Supplements Update on the Diagnosis and Treatment of Gout
Diagnosis of Gout: Clinical, Laboratory, and Radiologic Findings
Acute gouty arthritis typically presents with a sudden and severe exquisitely painful joint, most classically in the first metatarsophalangeal joint (toe). Demonstrating the presence of monosodium urate (MSU) crystals in the joint fluid or tophus has been the gold standard for the diagnosis of gout. However, many physicians do not perform synovial fluid analysis. In the absence of demonstrating the presence of MSU crystals in aspirated joint fluid or tophus, clinical, radiologic, and laboratory criteria are helpful. This article presents an overview of the various classification criteria, clinical presentations, and laboratory and radiologic studies needed to make the diagnosis of gout.
(Am J Manag Care. 2005;11:S443-S450)
Gout is a common systemic metabolic disease, affecting more than 1% of the population. It is the most common inflammatory arthritis, afflicting 1 or more joints in men older than 40 years of age.1 The majority of patients have primary gout, meaning that no identifiable underlying disease causing the hyperuricemia can be found. Secondary gout, which is less common, can result from many conditions (Table 1).
To understand gout adequately, it is important to define the relationship between uric acid, hyperuricemia, and gout. Humans do not express the enzyme urate oxidase (uricase), because of a mutation during evolution of the uricase gene, which converts urate to the more soluble and easily excreted compound allantoin. Among mammals, only humans and other primate species excrete uric acid as the end product of purine metabolism. Uric acid is a weak organic acid that exists mainly as the urate ion at pH >5.75 and as the un-ionized uric acid form at more acidic (lower) pH levels. Thus, the urate form predominates in all extracellular fluids, including serum, in which physiological pH is 7.4. In urine, which is usually acidic, the un-ionized uric acid form predominates.
When overproduction or underexcretion of uric acid occurs, the serum urate (SU) concentration may exceed the solubility of urate (a concentration approximately >6.8 mg/dL), and supersaturation of urate in the serum (and other extracellular spaces) results. This state, called hyperuricemia, imparts a risk of crystal deposition of urate in tissues from the supersaturated fluids.
Four clinical stages result from hyperuricemia, including asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout (intervals between acute attacks), and chronic tophaceous gout.2 Inflammatory arthritis in patients with gout is caused by crystals of monosodium urate (MSU) that form as a result of chronically elevated levels of urate in plasma and extracellular fluids.
Although the first descriptions of gout can be traced to the dawn of recorded medical history, questions remain regarding the diagnosis of gout.3 The gold standard for establishing a definite diagnosis of gout is the presence of MSU crystals in aspirated joint fluid or tophus.4 Physicians, however, do not routinely perform synovial fluid (SF) analysis, even in hospitalized patients with acute gout,5 opting instead to reach a diagnosis based on clinical features and demonstration of hyperuricemia.
There are many limitations to this diagnostic approach. In a study of 9108 consecutive new patients seen in an outpatient rheumatology clinic, 155 (1.7%) were diagnosed with gout. A higher number of patients (164, 1.8%) had been incorrectly diagnosed with gout in the community.6 Some have maintained that gout can be diagnosed clinically by the triad of inflammatory arthritis, elevated SU level, and response to colchicine.6
In the absence of demonstrating the presence of MSU crystals in aspirated joint fluid or tophus, clinical, radiologic, and laboratory criteria are helpful. It is important to diagnose gout early so that underlying hyperuricemia and the acute attack can be treated appropriately. This article describes current knowledge regarding the diagnosis of gout and provides an overview of the various classification criteria and clinical examination, laboratory, and radiologic findings needed to make the diagnosis of gout.
The first criteria for the classification of gout were proposed at the Rome symposium on population studies in the rheumatic diseases.7 According to the Rome criteria, to be diagnosed with gout, patients must meet 2 of the following 4 criteria: (1) an SU level >7 mg/dL in men or >6 mg/dL in women; (2) the presence of tophi; (3) the presence of MSU crystals in SF or tissues; and (4) a history of painful joint swelling with abrupt onset and remission within 2 weeks.
These criteria were modified in an international symposium held in New York in 1966. The major changes were the addition of a response to colchicine and the removal of SU levels from the list of criteria.8 The New York criteria are still helpful in routine clinical practice. They include the presence of a clear history of at least 2 attacks of painful joint swelling with complete resolution within 2 weeks, a clear history or observation of podagra, the presence of a tophus, and a rapid response to colchicine within 48 hours of starting treatment. Two of these criteria are required for a clinical diagnosis, but a definitive diagnosis can be made if MSU crystals are seen in SF or in the tissues.
Rigby and Wood9 compared the New York and Rome criteria in 59 patients with gout and 761 patients with other arthropathies. They found that the best individual criterion was 1 or more attacks of podagra (New York criteria). In contrast, the presence of a tophus was the least valuable criterion. The New York criteria were more sensitive and specific than the Rome criteria. Rigby and Wood also investigated the value of determining the SU level in new patients in a rheumatology outpatient clinic. The gold standard in this study was clinical assessment by rheumatologists. Determining the SU level was a criterion for the diagnosis of gout in the Rome criteria but not in the New York criteria. Rigby and Wood concluded that in a clinical picture resembling gout, with a low SU level independent of the gouty attack, the diagnosis of gout is very unlikely.
In 1977, the American College of Rheumatology published preliminary criteria for the classification of gout for use in either clinical settings or population-based epidemiologic studies.10 Subjects were classified as having gout when they had MSU crystals in their SF, the presence of a proven tophus, or at least 6 of the remaining 11 criteria (Table 2). These criteria were extrapolated from a rheumatic population in which 6 or more of the 11 criteria were present in 87.6% of the 178 patients with acute gout.10 Tophi were present or suspected in 30% of the 178 patients with acute gout, with a specificity of 99%. Most likely, the specificity was not 100% because there were 1 or more cases of bacterial arthritis in gouty patients with tophi.
No studies have been published on the validity and usefulness of any of these diagnostic criteria. New classification criteria need to be defined and validated.
In his classic description of a gouty attack, translated from Latin in 1848, Sir Thomas Sydenham wrote:
The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. This pain is like that of a dislocation...Then it is a violent stretching and tearing of the ligaments--now it is a gnawing pain and now a pressure and tightening...He cannot bear the weight of bedclothes nor the jar of a person walking in the room. The night is passed in torture, sleeplessness, turning of the part affected, and perpetual change of posture; the tossing about of the body being as incessant as the pain of the tortured joint.11
As described so vividly by Sydenham, acute gouty arthritis is characterized by rapid onset and buildup of pain. The speed of the onset of pain and swelling is relevant to making the diagnosis; symptoms that take days or weeks rather than hours to develop probably indicate a disorder other than gout. The pain is described as the worst pain that the person has ever endured. The exquisite pain in acute gout is associated with warmth, redness, and swelling of the affected joint.
In men, the initial episode is usually monoarticular (1 joint). The typical patient tends to experience gout initially in the lower extremities. The first metatarsophalangeal joint (misnamed podagra) is initially involved in approximately half of all men with gout. Other joints involved (in decreasing order of frequency) include insteps, knees, wrists, fingers, and olecranon bursae.12 Systemic symptoms and signs of fatigue, fever, and chills may accompany the acute arthritis. The first episode of gouty arthritis often begins at night. This may be because there is a stable level of urate in the joint fluid and during rest, water is absorbed more rapidly than urate, increasing the concentration of urate or MSU crystals in the joint and precipitating attacks. The natural course of untreated gouty arthritis varies from episodes that last several hours to several weeks.
With uncontrolled hyperuricemia, the body urate pool expands and joint involvement becomes additive and ascending. Later attacks may be polyarticular. Polyarticular attacks tend to be less abrupt in onset, less severely painful, and more likely to be associated with constitutional upset than monoarticular attacks.13 It is important to note that the acute inflammatory events of gout are not limited to joints. Patients who present with symptoms in bursae and tendons should be evaluated for gout, which can occur in these locations. Minor trauma, alcohol abuse, surgery, dietary excess, hypouricemic or diuretic therapy, and severe medical illness can precipitate attacks.14
Gout in women follows a different pattern from that in men. Only a small number of women start with acute podagra (first metatarsophalangeal joint arthritis). The most common presentation is acute polyarticular gout, especially of the hands, tarsal joints, knees, and ankles.15 Women tend to develop tophaceous deposits on Heberden's and Buchard's nodes (hard bony enlargements of the small joints of the fingers seen in osteoarthritis), sometimes with minimal inflammation.16 This atypical joint involvement can cause diagnostic confusion with rheumatoid arthritis. Gouty arthritis, however, tends to be less symmetric than typical rheumatoid arthritis.
Gouty arthritis is often less severe in the elderly than in younger patients,17 and is often mistaken for osteoarthritis. This is further complicated by the coexistence of gout and osteoarthritis in the same joints, especially Heberden's nodes.18
Chronic tophaceous gout usually develops after 10 or more years of acute intermittent gout, although in rare cases, tophi may be the initial manifestation of the disease.19 Tophi appear as firm swellings. If they are inflamed, there is erythema of the overlying skin. Whitish chalky material may be seen in ulcerated tophi. Tophi may appear at any site, but the most common sites are the digits of the hands and feet and the olecranon bursa. Tophi of the helix or antihelix of the ear are classic but less common. Tophi have also been reported in the eye,20 carpal tunnel,21 and heart valves.22 In these situations, diagnosis is often unsuspected until surgery. Tophi may be associated with destructive deforming arthritis and may ulcerate, in which case secondary infection may be a problem. Of note, tophi sometimes tend to be confused with rheumatoid nodules, and, therefore, when in doubt, needle aspiration should be done to detect MSU crystals.