At a glance......
Types of Gout
- Asymptomatic hyperuricemia – Gout undergoes 4 stages during its course starting with asymptomatic hyperuricemia. In this stage, patients have no symptoms or signs and are usually accidentally discovered when measuring SUA (serum level greater than 7 mg/dL). However, some patients with hyperuricemia may develop an acute gouty attack.
- Acute gouty attack – The acute gouty attack is usually monoarthritic that peaks within hours too severely inflamed joint with cardinal signs of inflammation including redness, hotness, tenderness, swelling, and loss of function. In large joints such as knees and ankles, skin signs are infrequent, but swelling and pain can be intense.
- Intercritical period – When the acute attack settles down within hours to days following the introduction of colchicine or NSAIDs, patients enter into a remission phase. This period is characterized by the absence of symptoms. It may be interrupted suddenly by newer attacks if proper treatment for hyperuricemia has not been introduced. This quiescent stage can be prolonged after the first attack. Without proper treatment, however, attacks become more frequent and more severe [Rx].
- Chronic tophaceous gout – The untreated disease progresses into the destruction of joints with the formation of palpable tophi. A tophus is a mass formed of large amounts of accumulated crystals. It happens in chronic untreated gout. It can be present around the joints in the ears, the subcutaneous tissue or the skin. It is a manifestation of chronicity and uncontrolled disease. Macroscopically, tophi contain a white chalky material. Tophi may lead to joint destruction and deformity. Bony erosions may also occur as growing tophi extend to the bone. Differentiation of tophi from other nodules such as rheumatoid nodules, osteoarthritic Heberden’s and Bouchard’s nodules, lipomas or is essential for further management. This can be easily done by taking a simple needle biopsy that will show MSU crystals characteristic of gout [Rx].
According to the Severity
Gout is divided into 4 stages (Rx):
- Asymptomatic deposits in tissues
- Acute gout – This is defined as rapidly-developing inflammation, usually of only one joint, with painful overheating and swelling. Uric acid crystals trigger the inflammation reaction in joints or tissues around joints.
- Intercritical periods – These are clinically inactive disease phases between 2 flares. During these periods, gout patients also have hyperuricemia, which can lead to increased deposition of urate crystals in tissues. Intercritical periods become shorter as the disease progresses.
- Chronic gout – This is characterized by long-term joint inflammation, which leads to joint pain at rest and/or on movement.
Causes of Gout
Although experts do not fully understand why some people get gout and others do not, many causes and risk factors of gout are well established.
- Diet – The risk of gout is increased by the frequent consumption of foods high in purines, including meats, seafood, certain vegetables and beans, and foods containing fructose.
- Alcohol use – Drinking alcohol decreases the body’s ability to flush out uric acid. Additionally, beer is made with brewer’s yeast, which is high in purines.
- Gender – Men are more likely to have gout. Women are less likely to get gout, however, their risk of developing gout increases after menopause.
- Age – Many people have their first episode of gout between the ages of 30 and 50, and the risk of gout continues to increase with age. It is estimated that nearly 12% of men aged 70 to 79 have had gout while less than 3% of men under the age of 50 have had it.
- Excess weight – People who are overweight have a greater risk of developing gout.
- Race – African American men are nearly twice as likely to report having had gout as Caucasian men, according to a study cited by the Centers for Disease Control and Prevention.
- Family history – Genetics plays a role, making some people’s bodies more prone to accumulating uric acid and developing the uric acid crystals that lead to gout. More research needs to be done to understand why some people have several risk factors and never get gout while other people have few or no risk factors and do get gout.
Certain medications. Taking certain medications can increase the risk of gout. Some of these medications include:
- Diuretics sometimes called “water pills”) used to treat high blood pressure
- Cyclosporine, an immunosuppressant sometimes prescribed to people who have rheumatoid arthritis or psoriasis, or who have had an organ transplant
- Levodopa often used to treat Parkinson’s disease
- Medicines that may cause gout include the following
- Niacin (a B-complex vitamin)
- Some drugs used to treat cancer
- Pyrazinamide and ethambutol, which are used to treat tuberculosis
Chronic renal failure – A person who has chronic renal failure no longer has fully functioning kidneys. When the kidneys’ ability to flush out uric acid is compromised, gout may develop.
Lead exposure – People who are exposed to lead in the environment have a higher incidence of gout. Though much less common today, gout caused by lead exposure was common years ago when people unwittingly drank from leaded crystal glassware.
A trigger event, such as injury, surgery, or medical therapy – Specific events can trigger a change in body chemistry and bring on a gout flare up. Such events include, but are not limited to, infection, trauma, surgery, psoriasis, and the initiation of chemotherapy. Stopping or starting allopurinol, which is used to treat gout, can also bring on gout symptoms
- Interestingly, many people who experience an episode of gout may not ever have symptoms again, or at least not for several years. People who do experience gout symptoms repeatedly may notice that episodes get longer and more severe. Gout and its precursor, hyperuricemia, should be addressed to prevent joint damage in the long term.
- Many forms of arthritis occur gradually, and in the early stages a person may experience only occasional mild pain. In contrast, gout strikes quickly, severely, and without warning. In fact, gout pain can be so severe that some people assume a more serious medical problem is at play, which can delay an accurate diagnosis.
Symptoms of Gout
- Pain – The most notable symptom of gout is extreme pain at the affected joint. Gout sufferers have compared the pain to being constantly stabbed with tiny, hot knives. Typically, it is uncomfortable if not impossible for a person to put weight on an affected foot or knee.
- Rapid onset – Acute gout can develop suddenly and without warning, taking only a few hours to become severely painful. (Though not usually the case, it is possible for gout symptoms to appear more gradually)
- Symptoms interrupt sleep – It is not uncommon to hear a gout sufferer recount how a gout flare-up struck in the middle of the night, waking the person from a sound sleep. The affected joint, often a big toe, causes so much pain that the person cannot tolerate even a bed sheet resting on it. The reason gout episodes often strike at night is that body temperature drops slightly during sleep, and this drop in temperature catalyzes the formation of uric acid crystals in the joint. This factor also helps explain why gout often affects joints in the feet and fingers – these extremities tend to maintain a lower temperature than the rest of the body.
- Only one joint is affected – In about 90% of gout cases, only one joint is affected.9About 50% of gout cases involve the big toe, although other joints in the foot are also commonly affected, including the ankle, instep and heel. Other joints susceptible to gout include the fingertips, wrist, knee and elbow.
- Short duration – Left untreated, an episode of gout can last from 3 to 10 days, or even a few weeks, during which time the pain tapers off. Usually, a person’s first episode of gout lasts just a few days but successive episodes may last longer.
- Swelling – The affected joint swells as the uric acid crystals create irritation and inflammation.
- Redness – The skin at and around the joint will appear red.
- Warmth – The skin at and around the joint will be warm to the touch.
- Stiffness – Swelling, and pain may significantly reduce the joint’s range of motion.
- Fever – The person may get a fever as the immune system reacts to the uric acid crystals.
- Tophi – In some cases, the collection of uric acid crystals create small white chunks called tophi that can be visible through the skin. Tophi (sing. tophus) usually only occur in people who have suffered from chronic gout for several years. This is referred to as chronic tophaceous gout and is the most disabling form of gout. Although gout symptoms normally resolve within several days or weeks, gout should not be left untreated. Over time gout can become chronic, tophi may develop, and permanent joint damage can occur.
- Wrist Pain – People who experience gout-related wrist pain typically have polyarticular gout, meaning their gout affects more than one joint. Gout pain appearing only in the wrist is rare but possible.7 When a person has gout in a joint that is not known for its susceptibility to gouts, such as the wrist or ankle, an accurate gout diagnosis can be elusive. If the joint is swollen, the physician may aspirate it with a needle and send the joint fluid to a lab for diagnostic analysis.
- Sacroiliac joint pain – Gout is commonly associated with the big toe joint (metatarsophalangeal joint), but only about half of cases occur there. The remaining cases affect other areas, such as knees, fingertips, and—less often—sacroiliac joints, which are located on either side of the pelvis between the sacrum and the ilium. Gout in a sacroiliac joint can cause low back pain or hip pain.
Diagnosis of Gout
The goals with testing are to identify gout, to distinguish it from other conditions, such as other types of arthritis that may have similar symptoms, and to investigate the cause of increased uric acid concentrations in the blood.
- Synovial fluid analysis – used to detect the needle-like crystals derived from uric acid or other crystals that may be present; to look for signs of joint infection.
- Uric acid – to detect elevated levels in the blood; if a diagnosis of gout is made, uric acid testing may be performed regularly to monitor levels.
- Basic metabolic panel (BMP) – this group of tests may be used to evaluate and monitor kidney function.
- Complete blood count (CBC) – to determine if there is an abnormal increase in the number of white blood cells (leukocytosis) and to help differentiate between septic arthritis and gout.
- Sometimes other tests, such as an RF (rheumatoid factor) or an ANA (anti-nuclear antibody), may be ordered to rule out other causes of arthritis symptoms. A blood culture and/or synovial fluid culture may be ordered if septic arthritis is suspected.
- Increased uric acid, often ≥ 410 µmol/L–US: 7.0 mg/ml, a level found in a significant minority of men (90% of gout occurs in men).
- X-rays of joints – will reveal joint damage if you have long-standing and poorly controlled gout. However, x-rays are rarely helpful in confirming the diagnosis because they’re usually normal in the early years of having gout. Ultrasound of joints can be used to detect earlier signs of gout and can be useful where the diagnosis is uncertain.
- Synovial fluid examinations – involve taking fluid samples from a joint through a needle and examining them under a microscope for urate crystals. This test can confirm the diagnosis but isn’t always practical – it can be difficult and sometimes uncomfortable to draw fluid from a small joint such as the big toe. However, it may be possible to identify a few crystals in a sample taken from your knee, even if you’ve not yet had an attack of gout there. A fine needle inserted into a tophus under your skin can also be used to identify urate crystals.
- Ultrasound – Musculoskeletal ultrasound can detect urate crystals in a joint or in a tophus. This technique is more widely used in Europe than in the United States.
- Dual-energy CT scan – This type of imaging can detect the presence of urate crystals in a joint, even when it is not acutely inflamed. This test is not used routinely in clinical practice due to the expense and is not widely available.
- Conventional Radiography (CR) – It is the most widely used method in clinical practice, however, in early stages of the disease, it is not very helpful [Rx]. Radiographic changes may be missed for a minimum of 10 years after the first gouty attack [Rx]. During the early stages of gout, radiographic images are usually normal or may show asymmetric soft tissue swelling near the affected joints, but subtle early lesions such as small erosions and tophi are difficult to detect [Rx].
In chronic tophaceous gout, the main radiographic features are:
- Tophi which are articular or periarticular soft tissue dense nodules [Rx], [Rx]
- MSU deposits in the cartilaginous part
- Joint space narrowing in advanced disease [Rx]
- Bone erosions are characteristic. They are well circumscribed intraarticular or juxta-articular lesions with overhanging margins [Rx]. They result from the growth of tophi into the bone, hence are usually seen near tophi [Rx].
- Periarticular osteopenia is usually absent and proliferating bone can be seen mostly as irregular spicules [Rx]
- Calcified MSU deposits can penetrate in the bone; in severe cases, they should not be confused with bone infarcts or enchondromas. Radiography has low sensitivity (31%), however, its specificity is high (93%) [Rx].
- CR is widely available, inexpensive, quick, and acceptable to patients. Radiation hazard is small [Rx]. The CR Sharp-van de Hejde scoring system for gout (SvdH-G), has been adapted from its RA counterpart and modified. The gout version includes scoring for bone erosions as well as joint space narrowing with the distal interphalangeal joints (DIPjs) added [Rx].
- Ultrasound (US) – Recently, progress in US technology (machines, transducers, techniques), encouraged its use by rheumatologists for the diagnosis and management of gout. In their excellent review, Nestrova and Foder [Rx], listed the main indications for using the US in crystal-induced arthritis. These include detection of joint effusion and synovitis, differentiating between active and inactive synovitis, studying cartilage, describing bone contour for erosions and osteophytes, evaluation of tendons, evaluation of crystal deposition, execution of US-guided procedures (diagnostic and/or therapeutic), monitoring disease evolution as well as being helpful for the differential diagnosis with other arthritides [Rx]
In gout, US features can be either nonspecific or specific. Nonspecific features include
- Synovial fluid – Synovial fluid varies from being totally anechoic to containing aggregates of variable echogenicity. Aggregates of MSU microcrystals can be detected as hyperechoic spots or bright stippled foci. They tend to float in the joint space sometimes giving a snow-storm appearance when applying gentle pressure on the skin surface [Rx], [Rx].
- Synovial proliferation and hypervascularization – The Doppler mode can differentiate active from inactive synovial tissue by assessing its vascularity. This is essential for diagnosis and in monitoring the disease and its response to therapy [Rx].
- Bone erosions – These are defined in gout as “intra- and/or extra-articular discontinuity of the bone surface (visible in two perpendicular planes) [Rx]. They are more likely found in patients who experience frequent attacks, or who have long disease duration, and tophi [Rx]. US has a threefold sensitivity than CR in detecting erosions < 2 mm (P < 0.001) . There is, however, standardized US scoring system for erosions in gout [Rx].
- Articular cartilage “double contour Sign” (DCS) – DCS is very specific for gout. It is defined as an abnormal hyperechoic band over the superficial margin of the articular hyaline cartilage, independent of the angle of insonation and which may be either irregular or regular, continuous or intermittent and can be distinguished from the cartilage interface sign [Rx]. DCS is reported in acute flare-up in clinically uninvolved joints, and in patients with asymptomatic hyperuricemia [Rx]. False-positive results have also been reported [Rx], [Rx]. Three and Schlesinger demonstrated that DCS can disappear when SUA levels were lowered to 6 mg/dl for 7 months or more [Rx].
MSU deposits (Tophi and Aggregates)
- A tophus is a circumscribed, inhomogeneous, hyperechoic, and/or hypoechoic aggregation (that may or may not generate posterior acoustic shadow), which may be surrounded by a small anechoic rim. Aggregates are heterogeneous hyperechoic foci that maintain their high degree of reflectivity even when the gain setting is minimized or the insonation angle is changed and which occasionally may generate the posterior acoustic shadow.
- Tophi have been also described by US as “wet sugar clumps” with an oval or irregular shape [Rx].
- Intra-articular and intrabursal tophi have been defined as heterogeneous hyperechoic (relative to subdermal fat) aggregates with poorly defined margins with or without areas with acoustic shadowing within the synovial recesses or bursae, respectively [Rx].
Doppler US can distinguish between active/hot tophi and inactive/cold ones based on their doppler signal [Rx]. Tophi can directly be measured by the US using special calipers. There is good sensitivity to change associated with ULT [Rx]. US is feasible as it can be performed in the clinic and there are no radiation hazards involved. The time required for scanning, however, may be significant and training costs may be considerable [Rx].
- Conventional CT (CCT) – CT is characterized by excellent resolution and high contrast, hence it is the best technique for the assessment and characterization of crystal arthropathies [Rx]. CCT is not helpful in the diagnosis of acute gout as it can’t detect inflammation, synovitis, tenosynovitis, and osteitis. This handicap is, however, more than counterbalanced by its role in chronic gout. It is able to detect erosions better than Magnetic Resonance Imaging (MRI) or CR [Rx]. These are described as well defined, punched out lytic bone lesions, with sclerotic overhanging edges [Rx]. The specificity of CCT for the assessment of tophi exceeds that of US or MRI [Rx]. CT of tophi has been confirmed microscopically by identifying MSU crystals [Rx]. Its measurement of tophi has also been compared to physical exam using Vernier calipers , . Tophi, soft tissue, intra-articular as well as intra-osseous ones appear as soft tissue masses with well-described attenuation, making it easier to distinguish them from other soft tissue lesions [Rx]. CCT can help to monitor disease burden and response to therapy [Rx] but has the disadvantage of radiation exposure [Rx]
- Dual-Energy CT (DECT) – The introduction of this new imaging technique opened a new horizon. It allows the differentiation of deposits based on their different X-ray spectra. It applies the concept that the attenuation of tissues depends on their density, atomic number as well as the photon beam energy [Rx]. Like CCT, it can detect damage but does not help in inflammation. It is superior to all other available imaging technologies in its ability to identify all urate deposition in the area imaged [Rx] DECT can offer a quick, non-invasive method to visualize MSU crystals, soft tissue changes, and early erosions at high-resolution, even before CR. This, particularly, helps in the differential diagnosis from pigmented villonodular synovitis, psoriasis, and septic arthritis which can share clinical features with gout [Rx]. DECT is highly accurate in detecting MSU crystals in joints, tendons, ligaments and soft tissues and can be used to identify subclinical gout with high specificity [Rx]. It, however, misses crystal deposition on the surface of cartilage, a feature US can detect as the DCS [Rx]. There are many causes of false negatives; lower density of tophi due to lower crystal concentrations, the small size of tophi or crystals (less than 2 mm.) or technical parameters [Rx]. On the other hand, false-positive results were described around nail beds, in the skin, in regions of metal artifacts and in severe OA [Rx]. DECT is not widely available, which limits its application for clinical and research purposes. Its costs are equivalent or higher than CCT and it entails radiation exposure [Rx].
- MRI – MRI features of arthritis are those of nonspecific inflammation, synovial thickening, effusion, erosion, and bone marrow edema. Tophi show homogenous T1 signal intensity (low to intermediate) and heterogeneous T2 signal intensity (variable low to intermediate), depending on the degree of its hydration and classification [Rx]. MRI role is limited because of expense and limited availability. It is, however, useful for evaluation of gout at unusual sites. The literature abounds with case reports in the axial skeleton [Rx]or presentation as spondyloarthritis [Rx], carpal tunnel syndrome [Rx], crown dens syndrome [Rx], paraspinal abscess [Rx], or intra-abdominal mass [Rx]. The diagnosis in these reports was made by MRI, which was occasionally combined with other modalities.
- Nuclear scintigraphy – Nuclear Scintigraphy is rarely used for evaluation. Positive results are often found incidentally when a study is performed for other indications.
- Positron emission tomography (PET) – Case reports of (PET/CT) in gout showed articular and periarticular FDG (18 F-fluoro-2-deoxy-D-glucose) uptake. Soft tissue FDG uptake identifying tophi has also been reported. This can be helpful when gout presents at unusual locations [Rx].
|Pattern of involvement||Ankle/foot|
– Erythema of joint
– Affected joint very sensitive to touch
– Movement very limited
All 3 symptoms
|Criteria for typical episode:|
– Pain develops within 24 hours
– Resolves after ≤14 days
– Complaint-free intervals
|1 typical episode|
Multiple typical episodes
|Evidence of tophus||Present||4|
– Serum uric acid (preferably without treatment, 4 weeks before/after an episode or highest value during episode)
– Joint fluid analysis following puncture (if performed)
6 to 8 mg/dL
8 to <10 mg/dl
No urate crystals
– Urate deposits on ultrasound or DECT
– Erosions characteristic of gout on conventional X-ray
According to Neogi et al. [Rx]
*If swelling score is 8 or more out of a maximum of 23 points, arthritis can be classified as gout with a sensitivity of 92% and a specificity of 89%. Evidence of uric acid crystals on puncture is a sufficient criterion.
DECT: Dual-energy computed tomography; MTP-1: Metatarsophalangeal joint I
Treatment of Gout
The immediate goals for treating a gout flare-up are to reduce intense pain, swelling, warmth, and redness. With proper treatment, gout pain and other symptoms can be under control within 24 hours and completely gone within a matter of days.
- Ice – A soft cool compress applied to the affected joint can help relieve discomfort.
- Avoid pressure – Avoid contact with anything. Anything that touches the affected joint may cause a sharp increase in pain.
- Rest – It is usually painful to use the affected joint, and resting it will help alleviate pain, swelling, and other symptoms.
- Elevation – Elevate the affected limb to help reduce swelling. If the foot is affected, sit down with the foot resting on a footstool or lie down with the foot propped up on a pillow.
- Patient education – As already emphasized above, patient education is key to gout management success, as shown by a preliminary study that explored the effect of a predominantly nurse-delivered education program. Following this program, 98 of 103 included patients had their uricemia at a target after one year of allopurinol treatment, in sharp contrast with what is usually observed [Rx]. Information should be given on the pathophysiology of the disease, its relationship with uricemia, its curable nature, uricemia targets to be reached, the life-long nature of the urate-lowering treatment, the importance to treat flares early, the mechanisms of ULD-induced flares and ways to prevent them. Patient education takes time and must frequently be repeated, but it is a mandatory tool to achieve success in long-term gout management.
- Over-the-counter medication – Over-the-counter anti-inflammatory medications, such as ibuprofen and naproxen, can relieve pain, particularly if pills are taken as soon as the patient perceives the gout attack coming on. A doctor should be consulted regarding the adequate dosage. Aspirin should be avoided, since it can impair the kidneys’ ability to filter out uric acid, making gout symptoms worse.
- Prescription pain relievers – When over-the-counter pain relievers are not sufficient, prescription painkillers such as codeine, hydrocodone, and oxycodone may be prescribed for short-term relief of acute pain.
- Colchicine – A prescription drug called colchicine is very effective at stopping an acute gout attack. Evidence shows that gout pain, swelling, and inflammation decrease when colchicine is taken within the first 12 to 24 hours of an attack, along with a second, smaller dose an hour or two later. When taken within 12 h after flare onset, 1.8 mg (1.2 mg then 0.6 mg one hour later) of colchicine has been shown to be as effective as the traditional higher doses [Rx]. In clinical practice, this drug appears as much less efficient when given long after the flare onset. The EULAR and American College of Rheumatology (ACR) have restricted the use of colchicine to patients presenting within 12 and 24 h of flare onset respectively. Colchicine should be taken only as directed. Many people taking colchicine to experience gastrointestinal side effects, such as vomiting or diarrhea.
- Corticosteroids injections – A doctor may inject the inflamed joint with steroids to relieve the pain. This treatment is particularly useful for people with sensitivities to certain medications. Repeated corticosteroid injections, however, can have side effects. Up until recently, colchicine was the treatment of choice for acute gout. However, due to recent safety concerns, colchicine is now only recommended if NSAIDs or corticosteroids are inappropriate. High dose colchicine therapy is no longer recommended because of its toxicity.
- NSAIDs – NSAIDs (non-steroidal anti-inflammatory drugs) – These are generally the medicines of choice for most patients who do not have underlying health problems. Aspirin should be avoided as it can alter urate levels and worsen the attack. NSAIDs or COXIBs are used at the maximum authorized dose, with proton inhibitors when indicated. Their efficacy is largely accepted, even though no placebo-controlled trial has been performed. Early prescription allows reducing administered doses.
- Steroids – Oral prednisone, at a daily dose of 30 mg/d for 7 days has been shown to be effective [Rx] and is recommended by the ACR and EULAR panels as potential first-line therapy in the management of gout flares [Rx]. However, steroids can worsen hypertension and diabetes [Rx] and are, in our view, best indicated in patients contraindicated for NSAIDs or colchicine (i.e. CKD patients). Co-prescription of a small dose (0.5–1 mg/d) of colchicine, when not contraindicated, may avoid rare inflammation relapses after steroid cessation. Open studies also suggest that ACTH can relieve gouty inflammation [Rx].
- Intra-articular steroid injections – appear as very efficient and are recommended by both the ACR and the EULAR in the management of mono or pauciarticular flares, despite the lack of randomized clinical trials (RCT).
- IL-1 blockers – Open studies of the IL-1 receptor antagonist anakinra [Rx], [Rx] support its off-label use in patients resistant or contraindicated to NSAIDs, colchicine, and steroids. Canakinumab, a long-lasting antibody to IL-1 beta, has been approved by the European Medical Agency, following 2 RCT trials against intramuscular triamcinolone acetonide [Rx]. The EULAR recommends considering IL-1 blockers for the management of gout flares in patients with frequent flares contraindicated to NSAIDs, colchicine, and steroids (oral or injectable). Current infection is a contraindication [Rx].