Gout Flashcards
Signs and symptoms?
Gout
Gout can present in multiple ways, although the most usual is a recurrent attack of acute inflammatory arthritis (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.
[8] Other joints, such as the heels, knees, wrists, and fingers, may also be affected.
Joint pain usually begins over 2–4 hours and during the nightThis is mainly due to lower body temperature.[Other symptoms may rarely occur along with the joint pain, including fatigue and a high fever.
Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, including hard, painless deposits of uric acid crystals known as tophi.
Extensive tophi may lead to chronic arthritis due to bone erosion.[13] Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.[14]
Cause?
Gout
The crystallization of uric acid, 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, 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 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.[12]
Lifestyle?
Gout
Among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast.Chicken and potatoes also appear related. Other triggers include physical trauma and surgery
Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or spirits
The eating or drinking of coffee, vitamin C, and dairy products, as well as physical fitness, appear to decrease the risk. Peanuts, brown bread, and fruit also appear protective.This is believed to be partly due to their effect in reducing insulin resistance.
Genetics?
Gout
Gout is partly genetic, contributing to about 60% of variability in uric acid level.[4] The SLC2A9, SLC22A12, and ABCG2 genes have been found to be commonly associated with gout and variations in them can approximately double the risk.[26][27] Loss-of-function mutations in SLC2A9 and SLC22A12 causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion.[27]
The rare genetic disorders familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout
Medical conditions?
Gout
Gout frequently occurs in combination with other medical problems. Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance, and abnormal lipid levels, occurs in nearly 75% of cases.[8] Other conditions commonly complicated by gout include lead poisoning, kidney failure, hemolytic anemia, psoriasis, solid organ transplants and myeloproliferative disorders such as polycythemia.[4][28]
A body mass index greater than or equal to 35 increases male risk of gout threefold.[16] Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.
Medication?
Gout
Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk.[30] Other medications that increase the risk include niacin, aspirin (acetylsalicylic acid), ACE inhibitors, angiotensin receptor blockers (except losartan), beta blockers, ritonavir, and pyrazinamide.[
Pathophysiology?
Gout
Rapid changes in uric acid may occur due to factors including trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol.[12] Calcium channel blockers and losartan are associated with a lower risk of gout compared to other medications for hypertension.[37]
Gout is a disorder of purine metabolism,[4] and occurs when its final metabolite, uric acid, crystallizes in the form of monosodium urate, precipitating and forming deposits (tophi) in joints, on tendons, and in the surrounding tissues.[13] Microscopic tophi may be walled off by a ring of proteins, which blocks interaction of the crystals with cells and therefore avoids inflammation.[33] 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.[33] When they break through the tophi, they trigger a local immune-mediated inflammatory reaction in macrophages
Gout
Diagnosis?
A definitive diagnosis of gout is based upon the identification of monosodium urate crystals in synovial fluid or a tophus.[8] All synovial fluid samples obtained from undiagnosed inflamed joints by arthrocentesis should be examined for these crystals.[
Hyperuricemia 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.[8][40] Thus, the diagnostic utility of measuring uric acid levels is limited.[8] Hyperuricemia is defined as a plasma urate level greater than 420 μmol/l (7.0 mg/dl) in males and 360 μmol/l (6.0 mg/dl) in females.[41] Other blood tests commonly performed are white blood cell count, electrolytes, kidney function and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection.[42][43] A white blood cell count as high as 40.0×109/l (40,000/mm3) has been documented.[12]
Differential diagnosis
The most important differential diagnosis in gout is septic arthritis.[4][8] This should be considered in those with signs of infection or those who do not improve with treatment.[8] To help with diagnosis, a synovial fluid Gram stain and culture may be performed.[8] Other conditions that can look similar include pseudogout, rheumatoid arthritis, psoriatic arthritis, and reactive arthritis.[8][31] Gouty tophi, in particular when not located in a joint, can be mistaken for basal cell carcinoma[44] or other neoplasms.[45]
Gout Prevention?
Both lifestyle changes and medications can decrease uric acid levels. Dietary and lifestyle choices that are effective include reducing intake of purine-rich foods of animal origin such as meat and seafood, alcohol, and fructose (especially high fructose corn syrup).[5] Eating dairy products, vitamin C, coffee, and cherries may help prevent gout attacks, as does losing weight.[5][46] Gout may be secondary to sleep apnea via the release of purines from oxygen-starved cells. Treatment of apnea can lessen the occurrence of attacks.[47]
A number of medications are useful for preventing further episodes of gout, including allopurinol, febuxostat, probenecid, and colchicine.[9][48] Long term medications are not recommended until a person has had two attacks of gout,[3] unless destructive joint changes, tophi, or urate nephropathy exist.[14] It is not until this point that medications are cost-effective.[3] They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack.[3] They are often used in combination with either an NSAID or colchicine for the first three to six months.
Urate-lowering measures should be increased until serum uric acid levels are below 300–360 µmol/l (5.0–6.0 mg/dl) and continue indefinitely.[3][4][49] If these medications are in chronic use at the time of an attack, it is recommended that they be continued.[8] Levels that cannot be brought below 6.0 mg/dl while attacks continue indicates refractory gout.[50]
Gout Treatment?
The initial aim of treatment is to settle the symptoms of an acute attack.[63] Repeated attacks can be prevented by medications that reduce serum uric acid levels.[63] Tentative evidence supports the application of ice for 20 to 30 minutes several times a day to decrease pain.[64] Options for acute treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and steroids.[3] While steroids and NSAIDs work equally well, steroids may be safer.[65] Options for prevention include allopurinol, febuxostat, and probenecid. Lowering uric acid levels can cure the disease.[4] Treatment of associated health problems is also important.[4] Lifestyle interventions have been poorly studied.[64] It is unclear whether dietary supplements have an effect in people with gout.[66]
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.[12] Those with gout are at increased risk of hypertension, diabetes mellitus, metabolic syndrome, and kidney and cardiovascular disease and thus are at increased risk of death.[4][76] It is unclear whether medications that lower urate affect cardiovascular disease risks.[77] This may be partly due to its association with insulin resistance and obesity, but some of the increased risk appears to be independent.[76]
Without treatment, episodes of acute gout may develop into chronic gout with destruction of joint surfaces, joint deformity, and painless tophi.[4] These tophi occur in 30% of those who are untreated for five years, often in the helix of the ear, over the olecranon processes, or on the Achilles tendons.[4] With aggressive treatment, they may dissolve. Kidney stones also frequently complicate gout, affecting between 10 and 40% of people and occur due to low urine pH promoting the precipitation of uric acid.[4] Other forms of chronic kidney dysfunction may occur.[4]
