deposit in joints, ]tendon
A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...
s, and surrounding tissues, resulting in an attack of gout. Gout occurs more commonly in those who: regularly drink beer or sugar-sweetened beverages; eat foods that are high in purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
s such as liver, shellfish, or anchovies; or are overweight. Diagnosis of gout may be confirmed by the presence of crystals in the joint fluid or in a deposit outside the joint. Blood uric acid levels may be normal during an attack.
Treatment with nonsteroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
(NSAIDs), glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s, or colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken ...
improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
or probenecid
Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.
Probenecid was developed as an alternative to caronamide to competitive ...
provides long-term prevention. Taking vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
and eating a diet high in low-fat dairy products may be preventive.
Gout affects about 1 to 2% of adults in the developed world at some point in their lives.[ It has become more common in recent decades.] This is believed to be due to increasing risk factors in the population, such as metabolic syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome ...
, longer life expectancy, and changes in diet.[ Older males are most commonly affected.] Gout was historically known as "the disease of kings" or "rich man's disease". It has been recognized at least since the time of the ancient Egyptians.[
]
Signs and symptoms
Gout can present in several ways, although the most common is a recurrent attack of acute inflammatory arthritis Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE).
...
(a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases.[ Other joints, such as the heels, knees, wrists, and fingers, may also be affected.] Joint pain usually begins during the night and peaks within 24 hours of onset. This is mainly due to lower body temperature. Other symptoms may rarely occur along with the joint pain, including fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
and a high fever.
Long-standing elevated uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
levels (hyperuricemia
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
) may result in other symptoms, including hard, painless deposits of uric acid crystals known as tophi
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
. Extensive tophi may lead to chronic arthritis
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
due to bone erosion.[ Elevated levels of uric acid may also lead to crystals precipitating in the ]kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s, resulting in stone
In geology, rock (or stone) is any naturally occurring solid mass or aggregate of minerals or mineraloid matter. It is categorized by the minerals included, its Chemical compound, chemical composition, and the way in which it is formed. Rocks ...
formation and subsequent urate nephropathy
Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).
Causes
Acute uric acid nephropath ...
.[
]
Cause
The crystallization
Crystallization is the process by which solid forms, where the atoms or molecules are highly organized into a structure known as a crystal. Some ways by which crystals form are precipitating from a solution, freezing, or more rarely deposi ...
of uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown o ...
, the salts of uric acid. Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%.[ About 10% of people with ]hyperuricemia
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
develop gout at some point in their lifetimes. The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dl), the risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year.[
]
Lifestyle
Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, sugar-sweetened beverages, meat, and seafood. Among foods richest in purines
Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...
yielding high amounts of uric acid are dried anchovies
An anchovy is a small, common forage fish of the family Engraulidae. Most species are found in marine waters, but several will enter brackish water, and some in South America are restricted to fresh water.
More than 140 species are placed in 1 ...
, shrimp, organ meat
Offal (), also called variety meats, pluck or organ meats, is the organs of a butchered animal. The word does not refer to a particular list of edible organs, which varies by culture and region, but usually excludes muscle. Offal may also refer ...
, dried mushrooms
A mushroom or toadstool is the fleshy, spore-bearing Sporocarp (fungi), fruiting body of a fungus, typically produced above ground, on soil, or on its food source. ''Toadstool'' generally denotes one poisonous to humans.
The standard for the na ...
, seaweed
Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of '' Rhodophyta'' (red), ''Phaeophyta'' (brown) and ''Chlorophyta'' (green) macroalgae. Seaweed species such as ...
, and beer yeast. Chicken and potatoes also appear related. Other triggers include physical trauma
An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, ...
and surgery.[
Studies in the early 2000s found that other dietary factors are not relevant.] Specifically, a diet with moderate purine-rich vegetables (e.g., beans
A bean is the seed of several plants in the family Fabaceae, which are used as vegetables for human or animal food. They can be cooked in many different ways, including boiling, frying, and baking, and are used in many traditional dishes th ...
, peas
The pea is most commonly the small spherical seed or the seed-pod of the flowering plant species ''Pisum sativum''. Each pod contains several peas, which can be green or yellow. Botanically, pea pods are fruit, since they contain seeds and d ...
, lentils
The lentil (''Lens culinaris'' or ''Lens esculenta'') is an edible legume. It is an annual plant known for its lens-shaped seeds. It is about tall, and the seeds grow in pods, usually with two seeds in each. As a food crop, the largest produ ...
, and spinach
Spinach (''Spinacia oleracea'') is a leafy green flowering plant native to central and western Asia. It is of the order Caryophyllales, family Amaranthaceae, subfamily Chenopodioideae. Its leaves are a common edible vegetable consumed either f ...
) is not associated with gout. Neither is total dietary protein.[ Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or ]spirits
Spirit or spirits may refer to:
Liquor and other volatile liquids
* Spirits, a.k.a. liquor, distilled alcoholic drinks
* Spirit or tincture, an extract of plant or animal material dissolved in ethanol
* Volatile (especially flammable) liquids, ...
. Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea.
Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout; however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout. Peanuts, brown bread, and fruit also appear protective.[ This is believed to be partly due to their effect in reducing ]insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
.[
Other than dietary and lifestyle choices, the recurrence of gout attacks is also linked to the weather. High ambient temperature and low relative humidity may increase the risk of a gout attack.
]
Genetics
Gout is partly genetic, contributing to about 60% of variability in uric acid level.[ The '']SLC2A9
Solute carrier family 2, facilitated glucose transporter member 9 is a protein that in humans is encoded by the ''SLC2A9'' gene.
This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a signifi ...
'', ''SLC22A12
Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the ''SLC22A12'' gene.
Function
The protein encoded by this gene is a uric acid, urate transpor ...
'', and ''ABCG2
ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ''ABCG2'' gene. ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs a ...
'' genes have been found to be commonly associated with gout and variations in them can approximately double the risk. Loss-of-function mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
s in ''SLC2A9'' and ''SLC22A12'' causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion.[ The rare genetic disorders familial juvenile hyperuricemic nephropathy, ]medullary cystic kidney disease
Medullary cystic kidney disease (MCKD) is an autosomal dominant kidney disorder characterized by tubulointerstitial sclerosis leading to end-stage renal disease. Because the presence of cysts is neither an early nor a typical diagnostic feature of ...
, phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme encoded in humans by the ''HPRT1'' gene.
HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This r ...
deficiency as seen in Lesch–Nyhan syndrome
Lesch–Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency occurs due to mutations in the ''HPRT1'' gene located on the X chromosome. LNS ...
, are complicated by gout.[
]
Medical conditions
Gout frequently occurs in combination with other medical problems. Metabolic syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome ...
, a combination of abdominal obesity
Abdominal obesity, also known as central obesity and truncal obesity, is a condition when excessive visceral fat around the stomach and abdomen has built up to the extent that it is likely to have a negative impact on health. Abdominal obesity has ...
, hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
, and abnormal lipid levels, occurs in nearly 75% of cases.[ Other conditions commonly complicated by gout include ]lead poisoning
Lead poisoning, also known as plumbism and saturnism, is a type of metal poisoning caused by lead in the body. The brain is the most sensitive. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, inferti ...
, kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
, psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, solid organ transplants, and myeloproliferative disorders
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid growt ...
such as polycythemia
Polycythemia (also known as polycythaemia) is a laboratory finding in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythr ...
. A body mass index
Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
greater than or equal to 35 increases male risk of gout threefold.[ Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.
]
Medication
Diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
s have been associated with attacks of gout, but a low dose of hydrochlorothiazide
Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in tho ...
does not seem to increase risk.[ Other medications that increase the risk include ]niacin
Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
, aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
(acetylsalicylic acid), ACE inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
s, angiotensin receptor blocker
Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...
s, beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s, ritonavir
Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...
, and pyrazinamide
Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It i ...
.[ The ]immunosuppressive drug
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified into ...
s ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...
and tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
are also associated with gout,[ the former more so when used in combination with hydrochlorothiazide. Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).
]
Pathophysiology
Gout is a disorder of purine metabolism
Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.
Biosynthesis
Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ri ...
, and occurs when its final metabolite, uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...
, crystallizes in the form of monosodium urate, precipitating
In an aqueous solution, precipitation is the process of transforming a dissolved chemical substance, substance into an insoluble solid from a Supersaturated solution, super-saturated solution. The solid formed is called the precipitate. In cas ...
and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues.[ Microscopic ]tophi
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation. Naked crystals may break out of walled-off tophi due to minor physical damage to the joint, medical or surgical stress, or rapid changes in uric acid levels. When they break through the tophi, they trigger a local immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
-mediated inflammatory reaction in macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
, which is initiated by the NLRP3
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1.
NLRP3 is ...
inflammasome protein complex. Activation of the NLRP3 inflammasome recruits the enzyme caspase 1
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis ...
, which converts pro-interleukin 1β into active interleukin 1β
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
, one of the key proteins in the inflammatory cascade. An evolutionary loss of urate oxidase
The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:
:Uric acid + O2 + H2O → 5-hydroxyisourate + H2O2
: 5-hydroxyisourate + H2O → al ...
(uricase), which breaks down uric acid, in humans and higher primate
Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...
s has made this condition common.
The triggers for precipitation of uric acid are not well understood. While it may crystallize at normal levels, it is more likely to do so as levels increase. Other triggers believed to be important in acute episodes of arthritis include cool temperatures, rapid changes in uric acid levels, acidosis
Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma.
The term ''acidemia'' describes t ...
, articular hydration and extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
proteins. The increased precipitation at low temperatures partly explains why the joints in the feet are most commonly affected. Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
and diuretics. The starting or increasing of urate-lowering medications can lead to an acute attack of gout with febuxostat
Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, m ...
of a particularly high risk. Calcium channel blocker
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s and losartan
Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin II receptor antagonist, angiotensin receptor blocker (ARB) family of medication, and is consider ...
are associated with a lower risk of gout compared to other medications for hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
.
Diagnosis
Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done if the diagnosis is in doubt.[ Plain ]X-rays
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 Picometre, picometers to 10 Nanometre, nanometers, corresponding to frequency, ...
are usually normal and are not useful for confirming a diagnosis of early gout.[ They may show signs of chronic gout such as bone erosion.][
]
Synovial fluid
A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid
Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular ...
or a tophus
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
. All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis
Arthrocentesis, or joint aspiration, is the clinical procedure performed to diagnose and, in some cases, treat musculoskeletal conditions. The procedure entails using a syringe to collect synovial fluid from or inject medication into the joint cap ...
should be examined for these crystals.[ Under ]polarized light
Polarization (also polarisation) is a property applying to transverse waves that specifies the geometrical orientation of the oscillations. In a transverse wave, the direction of the oscillation is perpendicular to the direction of motion of the ...
microscopy, they have a needle-like morphology and strong negative birefringence
Birefringence is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are said to be birefringent (or birefractive). The birefring ...
. This test is difficult to perform and requires a trained observer. The fluid must be examined relatively soon after aspiration, as temperature and pH affect solubility.[
]
Blood tests
Hyperuricemia
Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7&nbs ...
is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout.[ Thus, the diagnostic utility of measuring uric acid levels is limited.][ Hyperuricemia is defined as a ]plasma
Plasma or plasm may refer to:
Science
* Plasma (physics), one of the four fundamental states of matter
* Plasma (mineral), a green translucent silica mineral
* Quark–gluon plasma, a state of matter in quantum chromodynamics
Biology
* Blood pla ...
urate level greater than 420 μmol/L (7.0 mg/dl) in males and 360 μmol/L (6.0 mg/dl) in females. Other blood tests commonly performed are white blood cell count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
, electrolyte
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
s, kidney function
Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.
Functions of a healthy kidney include maintaining a person's fluid ...
and erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
(ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection. A white blood cell count as high as 40.0×109/l (40,000/mm3) has been documented.[
]
Differential diagnosis
The most important differential diagnosis
In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
in gout is septic arthritis
Acute septic arthritis, infectious arthritis, suppurative arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, hea ...
.[ This should be considered in those with signs of infection or those who do not improve with treatment.][ To help with diagnosis, a synovial fluid ]Gram stain
In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish ...
and culture may be performed.[ Other conditions that can look similar include CPPD (pseudogout), ]rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
, psoriatic arthritis
Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. Thi ...
, palindromic rheumatism, and reactive arthritis
Reactive arthritis, also known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can ...
.[ Gouty tophi, in particular when not located in a joint, can be mistaken for ]basal cell carcinoma
Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...
or other neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s.
File:Light microscopy of a touch preparation of a gout tophus, showing urate crystals.jpg, Light microscopy of a touch preparation of a gout tophus
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
, showing needle-shaped crystals.
File:Birefringence microscopy of gout, annotated.jpg, Uric acid crystals in polarized light, showing negative birefringence
Birefringence is the optical property of a material having a refractive index that depends on the polarization and propagation direction of light. These optically anisotropic materials are said to be birefringent (or birefractive). The birefring ...
, with yellow color when aligned parallel to the axis of the red compensator, and blue when aligned perpendicularly to it.
File:Birefringence microscopy of pseudogout, annotated.jpg, In contrast, CPPD (pseudogout) displays rhombus-shaped crystals with positive birefringence.
File:Gichtfuss im Roentgenbild 002.png, Gout on X-rays
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 Picometre, picometers to 10 Nanometre, nanometers, corresponding to frequency, ...
of a left foot in the metatarsal-phalangeal joint of the big toe. Note also the soft tissue swelling at the lateral border of the foot.
Prevention
Risk of gout attacks can be lowered by complete abstinence from drinking alcoholic beverages
An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The cons ...
, reducing the intake of fructose
Fructose, or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galacto ...
(e.g. high fructose corn syrup
High-fructose corn syrup (HFCS), also known as glucose–fructose, isoglucose and glucose–fructose syrup, is a sweetener made from corn starch. As in the production of conventional corn syrup, the starch is broken down into glucose by enzym ...
) and purine
Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
-rich foods of animal origin, such as organ meats and seafood
Seafood is any form of sea life regarded as food by humans, prominently including fish and shellfish. Shellfish include various species of molluscs (e.g. bivalve molluscs such as clams, oysters and mussels, and cephalopods such as octopus an ...
.[ Eating ]dairy product
Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
s, vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
-rich foods, coffee
Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulant, stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world.
S ...
, and cherries
A cherry is the fruit of many plants of the genus ''Prunus'', and is a fleshy drupe (stone fruit).
Commercial cherries are obtained from cultivars of several species, such as the sweet ''Prunus avium'' and the sour ''Prunus cerasus''. The nam ...
may help prevent gout attacks, as does losing weight. Gout may be secondary to sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...
via the release of purines from oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks.
Medications
As of 2020, allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
is generally the recommended preventative treatment if medications are used. A number of other medications may occasionally be considered to prevent further episodes of gout, including probenecid
Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.
Probenecid was developed as an alternative to caronamide to competitive ...
, febuxostat
Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, m ...
, benzbromarone
Benzbromarone is a uricosuric agent and non-competitive inhibitor of xanthine oxidase used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to ...
, and colchicine. Long term medications are not recommended until a person has had two attacks of gout,[ unless destructive joint changes, tophi, or ]urate nephropathy
Acute uric acid nephropathy (AUAN, also acute urate nephropathy) is a rapidly worsening (decreasing) kidney function (acute kidney injury) that is caused by high levels of uric acid in the urine (hyperuricosuria).
Causes
Acute uric acid nephropath ...
exist. It is not until this point that medications are cost-effective.[ They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.][ They are often used in combination with either an NSAID or colchicine for the first three to six months.]
While it has been recommended that urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/L (5.0–6.0 mg/dl),[ there is little evidence to support this practice over simple putting people on a standard dose of allopurinol. If these medications are in chronic use at the time of an attack, it is recommended that they be continued.][ Levels that cannot be brought below 6.0 mg/dl while attacks continue indicates refractory gout.
While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable.] Allopurinol blocks uric acid production, and is the most commonly used agent.[ Long term therapy is safe and well-tolerated and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.][ The ''HLA-B*58:01'' allele of the ]human leukocyte antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of th ...
B (''HLA-B
HLA-B (major histocompatibility complex, class I, B) is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B is part of a family of genes called the human leukocyte antigen (HLA) compl ...
'') is strongly associated with severe cutaneous adverse reactions
Severity or Severely may refer to:
* ''Severity'' (video game), a canceled video game
* "Severely" (song), by South Korean band F.T. Island
See also
*
*
{{disambig ...
during treatment with allopurinol and is most common among Asian
Asian may refer to:
* Items from or related to the continent of Asia:
** Asian people, people in or descending from Asia
** Asian culture, the culture of the people from Asia
** Asian cuisine, food based on the style of food of the people from Asi ...
subpopulations, notably those of Korean
Korean may refer to:
People and culture
* Koreans, ethnic group originating in the Korean Peninsula
* Korean cuisine
* Korean culture
* Korean language
**Korean alphabet, known as Hangul or Chosŏn'gŭl
**Korean dialects and the Jeju language
** ...
, Han-Chinese, or Thai
Thai or THAI may refer to:
* Of or from Thailand, a country in Southeast Asia
** Thai people, the dominant ethnic group of Thailand
** Thai language, a Tai-Kadai language spoken mainly in and around Thailand
*** Thai script
*** Thai (Unicode block ...
descent.
Febuxostat is only recommended in those who cannot tolerate allopurinol. There are concerns about more deaths with febuxostat compared to allopurinol. Febuxostat may also increase the rate of gout flares during early treatment. However, there is tentative evidence that febuxostat may bring down urate levels more than allopurinol.
Probenecid appears to be less effective than allopurinol and is a second line agent.[ Probenecid may be used if undersecretion of uric acid is present (24-hour urine uric acid less than 800 mg).] It is, however, not recommended if a person has a history of kidney stone
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
s.[ ]Pegloticase
Pegloticase (trade name Krystexxa) is a medication for the treatment of severe, treatment-refractory, chronic gout. It is a third line treatment in those in whom other treatments are not tolerated. The drug is administered by infusion intravenously ...
is an option for the 3% of people who are intolerant to other medications. It is a third line agent.[ Pegloticase is given as an intravenous infusion every two weeks,][ and reduces uric acid levels. Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it.][ Using ]lesinurad
Lesinurad (brand name Zurampic) is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is only recommended together with either allopurinol or febuxostat when these medications are not sufficient.
I ...
plus febuxostat
Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, m ...
is more beneficial for tophi resolution than lesinural with febuxostat, with similar side effects. Lesinural plus allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
is not effective for tophi resolution. Potential side effects include kidney stones, anemia and joint pain. In 2016, it was withdrawn from the European market.
Lesinurad
Lesinurad (brand name Zurampic) is a urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is only recommended together with either allopurinol or febuxostat when these medications are not sufficient.
I ...
reduces blood uric acid levels by preventing uric acid absorption in the kidneys. It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets. Side effects include kidney problem
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
s and kidney stone
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
s.
Treatment
The initial aim of treatment is to settle the symptoms of an acute attack. Repeated attacks can be prevented by medications that reduce serum uric acid levels. Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain. Options for acute treatment include nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s (NSAIDs), colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken ...
, and glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s.[ While glucocorticoids and NSAIDs work equally well, glucocorticoids may be safer. Options for prevention include ]allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
, febuxostat
Febuxostat, sold under the brand names Uloric and Adenuric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally recommended only for people who cannot take allopurinol. When initially started, m ...
, and probenecid
Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.
Probenecid was developed as an alternative to caronamide to competitive ...
. Lowering uric acid levels can cure the disease.[ Treatment of associated health problems is also important.][ Lifestyle interventions have been poorly studied.][ It is unclear whether dietary supplements have an effect in people with gout.
]
NSAIDs
NSAIDs are the usual first-line treatment for gout. No specific agent is significantly more or less effective than any other.[ Improvement may be seen within four hours and treatment is recommended for one to two weeks.][ They are not recommended for those with certain other health problems, such as ]gastrointestinal bleeding
Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may incl ...
, kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, or heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
.[ While ]indometacin
Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness
Stiffness is the extent to which an object resists deformation in response t ...
has historically been the most commonly used NSAID, an alternative, such as ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
, may be preferred due to its better side effect profile in the absence of superior effectiveness. For those at risk of gastric side effects from NSAIDs, an additional proton pump inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
They are the most potent inhibitors ...
may be given. There is some evidence that COX-2 inhibitor
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and i ...
s may work as well as nonselective NSAIDs for acute gout attack with fewer side effects.
Colchicine
Colchicine
Colchicine is a medication used to treat gout and Behçet's disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken ...
is an alternative for those unable to tolerate NSAIDs.[ At high doses, side effects (primarily gastrointestinal upset) limit its usage.] At lower doses, which are still effective, it is well tolerated.[ Colchicine may interact with other commonly prescribed drugs, such as ]atorvastatin
Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
Common ...
and erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
, among others.
Glucocorticoids
Glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s have been found to be as effective as NSAIDs and may be used if contraindications exist for NSAIDs. They also lead to improvement when injected into the joint.[ A joint infection must be excluded, however, as glucocorticoids worsen this condition.][ There were no short-term adverse effects reported.
]
Others
Interleukin-1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
inhibitors, such as canakinumab
Canakinumab (International Nonproprietary Name, INN), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including adult-onset Still's disease (AOSD). ...
, showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of adverse event
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can ther ...
s, such as back pain, headache, and increased blood pressure. They, however, may work less well than usual doses of NSAIDS.[ The high cost of this class of drugs may also discourage their use for treating gout.][
]
Prognosis
Without treatment, an acute attack of gout usually resolves in five to seven days; however, 60% of people have a second attack within one year.[ Those with gout are at increased risk of ]hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, metabolic syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome ...
, and kidney and cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
and thus are at increased risk of death. It is unclear whether medications that lower urate affect cardiovascular disease risks. This may be partly due to its association with insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
and obesity, but some of the increased risk appears to be independent.[
Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi.][ These tophi occur in 30% of those who are untreated for five years, often in the ]helix
A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...
of the ear, over the olecranon
The olecranon (, ), is a large, thick, curved bony eminence of the ulna, a long bone in the forearm that projects behind the elbow. It forms the most pointed portion of the elbow and is opposite to the cubital fossa or elbow pit. The olecranon ...
processes, or on the Achilles tendons
The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris muscle, plantaris, gastrocnemius muscle, gastrocnemius (calf ...
.[ With aggressive treatment, they may dissolve. ]Kidney stones
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
also frequently complicate gout, affecting between 10 and 40% of people, and occur due to low urine pH promoting the precipitation of uric acid.[ Other forms of chronic kidney dysfunction may occur.][
File:Case 30-top.jpg, Gouty ]tophi
A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people wit ...
presenting as nodules on the finger and helix of the ear
Image:ChronicGout.jpg, Tophus of the knee
Image:Case 30-bottom.jpg, Tophii on the toe and ankle
Image:Tophigout.JPG, Gout complicated by ruptured tophi, the exudate of which tested positive for uric acid crystals
File:Gout Comparison.jpg, Gout in the big toe of left foot, compared to the healthy right foot
Image:GoutCropped2016.jpg, Gout in the joint of the big toe
File:Gross pathology of tophus.jpg, Gross pathology
Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of ...
of a large tophus
Epidemiology
Gout affects around 1–2% of people in the Western world
The Western world, also known as the West, primarily refers to the various nations and state (polity), states in the regions of Europe, North America, and Oceania. at some point in their lifetimes and is becoming more common.[ Some 5.8 million people were affected in 2013.] Rates of gout approximately doubled between 1990 and 2010. This rise is believed to be due to increasing life expectancy, changes in diet and an increase in diseases associated with gout, such as metabolic syndrome and high blood pressure
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
. Factors that influence rates of gout include age, race, and the season of the year. In men over 30 and women over 50, rates are 2%.
In the United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, gout is twice as likely in males of African descent than those of European descent. Rates are high among Pacific Islanders and the Māori
Māori or Maori can refer to:
Relating to the Māori people
* Māori people of New Zealand, or members of that group
* Māori language, the language of the Māori people of New Zealand
* Māori culture
* Cook Islanders, the Māori people of the C ...
, but the disease is rare in aboriginal Australians
Aboriginal Australians are the various Indigenous peoples of the Australian mainland and many of its islands, such as Tasmania, Fraser Island, Hinchinbrook Island, the Tiwi Islands, and Groote Eylandt, but excluding the Torres Strait Islands ...
, despite a higher mean uric acid serum concentration in the latter group. It has become common in China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
, Polynesia
Polynesia () "many" and νῆσος () "island"), to, Polinisia; mi, Porinihia; haw, Polenekia; fj, Polinisia; sm, Polenisia; rar, Porinetia; ty, Pōrīnetia; tvl, Polenisia; tkl, Polenihia (, ) is a subregion of Oceania, made up of ...
, and urban Sub-Saharan Africa
Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
.[ Some studies found that attacks of gout occur more frequently in the spring. This has been attributed to seasonal changes in diet, alcohol consumption, physical activity, and temperature.
]
History
The term "gout" was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word ''gutta'', meaning "a drop" (of liquid). According to the ''Oxford English Dictionary
The ''Oxford English Dictionary'' (''OED'') is the first and foundational historical dictionary of the English language, published by Oxford University Press (OUP). It traces the historical development of the English language, providing a com ...
'', this is derived from humorism
Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek and Roman physicians and philosophers.
Humorism began to fall out of favor in the 1850s ...
and "the notion of the 'dropping' of a morbid material from the blood in and around the joints".
Gout has been known since antiquity. Historically, it was referred to as "the king of diseases and the disease of kings"[ or "rich man's disease".][ The Ebers papyrus and the ]Edwin Smith papyrus
The Edwin Smith Papyrus is an ancient Egyptian medical text, named after Edwin Smith who bought it in 1862, and the oldest known surgical treatise on trauma. From a cited quotation in another text, it may have been known to ancient surgeons as t ...
, () each mention arthritis of the first metacarpophalangeal joint as a distinct type of arthritis. These ancient manuscripts cite (now missing) Egyptian texts about gout that are claimed to have been written 1,000 years earlier by Imhotep
, other_names = Asclepius (name in Greek) Imouthes (also name in Greek)
, burial_place = Saqqara (probable)
, occupation = chancellor to the Pharaoh Djoser and High Priest of Ra
, years_active =
, known_for ...
. Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
physician Hippocrates
Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of ...
around 400 BC commented on it in his ''Aphorisms
An aphorism (from Ancient Greek, Greek ἀφορισμός: ''aphorismos'', denoting 'delimitation', 'distinction', and 'definition') is a concise, terse, laconic, or memorable expression of a general truth or principle. Aphorisms are often hand ...
'', noting its absence in eunuchs
A eunuch ( ) is a male who has been castrated. Throughout history, castration often served a specific social function.
The earliest records for intentional castration to produce eunuchs are from the Sumerian city of Lagash in the 2nd millennium ...
and premenopausal
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
women. Aulus Cornelius Celsus
Aulus Cornelius Celsus ( 25 BC 50 AD) was a Roman encyclopaedist, known for his extant medical work, ''De Medicina'', which is believed to be the only surviving section of a much larger encyclopedia. The ''De Medicina'' is a primary source on d ...
(30 AD) described the linkage with alcohol, later onset in women and associated kidney problems:
Benjamin Welles, an English physician authored the first medical book on gout, ''A Treatise of the Gout, or Joint Evil'', in 1669. In 1683, Thomas Sydenham
Thomas Sydenham (10 September 1624 – 29 December 1689) was an English physician. He was the author of ''Observationes Medicae'' which became a standard textbook of medicine for two centuries so that he became known as 'The English Hippocrate ...
, an English physician, described its occurrence in the early hours of the morning and its predilection for older males:
Dutch scientist Antonie van Leeuwenhoek
Antonie Philips van Leeuwenhoek ( ; ; 24 October 1632 – 26 August 1723) was a Dutch microbiologist and microscopist in the Golden Age of Dutch science and technology. A largely self-taught man in science, he is commonly known as " the ...
first described the microscopic appearance of urate crystals in 1679. In 1848, English physician Alfred Baring Garrod
Sir Alfred Baring Garrod (3 May 1819 – 28 December 1907) was an English physician.
Garrod was born in Ipswich, the son of Robert and Sarah (née Ennew) Garrod. He initially apprenticed at Ipswich Hospital, and later moved to University College ...
identified excess uric acid in the blood as the cause of gout.
Other animals
Gout is rare in most other animals due to their ability to produce uricase
The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:
:Uric acid + O2 + H2O → 5-hydroxyisourate + H2O2
:5-hydroxyisourate + H2O → allan ...
, which breaks down uric acid. Humans and other great apes
The Hominidae (), whose members are known as the great apes or hominids (), are a taxonomic family of primates that includes eight extant species in four genera: '' Pongo'' (the Bornean, Sumatran and Tapanuli orangutan); ''Gorilla'' (the east ...
do not have this ability; thus, gout is common.[ Other animals with uricase include fish, amphibians and most non-primate mammals.] The ''Tyrannosaurus rex
''Tyrannosaurus'' is a genus of large theropod dinosaur. The species ''Tyrannosaurus rex'' (''rex'' meaning "king" in Latin), often called ''T. rex'' or colloquially ''T-Rex'', is one of the best represented theropods. ''Tyrannosaurus'' live ...
'' specimen known as " Sue" is believed to have had gout.
Research
A number of new medications are under study for treating gout, including anakinra
Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modifi ...
, canakinumab
Canakinumab (International Nonproprietary Name, INN), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including adult-onset Still's disease (AOSD). ...
, and rilonacept
Rilonacept, sold under the brand name Arcalyst, is a medication used to treat cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome, and Muckle–Wells syndrome; deficiency of interleukin-1 receptor antagonist ...
. Canakinumab may result in better outcomes than a low dose of a glucocorticoid, but costs five thousand times more. A recombinant uricase
The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:
:Uric acid + O2 + H2O → 5-hydroxyisourate + H2O2
:5-hydroxyisourate + H2O → allan ...
enzyme (rasburicase
Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is kno ...
) is available but its use is limited, as it triggers an immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
response. Less antigenic
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
versions are in development.[
]
References
External links
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{{Authority control
Arthritis
Articles containing video clips
Inborn errors of purine-pyrimidine metabolism
Inflammatory polyarthropathies
Rheumatology
Wikipedia medicine articles ready to translate (full)
Wikipedia emergency medicine articles ready to translate
Skin conditions resulting from errors in metabolism
Steroid-responsive inflammatory conditions
Uric acid
Crystal deposition diseases