High-Resolution Magnetic Resonance Imaging Assessment of Dactylitis in Psoriatic Arthritis shows flexor tendon pulley and sheath related enthesitis

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1 High-Resolution Magnetic Resonance Imaging Assessment of Dactylitis in Psoriatic Arthritis shows flexor tendon pulley and sheath related enthesitis Award: Certificate of Merit Poster No.: C-0114 Congress: ECR 2014 Type: Scientific Exhibit Authors: E. Fukuba 1, A. L. Tan 2, N. A. Halliday 2, D. McGonagle 2, H. Keywords: DOI: Kitagaki 1 ; 1 Izumo/JP, 2 Leeds/UK Inflammation, Imaging sequences, MR, Musculoskeletal soft tissue, Musculoskeletal joint /ecr2014/C-0114 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 21

2 Aims and objectives Dactylitis is a hallmark of psoriatic arthritis (PsA) occurring in 39% of PsA cases at diagnosis (1). It is characterized by diffuse swelling of the digit - described as a "sausage-like" appearance - and can also be seen, albeit less commonly, in other spondyloarthritides (SpA) including reactive arthritis, and in other settings including gout, sarcoidosis, flexor sheath infections, and sickle cell disease. It has been suggested that the enthesis is the initial site of inflammation in SpA including PsA (2). Relating to the enthesis concept, it has also been suggested that tendon pressure points over bone - or "functional entheses" - are part of the enthesis related pathology (3). There is some evidence that dactylitis is primarily the result of digital flexor tenosynovitis (4). Using conventional magnetic resonance imaging (MRI), Olivieri et al reported no evidence for enthesitis in dactylitis but tenosynovitis, synovitis and mild oedema of the peritendon area was observed (5, 6). Other ultrasound and MRI studies on dactylitis reported on soft tissue oedema, joint based synovitis and osteitis but not specifically enthesitis (7, 8). Previously we have shown the utility of high-resolution magnetic resonance imaging (hrmri) for exploring the microanatomical basis for osteoarthritis and PsA of the distal interphalangeal joints where we commonly observed enthesitis (9). The present study used hrmri to explore the microanatomical basis for PsA associated dactylitis by looking at the entheses and functional entheses related structures. Given the link with flexor tenosynovitis, we paid particular attention to the flexor tendon pulleys that are sites of high mechanical stress and that have thus far not been explored as potential drivers in dactylitis. Methods and materials Patients and methods Patients Twelve patients (3 female, 9 male: mean age of 43.9 years [range years]) with dactylitis due to PsA (mean disease duration 56 months [range months]) were recruited for this study, and provided written informed consent, following approval from the local ethics committee. Patients were invited to participate from rheumatology outpatient clinics. Page 2 of 21

3 MRI Magnetic resonance imaging was performed using a 1.5-Tesla whole-body scanner (Philips, Gyroscan Intera) and a high resolution surface coil. The worst affected dactylitic fingers or toes were imaged. All images were acquired with a slice thickness of mm with the exception of the T1-weighted spin-echo coronal and axial image sequences and the water selective excitation sequences where the slice thickness was 1-2 mm and 2-3 mm respectively. All 2-D images were obtained with a gap of 0.1 mm between slices. The following sequences were used to examine the microanatomical basis of patients' fingers or toes with dactylitis: T2-weighted sagittal or coronal image sequence with a fat-selective presaturation pulse: Repetition time (TR) 3500 msec, echo time (TE) 100 msec, flip angle (FA) 90, echo train length (ETL) 13 and displayed pixel dimensions of mm. Water-selective excitation 3D sagittal image sequence: TR msec, TE msec, FA 45 and a displayed pixel size of mm. Proton-density-weighted turbospin-echo coronal image sequence: TR 2000 msec, TE 17 msec, FA 90 and a displayed pixel size of mm. T1-weighted spin-echo coronal and axial image sequences; TR 475 msec, TE 18 msec, FA 90, and a displayed pixel size mm. Contrastenhanced fat-saturated T1-weighted coronal, sagittal and axial image sequences: TR msec, TE msec, FA 90, and a displayed pixel size of mm. Contrast-enhanced MR images were obtained within a few minutes after intravenous injection of 10 ml of the contrast agent, gadolinium diethylene-triaminepentaacetic acid (Gd-DTPA). Image analysis MR images were transferred to a personal desktop computer and analyzed using an image analysis software package ImageJ (National Institute of Health, Maryland, USA, The following structures were evaluated by consensus by a radiologist (EF) and a rheumatologist (DM): flexor and extensor tendons, extracapsular soft tissues, bone cortex, bone marrow, intracapsular synovium, pulleys in the fingers, fibrous sheaths in the toes, enthesis organs (collateral ligaments, and flexor and extensor tendons), volar plates in the fingers, and plantar plate ligaments in the toes. Signal intensity changes in the tendons, intracapsular synovium, extracapsular soft tissues and bone marrow were semi-qualitatively classified into four grades: none, mild, moderate and severe. Enthesitis on MR images was defined as the following: increased signal intensity changes adjacent to insertions or origins of the collateral ligaments or the flexor/ extensor tendons on fat-saturated T2-weighted, water-selective excitation or contrastenhanced fat-saturated T1-weighted images, and/or ligament swelling that extended to the entheses with increased signal. MRI-determined bone erosions were recorded when a cortical break was evident on T1-weighted images, on both coronal and axial images. Page 3 of 21

4 Osteophytes at either the origins or insertions of ligaments or at insertion of tendons were termed enthesophytes. Statistical analysis This is a small observational descriptive study, so no formal statistical analysis was performed. Proportions of abnormalities are described and presented as percentages of the total observations. Results Magnetic resonance images of 4 dactylitic fingers (2 thumbs, 1 index finger and 1 middle finger) and 8 dactylitic toes (3 big toes and 5 lesser toes) in 12 patients with PsA were acquired. A total of 22 joints (5 joints of the fingers [2 interphalangeal (IP) joints of the thumbs, 2 proximal IP (PIP) joints and 1 metacarpophalangeal joints) and 17 joints of the toes [3 IP joints of the big toe, 4 distal IP (DIP) joints, 5 PIP joints and 5 metatarsophalangeal (MTP) joints) were covered by these MRI acquisition. One toe of one participant had no MRI abnormalities at the time of image acquisition. Entheseal changes around the joints MR findings of enthesitis at insertions of the collateral ligaments were observed in 2 fingers and 7 toes (75%) (Figure 1A) and enthesitis of the extensor tendon insertions was seen in 2 fingers and 4 toes (50%) (Figure 1B, C). Abnormal increased enhancement in the volar plate was seen in 2 fingers (2/5 the finger joints (40%), mild) and in the plantar plate ligament of 1 toe (1/5 MTP joint (20%), moderate). In contrast, no participants showed the appearance of enthesitis at the flexor tendon insertions. Extracapsular and Synovial changes In keeping with the clinical appearances of dactylitis, 11 patients (92%) showed diffuse extracapsular soft tissue oedema where contrast enhancement was observed (10 cases - moderate, 1 case - mild). Abnormal increased signal intensities in 5 extensor tendons (all mild changes) of 5 subjects (one finger and four toes, 42% of all cases) were noted. One of these subjects with finger involvement had the extensor tendon lesion adjacent to the middle phalangeal bone protuberance. In one subject who had dactylitis of the big toe, the tendonitis extended to the insertion on the base of distal phalanx. In two toes subjects, the extensor tendon lesions were observed adjacent to the proximal phalangeal bone protuberance, and in one toe subject, the lesion was adjacent to the middle phalangeal base (Figure 2). Five joints of 4 fingers and 10 joints of 7 toes (68% of all 22 joints) had intracapsular synovial enhancement or fluid collection regarded as synovitis. Of those, Page 4 of 21

5 2 joints of 2 fingers and 9 joints of 7 toes showed moderate synovitis and 3 joints of 2 fingers and one joint of one toe demonstrated mild synovitis. Bone or bone marrow changes In 3 fingers and 7 toes (83%), diffuse or focal increased bone marrow signal intensities were observed (Figure 1). One finger and 6 toes had bone erosions at insertions or origins of the collateral ligaments. In the base of distal phalanges of two big toes (12% of all 17 joints of the toes), syndesmophytes or osteoproliferative changes were seen. Flexor Tendons and Tendon Pulleys/fibrous sheaths Disease Flexor tenosynovitis was seen in 3 fingers and 6 toes of 9 patients (75%). Of those, 7 patients showed mild to moderate diffuse tenosynovitis, and 2 patients mild focal tenosynovitis (Figure 1C). In 3 fingers and 6 toes of 9 patients (75%), the finger pulleys or fibrous sheaths in the foot could be seen as low signal intensity structures wrapped around the flexor tendons on contrast-enhanced fat-saturated T1-weighted axial and coronal images. In 3 fingers, the A2 (2 joints), A3 (one joint) and A4 (2 joints) pulleys were clearly identified, and in 6 toes, the fibrous sheaths were observed below the PIP joints of toes (5 joints) and the IP joint of big toe (one region). Of these, 2 fingers and 4 toes (50% of all cases) showed morphological or signal intensity abnormalities in the pulleys including A2 (ill-defined), A3 and A4 (oedematous) pulleys and the fibrous sheaths at 4 PIP joints (2 oedematous and 2 ill-defined) (Figure 3). The ill-defined A2 pulley and 2 fibrous sheath lesions had asymmetrical change at the pulley/fibrous sheath enthesis (Figure 3A). The oedematous A3, A4 pulleys and 2 fibrous sheaths of the toes showed symmetrical change at the attachment (Figure 3B, C, D). Images for this section: Page 5 of 21

6 Fig. 1: All images of figure 1 are fat-saturated contrast-enhanced T1-weighted images. Fig.1A: Coronal image of the left big toe of a 37 year old male. Bilateral collateral ligament insertions and origins showed mild to moderate enhancement (arrows). Mild to moderate bone marrow enhancement adjacent to the origins and insertions of the ligaments can also be seen (asterisks). Page 6 of 21

7 Fig. 2: Fig.1B: Sagittal image of the left big toe of same patient as Fig. 1A showing focal bone marrow enhancement at the extensor tendon insertion (arrow) and diffuse enhanced bone marrow (asterisk). Intracapsular synovium of the interphalangeal joint was swollen and moderately enhanced (arrowheads). Page 7 of 21

8 Fig. 3: Fig.1C: Sagittal image of the right middle finger of a 41 year old male. The extensor tendon insertion demonstrated mild enhancement (white arrow) with associated bone oedema (white outlined arrowhead). Diffuse enhancement of the flexor tenosynovium (white asterisks), extracapsular soft tissues (black asterisk), and moderate enhanced intracapsular synovium (black arrow) in the PIP joint were also seen. Page 8 of 21

9 Fig. 4: Fig.1D: Coronal image of the right 2nd toe of a 42 year old female. The base of the middle phalangeal bone was partially enhanced (arrow) what was adjacent to the extensor tendon insertion. Diffuse soft tissue enhancement was also shown (black asterisks). Page 9 of 21

10 Fig. 5: All images of figure 2 are water-selective excitation sagittal images. Fig.2A: Focal increased signal intensity lesion in the extensor tendon of the right 2nd toe (arrow) of a 59 year old female. Note that this lesion was adjacent to the proximal phalangeal bone protuberance which forms a "functional enthesis". Page 10 of 21

11 Fig. 6: Fig.2B: The left big toe of a 36 year old male. The signal of the extensor tendon of the toe was increased diffusely at the "functional" enthesis (arrow). Note that peritendinous soft tissue oedema was also shown (asterisks). Page 11 of 21

12 Fig. 7: Fig.2C: The right 2nd toe of a 42 year old female. Diffuse increased signal intensity lesion in the extensor tendon could be seen (arrows). Page 12 of 21

13 Fig. 8: Fig.2D: The left 4th toe of a 40 year old male. The signal of the extensor tendon was increased diffusely near the proximal phalangeal bone protuberance (white arrows). Enthesitis at insertion of the extensor tendon was also visible (black arrow). Page 13 of 21

14 Fig. 9: All images of figure 3 are fat-saturated contrast-enhanced T1-weighted axial images. Fig.3A: Interphalangeal joint of the left thumb of a 57 year old male. The A2 pulley region adjacent to the bone was unilaterally oedematous and ill-defined (white arrow). Area of enhanced high signal representing thickened flexor tenosynovium was also noted (black arrowhead). Page 14 of 21

15 Fig. 10: Fig.3B: Distal site of PIP joint of the left index finger of a 62 year old male. There was oedematous change at bilateral A4 pulley attachments (white arrows). Page 15 of 21

16 Fig. 11: Fig.3C: PIP joint of the left index finger of same patient as Fig. 3B. Symmetrical rim-like enhancement was observed around the A3 pulley (black arrows). The flexor tenosynovium was thickened as noted by the area of high signal (arrowhead). Page 16 of 21

17 Fig. 12: Fig.3D: PIP joint of the right 2nd toe of same patient as Fig. 2C showing oedematous change of the fibrous sheath (white arrows). Page 17 of 21

18 Conclusion This is the first study using high-resolution MRI to explore the microanatomic basis for dactylitis in patients with PsA. Previous studies using ultrasound and MRI have showed that dactylitis appears to be primarily caused by digital flexor tenosynovitis (4, 8). To the best of our knowledge, no studies have explained the link between tenosynovitis and enthesitis. Herein we demonstrate enthesitis is generally common in PsA dactylitis and that enthesopathy changes related to the flexor tendon pulleys and fibrous sheaths offers a novel explanation for the association with flexor tenosynovitis. Olivieri et al noted no evidence of enthesitis at the insertion of the flexor digitorum tendons and of attachment of the capsule of the digit joints (5, 6). Using high-resolution MRI, we likewise saw no disease at the flexor tendon insertions. However, we noted that the small entheses associated with the tendon pulleys and tendon sheaths could be the sites of enthesitis relevant to the tenosynovitis pathology. Although impossible to prove in man, our findings are supported by previous animal models of dactylitic like swelling where early changes were evident at insertions prior to the disease spreading to adjacent tissues(10, 11). A prominent feature of dactylitis is extra capsular soft tissue inflammation which has remained difficult to explain. Extensor tendonitis was identified adjacent to the phalangeal bone protuberance with inflammatory changes within the tendon at the point where it exerts pressure on adjacent bone during joint movement. This region has been dubbed as a "functional" enthesis unit, where the friction of the extensor tendon enthesis against the bone appears to be related to inflammation. An epicenter of inflammation within this structure, rather than primarily within the synovium, offers a novel explanation for some of the extracapsular inflammatory change evident in dactylitis. It has been proposed that PsA is due to microtauma or 'deep Koebner' phenomenon as recognized in skin psoriasis (12), an observation that has recently been supported by animal model data (13). How could dactylitis and in particular the findings at the pulleys be relevant to this concept? Although this study did not indicate a predominance of abnormality at any one pulley due to the small number of joints scanned, the A2 pulley is a common site for injury in rock climbers, suggesting that this area is subjected to a high friction load (14). Indeed the MR changes in injury in rock climbers bear some remarkable similarities with the changes reported in the present study (15). The main limitations of this study were the small numbers of patients and the lack of a control group. Nevertheless, the high-resolution nature of the MRI allowed detailed and Page 18 of 21

19 adequate depiction of changes in small regions of interest in the fingers and toes required to study the anatomical mechanism of dactylitis. In conclusion, we investigated the microanatomical basis for digital dactylitis in PsA using high-resolution MRI. This study suggests that the enthesitis observed in dactylitis is closely related to flexor tenosynovitis, which is a major factor of dactylitis. More importantly, we demonstrated that there were inflammatory changes at the intersection of digital pulleys and tendons, suggesting a form of "functional" enthesitis. This conforms to the knowledge that enthesitis is characteristic of PsA and uniquely explains that diffuse swelling along the digits observed in dactylitis is linked to poly-enthesitis. Personal information Eiji Fukuba MD, Department of Radiology, Faculty of Medicine, Shimane University, Izumo, Japan; e-fukuba@med.shimane-u.ac.jp Ai Lyn Tan MD MRCP, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK. Nicola Ann Halliday PhD, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK. Dennis McGonagle PhD, FRCPI, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK. Hajime Kitagaki MD, Department of Radiology, Faculty of Medicine, Shimane University, Izumo, Japan References 1. Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and response to therapy in the biologic era. J Rheumatol 2013;40: McGonagle D, Gibbon W, Emery P. Classification of inflammatory arthritis by enthesitis. Lancet 1998;352: Page 19 of 21

20 3. McGonagle D, Marzo-Ortega H, Benjamin M, Emery P. Report on the Second international Enthesitis Workshop. Arthritis Rheum 2003;48: Olivieri I, Barozzi L, Favaro L, Pierro A, DeMatteis M, Borghi C, et al. Dactylitis in patients with seronegative spondylarthropathy - Assessment by ultrasonography and magnetic resonance imaging. Arthritis Rheum 1996;39: Olivieri I, Salvarani C, Cantini F, Scarano E, Padula A, Niccoli L, et al. Fast spin echo- T2-weighted sequences with fat saturation in dactylitis of spondylarthritis - No evidence of entheseal involvement of the flexor digitorum tendons. Arthritis Rheum 2002;46: Olivieri I, Scarano E, Padula A, D'Angelo S, Salvarani C, Cantini F, et al. Fast spin echo-t2-weighted sequences with fat saturation in toe dactylitis of spondyloarthritis. Clin Rheumatol 2008;27: Healy PJ, Groves C, Chandramohan M, Helliwell PS. MRI changes in psoriatic dactylitisextent of pathology, relationship to tenderness and correlation with clinical indices. Rheumatology 2008;47: Kane D, Greaney T, Bresnihan B, Gibney R, Fitzgerald O. Ultrasonography in the diagnosis and management of psoriatic dactylitis. J Rheumatol 1999;26: Tan AL, Grainger AJ, Tanner SF, Emery P, McGonagle D. A high-resolution magnetic resonance imaging study of distal interphalangeal joint arthropathy in psoriatic arthritis and osteoarthritis - Are they the same? Arthritis Rheum 2006;54: Lories RJU, Matthys P, de Vlam K, Derese I, Luyten FP. Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 2004;63: McGonagle D, Lories RJU, Tan AL, Benjamin M. The concept of a "Synovio- Entheseal complex" and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 2007;56: McGonagle D, Benjamin M, Tan AL. The pathogenesis of psoriatic arthritis and associated nail disease: not autoimmune after all? Curr Opin Rheumatol 2009;21: Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis Crowley TP. The flexor tendon pulley system and rock climbing. J Hand Microsurg 2012;4: Guntern D, Goncalves-Matoso V, Gray A, Picht C, Schnyder P, Theumann N. Finger A2 pulley lesions in rock climbers - Detection and characterization with magnetic resonance imaging at 3 Tesla - Initial results. Invest Radiol 2007;42: Page 20 of 21

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