Gout

Wikipedia

Gout is a medical condition that usually presents with recurrent attacks of acute inflammatory arthritis (red, tender, hot, swollen joint). It is caused by elevated levels of uric acid in the blood. The uric acid crystallizes and deposits in joints, tendons, and surrounding tissues. Gout affects 1% of Western populations at some point in their lives.[1]

Treatment with NSAIDs, steroids, or colchicine improves symptoms. Once the acute attack has subsided, levels of uric acid are usually lowered via lifestyle changes and long term prevention with allopurinol.[1]

Historically, it was known as "the disease of kings"[2] or "rich man's disease".[3]

[edit] Signs and symptoms

Tophi of the knee.

Gout usually presents as recurrent attacks of acute inflammatory arthritis (a red, tender, hot, swollen joint).[1] The joint that is most commonly affected is the first metatarsalphalangeal joint at the base of the big toe (approximately 75 percent of first attacks) and when this occurs it is known as podagra. The reason gout usually presents in the feet is in part due to their lower temperature.[1]

People with long-standing hyperuricemia can form tophi (uric acid crystal deposits) in tissues. These are usually hard, non-painful deposits. Extensive tophi that invade bone are associated with arthritis due to bone erosion.

Elevated levels of urine uric acid can lead to uric-acid crystals precipitating in the kidneys which may form kidney stones and lead to urate nephropathy.[4]

[edit] Causes

Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons including dietary, genetic, or underexcretion of urate.[1] About 10% of people with hyperuricemia develop gout.[5]

[edit] Lifestyle

About 12% of gout is attributed to dietary causes.[1] This includes a strong association with the consumption of alcohol,[6] sugar,[7] and meat and seafood.[8] The intake of dairy products, vegetables, and the total protein intake do not affect the occurrence of gout.[9]

A sedentary lifestyle also increases the risk of developing the disease.[10]

[edit] Medical conditions

Gout may present as a complication of other medical conditions.

• Metabolic syndrome (the combination of hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk)[11]
• Leukemia

Gout also can develop as a co-morbidity of other diseases, including polycythaemia, intake of cytotoxics, obesity, diabetes, hypertension, renal disorders, and hemolytic anemia. Gout is an important complication in a minority of solid organ transplants.[12]

Gout may occur as a result of renal failure.[13] An example of this is a condition known as Chronic Urate Nephropathy in which crystal deposits form in the renal tubules, interstitium and glomeruli. This results in elevated serum creatinine, urinary sediments, and hyperuricemia disproportionate to the degree of renal insufficiency. Renal impairment is common in patients with gout but usually occurs secondary to other conditions.

Some studies have established a statistical connection between gout and lead poisoning,[14] and a significant correlation between levels of lead in the body, urate excretion and gout.[15] It is known that lead sugar was formerly used to sweeten wine.[16][17] This condition is then known as saturnine gout, as saturnus is the alchemical term for metallic lead.[18]

[edit] Pharmaceuticals

Diuretics have been associated with attacks of gout; low doses of hydrochlorothiazide (HCTZ), however, do not seem to increase the risk.[19]

[edit] Pathophysiology

Uric acid

Gout occurs when crystals of uric acid, in the form of monosodium urate, precipitate on the articular cartilage of joints, on tendons, and in the surrounding tissues. Uric acid is a normal component of blood serum. Uric acid is more likely to form into crystals when there is hyperuricemia, although hyperuricemia is 10 times more common without clinical gout than with it.[20] Gout can also occur when serum uric acid is normal, and when it is abnormally low (hypouricemia). Paradoxically, acute attacks of gout can occur together with a sudden decrease in serum uric acid, such as due to use of drugs (uricosurics, xanthine oxidase inhibitors), or total parenteral nutrition.[21] However, the sudden decrease may be a consequence of abrupt formation of crystals (removing uric acid from the serum), rather than a cause.

Regardless of the serum concentration of uric acid, precipitation of uric acid is markedly enhanced when the blood pH is low (acidosis). A similar pH-sensitive effect occurs in urine,[22] contributing to uric acid nephrolithiasis (kidney stones).

Uric acid is a product of purine metabolism, and in humans is normally excreted in the urine. Purines are generated by the body via breakdown of cells in normal cellular turnover, and also are ingested as part of a normal diet. The kidneys are responsible for approximately two-thirds of uric acid excretion, with the liver responsible for the rest.

[edit] Chemical crystallization

An acute attack occurs as a result of an inflammatory reaction to crystals of sodium urate that are deposited in the joint tissue. The inflammatory response involves the local infiltration of granulocytes which phagocytise the urate crystals. Lactate is high in synovial tissues and in the leucocytes that associated with the inflammatory process which also favours the deposition of uric acid. [23]

[edit] Kamikaze leukocytes

Self Perpetuating Fatal Phagocytosis

KT Rajan studied phagocytosis of urate crystals by polymorphonuclear leucocytes. From his investigations with specific reference to phagocytosis of urate crystals by polymorphonuclear leucocytes he proposed a sequence of events that may initiate the inflammatory reaction in acute gout. He concluded that :

(1) that neutrophil leucocytes avidly ingest microcrystals of sodium monourate

(2) that this causes the rapid degranulation and disintegration of the leucocytes

(3) that fresh leucocytes ingest the debris and crystals liberated by the dead cells, and in their turn degranulate and die, thus possibly establishing a vicious circle in the system.

In support of his theory Rajan quoted research in the 1960’s where McCarty demonstrated that:

The severity of the inflammatory reaction is dependent on the number of neutrophils that are available at the time of invasion by the bacteria or toxic agent. In agranulocytosis the reaction to bacterial invaders by the host is functionally deficient and acute gouty effusions provoked by injecting crystals of uric acid into joints can be abolished by pretreating the host with drugs like vinblastine which reduce the total number of leucocytes available. (McCarty, 1965). [24].

[edit] The wild fire

(A Gradual Fuel Increase Resulting in an Uncontrolled Burn)

Theodore Fields Director, Rheumatology Faculty Practice Plan, Hospital for Special Surgery New York suggests that

Whatever the cause of elevated uric acid levels, the key event in gout is the movement of uric acid crystals into the joint fluid. Inflammatory chemicals are released when the body’s defense mechanisms, engulf the uric acid crystals. All the signs of inflammation, including heat, redness, swelling and pain are caused by these chemicals. (cytokines) The inflammation attracts more white blood cells to the joint, which increases the inflammation.

Theodore stated

“When thinking of gout, a useful model has been proposed by Wortmann. Uric acid crystals can be thought of like matches, which can sit quietly or can be ignited. Crystals can be present for years in the cartilage, or even in the joint fluid, without causing inflammation. Then, at some point, due to increasing number of crystals or other inciting factor, the matches are “struck” and the inflammation begins. This analogy is important both for conceptualizing the uric acid crystals in the joint and for understanding the various types of gout treatment (see below) – some of which attack the inflammation (pour water on the flaming matches) and some of which remove the uric acid crystals (take away the matches).” [25]

[edit] Diagnosis

Spiked rods of uric acid (MSU) crystals photographed under a microscope with polarized light from a synovial fluid sample. Formation of uric acid crystals in the joints are associated with gout.

[edit] Synovial fluid

A definitive diagnosis of gout is based upon the identification of monosodium urate (MSU) crystals in the synovial fluid.[1] They have a needle-like morphology and strong negative birefringence under polarized light. This test is difficult to perform and often requires a trained observer.[26]

[edit] Blood tests

Hyperuricemia is a common feature of gout, so its presence supports a diagnosis of gout. However, gout can occur without hyperuricemia.[27] Hyperuricemia is defined as a plasma urate (uric acid) level greater than 420 μmol/L (7.0 mg/dL) in males, or 380 μmol/L in females. However, a high uric acid level does not necessarily mean a person will develop gout. Urate is within the normal range in up to two-thirds of cases.[28] If gout was suspected, the serum urate test should be repeated once the attack has subsided. Other blood tests commonly performed are full blood count, electrolytes, renal function, thyroid function tests and erythrocyte sedimentation rate (ESR). This helps to exclude other causes of arthritis, most notably septic arthritis, and to investigate any underlying cause for the hyperuricaemia.

[edit] Differential

A critical differential diagnosis in gout is septic arthritis. The only way to definitively rule out this diagnosis is via a joint aspiration and culture.

Clinically, gout can be hard to distinguish from several other conditions, including chondrocalcinosis. Chondrocalcinosis is a very similar disease, caused by deposition of calcium pyrophosphate rather than uric acid.

Gouty tophi, particularly when not located in a joint, can be mistaken for basal cell carcinoma[29] or other neoplasm.[30]

[edit] Prevention

Both lifestyle modifications and medication can decrease uric acid levels. Medications however are not usually started until one to two weeks after an acute attack has resolved due to theoretical concerns of worsening the attack.[1] They are often not recommended until after a second attack of gout has occurred,[1] unless destructive joint changes, tophi, or urate nephropathy exists.[4] It is not until this point that medications have been found to be cost effective.[1] Urate lowering measures should be titrated to decrease serum uric acid levels below 360 µmol/L (6 mg/dL).[1]

[edit] Lifestyle

Dietary and lifestyle choices may decrease the risk of gout. Lowering intake of meat and seafood, consuming adequate vitamin C, limiting alcohol and fructose ingestion, and avoiding obesity have all been shown to be effective in preventing gout.[1] Any lifestyle change that reduces blood pressure will have a favorable effect, but there are concerns that medications for hypertension may aggravate gout.[31]

A low-calorie diet in obese men decreased uric acid levels by 100 µmol/L.[19] Vitamin C intake of 1,500 mg per day decreases the risk of gout by 45% compared to 250 mg per day.[32] Coffee but not tea consumption is associated with a lower risk of gout.[33]

[edit] Allopurinol

Allopurinol blocks uric acid production and is the most commonly used hypourecemic agent.[1] Chronic therapy is safe and well tolerated and can be used in people with renal impairment or urate stones. Hypersensitivity occurs in a small number of people.[1]

[edit] Probenecid

Probenecid is effective for treating hyperuricemia but has been found to be less effective than allopurinol.[1]

[edit] Others

Febuxostat, a non-purine inhibitor of xanthine oxidase, may be an alternative to allopurinol with equivalent effectiveness at reducing attacks of gout. The drug was approved by European Medicines Agency in 2008[34] and by the FDA in 2009.[35]

EDTA, a chelating agent, has successfully increased uric acid excretion.[36] In rare cases, gout may be secondary to untreated sleep apnea via the release of purines as a by-product of the breakdown of oxygen-starved cells. Treatment for apnea can therefore be effective in lessening incidence of acute gout attacks.[37]

[edit] Management

Treatment objectives include managing the symptoms of an acute attacks and preventing further attacks via reducing serum uric acid levels.[38] Options for treatment include application of cold, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and colchicine.[1]

[edit] Conservative

Ice applied for 20 to 30 minutes several times a day decreases pain.[39][1]

[edit] NSAIDs

NSAIDS are the usual first line treatment for gout with no significant difference between agents in effectiveness.[1] Improvement may be seen within 4 hours.[1] They however are not recommended in those with certain other health problems such as gastrointestinal bleeding, renal failure, or heart failure.[40] While indomethacin is historically the most commonly used NSAID, due to concerns of side effects and no evidence of greater benefit, an alternative like ibuprofen may be preferred.[19] For those at risk of gastric irritation from NSAIDs, an additional proton pump inhibitor may be given.[41]

[edit] Steroids

Glucocorticoids have been found to be equally effective to NSAIDs[42] and may be used if contraindications exist for NSAIDs.[1] Intra-articular steroids have also been found to be effective however the risk of concurrent joint infection must be ruled out.[1]

[edit] Colchicine

Colchicine is an alternative for those unable to tolerate NSAIDs.[1] Its side effects (primarily gastrointestinal upset) has decreased its usage.[43][44] Gastrointestinal upset however depends on the dose and the risk can be decreased by using smaller yet still effective doses.[19] Colchicine may interact with other commonly prescribed drugs such as atorvastatin and erythromycin among others.[44]

[edit] Epidemiology

Gout affects 1% of the Western population at some point in their lifetime and is increasing in prevalence.[1] This increases to 2% in men over the age of 30 and women over the age of 50.[40]

Different populations have different propensities to develop gout. In the United States, gout is twice as prevalent in African American males as it is in European-Americans.[45] It is high among the peoples of the Pacific Islands, and the Māori of New Zealand, but rare in Australian aborigines despite the latter's higher mean concentration of serum uric acid.[46]

In the United States and Italy, attacks of gout occur more frequently in the spring.[47][48]

[edit] History

Anton van Leeuwenhoek described the microscopic appearance of uric acid crystals in 1679.[49]

The first written description of gout dates from 2,600 BC, when Egyptians noted gouty arthritis of the big toe. Around 400 BC, the Greek physician Hippocrates also commented on gout.[49] Writing ca. 30 AD, Aulus Cornelius Celsus appeared to recognize many of the features of gout, including its link with a urinary solute, late onset in women, linkage with alcohol, and perhaps even prevention by dairy products:

"Again thick urine, the sediment from which is white, indicates that pain and disease are to be apprehended in the region of joints or viscera. … Joint troubles in the hands and feet are very frequent and persistent, such as occur in cases of podagra and cheiragra. These seldom attack eunuchs or boys before coition with a woman, or women except those in whom the menses have become suppressed. Upon the commencement of pain blood should be let; for when this is carried out at once in the first stages it ensures health, often for a year, sometimes for always. Some also, when they have washed themselves out by drinking asses' milk, evade this disease in perpetuity; some have obtained lifelong security by refraining from wine, mead and venery for a whole year; indeed this course should be adopted especially after the primary attack, even although it has subsided."[50]

Colchicum was described for treatment of rheumatism and swelling in the Ebers Papyrus, ca. 1500 B.C.[51] The use of Colchicum corm for gout probably traces back to ca. 550 A.D., as the "hermodactyl" recommended by Alexander of Tralles. Colchicum corm was used by ibn Sina Persian physician and other Islamic physicians, was recommended by Ambroise Pare in the sixteenth century, and appeared in the London Pharmacopoeia of 1618.[52] In 1833 P.L. Geiger purified an active ingredient, which he named colchicine.[53] Colchicum was brought to America by Benjamin Franklin; Franklin suffered from gout himself and had written humorous doggerel about the disease during his stint as Envoy to France.[54] As a drug predating the FDA, colchicine was sold as a generic in the United States for many years. In 2009 the FDA approved colchicine for gout flares, awarding Colcrys a three year term of market exclusivity, prohibiting generic sales, and increasing the price of the drug from $9 to $485 per bottle.[55][56]

Around 200 AD, the Roman gladiatorial surgeon Galen described gout as a discharge of the four humors of the body in unbalanced amounts into the joints. The word "gout" was initially used by Randolphus of Bocking, around 1200 AD. It is derived from the Latin word "gutta", meaning "a drop" (of liquid).[49]

The Dutch scientist Antonie van Leeuwenhoek described the microscopic appearance of urate crystals in 1679.[49] In 1848 English physician Alfred Baring Garrod realised that excess uric acid in the blood was the cause of gout.[57]

The Tyrannosaurus rex specimen known as "Sue" appears to have suffered from gout.[58]

Historical treatments for gout include gin and numerous medications that have since been found to be not effective. Sodium bicarbonate (baking soda) is a traditional remedy,[59] thought to work by raising blood pH (lowering blood acidity). However, the added sodium may be inappropriate for some people.

[edit] Etymology

The word gout comes from the Latin word gutta (a drop).[1]

[edit] See also

• List of cutaneous conditions
• Pseudogout, one of the names for calcium pyrophosphate deposition disease
• Uric acid nephrolithiasis
• Uricosuria

[edit] References

[edit] External links

• Gout: Medline Plus
• Saag KG, Choi H (2006). "Epidemiology, risk factors, and lifestyle modifications for gout". Arthritis Res. Ther. 8 Suppl 1: S2. doi:10.1186/ar1907. PMID 16820041. 

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Annotations

• N steve h on Sun 18 May 2003, 05:29pm. Flag this

  Speaking as a sufferer from gout, I can attest that it can be almost completely debilitating. It’s caused, we now know, by the buildup of uric acid crystals in joints, giving an almost unbearable pain. Fortunately, modern medicine can handle it, but at Pepys’s time there were only ineffective folk remedies, including eating lots of cherries(not easy to find most times of year in 1660).
  Gout has been called “the disease or kings” or “the patricians’ malady”. It seemed to have a connection with high living. Gout can be aggravated by alcohol, and certain foods (shellfish, beans) can make it worse. But my experience is that there is no easily identifiable cause for most attacks. Gout tends to get progressively worse with time, and can cause deformation of joints, most usually the toes or other [parts of the feet.

  Famous gout sufferers: Benjamin Franklin, Dr. Johnson, Kant, Gibbon, Jefferson, and Milton. Milton reportedly told a friend that if he were only free of gout pain, blindness would be tolerable.

  A book on the history of gout:
  http://www.amazon.com/exec/obidos/ISBN%3D0300073860/

• N Charlezzzzz on Mon 8 Dec 2003, 07:21am. Flag this

  Gout has been called

• N Charlezzzzz on Sat 27 Dec 2003, 06:15am. Flag this

  “He died, 1686, of gout in the stomach.”
  I wonder what this “gout” could really have been — something truly painful, I suppose, since gout in the joints can be amazingly painful. Perhaps it was cancer?

• N vincent on Tue 30 Dec 2003, 08:47pm. Flag this

  google gout for ones favourite remedy
  a )Treatment of Gout
  Therefore the following foods which are high in Purines should be restricted or avoided:
  Offal foods such as liver, kidneys, tripe, sweetbreads and tongue. Excessive amounts of red meat. Shellfish, fish roe and scallops. Peas. lentils and beans. Alcohol intake should be reduced. Two glasses of beer a day or less is sensible. On special occasions you can drink more. Weight loss may be very important. Medication for high blood pressure may need to be altered.

  http://www.rheumatology.org.nz/nz08003.htm
  It seems to say , the 17C diet was not an ideal eating style.
  

• N Ruben on Sun 7 Mar 2004, 10:07pm. Flag this

• N John in Austin on Sat 31 Dec 2005, 03:32pm. Flag this

  Sir John Falstaff:

  “A pox of this gout! or, a gout of this pox! for the one or the other plays the rogue with my great toe.”

  King Henry VIII, Part II
  

• N netta murray goldsmith on Sun 19 Feb 2006, 07:27pm. Flag this

  If anyone has more suggestions on what ‘gout of the stomach’ could have been, I would be glad to hear from them.I keep on coming across references to it e.g. in Trollope’s Phineas Finn where two minor characters expire because of it. For what it is worth I would not have thought it was cancer as 18th century doctors, let alone 19th century ones could diagnose that

• N Mary on Sun 19 Feb 2006, 10:14pm. Flag this

  gout of the stomach.

  There is an interesting site at www.antiquusmorbus.com/English that suggests explanations of many antique medical terms, including gouts of all descriptions.

• N in Aqua Scripto on Mon 20 Feb 2006, 05:35am. Flag this

  Mary your gout ref. could not be summoned; but here be OED oldest ref:
  Gout OED: I. 1. A specific constitutional disease occurring in paroxysms, usually hereditary and in male subjects; characterized by painful inflammation of the smaller joints, esp. that of the great toe, and the deposition of sodium urate in the form of chalk-stones; it often spreads to the larger joints and the
  internal organs.
  The name is derived from the notion of the ‘dropping’ of a morbid material from the blood in and around the joints.
  a. OF. goute, goutte (F. goutte) drop, gout: L. gutta drop, in med.L. applied to gout and other diseases attributed to a ‘defluxion’ of humours (see Du Cange).]
  c1290 S. Eng. Leg. I. 360/39 bare cam a goute In is kneo, of Anguische gret..So longue, xat is kneo to-swal.
  c. falling gout, epilepsy. Obs. [med.L. gutta cadiva or caduca: see Du Cange.]
  Stomach Gout may be an Ulcer;

• N pedro on Sat 4 Mar 2006, 10:05pm. Flag this

  Cure for gout?

  JOHN HILL educated as an apothecary, had lived in good style on the malice and fear of the community, he now found resources in its credulity. He brought out certain tinctures and essences of simple plants, sage, valerian, bardana, or water dock, asserting that they were infallible panaceas for all the ills that flesh is heir to. Their sale was rapid and extensive, and whatever virtues they may have possessed, no one can deny that they were peculiarly beneficial to their author, enabling him to have a townhouse in St. James’ Street, a country house and garden at Bayswater, and a carriage to ride in from one to the other. The quivers of the epigram writers were once more filled by these medicines, and thus some of their arrows flew:

  In spite of the efficacy of his Tincture of Bardana, which Hill warranted as a specific for gout, he died of that disease on the 21st of November 1775. The following is the last fling which the epigrammatists had at him:

  ‘Poor Doctor Hill is dead! Good lack!
  Of what disorder? An attack
  Of gout. Indeed! I thought that he
  Had found a wondrous remedy.
  Why, so he had, and when he tried,
  He found it true the doctor died!’
  (Book of Days)
  

• N Mary on Tue 7 Mar 2006, 02:30pm. Flag this

  gout/Antiquus Morbus.

  Indeed, the www.antiquusmorbus.com address does seem to have ceased to work, but if you simply Google for ‘antique medical terms’ you will find that this site appears and can then be searched for specific ailments. Not an elegant way of getting there, but apparently reliable.

• N dirk on Wed 8 Mar 2006, 04:10am. Flag this

  http://www.antiquusmorbus.com
  works fine for me.
  

References in the diary

1660

May: 17

1662

Dec: 30

1663

Feb: 16
Jun: 1, 7, 14, 21
Nov: 19

1664

May: 28
Jul: 14

1665

Jan: 15

1666

Feb: 14