Noninvasive imaging techniques are useful in
assessing the degree of damage rheumatoid arthritis has inflicted
on the bone, cartilage, supporting structures, and soft tissue. Imaging
tests vary in sensitivity and include plain film x-ray, magnetic resonance
imaging, bone scintigraphy, ultrasound, and bone densitometry. The
widespread use of these tools has been limited by cost, availability,
and utility. However, their use can be invaluable throughout disease
duration as they aid in the diagnosis, prognosis, evaluation of therapy,
and monitoring of disease progression.
X-ray Imaging
One of the 7 diagnostic criterion of RA, established
by the American College of Rheumatology (ACR) in 1987 (
Fig.2687) is the presence of bone erosion on radiograph. Prevention of bone
erosion is one of the main aims of treatment of the disease by rheumatologists
because bone erosion is generally irreversible in most patients. Waiting
until all of the ACR criteria for RA are met, especially the criteria
of radiological changes suggestive of joint erosion, is therefore
likely to result in a worse outcome for the patient. The radiological
manifestations of RA are an extension of the underlying pathological
processes. Radiographic Assessment of Rheumatoid Arthritis They include soft-tissue swelling, juxta-articular
(periarticular) osteoporosis ( Soft Tissue Swelling and Juxta-Articular Osteoporosis), erosions ( Erosions), and joint space narrowing ( Joint Space Narrowing). However, the true utility of radiographs is that they aid
in the diagnosis of RA, they can allow assessment of joint injury,
and may offer some predictive value early in the disease.10263,10718
Soft Tissue Swelling and Juxta-Articular Osteoporosis
Soft tissue abnormalities including periarticular
swelling and loss of definition of tissue planes are seen early (and
persist) in RA. These abnormalities are associated with inflammation.
These findings can be seen on standard radiographs. Joint effusions
may be evident as well, although they are typically indirectly detected
(through soft tissue abnormalities) in larger joints, such as the
knee. Juxta-articular osteoporosis is an early
radiographic finding in RA.6614 This
regional osteoporosis can be frequently observed in the long bones
of the hands and feet and is thought to be a result of the cytokine
release ( Cytokine Dysregulation) during the inflammation. Contributing factors
include local release of inflammatory mediators, local release of
proteolytic enzymes, and increased regional blood flow.6614,10719 Subcortical
cysts can develop in the subcortical bone and can contain fluid, synovium,
or both. There are a number of possible mechanisms for the development
of these cysts. These cysts tend to be inflammatory (e.g., invasion
of this region by pannus), but they may occasionally be noninflammatory
(osteoarthritic or simple bone cysts) as well.
Erosions
Radiographic erosion is one of the key features
used in the classification criteria for diagnosing RA. In the synovial
joint, most of the joint space is covered with articular cartilage.
At the site of the joint capsule attachment to bone, there is no cartilage
covering the bone. At this site inflammatory synovium (pannus) is
in direct contact with bone (
Fig.2912). Erosive changes typically begin, and are found, in the joint margins
at the site of this direct contact. Areas such as the metatarsal heads,
carpal bones, and the ulnar styloid may manifest erosions earlier
than other joints. Regions of focal bone resorption may also be detected
adjacent to the bone marrow space, into which the synovial inflammatory
tissues extend.
Fig.2667.10395 Compressive
erosions, described as osteoporotic bone with continual invagination
of one bone into another, and surface resorption, may also occur.
During advanced stages of the disease, large central erosions of the
joint may resemble cysts or pseudocysts, usually located about the
metacarpophalangeal and proximal interphalangeal joints. Radiographic
erosion is associated with a poor outcome in RA.10528,10706 These
focal bone changes tend to progress throughout the course of the disease
and their presence tends to correlate with more severe disease activity.10312Evaluating the Development of Erosions
Figure 2667 – Erosion of Bone in RA in One Patient
van der Heijde DM. Joint erosions and patients with
early rheumatoid arthritis. British Journal of Rheumatology 1995;34(Suppl 2), page 74-78 by permission of Oxford University
Press.
Some figures may not display clearly when rendered as a PDF or printed.
The reader is encouraged to visit www.medversation.com to view full-size versions.
Joint Space Narrowing
Joint space narrowing is a radiographic finding
that results from the gradual destruction of joint cartilage. In RA,
joint-space narrowing tends to be diffuse, as opposed to being the
focal presentation observed in osteoarthritis. As cartilage injury
progresses, the joint space may become partially or completely destroyed
by fibrous ankylosis.6815 The small joints of the hands and feet commonly display both
erosion and joint space narrowing, whereas the structures of the hip
and knee exhibit predominantly narrowing of the joint space. Ankylosis
of the bone is relatively rare in RA, but can occur when cartilage
degradation is severe and joint surfaces are juxtaposed, permitting
fusion of the joint. Joint space narrowing is clearly evident in the
joint in the figure.
Fig.2667.
Joints to Best Assess Radiographic Injury
The structural damage of RA, as observed in radiographs,
first presents in the hands, wrists, and feet.11113 The
earliest structural changes often occur in the fourth and fifth metatarsal
joints of the feet. In the hand, the changes are primarily seen in
the metacarpophalangeal (
Fig.2688) and proximal interphalangeal joints, while wrist injury typically
occurs in the intercarpal, radial, and ulnar styloid joints. As a
result of mechanical stress and inflammation, structural damage may
be increased in the dominant hand and in joints utilized more frequently.
Radiographic progression in larger joints, such as the knees and hips,
generally appears later in the course of the disease.11113
Radiographic Assessment of Rheumatoid Arthritis
Numerous studies have demonstrated that substantial
irreversible joint damage and erosions occur within the first 2-3
years after diagnosis of RA.11005X-ray Imaging In many patients, the disease process is severe, and results
in progressive joint destruction and severe disability (See Rheumatoid Arthritis-Related Disability and Other Concerns). Conversely, an important proportion of patients never develop
erosions or experience a benign course of disease with mild articular
damage and low disability.11005 In established RA, the correlation between functional disability
and radiographic damage has been well established. Since structural
damage appears to be largely irreversible (except in some animal models
of RA), early recognition and treatment are critical, with inhibition
of disease progression being one of the most important goals of treatment.10705
Data Limitations
Several problems arise when comparing the results
of radiographic studies of RA. Numerous types of studies have been
utilized, including cross-sectional evaluations and prospective follow-up studies of patients with early disease or varying
disease durations. Moreover, differing scoring methods, such as Steinbrocker,
Lawrence, Kellgren, Larsen, and Sharp, and modifications of Sharp’s
method, have been employed across studies. Finally, data presentation
and end points evaluated differ from observation to observation.7043 These issues make drawing firm conclusions regarding the
course of disease difficult.
Evaluating the Development of Erosions
The development of juxta-articular erosions is
an important indicator of progressive damage in RA. The likelihood
of patients with early RA developing erosions has been reported in
several prospective studies.10289,10311,10475,10539,10903,11113
These studies enrolled between 58 and 147 patients who were seen within
1 year of the onset of their RA. Prospective follow-up ranged from
1 to 5 years, with radiographs of the hands and feet taken in all
studies.
Within 2 years of disease onset, approximately
70% of all patients developed erosive disease.11113 See
Fig.1729, adapted from van Der Heijde.7043 By the conclusion of each study’s follow-up period,
60% - 93% of patients had radiographic evidence of erosions. Van der
Heijde, et al., evaluating 147 patients with less than 1-year symptom
duration at study onset, observed that 18% - 20% of all joints of
the hands and feet were affected after 3 years. During the first year
of follow-up, 4.7 out of 50 joints (9.4%) became newly damaged; values
for the second and third years were 2.2 joints (4.4%) and 1.7 joints
(3.4%), respectively.10475 Mottonen,
et al., found similar results; 2 of 36 joints (5.5%) became eroded
per year.10289 Plant,
et al, evaluating 114 patients with less than 3 years’ symptom
duration at study onset, observed that 38% of all joints evaluated
were eroded at 2 years, and 63% at 8 years. In addition, erosive damage
occurred most rapidly in the feet during the first 2 years of disease
onset.10856
Molenaar, et al., studied 187 patients in persistent
remission who had been treated with traditional disease-modifying
antirheumatic drugs. These researchers observed that new erosions
developed in previously unaffected joints in 15% of patients, judged
to be in persistent clinical remission of their RA using a modification
of the American College of Rheumatology criteria (fatigue was omitted).
The authors suggested that the absence of ongoing structural joint
damage be added to the criteria to define clinical remission.10858
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Many patients have erosions when they first present
with RA. One study of 130 patients with early RA (duration of symptoms
of less than 2 years) reported that after 12 months follow-up, 86%
of patients had evidence of erosions.4580 Patients experiencing longer duration of complaints at first
presentation (34 to 104 weeks) had significantly greater progression
of disease, compared with patients with shorter duration of symptoms
(0 to 13 weeks); see
Fig.1730. Machold, et al., described 47 patients with very early arthritis
seen within 3 months of symptom onset. At their first assessment,
13% of patients had detectable erosions; after 12 months, the proportion
rose to 28%.10364
Jansen LM, van der Horst-Bruinsma IE, van Schaardenburg
D, et al. Predictors of radiographic joint damage in patients with
early rheumatoid arthritis. Ann Rheum Dis 2001;60:(10):924-927,
Reproduced with permission from the BMJ Publishing Group. http://group.bmj.com/products/journals
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In contrast, Bukhari, et al., in an evaluation
of 416 inflammatory polyarthritis patients in a community-based setting,
observed minimal radiographic progression during the first 2 years
of disease.10382 Wolfe
and Sharp reported early and linear progression (
Fig.2803) of radiographic damage in a cohort of patients who were initially
seen an average of 9 months from the first onset of their signs and
symptoms of RA and were subsequently followed for 19 years.10167
Figure 2803 – Linear Radiographic Progression in a Cohort of RA patients Over a Period of 19 Years
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Patterns of Disease Progression
Studies evaluating patterns of radiological progression
have found varied results.10219 Wolfe
and Sharp evaluated the results of a prospective longitudinal study
on radiographic progression, as well as clinical predictors of RA.
The cohort consisted of 256 RA patients who were seen within 2 years
of onset, with a mean of 0.8 years disease duration.10167 The
presence of erosions during the early stages of disease was also noted,
in addition to observing that RA in this cohort progressed at a constant
linear rate.
An evaluation of 502 RA patients over 6 years,
conducted by Hulsmans, et al., also found a linear rate of progression.10084 Moreover,
after 6 years, 95% of patients developed more than 1 erosive joint.
Plant, et al., outlined 4 patterns of damage in patients with early
RA. These patterns comprised a flat course (25%), linear progression
(46%), initial lag with later acceleration (12%), or fast onset with
a later deceleration (17%).10856
Structural Damage and Disability
The association of radiographic joint damage
with physical function may vary with disease phase. In the early stages
of RA, the link between joint damage and physical function has not
been consistently established. While 2 prospective longitudinal studies
in patients seen initially within 1 - 3 years of diagnosis found low,
yet significant correlations between function and radiographic damage, 4750,10331 several
other observations have not replicated similar results.10473,10865,10903 See the figure adapted from Scott, Smith, and Kingsley.10219 Eberhardt, et al., conducted a prospective longitudinal study
of RA patients with disease duration of 1 year at inclusion. Nonsignificant
correlations between function and radiographic damage were observed
not only at both study initiation, but also after 5 years of study
follow-up.10903 In contrast, in a 10-year longitudinal
observational study of 238 patients utilizing generalized estimating
equations, Ødegård, et al., found that radiographic damage
and disease activity are independent contributors to impaired function
in early and late RA.4608
In established disease, however, joint damage
( Erosions, Joint Space Narrowing ) has been shown to be a major determinant
of functional disability. Clarke, et al., reported that the correlation
between radiographic scores and health assessment questionnaire (HAQ)
scores tends to increase with disease duration, from 0.15 after 0-5
years of disease onset to 0.42 after 10-15 years.10366 Welsing,
et al, found no significant correlation between the HAQ score and
radiographic damage scores during the early stages of disease, but
after 6 years, the correlation coefficient had increased to 0.75,
and remained positive at 9 years.10473 Similarly,
Drossaers-Bakker, et al, found in a cohort of 132 females with early
RA, that the initial correlation coefficient between the Sharp and
functional scores was 0.29, but the coefficient eventually reached
statistical significance by 12-year follow-up.10219
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) ( Imaging in Rheumatoid Arthritis) allows assessment of the integrity of bone, cartilage, tendons,
and ligaments. In rheumatoid arthritis (RA), MRI may have its greatest
utility in the detection of pathological lesions and inflammatory
changes, such as bone erosions ( Erosions), subchondral cysts, joint effusion, bone marrow edema (
Fig.2987), and joint space narrowing ( Joint Space Narrowing).10901 MRI
offers greater sensitivity for detection of early manifestations of
RA compared with conventional radiograph.10577 The
presence of these inflammatory changes may be detected with MRI when
radiographic findings (Please see X-ray Imaging) are negative.10407,10463 In
addition, MRI can reveal bone marrow edema. There have been relatively
few studies correlating the pathological lesion in RA with MRI erosions.
Ostendorf, et al., reported erosions identified via direct observation
correlated with MRI abnormalities.10108 Bone
marrow edema detected on MRI was a strong predictor of erosions in
the wrist.10235,10682 Tenosynovitis,
as well as abnormalities of the tendons, ligaments, and cartilage,
can be observed utilizing MRI technology.10212,10839 MRI
can be utilized to image the musculoskeletal complications of RA,
such as tendon rupture,10839 ischemic necrosis, and fractures. MRI is a critical tool
in the assessment of osteonecrosis. Importantly, MRI also holds the
potential to monitor the individual’s response to therapy longitudinally.10884,11112
MRI is critical in the assessment of cervical
spine involvement in RA. MRI can accurately reveal the integrity of
C1 and C2, assess the
degree atlantoaxial subluxation, determine the degree of spinal cord
impingement, and quantitate the pannus present.10498,10827 In
addition, MRI is also the imaging modality of choice when evaluating
temporomandibular joint involvement in RA.11020
Currently, the use of MRI is limited to availability,
cost, long scan times, and a lack of validated uniform scoring system.
There have been a number of smaller machines developed that have not
compromised resolution. These machines can potentially be used in
the office or outpatient setting. There is still a substantial cost
in purchasing these machines that may yet limit their use. In addition,
there is a lack of consensus developed for a unified scoring system
for MRI of the small joints.10469 There
is a proposed Outcome Measures in Rheumatology Clinical Trials (OMERACT)
scoring system currently undergoing validation10884 and
this may go a long way toward allowing this assessment in pivotal
clinical trials.
Figure 1033 – MRI Evidence of Erosions Not Visible on X-Ray
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Ultrasound
The use of ultrasound has become more widespread
in assessing arthritis, due in part, to the evolution of newer technology
that allows better imaging at a reduced cost.10315 It
has been used to assess synovial effusions, the articular surface,
synovial blood flow and inflammation (via Doppler), soft tissue structures,
tendons, muscle, bone, and cartilage.10379 There
have been number of reports about the utility of diagnosing early
RA with the use of ultrasound.10577 There is little data determining the validity, the reproducibility
of measurements of the same target, or reproducibility of assessing
change over time. This makes comparisons across studies difficult.10446 As
such, ultrasound has not been used in pivotal studies to assess disease
activity or the impact of intervention in RA.
Bone Densitometry (Dual-Energy X-Ray Absorptiometry)
Dual energy x-ray absorptiometry (DEXA) is a
noninvasive, diagnostic imaging test that measures bone mineral density
(BMD), is the most accurate, widely used, and the most studied bone
density measurement technology. Two radiograph beams with differing
energy levels (dual energy) are aimed at the bone to be imaged. When
soft tissue absorption is subtracted out, the BMD can be accurately
determined from the differential absorption of each beam by bone.
DEXA scans are used as a screening and diagnostic test for osteoporosis,
but can also detect bone loss associated with RA, secondary to the
disease process itself, or to the drugs (such as corticosteroids),
which are used to manage RA. Generalized and localized bone loss have
been a well-recognized manifestation of RA.10336 The
rate of bone loss in RA has been reported to be higher in the first
year of disease10972 and
early in disease.10719 There is a lack of studies validating the
use of DEXA as a diagnostic tool in RA. Its role in identifying patients
at risk for poorer outcomes is yet to be determined.11093
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