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Spondyloarthritis is the second most common inflammatory rheumatic disorder.
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Ultrasound can visualize several pathologic conditions in spondyloarthritis: enthesitis, bone erosions, synovitis, bursitis, and tenosynovitis.
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Ultrasound inflammation at the enthesis seems to be a characteristic finding in spondyloarthritis.
Definitions
Spondyloarthritis represents a group of inflammatory rheumatic disorders comprising ankylosing spondylitis (most common phenotype), psoriatic arthritis and spondylitis, reactive arthritis, arthritis with inflammatory bowel disease (i.e., Crohn’s disease or ulcerative colitis), and undifferentiated spondylarthropathies. Increased frequency of the HLA-B27 marker, familial aggregation, and axial skeleton involvement are characteristics of these disorders, and they frequently combine with peripheral arthritis, uveitis, psoriasis, and inflammatory bowel diseases.
With a prevalence of 0.3% to 0.5%, spondyloarthritis is the second most common inflammatory rheumatic disorder. Spondyloarthritis is characterized by peripheral arthritis and enthesitis, axial inflammation (i.e., sacroiliitis and spondylitis), and new bone formation leading to ankylosis. There is a major overlap between the different clinical spondyloarthritis entities and familial clustering. Possible mechanisms contributing to pathogenesis include genetic predisposition (i.e., HLA-B27 and other genes) and certain environmental influences (e.g., certain bacteria), which together initiate and perpetuate inflammation. Because spondyloarthritis starts relatively early in life and has a chronic, progressive course, the impact of the disease on health resources can be important. Following the original observation by Ball, several publications pointed out that enthesitis (i.e., inflammation at the insertion of tendons, ligaments, and capsules into bone) as a primary lesion may underlie all skeletal manifestations of spondyloarthritis. Enthesitis consists of focal, destructive, microscopic inflammatory lesions that evolve toward fibrous scarring and new bone formation. It may involve synovial and cartilaginous joints, syndesmoses, and extra-articular entheses.
Peripheral enthesitis is observed in all spondyloarthritis subtypes, including the undifferentiated forms, and it may sometimes manifest for a long period as an isolated clinical manifestation of an HLA-B27–associated disease. Besides spondyloarthritis patients, enthesitis is also common among athletes as a consequence of traumatic injuries. However, in the case of trauma, it does not combine with intra-articular inflammation (i.e., synovitis). Peripheral enthesitis is usually revealed by clinical findings that lack specificity, such as localized pain, tenderness, and swelling, and there are not definite clinical criteria for the diagnosis of this manifestation. It may also be asymptomatic and detected only by imaging such as conventional radiography, bone scintigraphy, magnetic resonance imaging (MRI), or ultrasound.
Ultrasound and Spondyloarthritis
Although most recent data are based on rheumatoid arthritis, there is an increasing interest in and evidence for the use of ultrasound for the assessment of spondyloarthritis. During the past few years, ultrasound has proved to be a highly sensitive and noninvasive tool, especially for assessing tendon and joint involvement, and it has proved to have greater sensitivity than clinical examination and other imaging techniques for the detection of peripheral enthesitis in spondyloarthritis. Several studies have described the gray-scale ultrasound features of lower limb enthesitis in spondyloarthritis, revealing a high frequency of asymptomatic but abnormal ultrasound findings. Moreover, the application of Doppler techniques seems to help differentiate inflammatory from noninflammatory enthesis diseases.
Ultrasound can visualize several pathologic conditions in spondyloarthritis: enthesitis, bone erosions, synovitis, bursitis, and tenosynovitis. This encompasses most of the musculoskeletal spondyloarthritis-associated pathology, with the exception of osteitis, because the ultrasound beam cannot penetrate the bone cortex. The ultrasound description of these elementary lesions is addressed in other chapters.
Diagnosis
Established Disease
Several studies have tried to demonstrate a difference between spondyloarthritis and other rheumatic diseases according to the type and extent of joint involvement.
McGonagle and colleagues showed that spondyloarthritis and rheumatoid arthritis patients present different findings for enthesis and joint involvement on MRI, such as frequent peri-entheseal fluid and bone marrow edema adjacent to the entheseal insertions in spondyloarthritis patients and soft tissue abnormalities resulting from severe synovitis with nonspecific extension of the inflammatory process beyond the joint capsule in rheumatoid arthritis patients. Despite the limitations of ultrasound in detecting bone marrow edema, it is likely that ultrasound can discriminate the findings of enthesitis regarding the pathogeneses of these two diseases.
Several studies have focused on the ability of ultrasound to differentiate spondyloarthritis from rheumatoid arthritis. The main target of these studies was enthesitis, except for two studies that also investigated synovitis. Using gray-scale ultrasound only, discordant data have been published about the capability of ultrasound to differentiate spondylorthritis from other pathologies, including rheumatoid arthritis. Genc and associates examined clinically and by gray-scale ultrasound 24 patients with rheumatoid arthritis, 18 patients with ankylosing spondylitis, and 20 healthy controls. Five entheseal sites in the lower limbs (i.e., Achilles tendon, plantar fascia, quadriceps tendon, and patellar ligament insertion on the inferior pole of the patella and on the tibial tuberosity) and two entheses of the upper limbs (i.e., insertions of the biceps brachii and supraspinatus) were evaluated. The rate of entheseal involvement in rheumatoid arthritis patients was similar to that of the ankylosing spondylitis group. The ultrasound appearance of rheumatoid arthritis enthesopathy was similar to that of ankylosing spondylitis. In both groups, the most frequently affected entheseal sites in the lower limbs were the base and the apex of the patella and the insertion of Achilles tendon. A major criticism of the study is that the investigators did not distinguish between enthesis involvement and tendon involvement; both were considered to be enthesitis. They also evaluated, as sign of enthesitis, tendon thickness, erosion, and enthesophytes, which are findings of chronic inflammatory process, and bursitis, which is considered the most common abnormal finding of enthesis “region” involvement in rheumatoid arthritis patients.
In a study by Frediani and colleagues, enthesitis of the quadriceps tendon was found to be more common in psoriatic arthritis than rheumatoid arthritis, and isolated enthesitis (without effusion of the knee joint) was demonstrated only in psoriatic arthritis. The pathologic findings detected by ultrasound were also different; rheumatoid arthritis patients had more evident signs of inflammatory components of enthesitis (i.e., edema, thickening, and focal hypoechogenicity), whereas psoriatic arthritis patients had more bony changes.
Similarly, a study comparing calcaneal enthesis in psoriatic arthritis, rheumatoid arthritis, and osteoarthritis showed that erosions and bony proliferation in particular target sites were specific for psoriatic arthritis. In this study, inflammatory lesions of calcaneal enthesis and bursae were more frequent in rheumatoid arthritis and psoriatic arthritis than in osteoarthritis.
Gibbon and colleagues showed that plantar aponeurosis was significantly thickened in patients with spondyloarthritis compared with patients with rheumatoid arthritis. In a cross-sectional study, D’Agostino and colleagues used power Doppler ultrasound to study seven bilateral enthesis sites in 164 spondylarthropathy patients, 34 rheumatoid arthritis patients, and 30 patients with degenerative spinal disease. The investigators showed a high rate of abnormal peripheral enthesitis among spondyloarthritis patients compared with controls. The landmark finding of power Doppler ultrasound for assessing enthesitis in spondyloarthritis patients was abnormal vascularization at the enthesis insertion into the cortical bone, which was exclusively detected in spondyloarthritis patients. In the rheumatoid arthritis group, vascularization was exclusively found in the retrocalcaneal bursa, confirming previous observations of the primary involvement of this structure in the “rheumatoid enthesitis symptom.” The distribution of enthesitis identified by power Doppler ultrasound was uniform among spondyloarthritis patients, irrespective of the disease phenotype (i.e., axial or peripheral), with a trend toward a more severe power Doppler ultrasound pattern in the peripheral forms (i.e., psoriatic arthritis and reactive arthritis). The specificity of the power Doppler sign seems to be high, but the quality of equipment for Doppler assessment is a crucial factor, as is knowledge of normal nutrition vessels.
Early or Suspected Disease
Several studies have reported that the lag time between the onset of the first signs of spondyloarthritis and its diagnosis is very long: 8.4 years for males and 9.8 years for females. The characteristic signs of disease, such as radiologic evidence of sacroiliitis, occur relatively late in the course of the disease.
In the early phases of spondyloarthritis, imaging techniques such as MRI and ultrasound can be used to demonstrate inflammation of enthesis or joint structures. MRI can confirm sacroiliitis and spondylitis in spondyloarthritis patients lacking radiographic signs, and studies suggest a diagnostic role for early inflammatory signs in sacroiliac joints. Considered to be highly specific, the sensitivity of this technique is estimated to be only 30% to 60%. Although manuscript titles may occasionally suggest so, no studies have investigated the diagnostic value of ultrasound in spondyloarthritis. The ability of ultrasound to visualize intra-articular and extra-articular changes should allow ultrasound to assist in diagnosing specific rheumatologic conditions, but this has not been scientifically verified. The lack of information may reflect the relatively new use of ultrasound in spondyloarthritis and the slow rate of disease progression. Current knowledge strongly encourages testing this hypothesis, particularly in patients with early, unclassified arthritis. Prospective studies are needed to confirm the predictive value of ultrasound findings for peripheral enthesitis and synovitis.
Follow-up and Prognosis
The treatment options for spondyloarthritis have been limited. The mainstays of treatment were regular physical therapy and nonsteroidal anti-inflammatory drugs. Disease-modifying antirheumatic drugs and corticosteroids, which are quite effective in treating rheumatoid arthritis, have very limited or no efficacy in treating spondyloarthritis. In the past, there was no interest in searching for an objective tool for follow-up assessment because of the lack of effective therapeutic choices. Only a few studies had investigated the value of ultrasound for spondyloarthritis follow-up. Recently, tumor necrosis factor alpha (TNF-α)–blocking agents have been demonstrated to have a strong and prompt effect on almost all features of spondyloarthritis, such as clinical disease activity, physical function, spinal mobility, peripheral arthritis, enthesitis, and acute-phase reactant levels.
Ultrasound has been used for detecting improvement in entheses and synovial involvement. The effect of sulfasalazine therapy on enthesitis was investigated in two studies, and both concluded that sulfasalazine was ineffective for enthesitis. These results may be attributed to the ineffectiveness of the therapy and to the old equipment used in the latter study, which was done in 1995, and to the use of only gray scale in both studies and no use of Doppler technique.
Evidence supporting the use of ultrasound combined with Doppler for monitoring pathologic findings indicative of soft tissue involvement in patients with spondyloarthritis has been provided by two case reports. Improvements in vascularization and structural changes were shown in the heel and retrocalcaneal bursa with the use of anti-TNF-α therapy and in the natural course of disease.
Few studies have focused on the treatment effects on synovitis. All were conducted in psoriatic arthritis patients. In rheumatoid arthritis patients, it was observed that ultrasound, especially when coupled with power Doppler, could be used objectively for following patients undergoing treatment. Accumulated data strongly suggest that it is possible to follow inflammatory changes at the enthesis and synovial joint level with ultrasound. There remain important reliability issues that must be answered before the method can be established for scientific and clinical purposes.
Until recently, no ultrasound data about the potential prognostic value of ultrasound for spondyloarthritis have been available.
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