Gout: a clinical and radiologic review - Johnny U. V. Monu, MB, BSa,*, Thomas L. Pope, Jr, MDb
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Radiol Clin N Am 42 (2004) 169 – 184
Gout: a clinical and radiologic review
Johnny U. V. Monu, MB, BSa,*, Thomas L. Pope, Jr, MDb
a
Departments of Musculoskeletal Radiology and Emergency Radiology, University of Rochester School of
Medicine and Dentistry, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA
b
Departments of Radiology and Orthopedics, Medical University of South Carolina, Post Office Box 250322,
Charleston, SC 29425, USA
Gout as a disease has been well known from the Epidemiology
time of Hippocrates. Recently, there has been progres-
sive understanding of the pathophysiology of the Gout is the most common form of microcrystal-
disease and a subtle change in its pattern of distribu- line arthropathy and has been estimated to affect
tion; therefore, the disease continues to generate 2.1 million persons in the United States or 0.5% to
attention in the medical literature. The radiologic 2.8% of men and 0.1% to 0.6% of women [4,5]. The
manifestations of gout are generally well known and peak age incidence occurs at 30 to 50 years, and the
have remained unchanged. condition is about five times more common in men
Gout is the culmination of several physiologic than in women in this age group [1,6]. Primary gout
disturbances that ultimately result in the deposition is a disease of mainly men and accounts for as many
of uric acid salts and crystals in and around the joints as 90% of cases, with only 5% of cases occurring in
and soft tissues. Decreased uric acid clearance through postmenopausal women [3].
the kidney is the most common cause of gout [1]. A The prevalence of the disease increases with age.
family history of gout or hyperuricemia is found in as At about the age of 60 years and above, the preva-
many as 80% of patients. Gout has traditionally been lence of the disease in women approaches that in men
regarded as primary or secondary [2]. Primary gout is [4,7]. Gout occasionally occurs in patients younger
caused by inborn defects of purine metabolism or by than 30 years [8 – 11]. Manifestations of arthritis in
inherited defects of the renal tubular secretion of urate. young patients have been referred to as ‘‘early onset
Secondary gout is caused by acquired disorders that idiopathic gouty arthritis’’ [8]. The Maoris of New
result in increased turnover of nucleic acids, by defects Zealand and the inhabitants of the Mariana Islands
in renal excretion of uric acid salts, and by the effects have an increased incidence of gout [8]. Although, in
of some drugs [3]. With improved understanding of the the past, the disease was noted to be relatively
pathologic bases of the various forms of the disease, uncommon in Africans, there is now an increased
the distinction between primary and secondary gout risk of gout in African Americans, and an increasing
has become blurred. The disease is best described in prevalence of the disease is closely linked with
four clinical phases: asymptomatic hyperuricemia, hypertension and the use of diuretic agents [12].
acute gouty arthritis, intercritical gout, and chronic Transplant patients and patients on cyclosporine
tophaceous gout [1,4]. therapy are at increased risk for the disease [13].
Patients with myeloproliferative disorders, poly-
cythemia vera, myeloid metaplasia, and chronic mye-
logenous leukemia are at increased risk because of
* Corresponding author. the hyperuricemia from high cellular turnover. Sec-
E-mail address: johnny_monu@urmc.rochester.edu ondary gout develops in approximately 5% to 10% of
(J.U.V. Monu). these patients who are often women in their sixth
0033-8389/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/S0033-8389(03)00158-1170 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
decade of life. Rarely, the syndrome of gout may mation or vice versa, depending on the state of mono-
precede the myeloproliferative disorder [2]. cyte to macrophage differentiation [21].
Acute gout most commonly affects the first meta- Most patients with gout have a serum urate level
tarsal joint of the foot (podagra), but almost any joint above 6 mg/dL (in women) or 7 mg/dL (in men) [4].
can be involved [1,2]. Tophaceous gout occurs in less Acute attacks are more directly related to the solubil-
than 10% of patients, and the highest incidence of ity of uric acid in the various body fluids than to its
attacks is reported in the spring [14,15]. Acute attacks absolute concentration. The solubility of uric acid
may be provoked by trauma, surgery, infection, star- decreases in cold weather and in a lowering pH.
vation, and alcoholic or dietary indiscretions. Acute These properties may provide an explanation for the
attacks have been known to follow a game of golf, a increase in gouty attacks in the peripheral joints in
long walk, or a hunting trip, leading to the name cold weather and with a lower body temperature.
‘‘pheasant hunter’s toe.’’ Estrogen protects against the membranolysis by urate
crystals and promotes uric acid clearance by the renal
tubules [22,23]. These two effects of estrogens partly
explain the low prevalence of gout in premenopausal
Pathophysiology women. Thiazide diuretics, alcohol, low-dose salicy-
lates, and cyclosporine decrease the renal excretion
Uric acid is the end product of purine degradation of uric acid and promote the development of gout
in humans because of lack of the enzyme uricase, [13,22,24]. Systemic conditions such as hypertension
which converts uric acid to allantoin, a more soluble and diabetes mellitus predispose to gout partly by a
excretory product. Hyperuricemia results from sev- reduction of glomerular filtration and tubular function
eral causes, including overactivity of phosphoribo- [25]. The association of gout and insulin resistance
sylpyrophosphate synthetase, an enzyme responsible seems to be related to fat distribution, and the link
for converting purine nucleotides to uric acid; en- with hyperlipidemia may be related to genetic factors
zyme deficiencies, such as glucose-6 phosphatase [12]. Uric acid is a weak acid with a pK of 5.35 in
deficiency (glycogen storage disease) and hypo- urine. In acidic urine, the undissociated form of uric
xanthine – guanine phosphoribosyltransferase defi- acid predominates and is poorly soluble, leading to
ciency (Lesch-Nyhan syndrome); and renal disease crystalluria and stone formation [1].
with failure of secretion of urate by the renal tubules
[2,16]. Uric acid salts, most notably monosodium
urate (MSU), form in the presence of elevated uric
acid levels and may be complexed with proteins in Clinical stages
body fluids. Precipitation occurs beyond their solu-
bility products or when they are perturbed. MSU Asymptomatic gout
crystals also may be found in the synovial fluid of
asymptomatic patients. Elevated uric acid levels are found in susceptible
The exact trigger that initiates an acute attack of individuals many years before the onset of symptoms.
gouty arthritis is poorly understood. The initial Hyperuricemia is believed to begin at puberty in males
events are most likely the shedding of crystals into and after menopause in females.
the synovial fluid and the adsorption of protein
molecules onto the crystalline surface. This crys-
tal – protein complex activates the complement sys- Gouty arthritis
tem, facilitating phagocytization by neutrophils [17].
Phagocytization of the crystal – protein complex This stage is the most common manifestation of
causes membranolysis, intracytoplasmic release of gout and refers to acute inflammation owing to the
lysosomal enzymes, and, ultimately, cell death, re- precipitation of urate crystals within the joint. The
leasing proteolytic enzymes into the joint [18,19]. arthritis is usually monoarticular and affects the pe-
The other effect of neutrophilic activation is the ripheral joints. The initial attacks are usually in the
elaboration and release of chemotactic factors, which lower limbs, but, as the disease becomes established,
attract other neutrophils to the site, amplifying the more joints may become involved. In the elderly and in
inflammatory process [20]. Mononuclear phagocyto- females, the disease tends to be polyarticular and may
sis, modulated by a variety of factors, may have a start at any joint. In the early stages of the disease,
key role within the synovial compartment, tipping the attacks are usually intermittent, episodic, or sporadic.
balance from the asymptomatic state to acute inflam- Later, the arthritis may become continuous with inter-J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 171
mittent flare-ups or exacerbations and may progress to joints are involved. Osteopenia, most likely from
be severe and incapacitating. disuse, may be seen in the involved joint, and well-
The first attack of gout involves the first metatar- marginated para-articular erosions with overhanging
sophalangeal joint approximately 50% of the time and edges or margins characterize this chronic phase
may last anywhere from several hours to 1 week (Fig. 1).
[2,6,24]. The pain often begins suddenly at night With chronic disease, any joint in the body may be
and can be excruciating. The involved joint rapidly involved. Joints in the central axis of the body are
becomes red, hot, and tender. The attack may be rarely affected, but there have been numerous recent
associated with systemic manifestations of fever, leu- reports of gout affecting the sacroiliac joints, facet
kocytosis, and elevation of the erythrocyte sedimen- joints, and even intervertebral disks [26 – 29]. Avascu-
tation rate. In younger persons, gouty attacks are lar necrosis has been reported in association with gout,
initially monoarticular and most frequently affect the but the association may be fortuitous and coincidental
joints of the lower limb, including the tarsal joints, the [2,30].
ankle, and the knee. The ankle and knee joints are
affected almost equally. Repeat attacks occur within Intercritical gout
shorter intervals, with the attacks lasting longer before
resolution. In the early phases, the patient may sustain The symptom-free interval between attacks in
two to three attacks a year. As the disease progresses, a patient with established gout is referred to as inter-
more than 12 attacks may occur in 1 year. With re- critical gout. During this time, the patient has hy-
peated attacks over a period of years, patients enter the peruricemia, and synovial fluid analysis may show
phase of chronic gouty arthritis in which multiple MSU crystals.
Fig. 1. Patient with chronic gouty arthritis. Radiographs of the left (A) and right (B) feet show soft tissue swelling with a cloudy haze
over the first and fifth metatarsophalangeal joints of both feet. The head of the first metatarsal of the left foot shows the typical
erosion of gout with the overhanging edge.172 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
Tophaceous gout tophi predisposes these structures to rupture. There is a
predilection for deposits to occur around the olecranon
Tophaceous gout results from established disease bursa, the cartilages of the ear, and the nose and
and refers to the stage of deposition of urate, protein menisci. Tophaceous deposits may also mimic a
matrix, inflammatory cells, and foreign body giant space-occupying lesion, resulting in carpal tunnel
cells in the tissues. The deposits may be in tendons and syndrome in the wrist, diskitis, and paraplegia in the
ligaments, cartilage, bone, and other soft tissues, spine (Fig. 2) [26,28,29].
including bursae and other synovial spaces, and are Deposits in the bone may appear as cysts [22,31]. If
para-articular in the subcutaneous tissues. The weak- there is calcium in the tophi, the lesion may appear as
ening of tendons and ligaments by the presence of a focal sclerotic lesion of bone (Fig. 3). Cysts may
Fig. 2. A 59-year-old man on hemodialysis with a long history of gout. The patient presented with generalized weakness,
paraparesis, and an inability to move the hands. Radiographs showed widespread tophaceous gout with extensive osteolytic lesions
of the limbs. CT and MR imaging examinations confirmed inflammatory spondyloarthritis with spinal stenosis at the cervical and
lumbar spine levels. (A) Radiograph of the wrist shows lumpy tissue swelling. Destructive osteolytic changes affect the bases of
the second, third, fourth, and fifth metacarpals. Observe the overhanging edge at the proximal fourth metacarpal. Cystlike changes
also are seen in other bones of the wrist. (B) Axial CT image shows widening of the medial ends of the clavicle at the
sternoclavicular joint owing to appositional bone growth. (C, D) Axial proton density – and T2-weighted fat-suppressed fast spin-
echo images of the left distal forearm show an enlarged pronator quadratus muscle (P) with abnormal signal. Abnormal signal is also
present medial to the ulna around the extensor carpi ulnaris tendon (arrow) and is compatible with the presence of gouty
tenosynovitis. (E) Sagittal three-dimensional gradient-echo image of the wrist shows erosions at the radius and lunate. The usual
signal of soft tissue is replaced by homogenous abnormal signal owing to tophaceous deposits around the visualized tendons.
(F ) Sagittal T1-weighted, contrast-enhanced, fat-suppressed image of the cervical spine shows destruction of the contiguous
aspects of the bodies of C5 – C6 and C6 – C7 by an enhancing lesion that is low signal on unenhanced T1-weighted images and high
signal on T2-weighted images. (G ) Axial CT image at the lower lumbar spine shows facet joint destruction at the level of L4/L5.
(H, I) Sagittal fat-suppressed, contrast-enhanced, T1-weighted and fast T2-weighted spin-echo images of the lumbar spine show
enhancing destructive changes at the facet joints of L4/L5 and L5/S1 from gouty involvement.J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 173
Fig. 2 (continued).174 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
Chronic urate nephropathy, also known as gouty
nephropathy, is found in patients who have long-
standing gout. The monosodium urate crystals depos-
ited in the distal renal tubules and the collecting ducts
induce tophus formation.
Imaging
Gouty arthritis
Radiographs remain the examination of choice
in the diagnosis of gouty arthritis. In the early phase
of the disease, the arthritis is monoarticular, which
subsequently progresses to a polyarthritis. A char-
acteristic of gout is the preservation of normal bone
mineral density until the late stages of the disease.
Disuse osteopenia occurs late in the disease after
Fig. 2 (continued). numerous attacks when pain limits the mobility of
the joint. Well-marginated para-articular erosion
with overhanging edges or margins is a characteristic
resolve following treatment and control of the gout and
hyperuricemia [31]. Osteolysis may occur in associa-
tion with soft tissue deposits simulating neoplasm.
Subcutaneous tophaceous nodules take years to de-
velop and may be confused with rheumatoid nodules.
The nodules may ulcerate and discharge whitish milky
material, which contains monosodium urate crystals.
Subcutaneous tophaceous deposits of monosodium
urate, in the absence of arthritis, may occasionally
occur as the initial manifestation of gout. The term
gout nodulosis has been proposed as a clinical entity
at one end of the spectrum of gout to describe the
subgroup of patients in whom tophi develop in the soft
tissues in the absence of a history of arthritis [32].
Gout myopathy
Several investigators have alluded to the effect of
gout on the muscles, observing that the muscles of
patients with long-standing gout have increased signal
intensity at MR imaging [3,33,34]. Frequently, the
patients have other coexisting conditions (see Fig. 2).
Gout uropathy
Fig. 3. An 83-year-old man with chronic renal failure
Two types of urinary syndromes, urolithiasis and
presented with a history of pain in the feet. The correct diag-
chronic urate nephropathy, are attributed to gout [3].
nosis of gout was suggested. Radiograph of the left foot
Uric acid stones account for 5% to 10% of all stones in shows osteolytic destruction of the middle phalanx fourth toe
the United States, and such stones develop in approxi- and erosions at the first metatarsophalangeal joint. Punctate
mately 22% of patients with gout [3]. Acidic urine, calcifications are present in the medial base distal phalanx
hyperuricuria, and low urine volume are the risk of the first toe, possibly owing to calcified tophus, and should
factors for uric acid stone formation. not be mistaken for enchondromas.J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 175 lesion of chronic gouty arthritis (see Fig. 1). Apposi- CT has not been used extensively in the study of tional bone deposition, thought to be responsible for gouty arthritis until recently. Gerster et al [35] have this feature, may also cause the apparent expansion of suggested that nodular lesions with Hounsfield units bone ends with a bulbous appearance (see Fig. 2). of 160 or above on CT may be diagnostic of gout. As Punctuate bone sclerosis owing to intraosseous depo- multislice scanners become more available, the in- sition of tophi (see Fig. 3) may mimic bone infarcts or creased scanning speed and multiplanar capabilities enchondromas [8]. With chronic and poorly controlled may result in increased use of the modality in the disease, extensive osteolysis and bone destruction may diagnosis and assessment of gouty arthritis. CT imag- be seen (see Figs. 2, 3). Cartilage destruction, which ing also will facilitate recognition of para-articular starts in the periphery of the joint and spreads centrally, calcifications when present. may result in articular space narrowing that simulates The MR imaging appearance of gout is variable. osteoarthritis; however, the joint destruction may An inflamed joint will show the usual appearances of be uneven, because there may be interposed areas arthritis, including joint effusion and para-articular of normal cartilage thickness. With para-articular edema (Fig. 5). In the presence of acute inflamma- deposition of tophi, there is asymmetric or ‘‘lumpy tion, the para-articular structures usually enhance bumpy’’ soft tissue swelling, which may show an following the administration of intravenous contrast. increased density that has been described as cloudlike Tophaceous deposits also show a variable appearance (see Fig. 1). These tophi may saucerize the underlying on MR imaging. The deposits may have a low to in- bone (Fig. 4) or may stimulate periostitis with faint termediate signal intensity on T1-weighted sequences periosteal new bone formation around the joints. The and a low signal intensity (if the tophi are calcified) tophi may show fluffy calcifications, especially in the or a high signal intensity on T2-weighted sequences presence of a disturbance of calcium metabolism. depending on the degree of hydration of the tophi and Fig. 4. Patient with a long-standing history of gout. Frontal (A) and lateral (B) radiographs of the index finger show circumferential soft tissue swelling and pressure erosion on the volar aspect of the middle phalanx. A differential consideration here was tendon sheath tumor, but the findings were caused by gout.
176 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
Fig. 5. A 29-year-old otherwise healthy man presented with a history of waking up one night with the spontaneous onset of
excruciating pain in the left shoulder. He had stopped taking his maintenance dose of allopurinol for about 2 months. Radiographs
(not shown) revealed unilateral erosive change at the left clavicle. MR imaging confirmed arthritis at the acromioclavicular joint.
(A) Axial fat-suppressed, fast spin-echo, proton density – weighted image shows erosion of the clavicle and abnormal signal at the
acromioclavicular joint. (B) Oblique sagittal fat-suppressed, contrast-enhanced, T1-weighted image shows enhancement of the
distal clavicle and the adjacent soft tissue. The acromion did not enhance.
crystals (see Figs. 2, 5; Fig. 6). A radionuclide bone condyles or the anterior tibial tubercle. Small bony
scan shows increased activity around any joint with cysts owing to intraosseous deposits of tophi may be
acute gouty inflammation. seen in the patella or in the condyles of the tibia and
femur [8,36 – 38]. Chondrocalcinosis may be encoun-
tered (Fig. 7). Tophi may be deposited around the
Anatomic distribution of gouty arthritis prepatellar bursa, and the bursa may be inflamed [39].
Large popliteal bursae and ruptured Baker’s cysts
Foot and ankle have been described in gout and tendon rupture
complicated by renal disease [40 – 48].
The first metatarsophalangeal joint is one of the
most commonly affected joints in gouty arthritis.
Common manifestations include erosions on the Hand and wrist
medial and dorsal aspect of the head of the first
metatarsal, although erosive changes may be seen in All of the findings described previously may be
the calcaneus and may be associated with retrocalca- observed in the hands and wrists. The anatomic sites
neal bursitis (see Fig. 6) [8]. The joints of the ankle most commonly involved in decreasing order are
may also be affected by gout, but it is rare to have the distal interphalangeal joints, the interphalangeal
isolated ankle joint involvement. joints, and the metacarpophalangeal joints [8,23,49].
The changes are frequently asymmetric, and ero-
Knees sions of varying sizes may occur in any joint of
the hand and wrist. Fragmentation and bony pro-
Manifestations of gout in the knee include ero- liferative changes may be seen in the wrist and
sions of the medial or lateral tibial and femoral ulnar styloid.
Fig. 6. A patient with long-standing gout presented with ankle swelling. (A) Lateral radiograph of the ankle shows focal thickening
of the Achilles tendon and small erosions on the posterior surface to the calcaneus. (B) Axial T1-weighted MR image shows
markedly thickened Achilles tendon infiltrated by a gouty tophus (intermediate signal on the T1-weighted images). (C) T2-
weighted MR image shows the infiltrating tophaceous material in the markedly thickened Achilles tendon as mixed intermediate
and high signal.J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 177
178 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
Fig. 7. A patient with established gouty arthritis presented with knee pain. (A) Frontal radiograph of the medial half of the knee
shows faint increased density in the lateral meniscus owing to calcification of the fibrocartilage in gout (chondrocalcinosis).
(B) Frontal radiograph of the great toe shows the characteristic erosion of gout at the medial aspect of the head of the great toe.
There is a normal articular space and preservation of normal bone density. In the head of the second metatarsal, there are mul-
tiple calcifications, a feature of intraosseous gout (arrow).
Elbow patients with gout [51], some of these changes
attributed to gout may be caused by osteoarthritis in
Soft tissue swelling around the elbow in patients elderly patients [8].
with gout may be caused by olecranon bursitis or
tophaceous deposits (Fig. 8). Small ossific fragments, Other joints
seen around the epicondyles and the olecranon pro-
cess, may be related to enthesopathic or bony pro- Although gout can affect any joint in the body,
liferative changes. involvement of the hip, shoulder, sternoclavicular
joint, and temporomandibular joints is infrequent.
Sacroiliac joint When gouty arthritis affects these joints, the changes
are similar to those described in other joints (see Fig. 5)
Estimates of the incidence of sacroiliac gouty [8,30,52 – 54].
arthritis range from 7% to 13% to 17% [50,51]. Sacro-
iliac involvement, usually asymmetric and more fre- Spine
quently seen in early onset disease, is manifested by
bony sclerosis, erosions, and subchondral cyst for- There has been an increase in reports of gout
mation [9,50]. Although MSU crystals and tophi affecting the spine. Erosive changes of the odontoid,
have been recovered in the sacroiliac joints of some vertebral bodies, and end plates have been reportedJ.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 179
depicted with ease. Deposits of tophi within the
corpora cavernosa predispose to the development of
chordee and erectile dysfunction.
Differential diagnosis
Septic arthritis
Acute gouty arthritis is frequently misdiagnosed
as a joint infection (Fig. 9). An accurate history can
help establish a firm diagnosis. Acute gouty arthritis
presents with pain of sudden onset, and a history of
recurrent or repeated attacks should indicate the
nature of the disease. Synovial fluid analysis is
Fig. 8. A patient with a known history of gout experienced
swelling and pain over the elbow. Radiograph shows soft
important in these patients. Microscopic analysis
tissue fullness over the olecranon with an olecranon spur. using compensated polarized light and a culture of
Gouty bursitis was diagnosed. synovial fluid helps distinguish gouty arthritis from
other arthropathies. The presence of monosodium
urate crystals firmly establishes the diagnosis of gout;
(see Fig. 2). Similar destructive changes may be however, the diagnosis of gout does not exclude the
noted at the facet joints [8,38,55,56]. possibility of concurrent arthritic conditions [57,58].
Rheumatoid arthritis
Other clinical variations and manifestations of
gout Occasionally, patients with atypical presentations
of gout or chronic gout may be confused with those
Early onset gouty arthritis having rheumatoid arthritis (Fig. 10) [59]. In patients
who have gout, the rheumatoid factor will be negative
The changes of early onset gouty arthritis are or only weakly positive, and the arthritis will often be
similar to those in the mature or adult variety. asymmetric. In cases of unusual presentations, gout
Increased involvement of the hip joint, the sacroiliac or gouty arthritis may be misdiagnosed as rheumatoid
joint, and the spine is reported in this group of arthritis, septic arthritis, or other rheumatic condi-
patients [8,9]. tions, leading to inappropriate treatment [58,60].
Gout nephropathy Osteoarthritis
Gouty tophi associated with round cell and giant When the destructive changes in gout are predomi-
cell infiltration may be seen on microscopy in the nantly articular, the presence of osteophytes and the
renal pyramids and interstitium. Their presence pre- relative preservation of bone mineralization may
disposes to proteinuria and isosthenuria, the inability mimic osteoarthritis. The soft tissue nodules seen in
to concentrate urine. osteoarthritis also may be confused for tophi. Gener-
Urolithiasis owing to uric acid deposition occurs ally, the articular space is preserved in gout until the
in 20% of patients, and sodium urate stones also late stages of the disease. The presence of erosions,
occur. The presence of uric acid acts as a nidus for not a feature of osteoarthritis, may aid in confirming
the crystallization and formation of calcium oxalate the diagnosis of gout.
stones, and the presence of stones predisposes to
pyelonephritis. The presence of a stone will result Erosive osteoarthritis
in findings typically associated with obstructive urop-
athy. The presence of urographic contrast will mask Erosive osteoarthritis, also known as inflamma-
the presence of urate stones, which, in the absence tory arthritis, may occasionally be confused with
of calcium, are not radiodense. CT imaging is particu- gouty arthritis. A disease primarily of middle-aged
larly well suited for evaluating gouty obstructive females, erosive osteoarthritis most commonly affects
uropathy, because the obstructing stone can be the joints of the hand and wrists, especially the first180 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
Fig. 9. A patient presented to the emergency department with red swollen painful digits of several days’ duration. Frontal
radiographs of both hands (A, B) show soft tissue swelling with underlying bone destruction of the contiguous aspects of the
middle and distal phalanges, mimicking septic arthritis and osteomyelitis. A joint aspirate showed MSU crystals.
carpometacarpal and trapezioscaphoid joints. The cium pyrophosphate dihydrate crystal deposition dis-
erosions frequently start centrally (as opposed to the ease (CPPD), also referred to as ‘‘pseudogout,’’ is a
peripheral origins of gouty erosions) and are associ- common finding in the elderly and a frequent cause of
ated with rapid joint narrowing and destruction. arthritis in this age group. In CPPD, cartilage calcifi-
cation (chondrocalcinosis) is frequently polyarticular
Psoriasis and affects hyaline and fibrocartilage, whereas in
gouty arthritis, only the fibrocartilage in one or two
A syndrome of gout, sarcoidosis, and psoriasis has joints may be affected [6,8]. Furthermore, in gouty
been described but is more likely a fortuitous associa- arthritis, the calcification in chondrocalcinosis is less
tion [2]. The presence of periosteal reaction, eccen- dense and is poorly visualized (see Fig. 7) [6].
tric articular erosion, and juxta-articular soft tissue Lobulated soft tissue swelling and preservation of
swelling with relatively normal bone density are the articular space with bony erosions will aid in
features seen in psoriasis and gout. The rapid cellular making a correct diagnosis of gout in most cases.
turnover from the skin lesions in psoriasis predisposes
to hyperuricemia, and the presence of hyperuricemia Xanthomatosis
in psoriatic patients further confuses the diagnosis.
Xanthomatosis is characterized by soft tissue nod-
Calcium pyrophosphate dihydrate crystal deposition ules that are usually located on the extensor surfaces
disease of the limbs. The eccentric subcutaneous nodules may
be associated with subjacent bone erosions and may
Crystal deposition within the joints from whatever be confused with gout. Usually, the clinical presenta-
cause may produce symptoms similar to gout. Cal- tion, the presence of hypercholesterolemia, and theJ.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 181
malin. If gout is included in the differential diagnosis,
tissue biopsy specimens should not be stored in
formalin, because this method may confound accu-
rate diagnosis [38].
Treatment
Treatment has several objectives: to relieve the pain
of the acute attack, restore normal function, and to
prevent the accumulation of crystals that can lead to
degenerative disease [55]. Patients with asymptomatic
hyperuricemia do not require treatment, but efforts
should be made to lower their urate levels by encour-
aging them to make changes in their diet and lifestyle.
Acute attacks of gout are treated with colchicine
or nonsteroidal anti-inflammatory drugs (NSAIDs).
In patients without complications, NSAID therapy is
preferred [1]. Low-dose therapy with these agents can
also prevent recurrent attacks [13,56,62,63]. Most
patients who have gout need long-term treatment
with uricosuric agents or xanthine oxidase inhibitors
[14,31]. Colchicine is associated with frequent ad-
verse reactions and reduced efficacy when adminis-
Fig. 10. A patient was treated for several years for rheumatoid tered more than 24 hours after the onset of an acute
arthritis and then treated for arthritis mutilans before a cor- attack; hence, the use of colchicine in the treatment of
rect diagnosis of gout was made. Radiograph of the right
acute attacks is controversial and declining. Cortico-
hand shows diffuse osteopenia, soft tissue swelling over
several joints, multiple osteolytic foci, and carpal collapse.
steroids are increasingly accepted in the treatment of
acute and intercritical gout. Urate-lowering drugs
seem to be cost effective in patients who have more
than one or two attacks per year [12,56]. NSAIDs are
the drugs of choice for the management of acute
gouty arthritis. Intra-articular corticosteroid therapy
absence of MSU crystals in joint or tissue aspirates (eg, methylprednisolone acetate) may be used in
will differentiate this condition from gout. acute monoarticular or oligoarticular gouty arthritis
in aged patients and in those with comorbid condi-
tions contraindicating therapy with either NSAIDs or
Amyloidosis colchicine [64].
For the treatment of hyperuricemia and chronic
Amyloid deposits may present as soft tissue gouty arthritis, allopurinol is the preferred urate-
swelling and erosions or cystic lesions in the bone. lowering drug. Adjusting the initial dose according
Amyloidosis may be confused with chronic topha- to the patient’s creatinine clearance can minimize its
ceous gout or vice versa. Periarticular osteopenia is a toxicity in elderly individuals, in patients with renal
frequent feature of amyloidosis. Moreover, amyloido- impairment, and in cyclosporine-treated transplant
sis tends to be bilaterally symmetric. Frequently, it is patients. In patients who react to allopurinol, cautious
difficult to differentiate the two conditions radio- desensitization to the drug using gradually increasing
graphically. Ultimately, a correct diagnosis is made doses is advised [64]. Patients who have massive
through laboratory work-up. tophi may require combined therapy with allopurinol
Gout may occur together with any of the other and a uricosuric agent [64,65]. The treatment of gout
diseases discussed previously. The definitive diagno- and hyperuricemia may lead to significant complica-
sis of gout is made by joint aspiration with demon- tions [34].
stration of birefringent crystals in the synovial fluid Recombinant urate oxidase can be used in the
and within neutrophils under a polarized light micro- short-term prophylaxis and treatment of chemo-
scope [1,2,55,61]. Urate crystals are soluble in for- therapy-associated hyperuricemia in patients who182 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
have lymphoproliferative and myeloproliferative dis- [3] Rosenberg AE. Crystal arthropathies. In: Coltran RS,
orders. Hyperuricemia and gout occur with increased Kumar V, Robbins SL, Schoen FJ, editors. Robbins
frequency in cyclosporine-treated allograft transplant pathologic basis of disease. 5th edition. Philadelphia:
W.B. Saunders; 1994. p. 1255 – 8.
recipients. The management of gout in these patients
[4] Fam AG. Gout in the elderly: clinical presentation and
is complicated by two factors: cyclosporine-induced
treatment. Drugs Aging 1998;13(3):229 – 43.
renal impairment and interactions with the medica- [5] Agudelo CA, Wise CM. Gout: diagnosis, pathogene-
tions used to preserve the allograft [66]. Surgical sis, and clinical manifestations. Curr Opin Rheumatol
evacuation of large unsightly tophaceous deposits 2001;13(3):234 – 9.
may be performed. Occasionally, amputation of a [6] Zayas VM, Calimano MT, Acosta AR, Pierre-Jerome
destroyed digit or chronically affected limb may C, Monu JUV. Gout: the radiology and the clinical
be necessary. manifestations. Appl Radiol 2001;30(11):15 – 24.
[7] Agudelo CA, Wise CM. Crystal-associated arthritis.
Clin Geriatr Med 1998;14(3):495 – 513.
[8] Resnick D, Niwayama G. Gouty arthritis. In: Resnick
Prevention D, Niwayama G, editors. Diagnosis of bone and joint
disorders. 2nd edition. Philadelphia: W.B. Saunders;
The factors contributing to hyperuricemia in most 1988. p. 1618 – 71.
[9] Resnick D, Reinke RT, Taketa RM. Early-onset gouty
patients with gout, such as obesity, a high-purine diet,
arthritis. Radiology 1975;114:67 – 73.
regular alcohol consumption, and diuretic therapy, [10] Treadwell BLJ. Juvenile gout. Ann Rheum Dis 1971;
may be correctable. In patients who have persistent 30:279.
hyperuricemia, regular medication should lower the [11] Wright IT. Unusual manifestations of gout. Australas
serum urate concentration to an optimal level [24]. Radiol 1966;70:365.
Alkalinization of the urine, high fluid intake, and [12] Wise CM, Agudelo CA. Gouty arthritis and uric acid
efforts directed at the reduction of uric acid formation metabolism. Curr Opin Rheumatol 1996;8(3):248 – 54.
will help prevent the disease [67]. [13] Chopra KF, Schneiderman P, Grossman ME. Finger
pad tophi [review]. Cutis 1999;64(4):233 – 6.
[14] Davis Jr JC. A practical approach to gout: current
management of an ‘old’ disease. Postgrad Med 1999;
Summary 106(4):115 – 23.
[15] Fam AG. What is new about crystals other than
monosodium urate? Curr Opin Rheumatol 2000;
Gout is a group of diseases characterized by
12(3):228 – 34.
arthritis and results from a disturbance of urate [16] Pascual E. Gout update: from lab to the clinic and
metabolism with the deposition of monosodium urate back. Curr Opin Rheumatol 2000;12(3):213 – 8.
crystals in the joints and soft tissues. Often, but not [17] Kozin F, McCarty DJ. Protein adsorption to mono-
invariably, the serum urate levels are elevated as sodium urate, pyrophosphate dihydrate and silica crys-
a result of overproduction or underexcretion of tals. Arthritis Rheum 1976;19(Suppl):433 – 8.
uric acid. Clinical manifestations include acute and [18] Cheung HS, Halverson PB, McCarty DJ. Release of
chronic arthritis, tophaceous deposits, interstitial re- collagenase, neutral protease and prostaglandins from
nal disease, and uric acid nephrolithiasis. The diag- cultured mammalian synovial cells by hydroxy apatite
and calcium pyrophosphate dihydrate crystals. Arthritis
nosis is based on the identification of uric acid
Rheum 1981;24(11):1338 – 44.
crystals in joints, tissues, or body fluids. Acute
[19] Hoffstein S, Weissman G. Mechanisms of lysozomal
episodes are treated with colchicine, NSAIDs, or enzyme release from leukocytes. IV. Interaction of
steroids. Long-term management includes treatment monosodium urate crystals with dogfish and human
with uricosuric agents or xanthine oxidase inhibitors. leukocytes. Arthritis Rheum 1975;18:153 – 65.
[20] Phelps P, Andrews R, Rosenbloom J. Demonstration
of chemotactic factor in human gout: further charac-
terization of occurrence and structure. J Rheumatol
References 1981;8(6):889 – 94.
[21] Landis RC, Haskard DO. Pathogenesis of crystal-in-
[1] Harris MD, Siegel LB, Alloway JA. Gout and hy- duced inflammation. Curr Rheumatol Rep 2001;3(1):
peruricemia. Am Fam Physician 1999;59(4):925 – 34. 36 – 41.
[2] Wyngaarden JB. Gout. In: Wyngaarden JB, Smith [22] Uri DS, Dalinka MK. Imaging of arthropathies: crystal
LH, Bennett JC, editors. Cecil textbook of medicine. disease. Radiol Clin North Am 1996;34(2):359 – 74.
19th edition. Philadelphia: W.B. Saunders; 1992. [23] Weissman G, Rita GA. Molecular basis of gouty
p. 1107 – 15. inflammation: interaction of monosodium urateJ.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184 183
crystal with lysozymes and liposomes. Nature 1972; [43] Lipson RL, Williams LE. The connective tissue disorder
240(101):167 – 72. of hyperparathyroidism. Arthritis Rheum 1968;11:198.
[24] Emmerson BT. The management of gout. N Engl J [44] Peavy PW, Franco DJ. Gout: presentation as a popliteal
Med 1996;334(7):445 – 51. cyst. Radiology 1974;111:103.
[25] Perazella MA. Lead and the kidney: nephropathy, hy- [45] Preston FS, Adicoff A. Hyperparathyroidism with
pertension, and gout. Conn Med 1996;60(9):521 – 6. avulsion of three major tendons. N Engl J Med 1962;
[26] Barrett K, Miller ML, Wilson JT. Tophaceous gout 266:968.
of the spine mimicking epidural infection: case report [46] Solomon L, Berman L. Synovial rupture of the knee
and review of the literature. Neurosurgery 2001;48(5): joint. J Bone Joint Surg Br 1972;54:460 – 7.
1170 – 3. [47] Stojanovic I, Tomic S. Rupture of the popliteal cyst in
[27] Bastani B, Vemuri R, Gennis M. Acute gouty sacro- gout. Scand J Rheumatol 1983;12:15 – 6.
iliitis: a case report and review of the literature. Mt [48] Trentham DE, Masi AT. Chronic synovitis in gout
Sinai J Med 1997;64(6):383 – 5. simulating rheumatoid arthritis: demonstration of bi-
[28] King JC, Nicholas C. Gouty arthropathy of the lumbar lateral popliteal cysts and wrist synovial corrugation.
spine: a case report and review of the literature. Spine JAMA 1976;235(13):1358 – 60.
1997;22(19):2309 – 12. [49] Gelberman RH, Doty DH, Hamer ML. Tophaceous
[29] Thornton FJ, Torreggiani WC, Brennan P. Tophaceous gout involving the proximal interphalangeal joint. Clin
gout of the lumbar spine in a renal transplant patient: Orthop 1980;147:225.
a case report and literature review. Eur J Radiol 2000; [50] Alarcon-Segovia D, Cetina JA, Diaz-Jouanen E. Sacro-
36(3):123 – 5. iliac joints in primary gout: clinical and roentgeno-
[30] Shin AY, Weinstein LP, Bishop AT. Kienbock’s disease graphic study of 143 patients. AJR Am J Roentgenol
and gout. J Hand Surg [Br] 1999;24(3):363 – 5. 1973;118:438.
[31] Raikin S, Cohn BT. Intraosseous gouty invasion of [51] Malawista SE, Seegmiller JE, Hathaway BE, Sokoloff
the talus. Foot Ankle Int 1997;18(7):439 – 42. L. Sacroiliac gout. JAMA 1965;194:954.
[32] Iglesias A, Londono JC, Saaibi DL, Pena M, Lizarazo [52] Fluur E, Haverling M, Malin C. Gout in the tempo-
H, Gonzalez EB. Gout nodulosis: widespread subcu- romandibular joint: report on a case. ORL J Otorhino-
taneous deposits without gout. Arthritis Care Res laryngol Relat Spec 1974;36:16.
1996;9(1):74 – 7. [53] Kleinman HZ, Ewbank RL. Gout of the temporoman-
[33] Pierre-Jerome C, Campbell SC, Borthne A, Reiseter T, dibular joint. Oral Surg 1969;27:281.
Seo GS, Monu JUV. Magnetic resonance imaging of [54] Sant GR, Dias E. Primary gout affecting the sternocla-
non-neoplastic tumors of muscles: a comprehensive vicular joint. BMJ 1976;1:262.
review. Clinical MRI 2002;12(1):3 – 16. [55] Swan A, Amer H, Dieppe P. The value of synovial
[34] Simkin PA. Gout and hyperuricemia. Curr Opin Rheu- fluid assays in the diagnosis of joint disease: a litera-
matol 1997;9(3):268 – 73. ture survey. Ann Rheum Dis 2002;61(6):493 – 8.
[35] Gerster JC, Landry M, Dufresne L, Meuwly JY. Imag- [56] Taylor CT, Brooks NC, Kelley KW. Corticotropin for
ing of tophaceous gout: computed tomography pro- acute management of gout. Ann Pharmacother 2001;
vides specific images compared with magnetic 35(3):365 – 8.
resonance imaging and ultrasonography. Ann Rheum [57] Butt TS, Khan A, Ahmad A, Khan MA, Parke A, Hill
Dis 2002;61(1):52 – 4. DR. Pasteurella multocida infectious arthritis with
[36] Foucar E, Buckwalter J, El-Khoury GY. Gout present- acute gout after a cat bite. J Rheumatol 1997;24(8):
ing as a femoral cyst. J Bone Joint Surg Am 1984;66: 1649 – 52.
294 – 7. [58] Uy JP, Nuwayhid N, Saadeh C. Unusual presentations
[37] Peloquin LU, Graham JH. Gout in the patella. N Engl of gout: tips for accurate diagnosis. Postgrad Med
J Med 1955;253:979 – 80. 1996;100(1):253 – 68.
[38] Talbott JH, Culver GJ, Mizraji M, Crespo DL. Roent- [59] Yunis N, Platnner PF, Masi AT, Shah IK, Lindahl LS,
genographic findings: description of a magnification Conner DE. Ulnar deviation of the fingers in gout simu-
technique. Symposium on gout. Metabolism 1957;6: lating rheumatoid arthritis. J Rheumatol 1982;9:619.
277 – 96. [60] Coltran RS, Kumar V, Robbin SL. Tubulointerstitial
[39] Abeles M. Sartorial ridge gout. Clin Orthop 1984;184: diseases caused by metabolic disturbances— urate
178 – 9. nephropathy. In: Robbins pathologic basis of dis-
[40] Costello PB, Kennedy AC, Green FA. Dissected pop- ease. 4th edition. Philadelphia: W.B. Saunders; 1989.
liteal cyst: an unusual presentation of acute gout. Am p. 1059 – 60.
J Med Sci 1980;279:57 – 9. [61] Schumacher HR. Crystal-induced arthritis: an over-
[41] Levitin PM, Keats TE. Dissecting synovial cyst of the view. Am J Med 1996;100(2A):46S – 52S.
popliteal space in gout. AJR Am J Roentgenol 1975; [62] Lange U, Schumann C, Schmidt KL. Current aspects
124:32 – 3. of colchicine therapy—classical indications and new
[42] Levy M, Seelenfreund M, Maor P, Fried A, Lurie M. therapeutic uses. Eur J Med Res 2001;6(4):150 – 60.
Bilateral and simultaneous rupture of the quadriceps [63] Molad Y. Update on colchicine and its mechanism of
tendons in gout. J Bone Joint Surg Br 1971;53:510. action. Curr Rheumatol Rep 2002;4(3):252 – 6.184 J.U.V. Monu, T.L. Pope, Jr / Radiol Clin N Am 42 (2004) 169–184
[64] Fam AG. Managing problem gout. Ann Acad Med [66] Fam AG. Difficult gout and new approaches for con-
Singapore 1998;27(1):93 – 9. trol of hyperuricemia in the allopurinol-allergic pa-
[65] van Doornum S, Ryan PF. Clinical manifestations of tient. Curr Rheumatol Rep 2001;3(1):29 – 35.
gout and their management. Med J Aust 2000;172(10): [67] Asplin JR. Uric acid stones. Semin Nephrol 1996;
493 – 7. 16(5):412 – 24.You can also read
