Enthesitis is one of the hallmarks of the spondyloarthritis (SpA) group, including psoriatic arthritis (PsA)1,2. Enthesitis is usually defined as inflammation at the site of attachment of a tendon, ligament, and capsule onto bone, which can cause significant pain and disability for patients2. In recent years, the interest in this domain of disease has grown with increasing evidence of its prevalence and potential importance in the pathogenesis of the disease3. One of the limitations in understanding the exact role of enthesitis in these diseases has been the difficulty in assessing this feature3,4. Usually enthesitis is evaluated by clinical assessment, which measured the pain provoked by physical examination of entheseal sites. However, tenderness at the entheseal site does not always denote inflammation, and its absence does not rule out enthesitis. The introduction of new drugs and the wider use of imaging, especially magnetic resonance imaging and ultrasound (US) in clinical and research practice, highlight the pivotal role of enthesitis for the diagnosis and management of both SpA (axial and peripheral) and PsA. Nevertheless, it has frequently been shown that clinical assessment of pain at tendon insertions does not always correlate with imaging assessment of inflammation5,6,7,8. The clinical examination of enthesitis may also identify pain from tendinosis, from nearby joint synovitis, or from other pain mechanisms without any true involvement of the adjacent enthesis.
In addition, it has been reported that a significant proportion of patients with PsA, and indeed patients with psoriasis, have subclinical enthesitis with inflammation seen on imaging, without tenderness at the insertion9.
US has been proven to be a valuable tool to assess entheseal involvement across the SpA spectrum, including PsA7,8,9. Extensive descriptions of the US findings defining enthesitis as well as the application of the technique as a management tool of both SpA and PsA have been published several times since the first observation by Lehtinen, et al in 19956,7,8,10,11,12.
In routine clinical practice, there has been an increase in the use of US for both diagnosis and monitoring of PsA. In borderline cases with psoriasis and musculoskeletal (MSK) pain, US can be very helpful to differentiate inflammatory synovitis or enthesitis from other common conditions including osteoarthritis (OA) and mechanical joint pain13,14,15. Once a diagnosis is established, US can also be used to quantify inflammation in joints and tendons if there is doubt in the clinical examination13.
The US appearance of enthesitis can be defined as a combination of morphological changes in greyscale and inflammatory findings in Doppler mode7,8,9,16. The Outcome Measures in Rheumatology (OMERACT) US group has established a definition of enthesitis and the different elementary inflammatory and structural components that can be visualized (hypoechogenicity, thickening, bone erosion, enthesophytes, calcification, Doppler signal) at entheses, as well as their scoring17,18. The development and validation process were performed on both SpA and PsA, allowing a standardization of this tool for research. Since the first OMERACT publication in 200419 proposing a preliminary definition of enthesopathy, and the more recent publication on which elementary features compose the enthesitis, an improvement in the quality of the published studies has been observed. Therefore, at the entheseal level, there is no need to develop new US scoring methods for detecting the presence of enthesitis.
The unmet questions at the moment are the following: Which and how many entheseal sites should be scanned for developing a scoring system at patient level? Should these entheseal sites be different according to the purpose of the US examination (i.e., diagnostic purpose or monitoring purpose)? And finally, should the entheseal sites examined in PsA differ from those examined in SpA?
In their study described in this issue of The Journal, Tom and colleagues tried to develop an entheseal scoring system at patient level that could identify which enthesis should be evaluated by US for detecting PsA20. They scanned a pre-defined set of entheses in 50 consecutive patients with active PsA to investigate US evidence of enthesitis. These patients were compared to 50 healthy controls who were similar in age and sex but did have a lower body mass index than the patients with PsA. In keeping with previous data, a significant proportion of patients (42%) had a clinically tender entheseal insertion, although this was also seen in 22% of controls. In the study, 11 different entheseal sites were scanned bilaterally20. The most frequent abnormalities, at entheseal level, found in PsA were enthesophytes, thickening, and hypoechogenicity, but these were also reasonably frequent in controls. In contrast, Doppler changes, bony proliferation, and erosions were less common (5–12% of PsA cases), but appeared to be more specific for PsA. When considering individual sites of enthesitis, key sites that differentiated PsA from controls were patellar ligament insertions, Achilles, plantar fascia insertion, common extensor tendon insertion at lateral epicondyle of the elbow, and supraspinatus insertion. These sites are similar to previously published reports8, with the addition of the greater trochanter insertion, which was not assessed in this study8.
Although the study provides further evidence of the high prevalence of entheseal changes in patients with PsA, and the high prevalence of asymptomatic findings (because the entheseal involvement was detected more frequently with US than with clinical assessment based on tenderness), it does not, however, answer completely the question of which sites are more specific for the presence of PsA and which should be scanned in priority21.
The results of this study highlight once again what has been recently published21,22: the discrepancy between clinical and US findings and the absence of correlation between clinical characteristics of active enthesitis and US inflammatory activity6,22.
The lack of correlation between clinical and US evaluation of enthesitis, as well as the different US definitions of enthesitis used to date, have generated discordant data about the capability of the technique to clearly differentiate between enthesis involvement in SpA or PsA and in other pathologies. A common US definition of enthesitis for the SpA group is therefore highly sought. This definition has been developed by the OMERACT US group17.
The OMERACT definition points out the importance of Doppler signal to distinguish between enthesitis in SpA or PsA and other pathologies or normal subjects. Although greyscale components are important for detecting the presence of structural changes, they are alone unable to differentiate between mechanical and inflammatory involvement7,23. The lack of discriminant capability of greyscale findings has been already reported6,23.
The results of this study20, along with those from the previous cited studies, lead to the question of whether inflammatory findings should be weighted more heavily than structural damage in the development of an US enthesitis score, at patient level, to differentiate better PsA-related enthesitis from other biomechanical factors potentially affecting the entheses.
In the Tom, et al study20, patients were compared to healthy controls, which does not mirror the potential use of US in diagnosis21. In this context it would be useful to follow on from this with a comparison of patients with psoriasis and other MSK complaints (e.g., OA, mechanical joint pain). This may help us understand the key differentiators to aid diagnosis of PsA within patients with psoriasis and MSK symptoms. Additional longitudinal data on patients with psoriasis who may develop PsA may also help us to understand more about the primary pathology of PsA and the spectrum of disease, and the role of the identified US lesions at different entheseal sites.
It is well recognized that clinical assessment of enthesitis has limitations and that imaging may have a key role to play in assessing this domain of PsA. Therefore, much effort should be put into keeping the field unified. There are 2 potential roles for imaging in this sphere: first, the opportunity to validate US as an outcome measure of enthesitis in PsA to be used in clinical practice. US definition of enthesitis and of the elementary lesions has been agreed on and published by the OMERACT US group. An extensive scanning protocol is currently being performed in a number of clinical trials. This will allow analysis of which features are sensitive to change in longitudinal studies and which sites of the body should be included in an optimal disease activity score.
Second, there is the potential to improve the use of US in diagnosis and classification of patients with PsA among those with psoriasis. Therefore, this study can be considered a first attempt to develop a US scoring system at the patient level that can identify which entheses should be scanned in patients with PsA and which lesions should be more weighted20. However, a big effort is required to identify specific inflammatory and structural changes that discriminate between disease and mechanical involvement.
Members of the GRAPPA US group have significant experience in longitudinal inception psoriasis cohorts, the OMERACT US group has developed a validated scoring, and there may be potential to include US in these studies, to support the differentiation of PsA from other MSK symptoms in patients with psoriasis.
Footnotes
See Sonographic enthesitis score, page 384
L.C. Coates is a UK National Institute for Health Research (NIHR) Clinician Scientist and Senior Clinical Research Fellow funded by an NIHR Clinician Scientist award. The research was supported by the NIHR Oxford Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the UK National Health Service, the NIHR, or the UK Department of Health.
