Version July 2025
INTRODUCTION —
Gout is caused by tissue deposition of monosodium urate (MSU) crystals and can cause a variety of clinical manifestations, including the following:
●Recurrent flares of inflammatory arthritis (gout flare)
●Chronic arthritis
●Tophaceous deposits in the joints and soft tissues (tophaceous gout)
Providers typically diagnose gout based on a combination of clinical features, laboratory testing (eg, serum urate, synovial fluid MSU crystals), and, in some cases, imaging. Biochemically, gout is typically characterized by hyperuricemia with serum or plasma urate concentrations exceeding 6.8 mg/dL (approximately 405 micromol/L); this level of urate is the approximate limit of urate solubility [1]. However, urate levels may be misleadingly normal during gout flares. Moreover, while hyperuricemia is a necessary precondition for the development of gout in almost all cases [2], it is not sufficient; most hyperuricemic individuals never develop gout (see "Asymptomatic hyperuricemia"). Visualization of MSU crystals in the synovial fluid of a symptomatic joint or bursa provides a more specific means to diagnose gout, but it requires involvement of a joint or bursae that is amenable to aspiration (ie, an intermediate- to large-sized joint) and access to an experienced provider to obtain and analyze fluid.
This topic reviews the clinical manifestations and diagnosis of gout flares, chronic gouty arthritis, and tophaceous disease. Topics discussed separately include:
●Mechanisms underlying hyperuricemia and gout (see "Urate balance" and "Gout: Pathophysiology")
●Treatment of gout flares (see "Gout: Treatment of flares")
●Prevention of gout flares with urate-lowering therapy and nonpharmacologic measures (see "Gout: Nonpharmacologic strategies for prevention and treatment" and "Gout: Pharmacologic urate-lowering therapy and treatment of tophi")
●Gout in recipients of kidney transplants (see "Hyperuricemia and gout in kidney transplant recipients")
HISTORIC PERSPECTIVE —
Descriptions of the epidemiology, clinical features, and natural history of gout have evolved over more than two millennia of observations and study. In the latter half of the 20th century, scientists confirmed that the pathogenesis of gout involves monosodium urate (MSU) crystal deposition. The introduction of polarized light microscopy into clinical practice was pivotal in this progress, as identification of MSU crystals in synovial fluid allowed for rapid and definitive diagnosis of gout and resolution of the formerly ambiguous relationship between hyperuricemia and gout [3]. Further study increased understanding of the molecular pathophysiology of gouty inflammation. (See "Gout: Pathophysiology".)
Another important historical turning point was the development of effective therapies to suppress gouty inflammation and lower serum urate. This provided means to prevent, and even reverse, the previously ravaging acute inflammatory and chronic destructive manifestations of MSU crystal deposition. (See "Gout: Treatment of flares" and "Gout: Pharmacologic urate-lowering therapy and treatment of tophi".)
While therapeutic advances have favorably influenced the disease course in the majority of appropriately treated individuals with gout, many patients still experience suboptimal clinical outcomes [4]. This is particularly true when patients face barriers to effective management, such as nonadherence, difficulty accessing care, and concurrent comorbidities and medications that complicate urate-lowering therapy [5-9]. (See "Gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prognosis'.)
EPIDEMIOLOGY AND RISK FACTORS —
The incidence and prevalence of gout have increased since approximately the late 1970s in the United States [10-13], United Kingdom [8], and globally [14]. As an example, one study estimated that the prevalence of gout worldwide in 2020 was 658 per 100,000, affecting a total of 55.8 million individuals; this represents an increase of 23 percent since 1990 [14]. For the United States, estimates of the prevalence of gout range from less than 12 to 17 million or more individuals, or approximately 5 percent of the population [13]. The increasing incidence and prevalence of gout may reflect changes in the risk factors outlined below, including increased longevity, racial and ethnic demographic changes, dietary changes, and higher rates of age-associated comorbid conditions and use of related medications that affect urate balance.
Most, but not all, patients who develop gout have hyperuricemia [2]. Therefore, many factors that increase serum urate also appear to increase the likelihood of developing gout. Risk factors for hyperuricemia and/or gout are summarized in the table (table 1), with selected factors discussed in greater detail below:
●Nonmodifiable risk factors – Prevalence is higher in older adults (10 to 15 percent) and males compared with females, particularly premenopausal females.
•Age – Increasing age is a risk factor for developing gout [14], and prevalence is higher in older adults (10 to 15 percent). The age of onset varies by sex; for males, the biggest increase in gout incidence occurs during the fourth or fifth decades of life, while in females it occurs later in the sixth or seventh decades [15].
Gout rarely affects children since their serum urate levels are typically 3 to 4 mg/dL, well below the level of urate solubility (approximately 6.8 mg/dL) [16]. However, children and adolescents may still develop marked hyperuricemia and subsequent gout due to urate overproduction (eg, inherited defects in enzymes of purine metabolism, diseases with greatly increased rates of cell proliferation (table 2)), or severely impaired renal uric acid clearance (eg, familial juvenile hyperuricemic nephropathy, other genetic variants affecting urate transport (table 3)).
•Sex – Gout affects more males than females [17-19]. As an example, one study estimated that the global prevalence of gout was 3.3 times higher in males versus females [14]. In addition, the onset of gout happens earlier in males compared with females, which is thought to reflect a higher urinary fractional excretion of urate during childbearing years due to estrogenic compounds [20]. In males, serum urate increases to 5 to 6 mg/dL around puberty, with little increase thereafter due to age alone [21]; in females of a similar age, urate levels are approximately 1.0 to 1.5 mg/dL lower until after menopause, when they become comparable to those in males [22].
•Race, ethnicity, and geography – The prevalence of gout is reported to be increasing in all ethnic and racial groups in the United States. However, gout appears to be more common among Asian American individuals; as an example, the largest increase in gout prevalence from 2017 to 2018 was in Asian American individuals, rising from 3.3 to 6.6 [13].
Gout is common globally, with an estimated prevalence of 15 percent in a random sample of French Polynesian patients [23] and 6 percent in the Taiwanese population [24]. There is a forecasted trend for increasing prevalence in most geographical regions in the world, independent of population aging and growth [14].
•Genetic factors – Many genetic loci have been associated with hyperuricemia, especially ones related to urate transport in the kidney and gastrointestinal tract. (See "Gout: Pathophysiology", section on 'Hyperuricemia and gout' and "Urate balance", section on 'Urate excretion'.)
●Modifiable risk factors – Modifiable risk factors affecting urate balance include obesity, hypertension, diabetes mellitus, chronic kidney disease, dietary factors (eg, intake of purine-rich meats, alcohol, high-fructose corn syrup), and medications that alter urate balance (eg, diuretics). More information on the role of these conditions in the development of gout is provided separately. (See "Gout: Nonpharmacologic strategies for prevention and treatment".)
Historically, the "classic" clinical profile of gout was a 30- to 60-year-old male with obesity, hypertension, and frequent alcohol use. However, as illustrated above, gout also affects females and can occur in younger patients who have high genetic risk variants [25] or traditional modifiable risk factors for hyperuricemia or gout, underscoring the importance of considering this diagnosis in a wide range of patients presenting with acute arthritis.
More information on factors impacting urate balance, as well as the epidemiology of asymptomatic hyperuricemia and the pathophysiology of gout, is provided elsewhere:
●(See "Urate balance".)
●(See "Asymptomatic hyperuricemia".)
●(See "Gout: Pathophysiology".)
NATURAL HISTORY —
Hyperuricemia is a common biochemical abnormality that results from excessive urate production and/or absolute or relative impairment of renal uric acid excretion (see "Urate balance"). Most hyperuricemic individuals never experience a clinical event resulting from monosodium urate (MSU) crystal deposition (see "Asymptomatic hyperuricemia", section on 'Epidemiology'). However, almost all people with gout have hyperuricemia at some point in their disease.
The three classic clinical stages in the natural history of gout are:
●Gout flare – Episode(s) of acute-onset painful inflammation affecting joints and other periarticular tissues (see 'Gout flares' below)
●Intercritical gout – Periods of time between gout flares, which are typically asymptomatic (see 'Recurrent flares and intercritical gout' below)
●Chronic gouty arthritis and tophaceous gout – Bone changes (eg, erosions) and tophi can develop over time, leading to a symptomatic arthritis and, in some cases, tophaceous gout (see 'Tophaceous gout' below)
The clinical stages of gout emerge sequentially with some overlap. The clinical severity of gout often parallels the frequency of gout flares. However, in rare cases, chronic gouty arthritis and tophaceous gout can appear without a preceding history of gout flares.
In the absence of effective urate-lowering treatment, patients tend to have recurrent gout flares occurring after progressively shorter asymptomatic periods; flares become increasingly polyarticular, prolonged, and disabling and may be associated with fever. In untreated patients, the interval from the first gout flare to the onset of chronic gouty arthritis or detectable tophi averages approximately 12 years, with a wide range from less than 5 to 40 years. After 20 years of untreated gout, almost 75 percent of patients develop tophi [26]; the rate and extent of tophus formation are correlated with the duration of gout and degree of hyperuricemia.
The introduction of urate-lowering therapy led to a dramatic reduction in chronic gouty arthritis and tophaceous gout, with a prevalence of less than 5 percent reported in some series [27]. Other large gout studies report a persistently high frequency of tophaceous disease of approximately 35 percent [25,28], likely reflecting heterogeneity in access to care. When progression occurs, it is most often among patients who have not been properly diagnosed or optimally managed (eg, due to subtherapeutic dosing of urate-lowering therapy, limited access to care, or patient nonadherence). In addition, patients may progress when they have contraindications to or intolerance of available agents, or when comorbid conditions and/or their respective treatments limit the use or efficacy of urate-lowering therapy [29,30].
Several studies describe subgroups of patients with gout who have varying outcomes. As an example, progression to chronic gouty arthritis and tophaceous gout may approach 50 percent in male patients with comorbid diuretic requirements, alcohol use disorder, and difficulty adhering to urate-lowering therapy [31,32]. For another group of patients with gout who tend to be older (ie, on average in their seventh or eighth decades of life) with kidney dysfunction and diuretic-induced hyperuricemia, there appears to be an increased rate of tophi or low-grade inflammation in osteoarthritic finger joints [5,33]. Finally, organ transplant recipients treated with cyclosporine are at increased risk for the accelerated development of tophaceous gout. (See "Hyperuricemia and gout in kidney transplant recipients".)
CLINICAL FEATURES
Clinical findings
Range of signs and symptoms — Patients with gout may develop a range of complications primarily related to tissue deposition of monosodium urate (MSU) crystals and subsequent inflammation and tissue damage:
●Joint involvement – Classically, gout primarily most commonly affects distal joints in the lower extremities, including the first metatarsophalangeal (MTP) joint, midfoot, and knees [34]. However, virtually any joint can become involved over time, including the finger joints, wrists, shoulders, hips, sternoclavicular joints, and, rarely, the spine [35]. Patients develop symptomatic arthritis during flares and over time can accumulate joint damage from crystal deposition and chronic inflammation. (See 'Typical clinical manifestations' below.)
●Periarticular involvement – Gout may also affect periarticular soft tissues, including ligaments, tendons, retinacula, and bursae. Patients can therefore develop focal inflammation in these locations (eg, tendonitis, bursitis) during gout flares, with or without concomitant joint involvement.
●Tophi – Tophi represent larger deposits of MSU crystals and surrounding host fibrotic or chronic inflammatory tissue [36] that may be visible and/or palpable in superficial locations. (See 'Tophaceous gout' below.)
●Kidney complications – As discussed above, virtually all people with gout have some degree of hyperuricemia. The two major kidney complications of chronic hyperuricemia are nephrolithiasis and chronic urate nephropathy, which are discussed in detail separately. (See "Kidney stones in adults: Uric acid nephrolithiasis" and "Uric acid kidney diseases", section on 'Chronic urate nephropathy'.)
Gout flares — A gout flare is typically monoarticular and intensely inflammatory, occurring in the lower extremities. Periarticular involvement in bursae or enthesis is also frequent. A variety of dietary and physical factors, comorbidities, medications, and other factors may predispose to or provoke the gout flare (see 'Provoking factors' below and 'Typical clinical manifestations' below). Joints in other regions may also be involved, and patients may experience polyarticular flares, which are more likely to occur in patients with longstanding disease (see 'Polyarticular gout flares' below). Patients with gout who have sustained chronic hyperuricemia may develop tophi with associated articular damage. (See 'Tophaceous gout' below.)
Provoking factors — Gout flares are thought to be provoked by conditions that increase the extracellular fluid urate concentration (eg, due to urate overproduction or underexcretion), decrease urate solubility, and/or increase the nucleation or growth of MSU crystals and proinflammatory response to MSU crystal deposits [37]. Specific circumstances that provoke gout flares, as summarized in the table (table 4)and described in more detail below:
●Physiologic alterations – Various physiologic alterations, including articular trauma, surgery, dehydration, and starvation, may prime patients to experience a gout flare [38,39]. As an example, ketoacidosis and lactic acidosis can decrease both renal urate secretion and urate solubility.
●Environmental alterations – High ambient temperature and extremes of humidity have been associated with an increased risk of gout flares [40].
●Changes in medications affecting urate balance
•Urate-lowering therapy – Although it is protective in the long term, initiating or intensifying urate-lowering therapy can precipitate gout flares, particularly in the early months of urate-lowering treatment [41-45]. Patients may also experience a flare if they take these medications intermittently. Concurrent antiinflammatory prophylaxis is usually given when initiating therapy to prevent this complication [30]. Interruption or discontinuation of gout flare prophylaxis can be associated with the development of gout flares [46]. (See "Gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prophylaxis during initiation of urate-lowering therapy'.)
•Other medications – Diuretics (eg, furosemide) have been associated with recurrent gout flares in both the outpatient and inpatient setting [47,48]. Low-dose aspirin is also associated with gout flares. Patients may experience a related gout flare when initiating, adjusting, or inconsistently taking these agents due to fluctuations in serum urate. Vaccination has also been reported as a potential trigger [49,50]. In addition, patients receiving chemotherapy for hematologic malignancy may experience gout flares due to the rapid increase in cell death and subsequent increase in serum urate. (See "Gout: Nonpharmacologic strategies for prevention and treatment", section on 'Addressing medications that affect urate balance' and "Diuretic-induced hyperuricemia and gout".)
●Intake of alcohol and other triggering foods – Alcohol consumption, including beer, spirits, and wine, is associated with a greater risk of gout flare in patients with established gout [51]. In addition, purine-rich foods (eg, red meat, shellfish) are associated with gout flares. (See "Gout: Nonpharmacologic strategies for prevention and treatment", section on 'Modifying diet'.)
●Hospitalization – Hospitalization is a well-recognized risk factor for flares in patients with gout [39], which likely reflects a combination of physiologic alterations and medication changes. A retrospective study among hospitalized patients in New Zealand described predictive factors for flare among hospitalized patients with gout including presence of acute kidney injury, use of diuretics, surgery, an elevated preadmission serum urate (>6 mg/dL), presence of tophi, not being on urate-lowering therapy, adjustment of the urate-lowering therapy while in the hospital, and initiation or increase of gout flare prophylaxis [38].
Often several factors are present together and may work in combination. As an example, gout flares are most likely to develop at night and in the early morning hours, when people tend to have a lower body temperature, relative dehydration, and relatively low blood cortisol levels [52].
More information on the pathophysiology of gout is provided elsewhere. (See "Gout: Pathophysiology", section on 'Acute inflammation'.)
Typical clinical manifestations — The typical gout flare is intensely inflammatory and often has the following clinical features:
●Symptoms and physical findings
•Intense, rapid-onset pain and disability – Patients experience severe pain in the affected area, even with light touch (eg, inability to tolerate a sheet resting over an affected toe). This may cause significant disability, especially when there is lower-extremity arthritis. The peak in severity usually occurs within 12 to 24 hours of symptom onset.
•Redness, warmth, and swelling of affected areas – Affected joints and bursae will often be visibly swollen and warm to the touch. Swelling may extend beyond a single joint or bursae due to involvement of several contiguous joints, tenosynovitis, and, with advanced gout, tophi. In the finger, this may resemble dactylitis (ie, a "sausage digit"). Redness or erythema occurs more commonly when the joint or bursa is superficial, with the exception of the knees. If redness is present, this may give the impression of cellulitis.
•Uncommon systemic symptoms – Uncommonly, patients may develop fever, chills, and malaise during gout flares, which may raise concern for an infectious process (eg, septic arthritis, bacteremia). This is more common in polyarticular flares [53].
●Location
•Asymmetrical involvement of the lower extremity – At least 80 percent of initial flares involve a single joint [54], most often at the base of the great toe (first MTP joint, known as podagra) or the knee (picture 1). While other lower-extremity structures (eg, the ankle, instep/midfoot, prepatellar bursa, and, less commonly, hip) can also be affected during the initial flare, they are typically involved with recurrent flares.
•Potential additional sites – Patients may also develop involvement of the small finger joints, wrists, elbows, and bursae (eg, the olecranon bursae). While these sites are more common with recurrent gout flares, they can be involved with initial flares; as an example, patients with comorbid osteoarthritis may present with a gout flare affecting their finger joints. Not uncommonly, periarticular sites (eg, bursae, tendon insertions) are exclusively involved instead of the joint itself.
•Uncommon involvement of other joints – Although much less common than peripheral involvement, gout can also occur in the shoulders, hips, sternoclavicular joints, spine, and sacroiliac joints, especially the lumbar spine [55,56]. Most proven cases of gout presenting as acute or chronic back pain have occurred in patients with tophaceous involvement. Patients may experience related neurologic signs and symptoms from radiculopathy and even cord compression. Axial gout may cause diagnostic confusion with other forms of axial arthritis and spinal pathology.
●Onset and clinical course
•Frequent onset at night – Gout flares are twice as likely to occur overnight and in the early morning (between midnight and 8:00 AM) compared with the daytime [52]. (See 'Provoking factors' above.)
•Gradual resolution – Complete resolution of the earliest flares almost always occurs within a few days to several weeks, even in untreated individuals. Sometimes with resolution there is desquamation of the skin overlying the affected joint. While the physiologic basis of the resolution of acute gouty inflammation is complex, it centers on the action of endogenous and exogenous suppressors of gouty inflammation [57]. (See "Gout: Pathophysiology", section on 'Resolution of acute MSU crystal-induced inflammation'.)
Other types of presentations have been described. Some patients appear to have milder and rapidly self-limited inflammatory episodes, especially if gout is relatively well controlled. However, this phenomenon is not well studied and may suggest alternative diagnoses, such as osteoarthritis.
Polyarticular gout flares — Polyarticular gout flares of more than one joint or periarticular area may affect sites that are distant or clustered together. They can occur simultaneously or in a sequential (migratory) pattern. Polyarticular flares may also be accompanied by fever and mimic sepsis [58,59].
While polyarticular arthritis only occurs in 20 percent of patients with their initial gout flare, it is increasingly common with later flares. This is especially true for patients with chronic, untreated gout who have multiple recurrences, short or absent symptom-free intervals, and palpable tophaceous deposits. Polyarticular flares have also been associated with the presence of multiple medical comorbidities, obesity, hypertension, and hospitalization [58,60]. In addition, a polyarticular initial presentation of gout may be more frequent in patients with an underlying myeloproliferative or lymphoproliferative disorder [61] and in organ transplant recipients who are receiving cyclosporine or tacrolimus [6]. (See "Hyperuricemia and gout in kidney transplant recipients".)
Recurrent flares and intercritical gout — Intercritical gout refers to periods of time between gout flares. Early in the course of gout, such periods are most often entirely asymptomatic, even after severe and incapacitating gout flares. This symptom pattern is highly suggestive of gout since it is uncommon in other types of inflammatory arthritis, aside from palindromic rheumatism and other crystal deposition diseases (eg, calcium pyrophosphate crystal deposition [CPPD] disease). Patients who present for an initial evaluation of gout during an intercritical period can still be diagnosed. (See 'Suspected intercritical or tophaceous gout' below.)
Intervals between gout flares are of variable duration. Most untreated patients with gout will experience a second episode within two years. As an example, one large group of patients studied prior to effective urate-lowering therapy found that a second flare occurred in 62 percent of patients within the first year, 78 percent within two years, and 93 percent within 10 years [62]. The risk of recurrent flares is higher in those with worse hyperuricemia at baseline [63] and chronic kidney disease. Patients with untreated gout may have progressively worse and more frequent flares. (See 'Natural history' above.)
During intercritical periods, MSU crystals may continue to deposit in affected tissues and tophi, causing bony erosions that can evolve into chronic gouty arthritis. This underscores the importance of counseling patients about managing hyperuricemia and, if indicated, pursuing urate-lowering therapy. (See "Gout: Nonpharmacologic strategies for prevention and treatment" and "Gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Management principles and initial postdiagnostic assessment'.)
Tophaceous gout — Tophaceous gout is characterized by articular and periarticular collections of MSU crystals and chronic inflammatory tissue, often accompanied by destructive changes [64]. Tophi are typically not painful or tender; however, occasionally acute inflammation occurs adjacent to one or several tophi (picture 2), mimicking a gout flare. A characteristic chronic granulomatous inflammatory response can be seen on histologic examination of the lesions [65]. (See "Gout: Pathophysiology", section on 'Tophi'.)
Tophi can form in any area containing connective tissue, including articular bone and cartilage, bursae, soft tissues, tendons, ligaments, entheses, and the meninges (but not the brain or spinal cord) [64]. They most commonly affect the first MTP joint, other foot joints and tendons (eg, Achilles tendon), prepatellar and olecranon bursae, and helix of the ear [34] (picture 3 and picture 4). When tophi are present on the ear, they should not transilluminate due to the density of the MSU crystal deposit. The overlying skin may be attenuated, revealing a yellow or white color and making tophi more prone to rupture. Ruptured tophi drain chalky fluid and, rarely, lead to chronic ulcers [66].
Most patients who develop tophaceous gout do so after many years of intermittent gout flares (see 'Natural history' above). However, several reports have described tophaceous gout in the absence of, or prior to, a gout flare [63,67]. Historically, this presentation was considered to be a rare occurrence restricted to patients with urate overproduction due to myeloproliferative disorders or hereditary enzyme defects. However, it also appears to be relatively more common in female patients and those with predominant or exclusive involvement of the fingers, chronic kidney disease, and concurrent use of diuretic or antiinflammatory drugs [67].
While tophi may be apparent clinically or detected with plain radiography, other imaging techniques are more sensitive, particularly ultrasonography and dual-energy computed tomography (DECT). It is likely that many patients with gout and sustained hyperuricemia have a much larger burden of urate crystal deposits than is suspected by clinical examination alone. (See 'Imaging findings' below.)
Laboratory findings
●Synovial fluid – During a gout flare, MSU crystals can be appreciated in synovial fluid obtained from affected joints or bursae by using compensated polarized light microscopy. MSU crystals are needle-shaped and strongly negatively birefringent, so they appear bright yellow when they are parallel to the red compensator axis (picture 5). They may be extracellular or appreciable inside of neutrophils. During intercritical periods, MSU crystals may also be found in aspirated tophaceous material and synovial fluid from previously affected joints or bursae [68]. (See "Synovial fluid analysis", section on 'Monosodium urate crystals'.)
Synovial fluid from a joint affected by a gout flare should be inflammatory, with a white blood cell count of 10,000 to 100,000 cells/m3 and a neutrophilic predominance (see "Synovial fluid analysis", section on 'Nucleated (white) cell count and differential'). While synovial fluid from an affected bursa is also inflammatory, the elevation in the white blood cell count is much less pronounced, similar to findings in patients with septic bursitis. (See "Bursitis: Clinical manifestations, diagnosis, and management", section on 'When to aspirate'.)
●Blood tests – During a gout flare, blood tests may show nonspecific changes consistent with inflammation and a high, normal, or low serum urate:
•Blood counts and inflammatory markers – Neutrophilic leukocytosis and/or elevation of the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) are common in gout flares. However, these laboratory findings are also common in other forms of inflammatory arthritis and therefore typically offer little diagnostic value. (See "Overview of bone stress injuries and stress fractures", section on 'Diagnosis'.)
•Serum urate – During a gout flare, serum urate may drop into the normal range and commonly is normal; elevations (≥6.8 mg/dL) are suggestive but not necessary or sufficient to make a diagnosis of gout. The most accurate time for assessment of serum urate (and establishment of a baseline value) is two weeks or more after a gout flare completely subsides (ie, during an intercritical period).
Overall, normal to low serum urate values have been noted in 12 to 43 percent of patients with gout flares [69-72]. Situations where this may be more common include patients who flare during the early months of urate-lowering drug therapy and those who develop postsurgical gout flares [73]. Lower urate levels during flares may reflect the effects of cytokines.
Imaging findings — Various imaging modalities can offer insights into different stages of gout. Longstanding bony erosions and tophi may be appreciated on radiography and magnetic resonance imaging (MRI), while evidence of MSU crystal deposition can be detected using ultrasonography and DECT:
●Plain radiography – Subcortical bone cysts apparent on plain radiography can be suggestive of gouty tophi or erosions. There may also be associated, delicate "overhanging edges" of bone. However, such changes usually occur with longstanding disease and are often not detectable at the time of the first gout flare.
●Ultrasonography – Findings on ultrasound examination can strongly and independently support the diagnosis of gout and may be useful in the early detection and monitoring of therapy [74-76]. Important diagnostic features include a hyperechoic linear density (double contour sign [DCS]) overlying the surface of joint cartilage (image 1) or tophaceous-appearing deposits in joints or tendons, which are represented by an ovoid stippled signal (hyperechoic cloudy area [HCA]) surrounded by a hypoechoic border (image 2) [74]. (See 'Role of imaging' below.)
Based on a systematic review and subsequent observational study with concurrent MSU crystal validation, the sensitivities of DCS and HCAs consistent with tophus are approximately 60 to 83 percent and 46 to 64 percent, respectively [28,75]. The specificity appears to be higher, estimated at 76 to 91 percent for DCS and 80 to 95 percent for HCAs. The lack of complete specificity may reflect that DCS and HCAs can also be seen in some patients with asymptomatic hyperuricemia [77]. In one study that subsequently compared performance in patients with gout for less versus more than two years, the specificity was similar for both groups while sensitivity increased meaningfully in those with longer disease duration, from 51 to 63 percent for DCA and from 34 to 51 percent for HCA [28].
●DECT – DECT examination can identify urate deposits in articular and periarticular locations and can distinguish urate from calcium deposition [64,74]. Researchers have described ways to minimize potential artifacts with DECT and avoid false-positive interpretations [78]. In a meta-analysis of 13 studies, the pooled sensitivity and specificity of DECT was reported as 89 and 91 percent, respectively [79]. Another study reported an excellent sensitivity for gout of 90 percent but emphasized that all false-negative cases happened in cases with less than six weeks of symptom duration [80].
Although typically used just for diagnosis, DECT may also be useful for determining response to therapy and prognosis. A systematic review of the literature suggested that DECT volume is associated with response to urate-lowering therapies as well as death, cardiovascular risk, and risk of future gout flares [81]. (See "Gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Prognosis'.)
●MRI – The main value of MRI in the diagnosis of gout is for its differentiation from bone or soft tissue infections. Severe cases of bone marrow edema are unsupportive of a diagnosis of gout and should favor infection [82]. The characteristics of tophi on MRI include relatively homogeneous intermediate to low signal intensity on T1-weighted images as well as variable signal intensity on T2-weighted images. Either homogeneous or peripheral enhancement may occur with the addition of gadolinium [74]. Although these MRI findings are sometimes supportive of gout, they are not specific; aspiration of a lesion is needed when the differential diagnosis includes infection or malignancy.
The role of imaging in the evaluation and diagnosis of gout is described below. (See 'Role of imaging' below and 'Establishing the diagnosis' below.)
EVALUATION —
The preferred approach to the diagnosis of gout illustrated in the algorithm (algorithm 1) is based upon the identification of intracellular monosodium urate (MSU) crystals on polarizing light microscopy of an affected joint, particularly when the diagnosis has not been established or is uncertain. When this is not feasible, a diagnosis may be made based upon clinical features, including the history, examination, laboratory, and imaging studies.
When to suspect — Gout flare should be suspected in patients presenting with a monoarthritis of the lower extremities, especially when there is involvement of the first metatarsophalangeal (MTP) joint. The suspicion should be further increased in the presence of hyperuricemia, recognized risk factors (eg, older age, comorbid kidney disease, diuretic use), and/or known triggers (eg, recent increased intake of purine-rich foods or alcohol). However, clinical manifestations of gout flares vary and may also include inflammation of periarticular tissues and/or polyarthritis. (See 'Range of signs and symptoms' above.)
Tophaceous gout should be suspected in patients with nodules in articular or periarticular tissues, especially when there is a history of chronic, intermittent joint pain or swelling. (See 'Tophaceous gout' above.)
Urgency of the evaluation — It is important to urgently evaluate patients with a suspected gout flare in order to appropriately exclude alternative, time-sensitive diagnoses (eg, septic arthritis, cellulitis). In addition, a rapid evaluation allows for the timely initiation of antiinflammatory therapy, which can shorten the severity and duration of a gout flare. For patients with established gout, it is sometimes possible to empirically initiate treatment prior to an in-person evaluation when there is a low suspicion of alternative diagnoses, including a low risk of infection. (See "Gout: Treatment of flares", section on 'Pretreatment considerations' and 'Suspected gout flare in patients with established gout' below.)
If symptoms of a suspected gout flare resolve and patients are in a potential intercritical period, then they can be evaluated on a nonurgent basis.
Initial evaluation for all patients — When evaluating a patient with suspected gout, we perform a comprehensive evaluation that includes the following aspects of their presentation and medical history:
●The quality, severity, location, and distribution of involvement in prior episodes. The description of specific symptoms (eg, pain, disability, swelling, redness, warmness) is often helpful in distinguishing gout from other forms of arthritis.
●When pain began and how quickly it escalated, including potential triggers (eg, recent change in medications that affect urate balance, joint trauma, intercurrent illness, or ingestion of purine-rich foods).
●Exacerbating or alleviating factors, including home use of over-the-counter medications (eg, nonsteroidal antiinflammatory drugs [NSAIDs]).
●Associated symptoms, such as fever or malaise.
●History of crystalline arthropathies, intermittent arthritis, hyperuricemia, and medical conditions associated with gout (eg, hypertension, diabetes, chronic kidney disease, obesity).
●Family history of gout.
The physical examination should likewise be comprehensive, with particular attention to the musculoskeletal system and signs of focal inflammation (ie, warmth, swelling, redness, and/or tenderness) in joints or surrounding tissues. We look and feel for evidence of tophi in common locations, such as the olecranon and prepatellar bursae and pinnae of the ears (picture 3 and picture 6). (See 'Tophaceous gout' above.)
The range of blood testing in patients presenting with a suspected gout flare will vary based on the specific clinical presentation. For patients without a crystal-proven diagnosis of gout, we generally check a serum urate, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and kidney function (ie, serum creatinine) to look for evidence of hyperuricemia, inflammation, and underlying kidney dysfunction. There is no blood test that is entirely sensitive or specific for diagnosing gout, including serum urate; however, urate is most likely to be accurate during the intercritical period. (See 'Laboratory findings' above.)
More information on the evaluation of adults presenting with monoarthritis and polyarthritis is presented separately. (See "Monoarthritis in adults: Etiology and evaluation", section on 'Evaluation' and "Evaluation of the adult with polyarticular pain".)
Subsequent evaluation — The subsequent evaluation depends on whether there is a concern for a gout flare at the time of evaluation and if the patient has a crystal-proven diagnosis of gout. Aspiration and fluid analysis of the affected joint or bursa are always indicated when there is suspicion for infection (eg, warm, swollen, painful joint with fever, evidence of extraarticular infection, and/or atypical features compared with any prior flares) (algorithm 1).
Suspected gout flare in patients without established gout — While synovial fluid aspiration and analysis to visualize MSU crystals is the surest way to diagnose gout, a clinical diagnosis can often be made when this is not possible. Plain radiographs of the affected area are standardly done, and advanced imaging may be helpful in cases of persistent diagnostic uncertainty.
Clinical diagnosis — Clinical features supportive of gout can be sufficient to establish an initial empirical diagnosis and start management of gout while ruling out alternative diagnoses. This is appropriate even in the absence of crystal confirmation. This process can be aided by a clinical diagnostic approach ("rule") based on a set of validated clinical, historic, and laboratory criteria used in the setting of a monoarthritis presentation [83,84]. This rule was developed to improve the accuracy of diagnosing gout flares without joint fluid analysis and was created by analyzing 328 patients with acute monoarthritis seen initially by family practitioners in the Netherlands who also underwent prompt expert synovial fluid analysis. The model uses seven variables (which were assigned weighted scores) to distinguish three levels of risk for gout:
●Male sex (2 points)
●Previous patient-reported arthritis flare (2 points)
●Onset within one day (0.5 points)
●Joint redness (1 point)
●First MTP joint involvement (2.5 points)
●Hypertension or at least one cardiovascular disease (1.5 points)
●Serum urate level greater than 5.88 mg/dL (3.5 points)
In the study cohort, scoring for low (≤4 points), intermediate (>4 to <8 points), and high (≥8 points) probability of gout identified groups with a prevalence of gout of 2.2, 31.2, and 82.5 percent, respectively [83]. In addition, the authors of the rule have developed a calculator for clinical use that provides a more precise absolute calculated risk of gout for the individual patient [85], based upon statistically refined characterization of the variables [83,84]. If patients score in the intermediate category, further investigation is required (eg, repeat arthrocentesis attempt, imaging), as gout cannot be excluded or confirmed based upon an intermediate score alone.
Role of arthrocentesis and synovial fluid analysis — If possible, we aspirate an affected joint or bursae when a gout flare is suspected in a patient without a previously established diagnosis of gout (algorithm 1). Testing of articular or bursal synovial fluid should include cell counts and differential white cell count, Gram stain and culture, and examination for crystals under polarizing light microscopy. Clinicians who are not skilled at joint aspiration should request the assistance of an experienced provider (eg, orthopedic surgeon, rheumatologist, or interventional radiologist) to obtain and analyze synovial fluid. Challenges with arthrocentesis and crystal confirmation in synovial fluid include patient acceptability and lack of experienced examiners or appropriate microscopy in laboratories. (See "Joint aspiration and injection in adults: Indications and technique" and "Synovial fluid analysis".)
The sensitivity of the joint fluid analysis can be improved by examination of the sediment in a centrifuged specimen [86]. Additional approaches to consider in the event of a negative (no urate crystals seen) study include aspiration of another concurrently inflamed joint, suspected tophus, or uninflamed but previously involved joint. Of note, aspirating a tophus or uninflamed joint is less helpful in excluding an accompanying cause for the acute event.
Role of imaging — We generally obtain plain radiographs of the affected area because of their low cost, almost universal accessibility, highly specific findings when positive for gouty erosions, and the possibility of exploring findings in the differential diagnosis of gout. As an example, in the setting of suspected finger and/or toe involvement, plain radiography may reveal findings that suggest alternative diagnoses (eg, osteoarthritis) and, in patients with more chronic disease, demonstrate a characteristic erosive appearance ("overhanging edge") that is very supportive of gout.
In addition, we consider advanced imaging to noninvasively visualize MSU crystal deposition in the setting of persistent diagnostic uncertainty and inability to visualize MSU crystals using other methods (eg, patient preference to avoid aspiration, failure to visualize MSU crystals on synovial fluid). Depending on local availability, we obtain either ultrasonography or dual-energy CT (DECT) of the affected joints, especially when there is a history of multiple episodes of intermittent, acute inflammatory arthritis primarily involving one or a few specific joints.
Although studies establishing the sensitivity and specificity of ultrasonography and DECT for diagnosing gout were done in patient subsets with more advanced disease, these imaging modalities can still identify crystal deposition in most early gout patients when they are performed and interpreted by practitioners with appropriate expertise. The yield of both DECT and ultrasound is not expected to vary when a patient is having a flare.
Imaging findings suggestive of gout are discussed above. (See 'Imaging findings' above.)
Suspected gout flare in patients with established gout — For patients with a history of crystal-proven gout who present with a likely flare, the evaluation depends on whether there are any features that suggest the possibility of an alternative diagnosis that would alter management. We generally seek to confirm a flare with diagnostic testing if one or more of the following apply:
●Symptoms are not typical for the patient's typical gout flare
●Features that suggest or predispose the patient to infection (eg, concurrent fever, evidence of extraarticular infection, use of immunosuppression) or other alternative diagnoses (eg, history of trauma)
In such cases, our evaluation is similar to that outlined for patients without an established history of gout (see 'Suspected gout flare in patients without established gout' above). Otherwise, patients with crystal-confirmed gout who have typical symptoms of a flare and no concerning features can often be treated empirically without pursuing additional diagnostic testing. (See "Gout: Treatment of flares", section on 'Pretreatment considerations'.)
Suspected intercritical or tophaceous gout — Patients sometimes present for an evaluation of suspected gout, including tophaceous gout, when they are not having symptoms (ie, in a suspected intercritical period). In such cases, our diagnostic approach is similar to that used for patients with a suspected gout flare who do not have established gout:
●Clinical diagnosis with or without imaging – A provisional diagnosis of gout can be made by a combination of clinical, laboratory (ie, hyperuricemia), and radiologic criteria. Ultrasound and DECT confirmation of gout, when available, have a growing role in this scenario (see 'Role of imaging' above). Non-crystal diagnostic criteria are validated only for a past presentation of monoarthritis, and their application during an intercritical period awaits further investigation. (See 'Clinical diagnosis' above.)
●Aspiration of previously affected joint or tophus – With a good history and access to advanced imaging, it is uncommon in our experience to have to aspirate a currently asymptomatic joint to diagnose gout. However, MSU crystals are still identifiable in synovial fluid from previously affected joints in virtually all untreated gouty patients and in approximately 70 percent of those receiving urate-lowering therapy [68,87,88]. (See 'Role of arthrocentesis and synovial fluid analysis' above.)
Likewise, clinically apparent tophi can also be aspirated [89], although this is rarely required. We typically aspirate tophi using a large bore needle inserted into a more soft and fluctuant part of the tophus. Tophaceous material can be difficult to aspirate because of its thickness, and for this reason, a large bore needle (18 or 20 gauge) is preferred for this process. The recovered material is laid out directly on a slide without any staining and examined under polarized microscopy. However, simple light microscopy of evident tophaceous material could be sufficient for diagnosis when there is no access to a polarized microscope. (See 'Role of arthrocentesis and synovial fluid analysis' above.)
●Crystal confirmation on tissue biopsy (uncommon) – Uncommonly, patients may have a tissue biopsy done for other reasons that can be evaluated histologically for MSU crystals. Ideally, tissues are examined as fresh or frozen sections or are preserved in alcohol (rather than in formalin) and later stained with a nonaqueous system such as Wright-Giemsa stain. However, formalin-fixed, paraffin-embedded tissue may still occasionally have demonstrable birefringent urate crystals if stained with a nonaqueous technique using alcoholic eosin [90]. Aqueous stains (eg, hematoxylin and eosin) allow urate crystals to dissolve, leaving behind a nondiagnostic eosinophilic matrix that may have foreign body giant cells.
ESTABLISHING THE DIAGNOSIS —
It is important to establish a definitive diagnosis of gout whenever possible, both to exclude alternative explanations for the acute event and to ensure that patients with other forms of inflammatory arthritis are not treated unnecessarily with long-term, expensive, and potentially toxic urate-lowering medications.
●During an acute flare – Some patients with a history of crystal-confirmed gout who experience symptoms suggestive of a flare in the absence of features concerning for infection may be diagnosed on their clinical presentation alone. Otherwise, the diagnosis of gout flare is most secure when an experienced examiner identifies MSU crystals in an inflammatory synovial fluid of an affected joint or bursa (sensitivity and specificity of 85 and 100 percent) (picture 5) [91,92] (see 'Laboratory findings' above). If this is not possible or successful, a clinical diagnostic rule can be considered. Ultrasonography or DECT can be an alternative and potentially complementary approach in patients without a previously established diagnosis of gout; however, this requires expertise in the relevant imaging techniques and their interpretation and may lack adequate sensitivity, especially in patients without chronic symptoms. (See 'Suspected gout flare in patients without established gout' above.)
Gout flares may occasionally coexist with another type of joint disease, such as septic arthritis or acute calcium pyrophosphate (CPP) crystal arthritis (pseudogout). Thus, for all patients with a high suspicion of septic arthritis, we pursue arthrocentesis and continue to monitor the synovial fluid culture over time, even when MSU crystals are detected. (See 'Role of arthrocentesis and synovial fluid analysis' above and 'Differential diagnosis' below.)
●During an intercritical period – As is the case when diagnosing an acute flare, the most reliable way to diagnose gout during the intercritical period is with confirmation of MSU crystals in material aspirated from a previously affected joint or suspected tophus. Otherwise, a likely diagnosis of gout can be made based on a combination of consistent features and findings in the history, physical examination, and imaging. (See 'Suspected intercritical or tophaceous gout' above.)
ROLE OF CLASSIFICATION CRITERIA —
The American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) developed classification criteria for gout not for clinical diagnostic purposes, but rather to facilitate identifying a homogeneous group of patients for clinical, genetic, and epidemiologic study. The criteria were created through an international collaborative effort and are based upon studies of a diverse group of patients [93].
The 2015 criteria permit classification as having gout in patients with at least one symptomatic episode (eg, swelling, pain, or tenderness) in a peripheral joint or bursae with either the presence of monosodium urate (MSU) crystals (eg, from a tophus or affected joint or bursa) or a sufficient number and type of a series of well-defined clinical and imaging findings [93]. In the latter case, a negative search for MSU crystals reduces the calculated score. Among patients with at least one episode of swelling, pain, or tenderness in a peripheral joint or bursa, the classification criteria have a sensitivity and specificity of 92 and 89 percent, respectively [93,94]. While of direct benefit to researchers, this classification scheme has not been evaluated for its utility in clinical practice, where demonstration of MSU crystals remains central to establishing a diagnosis of gout.
DIFFERENTIAL DIAGNOSIS —
A wide variety of conditions may result in acute monoarthritis or polyarthritis, as is discussed in detail separately (see "Monoarthritis in adults: Etiology and evaluation" and "Evaluation of the adult with polyarticular pain"). In most instances, gout can be distinguished from other forms of acute and chronic arthritis through a combination of monosodium urate (MSU) crystal identification in affected areas, as well as the use of validated clinical diagnostic criteria utilizing the clinical history, physical examination, and/or imaging findings. (See 'Establishing the diagnosis' above.)
The differential diagnosis of gout includes:
●Septic arthritis – Distinguishing monoarticular gout flare from septic arthritis is very challenging, as both may be accompanied by fever, leukocytosis, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). On rare occasions, a gout flare and septic arthritis coexist. Extremely high white blood cell counts in synovial fluid (>100,000 cells/mL) are most supportive of a diagnosis of septic arthritis, although this is occasionally found in gout [95] (see "Septic arthritis in adults", section on 'Interpreting synovial fluid test results'). In our experience, response to colchicine, nonsteroidal antiinflammatory drugs (NSAIDs), and systemic glucocorticoids cannot be reliably used to differentiate between crystalline and septic arthritis.
●Cellulitis – The extensive periarticular inflammation accompanying a gout flare (particularly involving contiguous joints) may result in a clinical picture resembling cellulitis. In most instances of cellulitis, the distribution of inflammatory signs and symptoms does not focus on a joint, progressively extends into nonarticular areas, and is accompanied by systemic symptoms such as fever and chills. Cellulitis can also be distinguished based on the results of synovial fluid testing, which in cellulitis is noninflammatory and does not contain MSU crystals. When aspirating a nearby joint, providers should avoid areas of potential cellulitis to reduce the risk of extending an infection into the joint. (See "Joint aspiration and injection in adults: Indications and technique", section on 'General principles'.)
●Calcium pyrophosphate (CPP) crystal deposition disease – A number of features can help to differentiate gout from CPP crystal deposition (CPPD) disease, as outlined in the table (table 5). In particular, synovial fluid aspiration during an episode of acute CPP crystal arthritis should demonstrate CPP crystals (picture 7). The presence of linear calcifications or amorphous calcium in the affected joint (chondrocalcinosis) increases the chances of CPPD disease. In some cases, CPPD disease and gout coexist. (See "Calcium pyrophosphate crystal deposition (CPPD) disease: Clinical manifestations and diagnosis".)
●Basic calcium phosphate (BCP) crystal disease – Arthritis or periarthritis due to the deposition of BCP crystals usually cannot be diagnosed with certainty by polarized microscopy because the individual crystals are below the resolution of standard light microscopy and clumps of crystal aggregates are not birefringent [96]. Features suggestive of BCP crystal disease include periarticular calcifications on radiography and a more moderate elevation in the synovial fluid white blood cell count. (See "Basic calcium phosphate (BCP) crystal arthritis, including Milwaukee shoulder syndrome" and "Basic calcium phosphate (BCP) crystal-associated calcific periarthritis (tendinopathy)".)
●Trauma – Gout flares of lesser severity may be mimicked by a stress fracture or traumatic process in the bone or joint. These processes can be distinguished from gout based on imaging. (See "Toe fractures in adults" and "Metatarsal shaft fractures" and "Overview of bone stress injuries and stress fractures", section on 'Diagnosis'.)
●Osteomyelitis – Rarely, the expansive and destructive changes associated with tophaceous gout may be mistaken for osteomyelitis (image 3) and have sometimes led to erroneous amputation of involved digits [97]. Gout and osteomyelitis have been found to coexist in patients with risk factors common to both conditions (eg, poorly controlled diabetes mellitus). Severe bone marrow edema by magnetic resonance imaging is probably the best way to determine if osteomyelitis involves an extremity, and is rarely seen in gout [82]. Although dual-energy CT (DECT) can confirm the presence of gouty deposits, it cannot confirm or rule out the presence of osteomyelitis. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults", section on 'Diagnosis'.)
●Psoriatic arthritis (PsA)/spondyloarthritis – The clinical appearance of a gout flare affecting a digit (with or without a tophaceous component) may be similar to dactylitis seen in other disorders such as spondyloarthritis (eg, PsA, axial spondyloarthritis, reactive arthritis). These conditions can usually be distinguished from gout based upon the history and physical examination. Of note, there is a high prevalence of hyperuricemia in patients with psoriasis, and patients can have comorbid PsA and gout [98]. The clinical manifestations and diagnosis of these other disorders is discussed in detail separately. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Periarticular disease' and "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Dactylitis' and "Reactive arthritis", section on 'Musculoskeletal signs and symptoms' and "Sarcoid arthritis", section on 'Patients with a chronic arthritis'.)
●Rheumatoid arthritis (RA) – Occasionally, tophi may be mistaken for rheumatoid nodules associated with RA (and vice versa). Features that suggest gout rather than RA include asymmetry and asynchrony of joint involvement, presence of MSU crystals, and distinctive radiographic features. (See "Rheumatoid nodules", section on 'Subcutaneous nodules'.)
●Other – The differential diagnosis among patients with a history of recurrent flares of acute arthritis with spontaneous resolution or rapid and complete improvement with use of NSAIDs includes other forms of inflammatory arthritis, palindromic rheumatism, acute rheumatic fever, and osteoarthritis (eg, of the first metatarsophalangeal [MTP] joint), as well as rare disorders such as Whipple's disease or sarcoid arthropathy. (See "Reactive arthritis" and "Clinical manifestations of rheumatoid arthritis", section on 'Palindromic rheumatism' and "Acute rheumatic fever: Clinical manifestations and diagnosis" and "Whipple's disease".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gout and other crystal disorders".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Gout (The Basics)")
●Beyond the Basics topics (see "Patient education: Gout (Beyond the Basics)")
PATIENT PERSPECTIVE TOPIC —
Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Gout".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology and risk factors – Gout is a chronic disease of monosodium urate (MSU) crystal deposition. Gout flares occur due to the innate immune response to deposited crystals. The incidence and prevalence of gout are increasing, affecting approximately 56 million individuals worldwide. Risk factors are listed in the table (table 1). (See 'Epidemiology and risk factors' above.)
●Clinical features
•Gout flares – Provoking factors for gout flares are listed in the table (table 4). (See 'Provoking factors' above.)
A typical gout flare is typically intensely inflammatory, with severe pain, redness, swelling, and disability (picture 1). At least 80 percent of initial flares involve a single joint, most commonly the base of the great toe or the knee. Other common sites are the ankle, instep, wrist, finger, and elbow.
Maximal severity of the flare is usually reached within 12 to 24 hours. Gout flares almost always resolve within a few days to several weeks, even without treatment. Without urate-lowering treatment, patients with gout can develop increasingly frequent, prolonged, polyarticular gout flares that may be associated with fever. (See 'Gout flares' above.)
•Tophaceous gout – Tophi are collections of densely packed MSU crystals in connective tissues accompanied by chronic inflammation and often by destructive changes. They can be visible and/or palpable but are usually not painful or tender, and they may affect the ears or soft tissues (eg, articular structures, tendons, bursas, or bone) (picture 3 and picture 4). (See 'Tophaceous gout' above.)
•Laboratory findings – Synovial fluid from an affected joint should be inflammatory (ie, a white blood cell count of 10,000 to 100,000 cells/m3 with a neutrophilic predominance); polarized light microscopy may reveal needle-shaped, strongly negatively birefringent MSU crystals that appear bright yellow when they are parallel to the red compensator axis (picture 5). Serum urate is elevated in almost all people with gout. However, the serum urate can drop into the normal range during a gout flare. (See 'Laboratory findings' above.)
●Evaluation
•When to suspect – Gout flare should be suspected in patients presenting with a monoarthritis of the lower extremities, especially when there is involvement of the first metatarsophalangeal (MTP) joint. Suspicion is further increased in the presence of hyperuricemia, recognized risk factors, and/or known triggers. Clinical manifestations may also include inflammation of periarticular tissues and/or polyarthritis. (See 'When to suspect' above.)
•Initial evaluation for all patients – All patients require a detailed history and physical examination as well as basic laboratory testing. The most accurate time for assessment of serum urate (and establishment of a baseline value) is two weeks or more after a gout flare completely subsides (ie, during an intercritical period). (See 'Initial evaluation for all patients' above.)
•Subsequent evaluation and diagnosis – The preferred approach to diagnosing gout is illustrated in the algorithm (algorithm 1).
-Suspected gout flare in patients without established gout – A clinical diagnosis can be established based on clinical history and physical examination findings. When possible, we aspirate synovial fluid for crystal confirmation through microscopy to confirm the diagnosis and exclude other conditions. Since gout flares and septic arthritis can occur simultaneously, arthrocentesis is always required when suspicion of septic arthritis is high.
An alternative and potentially complementary approach to synovial fluid analysis is demonstrating crystal deposition on imaging (eg, ultrasonography or dual-energy CT [DECT]). (See 'Suspected gout flare in patients without established gout' above.)
-Suspected gout flare in patients with established gout – Such patients may require arthrocentesis and synovial fluid analysis if symptoms are not typical for the patient's gout flare and/or if there are features that suggest or predispose the patient to infection (eg, concurrent fever) or other alternative diagnoses (eg, history of trauma). (See 'Suspected gout flare in patients with established gout' above.)
-Suspected intercritical or tophaceous gout – If patients present for an evaluation of suspected gout when they are not having symptoms (ie, during a suspected intercritical period), we try to establish a provisional diagnosis of gout by a combination of clinical and historic criteria as well as evidence of MSU deposition on imaging. Aspiration of a previously affected joint or tophus can be attempted for crystal confirmation. (See 'Suspected intercritical or tophaceous gout' above.)
ACKNOWLEDGMENT —
The editorial staff at UpToDate acknowledge Michael A Becker, MD, who contributed to an earlier version of this topic review.
