Peripheral Seronegative Spondyloarthritis – Updates on Critical Criteria
In the past decade, new clinical and imaging criteria have vastly improved the diagnosis and outcome of patients with seronegative spondyloarthritis (SpA). Both axial and peripheral SpA have an approximate global prevalence of 1%. It is estimated that up to 30% of patients with SpA may exhibit predominant (or only) peripheral manifestations of SpA. Furthermore, in several documented cases, a diagnostic delay of up to 8–9 years has occurred and it is, therefore, essential to diagnose and treat SpA as early as possible. SpA affects both males and females equally and usually within their second decade of life. In those diagnosed with SpA, there is a strong association with human leukocyte antigen-B27, which can be present in more than 90% of patients. The clinical manifestation of peripheral SpA includes most of the features common to the other forms of SpA. Patients are often referred for isolated large joint imaging by various specialties such as orthopedics who may be unaware of symptoms and criteria related to SpA, as they may be focused on orthopedic specific pathology [Figure 1]. Thus, it is important that the radiologist raises the suspicion of SpA and specialist review in these cases to avoid potential delay in diagnosis and early intervention. Enthesitis on its own does not equate to SpA as enthesitis can be inflammatory, mechanical, or metabolic in nature. SpA can only be diagnosed in the appropriate clinical context which is why it is important to suggest specialist review in radiology report. The most commonly affected entheseal sites in SpA are shown in [Figure 2].
The characteristic of peripheral SpA is inflammation of the enthesis (a thin fibrous or fibrocartilaginous region joining the tendon or ligament to bone).[4,5] SpA is associated not only with synovitis but also with spondylitis (spinal inflammation), dactylitis (sausage digit), and enthesitis (inflammation of the ligament, tendon, or capsule-bone insertion). Synovitis is characterized by inflammation of the synovial membrane which differs from enthesitis, where only specific inflammation of the fibrocartilage entheseal complex occurs. The distribution of enthesitis is usually periarticular but can also occur at sites distant from the joints. Entheseal inflammation is triggered by an innate immune response. Immune cell migration and deposition of inflammatory infiltrate at the entheses usually facilitate vasodilatation and hyperemia, which are the earliest signs revealed on magnetic resonance imaging (MRI) and ultrasound (US). Bone marrow edema at the enthesis is also seen. In the late stage, the proposed inflammatory pathophysiology involves a local release of pro-inflammatory cytokines and growth factors from the enthesis causing a secondary synovitis. Chronic synovitis in SpA results in both bone and cartilage erosion analogous to rheumatoid arthritis. A well-described enthesis is the Achilles tendon and it can commonly be involved in SpA [Figure 3]. Microanatomical changes occurring at entheseal fibrocartilage are linked to specific imaging findings as follows: (1) Bone marrow inflammation – periarticular osteopenia, (2) enlarged transcortical vessels – cortical bone irregularities and erosions at insertion sites, and (3) osteoblast differentiation and mesenchymal proliferation – calcification and new bone formation.[4,5] The lower extremity entheses are more often involved in SpA compared to those of the upper extremities.[6,7] Heel enthesitis is the most common followed by enthesitis of the patella and the tibial tubercle.
The essentials of peripheral SpA classification
Broad division of SpA is based on the involvement of the spine and axial skeleton and split, respectively, into axial SpA and peripheral/non-axial SpA. The Assessment of SpA International Society (ASAS) has developed the classification criteria for SpA, with emphasis on the role of presenting symptoms and imaging findings. The classification of peripheral SpA requires two steps in the algorithm to make the diagnosis [Figure 4].
Until recently, imaging diagnosis relied on conventional radiography. Radiographic changes of sacroiliitis in SpA usually develop at least 5 years after symptom onset, with poor interobserver reliability, which lead to delayed diagnosis and treatment. MRI is now part of the ASAS classification criteria, in early detection, disease monitoring, and the diagnosis of complications of peripheral SpA manifestations. The assessment criteria, role of imaging, and findings in the sacroiliac joint in seronegative arthritis are well established, whereas non-axial findings on MRI are still being recognized. The understanding of the appropriate terminology applied in the rheumatological classification systems in combination with the divisions of SpA allows a clinical centered reporting strategy for the radiologist.[9,10] This will allow radiologists to suggest appropriate referral to a specialist and considers further imaging of the axial skeleton with appropriate clinical and immunological assessments to expedite diagnosis.
Both US and MR imaging are highly specific in detecting inflammatory and chronic enthesis-centered abnormalities. Clinically, enthesitis is often underdiagnosed due to low sensitivity and specificity of clinical tests. Therefore, imaging plays a key role. US features of enthesitis can show decreased echogenicity with thickening, calcification, and increased Doppler vascularity [Figure 5a,b]. Osseous surface irregularity may represent erosions or enthesophytes which may also clinch the diagnosis. Power Doppler imaging can often demonstrate increased signal suggesting synovial and fat pad inflammation.
MRI is sensitive in detecting enthesitis and can evaluate both soft tissue changes and intraosseous abnormalities of active enthesitis. In SpA, edema and inflammatory changes are diffuse and not confined only to the enthesis. Hallmark of enthesitis is bone marrow edema [Figures 6,7] as well edema and inflammatory foci within the perienthesis soft tissues [Figures 5c-d and 8-12]. More chronic enthesopathic changes manifest as erosions and enthesophytes, which are extensions of marrow contents isointense to the medullary bone. To evaluate enthesitis, one must assess a number of structures on MRI, as shown in Table 1. Typically, inflammatory MR findings manifest as areas of high signal on fluid-sensitive sequences and regions of low SI on T1- weighted (W) imaging. Structural lesions such as erosions or enthesophytes are best seen on T1W sequences. Other features of inflammation such as tenosynovitis should prompt the reporting radiologist to consider SpA. One must ensure that sequences are sensitive enough to detect marrow edema which can be affected by low-field strengths and field inhomogeneity when using inversion recovery sequences. Dixon algorithm-based sequences may be a solution to produce uniform fat suppression.
|Evaluation of enthesitis on MRI|
|Thickness and signal intensity of tendons and ligaments|
|Perientheseal soft tissues for swelling or edema|
|Adjacent bone marrow to detect edema, best appreciated as high signal in fat-suppressed sequences|
|Adjacent bone for erosions|
|Adjacent bone for enthesophytes|
|Additional findings in adjacent structures (e.g., effusion, bursitis, and capsulitis)|
MRI: Magnetic resonance imaging
Diffuse soft tissue swelling within a digit, with uniform thickness and the non-recognition of a joint swelling is characteristic of dactylitis. The disease process can involve the whole digit or a smaller proximal section. Dactylitis is frequently seen associated with psoriatic arthropathy where other features of psoriatic seronegative arthritis can be seen [Figure 13]. Within a dactylitic digit, both US and MRI play a crucial role in correctly delineating the specific tissue compartments involved. Flexor tendon tenosynovitis and joint synovitis are present nearly 90% of cases and can be easily identified in both modalities. Furthermore, evident in up to 30% of cases is extensor tendon inflammation with or without extratendinous soft tissue thickening. On MRI, bone marrow edema can be present usually within a painful digit.
Peripheral manifestations, especially enthesitis, dactylitis, and arthritis, are the hallmarks of SpA. Patients with joint pain can present to a number of medical specialties and may not come from rheumatology. Interpretation of imaging may be influenced by the referral specialty and imaging features of peripheral SpA can, therefore, often be misinterpreted. Unexplained ongoing pain in a peripheral joint containing fibrocartilage should prompt the radiologist to check for hallmarks related to SpA. It is important to be aware of the imaging features of peripheral SpA as the radiologist may be the first clinician to suggest a diagnosis of SpA.