Assessment of the rheumatological patient
Investigations in
rheumatology
Robin Butler
Victor N Cassar-Pullicino
Abstract
Laboratory investigations play an important role in the diagnosis of
rheumatic disorders but many tests are of limited specificity. It is there-
fore important to select tests in the light of careful clinical assessment
rather than blindly sending off a battery of requests, as the results may
be confusing. We review the frequency of autoantibodies in different
disorders and their value for diagnosis and, in some cases, for prognosis
and monitoring. We also review the relative merits and disadvantages
of plain radiographs, ultrasound, isotope, CT and MR imaging for dif-
ferent types of musculoskeletal problem. Finally we describe the typi-
cal imaging characteristics of degenerative and inflammatory disorders
­including rheumatoid arthritis and seronegative spondyloarthropathies
in the ­peripheral joints and spine.
Keywords autoantibodies; CCP; ANF; ENA; ANCA; rheumatology; inves-
tigations; ultrasound; MRI; radiographs; CT
Investigations are of great value in rheumatology, but a single
test is rarely diagnostic because of the limited specificity of most
tests.1 Investigations should be selected and results interpreted in
the light of the clinical history and examination: simply sending
off a battery of investigations without assessing the clinical prob-
lem will often result in confusion rather than enlightenment.
Blood tests
Acute phase reactants
The acute phase response can be measured by erythrocyte
­sedimentation rate (ESR), plasma viscosity or C-reactive protein
(CRP). ESR is less specific than the other two and is increased by
Robin Butler FRCP is Consultant Rheumatologist at the Robert Jones
and Agnes Hunt Orthopaedic Hospital, Oswestry, UK. He qualified
from Charing Cross Hospital Medical School, London, and trained
in rheumatology at Charing Cross Hospital and Westminster
Hospital, London. His research interests include the management of
complicated rheumatoid arthritis, vasculitis and corticosteroid-induced
osteoporosis. Conflicts of interest: none declared.
Victor N Cassar-Pullicino MRCS FRCR DMRD is Consultant Radiologist at the
Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK. He
qualified from the University of Malta, and trained in radiology at the
University of Birmingham, UK. His research interests are spinal and
articular disorders, including sports injuries. Conflicts of interest: none
declared.
MEDICINE 34:9
What’s new?
• Antibodies to CCP have been recognized as having a
high specificity for the diagnosis of rheumatoid arthritis
and to be of prognostic value
• There is better understanding of the utility of ANCA and
phospholipid antibodies in the evaluation of vasculitis
and clotting disorders respectively
• MRI has become a standard investigation in the
assessment of musculoskeletal disorders, and
ultrasound is playing an increasingly important role in
the field
anaemia and hyperglobulinaemia and it rises with age. All can be
used to assess the activity of inflammatory rheumatic disorders,
although systemic lupus erythematosus (SLE) is unusual in that
CRP is typically normal or only slightly raised unless there is
­concurrent infection. A high ESR or CRP at onset is a poor prog-
nostic factor in rheumatoid arthritis.
Uric acid
Uric acid is of limited solubility in blood and tissue fluids and
so the higher the serum uric acid level the greater the risk of
­crystal precipitation in and around joints and hence of gout.
With increasing obesity and alcohol consumption in the general
­population the mean serum urate is rising and so is the frequency
of gout. It is important to remember that the ‘gold standard’ for
the diagnosis of gout is identification of urate crystals in synovial
fluid or other tissue. Because hyperuricaemia (>0.42  mmol/l in
men and >0.36  mmol/l in women) is much more common than
gout, hyperuricaemia can be at most consistent with gout but not
diagnostic. Furthermore, the serum uric acid can fall during an
acute attack, so that a normal value during an attack does not
exclude the diagnosis. Adequacy of allopurinol or other treat-
ment can be assessed by measurement of serum uric acid.
Autoantibodies (Table 1)
Rheumatoid factor (RF) and cyclic citrullinated protein (CCP)
antibodies: RF is found in about 75% of people with rheumatoid
arthritis (RA) but it is also found in about 5% of the general
population and an even higher proportion of the elderly, as well
as in various rheumatic and other disorders including infection,
chronic liver disease and lymphoproliferative disorders. As a
test, it therefore lacks sensitivity and is of very low specificity.
Nonetheless, high titre RF has been consistently shown to be a
marker for severe disease and hence of some use as a prognostic
marker.
Recently, antibodies to CCP have attracted much interest. Both
RF and anti-CCP antibodies can be found in the sera of people
many years before the development of overt disease, but anti-
CCP appear sooner and are more predictive of severe disease.2 As
with RF, about 75% of people with RA have antibodies to CCP
but these have a specificity of more than 95% for a diagnosis of
RA, although they are occasionally found in people with Sjögren’s
syndrome, psoriatic arthritis and rarely in other conditions.
350 © 2006 Elsevier Ltd. All rights reserved.
 Assessment of the rheumatological patient
Approximate frequency (%) of autoantibodies*
Antibody RA Sjogrens SLE
RF 80 70 25
ANF 25 65 95
DNA 5 - 65
Sm - - 20
Ro 5 70 35
La - 40 15
Cardiolipin 20 30 30
Scl-70 - - - -
Jo-1 - - - -
*Frequency varies to some extent according to assay used and population studied e.g. district hospital or tertiary referral centre. APS: anti-phospholipid
syndrome; PM/DM: polymyositis/dermatomyositis.
§Frequency increases with age and can exceed 25% in extreme old age. (-) < 5%.
Table 1
Antinuclear factor (ANF), DNA and extractable nuclear antigen
(ENA) antibodies: ANF is found in about 95% of people with SLE,
the remainder typically having antibodies to Ro. ANF is also fairly
common in other rheumatic and general medical disorders (e.g.
infections, chronic inflammatory disorders and malignancy) and
this limited specificity restricts its diagnostic value. By contrast
antibodies to ds-DNA and Sm have high specificity for SLE, and
the titre of ds-DNA antibodies is helpful for monitoring disease
activity. Antibodies to ENA are found in various connective tissue
disorders with some degree of overlap, but some are fairly specific
for certain disorders, for example, Scl-70 (anti-­topoisomerase 1)
for scleroderma and Jo-1 (anti-histidyl tRNA synthetase) for myo-
sitis associated with interstitial pulmonary disease. RNA binding
protein (RNP) is present in undifferentiated connective disorder
associated with severe Raynaud’s phenomenon, but is also seen
in about 30% of people with SLE. A centromere pattern of ANF is
strongly associated with the CREST variant of scleroderma.
Phospholipid antibodies: this group of antibodies comprises the
lupus anticoagulant and antibodies to cardiolipin and β2-­glycoprotein
I. They are associated with the anti-phospholipid syndrome (APS)
which is characterized by recurrent venous and arterial thrombosis
and, in women, recurrent fetal loss. They are also found in about
one-third of people with SLE who are similarly at risk of clotting.
IgG class antibodies are generally associated with a higher risk of
clotting than those of IgM class, and the higher the titre of antibod-
ies the greater the risk. Phospholipid antibodies are also sometimes
found in people with rheumatoid arthritis and other inflammatory
disorders without apparent clotting problems.
Although generally concordant, some people with APS have
low titre or negative tests for cardiolipin antibodies but lupus
anticoagulant can be detected by prolonged kaolin clotting
time (KCT) or by the Russell viper venom test, or antibodies to
β2-glycoprotein I are present. In cases with a high index of suspi-
cion, it is therefore appropriate to do more than one test.
Anti-neutrophil cytoplasmic antibodies (ANCA) are found in
different types of vasculitis and some other conditions. There
are two main types: cytoplasmic (c-ANCA) and peri-nuclear
MEDICINE 34:9
APS Scleroderma PM/DM Controls
20 5 5§
60 25 5
- - -
- - -
30 - -
5 - -
85 20 10 5
20 - -
- 20 -
(p- ANCA) based on their staining pattern on immunofluores-
cence. A c-ANCA pattern is typically produced by antibodies
reacting with serine proteinase 3 (PR3) and p-ANCA by those
which react with myeloperoxidase (MPO).
PR3 antibodies are present in most cases of Wegener’s granulo-
matosis (WG), although they are also seen in about 45% of those
with microscopic polyangiitis and sometimes in acute infections
and inflammatory bowel disease. The titre of antibodies tends
to vary according to the activity of the disease in WG and some
reports suggest that the titre can be used to monitor this. p-ANCA
antibodies are seen in about 65% of cases of Churg-Strauss syn-
drome and about 50% of those with microscopic polyangiitis,
but are sometimes seen in rheumatoid arthritis, inflammatory
bowel disease and other inflammatory disorders.
Complement
Inherited deficiency of complement components, especially C4,
is a risk factor for the development of SLE. During active disease
levels of C4 and less often C3 will fall and serial measurements
can be helpful to monitor disease activity. Hypocomplementae-
mia is also seen in mixed cryoglobulinaemia and other disorders
associated with circulating immune complexes.
HLA typing
HLA-B27 is found in approximately 95% of people with isolated
ankylosing spondylitis (AS), 70% of people with AS who have
­psoriasis, 50% of people with AS who have either Crohn’s disease
or ulcerative colitis, and 70% of people with reactive arthritis.
However, it is also found in about 8% of the healthy Caucasian
population, only a small proportion of whom develop these dis-
eases, and so it is of very limited value as a diagnostic test. In
people in whom a spondyloarthropathy is suspected it is more
appropriate to make the diagnosis by clinical assessment and X- ray
or MR imaging of the sacro-iliac joints or spine (see below).
RA is associated with the tissue type HLA-DRB1*04 but again
this is common in the healthy population and so tissue typing
is unhelpful for diagnosis. HLA-DRB1 alleles which encode a
­common structural element known as the shared epitope are
markers for severe disease, but testing for this is currently a
351 © 2006 Elsevier Ltd. All rights reserved.
 Assessment of the rheumatological patient

research tool. It appears that people who possess the shared epi-
tope and smoke are at significantly increased risk of developing
both CCP antibodies and RA.
Synovial fluid
Synovial fluid aspiration can be of diagnostic value in septic and
crystal arthritis and can help to distinguish inflammatory from
non-inflammatory disorders (Table 2). Fluid should be sent for
Gram stain and culture, as well as examination for urate or cal-
cium pyrophosphate dihydrate crystals which are found in gout
and pseudogout, respectively.
Imaging
A combined clinical and radiological approach is essential in the
diagnosis and management of rheumatological disorders and their
complications. There is significant overlap between the radiological
features of several rheumatic disorders; therefore, close collabora-
tion is required between clinician and radiologist when selecting
the appropriate imaging modality and interpreting the result.
Basic joint structure
In a typical synovial joint, the bone ends are covered by hyaline
cartilage and there is a synovial lining; the joint can move freely.
In cartilaginous joints (e.g. the intervertebral and manubrioster-
nal joints, the pubic symphysis), the bone ends are covered with
hyaline cartilage but the bones are linked by fibrocartilage and
strong ligaments; movement depends on compression of the rela-
tively soft intervening fibrocartilage. Different disease processes
occur in the two types of joint. Diseases of cartilaginous joints
are often associated with disorders of the enthesis (the site of
attachment of a tendon or ligament to bone). Different imaging
modalities are appropriate for bone, cartilage and synovium, all of
which may show abnormalities in different rheumatic ­disorders.
and weaknesses in different situations (Table 3). Routine views
can be supplemented by special projections (e.g. the hands, sac-
roiliac joints). Dynamic views can also give further information;
for example, to demonstrate spinal instability. The limitation of
plain radiography is that radiographic changes can take months
to appear in rheumatoid arthritis (RA); only septic arthritis is
likely to show abnormalities within days of disease onset. ‘Early’
radiographic signs of disease usually indicate a well-established
disease process and the changes are usually irreversible.
Tomography has been largely superseded by CT and MRI of the
spine, but can still be helpful in the temporomandibular, costo-
vertebral and sternoclavicular joints.
Contrast arthrography is performed by injecting contrast
medium or air into a joint before radiography or CT. It is par-
ticularly helpful in the knee and shoulder to identify meniscal or
rotator cuff tears, intra-articular loose bodies and transchondral
fractures. Contrast studies with MRI are gaining popularity.
Ultrasonography can be used to assess joint effusions, synovial
proliferation, erosions, intra-articular loose bodies (Figure 1),
tendon thickening or rupture and to detect para-articular cysts. It
is more accurate than clinical assessment in shoulder pain.3 Per-
fusion within synovial proliferation can be assessed with power
Doppler ultrasonography.
Ultrasound for early detection of RA. Compared with clinical
assessment, high resolution ultrasonography will detect synovial
proliferation more accurately and can distinguish it from effusion,
peri-articular inflammation and fat.4 Erosions can be detected
long before they become visible with plain radiographs which
aids diagnosis. The sensitivity of ultrasound in detection of new
erosions and persistent synovial proliferation makes it a valuable
tool in the serial assessment of the adequacy of ­treatment.

Imaging modalities Isotope scanning using technetium-99m is widely used to seek

Plain radiography is the mainstay of musculoskeletal imag- bone metastases. It also demonstrates bone or joint infection
ing and has a central role in rheumatological diagnosis. It is and inflammation, because it shows increased blood flow to, or
increasingly being complemented by other techniques, notably increased metabolic activity in, bones, joints or entheses. Isotope
­ultrasound, CT and MRI. Each of these modalities has strengths scanning is sensitive but not specific, and increased uptake is
seen in osteoarthritic joints and failed prostheses. This ­modality
is perhaps most useful in excluding significant inflammatory,
Typical characteristics of synovial fluid in infective or neoplastic musculoskeletal disease.
different condtions
CT is particularly useful for complex anatomy. It demonstrates
Type of fluid Special features Leucocytes per mm3 bone well and can be used for peripheral joints and the spine.
Recent developments enable three-dimensional reconstruction of
Normal Viscous, colourless < 200 (< 25% images, which can be useful in the spine (e.g. to diagnose spinal
neutrophils) stenosis). CT can be combined with conventional myelography
Non-inflammatory Viscous, clear, 200–2000 (< 25% or arthrography to provide more information.
yellow neutrophils)
Inflammatory Thin, pale yellow 2000–75,000 MRI is superior to CT in imaging soft tissues, including liga-
arthritis and cloudy. Glucose (> 50% neutrophils) ments, cartilage, intervertebral disc and muscle; it is thus par-
may be low ticularly helpful in the diagnosis of musculoskeletal disorders.
Septic arthritis Opaque or purulent. > 75,000 (> 75% The most commonly used magnetic resonance sequences are T1-
Glucose very low neutrophils) weighted, T2-weighted and STIR. The contrast resolution of these
sequences is superior to that of plain radiography and CT, but
Table 2 T1-weighted images are better for delineating anatomical detail,

MEDICINE 34:9 352 © 2006 Elsevier Ltd. All rights reserved.

 Assessment of the rheumatological patient

Relative merits of imaging modalities

Plain radiography Arthrography Plain CT Ultrasonography MRI Isotopes

•   Eflfusion + – ++ ++++ ++++ –

•   Synovitis + ++++ + ++++ ++++ +++
•   Cartilage loss + ++++ (plus CT) ++ ++ ++++ –
•   Calcification +++ – ++++ ++++ + –
•   Bone erosions + + ++++ ++++ ++++ –
‡
•   Enthesitis + – + + +++ ++++
•   New bone formation ++ – ++++ – + ++
•   Periosteal reaction ++++ – ++++ + ++ +
•   Avascular necrosis of bone + – ++ – ++++ ++++

–, modality of no use; +, poor; ++, average; +++, good; ++++, excellent; ‡, hands/feet (high-resolution mode).

Table 3

T2-weighted images are best for identifying the presence of fluid
e.g. CSF, effusions, and STIR for identifying bone and soft tis-
sue oedema (Figure 2). Gadolinium-DTPA intravenous injection
aids in the differentiation of synovitis from effusion and deter-
mines vascularity in osteonecrosis. MRI is the best method for
demonstration of intervertebral disc pathology and prolapse, and
pressure on the spinal cord or nerve roots from disc herniation,
rheumatoid subluxation or spinal stenosis. It has revolutionized
detection of soft tissue lesions in the knee and shoulder (e.g.
meniscal, rotator cuff). It can be used to assess muscle involve-
ment in polymyositis and is invaluable in soft tissue, articular
and bone tumours. Because the method shows bone marrow
well, it is used to diagnose and stage osteonecrosis. Progress in
software and magnetic resonance sequences has increased the
role of MRI in the assessment of articular cartilage; the thickness
of cartilage, the volume of loss and the extent of surface area
involvement can be calculated. The status of subchondral bone,
the extent of synovial proliferation and the results of treatment of
cartilage defects can also be delineated by MRI.
example, the presence of blood on MRI suggests trauma, haemo-
philia or pigmented villonodular synovitis.
Synovial hypertrophy is the hallmark of inflammatory arthritis.
It cannot be distinguished from an effusion on plain radiography
and is better shown by ultrasonography or MRI. It is impossible
to determine the type of inflammatory arthropathy using MRI.
Bursal enlargement and cysts can be readily demonstrated by
ultrasonography or MRI. Contrast CT can be useful in the identi-
fication of intra-articular loose bodies.
Calcium deposition occurs most commonly in calcium pyro-
phosphate dihydrate deposition (CPPD) disease and can be seen
on plain radiography or CT. It may affect both synovium and
cartilage. Synovial chondromatosis may be associated with intra-
articular loose bodies in addition to calcified lesions in synovium.
Small periarticular deposits of calcium near the interphalangeal
joints often represent hydroxyapatite crystals.

Radiological signs of synovial disease
Joint effusion may be evident on a plain radiograph as an area
of increased soft tissue density or displacement of periarticular
fat pads, but is more reliably demonstrated by ultrasonography
or MRI. The characteristics of the fluid may aid diagnosis; for
Haemosiderin deposition: iron can be recognized by its charac-
teristics on MRI. Large iron deposits are seen in haemochromato-
sis and following repeated intra-articular bleeding in haemophilia
and pigmented villonodular synovitis. Some iron may accumu-
late in the synovium in RA.

Changes in adjacent bone can often be seen on plain radio-

Figure 1 Ultrasound scan of the shoulder in the coronal plane showing
numerous ‘rice bodies’ surrounded by fluid in the subacromial and
subdeltoid bursae.
graphs, but may be better demonstrated by CT and MRI.
Periarticular osteopenia is typically seen in RA and other
chronic inflammatory arthropathies, though it typically does not
occur in psoriatic arthritis. It is a characteristic feature of acute
and chronic infection, and therefore occurs in septic arthritis,
osteomyelitis and tuberculosis and is a prominent feature of
reflex dystrophy syndrome (Sudeck’s atrophy).
Erosion – marginal erosion of bone is the radiological hall-
mark of RA (Figure 3), but also occurs in other inflammatory
arthropathies. Erosions typically begin in the ‘bare areas’ at the
margins of joints, where intra-articular bone is not covered by
cartilage. In psoriatic arthritis, joint involvement is typically
asymmetrical, unlike in RA, and erosions are less prominent. In

MEDICINE 34:9 353 © 2006 Elsevier Ltd. All rights reserved.

 Assessment of the rheumatological patient

Figure 2 Seronegative arthropathy. a Sagittal T1, b T1 post-contrast, and c STIR MR images of the hindfoot. Note enhancing synovial disease
anteriorly in the ankle joint with synovial rim enhancement posteriorly around a non-enhancing effusion. Marrow oedema on either side of the
subtalar joint is seen as dark signal in a and bright signal in c. Involvement of the retro-calcaneal bursa is present.

severe cases, however, there may be marked erosion with ‘whit-
tling’ of bone and progression to ‘pencil-in-cup’ deformities. In
gout, large ‘punched-out’ erosions may be seen, but these are
typically extra-articular and in the metaphyseal region, and have
a prominent ‘overhanging lip’ (Figure 4).
New bone formation – psoriatic arthritis and Reiter’s syn-
drome often show new bone formation in relation to marginal
erosions that gives a ‘whiskered’ appearance. Periosteal reaction
is also prominent in these conditions and in osteomyelitis, and
may be seen in juvenile chronic arthritis.

Figure 3 Rheumatoid arthritis of the metacarpophalangeal joints seen as a erosions and joint space loss radiographically and b with pannus
depiction adjacent to erosion of the 4th metacarpal head on the ultrasound image (arrow).

MEDICINE 34:9 354 © 2006 Elsevier Ltd. All rights reserved.

 Assessment of the rheumatological patient
Figure 4 Gout involving the first metatarsophalangeal joint.
Periarticular swelling with ‘punched out’ erosion located away from the
articular surface with an overhanging lip appearance. The joint space
is preserved and there is no osteopenia.
Radiological signs of cartilage damage
Joint space reduction: it is difficult to judge articular loss on
plain radiography because a flexion deformity may lead to an
apparent reduction in joint space. In the lower limbs, cartilage
thickness can be estimated on weight-bearing views. Cartilage
thickness can be better assessed using MRI or contrast arthrogra-
phy with CT. In RA and infection, cartilage loss affects the whole
cartilage surface, whereas in osteoarthritis the cartilage loss
tends to be irregular in distribution. Most arthropathies are asso-
ciated with cartilage damage and narrowing of the joint space,
but there are exceptions – notably systemic lupus erythematosus,
gout (except in advanced stages) and relatively uncommon dis-
orders such as pigmented villonodular synovitis and multicentric
reticulocytosis, in which the preservation of joint space is useful
in diagnosis.
Cartilage calcification (chondrocalcinosis) is a characteristic
feature of CPPD. It is also seen in hyperparathyroidism, gout,
haemochromatosis and, less commonly, Wilson’s disease.
Changes in subchondral bone: subchondral bone cysts occur
only where there is loss of integrity of the overlying cartilage. In
RA, they can be difficult to distinguish from erosions when the
plane of the film does not include the area of cortical destruction.
They are not disease-specific, and occur in osteoarthritis and
inflammatory arthropathies. Particularly large subchondral cysts
(‘geodes’) are seen in the robustus form of RA, CPPD and haemo-
philia. Subchondral bony sclerosis is a hallmark of ­osteoarthritis,
MEDICINE 34:9
but is nonspecific because reactive sclerosis is also a manifesta-
tion of seronegative arthropathies.
Osteophytosis with cortical buttressing is a characteristic ­feature
of osteoarthritis (Figure 5). An osteophyte is a cartilage-covered
bony projection at the margin of the joint; it seems to represent
a hypertrophic response to joint damage, in contrast to the atro-
phic process represented by cartilage loss and joint space narrow-
ing. Buttressing of bone results from thickening of the adjacent
bony cortex and is often seen in the hip; it probably represents a
response to altered biomechanics of the joint.
Joint migration represents loss of the normal congruity of the
joint. It may result from severe damage to periarticular structures
(e.g. ligaments and tendons in RA) or from severe joint damage
in septic arthritis, osteomyelitis or a Charcot’s joint. Collapse of
the acetabulum results in protrusio acetabulae; the femoral head
migrates centrally in RA and superolaterally in osteoarthritis.
Radiological signs of enthesopathy
The enthesis is particularly affected in seronegative spondylo-
arthropathies; pathological changes in the enthesis are analogous
to those that occur in the spine (see below). Plain radiographs
are unremarkable during the initial inflammatory reaction,
but an isotope bone scan often demonstrates increased uptake
(F­igure 6a). This is followed by erosion of bone, reactive sclero-
sis and bony proliferation to form a bone spur (Figure 6b); these
changes are visible on radiography. MRI is increasingly used to
demonstrate enthesopathy in both the axial and the appendicular
skeleton.
Imaging of spinal disease
Conventional radiographs are of limited use in spinal imaging
because they provide no information on soft tissue structures
including the intervertebral discs, spinal cord and nerve roots;
Figure 5 Osteoarthritis of the interphalangeal joints. Joint space loss,
marginal osteophytes, subchondral erosion and sclerosis are typical.
355 © 2006 Elsevier Ltd. All rights reserved.
 Assessment of the rheumatological patient
Figure 6 Active Reiter’s enthesitis and arthritis in the foot. a Increased
activity at the attachment of the plantar fascia and in the metatarso
joints on a technetium methylene diphosphate scintigram. b Radiograph
showing erosion and calcaneal spur formation.
these can be demonstrated by MRI. CT illustrates spinal stenosis,
facet joint abnormalities and spinal deformity.
Degenerative disease: degenerative disc disease may result in
disc prolapse and compression of nerve roots. Narrowing and
disorganization of the disc often leads to spondylosis (horizontal
outgrowths of bone around the circumference of the vertebral
rim, analogous to the osteophytes that occur in osteoarthritis
of peripheral joints). The apophyseal (facet) joints are synovial
joints, which may be affected by osteoarthritis.
MRI is the method of choice in detecting spinal cord or
nerve root compression. Diffuse idiopathic skeletal hyperostosis
(­Forestier’s disease) is a severe form of degeneration in which
florid osteophytes and flowing ossification between adjacent verte-
bral bodies occur, with thick prominent ossification of the anterior
longitudinal ligament (Figure 7). The osseous outgrowths begin at
the enthesis where the anterior longitudinal ligament inserts on
the vertebral body, and not at the intervertebral disc attachments.
These changes are usually apparent on radiography (best seen in
lateral views), but can often be demonstrated ­better  by CT.
RA affects the synovial joints of the spine (the apophyseal joints)
and the uncovertebral (neurocentral) joints of the cervical spine.
In addition, rheumatoid synovial proliferation (pannus) can lead
to spinal cord compression in the neck as a result of direct pressure
or subluxation secondary to ligamentous rupture. Such instabil-
ity can be demonstrated by obtaining lateral radiographs in both
flexion and extension. MRI is now the investigation of choice for
imaging the rheumatoid cervical spine because it shows pannus
and the spinal cord in addition to the bony structure (Figure 8).
Ankylosing spondylitis: sacroiliitis is usually the first radio-
logical manifestation of ankylosing spondylitis. Erosion of the
margins of the sacroiliac joint is associated with sclerosis in the
subchondral bone; ultimately, the joint may fuse (ankylosis).
Changes may be apparent on radiography, but special views may
be required because the appearance of the lumbar spine and
MEDICINE 34:9
Figure 7 Diffuse
idiopathic skeletal
hyperostosis in the
neck. Exuberant
new bone
formation along
the anterior border
of contiguous
vertebral bodies
spans normal
intervertebral discs.
pelvis on films can be misleading. In the early stages, the joint
appearance can be difficult to interpret, particularly in adoles-
cents, in whom widening is common and normal, though sclero-
sis is usually absent. In difficult cases, MRI or CT can be used to
detect early changes (Figure 9). MRI shows the bone outline less
well but has the advantage that it does not involve exposure of
the gonads to radiation, and demonstrates subchondral inflam-
mation within the marrow. Isotope scanning is no longer used.
Spinal disease in ankylosing spondylitis follows a similar pat-
tern. The first lesions (Romanus lesions) typically appear at the
anterosuperior or antero-inferior margins of the vertebral bodies
adjacent to the insertion of the annulus fibrosus (Figure 10). There
is erosion of the bone with subjacent sclerosis and the bony defect
is gradually filled in; this leads to squaring of the vertebral bodies
(loss of their normal anterior concavity) and production of syn-
desmophytes (projections of new bone that grow vertically and
eventually bridge adjacent vertebrae). A similar process affects the
facet joints. Severe cases may lead to a ‘bamboo spine’, in which
bony bridging of vertebrae anteriorly and of the posterior elements
is complete. These changes are generally shown adequately by
radiography, but CT is useful in showing changes in the apophy-
seal joints. MRI is much more sensitive than plain x-rays in the
identification of early changes, spondylodiscitis and lesions at the
insertion of the annulus fibrosus (Figure 11). MRI can also be
used to evaluate response to treatment with TNF-α inhibitors,5
although it is not yet clear that such improvement in MRI findings
will be associated with the prevention of classical syndesmophyte
formation and bony bridging seen on radiographs.
Reiter’s syndrome and psoriatic spondylitis: the spinal changes
in Reiter’s syndrome and psoriatic spondylitis are similar to those
seen in idiopathic ankylosing spondylitis. However, the sacroili-
itis is less likely to be symmetrical and ‘skip lesions’ (in which
some intervertebral levels show marked changes whereas oth-
ers are completely spared) are common. In addition, pronounced
356 © 2006 Elsevier Ltd. All rights reserved.
 Assessment of the rheumatological patient
paravertebral ossification may be seen; this is thicker and denser,
asymmetrical and irregular compared with the thin, regular and
symmetrical appearance typical of ankylosing spondylitis.
Infection: pyogenic infection can affect the disc space or verte-
bral body. Tuberculous infection of the spine is similar, but tends
to be more insidious in onset and associated with larger para-
spinal abscesses. Metastatic disease is often the main diagnostic
alternative to spinal infection, but in this case the disc space is
spared even when adjacent vertebrae have secondary deposits.
Thus, a preserved disc space between two eroded vertebrae is
an ominous finding because it suggests malignancy, whereas a
damaged disc suggests infection.
Figure 9 Active unilateral sacroiliitis. a Indistinct subchondral outline of the left joint and juxta-articular sclerosis compared with the right joint.
b Axial CT shows that most of the changes are on the iliac side of the joint.
MEDICINE 34:9 357
Figure 8 Rheumatoid arthritis of the cervical spine
showing combined anterior and vertical C1/C2
subluxation on sagittal T1 a and T1 post-contrast
b MR images. The odontoid peg has migrated
through the foramen magnum compressing the
medulla oblongata and cervical cord. Enhancement of
the pannus in b is seen at the C1/C2 and
disco-vertebral junctions.
Advanced changes are visible on radiography, but in the early
stages isotope scanning is helpful and either CT or MRI shows
vertebral damage. MRI is particularly useful in demonstrating the
extent of soft tissue involvement.
Malignancy: with the exception of multiple myeloma, primary
bone tumours are seldom encountered in rheumatological prac-
tice. However, metastatic disease can present with myalgia and
bone pain. Skeletal areas of residual red marrow (spine, pelvis,
proximal femora and proximal humeri) are the most common
sites of metastatic disease. The radiographic appearances can be
lytic or sclerotic, and vertebral body collapse is a not uncom-
mon presentation. Destruction of one or both pedicles with
© 2006 Elsevier Ltd. All rights reserved.
 Assessment of the rheumatological patient

Figure 10 Romanus lesion in ankylosing spondylitis. a Osteitis, bone loss and sclerosis at the anterior-inferior corner of the L2 vertebra is the
precursor of b the syndesmophyte that bridges the disc space causing bony ankylosis.

­ reservation of the adjacent intervertebral disc space suggests

p Assessing disease progression
the possibility of malignant disease. Scintigraphy and MRI are
helpful in the assessment of metastatic disease in the spine. MRI
has been shown to be more ­sensitive than plain radiography and
radionuclide bone scintigraphy in the detection of metastatic
disease (breast, renal, prostate cancer) and multiple myeloma.
Although bone scintigraphy assesses the whole skeleton, it
should be noted that isolated peripheral skeletal metastases were
seen in only 2% of patients in a study comparing whole body
scintigraphy with MRI of the spine, pelvis and proximal femora
in 200 patients with breast or prostate cancer. MRI of the spine
is more sensitive and specific for metastatic disease than bone
scintigraphy6 because the mechanism of detection relies on the
presence of tumour within the bone marrow, whereas scintigra-
phy relies on a bone response to the presence of disease.
RA: serial assessment of joint damage in RA is more complicated
than it appears. Several scoring systems have been devised,
most of which focus on the progression of erosive disease and
­cartilage loss. MRI and ultrasonography are more sensitive than
plain radiographs in the detection of erosions. Both are more
sensitive than clinical examination in the detection of synovitis
and may be useful for assessing response to treatment, although
X-ray changes remain the gold standard in clinical trials for the
time being.
Osteoarthritis: standard sets of radiographs have been produced
against which osteoarthritic changes in a given joint can be scored.
Cartilage thickness can be judged to some extent by measuring
the joint space on radiography with or without ­ magnification.

Figure 11 Ankylosing
spondylitis seen on sagittal
MR images of the lumbar
spine on T1 a and T2 b.
The enthesitis is seen as
bright T2 marrow signal at
L4 antero-superiorly (arrow)
and postero-superiorly at L5.
Discovertebral erosions at
L2/L3 are seen on T1 images
surrounded by marrow
oedema in the vertebrae seen
as bright T2 signal in b.

MEDICINE 34:9 358 © 2006 Elsevier Ltd. All rights reserved.

 Assessment of the rheumatological patient
However, it is difficult to position the joint such that the X-ray
beam is perpendicular to the axis of the joint and hence to take
follow-up films in precisely the same position. CT can be helpful,
particularly when combined with contrast arthrography, but MRI
demonstrates cartilage most satisfactorily and may be useful in
the assessment of the degree of cartilage loss. ◆
References
1 Sheldon J. Laboratory testing in autoimmune rheumatic diseases.
Best Pract Res Clin Rheumatol 2004; 18: 249–69.
2 Zendman A J W, van Venrooij W J, Pruijn G J M. Use and significance
of anti-CCP autoantibodies in rheumatoid arthritis. Rheumatol 2006;
45: 20–5.
3 Naredo E, Aguado P, De Miguel E et al. Painful Shoulder:
Comparison of physical examination and ultrasonographic findings.
Ann Rheum Dis 2002; 61: 132–6.
4 Szkudlarek M, Narvestad E, Klarlund M, Court-Payen M, Thomsen H S,
Ostergaard M. Ultrasonography of the metatarsophalangeal joints in
rheumatoid arthritis: comparison with magnetic resonance imaging,
conventional radiography and clinical assessment. Arthritis Rheum
2004; 50: 2103–12.
MEDICINE 34:9
5 Sieper J, Baraliakos X, Listing J et al. Persistent reduction in spinal
inflammation as assessed by magnetic resonance imaging in
patients with ankylosing spondylitis after 2 years of treatment with
the anti-tumour necrosis factor agent infliximab. Rheumatology
2005; 44: 1525–30.
6 Traill Z C, Talbot D, Golding S, Gleeson F V. MRI versus radionuclide
bone scintigraphy in screening for bone metastases. Clin Radiol
1999; 54: 448–51.
Further reading
Atlas of standard radiographs. Rheumatology 2005; 44(Suppl. 4):
iv43–72.
(Classic set of radiographs which show varying degrees of OA, RA
and ankylosing spondylitis.)
Resnick D. Bone and joint imaging. Philadelphia: Saunders, 2004.
(Authoritative textbook of musculoskeletal radiology and
imaging.)
Wakefield R J, Kong K O, Conaghan P G, Brown A K, O’Connor P J,
Emery P. The role of ultrasonography and magnetic resonance
imaging in early rheumatoid arthritis. Clin Exp Rheumatol 2003;
21(Suppl. 31): S42–9.
(Useful review of the clinical value of these methods.)
359 © 2006 Elsevier Ltd. All rights reserved.