MRI of enthesitis of the appendicular skeleton in spondyloarthritis
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Abstract:
Entheses are sites where tendons, ligaments, joint capsules or fascia attach to bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of spondyloarthritis (SpA). As entheses are associated with adjacent, functionally related structures, the concepts of an enthesis organ and functional entheses have been proposed. This is important in interpreting imaging findings in entheseal-related diseases. Conventional radiographs and CT are able to depict the chronic changes associated with enthesitis but are of very limited use in early disease. In contrast, MRI is sensitive for detecting early signs of enthesitis and can evaluate both soft-tissue changes and intraosseous abnormalities of active enthesitis. It is therefore useful for the early diagnosis of enthesitis-related arthropathies and monitoring therapy. Current knowledge and typical MRI features of the most commonly involved entheses of the appendicular skeleton in patients with SpA are reviewed. The MRI appearances of inflammatory and degenerative enthesopathy are described. New options for imaging enthesitis, including whole-body MRI and high-resolution microscopy MRI, are briefly discussed.Keywords:
Enthesis
Enthesopathy
Appendicular skeleton
Spondyloarthropathy
Axial skeleton
Objective The aims were to assess prevalence of enthesitis among different subtypes of early spondyloarthropathy (SpA) and to evaluate specificity of entheseal involvement in such patients using ultrasonography and power Doppler. Background Enthesitis is one of the characteristic etiopathogenic manifestations of spondyloarthritis; however, in clinical practice, its presence often goes unnoticed. Ultrasound (US) can visualize most of the relevant enthesitis-associated pathologies such as bone erosions, calcification, bursitis, tendon structure, and thickness. Patients and methods A total of 80 patients with SpA with early disease duration and 20 controls (10 with mechanical low back pain and 10 with rheumatoid arthritis) of matched age and sex underwent ultrasonographic evaluation of entheses and were scored according to Madrid Sonographic Enthesitis Index. Patients were distributed as 36 patients with ankylosing spondylitis, 18 patients with reactive arthritis, and 26 patients with psoriatic arthritis. Results On clinical examination of entheses, 22.5% of the examined sites were abnormal as compared with US, which achieved higher sensitivity of 62.5%. Mean US score was significantly higher in patients with SpAs (22.6 ± 6.34) as compared with controls (P Conclusion The entheses US score may be useful for improving the diagnostic accuracy of early SpA, which is difficult to diagnose.
Spondyloarthropathy
Enthesis
Enthesopathy
Bursitis
Power doppler
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The 2 major categories of idiopathic inflammatory arthritis are rheumatoid arthritis and the seronegative spondyloarthropathies. Whilst the synovium is the primary site of joint disease in the former, the primary site in the latter is less well defined. However, it has recently been proposed that enthesitis‐associated changes in the spondyloarthropathies are primary and that all other joint manifestations are secondary. Nevertheless, some of the sites of disease localisation have not been adequately explained in terms of enthesitis. This article summarises current knowledge of the structure, function, blood supply, innervation, molecular composition and histopathology of the classic enthesis (i.e. the bony attachment of a tendon or ligament) and introduces the concept of ‘functional’ and articular ‘fibrocartilaginous’ entheses. The former are regions where tendons or ligaments wrap‐around bony pulleys, but are not attached to them, and the latter are synovial joints that are lined by fibrocartilage rather than hyaline cartilage. We describe how these 3 types of entheses relate to other, and how all are prone to pathological changes in spondyloarthropathy. We propose that the inflammatory responses characteristic of spondyloarthropathies are triggered at these seemingly diverse sites, in genetically susceptible individuals, by a combination of anatomical factors which lead to higher levels of tissue microtrauma, and the deposition of microbes.
Enthesis
Spondyloarthropathy
Fibrocartilage
Microtrauma
Hyaline cartilage
Enthesopathy
Synovial joint
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Enthesophytes and enthesopathy, while easy to define, represent a phenomenon of unclear clinical significance. As the high frequency in skeletal populations suggests that enthesopathy may not be disease-specific, the nature of the reaction was assessed in 872 individuals from a representative skeletal population, subdivided into groups characterized by the presence or absence of rheumatoid arthritis, spondyloarthropathy, calcium pyrophosphate deposition disease and diffuse idiopathic skeletal hyperostosis (DISH). Achilles, plantar fascia, patellar and iliac crest entheses were examined for evidence of calcific overgrowth or "erosions." Enthesophytes were found to be a phenomenon of aging in individuals, and unrelated to the presence of inflammatory arthritis or DISH. The frequency increased with age, independent of sex or the site examined, plateauing in frequency after age 60. Enthesophytes in individuals under age 60 were usually unrelated to any underlying disorder. The absence of effect of underlying forms of arthritis on the frequency of enthesophytes at the patellar, Achilles and plantar sites suggests that mechanical factors outweigh the "enthesis calcifying" impact of such disorders as spondyloarthropathy, calcium pyrophosphate deposition disease and DISH. Individuals with rheumatoid arthritis, however, manifested a less severe iliac crest enthesial reaction, in keeping with the minimal reactive new bone formation characteristic of its erosions. Analysis of Achilles, plantar, and patellar enthesial reactions as a function of underlying inflammatory arthritis or DISH also revealed no significant variation with the underlying process. Cortical discontinuity at enthesial sites was a relatively infrequent phenomenon. While calcaneal discontinuities were originally thought to be erosive in nature, these observations suggest the possibility of tendon avulsion injuries.
Enthesopathy
Spondyloarthropathy
Enthesis
Iliac crest
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Background
Enthesitis is one of the most common and specific manifestations of spondyloarthropathy (SpA). Ultrasonography has demonstrated to be a highly sensitive tool in the evaluation of entheses in patients with spondyloarthropathy (SpA).Objectives
The objectives of the study were to determine the prevalence of subclinical entheseal involvement in spondyloarthropathy patients in lower limbs.Methods
The study was included 25 patients with spondylarthritis – 15 with ankylosing spondylitis and 10 with psoriatic arthritis, without known history of entheseal involvement. Besides, 20 healthy sex- and age-matched controls were included. All patients with no clinical evidence of arthritis or enthesitis underwent an US examination. All US findings were identified according to GUESS. Clinical examination and ultrasound were consecutively performed at each of the entheses to detect signs indicative of enthesopathy.Results
A total of 246 enthesis in patients with ankylosing spondylitis and psoriatic arthritis (due to the psoriatic lesions on the knee) were evaluated by US. In 88 of 246 (35.77%) entheses, grayscale US found signs indicative of enthesopathy and in 17/246 (6.9%) entheses PD signal was detected. In the healthy population, US found signs of enthesopathy in 12 of 200 (6.0%) entheses and no PD signal was detected. The GUESS score was higher in patients with ankylosing spondylitis than in the psoriasis group, and both scores were significantly higher than in healthy controls (P<0.0001).Conclusions
Our results indicate that both grayscale US and PD findings demonstrate a higher sensitivity for enthesopathy of ultrasonography, with respect to physical examination indicative. Due to the US ability to detect signs of subclinical enthesopathy, further study is needed about the prognostic value of the ultrasound findings for predicting clinical onset of entheseal involvement.Disclosure of Interest
None DeclaredEnthesopathy
Enthesis
Spondyloarthropathy
Bursitis
Spondylitis
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Enthesis
Ankylosis
Axial skeleton
Enthesopathy
Spondylarthritis
Aponeurosis
Spondylitis
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Higher subclinical enthesitis on US has been reported in IBD and celiac disease, separately. The objective of this study was to compare IBD and celiac disease for enthesitis on US. Higher enthesitis scores in IBD compared with celiac disease would support a shared pathogenic mechanism between IBD and spondyloarthritis, whereas similar scores may suggest a general impact of gut inflammation on the enthesis.Patients with IBD, celiac disease and healthy controls (HCs) were recruited and 12 entheses were scanned by US, blind to the diagnosis and clinical assessment. Elementary lesions for enthesitis were scored on a scale between 0 and 3, for inflammation, damage and total US scores.A total of 1260 entheses were scanned in 44 patients with celiac disease, 43 patients with IBD and 18 HCs. The three groups were matched for age and BMI. Patients with celiac disease and IBD had higher inflammation scores than HCs [10.4 (6.5), 9.6 (5.4) and 5.6 (5.2), respectively, P = 0.007) whereas damage scores were similar. Both age and BMI had significant effects on the entheseal scores, mostly for inflammation scores but when controlling for these the US enthesopathy scores were still higher in celiac disease and IBD.The magnitude of subclinical enthesopathy scores is similar between celiac disease and IBD in comparison with HCs. These findings suggest that the common factor between both diseases and enthesopathy is abnormal gut permeability, which may be modified by the genetic architecture of IBD leading to clinical arthropathy.
Enthesopathy
Enthesis
Spondyloarthropathy
Subclinical infection
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There has been an increasing focus on enthesitis in psoriatic arthritis (PsA). Enthesitis, defined as inflammation at the insertion of tendons and ligaments into bone, has been proposed as the primary pathological lesion of PsA, and this hypothesis has received support from animal models that have focused on the enthesis in spondyloarthropathy-like disease1,2. Enthesitis is part of the entry "stem" for the ClASsification for Psoriatic ARthritis criteria (CASPAR) criteria, although it must be emphasized that only a few cases of PsA had isolated entheseal involvement in that study3. Yet the clinical evaluation of enthesitis remains a vexing problem. When delivering educational symposia, I am often asked by dermatology and rheumatology colleagues how to assess and treat enthesitis. To the dermatologists I say look only at the Achilles insertion because (1) it is readily identifiable, (2) it is the major enthesis of the body, and (3) involvement is quite specific for spondyloarthropathy (SpA). I caution against misinterpreting a fusiform swelling of the Achilles tendon 5–10 cm proximal to the insertion as insertional tendinitis — Achilles paratendinitis is quite common and mostly unrelated to SpA. To the rheumatologist I give the same advice, but also advise using a simple enthesitis index for assessment, such as the Leeds enthesitis index, in which the patient is queried about pain when pressure is applied at each lateral epicondyle, medial femoral condyle, and Achilles tendon insertion. I warn about overinterpreting pure entheseal disease without arthritis for 2 reasons. First, there is a consistently … Address correspondence to Dr. P.S. Helliwell, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Harehills Lane, Leeds LS7 4SA, UK. E-mail: P.Helliwell{at}leeds.ac.uk
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Enthesis
Enthesopathy
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Objective
Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthropathy (SpA). It was investigated whether normal and injured human enthesis, the key target tissue in early SpA, harboured ILC3s in entheseal soft tissue (EST) and adjacent peri-entheseal bone (PEB).
Methods
Interspinous ligament and spinous process bone was collected from donors with no systemic inflammatory disease, enzymatically digested and immunophenotyped. The immunological profile of entheseal cells was examined and the transcriptional profile of sorted ILC3s was compared to those isolated from SpA synovial fluid. To assess the ability of entheseal tissue to produce IL-17 and IL-22 entheseal digests were stimulated with IL-23 and IL-1β. Osteoarthritic and ruptured Achilles tissue was examined histologically.
Results
Compared to peripheral blood, human EST had a higher proportion of ILCs (p=0.008), EST and PEB both had a higher proportion of NKp44+ ILC3s (p=0.001 and p=0.043). RORγt, STAT3 and IL-23R transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and SpA synovial fluid. Normal entheseal digests stimulated with IL-23/IL-1β upregulated IL17A transcript and histological examination of injured/damaged entheses showed RORγt expressing cells.
Conclusion
This work shows that human enthesis harbours a resident population of ILC3s, with the potential to participate in spondyloarthropathy pathogenesis. This article is protected by copyright. All rights reserved.
Enthesis
Spondyloarthropathy
Innate lymphoid cell
Enthesopathy
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Ankylosing spondylitis (AS) is a chronic inflammatory condition affecting the axial skeleton, enthesis, and peripheral joints and is included in a group of disorders termed spondyloarthropathy. Its diagnosis is based on clinical and radiological features. This article reports an atypical case of AS in a 24-year-old female presenting with bilateral hip arthritis without any back symptoms. The report discusses the causes of delayed diagnosis and the relevance of thorough clinical examination.
Spondyloarthropathy
Enthesis
Axial skeleton
Spondylitis
Spondylarthropathies
Clinical Significance
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A report from a symposium held at Klinikum Benjamin Franklin, Free University, Berlin, Germany, 25–26 February 2000 This symposium was organised by J Braun and J Sieper (Free University, Berlin) to review the current knowledge of the anatomical, inflammatory, microbiological, and immunological events in enthesitis. The term "enthesopathy" is relatively new and its medical history short, but some important contributions can be listed (boxFB1). Figure FB1 History of "enthesopathy" • 1966 Enthesopathy first used by Niepel • 1970 Entheses centrally affected in ankylosing spondylitis, in contrast with rheumatoid arthritis (RA; Heberden oration lecture by Ball) • 1975 Some enthesitis in sacroiliitis (François) • 1983 Syndrome of seronegative enthesopathy and arthropathy in children (Rosenberg) • 1982 Sacroiliitis starts in the subchondral bone (Shichikawa) • 1991 Enthesopathy discriminative feature of spondyloarthropathy (SpA; European Spondyloarthropathy Study Group criteria, Dougados) • 1998 Entheses more commonly affected in arthritis in SpA compared with RA (McGonagle) The spondyloarthropathies are among the most common inflammatory rheumatic diseases.1 In addition to the strong genetic predisposition, partly due to HLA-B27,2 there are characteristic clinical features of SpA3: inflammatory back pain often due to sacroiliitis4 and enthesitis occurring mostly at various well defined locations, predominantly of the legs, such as the Achilles tendon, the plantar aponeurosis, the knee, the trochanter regions of the femur, and several pelvic sites.5 Thus entheses are ubiquitous, resulting in a diversity of associated pathological manifestations. Sacroiliitis is the most common early sign of SpA.6Whether or not ligamentous and entheseal structures are affected in sacroiliac inflammation has not yet been entirely clarified. To answer some of the most critical questions an expert symposium on enthesitis was organised:
Enthesopathy
Enthesis
Spondyloarthropathy
Bursitis
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