Intx Rheum

Assessment of the rheumatological patient

Investigations in rheumatology

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

Robin Butler Victor N Cassar-Pullicino

• 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

Abstract Laboratory investigations play an important role in the diagnosis of rheumatic disorders but many tests are of limited specificity. It is therefore 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 different types of musculoskeletal problem. Finally we describe the typical imaging characteristics of degenerative and inflammatory disorders ­including rheumatoid arthritis and seronegative spondyloarthropathies in the ­peripheral joints and spine.

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 prognostic 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 treatment can be assessed by measurement of serum uric acid.

Keywords autoantibodies; CCP; ANF; ENA; ANCA; rheumatology; investigations; 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 problem 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

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 antiCCP 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.

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

350

© 2006 Elsevier Ltd. All rights reserved.

Assessment of the rheumatological patient

Approximate frequency (%) of autoantibodies* Antibody

RA

Sjogrens

SLE

RF ANF DNA Sm Ro La Cardiolipin Scl-70 Jo-1

80 25 5 5 20 -

70 65 70 40 30 -

25 95 65 20 35 15 30 -

APS

Scleroderma

PM/DM

Controls

85 -

20 60 30 5 20 20 -

5 25 10 20

5§ 5 5 -

*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 myositis 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.

(p- ANCA) based on their staining pattern on immunofluorescence. 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 granulomatosis (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 syndrome 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. Hypocomplementaemia is also seen in mixed cryoglobulinaemia and other disorders associated with circulating immune complexes.

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 antibodies 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 suspicion, it is therefore appropriate to do more than one test.

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 diseases, 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

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

351

© 2006 Elsevier Ltd. All rights reserved.

Assessment of the rheumatological patient

research tool. It appears that people who possess the shared epitope and smoke are at significantly increased risk of developing both CCP antibodies and RA.

and weaknesses in different situations (Table 3). Routine views can be supplemented by special projections (e.g. the hands, sacroiliac 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.

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 calcium pyrophosphate dihydrate crystals which are found in gout and pseudogout, respectively.

Tomography has been largely superseded by CT and MRI of the spine, but can still be helpful in the temporomandibular, costovertebral and sternoclavicular joints.

Imaging

Contrast arthrography is performed by injecting contrast medium or air into a joint before radiography or CT. It is particularly 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.

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 collaboration is required between clinician and radiologist when selecting the appropriate imaging modality and interpreting the result.

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 Perfusion within synovial proliferation can be assessed with power Doppler ultrasonography.

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 manubriosternal 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 relatively 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.

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 Plain radiography is the mainstay of musculoskeletal imaging and has a central role in rheumatological diagnosis. It is increasingly being complemented by other techniques, notably ­ultrasound, CT and MRI. Each of these modalities has strengths

Isotope scanning using technetium-99m is widely used to seek bone metastases. It also demonstrates bone or joint infection and inflammation, because it shows increased blood flow to, or increased metabolic activity in, bones, joints or entheses. Isotope 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, infective or neoplastic musculoskeletal disease.

Typical characteristics of synovial fluid in different condtions Type of fluid

Special features

Leucocytes per

Normal

Viscous, colourless

Non-inflammatory

Viscous, clear, yellow Thin, pale yellow and cloudy. Glucose may be low Opaque or purulent. Glucose very low

< 200 (< 25% neutrophils) 200–2000 (< 25% neutrophils) 2000–75,000 (> 50% neutrophils)

Inflammatory arthritis Septic arthritis

CT is particularly useful for complex anatomy. It demonstrates bone well and can be used for peripheral joints and the spine. Recent developments enable three-dimensional reconstruction of images, which can be useful in the spine (e.g. to diagnose spinal stenosis). CT can be combined with conventional myelography or arthrography to provide more information.

mm3

MRI is superior to CT in imaging soft tissues, including ligaments, cartilage, intervertebral disc and muscle; it is thus particularly helpful in the diagnosis of musculoskeletal disorders. The most commonly used magnetic resonance sequences are T1weighted, T2-weighted and STIR. The contrast resolution of these sequences is superior to that of plain radiography and CT, but T1-weighted images are better for delineating anatomical detail,

> 75,000 (> 75% neutrophils)

Table 2

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 •   Calcification •   Bone erosions

+ + + +++ +

– ++++ ++++ (plus CT) – +

++ + ++ ++++ ++++

++++ ++++ ++++ + ++++

– +++ – – –

•   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 tissue oedema (Figure 2). Gadolinium-DTPA intravenous injection aids in the differentiation of synovitis from effusion and determines 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 involvement 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, haemophilia or pigmented villonodular synovitis.

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 characteristics on MRI. Large iron deposits are seen in haemochromatosis and following repeated intra-articular bleeding in haemophilia and pigmented villonodular synovitis. Some iron may accumulate in the synovium in RA.

Figure 1 Ultrasound scan of the shoulder in the coronal plane showing numerous ‘rice bodies’ surrounded by fluid in the subacromial and subdeltoid bursae.

Changes in adjacent bone can often be seen on plain radiographs, 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 hallmark 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

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 identification of intra-articular loose bodies. Calcium deposition occurs most commonly in calcium pyrophosphate 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 intraarticular loose bodies in addition to calcified lesions in synovium. Small periarticular deposits of calcium near the interphalangeal joints often represent hydroxyapatite crystals.

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.

New bone formation – psoriatic arthritis and Reiter’s syndrome 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.

severe cases, however, there may be marked erosion with ‘whittling’ 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).

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

but is nonspecific because reactive sclerosis is also a manifestation 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 atrophic process represented by cartilage loss and joint space narrowing. 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 spondyloarthropathies; 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 sclerosis 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.

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.

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;

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 arthrography 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 associated 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 disorders 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 haemophilia. Subchondral bony sclerosis is a hallmark of ­osteoarthritis,

MEDICINE 34:9

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 7 Diffuse idiopathic skeletal hyperostosis in the neck. Exuberant new bone formation along the anterior border of contiguous vertebral bodies spans normal intervertebral discs.

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.

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 instability 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).

pelvis on films can be misleading. In the early stages, the joint appearance can be difficult to interpret, particularly in adolescents, in whom widening is common and normal, though sclerosis 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 inflammation within the marrow. Isotope scanning is no longer used. Spinal disease in ankylosing spondylitis follows a similar pattern. 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 syndesmophytes (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 apophyseal 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.

Ankylosing spondylitis: sacroiliitis is usually the first radiological 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

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 sacroiliitis is less likely to be symmetrical and ‘skip lesions’ (in which some intervertebral levels show marked changes whereas others are completely spared) are common. In addition, pronounced

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 vertebral 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.

MEDICINE 34:9

356

© 2006 Elsevier Ltd. All rights reserved.

Assessment of the rheumatological patient

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.

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.

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.

Infection: pyogenic infection can affect the disc space or vertebral body. Tuberculous infection of the spine is similar, but tends to be more insidious in onset and associated with larger paraspinal 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.

Malignancy: with the exception of multiple myeloma, primary bone tumours are seldom encountered in rheumatological practice. 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 uncommon presentation. Destruction of one or both pedicles with

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

© 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 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 scintigraphy relies on a bone response to the presence of disease.

Assessing disease progression 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. ◆

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.

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

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.