This article provides a concise review of gout and its clinical and radiographic manifestations, especially those seen in the musculoskeletal system, and their differential diagnosis. It also includes a succinct discussion of the current management options.
Dr. Zayas is a Fellow in Musculoskeletal Radiology and Dr.
Pierre-Jerome and Dr. Monu are Associate Professors in the
Department of Radiology, University of Rochester School of
Medicine and Dentistry, Rochester, NY; and Dr. Calimano and Dr.
Acosta are Fellows in Musculoskeletal Radiology in the
Department of Radiology, University of Florida College of
Medicine, Gainesville, FL.
Gout is a metabolic disorder characterized by a derangement of
purine metabolism manifested by hyperuricemia, deposition of
monosodium urate monohydrate crystals in the synovial fluid
leukocytes, gross deposits of sodium urate in the periarticular
soft tissues, and recurrent episodes of arthritis.
The disease primarily affects the musculoskeletal system. However,
many patients also present with associated genitourinary
manifestations, such as chronic interstitial nephropathy and
Gout may be classified as primary or secondary (Table 1).
Primary gout results from inborn errors in the metabolism of
purines or inherited defects in the renal tubular secretion of
urate. Primary gout accounts for 90% of all cases of gout.
Primary gout is a disease of adult men with only 5% of cases
occurring in postmenopausal women. Two effects of estrogen explain
this fact. Estrogen promotes renal clearance of uric acid and
protects against membranolysis by urate crystals.
Secondary gout occurs in disorders characterized by increased
turnover of nucleic acids, drugs, or by acquired defects in the
renal excretion of urates. Secondary gout accounts for 10% of all
cases of gout.
Gout, in all of its forms, accounts for about 5% of all cases of
The biochemical hallmark of gout is the elevation of serum urate
levels. The risk of developing gout increases with the degree of
hyperuricemia. Virtually all patients will have serum urate levels
above 7 mg/dL. However, the pathogenesis of the disease is more
closely related to the solubility of urate in the various body
fluids than to its absolute concentration. Solubility of urate is
affected by temperature and pH.
In the body, the solubility of urate is significantly less at the
lower temperatures seen in the peripheral joints; this may
partially explain the distribution of the disease in the skeletal
The clinical history of gout comprises four distinct stages:
asymptomatic hyperuricemia, acute gouty arthritis, chronic
tophaceous gout, and nephrolithiasis/nephropathy. These stages
proceed in a roughly chronological order in the majority of
patients. However, nephrolithiasis may precede the arthritis in up
to 20% of cases.
This stage of gout refers to elevation of serum urate levels
prior to the development of any symptoms. Acute attacks of
arthritis, urolithiasis, or both mark the end of this stage of the
Acute gouty arthritis
The most common manifestation of this stage is a painful
arthritis. Approximately 90% of early gout attacks are
monoarticular, usually involving the lower extremities. The first
metatarsophalangeal joint is the most common site of initial
involvement (seen in at least 50% of cases) and may be altered in
up to 90% of patients with gout over the course of the disease.
Other initial sites of involvement include the ankles, heels,
knees, wrists, fingers, and elbows. Inflammatory changes are
uncommon in the spine, hips, shoulders, and sacroiliac, and
temporomandibular joints. Any joint, however, may be affected by
Acute attacks may be precipitated by events such as trauma,
surgery, alcohol or other dietary indiscretions, or systemic
infection. Although the course varies, initial attacks are usually
self-limited with the pain resolving within a few hours or a few
days even without treatment.
Chronic tophaceous gout
This phase occurs in <50% of patients who experience
recurrent acute attacks.
The attacks in this stage will tend to be more severe and
prolonged, and will commonly be polyarticular. At this point in the
disease, there will be gross deposition of monosodium urate
crystals around the joints (tophi).
The tophus is the pathognomonic lesion of gout and is
essentially a foreign body granuloma. Tophaceous deposits appear in
cartilage, ligaments and tendons, bursae, and synovial membranes
and other periarticular soft tissues at a rate equal to the degree
and duration of hyperuricemia.
Tophi are frequently seen in the external ear and pressure points
over the elbows, hands, feet, knees, and forearms. Tophi may
ulcerate and express whitish, chalky material. Although painless,
their presence ultimately can limit joint motion.
As they become larger, tophi may calcify or ossify and produce
tendon rupture, nerve compression, and/or paralysis.
Reactions to the deposition of crystals in the soft tissues
include cartilage degeneration and destruction, synovial
proliferation and pannus, destruction of subarticular bone, and
proliferation of marginal bone. Fibrous or bony ankylosis may also
Gouty nephropathy/ nephrolithiasis
Two renal syndromes are associated with hyperuricemia: acute
urate nephropathy and uric acid urolithiasis.
Patients also have an increased incidence of calcium oxalate stones
because urate crystals serve as nidus for calcium stone formation.
Other renal manifestations include hypertension, isosthenuria
(inability to concentrate urine), pyelonephritis, and proteinuria.
Tophaceous deposits may be seen in the renal medullary interstitium
and in the corpus cavernosum, leading to erectile dysfunction.
Only 45% of patients with gout manifest radiographic changes.
These changes develop late in the disease and only after repeated
attacks. Therefore, negative radiographs do not exclude gout and
are usually of little value in the early diagnosis or evaluation of
the disease. Rarely, especially in atypical cases, the radiologist
may be the first to raise suspicion about the presence of gout.
The earliest radiographic signs of gout are joint effusion and
These nonspecific changes reflect the inflammatory reaction
elicited by the deposition of nonopaque urate crystals in the joint
synovial membrane and on the surface of the articular cartilage. As
the attack subsides, these radiographic changes will likely
Deposits of urate crystals (tophi) form along the margins of the
articular cortex and may erode the underlying bone, producing
small, sharply marginated, punched-out defects at the joint margins
of the small bones of the hand and foot. These erosions may have a
cyst-like appearance with thin sclerotic borders (figure 1). They
tend to be ovoid in shape, are oriented along the long axis of the
bone (figure 1) and frequently have characteristic overhanging
The erosions may be intra-articular, para-articular, or located
at a considerable distance from the joint.
The intra-articular erosions usually start in the margin of the
joint and proceed centrally. Para-articular erosions tend to be
eccentric and located beneath soft-tissue nodules. In advanced
disease, the extensive bony erosions may produce joint destruction
and mutilating arthritis (figures 2 and 3).
In about 40% of patients with erosions, an elevated bony margin,
known as an overhanging edge, extends outward in the soft tissues
apparently covering the tophus.
Although not pathognomonic, their appearance is strongly suggestive
of gout (figure 4).
The continued deposition of urate crystals in the para-articular
tissues causes the development of characteristic large, lumpy
soft-tissue nodules representing gouty tophi (figure 4). The
lesions may not be seen in radiographs until they reach 5 to 10 mm
In addition to the first metatarsophalangeal joint, other common
sites of tophi include the ear, olecranon bursa, and the Achilles
tendon (figure 5). Noncalcified tophi made up of only sodium urate
have soft-tissue density. Deposition of calcium in the urate
collections causes the tophaceous masses to become radiopaque
(figure 6). Calcification of a tophus is unusual and may reflect an
underlying abnormality of calcium metabolism. The calcific deposits
will appear as irregular radiodense areas and are initially seen in
the periphery of the tophus. Ossification of the tophi is
The joint space is well preserved until late in the course of
The presence of relatively normal joint space and preservation of
the articular cartilage with extensive erosions is a distinctive
radiographic feature of gout (figure 7). Joint-space narrowing is
frequent in advanced cases. Bony ankylosis has been observed, but
is a rare finding.
In gout, the bone mineral density is preserved until late in the
disease. Extensive osteoporosis is not a feature of gout.
The presence of normal mineralization may help differentiate this
condition from rheumatoid arthritis. It is believed that the reason
for the presence of normal mineralization is that the duration of
the attack is too short to allow the development of osteoporosis of
disuse as is seen in rheumatoid arthritis.
Proliferative bony abnormalities and intraosseous
Bony proliferative changes are occasionally seen in gout. These
may be seen as club-shaped metatarsals, metacarpals, and phalanges;
enlargement of the ulnar styloid process; and diaphyseal
Secondary osteoarthritic changes are common and can obscure the
more characteristic features of the disease.
Intraosseous calcifications reflect the deposition of urate in
the bone and are mostly seen in the hands and feet. These appear as
punctate or circular calcific lesions usually located in the
subchondral or subligamentous bony region.
The changes may resemble those of enchondromas or bone infarcts.
Rarely, cysts in the bone (pseudotumors) representing true
tophaceous or urate crystal-rich fluid deposits may be seen,
especially in juxta-articular locations (figures 8 and 9). The
lesions tend to be well marginated.
Five percent of patients with gout have cartilage calcification
Patients with gout often have chondrocalcinosis because they have a
predisposition for calcium pyrophosphate dihydrate crystal
deposition disease (CPPD). The presence of chondrocalcinosis in
gout is usually localized to one or two joints and involves the
fibrocartilage alone (figure 10).
The presence of tophi, intact joint spaces, osseous erosions, and
the distribution of disease usually permit differentiation of the
Bursal inflammation produces erosive and proliferative changes
in the subjacent bone and soft-tissue swelling.
These changes are most commonly observed in the olecranon bursa
along the extensor surface of the elbow (figure 11) and the
prepatellar bursa of the knee.
Uric acid stones
Renal stones occur in nearly 20% of patients with gout. In
patients with gout, 84% of stones are composed of pure uric acid,
4% are uric acid and calcium oxalate, and 12% are calcium oxalate
or phosphate alone.
The incidence of stones increases with the degree of hyperuricemia.
Pure uric acid stones are radiolucent on x-rays and appear as
filling defects in the collecting system after contrast
administration for intravenous pyelograms. However, pure uric acid
stones are hyperdense on non-contrast CT and echogenic under
Patients with gout do not develop radiographic changes until
late in the disease and after repeated arthritic attacks.
Radiographic evaluation helps establish the diagnosis and determine
the severity and extent of the disease. Several arthritic processes
form part of the radiographic differential diagnosis of gout; the
most common processes will be discussed in this section.
Calcium pyrophosphate dihydrate crystal deposition disease can
produce an acute arthritis with symptoms identical to gout
(pseudogout); up to 40% of patients with gout concomitantly have
CPPD. The characteristic radiographic changes of CPPD are
chondrocalcinosis and degenerative arthropathy. These changes are
also seen in gout. However, the chondrocalcinosis seen in CPPD is
polyarticular and involves both hyaline and fibrocartilage.
The arthropathy seen in CPPD involves the matacarpophalangeal,
radiocarpal, elbow, shoulder, and knee joints with joint-space
narrowing, subchondral sclerosis, and cyst formation. Although the
changes could resemble those seen in gout, the absence of tophi and
bone erosions helps distinguish CPPD from gouty arthritis.
Psoriatic arthritis may appear similar to gouty arthropathy.
Similar features include normal bone mineralization, erosion, and
asymmetric distribution. Also, both processes can produce
hyperuricemia, bony proliferation, and soft-tissue swelling. The
distinguishing radiographic changes seen in psoriasis include
progressive joint-space destruction, paravertebral ossification,
and sacroiliac joint involvement.
Although rheumatoid arthritis (RA) and gout are common diseases,
their coexistence is extremely rare. Rheumatoid arthritis is not
usually mistaken for gout, even though both present with bone
erosions and soft-tissue swelling. However, RA presents with
marginal bone erosions that are nonproliferative and with
soft-tissue swelling that is fusiform. The features that serve to
distinguish RA from gout are the presence of symmetric
distribution, early joint-space narrowing, and osteopenia.
The coexistence of joint infection and gout is unusual in the
general population, but the two conditions may coexist in diabetic
patients. Septic arthritis and gouty arthropathy may present with
similar radiographic changes including soft-tissue swelling, bone
erosions, and monoarticular distribution. The joint space is
preserved in gout until late in the disease, whereas rapid
destruction of joint space is the norm in septic arthritis.
In a septic joint, there is loss of the lamina dura (articular
cortex) over a continuous segment of the bone. This is not usually
seen in gout.
Amyloidosis may cause soft-tissue masses and cystic/erosive bony
lesions indistinguishable from gout. However, amyloidosis tends to
be bilateral and symmetric. Periarticular osteopenia is
Xanthomas (foci of soft-tissue deposition of cholesterol and
lipid products) are frequent in the extensor surfaces of the hand
and foot, patellar and Achilles tendons, and the subcutaneous soft
tissues of the elbows and knees. These xanthomas present
radiographically as eccentric soft-tissue masses with associated
subjacent bone erosions simulating gout. Differentiation from gout
is made by laboratory work-up.
Patients with osteoarthritis (OA) may develop distal nodal
soft-tissue swelling and erosions (erosive OA) similar to those
seen in gout. However, erosive OA is commonly a disease of elderly
women and has a symmetric distribution.
Imaging of gout
The mainstay of imaging in gout is plain radiography of the
bones and joints. Plain radiographs will demonstrate many of the
features discussed above and enable an accurate diagnosis. Other
imaging modalities may also be used in the evaluation or follow-up
of a patient with gout. Intravenous urograms may be obtained in the
work-up of urinary stones.
Computer tomography (CT) may be used to evaluate bones and
joints that may be difficult to image satisfactorily with plain
radiography. These include irregularly shaped structures like the
pelvic bones, the vertebra, and the sacroiliac and facet joints.
Computer tomography imaging will optimally demonstrate bony
erosions, destruction, calcifications, and bony proliferations.
However, CT does not play a significant role in the primary
diagnosis of gout.
Ultrasound is not indicated in the primary work-up of gouty
arthritis. It may be used to evaluate soft-tissue swelling or
masses when the diagnosis is not known or clear. However,
ultrasound may be used to evaluate the urinary system in cases of
nephropathy, renal stones, and obstruction.
Radionuclide studies have no significant role in the work-up of
gout. Bone scans will give nonspecific findings such as
accumulation of radiotracer around areas of inflammation or
Magnetic resonance imaging (MRI) is frequently requested when
osteomyelitis or septic arthritis is suspected. In acute gout, MRI
findings will be similar to those seen in infection. There may be
para-articular inflammation seen as abnormal signal on T2-weighted
images. In contrast-enhanced studies, there will be abnormal
enhancement in the soft tissues around the joint (figure 12). The
extent of abnormal signal in the tissues is usually less than would
be seen in septic arthritis or osteomyelitis. Calcifications within
a tophus will be seen as foci of low or absent signal on all pulse
sequences. However, hydrated crystal may show as high signal on
T2-weighted images (figure 11C). The MRI appearances of gout are
varied and should never be used in isolation to evaluate the
The availability of numerous drugs that abort or prevent acute
attacks of arthritis and mobilize tophaceous deposits underscores
the importance of establishing an early diagnosis. The use of these
drugs is important because many aspects of the disease are related
to the duration and severity of the hyperuricemia.
Management differs according to the stage of the disease and the
complications that are present.
Asymptomatic hyperuricemia usually requires no therapy except in
patients with marked elevated serum uric acid and a family history
of tophaceous gout. These patients should be treated with
allopurinol under close medical observation.
Acute attacks are treated with joint immobilization, colchicine,
non-steroidal anti-inflammatory agents (NSAIDs), and
corticosteroids. Uricosuric agents and allopurinol are of no value
in treatment of the acute attack.
During the interval phase (between acute attacks), patients
should avoid high purine foods and excessive alcohol use. Patients
should control their weight and hypertension, and maintain a high
fluid intake to promote uric acid excretion.
Allopurinol is the drug of choice for treatment of chronic gouty
Uricosuric drugs, such as probenecid and sulfinpyrazone, may also
be used. In selected patients, large deforming tophi may be excised
Gout is a metabolic disorder characterized by hyperuricemia and
tissue deposition of uric acid crystals in the joints, cartilage,
and kidneys. The disease may mimic an array of many different
skeletal abnormalities. Diagnosis mainly depends on laboratory
analysis of serum and synovial fluid to demonstrate hyperuricemia
and monosodium urate crystals. Radiologic studies provide a
multisystem evaluation to help establish the diagnosis and assess
the extent of disease. Plain radiographs of the musculoskeletal
system are the mainstay of this imaging assessment. Establishing a
prompt diagnosis allows for the timely implementation of therapy
with different pharmacologic agents, which are available for both
prevention of the disease and control of its more advanced