Gout

**Gout** is a very painful medical condition that affects a joint or joints. Acute gout usually affects one joint, usually the big toe (as podagra). Around one to two percent of people in the West will have gout during their lifetime. In 2011, in the US, around 6.1 million Americans had gout. It has become more common since 1990, or “the disease of rich men". 

It might show up or "present" red on skin (causing erythema) and as swelling of the joint affected. Gout may affect one joint (called monoarticular gout), two, three or (rarely) four joints (oligoarticular) or even five joints (polyarticular gout). The attacks affect the joint at the base of the big toe about half the time and 90% of people with gout will experience an attack in the toe. 50% of people that have untreated gout will develop tophi within 10 years, and after 20 years, the amount to develop tophi is 72%. The amount of people who get tophi after 5 years is 30%, after the first acute attack. 

It is usually sudden and severe. It also helps most people to not touch the swollen joint (and even letting it air out without a bedsheet or clothing covering the affected joint). With proper treatment, gout can be resolved within 4 days to a week (7 days) and would be treated for an extra 24-48 hours afterwards. Gout caused by having to much uric acid in the blood is called primary gout and can cause other problems in the body. Gout caused by problems in the body is called secondary gout.

With positive lifestyle changes, most gout can be treated It is important to continue with treatment and prevention, even when gout is gone, because blood levels of uric acid can rise back up quickly. of a left foot. The gout appears at the typical location at the base of the largest toe joint. Note also the soft tissue swelling at the lateral border of the foot]]In some cases, checking for high amounts of urate crystals in blood or fluid from joints is not possible. This could be for a joint that is potentially infected (10,000 cases of sepsis occur per year in the UK because of aspiration of infected joints) or that a flare-up is still happening. To diagnose, the ACR recommend checking for more signs. When the diagnosis of gout is not certain (sure), there should be a check for more than one sign out of a list of common signs and symptoms. In some cases though, a doctor might ask the patient to return to measure the serum uric acid levels once the gout attack has passed. This also occurs if gout is suspected but levels are below the 360/mmol threshold, and this is because the urate levels might go down during an attack.
* monosodium urate crystals found in the tophus
Or if 6 or more of the following list apply
* more than one attack of acute arthritis
* maximum inflammation developed within 1 day
* monoarthritis attack, redness observed over joints
* first metatarsophalangeal (MTP) joint painful or swollen
* unilateral (one side) first metatarsophalangeal joint attack
* unilateral tarsal joint attack
* tophus (confirmed or suspected)
* hyperuricemia
* asymmetrical swelling within a joint on X-ray film
* subcortical cyst without erosions on X-ray film
* joint culture negative for organism during attack

File:Case 30-top.jpg|Nodules of the finger and helix of the ear representing gouty tophi
Image:ChronicGout.jpg|Tophus of the knee
Image:Case 30-bottom.jpg|Tophus of the toe, and over the external malleolus
Image:Tophigout.JPG|Gout complicated by ruptured tophi (exudate tested positive for uric acid crystals)

A sign of chronic gout is painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to long-term, chronic arthritis due to bone damage and erosion. It can also cause pseudogout when it involves calcium phosphate crystals instead of uric acid. The hormone that is causing gout in this case is the parathyroid hormone (or PTH for short), and does this because PTH can cause renal function to be impaired.
* Tophi can happen over knees, elbows, Achilles tendon, the helix of the ears or dorsum of the hands or feet.

## Cause
A very high (abnormal) level of uric acid in the blood (hyperuricemia) is the basic cause of gout. When serum uric acid level is the cause, it is called primary gout. The crystallization of uric acid happens when there is too much of it in the blood. There may be too much uric acid because of: (i) diet; (ii) under-excretion (for example if the kidneys fail to work properly); (iii) over-production (the body making too much of it). Most people with gout have hyperuricemia while many people with hyperuricemia do not have gout. Most people have hyperuricemia from under-excretion, while around 10% are over-producers of uric acid.

There are a lot of reasons for why gout might occur, but hyperuricemia is the common sign among them all. Finding crystals (of monosodium urate) in samples of the synovial joint fluid is enough of a sign to clinically diagnose gout. When gout is caused by another problem in the body, it is called secondary gout. 

Age and gender are factors to be aware of in gout. It affects old people more than it does young people, and men more often than it does women (affects males:females 4:1) 

This is true for the medicines that are made to treat gout too. Diuretics, such as Thiazine, and other medications may cause gout. Studies suggest that gout may be secondary to sleep apnea through the release of purines from oxygen-starved cells. Treatment of sleep apnea can lower how many gout attacks happen.
### Lifestyle
The increase in risk factors might be causing the number of cases to increase in certain demographics, such as in New Zealand, but there is not much evidence to show that gout is on the rise everywhere. 

Diet and genetics are possible reasons for the high levels of uric acid causing gout. Levels can become high if the body can not excrete enough urate, the salts of uric acid. Fructose is the only carbohydrate which causes uric acid levels to increase. Injuries and surgery (organ transplant) may also start attacks of gout. Other research has found that not all vegetables are high in purines but some (including peas, seaweed, and asparagus) may increase the risk of someone developing gout regardless.

Medications to lower the uric acid concentration in the body are used to treat recurrent high levels of uric acid. These are taken to treat both under-excretion and over-production of urate. These things reduce insulin resistance and may reduce cases of gout. responsible for the variability in uric acid level.

Two genes called SLC2A9 and ABCG2 are commonly associated with gout. Variations in these genes can almost double the risk of developing this disease. Some people of African American, Asian (Han Chinese) descent, and from other SEA countries might respond poorly to gout or certain drugs (allopurinol) because of genetics. The HLA-B5801 allele is found more often in Han Chinese and African American populations and is a risk factor in these people. It affects them in gout and its treatment. There could be adverse reactions to allopurinol in these people affected such as Stevens–Johnson syndrome and toxic epidermal necrolysis. These are serious and can be life threatening. These people are also at an increased risk in gout and of severe bleeding when taking other medications. 

### Medical conditions
Gout often happens with other medical problems. Rapid changes in uric acid levels sometimes occur due to a number of these factors, including trauma, surgery, chemotherapy, diuretics, and stopping or starting the medication allopurinol.

## Changes in the body
Gout is a crystal arthropathy arising from the disorder of purine metabolism, Other factors believed to be important in triggering an acute episode of arthritis are cold temperatures, fast changes in uric acid levels, acidosis, articular hydration, and extracellular matrixproteins, such as proteoglycans, collagens, and chondroitin sulfate. X-rays are useful for identifying chronic gout only. X-rays are not useful for treating acute gout attacks. All synovial fluid samples obtained from undiagnosed, inflamed joints should be examined for these crystals as soon as possible. meaning the crystals have the same shape and appearance as tiny needles in the joint.  

This test is difficult to perform, and often requires a trained technician. The test is not usually done in joints that could be infected, meaning the test might have to wait 

Other blood tests commonly performed are white blood cell count, electrolytes, renal function, and erythrocyte sedimentation rate (ESR), and estimated glomerular filtration rate (eGFR). 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 in people with gout. or other cancers. Finding crystals made of calcium pyrophosphate and normal uric acid levels when testing can help differentiate (tell the difference between) gout and pseudogout. Prevention is usually started when there has been 1 or 2+ attacks in 12 months, tophi, or renal stones. In trying to prevent gout, the goal is to lower the amount of attacks and prevent damage to the joints, caused by crystal deposition. This is done by lowering the amount of urate in the blood. The aim in gout that is already highly affecting the body is to lower joint damage and stop tophi being made, or breaking the tophi down. Coffee, but not tea, drinking is associated with a lower risk of gout. Replacing dietary sugar and fructose with artificial sweeteners can help prevent gout, although there is debate on whether artificial sweeteners cause gout.

Clinical options for prevention are allopurinol, febuxostat and probenecid. Lowering uric acid levels can cure the disease. and may be useful in combination with colchicine to prevent the diarrhoea as a side effect.

The first goal of treating gout is to reduce the symptoms of an acute attack such as pain and inflammation. Ice applied for 20 to 30 minutes several times a day decreases pain. Treatment of comorbidities is also important. but it is sometimes used if the benefits (such as treating a heart condition) outweighs the risk as the initial treatment in the UK) will respond to any NSAID, but each work differently and for the person some can work better or worse than others. and PPI inhibitors are usually given to people over 45 years of age because of this risk. may be preferred due to its lack of side effects. Ibuprofen is often the preferred drug choice by patients too. The risks of using NSAIDs in the clinical management of gout are dose-dependant and start from the first dose. is an alternative treatment for people that are unable to tolerate NSAIDs. The occurrence of gastrointestinal upset depends on the dose. The risk of experiencing this side effect can be reduced by using smaller, yet still effective doses. 

Colchicine may interact with other commonly prescribed drugs such as atorvastatin and erythromycin. It has an very narrow therapeutic index and is extremely toxic in overdose (people at an increased risk are those at either extreme of age range, renal or hepatic failure (kidneys and liver, respectively), and GI (gastrointestinal) or cardiac (heart) disease). It does not make the body retain (keep) water, unlike NSAIDs, and can be given to patients who are taking anticoagulant drugs. Corticosteroids may be used if it is not possible to use NSAIDs or colchicine. This means it is a valid treatment option for the initial help offered. is a commonly used drug for this purpose. The most effective and safe dose is not yet understood well enough to be clear (Krystexxa) was approved in the USA to treat gout in 2010. It will be a treatment option for the 3% of people who are intolerant to other medications

### Uricosuric agents
Uricosuric drugs are preferred for treating gout if there is not enough uric acid in the urine. This is tested by finding how much the patient urinates within 24-hours, and checking urine for a specific concentration (less than 800&nbsp;mg of uric acid per amount). This test looks for a low amount of uric acid in the urine, with a high amount in the blood between attacks. If uric acid levels are high because of under-excretion, uricosuric agents help the kidneys excrete more liquid. despite it no longer being commonly used in most countries due to concerns about hepatotoxicity. 

### Prophylaxis (prevention) 
A number of medications are useful for preventing further episodes of gout. Common examples are xanthine oxidase inhibitors and sulfinpyrazone, This type of treatment is delayed until this point because it is not cost effective to offer this treatment sooner. 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. Gout supposedly happens more often in spring (season) but the reason for this is currently unknown. 

In the United States, gout is twice as likely to occur in African American males as it is in European Americans. Rates are high among the peoples of the Pacific Islands and the Māori of New Zealand, but rare in Australian aborigines, despite a higher average concentration of serum uric acid in the aboriginal group.

## History
 described the microscopic appearance of uric acid crystals in 1679

People have been aware of gout since ancient times. Historically, it has been referred to as "the king of diseases and the disease of kings" The first documentation of the disease is from Egypt in 2,600 BC. In a description of arthritis of the largest toe. The Greekhy physician Hippocrates around 400 BC. Commented on it in his *Aphorisms* and noted its absence in eunuchs (men who have had their testicles removed at a young age) and women before menopause. Aulus Cornelius Celsus (30 AD.) described the linkage with alcohol, later onset in women, and associated kidney problems:
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... some have obtained lifelong security by refraining from wine, mead and venery.

In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of the morning, and it is more frequent occurrence in older males:
Gouty patients are, generally, either old men, or men who have so worn themselves out in youth as to have brought on a premature old age - of such dissolute habits none being more common than the premature and excessive indulgence in venery, and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle or instep. The pain is like that of a dislocation, and yet parts feel as if cold water were poured over them. Then follows chills and shivers, and a little fever... The night is passed in torture, sleeplessness, turning the part affected, and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint, and being worse as the fit comes on.

The Dutch scientist, Antonie van Leeuwenhoek, first described the microscopic appearance of urate crystals in 1679.

## In other animals
Gout is rare in most other animals due to their ability to produce uricase, which breaks down uric acid. Humans and other great apes don't have this ability, which makes gout common.

## Research
A number of new medications are under study for treating gout, including anakinra, canakinumab, and rilonacept. 

A man made uricase enzyme (rasburicase) is also available, which aims to lower uric acid levels in blood by inhibiting its production. Its use is limited because it triggers an autoimmune response. Versions of this medication that are less prone to cause allergies are in development.

## Related pages 
* Kidney stones 
* Podagra (definition) 
* BUPA and GoutAlliance - Support groups for gout 

## References