A Comprehensive Rheumatological and Immunological Approach to Diagnosis of Psoriatic Arthritis [1 ed.] 9781527557475, 9781527549272

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A Comprehensive Rheumatological and Immunological Approach to Diagnosis of Psoriatic Arthritis

A Comprehensive Rheumatological and Immunological Approach to Diagnosis of Psoriatic Arthritis Edited by

Syuichi Koarada

A Comprehensive Rheumatological and Immunological Approach to Diagnosis of Psoriatic Arthritis Edited by Syuichi Koarada This book first published 2020 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2020 by Syuichi Koarada and contributors All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-4927-5 ISBN (13): 978-1-5275-4927-2

TABLE OF CONTENTS Preface .......................................................................................................................................................................... vi Acknowledgements .....................................................................................................................................................vii Chapter 1 ....................................................................................................................................................................... 1 Introduction and classification of psoriatic arthritis Syuichi Koarada, Nobuyuki Ono, Yoshifumi Tada Chapter 2 ....................................................................................................................................................................... 7 A: Alignment in psoriatic arthritis Syuichi Koarada, Mariko Sakai Chapter 3 ..................................................................................................................................................................... 63 B1: Osteogenesis in psoriatic arthritis Syuichi Koarada, Yoshinobu Nakao Chapter 4 ................................................................................................................................................................... 205 B2: Resorption of the bones in psoriatic arthritis Syuichi Koarada, Yukiko Takeyama Chapter 5 ................................................................................................................................................................... 265 C: Capsula articularis of psoriatic arthritis Syuichi Koarada, Yuri Shirahama Chapter 6 ................................................................................................................................................................... 320 D: Distribution of abnormalities in psoriatic arthritis Syuichi Koarada, Satoko Tashiro Chapter 7 ................................................................................................................................................................... 343 E: Extracapsular manifestations in psoriatic arthritis Syuichi Koarada, Akihito Maruyama Chapter 8 ................................................................................................................................................................... 417 F: Further information and examination of psoriatic arthritis Syuichi Koarada, Mariko Sakai Chapter 9 ................................................................................................................................................................... 426 G: Goal of diagnosis of psoriatic arthritis and H: Healing and healthy condition in psoriatic arthritis Syuichi Koarada, Yoshinobu Nakao Chapter 10 ................................................................................................................................................................. 434 I: Immunology of psoriatic arthritis Syuichi Koarada, Yukiko Takeyama

PREFACE When the cherry blossoms bloomed at the banks of Tafuse River, this book, "psoriatic arthritis – comprehensive rheumatological and immunological approach to diagnosis of psoriatic arthritis with one thousand illustrations" was drafted in Saga, Japan. Psoriatic arthritis is a chronic rheumatic disease that involves the inflammation of joints, entheses and skins. Although psoriatic arthritis has been considered as a milder arthritis, in the past decade psoriatic arthritis has been proven to be potentially a serious disease like rheumatoid arthritis. The radiographic findings, clinical presentation and laboratory tests reveal that psoriatic arthritis is a distinct joint disorder. However, early diagnosis of psoriatic arthritis is not always easy. There are numerous excellent textbooks and monographs of psoriatic arthritis. However, there are few books that illustrate the imaging, diagnosis and immunity of psoriatic arthritis for beginners, step by step from the basics. This book uses more than one thousand radiographs, photographs, and diagrams to help readers understand. Of course, in this edition, there are parts that I have not written in, and I wish that beautiful flowers will be brought in the next edition when the cherry blossoms bloom based on readers’ opinions. Syuichi Koarada

ACKNOWLEDGMENTS The authors thank the reviewers and editors of Cambridge Scholars Publishing for their excellent work and giving us the opportunity to publish this valuable book. We would like to express our deep appreciation to our patients who provided valuable data and images. I would like to show my greatest appreciation to colleagues whose enormous support and insightful comments were invaluable during my study. I also owe a very important debt to assistants who provided technical help and sincere encouragement. I would also like to express my gratitude to my family, my parents, my wife, and my daughter, for their warm support and encouragements.

CHAPTER 1 INTRODUCTION AND CLASSIFICATION OF PSORIATIC ARTHRITIS

SYUICHI KOARADA, NOBUYUKI ONO, YOSHIFUMI TADA Abstract Psoriatic arthritis is an inflammatory disease of the bones and the joints related to psoriasis. In this book, characteristic findings of psoriatic arthritis in conventional radiography, ultrasound, MRI, CT, PET-CT, and bone scintigraphy are discussed. As a methodology, systematic interpretation based on ABCDEFGHI method is required to understand joint diseases. The purpose of this book is to present theoretical commentary as detailed as possible to allow a comprehensive interpretation of psoriatic arthritis. Introduction Psoriatic arthritis (PsA) is a common inflammatory disease that can lead to a wide range of pathological changes in the peripheral and the axial joints and the entheses associated with psoriasis [Brockbank J. 2002]. Therefore, psoriatic arthritis has diverse clinical and radiographic signs and changes [Firestein G.S. 2017]. Also, psoriatic arthritis is a member of the spondyloarthropathy family due to various clinical features of axis skeletal lesions [Moll J.M. 1973]. Although the exact cause of psoriasis and psoriatic arthritis is still unknown, it seems that a chronic multifactorial disease is contributed by complex interactions between genetic, the environment and immunologic factors [Barnas J.L. 2015]. Psoriatic arthritis was once thought to be a rheumatic disease with a good prognosis, but nowadays the disease is progressive and in the absence of appropriate treatment, joint destruction occurs, resulting in impaired function [Torre Alonso J.C. 1991] [S. R. Gladman D.D. 1987] [Ory P.A. 2005] [Siannis F. 2006]. For this reason, early intervention, diagnosis and treatment of psoriatic arthritis, is becoming more important. Patients with psoriatic arthritis can benefit from the initiation of appropriate treatment and maintenance of continuous immunotherapy [T. A. Gladman D.D. 2011] [Queiro-Silva R. 2003] [Theander E. 2014]. For this purpose, accurate diagnosis is necessary, and then differentiation of similar rheumatic diseases is indispensable. Psoriatic arthritis is in general difficult to define because of clinically heterogeneous findings. Psoriatic arthritis affects only the peripheral joints, the spine or the entheseal lesions. Psoriasis can occur after arthritis, and psoriatic arthritis without psoriasis (PsA sine psoriasis, sine syndrome) also exists. Psoriatic arthritis has historically been defined as negative for rheumatoid factors (RFs), but anti-citrullinated peptide antibodies (ACPA) may be positive in some cases [S. R. Gladman D.D. 1987]. Another reason for requiring an accurate diagnosis is that the treatment is different based on the pathophysiological state, which has a great influence on the prognosis of the disease. Since differential diagnosis of psoriatic arthritis is usually performed based on clinical, immunological and radiological findings, the knowledge of these aspects is indispensable for accurate diagnosis.

2

Chapter 1

Psoriatic arthritis has aspects of both osteoclastic changes and osteo-proliferations. Various lesions are generated due to the difference in degree of these bilateral natures, and as a result, various radiographic findings are formed. Literately, it is described that radiographic bone proliferative lesions are characteristic and are included in the classification criteria for psoriatic arthritis (CASPAR criteria) [Taylor W. 2006]. And psoriatic arthritis can also be diagnosed after clinical and radiographic features such as dactylitis, enthesitis, sacroiliitis, and spondylitis are taken into consideration [Coates L.C. 2012]. However, it seems to be easy to write like this, but it is impossible without comprehensive interpretation to lead to accurate diagnosis. Comprehensive interpretation is difficult without knowing the characteristics and changes depending on the organs and the sites, and typical and atypical cases. In this book, as a methodology, we recommend systematic interpretation based on ABCDEFGHI to understand joint diseases. The following describes the elements of psoriatic arthritis we are practicing. ABCDEFGHI method A: Alignment. In psoriatic arthritis, pencil-in-cup deformity is characterized as an abnormality of alignment, but psoriatic arthritis can also cause various deformities. B: Bones. Bone and joint lesions are the most varied and important findings of psoriatic arthritis. In psoriatic arthritis, there are severe marginal and central erosions as erosive changes and, as bone proliferative lesions, they cause fraying or irregularity of the bone surfaces around the joints. C: Capsula articularis. Joint space widening or narrowing, joint fluid, and synovitis are observed in psoriatic arthritis. D: Distribution of abnormalities. Distribution of abnormalities in the bodies is generally different between psoriatic arthritis and other rheumatic diseases and is a very important finding. E: Extracapsular manifestations. Extra-articular or extracapsular findings include bursitis, tenosynovitis, and enthesitis, soft tissue, muscular, and vascular involvements. Psoriatic arthritis has the various articular and the extraosseous lesions, and changes in the entheseal sites, the tendon and the ligament attachments, are typical. F: Further information and examination. Furthermore, the accuracy of diagnosis can be dramatically increased by accumulating various information and examination, including clinical history, epidemiologic factor, family history, clinical findings, examination data, and imaging.

Introduction and classification of psoriatic arthritis

3

G: Goals of diagnosis. Based on the above information of A to F, we conduct differential diagnosis, and according to classification criteria of psoriatic arthritis, we make a comprehensive judgement of diagnosis. H: Healing and healthy condition. Based on the diagnosis, we select and start the treatment, according to the degree of lesions, features, presence or absence of complications. After the starting of treatment, assessment of the reactivity for the treatment should be performed. I: Immunological aspects. An understanding of the immunopathology of psoriatic arthritis is important to improve diagnosis and treatment of patients with psoriatic arthritis. In this book, the radiological features of psoriatic arthritis and immune-mediated mechanism are discussed. Here, we describe the radiographic features of each target and joint. We discuss the characteristic findings of ultrasound, MRI, CT, PET-CT, and bone scintigraphy, and present the images of these modalities. Of course, it is impossible to describe everything in this small book, but the images are important for the diagnosis of this disease, and more detailed research of psoriatic arthritis is required. Classification of joint symptoms Psoriatic arthritis involves various subgroups, and the patterns of joint lesions are of several types. Moll and Wright Classification The classic disease of psoriatic arthritis is a polyarticular disorder with a predilection for the DIP (distal interphalangeal) joints of the digits, but various other clinical types are observed and historically, five clinical subgroups have been described (Table 1). The clinical patterns of subgroups described by Moll and Wright are as follows [Moll J.M. 1973]: symmetric polyarticular arthritis, asymmetric oligoarthritis, distal interphalangeal arthritis, spondylitis, and arthritis mutilans. Table 1: Moll and Wright criteria for psoriatic arthritis • Polyarticular, symmetric arthritis (Rheumatoid arthritis-like)

15%

• Oligoarticular (< 5 joints), asymmetric arthritis

70%

• Distal interphalangeal joint predominant

5%

• Spondylitis predominant

5%

• Arthritis mutilans

5%

The frequency of each of these subgroups is given as a percentage. Four of them involve the small joints of the hands and the feet, and two of the four subgroups are the DIP joint lesions and arthritis mutilans. Arthritis mutilans is usually the same as the DIP lesions, but patients with the DIP lesions do not always show arthritis mutilans. The remaining three subtypes are symmetric polyarthritis, asymmetric oligoarthritis, and spondyloarthritis. Furthermore, because patients with psoriatic arthritis may simultaneously have

Chapter 1

4

rheumatoid arthritis, osteoarthritis, and/or gout, in clinical practice, the pathophysiology of psoriatic arthritis is more complicated. The various types are listed below. Varied Patterns of Psoriatic Arthritis 1.

Asymmetric oligoarthritis type

Asymmetric oligoarthritis type has less than five large and/or small joint lesions in an asymmetric distribution. This type includes monoarthritis and asymmetric oligoarthritis. 2.

Symmetric polyarthritis type

Symmetric polyarthritis type is like rheumatoid arthritis and sometimes indistinguishable from it. This type is symmetric polyarthritis without laboratory findings specific for rheumatoid arthritis. 3.

Distal arthritis type

Distal arthritis type is characterized by polyarthritis of the DIP joint lesions.

4.

Spondyloarthritis type

Spondyloarthritis (SpA) type includes sacroiliac arthritis (sacroiliitis) and spondylitis resembling ankylosing spondylitis (AS). 5.

Arthritis mutilans type

Mutilans arthritis is a deforming type characterized by deformity and destructive arthritis. 6㸬Rheumatoid arthritis type Some patients with psoriatic arthritis have typical clinical features, positive serological tests, and specific findings of radiography of rheumatoid arthritis. The coincidence of psoriasis and rheumatoid arthritis is possible. It is controversial whether this condition should be a combination of rheumatoid arthritis by chance or psoriatic arthritis itself should be considered identical to rheumatoid arthritis in the patient. 7. Other types Some patients with psoriatic arthritis may have different patterns from typical ones. The patients have clinical findings of dactylitis, enthesitis mainly [C. F. Salvarani C. 1997], and diffuse pitting edema of the extremities [C. F. Salvarani C. 1999]. 8㸬Complex type Because some patients present more than one pattern, they belong to a complex type.

Introduction and classification of psoriatic arthritis

5

Alternation of the pattern of psoriatic arthritis The pattern of arthritis is not fixed, and so even with the same patient, the subtypes of arthritis may alter over time [Jones S.M. 1994] [Khan M. 2003]. Moreover, the condition of the patient will change, and treatment may also affect the pattern of arthritis. Using ultrasound, many patients classified as having oligoarthritis have been shown to be reclassified as polyarthritis [Freeston J.E. 2014]. This reclassification can lead to significant changes in prognosis and treatment of psoriatic arthritis. Chronological classification Psoriatic arthritis is also classified based on the chronological relationship between skin symptoms and arthritis. Skin lesions preceding arthritis In most adult patients, psoriatic arthritis usually appears after the onset of psoriasis. Skin involvement precedes the onset of arthritis in approximately 80-85% of cases, and arthritis typically develops about 10 years after the onset of psoriasis [Ritchlin C.T. 2017] [Boyle D.L. 2008]. Some patients may not know that they have psoriasis. Simultaneous onset of skin lesions and arthritis Arthritis may coincide with the appearance of skin lesions. The patients may also develop arthritis simultaneously with dactylitis and nail changes. Arthritis preceding skin lesions Arthropathy may precede classic cutaneous symptoms or nail lesions in a small percentage of patients. In some reports, about 15-20% of patients with psoriatic arthritis have arthritis prior to skin abnormalities [Scarpa R. 1984] [Pavlica L. 2005] [Boyle D.L. 2008]. Arthritis precedes skin lesions by more than 10 years in 1.6% of patients with psoriatic arthritis [Scarpa R. 1984]. Especially, in children, arthritis often precedes skin lesions. This may have led to difficulties and delayed diagnosis of psoriatic arthritis. Arthritis can persist for several years, with an unclear diagnosis until the appearance of skin or nail lesions of psoriasis [Taniguchi A. 2007]. Sine syndrome, Psoriatic arthritis sine (without) psoriasis Psoriatic arthritis without psoriasis is also rare. Sine syndrome is reported to appear in 1.8% of 162 PsA patients in a retrospective study [Pavlica L. 2005]. Clinically, a sine syndrome is characterized by arthritis of the DIP joints and dactylitis without skin lesions. In patients with arthritis preceding skin lesions, a diagnosis of psoriatic arthritis sine psoriasis is made until the skin lesions appear. The patients with the sine syndrome share features with arthritis patients with late-onset skin lesions [Taniguchi A. 2007]. In sine syndrome, there are three subgroups: the patients without psoriasis, but having first- and second-degree relatives with psoriasis, the patients with arthritis preceding skin lesions, and with persistent arthritis sine psoriasis.

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Chapter 1

References Barnas J.L., Ritchlin C.T. Etiology and Pathogenesis of Psoriatic Arthritis. Rheum Dis Clin North Am, 2015, 41:643. Boyle D.L., Kavanaugh A. The pathobiology of psoriatic synovium. Curr Opin Rheumatol, 2008, 20:404-407. Brockbank J., Gladman D. Diagnosis and management of psoriatic arthritis. Drugs 2002; 62:2447. Drugs, 2002, 62: 2447. Coates L.C., Hodgson R., Conaghan P.G., Freeston J.E. MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis. . Best Prac Res Clin Rheumatol., 2012, 26:805–822. Firestein G.S., Budd R.C., Gabriel S.E., et al. In Kelley and Firestein's Textbook of Rheumatology. 10th edn. Philadelphia, PA: Elsevier, 2017. Freeston J.E., Coates LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res, 2014, 66:432-9. Gladman D.D., Shuckett R., Russell M.L., et al. Psoriatic arthritis (PSA)--an analysis of 220 patients. Q J Med, 1987, 62:127. Gladman D.D., Thavaneswaran A., Chandran V., et al. Do patients with psoriatic arthritis who present early fare better than those presenting later in the disease? . Ann Rheum Dis, 2011, 70:2152–4. Jones S.M., Armas J.B., Cohen M.G., et al. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. . Br J Rheumatol, 1994, 33: 834. Khan M., Schentag C., Gladman D.D. Clinical and radiological changes during psoriatic arthritis disease progression. J Rheumatol 2003; 30:1022., 2003, 30:1022. Moll J.M., Wright V. Psoriatic arthritis. Semin Arthritis Rheum, 1973, 3:55-78. Ory P.A., Gladman D.D., Mease P.J. Psoriatic arthritis and imaging. Ann Rheum Dis, 2005, 64 Suppl 2: ii55–7. doi: 10.1136/ard.2004.033928. Pavlica L., Peric-Hajzler Z., Jovelic A., Sekler B., Damjanovic M. Psoriatic arthritis: a retrospective study of 162 patients. Vojnosanit Pregl, 2005, 62: 613-620. Queiro-Silva R., Torre-Alonso J.C., Tinture-Eguren T., et al. A polyarticular onset predicts erosive and deforming disease in psoriatic arthritis. . Ann Rheum Dis, 2003, 62:68–70. Ritchlin C.T., Colbert R.A., Gladman D.D. Psoriatic arthritis. N Engl J Med Overseas Ed, 2017, 376:957–70. Salvarani C., Cantini F., Olivieri I., et al. Isolated peripheral enthesitis and/or dactylitis: A subset of psoriatic arthritis. J Rheumatol, 1997, 24: 1106. Salvarani C., Cantini F., Olivieri I., et al. Distal extremity swelling with pitting edema in psoriatic arthritis: Evidence of 2 pathological mechanisms. J Rheumatol, 1999, 26:1831. Scarpa R., Oriente P., Pucino A., et al. Psoriatic arthritis in psoriatic patients. Br J Rheumatol, 1984, 25:246-250. Siannis F., Farewell V.T., Cook R.J., Schentag C.T., Gladman D.D. Clinical and radiological damage in psoriatic arthritis. Ann Rheum Dis, 2006, 65: 478–81. doi: 10.1136/ard.2005.039826 . Taniguchi A., Kamatani N. A case of psoriatic arthritis without the appearance of psoriatic skin or nail lesions for 21. APLAR Journal of Rheumatology, 2007, 10: 306-309. Taylor W., Gladman D., Helliwell P., et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum., 2006, 54:2665-2673. Theander E., Husmark T., Alenius G.M., et al. Early psoriatic arthritis: short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis. Ann Rheum Dis, 2014, 73:407–13. Torre Alonso J.C., Rodriguez Perez A., Arribas Castrillo J.M., Ballina Garcia J., Riestra Noriega J.L., Lopez Larrea C. Psoriatic arthritis (PA): a clinical, immunological and radiological study of 180 patients. Br J Rheumatol, 1991, 30:245–50.

CHAPTER 2 A: ALIGNMENT IN PSORIATIC ARTHRITIS SYUICHI KOARADA, MARIKO SAKAI Abstract Alignment is the placement of the bones. One bone is to be properly matched with the facing bone. In psoriatic arthritis, flexion contractures of the fingers and deformities occur mainly in the DIP joints. Destruction of the joints is particularly extensive in the late stage of the disease. Some patients have mutilans type arthropathy. Flexion contractures and deformities can also be seen in the PIP joints. By comparison with the digits, the carpal bones are relatively retained. The pencil-in-cup deformity is a characteristic change in psoriatic arthritis. There are ankyloses of the joints of the digits and few subluxations. Introduction Conventional radiography can show bone structure and is suitable for comprehensive evaluation of alignment. In psoriatic arthritis, malalignment, deformities and subluxation of the hands and the feet may occur. Severe joint destruction and deformity are features of psoriatic arthritis. Therefore, complete dissolution of bones, fragmentation and destruction of the joint structure occur, sometimes resembling neuropathic osteoarthropathy. Deviation and deformity of the hands and the feet are relatively common complications of psoriatic arthritis [Belsky M.R. 1982]. The deformation of psoriatic arthritis varies from mild deviations to severe destructive diseases (arthritis mutilans). Some patients may present deformity without severe joint pain. Sometimes erosions and ankyloses coexist in the same hands or the same digits that is a unique finding in psoriatic arthritis [Anandarajah A. 2013]. The patients with psoriatic arthritis have few boutonniere and swan-neck deformity compared with rheumatoid arthritis.

Figure 1. Deformities in psoriatic arthritis. The pencil-in-cup deformity and subluxation.

8

Chapter 2

Deviation Ulnar deviation of the metacarpophalangeal (MCP) joints and fibular deviation of the metatarsophalangeal (MTP) joints are not as common in psoriatic arthritis as in the cases of rheumatoid arthritis. However, ulnar and/or radial deviation of the distal interphalangeal (DIP) and/or the proximal interphalangeal (PIP) joints may be seen in psoriatic arthritis. DIP joints

Figure 2. A patient with psoriatic arthritis. Ulnar deviation of the right fifth DIP joint is observed.

Figure 3. A patient with psoriatic arthritis. Radial deviation of the left second DIP joint is observed.

A: Alignment in psoriatic arthritis

9

Figure 4. A patient with psoriatic arthritis shows the ulnar deviation of the right fifth DIP joint and radial subluxation of the distal phalanges of the thumbs.

Figure 5. A plain radiograph of the hands of a patient with psoriatic arthritis shows radial deviation of the distal phalange at the DIP joint of the right fifth digit.

10

Chapter 2

Figure 6. A patient with psoriatic arthritis. Radial deviation of the distal phalange at the DIP joint of the right third digit.

Figure 7. A plain radiograph of the left third digit of a patient with psoriatic arthritis shows radial deviation of the distal phalange of the DIP joint.

A: Alignment in psoriatic arthritis

Figure 8. A patient with psoriatic arthritis. Over time, mild ulnar deviation of the DIP joint is seen. PIP joints

Figure 9. A patient with psoriatic arthritis. Ulnar deviation of both the third PIP joints is seen.

11

12

Chapter 2

DIP and PIP joints

Figure 10. A radiograph of the left hand of a patient with psoriatic arthritis. Deviation and subluxation of the DIP and the PIP joints are observed. However, the MCP joints and the wrist are relatively preserved.

A: Alignment in psoriatic arthritis

13

Figure 11. A radiograph of the right fingers of a patient with psoriatic arthritis. Deviation of the DIP and the PIP joints is observed.

Figure 12. A radiograph of the hands of a patient with psoriatic arthritis. Deviation of the DIP, the PIP and the MCP joints is observed. However, both the wrist joints are relatively preserved.

14

Chapter 2

MCP joints

Figure 13. Radiograph of a patient with psoriatic arthritis. The deviation of the MCP joint of the left thumb is observed. The joint structure is partially destroyed and the bone surfaces on both sides of the joint overlap. Subluxation is a displacement of the joint beyond the midline, and this case still holds the midline.

Figure 14. Radiograph of a patient with psoriatic arthritis. Ulnar deviation of the right third MCP joint is observed.

Figure 15. A patient with psoriatic arthritis. The mild ulnar deviation of the right fourth MCP joint is seen.

A: Alignment in psoriatic arthritis

15

Figure 16. A patient with psoriatic arthritis. Ulnar deviation of the right fifth MCP joint is observed. Shoulders The shoulder joint is composed of the glenohumeral, the acromial humeral, and the acromioclavicular (AC) joint.

Figure 17. A patient with psoriatic arthritis. AP view of the shoulder. The left humeral head elevates and the narrowing between the humerus and acromion occurs due to the rotator cuff tear of the acromial humeral joint. Cup-and-pencil deformities, Pencil-in-cup deformities Classical deformity, which is called the cup-and-pencil or the pencil-in-cup deformity, produces the characteristic finding in psoriatic arthritis. Typically the finding is composed of the protrusion of a blunted osseous surface into a neighboring expanded base of the bone. In the small joints of the hands and the feet, including the DIP, the PIP, the IP, the MCP and the MTP joints, erosions begin on the lateral aspects of the joint and progress to more central areas over time and taper the end of the bone of involved phalanges. Because the heads or distal ends of the phalanges and the metacarpal bones are more resistant than the bases of the bone of corresponding joint, central pointed ends of proximal bones remain. Therefore, the pointed heads of the metacarpals and the phalanges by the destruction with severe bone erosions and resorption may result in protrusion into deep central erosions of the neighboring phalangeal expanded bases [Wassenberg S. 2015] [Zaias N. 1969].

16

Chapter 2

The pencil-in-cup deformity may be bilateral or unilateral and symmetric or asymmetric.

Figure 18. Image of the pencil in a cup, and the "Pencil-in-cup" deformity. Although this deformity is not specific for psoriatic arthritis and is also seen in other rheumatic diseases including rheumatoid arthritis and scleroderma, it is most commonly observed in psoriatic arthritis. Hands DIP joints

Figure 19. A patient with psoriatic arthritis. In the left second DIP joint, the cup-and-pencil (the pencil-in-cup) deformity is seen. The blunted and distorted bone surface of the head of the second middle phalange protrudes into the base of the adjacent enlarged base of the second distal phalange.

A: Alignment in psoriatic arthritis

17

Figure 20. A patient with psoriatic arthritis. The pencil-in-cup deformity of the left fourth DIP joint.

Figure 21. The pencil-in-cup deformity of the left third DIP joint of a patient with psoriatic arthritis.

Figure 22. A conventional radiograph of a patient with psoriatic arthritis shows the pencil-in-cup deformity of the right second DIP joint.

18

Chapter 2

IP joints Severe erosive deformity and bone proliferation of the thumbs result in the severe pencil-in-cup deformity of the interphalangeal joints.

Figure 23. Conventional radiographs of the left thumb of a patient with psoriatic arthritis show the pencil-in-cup deformity of the IP joint.

Figure 24. A conventional radiograph of the right thumb of a patient with psoriatic arthritis shows the pencil-in-cup deformity of the IP joint.

A: Alignment in psoriatic arthritis

19

Figure 25. A patient with Psoriatic arthritis. Plain radiograph shows the pencil-in-cup deformity of the IP joint with dislocation. PIP joints

Figure 26. The pencil-in-cup deformity of the PIP joint of the right fourth digit.

Figure 27. There is the pencil-in-cup deformity of the PIP joint of the right fifth digit.

20

Chapter 2

Figure 28. The pencil-in-cup deformity of the right fifth PIP joint of a patient with psoriatic arthritis. MCP joints

Figure 29. A conventional radiograph of a patient with psoriatic arthritis shows the pencil-in-cup deformity of the MCP joints of the left second digit.

A: Alignment in psoriatic arthritis

21

Figure 30. A patient with psoriatic arthritis. Plain radiograph shows the pencil-in-cup deformity of the right second MCP joint.

Figure 31. A patient with psoriatic arthritis. Plain radiograph shows the pencil-in-cup deformity of the right third MCP joint.

22

Chapter 2

Feet

Figure 32. A patient with psoriatic arthritis. Plain radiograph shows the pencil-in-cup deformity of the MTP joint of the right fifth toe. Cup-and-saucer deformities The bones of phalanges create rounded surfaces and may form deformity that resembles the cup-and-saucer appearance.

Figure 33. The cup-and-saucer deformity of the IP joint of a patient with psoriatic arthritis.

A: Alignment in psoriatic arthritis

Hands

Figure 34. The cup-and-saucer deformity of the left fourth DIP joint in a patient with psoriatic arthritis.

Figure 35. A patient with psoriatic arthritis. The cup-and-saucer deformity of the DIP joint.

Figure 36. A patient with psoriatic arthritis. The cup-and-saucer deformity with subluxation of the DIP joint.

23

24

Chapter 2

Feet

Figure 37. A patient with psoriatic arthritis. The cup-and-saucer deformity of the IP joint of the right first toe.

Figure 38. A patient with psoriatic arthritis. The cup-and-saucer deformity of the MTP joint of the left fourth toe.

Figure 39. A patient with psoriatic arthritis. The cup-and-saucer deformity of the IP joint of the left first toe.

A: Alignment in psoriatic arthritis

25

Figure 40. A patient with psoriatic arthritis. The cup-and-saucer deformity with the subluxation of the PIP joint of the right third toe.

Figure 41. A patient with psoriatic arthritis. The cup-and-saucer deformity with the subluxation of the DIP joint of the fourth toe. Mouse ears sign In the DIP joints, in early stages, erosions occur at the joint margins and lead to typical protuberances resembling “mouse ears”. These findings can be distinguished from the central erosions (seagull wings) found in erosive osteoarthritis.

Figure 42. Mouse ears sign in a patient with psoriatic arthritis.

26

Chapter 2

Seagull deformities The seagull deformity appears in the erosive osteoarthritis, but also in psoriatic arthritis. Because the heads of the proximal and the middle phalanges are more resistant than the corresponding joint bases, distal joint surfaces may be grinded down, and a central pointed end of proximal bone remains.

Figure 43. A patient with psoriatic arthritis. Mild seagull deformity of the right fourth DIP joint.

Figure 44. A patient with psoriatic arthritis. Seagull deformity of the right third DIP joint.

A: Alignment in psoriatic arthritis

Figure 45. A patient with psoriatic arthritis. Seagull deformity of the right third DIP joint over time.

Figure 46. A patient with psoriatic arthritis. The seagull deformity of the right fifth PIP joint.

Figure 47. Severe seagull deformity in a patient with psoriatic arthritis.

27

28

Chapter 2

Flexion contracture and flexion ankylosis Arthritis of the interphalangeal joints can form flexion contractures. In psoriatic arthritis, flexion ankylosis of the PIP and the DIP joints can be observed, but no significant osteoporosis is noted.

Figure 48. Psoriatic Arthritis. A radiograph of the right hand shows flexion ankylosis of the DIP joints.

Figure 49. A plain radiograph of a patient with psoriatic arthritis. PA view of the hands shows ankylosis of the DIP joints.

A: Alignment in psoriatic arthritis

29

Figure 50. Multiple flexion ankyloses of the PIP and the DIP joints in a patient with psoriatic arthritis. Mallet Fingers, Drop fingers Mallet fingers are relatively uncommon in psoriatic arthritis. The loosening or rupture of the distal attachments of the extensor tendons of the distal phalanges can lead to instability of mallet fingers or drop fingers of the DIP joints.

Figure 51. A patient with psoriatic arthritis. A photograph shows mallet finger of the right third DIP joint.

30

Chapter 2

Figure 52. A patient with psoriatic arthritis. Mallet finger of the right second DIP joint is seen.

Figure 53. A patient with psoriatic arthritis. Severe destructive mallet finger of the right second DIP joint is seen.

Figure 54. A patient with psoriatic arthritis. Mallet finger of the right second digit over time.

A: Alignment in psoriatic arthritis

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Arthritis mutilans In psoriatic arthritis, less frequently, destructive and deforming condition of arthritis mutilans can occur [Moll J.M. 1973]. Arthritis mutilans is defined as the condition, in which more than 50% of the articular surfaces on both sides of the joint are osteolytic [Haddad A 2013]. Mutilans arthritis is a form of severe disability of psoriatic arthritis that greatly impairs the patient's functional capacity and thus requires strict control and treatment of the disease. Arthritis mutilans can eventually progress to the opera-glass deformity. Hands Arthritis mutilans results from psoriatic arthritis, with destructive changes and joint deformity of the hands.

Figure 55. A patient with psoriatic arthritis. Arthritis mutilans with destructive changes and radial subluxation of the IP joint of right thumb is observed.

Figure 56. A patient with psoriatic arthritis. A conventional radiograph of the right second digit shows arthritis mutilans of the DIP joint.

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Feet Patients with psoriatic arthritis may demonstrate osteolysis of the toes of the feet.

Figure 57. A patient with arthritis mutilans of psoriatic arthritis. A plain radiograph of the toe clearly demonstrated as osteolysis of the right second digit.

Figure 58. A patient with arthritis mutilans. A plain radiograph shows osteolysis of the left fifth PIP joint. Opera-glass deformities, telescoping of fingers Opera-glass deformity is severe osseous destruction with shortening of the phalanges and telescoping of one bone on its adjacent bone. The findings are relatively characteristic in psoriatic arthritis. Pharyngeal bone resorption and destructive arthritis of the DIP joints are often associated with nail lesions in the same digits.

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Figure 59. A patient with psoriatic arthritis. A plain radiograph of the patient shows arthritis mutilans of the first to the fifth distal phalanges.

Figure 60. Mutilating form of the hands in a patient with psoriatic arthritis. A plain radiograph shows telescoping and volar and dorsal subluxation and luxation of the MCP, and the DIP joints of the digits corresponding to late psoriatic arthritis. The patient with psoriatic arthritis shows telescoping of the DIP and the PIP joints, and the overlap of the skin of the fingers can be confirmed on the oblique view.

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Concertina-like appearance By the opera-glass hand, excess skin may be folded over resulting in a concertina-like appearance.

Figure 61. A patient with psoriatic arthritis shows a concertina-like appearance.

Figure 62. A patient with psoriatic arthritis. The excess skin is folded at the involved IP joint of the left thumb.

Figure 63. A patient with psoriatic arthritis. The excess skin is folded at the involved DIP and PIP joints of both the hands.

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Figure 64. A patient with psoriatic arthritis. The excess skin is folded at the involved DIP joints.

Figure 65. A patient with psoriatic arthritis shows a concertina-like appearance of both the hands.

Figure 66. A patient with psoriatic arthritis shows a concertina-like appearance.

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Figure 67. Plain radiographs of the third digit, obtained 10 years apart, indicate progression of a concertina-like appearance.

Figure 68. A patient with psoriatic arthritis. A plain radiograph also shows a concertina-like appearance.

Figure 69. A patient with psoriatic arthritis. The change of arthritis mutilans with concertina-like appearance over time.

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Destruction of the bones and joints In patients with psoriatic arthritis, complete bone dissolution, fragmentation, and joint destruction can occur.

Figure 70. Destruction of the DIP joint in a patient with psoriatic arthritis. The normal structure of the DIP joint disappears completely. Button-hole deformities, Boutonnière deformities Button-hole deformity (boutonnière deformity) consists of hyperextension at the DIP joint and flexion at the PIP joint. Boutonniere deformity may be seen in patients with psoriatic arthritis, but not as much as in patients with rheumatoid arthritis.

Figure 71. Button-hole deformities of a patient with psoriatic arthritis.

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Figure 72. Button-hole deformities of the right third and fourth digits are seen in a patient with psoriatic arthritis.

Figure 73. Button-hole deformities of both the second digits are seen in a patient with psoriatic arthritis. Swan-neck deformities Swan-neck deformity may occur in a patient with psoriatic arthritis but is not common. Swan-neck deformity consists of hyperextension at the PIP joint and flexion at the DIP joint, due to tenosynovitis of the flexor tendon.

Figure 74. A mild swan-neck deformity of the right third digit is seen in a patient with psoriatic arthritis.

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Figure 75. A swan-neck deformity of the left second digit is seen in a patient with psoriatic arthritis. Hitchhiker deformities Hitchhiker deformity consists of flexion of the MCP joint and hyperextension of the IP joint of the thumb.

Figure 76. A patient with psoriatic arthritis. Hitchhiker deformity of the left thumb is seen.

Figure 77. A patient with psoriatic arthritis. Hitchhiker deformities of the thumbs. Severe destructive changes and luxation of the IP joints can be seen.

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Deformities of the forefeet Hallux valgus deformity and various degrees of cock-up deformity of the lateral toes may be seen. Deformity of the forefeet of psoriatic arthritis includes fibular deviation of the toes (except for the fifth digit) and dorsal/volar/lateral subluxation (luxation) of the proximal phalanges at the MTP joints. Hallux valgus deformities Hallux valgus deformity is defined as lateral deviation of the hallux (great toe) in the first MTP joint. The hallux valgus angle (HVA), which is between the longitudinal axes of the proximal phalange and the first metatarsal bone of the hallux, is greater than 15–18°. The HVA angle grades the severity of hallux valgus deformity as mild: 15–20°, moderate: 21–39°, and severe: • 40° [Cerrato R 2016].

Figure 78. A patient with psoriatic arthritis. There are ankylosises of the fourth DIP joints and hallux valgus deformities of the big toes. Digitus minimus varus deformities

Figure 79. In psoriatic arthritis, digitus minimus varus deformity can be observed.

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"Cock-up" deformities

Cock-up deformity consists of dorsiflexion of the MTP joint and flexion of the PIP and DIP joints.

Figure 80. Cock-up deformity of a patient with psoriatic arthritis. The toes with deformities overlap the dorsal aspects of the next toes. Triangular deformities The forefeet may exhibit characteristic triangular deformities. Triangular deformity is defined as the hallux valgus with lateral deviation of the second, the third and the fourth toes and/or digitus quintus varus.

Figure 81. Triangular deformity of a patient with psoriatic arthritis. Fibular deviation and subluxation occur at the first to the fourth toes of the left foot (except for the fifth toe).

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Figure 82. Triangular deformity of a patient with psoriatic arthritis. Fibular deviation, subluxation/luxation of the toes and digitus minimus varus occur at the first to the fourth toes of the left foot. Subluxation and luxation Joint subluxation and luxation may be present in patients with psoriatic arthritis. Subluxation and luxation are ulnar, radial, and/or volar/dorsal in the hands. They are tibial, fibular, and volar/dorsal in the feet. Subluxation and severe luxation are also characteristic in the terminal stage of psoriatic arthritis [Wassenberg S. 2015]. DIP joints

Figure 83. Luxation of the second DIP joint is seen in a patient with psoriatic arthritis who also has nail lesions.

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Figure 84. A patient with psoriatic arthritis. The change of subluxation to the posterior of the distal phalange in the right fifth DIP joint over time. PIP joints Some patients may have subluxation of the PIP joints of the hands.

Figure 85. A patient with psoriatic arthritis shows subluxation of the left second PIP joint.

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IP joints of the thumbs Severe dorsal subluxation or luxation of the distal phalanges may be observed at the IP joint of the thumbs in patients with psoriatic arthritis.

Figure 86. A patient with psoriatic arthritis shows radial dorsal luxation of the distal phalanges of the thumbs.

Figure 87. A patient with psoriatic arthritis. "Pencil-in-cup" deformity of the IP joint of the thumb with dislocation.

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MCP joints There are subluxation and luxation of the proximal phalanges at the MCP joints.

Figure 88. PA view of the left second MCP joint in a patient with psoriatic arthritis shows that alignment appears to be normal. However, oblique view demonstrates palmar subluxation (white line) of the second MCP joint.

Figure 89. Oblique view of the right second MCP joint in a patient with psoriatic arthritis shows palmar subluxation.

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Figure 90. A patient with psoriatic arthritis shows ulnar subluxation of the right fifth MCP joint. MTP joints

Figure 91. A patient with psoriatic arthritis shows subluxation of the right first MTP joint.

Figure 92. A patient with psoriatic arthritis shows subluxation of the left first MTP joint.

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Figure 93. A patient with psoriatic arthritis shows subluxation of the right third MTP joint. Cervical spine Radiographs of anteroposterior (AP), lateral, and open-mouth odontoid views obtained in a neutral position are necessary to evaluate the cervical spine.

Figure 94. Radiographical anatomy of the cervical spine.

Figure 95. Plain radiographs of anteroposterior (AP) and lateral views. Flexion, neutral, and extension positions of the cervical spine.

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Flexion, neutral and extension positions can be used to measure the atlantodens interval (ADI) and prove instability. Atlantoaxial subluxation may occur, although the facet joints are relatively spared in psoriatic arthritis. Killebrew et al. reported that subluxation is at 45% of 20 patients with psoriatic spondylitis [Killebrew K 1973]. Anterior atlantoaxial subluxation is the most common form of instability in the occipito-atlanto-axial region, but lateral, rotatory and vertical subluxations can also occur. Rarely, subaxial and/or lower cervical instability with cord compression is found in some patients with psoriatic spondylitis [Fam AG 1982] [Lassoued S 1989] [Pease CT 1987]. Lower cervical instability with discovertebral erosions resembles the findings observed in rheumatoid arthritis [Lassoued S 1989].

Figure 96. Anatomy of the atlas (the first cervical vertebra). Anterior atlantoaxial subluxation In atlantoaxial subluxation, anterior subluxation is predominant. When an anterior subluxation is present, the distance between the posterior aspect of the anterior arch of the atlas and the anterior aspect of the dens (ADI: atlantodens or atlantodental interval) exceeds 3 mm in a neutral position and/or during flexion. Expansion of the ADI suggests incompetent transverse ligament and denotes instability. Anterior atlantoaxial subluxation can cause narrowing of the atlantoaxial canal presenting as a posterior atlantodental (-dens) interval (PADI) of less than 14 mm.

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Figure 97. Atlantodens interval (ADI) and posterior atlantodental (-dens) interval (PADI).

Figure 98. Anterior atlantoaxial subluxation can cause narrowing of the atlantoaxial canal. Lateral and rotatory atlantoaxial subluxation In psoriatic arthritis, lateral instability, resembling rheumatoid arthritis, is also observed [Yeadon C 1983]. The lateral mass of the atlas is displaced at least 2 mm with respect to the axis. The lateral mass is asymmetric with respect to the dens. Lateral subluxation is diagnosed on open-mouth anterior-posterior (AP) view.

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Figure 99. Open-mouth anterior-posterior (AP) view of a normal person. There is narrowing of the atlantoaxial joint with superficial bone erosion and lateral displacement of the axis relative to the lateral masses of the atlas.

Figure 100. Open-mouth anterior-posterior (AP) view of a patient with psoriatic arthritis shows superficial bone erosion (arrow) and lateral displacement of the axis relative to the lateral masses of atlas. Anterior subluxation and lateral subluxation coexist because of anatomical proximity of the atlas and the axis; however, anterior subluxation predominates. Atlantoaxial rotary subluxation (ARS) The atlantoaxial joint is responsible for 50% of the rotation in the craniocervical region, and rotatory dislocation, atlantoaxial rotary subluxation (ARS), displacement, and fixation may occur. The asymmetric distances between the lateral masses and dens are findings of rotatory displacement. The anteriorly displaced lateral mass appears wider and closer to the midline than the posteriorly displaced lateral mass.

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Figure 101. Atlantoaxial rotary subluxation (ARS). Anteriorly displaced lateral mass appears wider and closer to the midline. Stenosis of the spinal canal can occur due to severe rotation with the competent transverse ligament. Posterior atlantoaxial subluxation Posterior atlantoaxial subluxation with the moving of the anterior arch of the atlas over the odontoid process is rarely seen. However, posterior atlantoaxial subluxation may coexist with fracture of the dens. Vertical atlantoaxial subluxation Vertical subluxation can be fatal because of the proximity of the dens to the medulla oblongata and the proximal portion of the spinal cord. In patients with a flexion instability and erosive changes in the atlantoaxial and/or atlantooccipital joints, vertical subluxation with projections of the dens into the occipital foramen occurs, and there is a risk of compression and injury of the spinal cord.

Measurement methods of vertical atlantoaxial subluxation It is recommended to combine the Redlund-Johnell method and the Clark and Ranawat method for the diagnosis of vertical subluxation [Riew KD 2001]. When any of the method suggests vertical subluxation, MRI should be considered to visualize the spinal cord. McRae’s line Vertical atlantoaxial subluxation, also referred to as atlantoaxial impaction, basilar invagination, or cranial setting, is defined as the prominence of the odontoid tip with respect to the McRae’s line corresponding to the occipital foramen. McGregor’s line McGregor’s line is between the postero-superior aspect of the hard palate and the most caudal point of the occipital curve. Vertical subluxation occurs when the tip of the dens moves more than 4.5 mm from McGregor line.

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Figure 102. Lateral view of cervical spine with McGregor’s line. A lateral radiograph in a neutral position shows the McGregor’s line drawn between the posterior-superior aspect of the hard palate and the most posterior point of the occipital curve. Ranawat’s method

Figure 103. Ranawat’s method. Determination of the distance between the center of the second cervical pedicle and the transverse axis of the atlas [Riew KD 2001]. A distance less than 15 mm in men and less than 13 mm in women suggests vertical subluxation [Riew KD 2001]. However, the occurrence of bone erosion of the dens makes this measurement difficult.

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Redlund-Johnell method and Pettersson’s method

Figure 104. The Redlund-Johnell method. The Redlund-Johnell method is based on the minimum distance between McGregor’s line and the midpoint of the inferior margin of the axial vertebral body in the lateral view of a neutral position [Riew KD 2001]. The distance is used to evaluate vertical subluxation by the Redlund-Johnell and the Pettersson’s method. The distance less than 34 mm for men and less than 29 mm for women is vertical subluxation. The Clark’s method Visualization of the palate and dens is not always available. Therefore, a method has been introduced in which the dens and/or the palate is not required as landmarks [Riew KD 2001]. The axis is divided into three equal parts in the lateral view, and the position of the atlas is assessed. Mild vertical subluxation is suggested when the anterior arch is in the level with the middle third of the axis (II), and severe vertical subluxation if the caudal third of the axis (III).

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Figure 105. Clark’s method. Sagittal CT reconstruction of the cervical spine of a normal subject.

Figure 106. MRI of the cervical spine in a patient with neck pain. The image of the anterior arc of the atlas in the level of the middle third of the axis suggests mild vertical subluxation. Lower cervical vertebrae The lower cervical vertebrae are the C3 to the C7, also referred to as the subaxial region. The vertebrae are similar in structure. The vertebral bodies of the lower cervical spine have protruding structures on the lateral sides called the uncinate processes. These processes form the uncovertebral joints with the upper vertebral body also called the joints of Luschka.

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Figure 107. Lateral view of the lower cervical vertebrae.

Figure 108. Luschka's joints (uncovertebral joints). Anterior subluxation Anterior subluxation is defined as at least 3 mm forward slippage of the vertebra relative to the lower vertebra by a radiographical image including the lateral view in a flexion position. If the diameter of the spinal canal is less than 14 mm, it suggests the possibility of compression of the spinal cord [Kim DH 2005].

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Olisthesis Olisthesis is slipping or sliding of the lumbar spine in any directions. Forward displacement (forward slip) can be specifically referred to as anterolisthesis. Backward displacement is called retrolisthesis. Lateral displacement is called lateral olisthesis or laterolisthesis.

Figure 109. Olisthesis. Anterolisthesis and retrolisthesis.

Figure 110. Lateral views of the cervical spine of a patient with psoriatic arthritis show mild retrolisthesis at the C5-C6 level.

Figure 111. Lateral views of the lumbar spine of a patient with psoriatic arthritis show retrolisthesis at the L3-L4 level.

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Military neck Military neck is a term used to describe the loss of the normal curve in the cervical spine.

Figure 112. Military neck in a patient with psoriatic arthritis. Scoliosis Scoliosis is a sideways curvature of the spine.

Figure 113. Scoliosis at the thoracolumbar junction in patient with psoriatic arthritis.

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Figure 114. AP view of the lumbar spine shows scoliosis in a patient with psoriatic arthritis. Temporomandibular joints Changes of the temporomandibular joints include malpositions and limited mobility. Collapse

Figure 115. A patient with psoriatic arthritis. Carpal collapse can be seen in the hands. Carpal height is used to assess the severity of carpal collapse. Carpal height The carpal height is defined as the distance between the base of the third metacarpal bone and the subchondral bone cortex of the distal radius. However, there are individual variations, and it is more appropriate to calculate and evaluate the carpal height ratio. The carpal height ratio is calculated by dividing the carpal height by the length of the third metacarpal bone [Youm Y 1978]. The normal range of the carpal height ratio is commonly between 0.51 and 0.57.

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Collapse of naviculars

Figure 116. A patient with psoriatic arthritis. Collapse of the navicular of the right foot. Fractures Feet

Figure 117. A fracture is found in the proximal part of the right fifth metatarsal in a patient with psoriatic arthritis. Lumbar spine Patients with psoriatic arthritis may have compression fractures of the lumbar spine and severe degenerative lumbar spondyloses. Although the use of CT is very limited in the spine, it is useful when there is suspected vertebral fracture but negative signs of radiography.

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Figure 118. A patient with psoriatic arthritis has compression fractures and severe degenerative lumbar spondylosis. Pubic fractures

Figure 119. Pubic fractures in a patient with psoriatic arthritis.

Figure 120. Pubic fracture in a patient with psoriatic arthritis.

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Figure 121. Enlarged image of pubic fracture of a patient with psoriatic arthritis. References Anandarajah A., Anandarajah. Imaging in psoriatic arthritis. Clin Rev Allergy Immunol. 2013;44(2):157–65. doi: 10.1007/s12016-012-8304-4. Clin Rev Allergy Immunol, 2013, 44:157–65. doi: 10.1007/s12016-012-8304-4. Barnas J.L., Ritchlin C.T. Etiology and Pathogenesis of Psoriatic Arthritis. Rheum Dis Clin North Am, 2015, 41:643. Belsky M.R., Feldon P., Mullender L.H., et al. Hand involvement in psoriatic arthritis. J Hand Surg, 1982, 7:203. Boyle D.L., Kavanaugh A. The pathobiology of psoriatic synovium. Curr Opin Rheumatol, 2008, 20:404-407. Brockbank J., Gladman D. Diagnosis and management of psoriatic arthritis. Drugs 2002; 62:2447. Drugs, 2002, 62: 2447. Cerrato R, Cheney N. Hallux Valgus. American Orthopaedic Foot & Ankle Society., 2016, Retrieved 2016-12-30. Last reviewed June 2015. Coates L.C., Hodgson R., Conaghan P.G., Freeston J.E. MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis. . Best Prac Res Clin Rheumatol., 2012, 26:805–822. Fam AG, Cruicksank B. Subaxial cervical subluxation and cord compression in psoriatic spondylitis. Arthritis Rheum, 1982. Firestein G.S., Budd R.C., Gabriel S.E., et al. In Kelley and Firestein's Textbook of Rheumatology. 10th edn. Philadelphia, PA: Elsevier, 2017. Freeston J.E., Coates LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res, 2014, 66:432-9. Gladman D.D., Shuckett R., Russell M.L., et al. Psoriatic arthritis (PSA)--an analysis of 220 patients. Q J Med, 1987, 62:127. Gladman D.D., Thavaneswaran A., Chandran V., et al. Do patients with psoriatic arthritis who present early fare better than those presenting later in the disease? . Ann Rheum Dis, 2011, 70:2152–4. Haddad A, Chandran V. Arthritis mutilans. Curr Rheumatol Rep., 2013, 15(4):321. doi: 10.1007/s11926-013-0321-7 . Jones S.M., Armas J.B., Cohen M.G., et al. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. . Br J Rheumatol, 1994, 33: 834. Killebrew K, Gold RH, Sholkoff SD. Psoriatic spondylitis. Radiology, 1973, 108:9. Kim DH, Hilibrand AS. Rheumatoid arthritis in the cervical spine. J Am Acad Orthop Surg, 2005, 13:463–474. Lassoued S, Hamidou M, Fournie A, et al. Cervical spine involvement in psoriatic arthritis. J Rheumatol, 1989. Moll J.M., Wright V. Psoriatic arthritis. Semin Arthritis Rheum, 1973, 3:55-78. Pavlica L., Peric-Hajzler Z., Jovelic A., Sekler B., Damjanovic M. Psoriatic arthritis: a retrospective study of 162 patients. Vojnosanit Pregl, 2005, 62: 613-620. Pease CT, Pozo JL. Atlantoaxial subluxation and spinal cord compression in psoriatic arthropathy. Ann Rheum Dis, 1987. Queiro-Silva R., Torre-Alonso J.C., Tinture-Eguren T., et al. A polyarticular onset predicts erosive and deforming disease in psoriatic arthritis. . Ann Rheum Dis, 2003, 62:68–70. Riew KD, Hilibrand AS, Palumbo MA, Sethi N, Bohlman HH. Diagnosing basilar invagination in the rheumatoid patient. The reliability of radiographic criteria. J Bone Joint Surg Am, 2001, 83:194–200. Ritchlin C.T., Colbert R.A., Gladman D.D. Psoriatic arthritis. N Engl J Med Overseas Ed, 2017, 376:957–70. Salvarani C., Cantini F., Olivieri I., et al. Isolated peripheral enthesitis and/or dactylitis: A subset of psoriatic arthritis. J Rheumatol, 1997, 24: 1106.

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Salvarani C., Cantini F., Olivieri I., et al. Distal extremity swelling with pitting edema in psoriatic arthritis: Evidence of 2 pathological mechanisms. J Rheumatol, 1999, 26:1831. Scarpa R., Oriente P., Pucino A., et al. Psoriatic arthritis in psoriatic patients. Br J Rheumatol, 1984, 25:246-250. Taylor W., Gladman D., Helliwell P., et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum., 2006, 54:2665-2673. Wassenberg S. Radiographic scoring methods in psoriatic arthritis. Clin Exp Rheumatol, 2015, 33 (Suppl. 93): S55-9. Yeadon C, Dumas J-M, Karsh J. Lateral subluxation of the cervical spine in psoriatic arthritis: A proposed mechanism. Arthritis Rheum, 1983. Youm Y, McMurthy RY, Flatt AE, Gillespie TE. Kinematics of the wrist. An experimental study of radial-ulnar deviation and flexion-extension. J Bone Joint Surg Am, 1978, 60:423-431. Zaias N. Psoriasis of the nail: A clinico-pathological study. Arch Dermatol, 1969, 99:567.

CHAPTER 3 B1: OSTEOGENESIS IN PSORIATIC ARTHRITIS SYUICHI KOARADA, YOSHINOBU NAKAO

Abstract The principle of bone changes in psoriatic arthritis is the coexistence of osteolysis and osteogenesis within the same places. Bone proliferation occurs in four categories including bone excrescences, periostitis, ankyloses, and syndesmophytes. Recently, it has become important to evaluate bone marrow edemas by MRI and bone erosions by ultrasound. In this chapter, we discuss these characteristic features about the bones of psoriatic arthritis. Part B1 is osteogenesis of bones in psoriatic arthritis. Introduction Assessment of the bones in psoriatic arthritis includes bone mineralization and bone morphology. There are systemic and periarticular bone mineralization. Normal mineralization and the lack of periarticular osteopenia are the typical features of psoriatic arthritis. Recently, it has become possible to evaluate bone marrow edemas by MRI and bone erosions by ultrasound. The principle of bone changes in psoriatic arthritis is the coexistence of osteolysis and osteogenesis within the same microenvironment [Kapitonova M.Y. 2003]. Bone proliferation occurs in four categories including bony excrescences, periostitis, ankyloses, and syndesmophytes. Bone mineralization Generalized mineralization is evaluated by observing the metacarpal shaft (diaphysis) of the second or the third digit. Systemic osteoporosis can be judged by the sum of the two cortices in relationship to the width of the diaphysis. The finding of the maintenance of normal mineralization helps to distinguish psoriatic arthritis from rheumatoid arthritis.

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Figure 122. The bone density of the diaphysis of the second metacarpal suggests the diagnosis of normal mineralization. On the center line drawn to the diaphysis, the sum of two cortices is more than half the width of the shaft. In later stage of psoriatic arthritis, generalized osteoporosis may be present and is exacerbated by arthritis.

Figure 123. Mild osteoporosis is present in a patient with psoriatic arthritis. On the center line drawn to the diaphysis, the sum of two cortical bones is less than half the width of the shaft.

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Figure 124. Generalized osteoporosis in a patient with psoriatic arthritis treated with corticosteroids. Periarticular bone density In psoriatic arthritis, usually there is no pronounced periarticular osteoporosis. Normal mineralization and the lack of periarticular osteopenia are typical features of psoriatic arthritis. The lack of osteoporosis and the propensity for bone proliferation are useful distinguishing features of psoriatic arthritis from rheumatoid arthritis. In particular, the presence of erosions in the small joints without bone osteopenia is of great diagnostic value. However, the presence of osteoporosis does not eliminate the diagnosis of psoriatic arthritis, because periarticular osteopenia may be observed in the early stage of the disease and some patients with psoriatic arthritis may have periarticular and generalized osteoporosis (less frequent than in rheumatoid arthritis). Frediani et al. reported that demineralization was observed in more than 2/3 of patients with psoriatic arthritis without axial involvement [Frediani B. 2001]. However, it is known that the assessment of periarticular bone density relies heavily on radiographic techniques. Periarticular osteopenia in the early stages Juxta-articular osteoporosis (periarticular osteopenia) is not a hallmark of psoriatic arthritis but can be demonstrated in the early stage of the disease. In the early stages of the disease, there may be transient juxta-articular osteoporosis, but restoration of normal bone mineralization without permanent changes is seen in most patients. Furthermore, when bone density is analyzed in a more sensitive technique than conventional radiography, osteoporosis is commonly found in more cases of psoriatic arthritis [Frediani B. 2001].

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DIP joints

Figure 125. Psoriatic arthritis. A radiograph of the right hand shows ankyloses and periarticular osteoporosis of the DIP and PIP joints. PIP joints

Figure 126. A radiograph shows juxta-articular osteoporosis, especially in the PIP joints of the hands of a patient with psoriatic arthritis.

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MCP joints

Figure 127. A patient with psoriatic arthritis. A radiograph of the right hand demonstrates changes, including joint space narrowing, osteosclerosis and significant osteoporosis of the MCP joints.

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Lack of osteoporosis Usually, no periarticular osteopenia is observed in patients with psoriatic arthritis. Normal mineralization is usually well maintained even in the presence of severely erosive and destructive disease in patients with psoriatic arthritis.

Figure 128. Despite the chronic changes of the disease, including joint space narrowing and bone excrescences of the DIP joints in a patient with psoriatic arthritis, bone mineralization had been normal over time (10 and 5 years ago).

Figure 129. Bone mineralization has been normal over time, even with a destructive disease of psoriatic arthritis.

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Figure 130. A radiograph of the hands of a patient with psoriatic arthritis shows preservation of bone mineral density in the DIP and PIP joints. Hands DIP joints

Figure 131. A patient with psoriatic arthritis. A radiograph of the hands shows chronic changes, including joint space narrowing and osteosclerosis mainly at the DIP joints. However, there is no significant osteoporosis.

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PIP joints

Figure 132. A patient with psoriatic arthritis. A radiograph of the right hand demonstrates changes, including joint space narrowing, osteosclerosis and bone proliferation at the PIP and DIP joints, but the lack of significant osteoporosis.

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Wrists Mineralization tends to be maintained in the wrists of psoriatic arthritis. Even severe pan compartmental involvement of the wrists with joint space narrowing, intra-articular osseous fusion, multiple erosions, and bone proliferation does not have severe osteoporosis.

Figure 133. A patient with psoriatic arthritis. A radiograph of the hands demonstrates severe changes, including joint space narrowing, intra-articular osseous fusion, multiple erosions, and bone proliferation in the wrists, but the lack of significant osteoporosis. Knees

Figure 134. A patient with psoriatic arthritis. Mineralization of the left knee is maintained.

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Feet In the feet, generally the mineralization is maintained. Lesions are primarily in the interphalangeal and MTP joints and are characterized by the lack of osteoporosis. Osteosclerosis The hallmark of disease progression is subchondral sclerosis due to reactive bone growth. Patients with psoriatic arthritis have osteosclerosis in the joints.

Figure 135. Osteosclerosis in a patient with psoriatic arthritis occurs initially at the back of the joint without joint space narrowing.

Figure 136. A patient with psoriatic arthritis. Subchondral sclerosis by reactive bone proliferation is observed at the DIP joints of both the hands.

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Findings of joints DIP joints Second DIP joints

Figure 137. Osteosclerosis of the right second DIP joints in patients with psoriatic arthritis.

Figure 138. Although mild osteosclerosis of the right second DIP joint was observed from the early stage, over time there is an increase in osteosclerosis. Joint space narrowing is not seen in the early stage, which is different from osteoarthritis. However, at the end of the disease, joint space narrowing has occurred, and it is practically difficult to distinguish psoriatic arthritis from osteoarthritis.

Figure 139. There are severe erosive changes; the joint space is rather widened due to destructive arthritis. Osteosclerosis appears even though joint space has not narrowed.

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Figure 140. Widening of the joint space is confirmed in oblique view.

Figure 141. Osteosclerosis of the left second DIP joint of a patient with psoriatic arthritis has appeared over time.

Figure 142. Osteosclerosis of the left second DIP joints in patients with psoriatic arthritis. Third DIP joints

Figure 143. Osteosclerosis of the right third DIP joints in patients with psoriatic arthritis.

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Figure 144. Osteosclerosis of the left third DIP joints in patients with psoriatic arthritis. Fourth DIP joints

Figure 145. Osteosclerosis in a patient with psoriatic arthritis. Osteosclerosis at the back of the right fourth DIP joint without joint space narrowing is observed.

Figure 146. Osteosclerosis with bone proliferation in a patient with psoriatic arthritis. Osteosclerosis at the back of the right fourth DIP joint is observed.

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Figure 147. A patient of psoriatic arthritis. Osteosclerosis with multiple erosions (arrows) of the right fourth DIP joint.

Figure 148. Osteosclerosis of the left third DIP joints in patients with psoriatic arthritis.

Figure 149. Osteosclerosis with joint space narrowing of the left fourth DIP joint is progressive in a patient with psoriatic arthritis over time. Fifth DIP joints

Figure 150. Osteosclerosis of the right fifth DIP joints in patients with psoriatic arthritis.

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Figure 151. Osteosclerosis of the left fifth DIP joints in patients with psoriatic arthritis.

Figure 152. PA and oblique views of the left fifth DIP joint of a patient with psoriatic arthritis. Osteosclerosis with bone proliferation at the back of the joint is observed. IP joints

Figure 153. Osteosclerosis of the right IP joints of the thumbs in patients with psoriatic arthritis. Osteosclerosis is observed at the back of the joints (arrows).

Figure 154. Osteosclerosis of the left IP joints of the thumbs in patients with psoriatic arthritis. Osteosclerosis is observed at the back of the joints.

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PIP joints Second PIP joints

Figure 155. Osteosclerosis of the right second PIP joints in patients with psoriatic arthritis.

Figure 156. Osteosclerosis of the left second PIP joints in patients with psoriatic arthritis. Third PIP joints

Figure 157. Osteosclerosis of the right third PIP joints in patients with psoriatic arthritis.

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Figure 158. Osteosclerosis in a patient with psoriatic arthritis. Osteosclerosis without joint space narrowing is observed in the right third PIP joint.

Figure 159. Osteosclerosis of the left third PIP joints in patients with psoriatic arthritis. Fourth PIP joints

Figure 160. Osteosclerosis of the right fourth PIP joints in patients with psoriatic arthritis.

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Figure 161. PA and oblique views of the right fourth PIP joint of a patient with psoriatic arthritis. Osteosclerosis with joint space narrowing is observed at the back of the joint.

Figure 162. Osteosclerosis of the left fourth PIP joints in patients with psoriatic arthritis. Fifth PIP joints

Figure 163. Osteosclerosis of the right fifth PIP joints in patients with psoriatic arthritis.

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Figure 164. Osteosclerosis of the left fifth PIP joints in patients with psoriatic arthritis. MCP joints First MCP joints

Figure 165. Osteosclerosis of the right first MCP joints in patients with psoriatic arthritis.

Figure 166. Osteosclerosis of the left first MCP joints in patients with psoriatic arthritis.

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Second MCP joints

Figure 167. Osteosclerosis of the right second MCP joints in patients with psoriatic arthritis.

Figure 168. Osteosclerosis of the left second MCP joints in patients with psoriatic arthritis. Third MCP joints

Figure 169. Osteosclerosis of the right third MCP joints in patients with psoriatic arthritis.

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Figure 170. Osteosclerosis of the left third MCP joints in patients with psoriatic arthritis. Fourth MCP joints

Figure 171. Osteosclerosis of the right fourth MCP joints in patients with psoriatic arthritis.

Figure 172. Osteosclerosis of the left fourth MCP joints in patients with psoriatic arthritis.

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Fifth MCP joints

Figure 173. Osteosclerosis of the right fifth MCP joints in patients with psoriatic arthritis.

Figure 174. Osteosclerosis of the left fifth MCP joints in patients with psoriatic arthritis. Shoulders

Figure 175. Osteosclerosis of the humeroscapular joint and the acromion of the left shoulder is observed in a patient with psoriatic arthritis.

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Figure 176. Osteosclerosis of the greater tubercles of the humeral heads and a subacromial spur of the left shoulder are observed in a patient with psoriatic arthritis.

Figure 177. Mild osteosclerosis of the greater tubercles (arrow heads) of the humeral heads and osteohypertrophy of the acromion (arrow) are observed in a patient with psoriatic arthritis. Hips

Figure 178. Osteosclerosis of the right hip in a patient with psoriatic arthritis.

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Figure 179. Osteosclerosis of the left hip in a patient with psoriatic arthritis. Knees

Figure 180. Osteosclerosis of the right knee in a patient with psoriatic arthritis.

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Figure 181. Osteosclerosis of the right knee in a patient with psoriatic arthritis. Osteosclerosis predominantly occurs on the articular surfaces and at the entheses.

Figure 182. Osteosclerosis of the left knee in a patient with psoriatic arthritis. Osteosclerosis predominantly occurs on the articular surfaces and at the entheses.

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Figure 183. AP views of the knees show mild osteosclerosis in a patient with psoriatic arthritis.

Figure 184. Lateral views of the knees show mild osteosclerosis in a patient with psoriatic arthritis.

Figure 185. Sunrise views of the knees show osteosclerosis of the patellae in a patient with psoriatic arthritis. Osteosclerosis predominantly occurs on the articular surfaces of the patellae.

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Ankles

Figure 186. AP and lateral views of the ankles show mild osteosclerosis in a patient with psoriatic arthritis.

Figure 187. AP views of the ankles show osteosclerosis with juxta-articular osteoporosis in a patient with psoriatic arthritis.

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Figure 188. Lateral views of the ankles show osteosclerosis with juxta-articular osteoporosis in a patient with psoriatic arthritis.

Figure 189. AP views of the ankles show mild osteosclerosis in a patient with psoriatic arthritis.

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Calcaneuses In the calcaneus, extensive osteosclerosis often occurs at the enthesis of the Achilles tendon and the plantar ligament. Enthesitis may have osteosclerosis with irregular and poorly defined enthesophyte at the attachment site.

Figure 190. There is osteosclerosis at the attachment of the Achilles tendon of the right calcaneus in a patient with psoriatic arthritis. Osteosclerosis of the entire inferior surface of the calcaneus occurs.

Figure 191. Osteosclerosis of the entire inferior surfaces of the calcaneuses is observed in a patient with psoriatic arthritis. However, there is no bone proliferation. Osteosclerosis of the inferior surfaces of the calcaneuses is associated with the plantar bone excrescence.

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Figure 192. Osteosclerosis of the inferior surface of the calcaneus with bone proliferation is seen in a patient with psoriatic arthritis. Enthesitis may have osteosclerosis with irregular bone erosions at the attachment site of the Achilles tendon.

Figure 193. Osteosclerosis (arrow) with bone erosion at the attachment of the Achilles tendon (arrowhead) is observed in a patient with psoriatic arthritis. Bone proliferation (dashed arrow) is seen at the inferior surface of the calcaneus.

Figure 194. Osteosclerosis of the entire inferior surfaces of the calcaneuses with bone erosions at the attachment of the Achilles tendons (arrows) is evident in a patient with psoriatic arthritis.

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Figure 195. Osteosclerosis of the right first MTP joints in patients with psoriatic arthritis.

Figure 196. Osteosclerosis of the left first MTP joints in patients with psoriatic arthritis.

Figure 197. Osteosclerosis of the right second MTP joints in patients with psoriatic arthritis.

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Sacroiliac joints In patients with psoriatic arthritis, osteosclerosis with osseous erosions and joint space irregularity of the sacroiliac joints occurs. There is osteosclerosis, but osteosclerosis of the iliac side predominates. Some patients have large erosions and extensive bone repair.

Figure 198. Subchondral osteosclerosis and widening of the joint space of the sacroiliac joints indicate bilateral sacroiliitis in a patient with psoriatic arthritis.

Figure 199. Osteosclerosis of the sacroiliac joints indicate bilateral sacroiliitis in a patient with psoriatic arthritis.

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Figure 200. A PET-CT image shows sacroiliitis of the sacroiliac joints in the same patient with psoriatic arthritis.

Figure 201. A radiograph of the sacroiliac joints reveals joint space narrowing and sclerosis with blurring of the interosseous spaces in a patient with psoriatic arthritis.

Figure 202. Bilateral mild sclerosis of the sacroiliac joints is found in a patient with psoriatic arthritis.

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Figure 203. The sclerosis of the lower parts of the sacroiliac joints is found in a patient with psoriatic arthritis.

Figure 204. Sclerosis with joint space widening of the sacroiliac joints is observed in a patient with psoriatic arthritis.

Figure 205. Unilateral sclerosis of the left sacroiliac joint is found in a patient with psoriatic arthritis.

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Figure 206. Sclerosis of the sacroiliac joints is observed in a patient with psoriatic arthritis.

Figure 207. Sclerosis of the sacroiliac joints is observed in a patient with psoriatic arthritis.

Figure 208. Plain CT of a patient with psoriatic arthritis. Osteosclerosis of the sacroiliac joints is stronger on the iliac sides.

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Figure 209. Plain CT of a patient with psoriatic arthritis. Osteosclerosis of the sacroiliac joints is found. When bony ankyloses occur across the sacroiliac joints, sclerosis may disappear. Pelvis

Figure 210. Osteosclerosis of the ligament attachments of the pelvis in a patient with psoriatic arthritis.

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Figure 211. Osteosclerosis of the iliac crests in a patient with psoriatic arthritis.

Figure 212. Osteosclerosis of the ligament attachments of the pelvis and the hip joints in a patient with psoriatic arthritis.

Figure 213. Osteosclerosis of the ischial tuberosities in a patient with psoriatic arthritis.

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Figure 214. Osteosclerosis of the pubic symphysis in a patient with psoriatic arthritis.

Figure 215. A PET-CT image shows inflammation of the pubic symphysis in a patient with psoriatic arthritis.

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Figure 216. Osteosclerosis with joint space narrowing and erosions of the pubic symphysis in a patient with psoriatic arthritis.

Figure 217. Mild osteosclerosis of the pubic symphysis in a patient with psoriatic arthritis.

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Figure 218. Osteosclerosis of the right great trochanter in a patient with psoriatic arthritis over time.

Figure 219. Osteosclerosis of the left great trochanter in a patient with psoriatic arthritis over time.

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Cervical spine Odontoid processes Sclerotic change of the odontoid process is found in patients with atlantoaxial subluxation. Discovertebral joints Sclerosis at the discovertebral joints may occur [Dzioba RB 1985].

Figure 220. Sagittal (left panel) and coronal (right panels) reconstructed CT images of the lumbar spine show sclerosis of the end plates with erosions and bone proliferation in a patient with psoriatic arthritis. Temporomandibular joints Sclerosis of the condylar process of the mandible can be seen in patients with psoriatic arthritis. Bone proliferation (New bone formation) Bone proliferation (new bone formation) is the most important feature of psoriatic arthritis and is as important as bone erosions. Proliferation of the bone is almost always present in some way in patients with psoriatic arthritis. Proliferation of the bones is not limited to the joints, but also occurs in the periarticular and the subperiosteal sites, particularly at the points where the ligaments, the tendons and the muscles are inserted into the bones. In summary, bone proliferation occurs in four categories including bone excrescences adjacent to erosions, periosteitis along the shafts, ankyloses and bone fusion across joints, and syndesmophytes at tendinous and ligamentous insertion. In particular, radiographic evaluation of bone proliferation is a definitive feature so that it is included in the classification criteria of psoriatic arthritis (CASPAR, the ClASsification of Psoriatic ARthritis). A useful method of radiography in the evaluation of bone proliferation is the Nørgaard view (ball-catch view). In the Nørgaard view, bone growth formation and state of erosions are more easily understood.

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Figure 221. PA view of the hands of a patient with psoriatic arthritis. In PA view, to find erosions and bone proliferation are not always easy.

Figure 222. The Nørgaard view of the hands of the same patient shows bone formations (arrows) and an erosion of the right third MCP joint (circle).

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Figure 223. Comparison of PA view and the Nørgaard view. In PA views, the DIP joints of both patients with rheumatoid arthritis and psoriatic arthritis do not show evident bone proliferation. In the Nørgaard views, although the DIP joints of the same patient with rheumatoid arthritis do not show any bone proliferation, new bone formation is evident in the DIP joints of the patient with psoriatic arthritis. Difference of bone proliferation between psoriatic arthritis and rheumatoid arthritis Periarticular new bone formation distinguishes psoriatic arthritis from rheumatoid arthritis. Unlike rheumatoid arthritis, bone proliferation is characterized by the presence of bone growth around the sites of erosions in the DIP joints. Bone proliferation is probably related to the excessive healing response of the damaged bones. Micro-CT scans confirmed bone proliferation, not seen in patients with osteoarthritis, in patients with psoriasis and patients with psoriatic arthritis [Simon D 2016] [Finzel S 2014]. In MR imagings, bone proliferation results in the reduction of the signal on both T1weighted and T2-weighted images due to the immobilization of protons [Spira D 2010]. On MRI, erosions of the DIP joints and hypertrophic bone changes are characteristic findings in psoriatic arthritis and the findings may help distinguish psoriatic arthritis from rheumatoid arthritis [Merola JF 2018]. Psoriatic arthritis is more active in bone repair than rheumatoid arthritis, and destructive elements and bone formation coexist. As a result, periostitis, formation of enthesophytes, and osteophytes occur [Narváez J 2012]. While rheumatoid arthritis is characterized exclusively by bone destructive lesions, psoriatic arthritis is also characterized by the coexistence with bone destruction and bone growth in the same joints of the same patients.

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Figure 224. Bone proliferations in psoriatic arthritis and osteoarthritis. Both psoriatic arthritis and osteoarthritis have bone proliferative changes. In psoriatic arthritis, joint spaces are preserved, and bone proliferation stretches at an angle. On the other hand, in osteoarthritis, bone proliferation (osteophytes) with the joint space narrowing extends laterally. Of course, with the progress of the disease of psoriatic arthritis, the joint spaces narrow, and the bones also extend sideways, which may be indistinguishable from osteoarthritis, but the joints tend to fuse and ankylose due to the excessive healing reaction. 1. Syndesmophytes and enthesophytes, bone proliferations of attachments Bone proliferation of syndesmophytes and enthesophytes occurs at the sites where the tendons, the ligaments and the articular capsules insert in the bones. Although bone proliferation at the attachments is not always associated with symptoms, it is often detected by radiography. Chronic changes in the adhesions, such as osteophytes, are nonspecific and may also be found in the entheses due to mechanical stress even in normal subjects [Jane E Freeston 2014]. However, the attachment lesions of spondyloarthritis are larger in size than those by mechanical origin [Tan AL 2010]. Ultrasound examination can detect the attachment lesions. Large enthesophytes produce acoustical shadows and cannot detect complete images of the bones [Aydin SZ 2013] [D'Agostino MA 2003]. In contrast, Doppler signals at the cortical bone insertions are specific for spondyloarthritis [D'Agostino MA 2003] [Aydin SZ 2013].

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Findings of joints Hands Bone proliferation of the entheses of the tendons and ligaments of the digits and the wrists is contiguous with the periosteal responses. Irregular ossification on the attachments of the flexor tendons is also seen. Bone formation of the cup-side occurs in classic pencil-in-cup deformity. In rheumatoid arthritis, there may be pencil formation, but typical cup deformity is rare, because bone formation is not remarkable due to pathophysiological features.

Figure 225. In patients with psoriatic arthritis, bone formation of the cup-sides occurs in classic pencil-in-cup deformity. DIP joints Usually there are findings of bone growth of the DIP lesions in patients with psoriatic arthritis. Erosive deformity and bone proliferation of the joints result in pencil-in-cup deformity of the DIP joints. Distinctive spike-like or fluffy proliferative alteration on the margin of the joint surfaces and the phalangeal tufts is also seen in the DIP joints. Second DIP joints

Figure 226. Bone proliferation of the right second DIP joints in patients with psoriatic arthritis.

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Figure 227. A long-axis power Doppler US image over the dorsal aspect of the right second DIP joint shows proliferative bone change and exhibits the small amount of Doppler signal on it.

Figure 228. Bone proliferation of the left second DIP joints in patients with psoriatic arthritis. Third DIP joints

Figure 229. Bone proliferation of the right third DIP joints in patients with psoriatic arthritis.

Figure 230. Bone proliferation of the left third DIP joints in patients with psoriatic arthritis.

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Fourth DIP joints

Figure 231. Bone proliferation of the right fourth DIP joints in patients with psoriatic arthritis.

Figure 232. Bone proliferation of the left fourth DIP joints in patients with psoriatic arthritis.

Figure 233. The Nørgaard view shows bone proliferation of the left fourth DIP joint clearer than the PA view in a patient of psoriatic arthritis.

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Fifth DIP joints

Figure 234. Bone proliferation of the right fifth DIP joints in patients with psoriatic arthritis.

Figure 235. A long-axis power Doppler US image over the dorsal aspect of the right fifth DIP joint shows proliferative bone change without Doppler signals on it.

Figure 236. Bone proliferation of the left fifth DIP joints in patients with psoriatic arthritis.

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Phalanges

Figure 237. Spike-like proliferative change of the tufts of the right second distal phalanges are seen in patients with psoriatic arthritis.

Figure 238. Spike-like proliferative change of the tufts of the left third distal phalanges are seen in patients with psoriatic arthritis. IP joints

Figure 239. Bone proliferation of the right IP joints in patients with psoriatic arthritis.

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Figure 240. Bone proliferation of the left IP joints in patients with psoriatic arthritis. PIP joints Bone proliferation and deformity of the PIP joints are seen in patients with psoriatic arthritis. Second PIP joints

Figure 241. Bone proliferation of the left and right second PIP joints in patients with psoriatic arthritis. Third PIP joints

Figure 242. Bone proliferation of the left and right third PIP joints in patients with psoriatic arthritis.

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Fourth PIP joints

Figure 243. Bone proliferation of the left and right fourth PIP joints in patients with psoriatic arthritis. Fifth PIP joints

Figure 244. Bone proliferation of the left and right fifth PIP joints in patients with psoriatic arthritis. MCP joints First MCP joints

Figure 245. Bone proliferation of the left first MCP joint in a patient with psoriatic arthritis. Bone proliferation is evident in the first metacarpal head on both the radial and ulnar side.

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Second MCP joints

Figure 246. Bone proliferation of the right second MCP joint in a patient with psoriatic arthritis.

Figure 247. Bone proliferation of the right second MCP joint in a patient with psoriatic arthritis.

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Third MCP joints

Figure 248. Bone proliferation (arrows) of the right third MCP joint in a patient with psoriatic arthritis.

Figure 249. Bone proliferation of the right third MCP joint in a patient with psoriatic arthritis.

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Fifth MCP joints

Figure 250. Bone proliferation of the right fifth MCP joint in a patient with psoriatic arthritis.

Figure 251. Bone proliferation of the left fifth MCP joint in a patient with psoriatic arthritis.

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CMC joints (Carpometacarpal joints) The CMC (an abbreviation for carpometacarpal) joints of the thumbs are where the metacarpal bones of the thumbs attach to the trapezium bones. The joints are sometimes referred to as the trapeziometacarpal or the basal joints of the thumbs. The findings of osteogenesis are most commonly seen on the radial aspects of the CMC joints of the thumbs and on the radial styloids. These findings can distinguish arthritis of the wrists in psoriatic arthritis from rheumatoid arthritis [Brower A 2012].

Figure 252. Bone proliferation of the right first CMC joint in a patient with psoriatic arthritis.

Figure 253. Bone proliferation of the trapezium at the right first CMC joint in a patient with psoriatic arthritis.

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Figure 254. Bone proliferation of the right second CMC joints in patients with psoriatic arthritis.

Figure 255. Bone proliferation of the left second CMC joint in a patient with psoriatic arthritis.

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Carpal joints

Figure 256. Bone proliferation is seen at the radial aspect of the right scaphoid in a patient with psoriatic arthritis.

Figure 257. Bone proliferation is seen at the radial aspect of the left scaphoid in a patient with psoriatic arthritis.

Figure 258. PA and the Nørgaard views of the right wrist. Bone proliferation is seen at the radial surface of the styloid process of the radius in a patient with psoriatic arthritis.

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Figure 259. PA and the Nørgaard views of the left wrist. Bone proliferation are seen at the radial surface of the styloid process of the radius in a patient with psoriatic arthritis.

Figure 260. Bone proliferation of the styloid process of the ulna over time in a patient with psoriatic arthritis.

Figure 261. Remarkable bone proliferation of the styloid process of the ulna in a patient with psoriatic arthritis.

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Figure 262. Bone proliferation of the head of the ulna in the ulnocarpal joint of a patient with psoriatic arthritis.

Figure 263. Bone proliferation of the styloid process of the left ulna over time in a patient with psoriatic arthritis. Elbows

Figure 264. Bone proliferation of the coronoid process of the right ulna in a patient with psoriatic arthritis.

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Figure 265. Bone proliferation of the medial epicondyle of the right humerus in a patient with psoriatic arthritis. Shoulders

Figure 266. AP and axial views of the shoulder in a normal subject.

Figure 267. Bone proliferation of the infraglenoid tubercle, supraglenoid tubercle, acromion process and greater tuberosity of the right shoulder in a patient with psoriatic arthritis.

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Figure 268. Bone proliferation of the infraglenoid tubercle and acromion process of the left shoulder in a patient with psoriatic arthritis. Acromioclavicular joints

Figure 269. Bone proliferation of the clavicle at the acromioclavicular joint in a patient with psoriatic arthritis.

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Figure 270. An axial CT image of the right shoulder shows bone proliferation of the acromion process at the acromioclavicular joint in a patient with psoriatic arthritis. Acromions Lateral sides

Figure 271. A coronal T1 MR image and a conventional radiograph of the left shoulder show bone proliferation of the lateral acromion process in a patient with psoriatic arthritis.

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Figure 272. Bone proliferation of the lateral acromion process with narrowing of the acromiohumeral interval in the left shoulder of a patient with psoriatic arthritis.

Figure 273. Bone proliferation of the lateral acromion process of the right shoulder in a patient with psoriatic arthritis.

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Figure 274. Coronal CT reconstruction of the right shoulder shows bone proliferation of the lateral acromion process in a patient with psoriatic arthritis. Subacromial spaces

Figure 275. AP view of the left shoulder of a patient with psoriatic arthritis. Osteosclerosis of the greater tuberosity and subacromial bone proliferation are noted. No apparent narrowing, widening and calcification are seen between the humeral head and the acromion.

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Figure 276. Axial view of the right shoulder shows bone proliferation of the lesser tuberosity (large arrow) in a patient with psoriatic arthritis.

Figure 277. Axial view of the left shoulder shows bone proliferation of the lesser tuberosity in a patient with psoriatic arthritis. Bone proliferation can be seen at the insertions of the coracoclavicular ligaments and the rotator cuffs in the shoulders. Hips

Figure 278. AP views of the hips show bone proliferation of the greater trochanters in a patient with psoriatic arthritis.

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Common sites of proliferation are the femoral trochanters and the ischial tuberosities in the hips. Knees

Figure 279. AP and lateral views of the right knee in a normal subject.

Figure 280. AP view. Radiographic anatomy of the right knee.

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Figure 281. Lateral view. Radiographic anatomy of the right knee.

Figure 282. AP view of the right knee. Bone proliferation of the lateral femoral condyle, the lateral tibial condyle, the medial femoral condyle, the medial tibial condyle, and the intercondylar eminence is observed in a patient with psoriatic arthritis.

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Figure 283. Bone proliferation on the superior surface of the patella, the anterior surface of the femoral condyles, and the tibial plateau is observed in a patient with psoriatic arthritis.

Figure 284. AP and lateral views of the right knee. Bone proliferation of the right knee in a patient with psoriatic arthritis.

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Figure 285. AP and lateral views of the right knee. Bone proliferations of the right knee is observed in a patient with psoriatic arthritis.

Figure 286. AP and lateral views of the left knee. Mild bone proliferation of the left knee is seen in a patient with psoriatic arthritis.

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Figure 287. AP and lateral views of the left knee. Bone proliferation of the left knee in a patient with psoriatic arthritis.

Figure 288. A longitudinal sonogram of the medial aspect of the left knee. A patient with psoriatic arthritis has a mild bone proliferation of the proximal tibia (arrow). The medial collateral ligament directly covers the medial meniscus.

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Epicondyles

Figure 289. AP view of the right knee shows bone proliferation of the epicondyles in a patient with psoriatic arthritis.

Figure 290. Lateral views of the knees show bone proliferation of the left lateral femoral condyle.

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Anterior surfaces of the patellae There is a bone growth on the superior surfaces of the patellas. Patellar tendons Bone proliferation at the insertions of the patellar tendons can be seen. Medial and lateral malleoli

Figure 291. AP view of the right ankle. Bone proliferation of the medial malleolus in a patient with psoriatic arthritis.

Figure 292. AP view of the left ankle. Bone proliferation of the medial malleolus in a patient with psoriatic arthritis.

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Calcaneuses As with other spondyloarthritides, erosions and bone growth of the posterior and the inferior surfaces of the calcaneuses are prominent in psoriatic arthritis [Resnick D. 1974]. Erosions on the inferior surfaces, the plantar aspects, of the calcaneuses are associated with surrounding irregular and poorly defined bone proliferation, the enthesophytes, at the attachment sites of the plantar ligaments and the aponeurosises. The large plantar calcaneal enthesophytes can be seen. The enthesophytes do not tend to point downward along the course of the plantar aponeurosises but to point upward towards the calcaneuses [Brower A 2012]. Although detailed evaluation should be performed in lateral view, enthesophytes of calcaneuses can be seen in oblique view. Posterior and inferior surfaces of the calcaneuses

Figure 293. Lateral view of the right foot of a patient with psoriatic arthritis. Bone proliferation, the enthesophyte, at the attachment site of the plantar ligament and aponeurosis and the Achilles tendon. Enthesophyte of the aponeurosis is large.

Figure 294. Lateral views of the feet of a patient with psoriatic arthritis. Bone proliferations at the attachment sites of the plantar ligaments and aponeuroses.

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Figure 295. Lateral view of the right foot of a patient with psoriatic arthritis. Bone proliferations at the attachment sites of the plantar ligament, aponeurosis and the Achilles tendon.

Figure 296. Lateral views of the feet of a patient with psoriatic arthritis. Bone proliferation at the attachment sites of the Achilles tendons, the plantar ligaments and aponeuroses.

Figure 297. Mild bone proliferation at the attachment site of the right Achilles tendon.

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Figure 298. Oblique views of the feet of a patient with psoriatic arthritis. Bone proliferation at the attachment sites of the Achilles tendons. Forefeet Naviculars

Figure 299. Bone proliferation or the accessory ossicle of the right navicular of a patient with psoriatic arthritis.

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Figure 300. Bone proliferation of the left navicular of a patient with psoriatic arthritis.

Figure 301. Bone proliferation of the right navicular of a patient with psoriatic arthritis.

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Cuboids

Figure 302. Bone proliferation or the accessory ossicle of the right cuboid of a patient with psoriatic arthritis. Metatarsal bones

Figure 303. Bone proliferation of the right first metatarsal bone of a patient with psoriatic arthritis.

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Figure 304. Bone proliferation of the left first metatarsal bone of a patient with psoriatic arthritis. .

Figure 305. Bone proliferation of the left third metatarsal bone of a patient with psoriatic arthritis.

Figure 306. Bone proliferation of the right third metatarsal bone of a patient with psoriatic arthritis.

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MTP joints

Figure 307. Bone proliferation of the right first metatarsophalangeal (MTP) joint of a patient with psoriatic arthritis. Phalanges

Figure 308. Bone proliferation of the right first distal phalanges of patients with psoriatic arthritis.

Figure 309. Bone proliferation of the left first distal phalanges of patients with psoriatic arthritis.

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Spine Syndesmophytes of the spine in psoriatic arthritis are characterized by large and bulky bone growth distributed unilaterally or asymmetrically. Syndesmophytes of psoriatic arthritis can be differentiated from those of ankylosing spondylitis because these are often bulkier and paramarginal, and then skip vertebral levels. However, even in psoriatic arthritis, slender and symmetrical spinal bone growth rarely occurs, which is the same as syndesmophytes in ankylosing spondylitis. Although paravertebral ossification in psoriatic arthritis may result in less involvement of the apophyseal joints, there may be lesions of the apophyseal joints in the cervical spine. There is some confusion as to the exact meaning of non-marginal syndesmophytes, with similar expressions such as parasyndesmophytes, paramarginal, non-marginal, osteophytes, and so on [Taylor WJ 2003].

Figure 310. Anatomy of the lumbar spine.

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Figure 311. Diagram of the spine.

Figure 312. Diagram of diseases in the spine.

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DISH, Diffuse idiopathic skeletal hyperostosis ASH, ankylosing spinal hyperostosis PsA, psoriatic arthritis AS, ankylosing spondylitis OA, osteoarthritis OPLL, ossification of the posterior longitudinal ligament OYL, ossification of the yellow ligament

Figure 313. A typical example of the spinal lesions of psoriatic arthritis.

Figure 314. Enthesopathy of the spine in psoriatic arthritis.

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Figure 315. Parasyndesmophytes of psoriatic arthritis in plain radiography.

Figure 316. Attachment lesions of the lumbar spine in psoriatic arthritis. In psoriatic arthritis, usually arthritis and ankylosis of the apophyseal joints of the lumbar spine do not exist, so rear mobility of the vertebrae is relatively maintained in the spine. Therefore, the sites to which the anterior longitudinal ligaments adhere, are subjected to excessive mechanical stress and the enthesitis occurs. The mobility of the apophyseal joints is maintained even if the inflammation of the entheses of the anterior longitudinal ligament is prolonged. Anterior tension and mechanical stress are still applied to the anterior vertebral bodies. The tension of the anterior longitudinal ligament and the attachments in the front of the intervertebral discs makes enthesitis persist. In this process, further inflammation of the paravertebral regions induces bone formation to expand forward. The bone formation becomes parasyndesmophytes in psoriatic arthritis.

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Figure 317. Mechanical stress and syndesmophytes in psoriatic arthritis. Because the posterior components of the vertebrae remain mobile, mechanical stress is excessive on the anterior longitudinal ligament, especially along the anterior disc spaces.

Figure 318. The anterior and the posterior components in psoriatic arthritis. Although the anterior longitudinal ligament as the anterior component of the spine is intensively ossified, the apophyseal joints as the posterior components are maintained.

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Parasyndesmophytes and syndesmophytes Paravertebral ossification can take three forms, marginal (syndesmophytes), nonmarginal (“chunky” and “comma”, advanced syndesmophytes), and paravertebral ossification (parasyndesmophytes). Paravertebral ossification of the lower thoracic, the upper lumbar and the cervical spine can occur in psoriatic arthritis, which may be the earliest finding of the disease. Early spinal lesions in psoriatic arthritis are usually asymmetric ossification. Ossification is roughly linear or thin curvilinear, thick, fluffy, fuzzy, and parallel to the lateral surfaces of the vertebral bodies [Gladman DD 2005]. Also, the intervertebral spaces may be maintained. These changes are defined as nonmarginal, bulky syndesmophytes. Paravertebral ossification has been reported in 17% of 122 psoriasis patients with spinal radiographs [Hahn K 1980]. Syndesmophytes gradually spread to varying degrees, eventually resulting in large and bulky bone growth. Syndesmophytes integrate with the bones and discs of the vertebrae. In psoriatic arthritis, parasyndesmophytes are the form of a so-called "bulky or chunky" paravertebral ossification, which is substantial and structurally different from marginal and symmetrical syndesmophytes observed in ankylosing spondyloarthritis. The locations of parasyndesmophytes are farther away from the vertebral column in patients with psoriatic arthritis. Moreover, the annulus fibrosus itself is not ossified [Bywaters EGL 1965]. The thoracolumbar spine may exhibit large comma-shaped paravertebral ossification. Histological findings associated with paravertebral ossification in psoriatic arthritis are unclear. The inflammation in the paravertebral connective tissue and the periosteal reaction at the entheses are important [Bywaters EGL 1965] [Schacherl M 1967].

Figure 319. A radiograph of the lumbar spine shows parasyndesmophytes, comma-shaped paravertebral ossification.

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Figure 320. Parasyndesmophytes at an intervertebral disc area in patient with psoriatic arthritis.

Figure 321. Parasyndesmophytes grow at the intervertebral discs in a patient with psoriatic arthritis.

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Figure 322. Parasyndesmophyte at the intervertebral disc area. Squaring of vertebral bodies (see the section of periostitis) The squaring of the vertebral bodies is characteristic of ankylosing spondylitis. However, squaring of the vertebral bodies is also seen in some patients with psoriatic arthritis [Sudoá-SzopiĔska I 2016]. Apophyseal joint involvement Apophyseal joint involvement, which is characteristic of ankylosing spondylitis, may be seen occasionally in patients with psoriatic arthritis. Differentiation from Ankylosing spondylitis In advanced cases of spinal lesions in psoriatic arthritis, they look like bamboo spine, and at first glance they cannot be distinguished from those in patients with ankylosing spondylitis; how do physicians distinguish spinal lesions of psoriatic arthritis from ankylosing spondylitis?

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Figure 1. In an advanced case of spinal lesion, it looks like a bamboo (bamboo spine).

Figure 323. Sharpey fibers are present at the outermost sides of the annuli fibrosi of the intervertebral discs.

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Figure 324. Diagram of ankylosing spondylitis. Ankylosing spondylitis is a disease with inflammation and ossification of the insertion sites of Sharpey fibers. Since Sharpey fibers are the outer zones of the intervertebral discs, there is no protrusion to the outside, and ossification is straight and thin in lines along with the vertebral bodies. The posterior components of the apophyseal joints also become lesions in ankylosing spondylitis.

Figure 325. Radiographs show the chronic inflammatory changes of syndesmophytes.

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Figure 326. Inflammatory changes of the vertebral body corners, which are the attachment sites of Sharpey fibers, are said to be shiny corners, Romanus lesions.

Figure 327. An MR image shows inflammatory changes of the vertebral body corners and Schmorl’s nodule, which is the protrusion of the nucleus pulposus of the intervertebral disc through the vertebral body endplate and into the adjacent vertebra.

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Figure 328. In ankylosing spondylitis, MR images show chronic inflammatory changes in the vertebral body corners which are the attachment sites of Sharpey fibers.

Figure 329. In ankylosing spondylitis, inflammatory changes in the vertebral body corners and the anterior surfaces of vertebral bodies, which are the attachment sites of Sharpey fibers, are prominent.

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Figure 330. Mechanical stress in ankylosing spondylosis. The mobility of the spine in the spine is generally reduced due to the occurrence of lesions in the posterior interspinous ligaments and apophyseal joints, which are the posterior regions of the vertebrae, as well as the Sharpey fibers in the anterior components of the spine. Therefore, the anterior longitudinal ligament is not subjected to a large tension, and the bone growth (protrusion) caused by mechanical stress becomes milder. The ossification starting from Sharpey fibers extend anatomically to the deep layers of the anterior longitudinal ligament that are right in front of them. However, they do not extend to the shallow layers. Chronic inflammation in the deep layer of the anterior longitudinal ligament forms syndesmophytes. The ossification leads clearly to the adjacent vertebral bodies, but without being large and bulky, it runs like a thin vertical flow.

Figure 331. Parasyndesmophytes in psoriatic arthritis (PsA) and syndesmophytes in ankylosing spondylitis (AS).

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Figure 332. Syndesmophytes in patients with ankylosing spondylitis.

Figure 333. Ossification of Sharpey fibers with fatty changes of the anterior corner of the vertebral bodies in a patient with ankylosing spondylitis.

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Figure 334. Bamboo spine in ankylosing spondylitis.

Figure 335. As ankylosing spondylitis progresses, ossification of the spine become prominent and bulky overhangs occur. However, the form of ossification is still smooth.

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Figure 336. Ankyloses of the apophyseal joints in a patient with ankylosing spondylitis.

Figure 337. The posterior components of the spine make three lines of ossification, the tramline, or the trolley track and the dagger sign: central line of ossification (the supraspinous and interspinous ligaments) with two lateral lines of ossification (the apophyseal joints).

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Figure 338. The trolley lines or the tramlines in a patient with ankylosing spondylitis.

Figure 339. The incomplete trolley lines or tramlines in a patient with ankylosing spondylitis.

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Figure 340. Thickening of the posterior longitudinal ligament in a patient with ankylosing spondylitis.

Figure 341. Thickening of the ligament flava in a patient with ankylosing spondylitis.

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Figure 342. Chalk-like fracture or chalk stick fracture in a patient with ankylosing spondylitis.

Figure 343. Andersson lesion with fracture of the spine in a patient with ankylosing spondylitis.

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Cervical spine Radiographic abnormalities of the cervical spine include syndesmophytes that occur in the adjacent soft tissue with calcifications of the ligaments along the anterior aspects of vertebral bodies [Paparo F 2014] [Ory PA. 2003]. Eightyfive percent of patients have ankylosis, syndesmophytes and ligamentous ossification [Jenkinson T 1994]. The posterior ligamentous calcification may be also seen.

Figure 344. Stenosis of the spinal canal is recognized at the C4 /5 to C6 /7 levels due to degeneration and the posterior protrusion of the intervertebral discs, osteophytes of the vertebral bodies, and thickening of the posterior longitudinal ligament. Thoracic spine Lesions of the thoracic spine are observed as the paravertebral bone formation.

Figure 345. Parasyndesmophytes in the thoracic spine of a patient with psoriatic arthritis.

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Figure 346. Plain radiograph and CT image show parasyndesmophytes in the thoracic spine of a patient with psoriatic arthritis.

Figure 347. Parasyndesmophytes in the thoracic spine of a patient with psoriatic arthritis.

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Figure 348. Parasyndesmophytes in the thoracic spine of a patient with psoriatic arthritis.

Figure 349. Sagittal T1- and T2-weighted MR images show parasyndesmophytes of the spine in a patient with psoriatic arthritis.

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Figure 350. CT images show parasyndesmophytes in the thoracic spine of a patient with psoriatic arthritis.

Figure 351. Coronal and sagittal CT reconstructed images of the spine show multiple parasyndesmophytes in a patient with psoriatic arthritis.

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Thoracolumbar junctions

Figure 352. Unilateral parasyndesmophyte at the thoracolumbar junction of a patient with psoriatic arthritis.

Figure 353. Minor parasyndesmophytes of the vertebral bodies at the thoracolumbar junction in a patient with psoriatic arthritis.

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Lumbar spine Involvement of the lumbar spine is observed as paravertebral ossification. Bulky bone formation appears and merges with the underlying vertebral bodies and intervertebral discs.

Figure 354. A photograph shows spinal ankylosis of a patient with psoriatic arthritis.

Figure 355. Minor parasyndesmophytes in the lumbar spine of a patient with psoriatic arthritis.

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Figure 356. Parasyndesmophytes in the thoracic and the lumbar spine of a patient with psoriatic arthritis.

Figure 357. Multiple parasyndesmophytes in the lumbar spine of a patient with psoriatic arthritis.

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Figure 358. Advanced parasyndesmophytes in the lumbar spine of a patient with psoriatic arthritis.

Figure 359. Osteophytes in the lumbar spine of a patient with psoriatic arthritis.

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Figure 360. Minor osteophytes in the lumbar spine of a patient with psoriatic arthritis.

Figure 361. Osteophytes in the lumbar spine of a patient with psoriatic arthritis.

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Ischial tuberosities

Figure 362. Advanced bone proliferation of the ischial tuberosities in a patient with psoriatic arthritis.

Figure 363. Bone proliferation of the ischial tuberosities in a patient with psoriatic arthritis.

Figure 364. Bone proliferation of the ischial tuberosities in a patient with psoriatic arthritis.

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Figure 365. Advanced bone proliferation of the ischial tuberosities in a patient with psoriatic arthritis. Sacroiliac joints In the sacroiliac joints of psoriatic arthritis, blurry ossification of the sacrums and the ilia, calcification, and ossification of the interosseus ligaments may occur. Proliferative bone repair is observed as the erosions of the sacral sides expand. Around the synovial parts of the sacroiliac joints, ossification of the ligaments between the sacrums and the ilia can occur even without the ankyloses of synovial joints. Tendon attachments can become ossified.

Figure 366. In the sacroiliac joints, bone proliferation is seen in a patient with psoriatic arthritis.

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Pubic symphysises

Figure 367. Bone proliferations of the pubic symphysis in a patient with psoriatic arthritis. 2 Bone excrescences Proliferative changes of the bones in psoriatic arthritis result in unclear and ill-defined ossification of the joints and new bone formation around the erosions. Irregular overgrowth of the bones, excrescences, may occur in the places where the tendons, the ligaments, and the joint capsules insert into the bones. Fluffy, spiculated, frayed lesions or “paintbrush appearance” may be present. Over time, these excrescences become the well-defined bones. Therefore, the bone excrescences may be unclear in appearance, but well-defined in some cases. The finding of juxta articular new bone formation is considered a characteristic feature of psoriatic arthritis and is important in the Classification criteria for psoriatic arthritis (CASPAR criteria) [Taylor W. 2006].

Figure 368. Fluffy, spiculated, frayed lesion or “paintbrush appearance” is present in a patient with psoriatic arthritis.

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Bone proliferation adjacent to erosive changes The bone proliferation adjacent to the erosions may take several forms as irregular excrescences with a spiculated, frayed, whisker and a fluffy appearance. Compared with plain radiography, CT is much more sensitive to the detection of small erosions and the bone proliferation in the hands.

Figure 369. The bone proliferations adjacent to erosive changes are observed at the IP, the DIP and the PIP joints in patients with psoriatic arthritis. The finding of fraying or irregularity of the periarticular bone surfaces is not evident in rheumatoid arthritis. Mouse-ear signs

Figure 370. Mouse-ear sign over time at the DIP joint of a patient with psoriatic arthritis. Fluffy appearance Fluffy periostitis caused by periosteal ossification is seen in psoriatic arthritis. Whiskering, Fuzzy appearance The bone proliferation makes the irregular appearance of the marginal bones of the involved joints, characterized as “fuzzy” appearance or “whiskering”. Whiskering is characteristic frayed and ill-defined look caused by multiple, small fluffy bone proliferations adjacent to the marginal erosions.

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Findings of joints DIP joints Changes of the DIP joints include osseous erosions with accompanying proliferation. In some patients with psoriatic arthritis, advanced changes with a combination of destruction and new bone formation are seen.

Figure 371. Fluffy appearance around the right second DIP joints in patients with psoriatic arthritis.

Figure 372. Fluffy appearance around the left second DIP joint in a patient with psoriatic arthritis.

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IP joints

Figure 373. Whisker appearance at the right IP joint over time in a patient with psoriatic arthritis.

Figure 374. Whisker appearance at the left IP joint in a patient with psoriatic arthritis.

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PIPs Protuberances and erosions of the PIP joints may be seen in patients with psoriatic arthritis.

Figure 375. Frayed appearance of the right third PIP joint in a patient with psoriatic arthritis. IP joints Bone proliferation around the interphalangeal joints may be observed. MCP joints Abnormalities in the MCP joints are less pronounced and relatively spared, although occasionally, severe destruction, resorption and proliferation may also be found. In the MCP joints of psoriatic arthritis, irregular contours, "frayed" contours, of the metacarpal and the phalangeal bones caused by a combination of bone erosions and bone proliferation are observed. Bone excrescences about erosions of the metacarpal heads may be seen. Wrists Involvement of the wrists includes bone proliferation. Irregular contours of the carpal and the metacarpal bones caused by a combination of erosions and proliferation may be seen. Radiographs of the hands show typical changes, including protuberances and erosions of the styloid processes of the ulnas and the distal parts of the radiuses. Elbows, shoulders and knees Involvement of the shoulders, the elbows, and the knees of patients with psoriatic arthritis tends to be asymmetrical, with erosive changes and proliferation of the adjacent bones. In the shoulders of psoriatic arthritis, radiographs may reveal bone proliferation of the greater tuberosities. Radiographs of the knees may show dramatic bone proliferation in the posterior surfaces of the tibias.

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Hips Hip lesions of psoriatic arthritis are characterized by varying degrees of erosive changes and adjacent bone proliferation. Bone proliferations at the tendinous and the ligamentous insertions is frequently observed around the hip joints. Ankles Arthritis of the ankles tends to be asymmetrical, with erosive changes and proliferation of the adjacent bones. Irregular excrescences arising from the medial malleoli of the ankles are characteristic of psoriatic arthritis.

Figure 376. Fluffy appearance at the left medial malleolus in a patient with psoriatic arthritis. This finding is characteristic of psoriatic arthritis.

Figure 377. Osteolysis and fluffy bone proliferation occur at the left medial malleolus in a patient with psoriatic arthritis.

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Feet Bone proliferation is identified as new bone formation around erosions in the feet. IP joints Lesions of the IP joints of psoriatic arthritis include osseous erosions and proliferation, particularly about the IP joints of the great toes. MTP joints

Figure 378. Whisker appearance around the left first MTP joint in a patient with psoriatic arthritis.

Figure 379. Fluffy bone proliferation around the left first MTP joint in a patient with psoriatic arthritis.

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Figure 380. Fluffy bone proliferation around the right second MTP joint in a patient with psoriatic arthritis. 3 Periostitis, Periosteal new bone formation Bone growth along the diaphysises is observed, which is a classic periostitis. Bone erosions are more common in rheumatoid arthritis, but in psoriatic arthritis, periostitis is more frequent [Schoellnast H 2006]. MRI findings of the wrists and the hands in patients with psoriatic arthritis and rheumatoid arthritis show that periostitis is statistically seen more frequently in patients with psoriatic arthritis (78% vs 0%) [Schoellnast H 2006]. Soft tissue swelling occurs due to periostitis, which usually affects the bone shafts. Bone formation may be a form of periostitis of the shafts of the phalanges and this is also sometimes the first radiographic manifestation [Firestein GS 2017]. Periostitis may be seen along the shafts of the bones. Periosteal new bone formation tends to occur in the vicinity of and parallel to the cortex of the phalanges, the metacarpals and the metatarsals. At first periostitis is exuberant and looks like cotton cushions in appearance. Finally, periostitis becomes a solid new bone along the diaphyses, and it widens the width of the phalanges. Periostitis of the metaphyses and the diaphyses of the bones in the hands and the feet is common in psoriatic arthritis [Forrester DM 1976] [Resnick D 1977]. Pathologically, periostitis with periosteal new bone formation is a result of osteoblastic activity, and subperiosteal deposition of the bones has subchondral sclerosis. Periostitis takes several forms. It appears as a thin periosteal layer of the new bone adjacent to the cortical bones, a thick, irregular layer, and irregular thickening of the bone cortex itself [Jacobson JA 2008]. Periostitis may also occur in the areas without bone erosions. Periostitis is found in the radial aspects of the wrists extending into the first metacarpal bones. Cloaking Periosteal bone formation due to periosteitis associated with tenosynovitis leads to “cloaking” of the entire phalanges, a part of the metacarpals and the metatarsals over time. Cloaking can appear as the early changes with soft tissue swelling

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before significant abnormalities occur in the adjacent joints. The entire phalanges may become “cloaked” in new bone formation. Widening of phalanges Periostitis causes proliferation and irregular or smooth thickening of the cortical bones in the later stages. Periostitis is a hallmark of psoriatic arthritis [H. J. Spira D 2009]. Eventually periosteitis will make solid new bones along the diaphysises and widening of the phalanges. Lamellar or undulating Lamellar or undulating periosteal reactions of the phalanges may be seen in psoriatic arthritis. Ultrasound Although the findings of ultrasound cannot differentiate various inflammatory arthritides based on bone changes, irregularities on the bone cortex due to periosteal new bone formation suggest the presence of psoriatic arthritis [Chiavaras MM 2014]. MRI Hyperemia of the periarticular periosteums can be directly visualized in MR images. Periosteum inflammation is a part of enthesitis and is found along the diaphyses in MR images. However, bone marrow edema usually overlaps with the cortical bones and no abnormalities occur and it is unclear.

Figure 381. A 35-year-old woman with psoriatic arthritis. MR images show periostitis along the shaft of the right third phalange. Coronal fat-saturated gadolinium enhanced T1-weighted MR image suggests periostitis with thickening and hyperemia. Periostitis has continuity with enthesitis and synovitis of the capsule of the third MCP joint.

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Bone scan Intense uptake in bone scintigraphy of patients with psoriatic arthritis is seen in response to soft tissue swelling and periostitis. Ivory phalanges As a result of extensive new bone growth around the phalanges, "ivory" phalanges with an increased osseous density of the entire bones are formed. Ivory phalanges are most frequent in the distal phalanges of the toes, particularly the first toes [Resnick D 1977] [Goupille P 1996]. Ivory phalanges can occur in the early stages of the disease. Soft tissue swelling and nail lesions are almost always present in the same digits, with no apparent joint abnormalities or osteophyte formation. Increased radiodensity of the phalanges is due to osteogenesis on the periosteal and endosteal surfaces of the cortices and trabecular thickening in the spongiosa. Although ivory phalanges are rare, they are characteristic and specific radiographic manifestations of psoriatic arthritis.

Figure 382. “Ivory phalange” of the proximal phalange of the first toe in a patient with psoriatic arthritis.

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Figure 383. The bone density of the right third distal phalange increases. Bone condensation on the surface of the cortical bone and thickening of the trabeculae in the bone result in entire increased bone density over the phalange. Findings of joints Tufts of distal phalanges Distinctive spike-like or fluffy proliferative alterations are found at the tufts of the distal phalanges.

Figure 384. Fluffy bone proliferation at the tuft of the distal phalange is seen.

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Middle phalanges Fluffy or solid periostitis with widening of the shaft of the middle phalanges is seen.

Figure 385. Periostitis (arrow) along the shaft of the right second middle phalange in a patient with psoriatic arthritis.

Figure 386. Oblique view of the right third proximal phalange. Periostitis along the shaft of the right second middle phalange.

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Figure 387. Periostitis along the shafts of the left third middle and the proximal phalanges.

Figure 388. Periostitis along the shaft of the left third middle phalange in a patient with psoriatic arthritis.

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Figure 389. Periostitis along the shafts of the right fourth middle and the proximal phalanges in a patient with psoriatic arthritis.

Figure 390. Periostitis along the shaft of the left fourth middle phalange in a patient with psoriatic arthritis.

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Figure 391. New bone formations along the shafts of the second proximal and the fourth middle phalanges. The widening shafts of the phalanges in a patient with psoriatic arthritis. Proximal phalanges The undulating periosteal reaction of the proximal phalanges is seen.

Figure 392. Periostitis along the shaft of the right third proximal phalange in a patient with psoriatic arthritis.

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Figure 393. New bone formation along the shaft of the left second proximal phalange and the widening of the phalange in a patient with psoriatic arthritis. Metacarpals Periostitis of the metacarpal diaphysises is seen. Periosteal new bone formation results in significant cloaking of the metacarpal bones.

Figure 394. Fluffy periosteal new bone formation is seen in the right first proximal phalange in a patient with psoriatic arthritis.

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Figure 395. Fluffy periosteal new bone formation is seen in the left first proximal phalange in a patient with psoriatic arthritis.

Figure 396. New bone formations along the shafts of the right fourth and the fifth metacarpals. Widening shafts of the phalanges in a patient with psoriatic arthritis.

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Figure 397. New bone formation along the shaft of the left fifth metacarpal and widening shaft of the phalange in a patient with psoriatic arthritis. Wrists Periosteitis of the radial aspects of the wrists may be seen in psoriatic arthritis.

Figure 398. Periosteal new bone formation is seen in the right radius in a patient with psoriatic arthritis.

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Shoulders

Figure 399. Osteohypertrophy of the right acromion (arrow) is observed in a patient with psoriatic arthritis.

Figure 400. Osteohypertrophy of the right clavicle (arrow) is observed in CT of a patient with psoriatic arthritis.

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Knees The periostitis in the tibias and the fibulas may be observed. Ankles There is fluffy periosteal bone formation along the distal tibias and the fibulas.

Figure 401. T2 weighted short tau inversion recovery (T2-STIR) imaging of the left ankle shows periostitis along the shaft of the tibia.

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Feet Metatarsals Periosteal bone formation of the metatarsals may be seen.

Figure 402a. Periosteal new bone formation is seen in the right fifth metatarsal in a patient with psoriatic arthritis.

Figure 402b. Widening of the shaft of the right second metatarsal in a patient with psoriatic arthritis.

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Figure 402c. Fluffy new bone formation at the right first MTP joint in a patient with psoriatic arthritis. Distal phalanges In the distal phalanges, extensive new bone formation may result in ivory phalanges with an increased osseous density of the entire bones. Fluffy periostitis of the distal phalanges is also observed.

Figure 403. Periostitis and new bone formation of the right distal phalange of a patient with psoriatic arthritis.

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Vertebral bodies Osteitis and squaring of the anterior surfaces of the vertebral bodies are relatively rare in psoriatic arthritis. Bone proliferation of osteitis is thicker than the syndesmophytes of ankylosing spondylitis and asymmetric distribution should suspect psoriatic arthritis. Osteitis of vertebral bodies Osteitis with extensive bone proliferation along the anterior surfaces of the spine may be seen. Squaring of vertebral bodies In psoriatic arthritis, squaring of the vertebral bodies occurs less frequent than in ankylosing spondyloarthritis. Although squaring of the vertebral bodies may occur throughout the spine, it is initially observed in the lumbar spine. Fat deposition of the bone marrow is an important sign that correlates with the squaring of the vertebral bodies [Madsen KB 2009].

Figure 404. Squaring of the vertebral bodies in ankylosing spondylitis in the right panel. Osteitis in early stages In the early stages, ossification appears on one side of the spine, parallel to the vertebral bodies and the outer surfaces of the intervertebral discs, as thick, fluffy or as thin, curved areas of reduced permeability. Osteitis in advanced stages Ossification due to osteitis gradually spreads at various rates, but ultimately results in large and bulky lesions that include vertebrae and the discal tissue.

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4 Ankyloses, Bone fusions Intra-articular bone fusions or ankyloses are signs of bone growth in psoriatic arthritis. Ankyloses of joints occur frequently in advanced disease and are characteristic of psoriatic arthritis. Intra-articular bone fusions may develop relatively early. Radiographic features of interphalangeal ankyloses are particularly characteristic [Wassenberg S. 2015]. Although intra-articular bone fusions are also observed in inflammatory osteoarthritis, septic arthritis, and rheumatoid arthritis (the carpal and the tarsal areas), they are important radiographic signs of the seronegative spondyloarthropathies including psoriatic arthritis. Such bone ankyloses are observed in large joints such as the knees, but are particularly prominent in the hands and the feet, usually affecting the PIP and the DIP joints. Physicians should always consider whether patients with inflammatory arthritis are psoriatic arthritis when bone ankyloses of the interphalangeal joint are seen [Forrester DM. 1987]. When the ankyloses are complete, adjacent erosions and bone growth may become less pronounced. DIP joints In the DIP joints of the hands, bone ankyloses can be seen.

Figure 405. Bone ankyloses of the right second, the right fourth, the fifth and the left fifth DIP joints.

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Figure 406. Bone ankylosis with erosions at the right second DIP joint in a patient with psoriatic arthritis.

Figure 407. Bone ankylosis of the right second DIP joint in a patient with psoriatic arthritis.

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Figure 408. Bone ankylosis of the right second DIP joint in a patient with psoriatic arthritis.

Figure 409. Bone ankylosis of the right fourth DIP joint in a patient with psoriatic arthritis.

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Figure 410. Bone ankylosis of the right fourth DIP joint in a patient with psoriatic arthritis.

Figure 411. Bone ankylosis of the right fifth DIP joint in a patient with psoriatic arthritis.

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Figure 412. Bone ankylosis of the left fifth DIP joint in a patient with psoriatic arthritis.

Figure 413. Bone ankylosis of the left fifth DIP joint in a patient with psoriatic arthritis.

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PIP joints

Figure 414. There is bone ankylosis with a syndesmophyte of the right fifth PIP joint in a patient with psoriatic arthritis.

Figure 415. There is bone ankylosis of the left fifth PIP joint in a patient with psoriatic arthritis.

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Wrists Intra-articular ankyloses of the carpals may be seen in psoriatic arthritis. There are pan compartmental bone ankyloses with erosive changes or partial bone fusions of the wrists. There are also bone ankyloses of the scaphoids to the trapeziums and the carpals to the metacarpals. Knees Bone fusions may be observed in the large joints such as the knees. Forefeet IP joints Bone ankyloses of multiple IP joints with osseous erosions and proliferations are seen. Particularly bone ankyloses in the IP joints of the great toes are prominent. DIP joints There are bone ankyloses of the DIP joints may be seen.

Figure 416. Bone ankylosis of the right third DIP joint in a patient with psoriatic arthritis.

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Figure 417. There are bone ankyloses of the DIP joints of the toes in a patient with psoriatic arthritis. Manubriosternal symphysises Eburnation and synostosis may be seen in the manubriosternal symphysises. Spine In psoriatic arthritis, voluminous paravertebral new bone formation is seen in addition to vertebral bone fusions. Rarely, ankyloses of the apophyseal joints may be seen. Also, spontaneous fusions of the atlanto-axial regions have been observed in psoriatic spondylitis [Daunt SON 1985]. Sacroiliac joints Bone growth leads to bone bridging and joint space narrowing, sometimes intra-articular bone ankyloses in the sacroiliac joints. Although bone ankyloses can occur, the prevalence of the ankyloses has been much less frequent than that in ankylosing spondylitis and the spondylitis associated with inflammatory bowel diseases. Even without ankyloses of the synovial joints, ossification of the ligaments between the sacrums and the iliums can occur. When intra-articular osseous fusions of the sacroiliac joints are complete, the sclerosis may disappear. Temporomandibular joints Intra-articular bony ankyloses of the temporomandibular joints have been recorded [Stimson CW 1982]. References Aydin SZZR, Tinazzi I, Castillo-Gallego C, Kwok C, Wilson C, Goodfield M, Gisondi P, Tan AL, Marzo-Ortega H, Emery P, Wakefield RJ, McGonagle DG.Ash. The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development. Ann Rheum Dis, 2013, 72:992-5. Brower AD.Flemming. Arthritis in Black and White. 3rd Ed. London: Elsevier Health Sciences, 2012. Bywaters EGLAS.Dixon. Paravertebral ossification in psoriatic arthritis. Ann Rheum Dis, 1965, 25:313.

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Chiavaras MMJA, Yablon CM, Brigido MK, Girish G.Jacobson. Pitfalls in wrist and hand ultrasound. AJR Am J Roentgenol, 2014, 203:531-40. D'Agostino MAR, Hacquard-Bouder C, Brasseur JL, Dougados M, Breban M.Said-Nahal. Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum, 2003, 48:523-33. Daunt SONJC.Robertson. Spontaneous fusion of atlanto-axial dislocation in psoriatic spondylitis. Clin Rheumatol 4:465, 1985. Clin Rheumatol, 1985, 4:465. Dzioba RBJBenjamin. Spontaneous atlantoaxial fusion in psoriatic arthritis. Spine, 1985, 70:102. Finzel SE, Kocijan R, Engelke K, Englbrecht M, Schett G.Sahinbegovic. Inflammatory bone spur formation in psoriatic arthritis is different from bone spur formation in hand osteoarthritis. Arthritis Rheumatol, 2014, 66:2968-75. Firestein GS. Kelley & Firestein’s Textbook of Rheumatology. ➨ 1 ᕳ. ඲ 2 ᕳ. Philadelphia, PA: Elsevier, 2017. Forrester DM.JC.Brown. The Radiology of Joint Disease. Philadelphia: W.B. Saunders Company, 1987. Forrester DMJ.Kirkpatrick. Periostitis and pseudoperiostitis. Radiology, 1976, 118:597. Frediani B.A., Falsetti P., et al.Allegri. Bone mineral density in patients with psoriatic artiiritis. J Rheumatol, 2001, 28:138-143. Gladman DDC, Mease P, Clegg DO, Nash P.Antoni. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis, 2005, 64 Suppl 2:ii14-7. Goupille PV, Roulot B, Brunais J, Valat JP.Védère. Incidence of osteoperiostitis of the great toe in psoriatic arthritis. J Rheumatol, 1996, 23:1553-6. Hahn KG, Eibner D, et al.Thiers. Skelettszintigraphische Befimde bei der Psoriasis. Nuklearmedizin, 1980, 79:178. Jacobson JAG, Jiang Y, Resnick D.Girish. Radiographic evaluation of arthritis: inflammatory conditions. Radiology, 2008, 248:378–89. doi: 10.1148/ radiol.2482062110 . Jane E FreestonC Coates, Jackie L Nam, Anna R Moverley, Elizabeth M A Hensor, Richard J Wakefield, Paul Emery, Philip S Helliwell, Philip G ConaghanLaura. Is There Subclinical Synovitis in Early Psoriatic Arthritis? A Clinical Comparison With Gray-Scale and Power Doppler Ultrasound. Arthritis Care Res (Hoboken), 2014, 66:432–439. Jenkinson TJ, Evison G, Cohen M, Lovell C, McHugh NJ.Armas. The cervical spine in psoriatic arthritis: a clinical and radiological study. Br J Rheumatol, 1994, 33:255-9. Kapitonova M.Y.O.Mansor. Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death. Malays J Pathol, 2003, 25:15-27. Madsen KBAG.Jurik. MRI grading method for active and chronic spinal changes in spondyloarthritis. Clin Radiol, 2009, 65:6-14. Merola JFLR, Fleischmann R.Espinoza. Distinguishing rheumatoid arthritis from psoriatic arthritis. RMD Open. 2018 Aug 13;4(2):e000656., 2018, 4(2):e000656. . Narváez JJA, de Albert M, Gómez-Vaquero C, Nolla JM.Narváez. Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin Arthritis Rheum, 2012, 42:234-45. Ory PA. Radiography in the assessment of musculoskeletal conditions. Best Pract Res Clin Rheumatol, 2003, 17:495– 512. Paparo FM, Semprini A, Camellino D, Garlaschi A, Cimmino MA, et al.Ravelli. Seronegative spondyloarthropathies: what radiologists should know. Radiol Med, 2014, 119:156–163. Resnick D. Radiology of the talocalcaneal articulations: Anatomic considerations and arthrography. Radiology, 1974, 111:581-6. Resnick DRW.Broderick. Bony proliferation of terminal toe phalanges in psoriasis: The "ivory" phalanx. J Can Assoc Radiol, 1977, 28:187. Schacherl MF.Schilling. Rontgenbefimde an den Gliedmassengelenken bei Polyarthritis psoriatica. Z Rheumaforsch, 1967, 26:442. Schoellnast HHA, Hermann J, Schaffler GJ, Reittner P, Kammerhuber F, Szolar DH, Preidler KW.Deutschmann. Psoriatic arthritis and rheumatoid arthritis: findings in contrast-enhanced MRI. AJR Am J Roentgenol, 2006, 187:351-7. Simon DF, Kleyer A, Haschka J, Englbrecht M, Kraus S, Hueber AJ, Kocijan R, Sticherling M, Schett G, Rech J.Faustini. Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis. Ann Rheum Dis, 2016, 75:660-6. . Spira DI, Henes J, Kümmerle-Deschner J, Schulze M, Boss A, Horger M.Kötter. MRI findings in psoriatic arthritis of the hands. AJR Am J Roentgenol, 2010, 195:1187-93. Spira DJ, Kötter I, Vogel M, Horger M.Henes. Psoriatic arthritis--conventional X-ray diagnosis in the hand and foot. Rofo, 2009, 181:517-20. Stimson CWSG.Leban. Recurrent ankylosis of the temporomandibular joint in a patient with chronic psoriasis. J Oral Maxillofac Surg, 1982, 40:678. Sudoá-SzopiĔska IG, Kwiatkowska B, PracoĔ G.Matuszewska. Diagnostic imaging of psoriatic arthritis. Part I: etiopathogenesis, classifications and radiographic features. J Ultrason., 2016, 16:65–77.

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CHAPTER 4 B2: RESORPTION OF THE BONES IN PSORIATIC ARTHRITIS SYUICHI KOARADA, YUKIKO TAKEYAMA

Abstract The principle of bone changes in psoriatic arthritis is the coexistence of bone resorption and osteogenesis within the same places. Bone resorption includes erosions, osteolysis, bone cysts and bone marrow edema. In this chapter, we discuss these characteristic features of the resorption of the bones of psoriatic arthritis. Bone resorption The presence of erosions in the small joints without osteoporosis is characteristic of psoriatic arthritis and the erosive changes are prominent. Comparison with rheumatoid arthritis Bone erosions in psoriatic arthritis are structurally different from those found in rheumatoid arthritis and osteoarthritis. While rheumatoid arthritis is characterized primarily by destructive bone lesions, psoriatic arthritis causes destruction and growth of the bones and may co-exist in the same patients and in the same joints [van der Heijde D. 2009]. Bone erosions in psoriatic arthritis are often obscured as they are made unclear by additional growth of the bones. This feature is not usually found in rheumatoid arthritis. Early erosive changes The presence of articular and tendinous erosions is seen in patients with early psoriatic arthritis through conventional radiography [C. A. Scarpa R. 2008]. Erosions initially occur at the margins of the joints, but then progress towards the centers. The early erosive changes in psoriatic arthritis are very common, with occurring of erosions in 15-47% of patients within the first two years [Narváez J 2012]. Early erosions, like in rheumatoid arthritis, are marginal erosions and their boundaries are clear [Ory P.A. 2003] [Brown A.K. 2013].

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Figure 418. T-type erosions in patients with psoriatic arthritis. Micro CT In studies using high-resolution micro-computed tomography (ȝCT), unlike erosions in rheumatoid arthritis, erosions in psoriatic arthritis are small and deep, and do not dominate at the radial sides [Narváez J 2012]. A comparative study of micro-CT at the MCP joints in patients with psoriatic arthritis and rheumatoid arthritis showed that the erosions of patients with rheumatoid arthritis are U-shaped, and the erosions of psoriatic arthritis patients are ȍ-shaped [Finzel S. 2011]. MRI A study of patients with psoriatic arthritis has shown that the presence of bone marrow edema and erosions is closely related, and it has suggested that bone marrow edema causes erosions [Tan YM 2009]. In addition, the presence of subchondral contrast regions before bone erosion formation is also detected by MRI. Marginal erosions Erosions in psoriatic arthritis are often located near the collateral ligaments, but erosions in osteoarthritis tend to occur in the center of joints [Braum LS 2013]. Early erosions begin at the joint margins both in psoriatic arthritis and rheumatoid arthritis. Although in rheumatoid arthritis, early erosions occur in the bare areas of the joints, in psoriatic arthritis very early erosions begin at the attachment sites of the joint capsules and the ligaments.

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Figure 419. Very early marginal erosions of the DIP joints in a patient with psoriatic arthritis.

Figure 420. Marginal erosions at the DIP joints in patients with psoriatic arthritis.

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Figure 421. Marginal erosions of the PIP joint in a patient with psoriatic arthritis. Bone formation adjacent to erosions Although early marginal erosions are well-defined, erosions become irregular and obscure as the disease progresses because periosteal bone formation adjacent to the erosions occurs. Erosions have spiculated appearances, especially towards the margins [Ory P.A. 2003] [Brown A.K. 2013]. Erosive changes in advanced stages As the progression of the psoriatic arthritis, findings of radiographs become like rheumatoid arthritis, with joint space narrowing and growth of erosions. The erosions progress over time, and the lesions also become to involve the central areas. Subchondral erosions expand and become pencil-in-cup deformities, cup-like deformities, cup-and-saucer deformities, mushroom-like phalanges, and club-shaped phalanges. Joint damages may manifest as erosive changes with new bone formation around the joints, which allows psoriatic arthritis to be differentiated from rheumatoid arthritis.

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Central erosions Bone erosions are prominent in psoriatic arthritis [Taniguchi A. 2007]. In advanced stages, central erosions also occur.

Figure 422. Central erosions of the DIP joints in patients with psoriatic arthritis. Subchondral erosions Subchondral erosions may be observed in patients with psoriatic arthritis. When subchondral erosions are extensive, the subchondral bones can be destroyed, leading to joint space widening. Erosions at the entheses may be seen. However, the long-term changes at the entheses are nonspecific and may also be found in weight-bearing entheses due to mechanical stress [Freeston JE 2014]. The erosions of the entheses also suggest spondyloarthritis [W. R. McGonagle D 2008]. Radiological findings of joint capsular calcifications and erosions at the insertion sites of the tendons and joint capsules in psoriatic arthritis suggest that pathological changes in the DIP joints are due to enthesitis. CT Compared to radiography, CT is more sensitive and highly reliable for the detection of small bone erosions of the hands. Studies using high-resolution CT compare bone structures between patients with rheumatoid arthritis and patients with psoriatic arthritis. Small inverse omega-shaped and tubule-shaped bone erosions are typical of psoriatic arthritis. In high-resolution micro-CT, the erosions of psoriatic arthritis are small and deep, unlike erosions of rheumatoid arthritis, and they are not predominant to radial sides [Narváez J 2012]. Erosions of psoriatic arthritis become more irregular and unclear as the repair mechanism works. High resolution micro-CT is useful for differential diagnosis.

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MRI Synovitis and bone erosions of peripheral joints in psoriatic arthritis have no disease-specific features on MRI. For bone erosions, there were no changes that could distinguish psoriatic arthritis and rheumatoid arthritis on MRI [Coates LC 2012]. Findings of joints Distal phalanges Uneven outlines with erosions and osteolysis of the phalangeal tufts may be seen in the distal phalanges. Hands Radiographic changes of the interphalangeal joints of the hands are observed. DIP joints Erosive lesions of the DIP joints are most common in psoriatic arthritis.

Figure 423. Erosions of the right second DIP joints in patients with psoriatic arthritis.

Figure 424. Erosions of the left second DIP joints in patients with psoriatic arthritis.

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Figure 425. Erosions of the right third DIP joints in patients with psoriatic arthritis.

Figure 426. Central erosion at the right third DIP joint in a patient with psoriatic arthritis over time.

Figure 427. Erosions of the left third DIP joints in patients with psoriatic arthritis.

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Figure 428. Erosions of the right fourth DIP joints in patients with psoriatic arthritis.

Figure 429. Central erosion of the right fourth DIP joint in a patient with psoriatic arthritis. T1-weighted MR image shows central erosion and T2-weighted STIR MR image suggests bone marrow edema in the same place.

Figure 430. Erosions of the left fourth DIP joints in patients with psoriatic arthritis.

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Figure 431. Erosions of the right fifth DIP joints in patients with psoriatic arthritis.

Figure 432. Erosions of the left fifth DIP joints in patients with psoriatic arthritis. PIP joints At the PIP joints, erosive changes consist of marginal and central erosions.

Figure 433. Erosions of the right second PIP joints in patients with psoriatic arthritis.

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Figure 434. Erosions of the left second PIP joints in patients with psoriatic arthritis.

Figure 435. Erosions of the right third PIP joints in patients with psoriatic arthritis.

Figure 436. Erosions of the left third PIP joints in patients with psoriatic arthritis.

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Figure 437. Erosion of the left third PIP joint over time in a patient with psoriatic arthritis.

Figure 438. MR images show erosion at the left third PIP joint in a patient with psoriatic arthritis.

Figure 439. Erosions of the right fourth PIP joints in patients with psoriatic arthritis.

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Figure 440. Erosions of the left fourth PIP joints in patients with psoriatic arthritis.

Figure 441. Erosions of the right fifth PIP joints in patients with psoriatic arthritis.

Figure 442. Erosions of the left fifth PIP joints in patients with psoriatic arthritis.

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IP joints

Figure 443. Erosions of the right first IP joints in patients with psoriatic arthritis.

Figure 444. Erosions with repair reaction of the right first IP joint in a patient with psoriatic arthritis.

Figure 445. Erosions of the right first IP joints in patients with psoriatic arthritis.

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MCP joints Abnormalities of the MCP joints are less pronounced, but there are marginal erosions. First MCP joints At the first MCP joints, sesamoid destruction may be associated with other articular abnormalities.

Figure 446. Erosions of the right first MCP joints in patients with psoriatic arthritis.

Figure 447. Erosions of the left first MCP joints in patients with psoriatic arthritis. Second MCP joints

Figure 448. Erosions of the right second MCP joints in patients with psoriatic arthritis.

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Figure 449. MR images show erosion of the right second MCP joint in a patient with psoriatic arthritis.

Figure 450. Erosions of the left second MCP joints in patients with psoriatic arthritis.

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Figure 451. Erosion of the left second MCP joint over time in a patient with psoriatic arthritis. Third MCP joints

Figure 452. Erosions of the right third MCP joints in patients with psoriatic arthritis.

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Figure 453. Erosions of the left third MCP joints in patients with psoriatic arthritis. Fourth MCP joints

Figure 454. Erosions of the right fourth MCP joints in patients with psoriatic arthritis.

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Figure 455. Erosion of the right fourth MCP joint over time in a patient with psoriatic arthritis.

Figure 456. Erosions of the left fourth MCP joints in patients with psoriatic arthritis.

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Fifth MCP joints

Figure 457. Erosions of the right fifth MCP joints in patients with psoriatic arthritis.

Figure 458. Erosions of the left fifth MCP joints in patients with psoriatic arthritis.

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Figure 459. Plain radiograph and MR images show erosion of the left fifth MCP joint in a patient with psoriatic arthritis. Wrists

Figure 460. PA views of the hands of a patient with psoriatic arthritis. Erosions of the right trapezium and trapezoid are observed.

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Figure 461. Erosion of the right trapezoid in a patient with psoriatic arthritis.

Figure 462. Erosions of the right capitate over time in a patient with psoriatic arthritis.

Figure 463. Erosions of the left hamates in patients with psoriatic arthritis.

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Figure 464. Erosion of the right scaphoid in a patient with psoriatic arthritis.

Figure 465. Erosion of the left scaphoid in a patient with psoriatic arthritis.

Figure 466. Erosion of the right pisiform bone in a patient with psoriatic arthritis.

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Figure 467. Erosion of the right ulna is seen in a patient with psoriatic arthritis.

Figure 468. Erosion with destructive changes of the right ulnar styloid process is seen in a patient with psoriatic arthritis.

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Figure 469. Erosions of the right ulnar styloid process are seen in a patient with psoriatic arthritis.

Figure 470. Erosions of the left ulnar styloid process and erosion of the ulnar head.

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Figure 471. PA view of the right hand of a patient with psoriatic arthritis. Deformation of the right ulnar styloid process suggests the presence of erosions.

Figure 472. PA and oblique views of the ulnas. Deformations of the ulnar styloid processes.

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Figure 473. Disappearance of the left lunar styloid process due to erosions in a patient with psoriatic arthritis.

Figure 474. Erosions of the left ulnar head in a patient with psoriatic arthritis.

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Figure 475. MR images show erosions of the carpal bones of the hands in a patient with psoriatic arthritis.

Figure 476. MR images show early changes of erosions of the carpal bones of the right hand in a patient with psoriatic arthritis.

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Elbows Involvement of the elbows tends to be asymmetrical with erosive changes. Findings may vary from minor degrees of erosions to extensive osteolysis.

Figure 477. A small osseous erosion is seen at the left elbow in a patient with psoriatic arthritis. Shoulders

Figure 478. Bone erosions of the right shoulder in a patient with psoriatic arthritis.

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Figure 479. A bone erosion of the right shoulder in a patient with psoriatic arthritis.

Figure 480. An erosion of the left shoulder in a patient with psoriatic arthritis.

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Figure 481. MR images show erosions of the left shoulder in a patient with psoriatic arthritis.

Figure 482. Erosions of the right acromioclavicular joint in a patient with psoriatic arthritis.

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Knees

Figure 483. Erosions of the left knee in a patient with psoriatic arthritis.

Figure 484. MR images show an erosion of the right knee in a patient with psoriatic arthritis. Ankles

Figure 485. An erosion of the left talus in a patient with psoriatic arthritis.

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Calcaneuses Erosions are common on the posterior and inferior surfaces of the calcaneuses [Resnick D. 1974]. Erosions occur in the attachments of the Achilles tendons of the posterosuperior surfaces of the calcaneuses, and the attachments of the plantar aponeurosises on the inferior surfaces. Retrocalcaneal bursitises are associated with erosions of the posterosuperior surfaces of the calcaneuses. Some erosions may be accompanied by calcaneus spurs.

Figure 486. An erosion (large arrow) and bone proliferation (small arrow) at the attachment of the Achilles tendon.

Figure 487. A small erosion and bone proliferation with osteosclerosis at the attachment of the Achilles tendon in a patient with psoriatic arthritis.

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Figure 488. A small erosion without bone proliferation at the attachment of the Achilles tendon.

Figure 489. An erosion of the left cuboid in a patient with psoriatic arthritis.

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Forefeet

Figure 490. PA views of the forefeet. Erosions of the MCP joints are seen in a patient with psoriatic arthritis.

Figure 491. Oblique views of the forefeet. Erosions are seen in a patient with psoriatic arthritis.

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Feet MTP joints

Figure 492. Erosions of the right first MTP joints in patients with psoriatic arthritis.

Figure 493. Erosions of the left first MTP joints in patients with psoriatic arthritis.

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Figure 494. Erosions of the right second MTP joints in patients with psoriatic arthritis.

Figure 495. Erosions of the left second MTP joints in patients with psoriatic arthritis.

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Figure 496. Erosions of the right third MTP joints in patients with psoriatic arthritis.

Figure 497. Erosions of the left third MTP joints in patients with psoriatic arthritis.

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Figure 498. Erosions of the right fourth MTP joints in patients with psoriatic arthritis.

Figure 499. Erosions of the left fourth MTP joints in patients with psoriatic arthritis.

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Figure 500. Erosions of the right fifth MTP joints in patients with psoriatic arthritis.

Figure 501. Erosions of the left fifth MTP joints in patients with psoriatic arthritis.

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PIP joints

Figure 502. Erosions of the left second PIP joint in a patient with psoriatic arthritis.

Figure 503. An erosion of the right fifth PIP joint in a patient with psoriatic arthritis.

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IP joints

Figure 504. An erosion of the right first IP joint of a patient with psoriatic arthritis.

Figure 505. Erosions of the left first IP joints of patients with psoriatic arthritis.

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DIP joints

Figure 506. An erosion of the left second DIP joint of a patient with psoriatic arthritis.

Figure 507. an erosion of the left third DIP joint in a patient with psoriatic arthritis.

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Figure 508. An erosion of the left third DIP joint in a patient with psoriatic arthritis. Spine In the thoraco-lumbar spine, erosions have been reported in psoriatic arthritis, but are rare [Scarpa R. 2000]. There are erosions at the discovertebral junctions and the apophyseal joints. Erosions in the spine are more sensitively detected by MRI than conventional radiography, and MR images may show bone marrow fat depositions as a result of osseous inflammation [Madsen KB 2009].

Figure 509. Coronal and sagittal CT reconstructions show discovertebral erosions in the lumbar spine of a patient with psoriatic arthritis.

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Figure 510. Sagittal CT reconstruction of the lumbar spine showing the discovertebral erosions in a patient with psoriatic arthritis. Pubic symphyses

Figure 511. An erosion of the pubic symphyses in a patient with psoriatic arthritis. Osteolysis, Osteolytic lesions In psoriatic arthritis there are tapering and dissolution due to bone resorption of the distal phalanges. In particular, the resorption of the tufts of the distal phalanges in the hands and the feet is characteristic [Fassbender HG. 1974]. However, the resorption of the tufts is a nonspecific sign. Eroded bones are smooth or irregular, often with soft tissue edema and abnormalities of the adjacent interphalangeal joints. In psoriatic arthritis, periarticular osteolysis is greater than reactive arthritis and ankylosing spondylitis. "Morning-star" appearance Destruction of the ungual tuberosities (acro-osteolysis) creates a morning-star appearance.

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Phalangeal tuft acro-osteolysis Phalangeal tuft acro-osteolysis of the distal phalanges of the hands and the feet is characteristic of psoriatic arthritis. Erosions occur at the distal tufts of the digits to create a pattern of acro-osteolysis. Bone resorption of the tufts may be evident in one or more distal phalanges, which may be bilateral or unilateral, and symmetric or asymmetric. Smooth tapered or irregular eroded bones in contour can be seen. Bone resorption of the tufts is almost always accompanied by severe nail lesions. Soft tissue swelling and lesions of the adjacent interphalangeal joints are also common. Osteolysis of the phalanges may also occur along with the resorption of the tufts. Although severe resorption of the tufts is associated with destructive joint lesions, bone resorption is mild if there are no obvious joint anomalies [Miller JL 1971]. In the absence of obvious joint abnormalities, resorption of the rafts is like the changes caused by collagen vascular diseases, such as scleroderma and thermal injury. However, prevalence of resorption in the tufts of the distal phalanges is rare in rheumatoid arthritis (1.8%) [Izquierdo YE 2017].

Figure 512. Osteolysis of the tufts of the right first distal phalanges in patients with psoriatic arthritis.

Figure 513. Osteolysis of the tufts of the left first distal phalanges in patients with psoriatic arthritis.

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Figure 514. Osteolysis of the tufts of the right second distal phalanges in patients with psoriatic arthritis.

Figure 515. Osteolysis of the tufts of the left second distal phalanges in patients with psoriatic arthritis.

Figure 516. Osteolysis of the tufts of the right third distal phalanges in patients with psoriatic arthritis.

Figure 517. Osteolysis of the tufts of the left third distal phalanges in patients with psoriatic arthritis.

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Figure 518. Osteolysis of the tufts of the right fourth distal phalanges in patients with psoriatic arthritis.

Figure 519. Osteolysis of the tufts of the left fourth distal phalanges in patients with psoriatic arthritis.

Figure 520. Osteolysis of the tufts of the right fifth distal phalanges in patients with psoriatic arthritis.

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Figure 521. Osteolysis of the tufts of the left fifth distal phalanges in patients with psoriatic arthritis.

Figure 522. Acro-osteolysis of the distal tufts of the right foot in a patient with psoriatic arthritis. Peg-shaped phalanges, Pencil in cup deformities The whittling or penciling of the tufts can be peg-shaped phalanges. The ends of the bones are pointed and a pencil-in-cup deformities occur. Bone resorption of the phalanges and destructive arthritis of the DIP joints are often associated with the nail changes of the same digits.

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Hands In psoriatic arthritis, extensive osteolysis can occur in the proximal segments of the hands, but such lesions are relatively rare. Inferior radioulnar compartments Occasionally, lesions in the inferior radioulnar compartments are extensive, and osteolysis may occur [Sherman MS. 1952]. Elbows and shoulders Findings in the elbows and the shoulders vary from mild bone erosions to extensive osteolysis. Feet Osteolysis of the diaphyses of metatarsals, the phalanges and the tufts may be present.

Figure 523. Time course of osteolysis in psoriatic arthritis - from marginal erosions to luxation through pencil-in-cup deformity.

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Osteolysis of sternoclavicular joints

Figure 524. Osteolysis and swelling of the right sternoclavicular joint in a patient with psoriatic arthritis.

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Figure 525. Plain and enhanced CT images show osteolysis and inflammation of the right sternoclavicular joint in a patient with psoriatic arthritis. Bone cysts Bone cysts may be seen in patients with psoriatic arthritis. Subchondral cysts are commonly detected in the DIP joints of the hand and the feet and the IP joints of the first toes.

Figure 526. Cystic change of the right DIP joint in a patient with psoriatic arthritis.

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Figure 527. Bone cysts of the left DIP joints in patients with psoriatic arthritis.

Figure 528. Disappearance of bone cyst in a patient with psoriatic arthritis.

Figure 529. Bone cyst of the right scaphoid in a patient with psoriatic arthritis.

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Figure 530. Bone cyst of the left triquetrum in a patient with psoriatic arthritis.

Figure 531. Bone cyst of the right ulna in a patient with psoriatic arthritis.

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Figure 532. MR images show an erosion of the left shoulder in a patient with psoriatic arthritis.

Figure 533. Bone cyst of the right second MTP joint in a patient with psoriatic arthritis.

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Bone marrow edema, Bone edema Bone marrow edema is uniquely visualized by MRI. Bone marrow edema in psoriatic arthritis can be evident in conjunction with inflammation and bone formation. A relationship between bone marrow edema and the development of bone erosions detected by CT has been suggested [Poggenborg RP 2014]. Synovitis of psoriatic arthritis has the similar features generally when compared to rheumatoid arthritis. However, bone marrow edema is more prominent in psoriatic arthritis compared with rheumatoid arthritis. In rheumatoid arthritis, bone marrow edema occurs generally in the subchondral bones [C. P. McGonagle D 1999]. However, in psoriatic arthritis, bone marrow edema occurs near the entheses [Totterman SM. 2004]. Furthermore, mutilans arthritis type of psoriatic arthritis has more severe bone marrow edema than other types [Tan YM 2009]. In psoriatic arthritis, bone marrow edema in MRI can occur in any bone. Bone marrow edema of peripheral psoriatic arthritis does not have disease-specific features on MRI [McQueen F 2006] [Ghanem N 2007] [Tehranzadeh J 2008] [Wiell C 2007].

Figure 534. MR (T2-STIR) image shows bone marrow edema of the left fifth DIP joint in a patient with psoriatic arthritis.

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Figure 535. MR images show bone marrow edema of the right foot in a patient with psoriatic arthritis. In psoriatic arthritis, bone marrow edema starts at the corners of the phalanges where the joint capsules are attached, and it spreads to the entire bones as it progresses. Bone marrow edema of diaphysises In psoriatic arthritis, bone marrow edema is more extensive and widespread toward the diaphysis of the bones [Poggenborg RP 2014]. In a comparative study of MRI findings on the wrists and the hands of patients with psoriatic arthritis and rheumatoid arthritis, enthesitis, bone marrow edema of the diaphysis, and subcutaneous tissue lesions were characteristic of psoriatic arthritis [Narváez J. 2012]. Bone marrow edema of the diaphysises in psoriatic arthritis is profound, possibly associated with inflammation, and may be a factor in new bone formation.

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Figure 536. MR images show bone marrow edema of the right calcaneus at the enthesis of the Achilles tendon. Spine In the spine of psoriatic arthritis, bone marrow edema in the attachment sites is seen.

Figure 537. MR images show bone marrow edema of the lumbar spine in a patient with psoriatic arthritis.

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Figure 538. Bone marrow edema of the lumbar spine in a patient with psoriatic arthritis.

Figure 539. Bone scan of a patient with psoriatic arthritis. MR image shows bone marrow edema of the manubriosternal symphysis.

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References Braum LSD, Bruns A, Philipp S, Hermann S, Aupperle K, Tan AL, Diekhoff T, Hamm B, Hermann KG.McGonagle. Characterisation of hand small joints arthropathy using high-resolution MRI--limited discrimination between osteoarthritis and psoriatic arthritis. Eur Radiol, 2013. Brown A.K. How to interpret plain radiographs in clinical practice. Best Prac Res Clin Rheumatol, 2013. Coates LCR, Conaghan PG, Freeston JE.Hodgson. MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis. Best Prac Res Clin Rheumatol, 2012, 26:805–822. Fassbender HG. Pathomechanismen der Arthritis psoriatica. Z Rheuma-forsch, 1974, 55(Suppl 3):286. Finzel S.M., Engelke K., Stach C., Schett G.Englbrecht. A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann Rheum Dis, 2011. Freeston JELC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG.Coates. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res (Hoboken), 2014, 66:432-9. Ghanem NM, Pache G, Bley T, Walker UA, Langer M.Uhl. MRI in psoriatic arthritis with hand and foot involvement. Rheumatol Int, 2007, 27:387-93. . Izquierdo YEEC, Castañeda LM, Gómez SV, Zambrano FS.Páramo. Radiographic changes in the distal phalanx tuft of the hands in subjects with rheumatoid arthritis. Systematic review. Revista Colombiana de Reumatología, 2017, 24:32-39. Madsen KBAG.Jurik. MRI grading method for active and chronic spinal changes in spondyloarthritis. Clin Radiol, 2009, 65:6-14. McGonagle DPG, O’Connor P et al.Conaghan. The relationship between synovitis and bone changes in early untreated rheumatoid arthritis: a controlled magnetic resonance imaging study. Arthritis Rheum, 1999, 42:1706– 1711. McGonagle DRJ, Tan AL, D'Agostino MA, Toumi H, Hayashi K, Emery P, Benjamin M.Wakefield. Distinct topography of erosion and new bone formation in achilles tendon enthesitis: implications for understanding the link between inflammation and bone formation in spondylarthritis. Arthritis Rheum, 2008, 58:2694-9. McQueen FM, Østergaard M.Lassere. Magnetic resonance imaging in psoriatic arthritis: a review of the literature. Arthritis Res Ther, 2006, 8:207. Miller JLK, Tomtellotte CD.Soltani. Psoriatic acro-osteolysis without arthritis: A case study. J Bone Joint Surg Am, 1971, 55:371. Narváez J.JA, de Albert M, Gómez-Vaquero C, Nolla JM.Narváez. Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin Arthritis Rheum, 2012, 42:234–2. Narváez JJA, de Albert M, Gómez-Vaquero C, Nolla JM.Narváez. Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin Arthritis Rheum, 2012, 42:234–2. Ory P.A. Radiography in the assessment of musculoskeletal conditions. Best Pract Res Clin Rheumatol, 2003. Poggenborg RPC, Bøyeses P, Boonen A, Bird P, Pedersen SJ et al.Wiell. No overall damage progression despite persistent inflammation in adalimumab-treated psoriatic arthritis patients: results from an investigator–initiated 48-week comparative magnetic resonance imaging, computed tomography and radiography trial. Rheumatology (Oxford), 2014, 53:746–756. Resnick D. Radiology of the talocalcaneal articulations: Anatomic considerations and arthrography. Radiology, 1974, 111:581-6. Scarpa R. Discovertebral erosions and destruction in psoriatic arthritis. J Rheumatol, 2000. Scarpa R.A., Peluso R., Atteno M., Gisonni P., Iervolino S., Di Minno M.N., Nicolai E., Salvatore M., del Puente A.Cuocolo. Early psoriatic arthritis: the clinical spectrum. J Rheumatol, 2008. Sherman MS. Psoriatic arthritis: Observations on the clinical, roentgenographic, and pathological changes. J Bone Joint Surg Am, 1952, 54:831. Tan YMM, Doyle A, Dalbeth N, Lobo M, Reeves Q, Robinson E, Taylor WJ, Jones PB, Pui K, Lee J, McQueen FM.Østergaard. MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage. Arthritis Res Ther, 2009, 11(1):R2. Taniguchi A.N.Kamatani. A case of psoriatic arthritis without the appearance of psoriatic skin or nail lesions for 21. APLAR Journal of Rheumatology, 2007, 10: 306-309. Tehranzadeh JO, Anavim A, Shin J.Ashikyan. Detailed analysis of contrast-enhanced MRI of hands and wrists in patients with psoriatic arthritis. Skeletal Radiol, 2008, 37:433-42. Totterman SM. Magnetic resonance imaging of psoriatic arthritis: insight from traditional and three-dimensional analysis. Curr Rheumatol Rep, 2004, 6:317-21. van der Heijde D.M..Østergaard. Assessment of disease activity and damage in inflammatory arthritis. JWJ Bijlsma The EULAR compendium on rheumatic diseases. 2009 BMJ Publishing Group London. 2009.

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Wiell CM, Hasselquist M, Møller JM, Vestergaard A, Nørregaard J, Terslev L, Østergaard M.Szkudlarek. Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis. Arthritis Res Ther, 2007, 9:R119.

CHAPTER 5 C: CAPSULA ARTICULARIS OF PSORIATIC ARTHRITIS SYUICHI KOARADA, YURI SHIRAHAMA

Abstract Regarding the lesions in the joint capsules, evaluation of synovial proliferation and blood flow detection in the intraarticular synovium, intraarticular calcifications, and articular cartilages should be performed. For lesions in the joints, detection of synovitis by conventional radiography is difficult; ultrasound, MRI, and PET-CT are used. However, conventional radiography is suitable for detection of the intraarticular calcifications such as pseudogout. One of the characteristic findings is joint space widening in psoriatic arthritis. Cartilages Joint space narrowing or widening Although radiography is not sensitive nor specific for soft tissue lesions, it can evaluate the joint space as joint space can be narrowed or widened, as can the articular cartilages, indirectly. Cartilage surface fibrillation progresses and chondrocytes undergo apoptosis, which results in permanent cartilage damage, followed by joint space narrowing as a measure of cartilage loss [Kapitonova MY, 2003] [Wassenberg S, 2015]. In the large joints such as the knees, the ankles, the elbows, and the hips, the joint space disappears diffusely, like that seen in rheumatoid arthritis. Joint space narrowing (JSN) Joint lesions of psoriatic arthritis are typically associated with uniform narrowing of the cartilage layer. Joint space narrowing occurs due to destruction of the cartilage and the bones. Pseudo-narrowing of joint space may be present due to the resorption process of the subchondral bone plates. There is narrowing of the joint space often accompanied by osteophyte formation and periostitis. Diffuse loss of joint space, Uniform reduction of joint space As the disease progresses, plain radiographs show joint space narrowing and erosions. Joint space narrowing is one of the radiographic findings of cartilage loss and can occur in any joint, but most commonly occurs in the DIP and the PIP joints, and less in the MCP joints. The progression of severe joint space narrowing results in bone ankyloses in the late stages of psoriatic arthritis, especially in the digits.

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Findings of joints Hands In the hands, there may be joint space narrowing in the interphalangeal joints.

Figure 540. A patient with psoriatic arthritis. In the hands, joint space narrowing is found in the DIP, the PIP and MCP joints and the left wrist.

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DIP joints Joint space narrowing is most common and typical in the DIP joints of psoriatic arthritis.

Figure 541. Joint space narrowing of the DIP joints is predominant in a patient with psoriatic arthritis.

Figure 542. Narrowing of the joint space at the second DIP joint over time in a patient with psoriatic arthritis.

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Figure 543. Joint space narrowing of the right second DIP joints in patients with psoriatic arthritis.

Figure 544. Joint space narrowing of the left second DIP joints in patients with psoriatic arthritis. Third DIP joints

Figure 545. Joint space narrowing of the right third DIP joints in patients with psoriatic arthritis.

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Figure 546. Joint space narrowing of the left third DIP joints in patients with psoriatic arthritis. Fourth DIP joints

Figure 547. Joint space narrowing of the right fourth DIP joints in patients with psoriatic arthritis.

Figure 548. PA and oblique views show joint space narrowing of the right fourth DIP joints in patients with psoriatic arthritis.

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Figure 549. Joint space narrowing of the left fourth DIP joints in patients with psoriatic arthritis. Fifth DIP joints

Figure 550. Joint space narrowing of the right fifth DIP joints in patients with psoriatic arthritis.

Figure 551. Joint space narrowing of the left fifth DIP joints in patients with psoriatic arthritis.

Figure 552. Joint space narrowing of the DIP joint in a patient with psoriatic arthritis. MR images show bone marrow edema in the same joint.

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PIP joints In psoriatic arthritis, joint space narrowing occurs in the PIP joints as well as in the DIP joints. Second PIP joints

Figure 553. Joint space narrowing of the right second PIP joints in patients with psoriatic arthritis.

Figure 554. Joint space narrowing of the left second PIP joints in patients with psoriatic arthritis.

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Figure 555. Joint space narrowing of the right third PIP joints in patients with psoriatic arthritis.

Figure 556. Joint space narrowing of the left third PIP joints in patients with psoriatic arthritis. Fourth PIP joints

Figure 557. Joint space narrowing of the right fourth PIP joints in patients with psoriatic arthritis.

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Figure 558. Joint space narrowing of the left fourth PIP joints in patients with psoriatic arthritis. Fifth PIP joints

Figure 559. Joint space narrowing of the right fifth PIP joints in patients with psoriatic arthritis.

Figure 560. Joint space narrowing of the left fifth PIP joints in patients with psoriatic arthritis.

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IP joints Changes of the IP joints in patients with psoriatic arthritis include articular space narrowing.

Figure 561. Joint space narrowing of the right IP joint of the thumb in a patient with psoriatic arthritis. MCP joints Joint space narrowing, although less marked, could be seen at the MCP joints in psoriatic arthritis. Joint space narrowing of the MCP joints may be associated with soft tissue swelling, bone erosions and proliferation of the phalanges. First MCP joints

Figure 562. Joint space narrowing of the MCP joint of the right thumb in a patient with psoriatic arthritis.

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Figure 563. Joint space narrowing of the MCP joint of the left thumb in a patient with psoriatic arthritis. Second MCP joints

Figure 564. Joint space narrowing of the right second MCP joint in a patient with psoriatic arthritis.

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Figure 565. Joint space narrowing of the left second MCP joint in a patient with psoriatic arthritis. Third MCP joints

Figure 566. Joint space narrowing of the right third MCP joint in a patient with psoriatic arthritis.

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Figure 567. Joint space narrowing with calcifications of the left third MCP joint in a patient with psoriatic arthritis and pseudogout. Fourth MCP joints

Figure 568. Joint space narrowing of the right fourth MCP joint in a patient with psoriatic arthritis.

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Figure 569. Joint space narrowing with calcifications of the left fourth MCP joint in a patient with psoriatic arthritis and pseudogout. Fifth MCP joints

Figure 570. Joint space narrowing of the right fifth MCP joints in patients with psoriatic arthritis.

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Figure 571. Joint space narrowing of the left fifth MCP joint in a patient with psoriatic arthritis. Wrists There is joint space narrowing at the radiocarpal, midcarpal and carpometacarpal joints in the wrists. Lesions of the entire hands are characterized by joint space narrowing and intraarticular bone fusions but lack of osteoporosis.

Figure 572. A patient with psoriatic arthritis. There are joint space narrowing and ankylosis in the right wrist. However, osteoporosis is not seen.

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Figure 573. The distance between articular surface of the distal radius and the base of the third metacarpal bone suggests joint space narrowing of the right wrist in a patient with psoriatic arthritis over time. Elbows In the large joints, such as the elbows, the joint space disappears.

Figure 574. Uniform joint space narrowing of the right elbow in a patient with psoriatic arthritis. Shoulders Radiographs of the shoulders show narrowing of the glenohumeral joints.

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Hips The hips have loss of joint space, which is identical to rheumatoid arthritis. There is uniform or concentric loss of the cartilages of the joints.

Figure 575. Joint space narrowing of the right hip in a patient with psoriatic arthritis. Knees In the knees, diffuse loss of joint space is identical to rheumatoid arthritis.

Figure 576. A patient with psoriatic arthritis. Joint space narrowing and bone proliferation are seen in the knees.

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Figure 577. Lateral views of the knees of a patient with psoriatic arthritis show joint space narrowing and bone proliferation on the superior surface of the right patella and both the anterior proximal tibias.

Figure 578. Joint space narrowing of the left patellofemoral joint (PFJ) in a patient with psoriatic arthritis.

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Figure 579. A patient with psoriatic arthritis. The joint space narrowing of the knees can be proved more clearly in the standing position than AP view.

Figure 580. A patient with psoriatic arthritis. The changes of joint space narrowing at the right knee over time.

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Figure 581. A patient with psoriatic arthritis. The changes of joint space narrowing at the left knee over time. Feet Bilateral asymmetric changes predominate in the IP and the MTP joints, characterized by marginal erosions, bone growth, joint space alternation (narrowing or opening), and lack of osteoporosis. MTP joints In the MTP joints of the feet, there is joint space narrowing.

Figure 582. Joint space narrowing of the right first MTP joint in a patient with psoriatic arthritis.

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Figure 583. Joint space narrowing of the left first MTP joint in a patient with psoriatic arthritis. IP joints Joint space narrowing and bone ankyloses of the IP joints may be seen in psoriatic arthritis. Sacroiliac joints Significant joint space narrowing and bone ankyloses can occur but are less common than ankylosing spondylitis.

Figure 584. In the sacroiliac joints, joint space narrowing and osteosclerosis accompanied by blurring of joint space are observed.

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Figure 585. The right sacroiliac joint reveals joint space narrowing and osteosclerosis with blurring of the interosseous space in a patient with psoriatic arthritis. Pubic symphysises

Figure 586. Joint space narrowing of the pubic symphysis in a patient with psoriatic arthritis. Joint space widening (JSW) In psoriatic arthritis, because osteolysis produces wide and sharply demarcated joint space, this pseudo widening of interosseous joint space is characteristic. Erosions of psoriatic arthritis can be extensive and destroy the underlying subchondral bones, so the joint space may appear to be widened. The irregular bone surfaces are so extensive that they may even be as separated as one another. When arthritis widens the joint space, joint fluid and/or proliferated synovium may be present inside the joint capsules.

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Digits In the small joints of the digits, severe destruction of the marginal and the subchondral bones can result in significant joint space widening.

Figure 587. Erosive changes create the appearance of widened joint spaces of the left fourth DIP joint in a patient with psoriatic arthritis. Joint space narrowing has been seen in this joint a year ago. One year later, bone destruction of the joint has been associated with widening of the interosseous space. Sacroiliac joints Sacroiliitis may produce widening of the sacroiliac joints. The sacroiliac joints may show inflammatory findings and may lead to bone erosions and mild joint space widening. And then, the enlargement of the erosions causes the bone surfaces to become irregular, resulting in uneven and unequal joint space widening. Within the sacroiliac joints, joint space narrowing (early bone ankyloses) and widening (erosions) may be present at the same time.

Figure 588. The joint space of the left sacroiliac is widened.

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Figure 589. The joint space of the left sacroiliac joint is widened. However, minimal changes are present in the right sacroiliac joint.

Figure 590. The axial computed tomographic (CT) scan shows joint space widening of the left sacroiliac joint.

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Feet In the small joints of the toes, severe destruction of the marginal and the subchondral bones may result in considerable widening of the articular space.

Figure 591. Bone destruction of the DIP joint of third toe is strong, with joint space widening, dilation of the phalanx base and soft tissue swelling. Lack of articular space loss In some patients with psoriatic arthritis, the degree of chondrolysis by the inflamed synovium is variable, and articular space loss is much less constant, compared with rheumatoid arthritis. Since there is no reference value, it is difficult to evaluate joint space of the digits. It is important to compare with the left and right sides in order to find the early changes in joint space (narrowing and opening). Unlike rheumatoid arthritis, this method is useful because it progresses asymmetrically in psoriatic arthritis.

Joint space of the right third DIP joint appears to be narrow at first glance due to the formation of osteophytes, but there is no significant difference compared to the left. In addition, accurate assessment of the changes in the joint space requires comparing radiograph of the same joints over time.

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Figure 592. Although joint space appeared to be narrowed due to the osteophyte formation (bone proliferative changes) six years ago, the joint space is maintained over time. Synovial fluid In radiography, synovial fluid cannot be distinguished from the cartilages, the muscles, the tendons, the ligaments and synovium because they have the same density. Soft tissue swelling may occur at the affected joints and may reflect the presence of synovial fluid. Moreover, because the fat tissue appears as separate density, it may be possible to observe the fat tissue that has overhung by the retention of joint fluid. Ultrasound examination In an ultrasound examination, synovial fluid is distributed as hypoechoic areas within the joint capsules. By compressing the soft tissue with the probe, synovial fluid can be differentiated from synovial proliferation. If it is synovial fluid, it moves easily by compression. However, if it is synovial proliferation, it does not change by compression with the probe. MRI Fat-suppressed T2-weighted sequences of MRI sensitively detect synovial fluid.

T2-STIR image shows the synovial fluid in the right wrist in a patient with psoriatic arthritis.

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Figure 593. MR images show synovial fluid of the left elbow.

Figure 594. US images show synovial fluid of the right knee in a patient with psoriatic arthritis.

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Figure 595. MR images show synovial fluid in the knee of a patient with psoriatic arthritis.

Figure 596. MR images show synovial fluid in the knee of a patient with psoriatic arthritis. Synovitis Patients with psoriatic arthritis have synovitis. Patients with psoriasis also have more frequent changes of arthritis by MRI than healthy subjects [Offidani A, 1998]. Subclinical synovitis is common in patients with psoriatic arthritis [Freeston J.E., 2014], which, like RA, can lead to structural destruction [El Miedany Y, 2015]. Synovial changes in ultrasound examination can be like those of rheumatoid arthritis. In ultrasound assessment, the synovial pannus both in the small and large joints of psoriatic arthritis appears highly hyperemic respect to other chronic inflammatory conditions including rheumatoid arthritis. This feature appears to be associated with histopathological findings of psoriatic arthritis.

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Figure 597. Peri-arthritis of the left second PIP joint and arthritis of the right wrist.

Figure 598. Ultrasonography shows peri-articular PD signals and synovial proliferation of the third DIP joint in a patient with psoriatic arthritis. Bone scintigraphy Bone scintigraphy shows increased radionuclide accumulation and the distribution of synovitis of psoriatic arthritis, which can be used as a diagnostic reference. Hands In the peripheral joints of patients with psoriatic arthritis, synovitis is more common than bone marrow edema and bone erosions. Psoriatic arthritis often causes synovitis in the hands, especially in the DIP and the PIP joints, as compared with spondyloarthritis and normal subjects.

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DIP joints

Figure 599. Bone scintigraphy shows increased uptake in the right second DIP joint of a patient with psoriatic arthritis.

Figure 600. A patient with psoriatic arthritis who has strong arthralgia at the DIP joints. It is a strong arthritis of DIP joints that can be clearly seen by a visual inspection. However, in T2-STIR MR image, when it is not contrasted, synovitis of the DIP joints appears to be mild.

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Figure 601. The same patient as shown in the previous figure. In contrast-enhanced MR images, the synovium is clearly enhanced. MR images suggest strong synovitis of the DIP joints. PIP joints

Figure 602. MR image shows peri-arthritis and synovitis of the left third PIP joint in a patient with psoriatic arthritis.

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Figure 603. Peri-arthritis and synovitis of the right fifth PIP joint in a patient with psoriatic arthritis.

Figure 604. Synovitis and the peritenon extensor tendon (the central slip) inflammation of the right second PIP joint in a patient with psoriatic arthritis.

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Figure 605. Synovitis of the right third PIP joint in a patient with psoriatic arthritis.

Figure 606. Synovitis of the right fourth PIP joint in a patient with psoriatic arthritis.

Figure 607. Synovitis and the peritenon extensor tendon (the central slip) inflammation of the right second PIP joint in a patient with psoriatic arthritis.

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Figure 608. Synovitis of the right fourth PIP joint in a patient with psoriatic arthritis.

Figure 609. Synovitis of the right fifth PIP joint in a patient with psoriatic arthritis.

Figure 610. Synovitis of the right fifth PIP joint.

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Figure 611. Synovitis of the left fifth PIP joint. MCP joints First MCP joints

Figure 612. An ultrasound image shows synovial hypertophy of the right first MCP joint.

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Figure 613. Ultrasound images show synovitis of the right second MCP joint in a patient with psoriatic arthritis.

Figure 614. Synovitis of the right second MCP joint.

Figure 615. The fat-saturated gadolinium-enhanced T1-weighted MRI shows the synovium of the second MCP joint with enhancement in a patient with psoriatic arthritis.

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Third MCP joints

Figure 616. Ultrasound images shows synovitis of the right third MCP joint in a patient with psoriatic arthritis.

Figure 617. The MR image shows synovitis of the right third MCP joint. Fourth MCP joints

Figure 618. Ultrasound images show synovitis of the right fourth MCP joint.

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Fifth MCP joints

Figure 619. Ultrasound images show synovitis of the right fifth MCP joint in a patient with psoriatic arthritis.

Figure 620. The MR images show synovitis of the right fifth MCP joint.

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Wrists

Figure 621. Ultrasound images of dorsal longitudinal scans of the left wrist show marked joint cavity widening of the radiocarpal and the intercarpal joints with power Doppler signals.

Figure 622. Ultrasound image of a dorsal longitudinal scan of the right wrist shows joint cavity widening of the wrist.

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Figure 623. Ultrasound images of dorsal longitudinal scans of the right wrist show mild joint cavity widening of the radiocarpal joint.

Figure 624. An ultrasound image of a dorsal longitudinal scan of the right wrist shows moderate joint cavity widening of the radiocarpal and the intercarpal joint.

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Figure 625. Ultrasound images of dorsal longitudinal scans of the right wrist show moderate joint cavity widening of the radiocarpal joint.

Figure 626. Ultrasound images of dorsal longitudinal scans of the right wrist show moderate joint cavity widening with power Doppler signals of the radiocarpal and the intercarpal joints.

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Figure 627. The T2-STIR MR image shows synovitis of the hands in a patient with psoriatic arthritis.

Figure 628. The T2-STIR MR images show synovitis of the hands in a patient with psoriatic arthritis.

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Figure 629. The MR images show synovitis at the ulnar styloid processes. Shoulders

Figure 630. The PET-CT image shows synovitis of the right shoulder of a patient with psoriatic arthritis.

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Sternoclavicular joints

Figure 631. Swelling of the right sternoclavicular joint in a patient with psoriatic arthritis.

Figure 632. The MR images show synovitis of the right sternoclavicular joint in a patient with psoriatic arthritis.

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Figure 633. Bone scintigraphy shows increased uptake of the right sternoclavicular joint in a patient with psoriatic arthritis.

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Spine In psoriatic arthritis, there is arthritis at the apophyseal joints. Ultrasound examination and PET-CT may show arthritis.

Figure 634. Ultrasound examination of the spine and PET-CT images show arthritis of the apophyseal joints.

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Figure 635. PET-CT image shows inflammation at the apophyseal joints in a patient with psoriatic arthritis.

Figure 636. Ultrasound examination of the spine show arthritis of the apophyseal joints with power Doppler signals.

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Figure 637. Ultrasound examination of the sacrum and the sacroiliac joints.

Figure 638. PET-CT image shows inflammation at the pubic symphysis in a patient with psoriatic arthritis. Calcifications Calcifications of the joint capsules and the entheses may be seen in psoriatic arthritis [Pozzato C, 1985] [Kane D, 2003]. In some cases, small calcifications in the soft tissue at the DIP joints are visible. According to clinical and laboratory data, these lesions could be associated with psoriatic arthritis [Pozzato C, 1985].

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Figure 639. Calcifications of the right second DIP joints in patients with psoriatic arthritis.

Figure 640. Calcifications of the right third DIP joints in patients with psoriatic arthritis.

Figure 641. Calcifications of the right first IP joints in patients with psoriatic arthritis.

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Figure 642. Calcification of the left IP joint in a patient with psoriatic arthritis.

Figure 643. Calcifications of the left second PIP joints in patients with psoriatic arthritis.

Figure 644. Calcifications of the third right PIP joints in patients with psoriatic arthritis.

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Figure 645. Calcification of the left third PIP joint in a patient with psoriatic arthritis.

Figure 646. Calcifications of the right fifth PIP joints in patients with psoriatic arthritis.

Figure 647. Calcifications of the left fifth PIP joints in patients with psoriatic arthritis.

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Figure 648. Calcifications of the right first IP joints in patients with psoriatic arthritis.

Figure 649. Calcifications of the left first IP joints in patients with psoriatic arthritis.

Figure 650. Calcifications of the right second MCP joints in patients with psoriatic arthritis.

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Figure 651. Calcifications of the left second MCP joints in patients with psoriatic arthritis.

Figure 652. Calcification of the right third MCP joint in a patient with psoriatic arthritis.

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Figure 653. Calcifications of the left third MCP joints in patients with psoriatic arthritis.

Figure 654. Calcification of the right fifth MCP joint in a patient with psoriatic arthritis.

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Figure 655. Calcification of the right first CMC joint in a patient with psoriatic arthritis.

Figure 656. Calcifications of the left wrists in patients with psoriatic arthritis. References El Miedany YGaafary M, Youssef S, Ahmed I, Nasr A.El. (2015). Tailored approach to early psoriatic arthritis patients: clinical and ultrasonographic predictors for structural joint damage. Clin Rheumatol. Freeston J.E.LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG.Coates. (2014). Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res. Kane DL, Bresnihan B, FitzGerald O.Stafford. (2003). A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford). Kapitonova MYO.Mansor. (2003). Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death. Malays J Patho. Offidani AA, Valeri G, Giovagnoni A.Cellini. (1998). Subclinical joint involvement in psoriasis: magnetic resonance imaging and X-ray findings. Act Derma Venerol. Pozzato CF, Baldini U, Marmini A, Cattaneo M, Uslenghi C.Gattoni. (1985). Periarticular calcifications. A little-known sign of psoriatic arthritis. Radiol Med. Wassenberg S. (2015). Radiographic scoring methods in psoriatic arthritis. Clin Exp Rheumatol.

CHAPTER 6 D: DISTRIBUTION OF ABNORMALITIES IN PSORIATIC ARTHRITIS SYUICHI KOARADA, SATOKO TASHIRO

Abstract The distribution of lesions in the bones and joints is important for diagnosis of psoriatic arthritis. There are four factors of the distributions of the lesions: whole-body distribution, distribution in anatomical areas, intraarticular distribution, and temporal distribution. Taking these factors into consideration contributes to the appropriate diagnosis of psoriatic arthritis. Introduction The distribution patterns of joint lesions are useful for differential diagnosis of psoriatic arthritis. The typical distribution of psoriatic arthritis is a polyarticular disorder including the DIP joints of the hands, but various clinical patterns such as symmetric polyarthritis like rheumatoid arthritis, arthritis mutilans, oligoarthritis, monoarthritis, sacroiliitis, and spondylitis are observed. The clinical findings of psoriatic arthritis are more diverse, involving the spine, the sacroiliac joints, the entheses, and the tenosynovium. Therefore, psoriatic arthritis is the disease that affects the peripheral and the axial joints, and the attachment sites of the ligaments and the tendons. Although the joint distribution of psoriatic arthritis is quite diverse, certain distribution features should be emphasized. On this point, psoriatic arthritis is like spondyloarthropathies. On the other hand, in rheumatoid arthritis, the lesions of the cartilaginous joints and the entheses are inconspicuous. Because psoriatic arthritis exhibits characteristic changes in radiography with both specific and various distributions, the distribution can lead to diagnosis. Diagnosis of joint disease by analysis of the target areas is important. The target areas in rheumatoid arthritis are basically the synovial membranes that line the joints, but in psoriatic arthritis there are five major target areas. 1. Peripheral arthritis 2. Skin/nail changes 3. Axial arthritis 4. Dactylitis 5. Enthesitis

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1. Whole-body Distribution Psoriatic arthritis can affect any joint, and there are several distribution patterns of monoarthritis, oligoarthritis, and polyarthritis. The typical sites where the lesions occur in psoriatic arthritis are the interphalangeal joints of the hands and the feet, the MCP and the MTP joints, the calcaneuses, the sacroiliac joints and the spine. Psoriatic arthritis also affects the knees, the ankles, the manubriosternal, the sternoclavicular, the acromioclavicular, the costovertebral joints, the symphysis pubis, the entheses of the pelvis, the elbows, and the wrists. However, the patterns of joint lesions vary from patient to patient and change with time in each patient. Some patients have severe back pain as a result of the spinal and the sacroiliac lesions. Large joints are fewer affected if the distribution pattern is like rheumatoid arthritis. Bone proliferations at the entheses is often observed around the larger joints. The distribution is mainly in the order of the hands, the feet, the sacroiliac joints, and the spine. The hands are the most frequent lesion sites in psoriatic arthritis, occurring in about 40% of patients [Lee EY 2008]. In psoriatic arthritis, the hands are more frequently affected than the feet, with a ratio of nearly 2: 1 [Sudoá-SzopiĔska I 2016]. Generally, the large joints of the upper and the lower extremities in psoriatic arthritis have fewer lesions than the small joints of the hands and the feet.

Figure 657. Bone scan shows increased radionuclide accumulation and the distribution of the lesions of the joints, the bones and the entheses.

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Figure 658. Gallium scan also shows increased radionuclide accumulation and the distribution of the lesions of the joints, the bones and the entheses.

Figure 659. Bone scan shows increased radionuclide accumulation and the distribution of the lesions of the joints, the bones and the entheses in a patient with psoriatic arthritis.

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Figure 660. Bone scan shows increased radionuclide accumulation and the distribution of the lesions of the joints, especially the DIP joints and the right fifth PIP joint, the bones and the entheses in a patient with psoriatic arthritis.

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Figure 661. Bone scan shows increased radionuclide accumulation and the distribution of the lesions of the joints, the bones and the entheses in a patient with psoriatic arthritis.

Figure 662. Bone scan shows increased radionuclide accumulation and the distribution of the lesions of the joints, the bones and the entheses in a patient with psoriatic arthritis.

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Figure 663. Bone scan shows increased radionuclide accumulation of the digits and the joints in a patient with psoriatic arthritis.

Figure 664. Gallium and bone scan in the same patient with psoriatic arthritis.

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Polyarthritis and oligoarthritis In psoriatic arthritis, joint involvement may be oligoarthritis or polyarthritis, but most of patients have polyarthritis with 5 or more joints [Gladman DD. 2015] [Scher JU 2015] [Mc Ardle A 2015] [Veale DJ 2015] [Helliwell PS 2007]. Another frequent pattern is oligoarthritis mainly affecting the large joints. Although monoarthritis is not common in psoriatic arthritis, 5-10% of patients may present only with the isolated distal joint lesion [Gladman DD. 2015]. In juvenile psoriatic arthritis, arthritis of the knee is common, and in most of cases asymmetric polyarthritis eventually develops [Shore A 1982]. Uncommon sites of arthritis In psoriatic arthritis, in general, the large joints of the upper and lower extremities have fewer lesions than the small joints of the hands and feet. Involvement of the hips and shoulders is uncommon. Asymmetric distribution. In psoriatic arthritis, arthritis of one side of the bodies may be associated with changes on the other side, but asymmetric or unilateral distribution is much more common than in rheumatoid arthritis. Asymmetry of arthritis helps in the differentiation of psoriatic arthritis from rheumatoid arthritis. Usually, defining the distribution of symmetry requires at least 50% lesions of asymmetric joint pairs. Bilateral asymmetrical changes predominate in the IP and the MTP joints. The distribution of arthritis is shown to be asymmetric in bone scintigraphy (99 mTc). This asymmetry in bone scintigraphy frequently makes it possible to distinguish psoriatic arthritis from rheumatoid arthritis. Although the findings of psoriatic arthritis are similar to ankylosing spondylitis, lesions of psoriatic arthritis may be extensive and more asymmetric than ankylosing spondylitis [Bollow M 2000] [Williamson L 2004]. Exception to application The exception of the distribution patterns is the hemiplegic patients, who may have psoriatic arthritis only on the non-paralyzed side of the bodies [Weiner SR 1985]. Enthesitis Enthesitis is commonly found and can accompany any of the other manifestations [Gladman DD 2005]. Enthesitis is most frequently seen in the Achilles tendons and the plantar aponeurosis entheses at the calcaneus and at the sites of the tendinous and the ligamentous attachments around the pelvis. In rare cases, enthesitis may be the only symptom of psoriatic arthritis. 2. Distribution in anatomical areas in peripheral psoriatic arthritis Coexistence of osteolysis and hyperostosis in the same anatomical areas is the most important feature of psoriatic arthritis [Sudoá-SzopiĔska I 2016]. Hands The hands are the most common sites involved in psoriatic arthritis. In the hands, psoriatic arthritis has several different patterns of distribution: transverse type (row pattern), axial type (ray pattern), mixed type and rheumatoid arthritis type. Transverse type is the row pattern, primarily, which affects the DIP joints. Axial type is the ray pattern,

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which is mainly confined to the tendon sheath synovia (dactylitis). While arthritis can occur in any joint, more typically, it is at the DIP and the PIP joints, and more infrequently at the MCP joints. In psoriatic arthritis, articular lesions occur not only in the PIP, the MCP joints, and the wrists, but also in the DIP joints. Also, abnormalities of the tufts of distal phalanges are characteristic.

Figure 665. The patterns of distribution in the hands of patients with psoriatic arthritis and rheumatoid arthritis are useful for differential diagnosis.

Figure 666. Various patterns of distribution in the hands of patients with psoriatic arthritis.

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Patterns of involvement In the hands, various patterns, including bilateral, symmetrical, asymmetrical, or unilateral changes are observed. DIP+PIP (IP) transverse type

Figure 667. Transverse pattern of the IP joints (the DIPs+ the PIPs).

Figure 668. Bone scintigraphy shows transverse pattern of the IP joints.

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Figure 669. Transverse pattern of the DIP joints.

Figure 670. Transverse pattern of the DIP joints.

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Figure 671. Bone scintigraphy shows transverse pattern of the DIP joints. Axial type, ray pattern Axial type or ray pattern distributes arthritis to the MCP, the PIP and the DIP joints of one or several digits. The ray pattern usually affects all joints of one to three digits, while the other digits and the joints are spared. In the ray pattern, potentially the wrists may be involved.

Figure 672. Ray pattern of the hands. A conventional radiograph and the MR image show axial type (the right third MCP, PIP, and DIP joints) in a patient with psoriatic arthritis.

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Rheumatoid arthritis-like pattern The rheumatoid arthritis-like pattern is the distribution like as rheumatoid arthritis. In the rheumatoid arthritis-like distribution pattern, other features may be able to distinguish between psoriatic arthritis and rheumatoid arthritis.

Figure 673. Rheumatoid arthritis-like pattern of the hands (the MCP and the PIP joints).

Figure 674. Rheumatoid arthritis-like pattern of the hands (like as advance rheumatoid arthritis).

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Figure 675. Bone scintigraphy shows rheumatoid arthritis-like pattern in psoriatic arthritis. Mixed type (pattern) The mixed type is the combination of the transverse and the axial types.

Figure 676. Mixed pattern of psoriatic arthritis in the hands.

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Figure 677. Mixed pattern of psoriatic arthritis in the hands.

Figure 678. Mixed pattern with dactylitis of psoriatic arthritis. DIP joints In patients with psoriatic arthritis, typical radiographic changes are seen in the DIP joints. The changes in the DIP joints include soft tissue swelling, lack of periarticular osteoporosis, joint space narrowing, bone erosions with bone proliferation, "pencil and cup" appearance, enthesopathy and tuft resorption. Destructive arthritis of the DIP joints is the characteristic lesion of psoriatic arthritis [Gold RH 1982]. The presence of the DIP joint lesions is unique to psoriatic arthritis and so typical that it helps to distinguish psoriatic arthritis from rheumatoid arthritis. The lesions of the DIP joints are associated with the nail lesions and can range from mild to severe change, destructive arthropathy [McHugh NJ 2003]. The DIP joints are often affected with involvement including the nails of dystrophy, pitting, and onychosis. Bone erosions initially occur at the margins of the joints and progress towards the centers. Marginal erosions around the DIP joints are generally small compared to erosions of the PIP and the MCP joints.

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PIP joints The PIP joints of the hands generally become the lesion sites of psoriatic arthritis. Although the PIP joints adjacent to the lesions of the DIP joints are frequently affected, asymmetrical or spotty distribution is common. MCP joints Generally, the MCP joint abnormalities are spared and less marked, and include joint space narrowing, marginal erosions, and bone proliferation. However, the lesions of the MCP joints may be found in patients with psoriatic arthritis [Olivieri I 1998]. Inflammatory lesions in the MCP joints are occasionally consistent with disease activity and lead to joint damages, including severe destruction, resorption and proliferation [Olivieri I 1998]. First MCP joints The destruction of the sesamoid bones may be associated with other joint abnormalities in the first MCP joints. The bone ankyloses of the MCP joints are very rare, except those of the thumbs. Wrists Abnormalities in the wrists of patients with psoriatic arthritis are not common than the hands and rarely occur without the lesions of the DIP joints. Changes in the tendinous connections of the wrists may be not uncommon. Dactylitis Dactylitis can occur on any digit, but lesions can occur on several digits simultaneously (poly-dactylitis).

Figure 679. Asymmetrical distribution of tenosynovitis in MRI. Tenosynovitis of the right third digit and the left wrist is predominant in a patient with psoriatic arthritis.

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Elbows Psoriatic arthritis can lead to changes in the elbows [Yood RA 1980]. In the elbows, findings vary from slight bone erosions to a wide range of osteolysis. Shoulders Patients with psoriatic arthritis may have the changes in the glenohumeral and the acromioclavicular joints [Yood RA 1980]. Hips Involvement of the hips is relatively uncommon. Knees Articular involvement in psoriatic arthritis may be apparent in the knees. Ankles Involvement in psoriatic arthritis may occur in the ankles. Feet Joint involvement in psoriatic arthritis can occur in the midfeet and the hindfeet. Also, the forefeet are common lesion sites for psoriatic arthritis. In the toes, psoriatic arthritis causes erosive lesions in the MTP and the interphalangeal joints. Particularly the IP joints of the first toes are of common involvement. One of the hallmarks of the lesions of the feet in psoriatic arthritis is the ivory phalanges. The ivory phalanges are typically prone to lesions in the distal phalanges, particularly the first toes, with osteosclerosis, enthesitis, periostitis, and soft tissue swelling. Bilateral asymmetrical changes predominate in the IP and the MTP joints, and are characterized by marginal erosions, bone proliferation, joint space narrowing or widening, and lack of osteoporosis. Calcaneuses The calcaneuses are one of the most typical sites of abnormalities in psoriatic arthritis. Abnormal changes are seen on the posterior and the inferior aspects of the calcaneuses [Resnick D. 1974]. Bone erosions and proliferation occur at the sites of the attachments of Achilles tendons of the calcaneuses posteriorly and superiorly. Occasionally, lesions occur on the entire inferior surfaces of the calcaneuses. Patterns of involvement Three different patterns of distribution occur in the feet in patients with psoriatic arthritis. DIP and PIP joint pattern Involvement of the DIP and the PIP joints is common in the feet of psoriatic arthritis.

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MTP joint pattern Lesions of the MTP joints are more common than the MCP joints of the hands. Ray pattern Also, as with the hands, in the ray pattern, one to three toes may be affected, while the other toes are free of the lesions. Metatarsals Periosteal osteogenesis tends to occur near and parallel to the cortex of the metatarsals. Phalanges Abnormalities of the pharyngeal tufts are also characteristic in psoriatic arthritis. Sesamoids The involvement of the sesamoids of the feet is relatively common in psoriatic arthritis. 2-2. Distribution of anatomical areas in axial psoriatic arthritis Axial psoriatic arthritis has characteristic findings, including asymmetric sacroiliitis, asymmetric syndesmophytes, paravertebral ossifications, cervical vertebral lesions, and sacroiliac ankyloses, which are useful for diagnosis [Lubrano E 2012]. The distribution in the axial skeleton is mainly at the sacroiliac joints and the spine. Sacroiliac joints In the sacroiliac joints of psoriatic arthritis, both the synovial parts and the syndesmotic parts can be involved [Sudoá-SzopiĔska I 2016]. There are bone erosions and sclerosis predominantly in the iliums as changes of bilaterality and symmetry. Unilateral involvement of the sacroiliac joints may occur as well. Lesions occur initially on the iliac sides of the synovial joints, probably due to mechanical factors and anatomical features such as the thinness of the cartilages of the iliac sides. Sacroiliitis can also occur without spondylitis. Moreover, spondylitis may appear without sacroiliitis. However, spondylitis is uncommon in the absence of sacroiliitis. In psoriatic arthritis, bilateral changes in the sacroiliac joints are considerably more than unilateral changes. However, asymmetric findings may be apparent in some cases [McEwen C 1971] [Jajiü I. 1968] [Helliwell PS. 1998] [Killebrew K 1973]. Diagnosis of early lesions is limited because plain radiography generally has low sensitivity for detecting abnormalities, and CT scans cannot detect early changes. Proliferative bone repair is observed as the erosions enlarge and the sacral lesions are seen. Bone proliferation may be more pronounced than ankylosing spondylitis as the erosions develop and affect the sacrum sides. In the sacroiliac joints, CT scans can display changes in joint spaces, bone erosions, sclerosis and ankyloses with very high resolution, and are generally considered to be a standard reference for evaluation of the structural damages [Diekhoff T 2017]. MRI is useful for early detection of the lesions in the sacroiliac joints, and findings of MRI include bone marrow edema in the iliums and the sacrums, erosions, and chronic changes including periarticular fat deposition,

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sclerosis, and new bone formation [McQueen F 2007]. Spine The spine can be involved in psoriatic arthritis. However, the spinal lesions of psoriatic arthritis are less severe, and asymmetric than classic ankylosing spondylitis. Furthermore, the annulus fibrosus itself is not ossified [Bywaters EG 1965]. Axial psoriatic arthritis is characterized by non-marginal asymmetric parasyndesmophytes and lumpy new bone formation, and then is distinguished from ankylosing spondylitis [Helliwell PS. 1998]. The lesions of the spine can be extensive and may be seen from the early stages of the disease. However, the initial lesions of the spine compared with the sacroiliac joints are lower in psoriatic arthritis compared with spondyloarthritis [Helliwell PS. 1998]. Although syndesmophytes of ankylosing spondylitis advance from the lumbar to the cervical spine, a more random distribution is common in axial psoriatic arthritis. Paravertebral ossifications in psoriatic arthritis may result in less involvement of the apophyseal joints [Resnick DL. 2002]. Paravertebral ossifications of the lower thoracic and the upper lumbar spine may occur in psoriatic arthritis. The cervical spine lesions may occur, with or without the lesions in other segments of the spine. The lesions of the cervical spine may be severe in patients with psoriatic arthritis [Killebrew K 1973] [Kaplan D 1964]. As the cervical lesions, there are narrowing of the facet joints and the disc space, posterior ligamentous calcifications, atlantoaxial subluxation, odontoid erosions, subaxial erosions and occasionally ankyloses. In the cervical spine, there are lesions of the apophyseal joints including narrowing, erosions, bone proliferation, and ankyloses. The discovertebral lesions (Anderson lesions) may be the first finding of psoriatic arthritis (approximately 6% of patients with psoriatic arthritis and ankylosing spondylitis) [Queiro R 2013]. In the spine, inflammatory changes in MR images are bone marrow edema and soft tissue edema in the joints and the entheses [Felbo SK 2018]. Inflammatory changes are found in the anterior and the posterior corners of the vertebral bodies, and in the costovertebral, the apophyseal and the costotransverse joints. However, there are few studies of axial psoriatic arthritis, and knowledge is primarily derived from the studies of patients with spondyloarthritis and ankylosing arthritis. The manubriosternal joints, the sternoclavicular, the costovertebral joints, and the symphysis pubis can also reveal alterations [Kormano M 1975]. Sternoclavicular joints The lesions of the sternoclavicular joints are seen in some patients with psoriatic arthritis. CT imaging is useful in the detection of abnormalities of the sternoclavicular joints. Pelvis The symphysis pubis and the tendinous connections of the pelvis may show significant lesions. Temporomandibular joints The temporomandibular joints can also be significantly affected in psoriatic arthritis [Rasmussen OC 1982] [Könönen M. 1987] [Resnick D. 1974] [Lundberg M 1967] [Blair GS. 1976] [Franks AST. 1965]. CT and MR images are useful for the evaluation of the temporomandibular joints in psoriatic arthritis [Avrahami E 1986] [Koorbusch GF 1991].

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3. Intraarticular distribution, Distribution in joints Hands Using high-resolution micro-CT, erosions in psoriatic arthritis are smaller and deeper, unlike in rheumatoid arthritis. Also, erosions are not preponderantly to the radial sides like rheumatoid arthritis [Narváez J 2012]. For tenosynovitis, the flexor tendons are more in psoriatic arthritis, but in rheumatoid arthritis more with the extensor tendons [Narváez J 2012]. DIP joints Inflammatory changes in psoriatic arthritis are present at the entheses of the collateral ligaments, as evidenced by the fact that the bone areas at the attachments of the collateral ligaments are clearly indicative of bone marrow edema. Initial erosions occur at the margins of the joints and progress towards the centers. Diffuse bone marrow edema is seen in the distal phalanges, the nail bed and the DIP joints. The nails are the initial sites of inflammation, from where inflammation spreads to the distal phalanges and the DIP joints [Scarpa R 2006]. Another study reports that inflammation may be derived from the bones and subsequently extend to the nail beds [Dalbeth N 2012]. Phalangeal tufts The phalangeal tufts may be involved in psoriatic arthritis and they are characteristic. Spine Spinal lesions may begin at the attachments of the anterior longitudinal ligaments. Ossifications initially appear on one side of the spine, parallel to the vertebral bodies and the lateral surfaces of the intervertebral discs, as thick, fluffy or as thin and curvilinear areas of reduced permeability. The ossifications of the spine (parasyndesmophytes) in psoriatic arthritis have features such as asymmetric distribution, larger in size, sometimes unilateral distribution, skipped vertebral body levels, and separated from the lateral aspects of the vertebral bodies. These features are differing points from syndesmophytes in ankylosing spondylitis and other spondylitises [Sudoá-SzopiĔska I 2016]. 4. Temporal distribution Psoriatic arthritis, once thought to be a benign rheumatic disease, is a progressive disease with a significant number of patients having severe erosive disease and significant structural impairment. Peripheral joint lesions are common, and more than half of patients with psoriatic arthritis suffer joint damages on radiography within two years. Radiological changes are present even at the early stages of psoriatic arthritis, suggesting that there are aggressive diseases and/or arthritis of longer term than patient-reported symptoms. Psoriatic arthritis can develop rapidly after an injury [Sandorfi N 1997]. Earliest phases In the earliest and early phases of psoriatic arthritis, conventional radiography may be entirely normal. Early inflammatory changes in psoriatic arthritis are soft tissue edema and bone marrow edema. Therefore, the changes cannot be easily detected with conventional radiography, and the images such as swelling of soft tissues and increased density of the periarticular soft tissue are nonspecific [Brown AK. 2013]. Early radiographic abnormalities may also

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include some degree of periarticular osteoporosis. Early radiographic abnormalities such as swelling of soft tissues and periarticular osteoporosis, may improve without permanent damages. Early in the disease, inflammatory synovitis with periarticular edema is seen in ultrasound examination. In early phases, the power Doppler signals may be present. In some cases, there are no other abnormalities, but power Doppler signals may be distributed only in the fat pads. Although the DIP joints are usually initially affected, asymmetric erosions may be detected at the MCP, the PIP and the carpal joints in conventional radiography. Periostitis of the shafts of the phalanges is sometimes the first radiographic manifestation. Bone scintigraphy can detect musculoskeletal abnormalities of psoriatic arthritis prior to the appearance of abnormalities on conventional radiographs [Weissberg DL 1978] [Namey TC 1976]. Accumulations of radionuclides are detected at the IP, the MCP and MTP joints of the hands and the feet. Dactylitis may appear as the initial symptom in 29% to 33.5% of patients with psoriatic arthritis. The changes of periosteal bone formation, cloaking, may appear earlier, in conjunction with soft tissue swelling, before significant abnormalities occur in the adjacent joints. Early phases The first radiologic sign of psoriatic arthritis may be related to permanent structural damages, bone erosions. Of patients with the established psoriatic arthritis, 67% show radiographic abnormalities and 47% of patients with recent-onset psoriatic arthritis develop erosions within 2 years from the onset [Kane D 2003]. Bone erosions begin in the marginal areas of the joints and progress to a more central areas over time.

Figure 680. Erosions in early and advanced phases.

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Figure 681. Early phase and advanced phase of osteosclerosis. Inflammatory changes of the early phases can be seen on MR imaging and ultrasound examination, in the peripheral joints (synovitis), the tendon sheaths (tenosynovitis), and the entheses (enthesitis). Initial signs of bone proliferation are exuberant and fluffy in appearance. Paravertebral ossifications may occur as early findings of psoriatic arthritis about the lower thoracic and the upper lumbar spine. As initial changes, thick, fluffy or curvilinear lesions occur on one side of the spine, parallel to the surfaces of the vertebral bodies and the intervertebral discs. Advanced phases With the clinical progression of joint lesions, more extensive radiologic abnormalities may appear and be exacerbated to varying degrees [Juozevicius JL 1986]. In the advanced phases, ultrasound examination presents typical findings such as extensive synovial proliferation with bone erosions. In the advanced phases of psoriatic arthritis, inflammation in the joints and the entheses is sustained, and then the bone cortexes with the inflammatory changes in the cancellous bones are disrupted [Lee EY. 2008]. If the disease is resistant to treatment, bone destruction progresses, and erosions become more irregular and indistinct. At the same time bone formation will also occur. As the disease progresses, there may be joint space narrowing and progression of erosions, which may be like rheumatoid arthritis. One of the distinctive findings as disease progression is subchondral sclerosis caused by reactive bone growth [Lee EY. 2008]. In addition, in the advanced phases, changes in the bone cortexes associated with the enthesophytes and bone erosions also occur. Terminal phases In the terminal phases, various distinctive deformities including pencil-in-cup deformities, cup-like deformities and gross osteolysis can be seen. At the ends of the disease, typical changes occur as arthritis mutilans, and finally, there may also be deformities of the opera -glass hand. Subluxation and ankyloses are also relatively common features of the terminal phases of psoriatic arthritis. The bone formations in the spine gradually enlarge, eventually resulting in large and bulky bone growth that merges with the underlying vertebrae and the discal tissue. In the sacroiliac joints, initially, changes appear on the iliac sides of the synovial joints, and the lesions occur on the sacral sides by development of the erosions, and also proliferative bone repair is observed.

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Arthritis Res Ther, 2007, 8:207 . Namey TCL.Rosenthall. Periarticular uptake of 99mtechnetium diphosphonate in psoriatics: correlation with cutaneous activity. Arthritis Rheum, 1976, 19:607-12. Narváez JJA, de Albert M, Gómez-Vaquero C, Nolla JM.Narváez. Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin Arthritis Rheum, 2012, 42:234–245. Olivieri IL, Padula A, et al.Barozzi. Olivieri I, Barozzi L, Padula A, et al. Clinical manifestations of seronegative spondylarthropathies. Eur J Radiol, 1998, 27(Suppl 1):S3–6. Queiro RP, Alonso S, Alperi M, Ballina J.Tejón. Erosive discovertebral lesion (Andersson lesion) as the first sign of disease in axial psoriatic arthritis. Scand J Rheumatol, 2013, 42:220-5. Rasmussen OCM.Bakke. Psoriatic arthritis of the temporomandibular joint. Oral Surg Oral Med Oral Pathol, 1982, 53:351-7. Resnick D. Radiology of the talocalcaneal articulations. Anatomic considerations and arthrography. Radiology, 1974, 111:581-6. Resnick D. Temporomandibular joint involvement in ankylosing spondylitis. Comparison with rheumatoid arthritis and psoriasis. Radiology, 1974, 112:587-91. Resnick DL. Diagnosis of Bone and Joint Disorders. 4th Edition . Saunders, 2002, page 1-5472. Sandorfi NB.Freundlich. Psoriatic and seronegative inflammatory arthropathy associated with a traumatic onset: 4 cases and a review of the literature. J Rheumatol, 1997, 24:187-92. Scarpa RE, Peluso R, Atteno M, Manguso F, Del Puente A et al.Soscia. Nail and distal interphalangeal joint in psoriatic arthritis. J Rheumatol, 2006, 33:1315–1319. Scher JUC, Artacho A, et al.Ubeda. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. 67:128–39, 2015. Shore ABM.Ansell. Juvenile psoriatic arthritis: An analysis of 60 cases. J Pediatr, 1982, 100:529. Sudoá-SzopiĔska IG, Kwiatkowska B, PracoĔ G.Matuszewska. Diagnostic imaging of psoriatic arthritis. Part I: etiopathogenesis, classifications and radiographic features. J Ultrason., 2016, 16:65–77. Veale DJU.Fearon. What makes psoriatic and rheumatoid arthritis so different? RMD Open, 2015, 1:e000025. Weiner SRLW, Reichman RP.Bassett. Protective effect of poliomyelitis on psoriatic arthritis. Arthritis Rheum, 1985, 28:703-6. Weissberg DLD, Taylor A, Becker M, Alazraki N.Resnick. Rheumatoid arthritis and its variants: analysis of scintiphotographic, radiographic, and clinical examinations. AJR Am J Roentgenol, 1978, 131:665-73. Williamson LJL, Dalbeth N, et al.:Dockerty. Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis. Rheumatology (Oxford), 2004, 43:85-88. Yood RADL.Goldenberg. Sternoclavicular joint arthritis. . Arthritis Rheum, 1980, 25:232.

CHAPTER 7 E: EXTRACAPSULAR MANIFESTATIONS IN PSORIATIC ARTHRITIS SYUICHI KOARADA, AKIHITO MARUYAMA

Abstract Psoriatic arthritis has a wide variety of lesions, but the extracapsular manifestations are very important and there are many findings that are crucial for the diagnosis of psoriatic arthritis. Soft tissue swelling and dactylitis are extremely characteristic findings, and the presence of tenosynovitis and enthesitis also contributes to the diagnosis. Of course, psoriatic plaques such as skin lesions and nail lesions are also findings that should be known. Soft tissue swelling around joints In psoriatic arthritis distinct soft tissue swelling may be seen. Fusiform soft tissue swelling often occurs at the joints, reflecting the presence of synovial thickening and synovial fluid [Yvmus M. 1981]. The lesions of the DIP and the PIP joints and the tendon sheaths also cause enlargement of the entire digits, which may result in the sausage digits [Forrester DM. 1983]. There may also be diffuse swelling of all or part of the extremities. Skin and joint lesions of psoriasis and psoriatic arthritis are thought to be related to the so-called Koebner phenomenon [Tinazzi I 2018]. Redness may be seen on the back of the DIP and the PIP joints, which may reflect the deep Koebner phenomenon seen in psoriatic arthritis. In rheumatoid arthritis, redness of the joints is not common. Inflammation due to deep Kepnel phenomenon may be seen through the skin.

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DIP joints

Figure 682. Swelling and redness of the DIP joints in a patient with psoriatic arthritis.

Figure 683. Swelling and redness of the right fourth DIP joint in a patient with psoriatic arthritis.

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Figure 684. Swelling and redness of the right firth DIP joint in a patient with psoriatic arthritis. PIP joints

Figure 685. Swelling and skin rash of the PIP joints in a patient with psoriatic arthritis.

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Figure 686. A radiograph shows soft tissue swelling of the PIP joints in a patient with psoriatic arthritis.

Figure 687. Soft tissue swelling of the right third PIP joints in patients with psoriatic arthritis.

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Figure 688. Soft tissue swelling of the right fourth PIP joint in a patient with psoriatic arthritis.

Figure 689. Swelling and redness of the left fifth PIP and the DIP joints in a patient with psoriatic arthritis.

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Ankles

Figure 690. Swelling of the right ankle in a patient with psoriatic arthritis.

Figure 691. Swelling of the left ankle in a patient with psoriatic arthritis.

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Figure 692. Changes over time suggest a soft tissue swelling of the right ankle in a patient with psoriatic arthritis.

Figure 693. Changes of soft tissue swelling of the right ankle over time in a patient with psoriatic arthritis. Extracapsular inflammation, Extra synovial soft tissue inflammation, Pseudo synovitis Extracapsular inflammation in psoriatic arthritis is one of the characteristic lesions. Inflammation of extracapsular soft tissues of the hands with thickening of the collateral ligaments is observed, especially in the early stages of the disease [Fournié B 2006]. Interestingly, there are some cases of extracapsular inflammation without synovitis. However, extracapsular inflammation is not specific to psoriatic arthritis and can also occur in rheumatoid arthritis [SudoáSzopiĔska I 2016]. For assessment of soft tissues, ultrasound and MRI are the most sensitive options. Soft tissue swelling in the early stages of the disease can be detected with radiography, but it may improve without permanent damages. However, it is difficult to assess the causes of extracapsular soft tissue swelling with conventional radiography, such as synovial thickening, tendinitis, tenosynovitis, enthesitis, and bursitis.

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Ultrasound examination allows the evaluation of extracapsular inflammation such as tenosynovitis, dactylitis, soft tissue edema and bursitis [G. T. Kane D 1999] [Olivieri I 1996]. Ultrasound examination is useful for differential diagnosis of psoriatic arthritis and rheumatoid arthritis. Soft tissue inflammation and enthesitis are often detected in the digits of patients with psoriatic arthritis but are essentially undetectable in patients with rheumatoid arthritis. Although power Doppler signals are negative for subclinical enthesitis in psoriasis, which of psoriatic arthritis shows stronger Doppler signals [Lin Z 2015] [Aydin SZ 2013]. MR images also can detect the lesions of soft tissue sensitively. Dactylitis, Soft tissue swelling of entire digits (sausage or cocktail hot dog digits) In patients with psoriatic arthritis, swelling of soft tissue results in the sausage-shaped (-like) digits (or a cocktail hot dog digits) or dactylitis. Dactylitis is a common feature [S. L. Kane D 2003] and a hallmark of spondyloarthritis including psoriatic arthritis and is also useful as a diagnostic feature [G. T. Kane D 1999]. Dactylitis is caused by tenosynovitis, especially that of the flexor tendons, and enthesopathy with additional diffuse soft tissue edema and synovitis of the DIP and the PIP joints. There may also be extra tendinous soft tissue thickening and extensor tendinitis. Although arthritis contributes to the development of dactylitis, flexor tendon tenosynovitis is the most common pathologic process leading to dactylitis. The lesions of bones and soft tissue in the areas away from the joints lead to typical dactylitis of psoriatic arthritis. Dactylitis is often the first clinical manifestation. Tender dactylitis has more frequently bone marrow edema and a progressive disease course compared to nontender dactylitis [Healy PJ 2008]. Dactylitis can be seen by radiography but is indistinctive finding. Lesions of synovitis of the DIP and the PIP joints, the flexor and the extensor tendons, inflammation of the subcutaneous and extra synovial soft tissue result in soft tissue swelling of the entire digits. It has also been reported that soft tissue swelling of dactylitis can be observed in the absence of current or past tenosynovitis or synovitis [Sudoá-SzopiĔska I 2016].

Figure 694. Changes of dactylitis of the right second and the third digits over time. Sausage-like swelling of entire digits is seen in a patient with psoriatic arthritis.

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Figure 695. Radiographs show the changes of dactylitis of the right second and the third digits over time. Sausagelike swelling of entire digits is seen in a patient with psoriatic arthritis.

Figure 696. Changes of swelling of the entire digit over time in a patient with psoriatic arthritis.

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Figure 697. Affected the right third digit (dactylitis) and unaffected the left third digit of dactylitis in a patient with psoriatic arthritis.

Figure 698. PA and oblique views of the hands. Oblique view is better to detect dactylitis than PA view.

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Figure 699. Oblique view of the left hand is better to detect dactylitis than PA view in a patient with psoriatic arthritis.

Figure 700. Changes of dactylitis of the right third digit in a patient with psoriatic arthritis over time.

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Figure 701. MR image (T2-STIR) of the hands shows dactylitis of the left fifth digit in a patient with psoriatic arthritis.

Figure 702. Dactylitis of both the first and the second fingers in a patient with psoriatic arthritis.

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Figure 703. PA view of the left first and second fingers shows dactylitis in a patient with psoriatic arthritis.

Figure 704. Dactylitis of the right first finger in a patient with psoriatic arthritis.

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Figure 705. Dactylitis of the right first finger in a patient with psoriatic arthritis.

Figure 706. Dactylitis of the left first finger in a patient with psoriatic arthritis.

Figure 707. PA and oblique views of the hands show dactylitis of both the first fingers in a patient with psoriatic arthritis.

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Figure 708. PA views of the left and right hands show dactylitis of both the first and second fingers in a patient with psoriatic arthritis.

Figure 709. PA view of the hands shows dactylitis of the right fourth finger in a patient with psoriatic arthritis.

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MRI Recently, MRI studies have shown polyenthesitis including the flexor tendon pulleys and the fibrous sheaths in dactylitis [F. E. Tan AL 2015]. In rheumatoid arthritis, tenosynovitis is most common in the hands and the wrists, but in psoriatic arthritis, inflammation of the soft tissue around the tendon sheath is a feature of dactylitis [Forney MC 2011].

Figure 710. The coronal and axial gadolinium-enhanced T1-weighted MR images of both the hands show marked extra synovial enhancement of flexor tendon sheath of the second finger and the corresponding tendon in a patient with psoriatic arthritis. Inflammation of the soft tissue around the tendon sheath is clearly observed.

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Figure 711. MR images show dactylitis of the right second and third fingers in a patient with psoriatic arthritis. PET-CT

Figure 712. The PET-CT images show dactylitis in a patient with psoriatic arthritis.

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Subcutaneous calcifications

Figure 713. Ultrasound examination and a plain radiograph show subcutaneous calcifications at the third PIP joint in a patient with psoriatic arthritis.

Figure 714. Subcutaneous calcifications in patients with psoriatic arthritis.

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Subungual calcifications are also seen [Fischer E. 1982]. Bursitis Bursitis is inflammation of one or more bursae of synovial fluid sacs. Bursitis can create local soft tissue masses. Elbows Olecranon bursitis is characterized by pain and swelling in the elbows.

Figure 715. Plain radiographs of the right elbow show olecranon bursitis in a patient with psoriatic arthritis.

Figure 716. Olecranon bursitis in a patient with psoriatic arthritis.

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Figure 717. Olecranon bursitis. Shoulders Subacromial bursitis causes shoulder pain and is the most common form of bursitis.

Figure 718. MR images show subacromial bursitis in a patient with psoriatic arthritis.

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Figure 719. MR images show subacromial bursitis in a patient with psoriatic arthritis.

Figure 720. Diagram of bursae surrounding the shoulder joint: subacromial-subdeltoid bursae (red and pink). Tendinitis Flexor tendons of the fingers

Figure 721. Tenosynovitis of the flexor tendon of the left first finger is seen in a patient with psoriatic arthritis.

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Shoulders

A radiograph of the right shoulder shows calcified substances of tendinitis in a patient with psoriatic arthritis.

Figure 722. Calcification of the tendon of the right shoulder in a patient with psoriatic arthritis.

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Figure 723. The MR image shows rotator cuff tear of the right shoulder in a patient with psoriatic arthritis.

Figure 724. The MR image shows inflammation of the rotator cuff in a patient with psoriatic arthritis.

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Achilles tendons

Figure 725. Swelling of the Achilles tendon.

Figure 726. Calcification of the Achilles tendon of the left ankle in a patient with psoriatic arthritis.

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Figure 727. The Achilles tendinitis of the left ankle. The MRI T2 STIR sagittal and axial images show diffuse hyperintensities in the distal Achilles tendon with bone marrow edema in the calcaneus at the insertion site and severe peritendinous inflammatory changes suggestive of the Achilles tendinitis in a patient with psoriatic arthritis. Tenosynovitis

Figure 728. Ultrasound image shows flexor tendon tenosynovitis of the second digit in a patient with psoriatic arthritis.

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Figure 729. Ultrasound image shows tenosynovitis of the extensor tendon at the third PIP joint in a patient with psoriatic arthritis.

Figure 730. Volar longitudinal and transverse ultrasound scans show the flexor tendon sheath widening with signs of synovial proliferation and power Doppler signals surrounding the tendon at the second MCP joint of a patient with psoriatic arthritis.

Figure 731. Volar longitudinal and transverse ultrasound scans show the flexor tendon sheath widening with signs of synovial proliferation and power Doppler signals surrounding the tendon at the third MCP joint of a patient with psoriatic arthritis.

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Figure 732. The Extensor tendons. Six compartments of the right wrist.

Figure 733. Ultrasound image shows severe inflammation of the tendons, including six compartments of the extensor tendons of the wrist in a patient with psoriatic arthritis.

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Figure 734. Ultrasound image shows tenosynovitis of the extensor digitorum and the extensor indicis (compartment 4) of the wrist in a patient with psoriatic arthritis.

Figure 735. Ultrasound image shows tenosynovitis of the extensor digitorum and the extensor indicis (compartment 4) of the wrist in a patient with psoriatic arthritis.

Figure 736. Ultrasound image shows tenosynovitis of the extensor carpi ulnaris (compartment 6) of the wrist in a patient with psoriatic arthritis.

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Figure 737. Ultrasound images show severe tenosynovitis of the extensor carpi ulnaris (compartment 6) of the wrist in a patient with psoriatic arthritis.

Figure 738. The MR image shows tenosynovitis of the right third digit in a patient with psoriatic arthritis.

Figure ࢚࣮ࣛ! ࣈࢵࢡ࣐࣮ࢡࡀᐃ⩏ࡉࢀ࡚࠸ࡲࡏࢇࠋ. Ultrasound image shows tenosynovitis of the common flexor tendon of the wrist in a patient with psoriatic arthritis.

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Figure 739. Ultrasound image shows tenosynovitis of the common flexor tendon of the wrist in a patient with psoriatic arthritis.

Figure 740. The MR images show tenosynovitis of the flexor tendon sheaths of the wrists in a patient with psoriatic arthritis. Coronal T1FS Gd-enhanced images show the extent of the inflammation of the tenosynovitis.

Figure 741. The MR images show tenosynovitis of the flexor tendon sheaths of the wrist in a patient with psoriatic arthritis.

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Figure 742. The MR images show tenosynovitis of the flexor tendon sheaths of the wrists in a patient with psoriatic arthritis.

Figure 743. The MR images show tenosynovitis of the flexor tendon sheaths and dactylitis in a patient with psoriatic arthritis.

Figure 744. The PET-CT image shows tenosynovitis of the right flexor tendon sheaths in a patient with psoriatic arthritis.

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Peritenon extensor tendon inflammation (PTI) The tendons without synovial sheaths are characteristically involved in patients with psoriatic arthritis [Firestein GS 2016]. Although the overall prevalence of synovitis is higher in rheumatoid arthritis (about 90% of affected joints) than in psoriatic arthritis (about 60% of affected joints), peritenon extensor digitorum tendon inflammation in early psoriatic arthritis (54.1%) is more common than in early rheumatoid arthritis (2.5%) [Zabotti A 2016]. In psoriatic arthritis, although synovitis had no association with enthesitis, peritenon extensor tendon inflammation is associated to enthesitis [Macía-Villa C. 2019].

Figure 745. Schema of peritenon extensor digitorum tendon inflammation (PTI) of the MCP joint in psoriatic arthritis.

Figure 746. US images of the dorsal aspect of the right third MCP joint in a patient with psoriatic arthritis. Peritenon extensor tendon inflammation (PTI), strong synovitis and hypoechoic swelling surrounding the extensor digitorum tendon with power Doppler signals and subcutaneous edema, is shown.

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Figure 747. Ultrasound images of the dorsal aspect of the right fifth MCP joint show peritenon extensor tendon inflammation (PTI) in a patient with psoriatic arthritis.

Figure 748. US images of the left IP joint of a patient with psoriatic arthritis show peritenon extensor tendon inflammation (PTI). Hypoechoic swelling of the soft tissue surrounding the tendon with power Doppler signals is observed.

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Figure 749. Ultrasound imaging and anatomy of the PIP joint.

Figure 750. Ultrasound images of dorsal longitudinal scans of the left third PIP joint in a patient with psoriatic arthritis show swelling of the extensor tendon, the central slip, and peritenon inflammation (PTI). Hypoechoic swelling of the soft tissue surrounding the tendon is observed.

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Figure 751. Ultrasound images of dorsal longitudinal scans of the right fifth PIP joint in a patient with psoriatic arthritis show peritenon inflammation (PTI). Hypoechoic swelling of the soft tissue surrounding the tendon (arrows) with power Doppler signals and the spur (arrowhead) is observed.

Figure 752. Ultrasound findings of the PIP joints in psoriatic arthritis and rheumatoid arthritis.

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Ultrasonography PTI with hypoechoic areas may appear in the soft tissue surrounding the tendons with power Doppler signals. Gutierrez M. et al. reported that PTI patterns are much more characteristic of psoriatic arthritis, suggesting a potential role of ultrasound in the differential diagnosis between rheumatoid arthritis and psoriatic arthritis at the MCP joint levels [F. E. Gutierrez M 2011]. Another study confirms that both intra articular synovitis and PTI cause swelling of the MCP joints, where PTI is as frequent as intra articular synovitis of the causes of swelling. The reliability of PTI is as good as for intra articular synovitis [Macía-Villa C 2018]. MRI Tenosynovitis is a frequent finding on MRI in inflammatory arthritides. In rheumatoid arthritis, tenosynovitis is common in the hands and the wrists, but in psoriatic arthritis, inflammation of the soft tissue around the tendon sheaths is a feature of dactylitis [Forney MC 2011]. Ligaments

Figure 753. Calcifications of the ligaments at the DIP joints in patients with psoriatic arthritis.

Figure 754. Calcifications of the ligaments at the MCP joints in patients with psoriatic arthritis.

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Figure 755. Ultrasound image of longitudinal scan of the right second PIP joint shows swelling of the collateral ligament with a spur in a patient with psoriatic arthritis.

Figure 756. Swelling of the radial collateral ligament at the right second MCP joint in a patient with psoriatic arthritis.

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Figure 757. Calcifications of the collateral ligaments at the left second DIP joint in a patient with psoriatic arthritis.

Figure 758. Calcifications of the collateral ligaments at the left second DIP joint time over.

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Figure 759. Calcifications of the collateral ligaments at the left fifth PIP joint in a patient with psoriatic arthritis.

Figure 760. MR images show the thickness of the posterior longitudinal ligament in a patient with psoriatic arthritis.

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Figure 761. MR image shows the thickness of the yellow ligaments in a patient with psoriatic arthritis. Enthesitis Enthesitis is inflammation of the connective tissue between the tendons or the ligaments and the bones. Enthesitis is common in patients with psoriatic arthritis. Patients with psoriasis have more frequent changes of MRI in the entheses than healthy subjects [Emad Y 2010] [Offidani A 1998] [Erdem CZ 2008]. Bone proliferation also occurs at the entheses [Salvarani C 1999]. Features of enthesitis are typical of psoriatic arthritis and are useful in the diagnosis. Features of enthesopathy include mineralized scars, bone proliferative changes, erosions, cysts at the entheses. However, long-term changes such as bone erosions and enthesophytes are nonspecific findings and may also be found in entheses that are loaded by mechanical stresses [Freeston JE1 2014]. Enthesis organs, Synovio-entheseal complexes Enthesitis is not limited to the local lesions, and then has been recognized as inflammation of wider "enthesis organs" or "synovio-entheseal complexes" [Benjamin M 2004] [McGonagle D 2012]. Enthesis organs or synovio-entheseal complexes also include the adjacent tendons, the periosteums, the fibrocartilages, the synovium and the bones at the attachment sites apart from the entheses. It is hypothesized that in psoriatic arthritis enthesitis is the primary cause that forms pathological conditions. The enthesitis with bone marrow edema is prominent on MRI. The radiographic features of enthesitis are bone erosions and ossifications at the insertion sites of the tendons and the ligaments. The most common sites of enthesitis in patients with psoriatic arthritis are the insertion sites of the plantar fascias of the calcaneuses, the Achilles tendons and the ligamentous attachments of the knees [Schett G 2017].

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DIP joints Since the nail beds and the DIP joints share the common tendinous insertions, the arthritis of the DIP joints is related to inflammation of the nail beds and causes enthesitis [B. M. Tan AL 2007]. High resolution (hr) MRI studies show inflammation of the fibers extending from the capsular entheses of the dorsal DIP joints to the nail beds.

Figure 762. MR images show enthesitis of the right third DIP joint in a patient with psoriatic arthritis.

Figure 763. Ultrasound image of a dorsal longitudinal scan of the right second DIP joint shows enthesitis in a patient with psoriatic arthritis.

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Figure 764. Ultrasound images of dorsal longitudinal scans of the right second DIP joint show enthesitis with power Doppler signals in a patient with psoriatic arthritis. PIP joints

Figure 765. Ultrasound image of a dorsal longitudinal scan of the left fourth PIP joint shows enthesitis of the central slip in a patient with psoriatic arthritis.

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Figure 766. Ultrasound image of a dorsal axial scan of the left forth PIP joint shows enthesitis of the central slip in a patient with psoriatic arthritis. Enthesitis of central slips Enthesitis of the central slips of the PIP joints may be seen in patients with psoriatic arthritis but not in patients with rheumatoid arthritis, and potentially it serves as a distinct feature of psoriatic arthritis [Zabotti A. 2016]. Elbows

Figure 767. Enthesopathies with calcifications and osteosclerosis at the elbows in a patient of psoriatic arthritis.

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Figure 768. Ultrasound images of longitudinal scans of the right elbow shows enthesitis of the lateral epicondyle of the humerus in a patient with psoriatic arthritis.

Figure 769. Bone scintigraphy shows increased uptake in the entheses of the lateral epicondyle of the humerus of the elbows in a patient with psoriatic arthritis.

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Shoulders

Figure 770. Calcifications of the entheses of the shoulders in a patient with psoriatic arthritis.

Figure 771. Calcifications and osteosclerosis of the entheses of the shoulders in a patient with psoriatic arthritis.

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Knees

Figure 772. Calcifications of the entheses of the knees in a patient with psoriatic arthritis.

Figure 773. Ultrasound images show edematous changes at the enthesis of the left fibula in a patient with psoriatic arthritis.

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Figure 774. MR images of enthesitis of the knee in a patient with psoriatic arthritis. Erosions with bone marrow edema and bone cyst formation are observed near the attachment of the anterior cruciate ligament at the femoral condyle.

Figure 775. Bone scintigraphy shows increased uptake at the entheses of the tibial tuberosities, the attachments to the patellar ligaments, in a patient with psoriatic arthritis.

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Figure 776. Bone scintigraphy shows increased uptake at the enthesis of the right lateral collateral ligament of the knee in a patient with psoriatic arthritis.

Figure 777. Entheses of the knee.

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Figure 778. Ultrasound image shows enthesitis at the tibial tuberosity in a patient with psoriatic arthritis.

Figure 779. Ultrasound image shows enthesitis with power Doppler signals at the tibial tuberosity in a patient with psoriatic arthritis.

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Feet

Figure 780. Bone scintigraphy shows increased uptake at the left enthesis of the Achilles tendon in a patient with psoriatic arthritis.

Figure 781. Ultrasound image shows enthesitis with power Doppler signals of the Achilles tendon.

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Pelvis

Figure 782. Enthesopathies at the ischial tuberosities in a patient with psoriatic arthritis.

Figure 783. Enthesopathies with osteosclerosis at the ischial tuberosities in a patient with psoriatic arthritis. Spine

Figure 784. Ultrasound image of a longitudinal scan on the spine shows an erosive lesion on the spinal process of L3, L4, L5 and S1-5 in a patient with psoriatic arthritis.

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Figure 785. Ultrasound images of longitudinal and axial scans on the spine shows an erosive lesion with power Doppler signals on the spinal process of L5 in a patient with psoriatic arthritis.

Figure 786. The PET-CT image shows enthesitis at the spinous process of vertebra in a patient with psoriatic arthritis.

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Figure 787. The PET-CT image shows enthesitis at the interspinous ligament in a patient with psoriatic arthritis. Psoriatic plaques Plaque psoriasis or psoriasis vulgaris is the most common skin phenotype of psoriatic arthritis. However, other types of skin lesions may be seen in patients with psoriatic arthritis.

Figure 788. Scalp psoriasis in a patient with psoriatic arthritis.

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Figure 789. Scalp psoriasis in a patient with psoriatic arthritis.

Figure 790. Scalp psoriasis in a patient with psoriatic arthritis.

Figure 791. Scalp psoriasis in a patient with psoriatic arthritis.

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Figure 792. Psoriasis rash of the forearm in a patient with psoriatic arthritis.

Figure 793. Psoriasis rashes of the forearms in a patient with psoriatic arthritis.

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Figure 794. Psoriasis rashes of the elbows in a patient with psoriatic arthritis.

Figure 795. Psoriasis rashes of the elbows in a patient with psoriatic arthritis.

Figure 796. A small psoriasis rash of the upper arm in a patient with psoriatic arthritis.

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Figure 797. A psoriasis rash of the upper arm in a patient with psoriatic arthritis.

Figure 798. Psoriasis rashes of the axillary in a patient with psoriatic arthritis.

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Figure 799. Psoriasis rashes of the abdomen in a patient with psoriatic arthritis.

Figure 800. Psoriasis rashes of the knees in a patient with psoriatic arthritis.

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Figure 801. Psoriasis rashes of the knees in patients with psoriatic arthritis.

Figure 802. A psoriasis rash on the lower leg in a patient with psoriatic arthritis.

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A psoriasis rash of the right ankle in a patient with psoriatic arthritis.

Figure 803. Small psoriasis rashes of the ankles in a patient with psoriatic arthritis.

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Figure 804. A small psoriasis rash of the right ankle in a patient with psoriatic arthritis.

Figure 805. A small psoriasis rash of the right ankle in a patient with psoriatic arthritis.

Figure 806. Psoriasis rashes of the foot in a patient with psoriatic arthritis.

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Figure 807. Scales on psoriasis rashes of the foot in a patient with psoriatic arthritis.

Scales on psoriasis rashes of the feet in a patient with psoriatic arthritis.

Figure 808. Scales on psoriasis rashes of the foot in a patient with psoriatic arthritis.

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Figure 809. Scales on psoriasis rashes of the foot in a patient with psoriatic arthritis.

Figure 810. Scales on psoriasis rashes of the foot in a patient with psoriatic arthritis.

Figure 811. Plantar eruptions in a patient with psoriatic arthritis.

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Figure 812. Plantar lesions in a patient with psoriatic arthritis.

Figure 813. Skin eruptions in a patient with psoriatic arthritis. Ultrasound examination of skin Psoriatic plaques can be evaluated using ultrasound with a resolution of greater than 0.1 mm. Ultrasound features of psoriatic plaques include thickening of the epidermis and dermis, a hypoechoic zone in the upper dermis, and increased power Doppler signals [Gutierrez M. 2009]. When a marked increase of the thickness of the epidermis and distinct acoustic shadow occurs, the evaluation of the dermis beneath it may be limited. Various degrees of blood flow with power Doppler signals may be observed within the dermis.

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Figure 814. Ultrasound examination shows psoriatic plaques. Hypoechoic dermal thickening with power Doppler signals and epidermal thickening are seen. The epidermal layer of the psoriatic plaque is thickened and inhomogeneous, however in normal skin around the plaque, the epidermal is a thin, relatively uniform hyperechoic band structure. The hypoechoic band in the upper dermis corresponds to the lesion of the psoriatic plaque. Subcutaneous nodules Usually subcutaneous nodules are not seen in psoriatic arthritis. Subcutaneous nodules are neither characteristic nor obvious. However, rarely, the nodular like lesion can be seen at the joints.

Figure 815. Subcutaneous lesions in a patient with psoriatic arthritis. A 53-year-old woman presented with a seven-year history of psoriatic arthritis at our hospital. The patient was diagnosed with psoriatic arthritis by psoriatic nail dystrophy, dactylitis, and radiographic evidence of juxta-articular new bone formation. She had been treated with salazosulfapyridine and prednisolone. Recently, she has been referred to our

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hospital with the development of multiple nodule-like lesions on the lateral sides of the proximal interphalangeal (PIP) and the distal interphalangeal (DIP) joints (Figure A and B). She had no history of trauma. The nodule-like lesions were elongated, oval, and located in the joints and were elastic hard with mild tenderness. The nodule-like lesions were several millimeters in size. Her uric acid level was normal, and C-reactive protein was 1.93 mg/dL. Long-axis ultrasound view of the third proximal interphalangeal joint lateral aspect showed swelling of the synovium with power Doppler signals (Figure C1 and C2). On the dorsal aspect of the PIP joint, peritenon extensor tendon inflammation of the central slip was also observed. From the distribution of arthritis and ultrasound images, nodule-like lesions were associated with psoriatic arthritis. Her treatment with secukinumab, a recombinant human monoclonal immunoglobulin G1 (IgG1)/ț antibody that selectively targets IL-17A and blocks its interaction with the IL-17 receptor, was started. After administration of secukinumab, nodule-like lesions and arthralgia disappeared promptly and her CRP level turned negative. Nodular lesions in the joints are usually identified as rheumatoid nodules, gouty nodules, or Heberden's or Bouchard's nodules. However, in this case, multiple nodular-like lesions of the interphalangeal joints are based on enthesitis and synovitis due to psoriatic arthritis. Pitting edema and cellulitis In some patients, diffuse pitting edema [Salvarani C. 1997] [Salvarani C 1999] or cellulitis in the extremities may be seen. Ganglions

Figure 816. A ganglion at the wrist in a patient with psoriatic arthritis. Onychopathies Nail lesions characterized by onycholysis, pitting, discoloration and hyperkeratosis are important clinical manifestations of psoriatic arthritis [Gladman DD. 2015]. These findings are much more frequent in patients with psoriatic arthritis than in psoriasis patients who do not have arthritis [Langenbruch A. 2014] [Langley RG. 2005] [Jones SM. 1994]. More importantly, the presence of the nail lesions provides an independent predictor of later development of psoriatic arthritis. [Wilson FC 2009]. Nail lesions are common at the onset of joint symptoms and are much more common on the same

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digits with abnormalities in the DIP joints. In psoriatic arthritis, arthritis of the DIP joints extending to the nail beds can be seen on MRI. Ultrasound examinations Enthesitis of the extensor tendons, thickening of the subcutaneous soft tissue and positivity power Doppler signals at the bases of the nails suggest periungual psoriatic lesions of psoriatic arthritis. The ultrasound features of the nail plates of psoriatic arthritis include loss of definition of the nail plates, hyperechoic spots in the nail plates, nail bed thickening, and increased power Doppler signals in the nail matrices / nail beds [W. X. Gutierrez M 2009] [Aydin S.Z. 2012]. Cynha JS et al. proposed an index for evaluating nail changes [Cunha JS 2017].

Figure 817. Ultrasound image and anatomy of the nail.

Figure 818. Ultrasound image shows power Doppler signals in the nail matrix and the nail bed and enthesopathy of the extensor enthesis in a patient with psoriatic arthritis.

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Figure 819. Nail changes in a patient with psoriatic onychopathy and arthritis.

Figure 820. Nail psoriasis in a patient with psoriatic arthritis.

Figure 821. Nail psoriasis in a patient with psoriatic arthritis.

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Figure 822. Nail psoriasis in a patient with psoriatic arthritis.

Figure 823. Nail psoriasis in a patient with psoriatic arthritis.

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Figure 824. Nail psoriasis in a patient with psoriatic arthritis.

Figure 825. Nail psoriasis in a patient with psoriatic arthritis.

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Figure 826. Nail psoriasis in a patient with psoriatic arthritis.

Figure 827. Nail psoriasis in a patient with psoriatic arthritis.

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Figure 828. Nail psoriasis in a patient with psoriatic arthritis.

Figure 829. Nail psoriasis in a patient with psoriatic arthritis.

Figure 830. Nail psoriasis in a patient with psoriatic arthritis.

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Myopathy Rarely, myopathy may be seen in patients with psoriatic arthritis [Thomson GT 1990]. Psoriatic myopathy is an uncommon descriptive condition in patients with psoriatic arthritis. Steroid induced myopathy shares some nonspecific features with psoriatic myopathy. However, they can be differentiated by the clinical response to cessation of steroid therapy. Some patients with psoriatic arthritis may have symptoms of dermatomyositis with Gottron's papules, arthritis of the DIP joints, and autoantibody production. References Aydin S.Z.C, Ash ZR, Marzo-Ortega H, Emery P, Wakefield RJ, Wittmann M, McGonagle D.Castillo-Gallego. Ultrasonographic assessment of nail in psoriatic disease shows a link between onychopathy and distal interphalangeal joint extensor tendon enthesopathy. Dermatology, 2012, 225:231-5. Aydin SZ.C, Ash ZR, Marzo-Ortega H, Emery P, Wakefield RJ, Wittmann M, McGonagle D.Castillo-Gallego. Ultrasonographic assessment of nail in psoriatic disease shows a link between onychopathy and distal interphalangeal joint extensor tendon enthesopathy. Dermatology, 2012, 225:231-5. Aydin SZZR, Tinazzi I, Castillo-Gallego C, Kwok C, Wilson C, et al.Ash. The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development. Ann Rheum Dis, 2013, 72:99. Benjamin MB, Brenner E, Emery P, McGonagle D, Redman S.Moriggl. The "enthesis organ" concept: why enthesopathies may not present as focal insertional disorders. Arthritis Rheum, 2004, 50:3306-13. Cunha JSAA, Reginato AM.Qureshi. Nail Enthesis Ultrasound in Psoriasis and Psoriatic Arthritis: A Report from the 2016 GRAPPA Annual Meeting. J Rheumatol, 2017, 44:688-690. Emad YBassyouni I, Moawayh O, Fawz M, Saad A, et al.Ragab,. Enthesitis and related changes in the knees in seronegative spondyloarthropathies and skin psoriasis: magnetic resonance imaging case-control study. J Rheumatol, 2010, 37:1709-17. Erdem CZNS, Sarikaya S, Erdem LO, Gulec S.Tekin. MR imaging features of foot involvement in patients with psoriasis. Eur J Radiol, 2008, 67:521-5. Firestein GS. Kelley & Firestein’s Textbook of Rheumatology. 10. Philadelphia, PA: Elsevier, 2016. Fischer E. Subunguale Verkalkungen. ROFO, 1982, 157:580. Forney MCCS, Schils JP.Winalski. Magnetic resonance imaging of inflammatory arthropathies of peripheral joints. Top Magn Reson Imaging, 2011, 22:45-59. Forrester DM. The “cocktail sausage” digit. Arthritis Rheum, 1983, 26:664. Fournié BN, Champetier de Ribes TL, Zabraniecki L, Jouan A, Vincent V, et al.Margarit-Coll. Extrasynovial ultrasound abnormalities in the psoriatic finger. Prospective comparative power-Doppler study versus rheumatoid arthritis. Joint Bone Spine, 2006, 73:527–531. Freeston JE1LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG.Coates. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res (Hoboken), 2014, 66:432-9. Gladman DD. Clinical Features and Diagnostic Considerations in Psoriatic Arthritis. Rheum Dis Clin North Am, 2015, 41:569-79. Gutierrez M.X, Filippucci E, De Angelis R, Filosa G, Grassi W.Wortsman. High-frequency sonography in the evaluation of psoriasis: nail and skin involvement. J Ultrasound Med, 2009, 28:1569-74. Gutierrez ME, Salaffi F, Di Geso L, Grassi W.Filippucci. Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level. Ann Rheum Dis, 2011, 70:1111-4. Gutierrez MX, Filippucci E, De Angelis R, Filosa G, Grassi W.Wortsman. High-frequency sonography in the evaluation of psoriasis: nail and skin involvement. J Ultrasound Med, 2009, 28:1569-74. Healy PJC, Chandramohan M, Helliwell PS.Groves. MRI changes in psoriatic dactylitis: extent of pathology, relationship to tenderness and correlation with clinical indices. RHeumatology, 2008, 47:92 –95. Jones SM.JB, Cohen MG, Lovell CR, Evison G, McHugh NJ.Armas. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumato, 1994, 33:834-9. Kane DL, Bresnihan B, FitzGerald O.Stafford. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology, 2003, 42:1460–1468. Kane DT, Bresnihan B, Gibney R, FitzGerald O.Greaney. Ultrasonography in the diagnosis and management of psoriatic dactylitis. J Rheumatol, 1999, 26:1746-51. Langenbruch A.MA, Krensel M, Jacobi A, Reich K, Augustin M.Radtke. Nail involvement as a predictor of concomitant

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psoriatic arthritis in patients with psoriasis. Br J Dermatol, 2014, 171:1123-8. Langley RG.GG, Griffiths CE.Krueger. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis, 2005, 64 Suppl 2:ii18-23. Lin ZY, Mei Y, Zhao Y, Zhang Z, et al.Wang. High-frequency ultrasound in the evaluation of psoriatic arthritis: a clinical study. Am J Med Sci, 2015, 350:42-6. Macía-Villa C.S, Gutierrez M, Medina J, Hammer HB, De Miguel E.Falcao. Peritenon extensor tendon inflammation in Psoriatic Arthritis is an enthesitis-related lesion. J Rheumatol, 2019, 2019 Feb 1. pii: jrheum.180856. doi: 10.3899/jrheum.180856. [Epub ahead of print]. Macía-Villa CS, Gutierrez M, Medina J, Hammer HB, De Miguel E.Falcao. What is metacarpophalangeal joint swelling in psoriatic arthritis? Ultrasound findings and reliability assessment. Clin Exp Rheumatol, 2018, 36:896-899. McGonagle DSZ, Tan AL.Aydin. The synovio-entheseal complex and its role in tendon and capsular associated inflammation. J Rheumatol Suppl., 2012, 89:11-4 . Offidani AA, Valeri G, Giovagnoni A.Cellini. Subclinical joint involvement in psoriasis: magnetic resonance imaging and X-ray findings. Act Derma Venerol, 1998, 78:463-5. Olivieri IL, Favaro L, et al.Baroozi. Dactylitis in patients with seronegative spondyloarthropathy: Assessment by ultrasonography and magnetic resonance imaging. Arthritis Rheum, 1996, 59:1524. Salvarani C.F, Olivieri I, Macchioni P, Niccoli L, Padula A, Ferri S, Portioli I.Cantini. Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic arthritis. J Rheumatol, 1997, 24:1106-10. Salvarani CF, Olivieri I, et al.Cantini. Distal extremity swelling with pitting edema in psoriatic arthritis: Evidence of 2 pathological mechanisms. J Rheumatol, 1999, 26:1831. Schett GRJ, D’Agostino M-A, et al.Lories. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol, 2017, 13:731–41. Sudoá-SzopiĔska IG.PracoĔ. Diagnostic imaging of psoriatic arthritis. Part II: magnetic resonance imaging and ultrasonography. J Ultrason, 2016, 16:163-74. . Tan ALE, Halliday NA, Tanner SF, Emery P, McGonagle D.Fukuba. High-resolution MRI assessment of dactylitis in psoriatic arthritis shows flexor tendon pulley and sheath-related enthesitis. Ann Rheum Dis, 2015, 74:185-9. Tan ALM, Toumi H, Grainger AJ, Tanner SF, Emery P, McGonagle D.Benjamin. The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis--a high-resolution MRI and histological study. Rheumatology (Oxford), 2007, 46:253-6. Thomson GTJL, Baragar FD, Toole JW.Johnston. Psoriatic arthritis and myopathy. J Rheumatol, 1990, 17:395-8. Tinazzi ID, Aydin SZ, Chessa D, Marchetta A, Macchioni P.McGonagle. 'Deep Koebner' phenomenon of the flexor tendon-associated accessory pulleys as a novel factor in tenosynovitis and dactylitis in psoriatic arthritis. Ann Rheum Dis, 2018, 77:922-925. Wilson FCM, Crowson CS, McEvoy MT, Gabriel SE, Kremers HM.Icen. Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study. Arthritis Rheum, 2009, 61:233-9. Yvmus M. Huge knee effusion: A record? Arthritis Rheum, 1981, 24:109. Zabotti A.S, Quartuccio L, et al.Salvin. Differentiation between early rheumatoid and early psoriatic arthritis by the ultrasonographic study of the synovio-entheseal complex of the small joints of the hands. Clin Exp Rheumatol, 2016, 34:459–65. Zabotti AS, Quartuccio L, et al.Salvin. Differentiation between early rheumatoid and early psoriatic arthritis by the ultrasonographic study of the synovio-entheseal complex of the small joints of the hands. Clin Exp Rheumatol, 2016, 34:459–65.

CHAPTER 8 F: FURTHER INFORMATION AND EXAMINATION OF PSORIATIC ARTHRITIS SYUICHI KOARADA, MARIKO SAKAI

Abstract Further information and examinations include clinical signs and symptoms, laboratory parameters, and pathological findings. Clinical manifestations of psoriatic arthritis are systemic symptoms and various symptoms associated with multiple organ lesions. There are no laboratory tests that can diagnose psoriatic arthritis. Histological findings of the skin and the joint are important for diagnosis of psoriatic arthritis. Signs and symptoms Asymptomatic psoriatic arthritis Psoriatic arthritis may be clinically silent, and especially enthesitis may be asymptomatic. Asymptomatic psoriatic arthritis can be more sensitively detected by ultrasound and MRI than clinical palpation. The clinical significance of these findings has not been clarified yet. Systemic symptoms The systemic symptoms of psoriatic arthritis include fatigue and fever. Except for the skin and the nail lesions, extra-articular involvement is less common in psoriatic arthritis than in rheumatoid arthritis. Symptoms of Joints The joint lesions in patients with psoriatic arthritis are highly variable and changeable over time [Gladman DD 2005]. Patients with psoriatic arthritis present with signs and symptoms of inflammation of the joints, the entheses and the spine. The onset of joint symptoms may be acute or insidious in psoriatic arthritis. Arthralgia On physical examination of patients with psoriatic arthritis, there are stress pain and tenderness of the affected joints, often in an asymmetric distribution pattern [Oriente P 1994]. Patients with psoriatic arthritis tend to have milder tenderness on physical examination than patients with other inflammatory arthritis such as rheumatoid arthritis [Buskila D 1992]. Therefore, patients with psoriatic arthritis may exhibit joint deformities without severe arthralgia. Axial disease of psoriatic arthritis, like ankylosing spondylitis, is correlated with clinical measures of disease activity, disability, and spinal motion.

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Stiffness Also, patients with psoriatic arthritis present with stiffness in the affected joints. Morning stiffness lasting more than half an hour occurs in one-half of the patients. Stiffness are enhanced by prolonged immobility and relieved by physical activity. Skin diseases Psoriasis is found in approximately 70% of patients presenting with arthritis. Inflammatory bowel diseases Patients with psoriatic arthritis have the high prevalence of inflammatory bowel diseases and sometimes are asymptomatic. Ophthalmologic symptoms Ophthalmologic problems in patients with psoriatic arthritis include conjunctivitis, iritis, and scleritis. Ocular disorders are common as extra-articular symptoms in psoriatic arthritis [Rosenbaum JT. 2015]. In patients with psoriatic arthritis, uveitis is usually a bilateral insidious disease that affects the anterior and the intermediate layers of the eyes. Iritis and uveitis commonly occur in patients with spinal involvement. Other symptoms Edema and lymphedema of the limbs are relatively common in psoriatic arthritis. Amyloidosis is rare but is reported in psoriatic arthritis. Laboratory parameters Anemia Mild anemia may be seen in patients with psoriatic arthritis. Acute phase markers Acute phase markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum amyloid A may be elevated in patients with psoriatic arthritis, but at lower levels compared with patients with rheumatoid arthritis. Erythrocyte sedimentation rate (ESR) Usually, inflammatory markers are raised [E. L. Merola JF 2018]. An elevated ESR is observed. The elevation in ESR is correlated with the number of swollen joints in psoriatic arthritis. ESR is particularly considered to be one of the best predictors of progression of joint damages of psoriatic arthritis. Patients with psoriatic arthritis generally show higher ESR compared with psoriasis patients without arthritis.

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C-reactive proteins (CRPs) Patients with psoriatic arthritis generally show higher concentrations of CRPs compared with psoriasis patients without arthritis [E. L. Merola JF 2018]. Elevated CRP levels are significantly correlated with the number of swollen joints in patients with psoriatic arthritis. Anti-nuclear antibodies (ANAs) Tests for anti-nuclear antibodies (ANAs) are usually negative [Taniguchi Y 2011]. Rheumatoid factors (RFs) Psoriatic arthritis is a seronegative inflammatory arthropathy and negative for rheumatoid factors (RFs) [E. L. Merola JF 2018]. Therefore, the absence of RFs is an important feature in differentiation from rheumatoid arthritis. However, some patients (around 10%) with psoriatic arthritis may have positive test findings for RFs and the titers are usually low. Up to 15% of the normal subjects have positive tests for RFs. The levels of RFs are particularly elevated in patients with polyarticular disease and are considered a marker of poor prognosis. Anti-citrullinated protein antibodies (ACPAs) Initially, anti-citrullinated protein antibodies (ACPAs) were thought to be specific for rheumatoid arthritis, but ACPAs are also found in about 5% of patients with psoriatic arthritis [Korendowych E 2005]. The levels of ACPAs are particularly elevated in patients with polyarticular disease and are markers of poor prognosis of psoriatic arthritis. Even if patients have positive tests for ACPAs, their titers are usually low [Veale DJ 2015]. A mean titer of ACPA values is significantly lower in patients with psoriatic arthritis compared with patients with rheumatoid arthritis [L. T. Merola JF 2016]. When the titers of ACPAs are 11.6 U / mL or more, the patients are likely to have rheumatoid arthritis rather than psoriatic arthritis [L. T. Merola JF 2016]. In both patients with psoriatic arthritis and patients with rheumatoid arthritis, the levels of ACPAs are associated with bone destruction and the osteo-catabolic effects. Uric acids In psoriatic arthritis, elevated levels of uric acids are sometimes seen and were thought to be associated with cellular turnover in psoriatic cutaneous lesions. Hyperuricemia is found in association with metabolic disorders in psoriatic arthritis patients and may not reflect the extent of the skin lesions. Immunoglobulins In psoriatic arthritis the concentration of immunoglobulins is elevated. There are differences in serum immunoglobulin levels between psoriasis patients with arthritis and those without arthritis [Vinje O 1980]. Pathological abnormalities Histological findings of the skin Typical histologic features of psoriasis skin include regular acanthosis, hyper granulosis, ectasia of the capillaries in the dermal papilla, and Munro micro abscess.

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Figure 831. The histological findings of the psoriasis skin include regular acanthosis, hypogranulosis, ectasia of the capillaries in the dermal papilla, and Munro micro abscess.

Figure 832. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

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Figure 833. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

Figure 834. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

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Figure 835. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

Figure 836. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

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Figure 837. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

Figure 838. The histological findings of the psoriasis skin of a patient with psoriatic arthritis.

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Figure 839. The histological findings of the psoriasis skin consistent with palmoplantar pustulosis.

Figure 840. The histological findings of the psoriasis skin consistent with palmoplantar pustulosis. Synovial Articulations Synovial inflammation characterized by increased angiogenesis and immune cell infiltration is an important feature of psoriatic arthritis [Veale D1 1993] [Kruithof E 2005] [Veale DJ. 2015]. While both psoriatic arthritis and rheumatoid arthritis show endothelial cell proliferation, topological differences in endothelial cells suggest different pathological features [Leibovich SJ 1987]. In patients with synovitis of the knees, in rheumatoid arthritis, straight and branching vessels are observed, while in psoriatic arthritis, tortuous and bushy vessels are observed [Ceponis A 1998]. The physiological differences are considered to be caused by differences in the expression pattern of synovial cytokines, as a significantly higher expression of IL-1ȕ, IL-2, IL-10 and IFN-Ȗ is seen in psoriatic arthritis synovial explants compared with rheumatoid arthritis synovial explants [Reece RJ 1999].

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References Buskila DP, Gladman DD, Urowitz S, Smythe HA.Langevitz. Patients with rheumatoid arthritis are more tender than those with psoriatic arthritis. J Rheumatol, 1992, 19:1115-9. Ceponis AYT, Imai S, Tamulaitiene M, Li TF, Xu JW, Hietanen J, Santavirta S, Fassbender HG.Konttinen. Synovial lining, endothelial and inflammatory mononuclear cell proliferation in synovial membranes in psoriatic and reactive arthritis: a comparative quantitative morphometric study. Br J Rheumatol, 1998, 37:170-8. Gladman DDC, Mease P, Clegg DO, Nash P.Antoni. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis, 2005, 64 Suppl 2:ii14-7. Korendowych EP, Ravindran J, Carmichael C, McHugh N.Owen. The clinical and genetic associations of anti-cyclic citrullinated peptide antibodies in psoriatic arthritis. Rheumatology (Oxford), 2005, 44:1056-60. Kruithof ED, De Rycke L, Vandooren B, Foell D, Roth J, Cañete JD, Boots AM, Veys EM, De Keyser F.Baeten. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. Arthritis Res Ther, 2005, 7:R569-80. Leibovich SJPJ, Shepard HM, Wiseman DM, Shively V, Nuseir N.Polverini. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature, 1987, 329:630-2. Lindqvist URGM, Husmark T, et al.Alenius. The Swedish early psoriatic arthritis register—2-year followup: a comparison with early rheumatoid arthritis. J Rheumatol, 2008, 35:668–73. Merola JFLR, Fleischmann R.Espinoza. Distinguishing rheumatoid arthritis from psoriatic arthritis. RMD Open, 2018, 4:e000656. . Merola JFT, Li WQ, et al.Li. Prevalence of psoriasis phenotypes among men and women in the USA. Clin Exp Dermatol, 2016, 41:486–9. Oriente PC, Scarpa R.Biondi-Oriente. Psoriatic arthritis. Clinical manifestations. Baillieres Clin Rheumatol, 1994, 8:277. Reece RJJD, Parsons WJ, Emery P, Veale DJ.Canete. Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis. Arthritis Rheum, 1999, 42:1481-4. Rosenbaum JT. Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease. Clin Rheumatol, 2015, 34:999–1002. Taniguchi YY, Shimamura Y, Kobayashi S, Terada Y.Kumon. Rapidly progressive destructive arthritis in psoriatic arthritis sine psoriasis: do bone resorption marker levels predict outcome of bone destruction in psoriatic arthritis? Mod Rheumatol, 2011, 21:106-8. Veale D1G, Rogers S, Barnes L, Bresnihan B, Fitzgerald O.Yanni. Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis. Arthritis Rheum, 1993, 36:893-900. Veale DJ.U.Fearon. What makes psoriatic and rheumatoid arthritis so different? RMD Open, 2015, 1:e000025. . Veale DJU.Fearon. What makes psoriatic and rheumatoid arthritis so different? RMD Open, 2015, 1:e000025. Vinje OP, Mellbye OJ.Møller. Laboratory findings in patients with psoriasis, with special reference to immunological parameters, associations with arthropathy and sacro-iliitis. Scand J Rheumatol, 1980, 9:97-105.

CHAPTER 9 G: GOAL OF DIAGNOSIS OF PSORIATIC ARTHRITIS AND H: HEALING AND HEALTHY CONDITION IN PSORIATIC ARTHRITIS

SYUICHI KOARADA, YOSHINOBU NAKAO

Abstract There are currently no tests that can diagnose psoriatic arthritis. The diagnosis of psoriatic arthritis is made by the combination of findings such as enthesitis, arthritis, tenosynovitis, bone marrow edema, periostitis, and so on. Moreover, clinical characteristics including a personal or family history of psoriasis, psoriatic nail dystrophy and dactylitis are important. The goal of treatment is complete remission or minimal disease activity in psoriatic arthritis. Introduction In clinical trials, the diagnosis of psoriatic arthritis is carried out according to the classification criteria by the CASPAR (ClASsification criteria for psoriatic arthritis) group [Taylor W. 2006]. However, several other criteria have also been proposed. The Imaging provides important supplementary information for physicians to distinguish between psoriatic arthritis and other inflammatory arthritis. The characteristics of involvement of the hands and the wrists in psoriatic arthritis make it possible in particular to distinguish between psoriatic arthritis and inflammatory (erosive) osteoarthritis [Martel W 1980]. Effective treatment halts the progression of the disease, so that the goal of treatment has evolved from simple reduction of pain to complete remission or minimal disease activity. Classification criteria The classification criteria for psoriatic arthritis serve to classify inflammatory joint disease patients for clinical trials. Classification criteria and diagnostic criteria should not be confused. In 2006, classification criteria by ClASsification criteria for Psoriatic ARthritis (CASPAR) group were introduced as a classification criterion for psoriatic arthritis. The CASPAR classification criteria are cited the most, but several alternative criteria have been proposed. Moll and Wright criteria The original criteria by Moll and Wright (1973) were the simplest and most used prior to 2006.

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The criteria include: 1.

Inflammatory arthritis (peripheral arthritis and/or sacroiliitis or spondylitis)

2.

The presence of psoriasis

3.

The (usual) negative serological test for RF.

The Moll and Wright classification criteria are still widely used and accepted. Caspar Study Group criteria The CASPAR criteria have been identified as useful and standard. The criteria are most commonly used by physicians. The CASPAR criteria include the presence of osteogenic phenomena detected in radiography. In contrast to Moll and Wright criteria, the CASPAR criteria allow diagnosis of psoriatic arthritis in patients without skin psoriasis. Moreover, in order to increase sensitivity, characteristic features such as dactylitis, nail psoriasis, and family history are added. Most importantly, the CASPAR classification criteria are capable of diagnosis of psoriatic arthritis sine psoriasis (sine syndrome). The CASPAR criteria are well validated by many prospective and retrospective studies, including patients with early psoriatic arthritis, with high sensitivity and high specificity. The CASPAR criteria have a specificity of 0.987 and a sensitivity of 0.914. However, in the classification criteria, early cases and atypical cases may be missed, especially with sine syndrome or with arthritis preceding psoriasis. For this reason, the classification criteria have a high specificity, but the sensitivity drops slightly. Although they are useful for diagnosis, the criteria do not reflect the severity and disease type of an individual. The CASPAR classification criteria include evidence of psoriasis (current, personal or family history), psoriatic nail dystrophy, negative tests for rheumatoid arthritis, dactylitis and radiographic evidence of juxta-articular new bone formation [Taylor W. 2006]. Psoriatic arthritis is diagnosed in a patient presenting with inflammatory articular disease (peripheral arthritis, spondylitis and sacroiliitis, or enthesitis) with 3 or more points from the following 5 categories. 1.

Evidence of current psoriasis, a personal history of psoriasis, or a family history of psoriasis. Current psoriasis

is defined as psoriatic skin or scalp disease present today as judged by a rheumatologist or dermatologist. A personal history of psoriasis is defined as a history of psoriasis that may be obtained from a patient, family physician, dermatologist, rheumatologist, or other qualified health care provider. A family history of psoriasis is defined as a history of psoriasis in a first- or second-degree relative according to patient report. 2.

Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis observed on current

physical examination. 3.

A negative test result for the presence of rheumatoid factor by any method except latex but preferably by

enzyme-linked immunosorbent assay or nephelometry, according to the local laboratory reference range. 4.

Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis recorded by a

rheumatologist. 5.

Radiographic evidence of juxta articular new bone formation, appearing as ill-defined ossification near joint

margins (but excluding osteophyte formation) on plain radiographs of the hand or foot.

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Current psoriasis is assigned a score of 2; all other features are assigned a score of 1. The osteo-proliferative lesions on radiography are considered pathognomonic for psoriatic arthritis and are important in the CASPAR criteria. Bennett’s criteria Criteria for psoriatic arthritis proposed by Bennett [Bennett RM. 1979] Mandatory Clinically apparent psoriasis (skin or nails) Pain and soft tissue swelling and/or limitation of motion in at least one joint observed by a physician for six weeks or longer. Supportive Pain and soft tissue swelling and/or limitation of motion in one or more other joints observed by a physician. Presence of an inflammatory arthritis in a distal interphalangeal joint. Specific exclusions: Bouchard’s or Heberden’s nodes. Presence of ‘‘sausage’’ fingers or toes. An asymmetric distribution of arthritis in the hands and feet. Absence of subcutaneous nodules. A negative test for rheumatoid factor in the serum. An inflammatory synovial fluid with a normal or increased C3 or C4 level and an absence of infection (including acid fast bacilli) and crystals of monosodium urate or pyrophosphate. A synovial biopsy showing hypertrophy of the synovial lining with a predominantly mononuclear cell infiltration and an absence of granuloma or tumor. Peripheral radiographs showing erosive arthritis of the small joints with a relative lack of osteoporosis. Specific exclusion: erosive osteoarthritis. Axial radiographs showing any of the following: sacroiliitis, syndesmophytes, paravertebral ossification. Definite PsA: mandatory plus six supportive Probable PsA: mandatory plus four supportive Possible PsA: mandatory plus two supportive

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Gladman et al.’s criteria [Gladman DD 1987] Current psoriasis, history of psoriasis, or nail disease, and inflammatory joint disease, clinical sacroiliitis or inflammatory spinal disease: and not rheumatoid nodules, grade 4 osteoarthritis, reactive arthritis, enteropathic arthritis, gout, or systemic lupus erythematosus McGonagle et al.’s criteria [McGonagle D 1999] McGonagle proposes that one of the features of classification criteria of psoriatic arthritis is radiographic findings of enthesitis. Current psoriasis, history of psoriasis, or family history of psoriasis, and inflammatory heel pain, anterior chest wall pain, any tender enthesis: any of these x-ray features—tuft erosion, ankylosis, juxta-articular new bone formation, syndesmophytes, paravertebral ossification, Romanus lesion, erosion at an entheseal insertion, new bone formation at an entheseal insertion: finger DIP joint involvement, inflammatory spinal symptoms, clinical sacroiliitis: any of—synovitis, acne, pustulosis, hyperostosis, osteitis, spondylodiscitis, arthritis mutilans, onycho-pachydermoperiostitis, chronic recurrent multifocal recurrent osteomyelitis: dactylitis, or several involved joints is less than five Fournié’s criteria [Fournié B 1999] Personal psoriasis antedating or concomitant with joint symptoms onset (score 6) Familial history of psoriasis or psoriasis postdating joint symptoms onset (score 3) Arthritis of DIP (score 3) InÀammatory involvement of the cervical and thoracic spine (score 3) Asymmetric monoarthritis or oligoarthritis (score 1) Buttocks pain, heel pain, spontaneous anterior chest-wall pain or diffuse inÀammatory pain in the enthuses (score 2) Presence of HLA B16 (B38, B39) or B17 (score 6) RF negative (score 4) Radiological changes – DIP erosion, joint osteolysis, ankylosis, juxta-articular new bone formation or tuft erosion (score 5 if any one criterion is present) The threshold of positivity is 11 points

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Criteria of European Spondyloarthropathy Study Group, ESSG [Dougados M1 1991] InÀammatory spinal pain or Synovitis (either asymmetrical or predominantly lower limb) One or more of the following: positive FH of psoriasis ESSG criteria is satis¿ed if one of two features criteria in 1 is present together with one or more in 2. Vasey and Espinoza’s criteria [Vasey FB 1984] Current psoriasis, history of psoriasis, or nail disease, and finger DIP involvement, dactylitis, asymmetry, symmetry, and rheumatoid factor negative, and absence of nodules, radiographic osteolysis, tuft erosion, ankylosis, or juxtaarticular new bone formation, inflammatory spinal disease, or radiographic sacroiliitis *Asymmetry defined as number of matched involved joint pairs greater than the number of nonmatched involved joint pairs when 11 joint pairs considered (shoulder, elbow, wrist, metacarpophalangeals, PIPs, DIPs, hip, ankle, metatarsophalangeals, and toe IPs). † Predominant lower limb arthritis defined as number of involved lower limb joints (hip, knee, ankle, tarsus, metatarsophalangeals, and toe IPs) greater than the number of involved upper limb joints (shoulder, elbow, wrist, metacarpophalangeals, PIPs, DIPs). DIP—distal interphalangeal; IP—interphalangeal joints; PIP—proximal interphalangeal. H. Healing and healthy condition The biological agents in the strategy for the management of psoriatic arthritis have improved the outcome of the disease. However, a significant number of patients with psoriatic arthritis are not sufficiently responsive to the treatment. Therefore, there is a need to improve understanding of the pathophysiological background of psoriatic arthritis, to identify prognostic and predictive markers of progression and responsiveness to the therapy, and to find a way to a “personalized” approach for healing and healthy condition. The goal of treatment Ideally, treatment of patients with psoriatic arthritis is to eliminate musculoskeletal symptoms and to reach a state without signs of psoriatic skin disease. Thus, the symptoms related to the joints, the skin and the entheses are completely controlled and patients with psoriatic arthritis do not compromise physical function and quality of life. Recognizing the importance of early diagnosis and enabling targeted treatment, the goals of treatment can be achieved as low disease activity status or remission [Eberle FC 2016]. Effective treatment halts the progression of the disease, so that the goal of treatment has evolved from simple reduction of pain to complete remission or minimal disease activity in psoriatic arthritis. Strategy of treatment The treatment of psoriatic arthritis can be referred to the GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) treatment recommendations and European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis gathered by experts in the US and Europe [Gossec L 2020]. Effects of joint symptoms and skin symptoms on therapeutic agents do not always parallel. Treatment

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of psoriatic arthritis is a combination of physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs), cytostatic, immunosuppressive and biological drug therapies. Drug therapies NSAIDs (Non-steroidal anti-inflammatory drugs) In some cases, psoriatic arthritis may remain mild and allow management with NSAIDs. csDMARDs (Conventional synthetic disease-modifying antirheumatic drugs) As disease modifying antirheumatic drugs (DMARDs), there are methotrexate (MTX), sulfasalazine, leflunomide, apremilast, etretinate, cyclosporin, and gold salts, but often it is difficult to control the disease by csDMARDs. Biologic disease-modifying antirheumatic drugs (bDMARDs) Biological DMARDs (or "biologicals") are used to treat patients with moderate to severe psoriatic arthritis whose disease did not respond appropriately to other types of treatment. Biological DMARDs include; 1.

Tumor necrosis factor-alpha (TNF-alpha) inhibitors

TNF-alpha inhibitors block TNF-alpha, a cytokine that prompts the body to create inflammation. certolizumab pegol, etanercept, adalimumab, infliximab, golimumab 2.

Interleukin 12 and 23 (IL-12/23) inhibitors

ustekinumab 3.

Interleukin 17 (IL-17) inhibitors

secukinumab, ixekizumab, brodalumab, bimekizumab 4.

T cell inhibitors

abatacept 5.

Interleukin 23 (IL-23) inhibitors

tildrakizumab-asmn, risankizumab-rzaa, guselkumab, mirikizumab, briakinumab, ustekinumab

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Figure 841. Biological DMARDs.

Figure 842. Nail lesions before and after the treatment. Jak inhibitors (Janus kinase inhibitors) The Janus kinase inhibitors (Jak inhibitors) maybe benefit for the use in active psoriatic arthritis. References Bennett RM. Psoriatic arthritis. Philadelphia: Lea & Febiger: In: McCarty DJ, editor. Arthritisand allied conditions. 9th ed., 1979, 645. Dougados M1der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, Cats A, Dijkmans B, Olivieri I, Pasero G, et al.van. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum, 1991, 34:1218-27.

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Eberle FCJ, Holstein J, Hirahara K, Ghoreschi K.Brück. Recent advances in understanding psoriasis. F1000Res, 2016, 5. pii: F1000 Faculty Rev-770. Fournié BL, Arnaud C, Zabraniecki L, Lascaux-Lefebvre V, Marc V, Ginesty E, Andrieu V, Dromer C, Fournié A.Crognier. Proposed classification criteria of psoriatic arthritis. A preliminary study in 260 patients. Rev Rhum Engl Ed., 1999, 66:446-56. Gladman DDR, Russell ML, Thorne JC, Schachter RK.Shuckett. Psoriatic arthritis (PSA)--an analysis of 220 patients. Q J Med, 1987, 62:127-41. Gossec L, Baraliakos X, Kerschbaumer A, de Wit M, McInnes I, Dougados M, Primdahl J, McGonagle DG, Aletaha D, Balanescu A, Balint PV, Bertheussen H, Boehncke WH, Burmester GR, Canete JD, Damjanov NS, Kragstrup TW, Kvien TK, Landewé RBM, Lories RJU, et al. "EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update." Ann Rheum Dis. 79 (2020): 700-712. Martel WKJ, Dworin AM, Hylland RG.Stuck. Erosive osteoarthritis and psoriatic arthritis: a radiologic comparison in the hand, wrist, and foot. AJR Am J Roentgenol, 1980, 134:125-35. McGonagle DPG, Emery P.Conaghan. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum, 1999, 42:1080-6. Taylor W.D, Helliwell P, Marchesoni A, Mease P, Mielants H.Gladman. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum, 2006, 54:2665-73. Vasey FBLREspinoza. Psoriatic arthritis. Orlando. Grune and Stratton: In: CALIN A (Ed.) Spondyloarthropathies., 1984, 151-85.

CHAPTER 10 I: IMMUNOLOGY OF PSORIATIC ARTHRITIS SYUICHI KOARADA, YUKIKO TAKEYAMA

Abstract Genetic factors and environmental events trigger the autoimmune reaction of psoriatic arthritis. However, the pathogenesis of psoriatic arthritis has not been completely elucidated. Gut dysbiosis is associated with the pathogenesis of psoriatic arthritis. In psoriatic arthritis, human leukocyte antigens (HLAs) are associated with disease susceptibility and severity. The primary genetic factor associated with psoriatic arthritis is HLA-B27. In psoriatic arthritis, activated T cells and macrophages produce inflammatory chemokines and cytokines including IL-17, IL-22, IL-23, IL-1 beta, IL-6, IFN-gamma and TNF-alpha. Elevated levels of IL-17 + CD8 + T cells are observed in the joints of patients with psoriatic arthritis but not in patients with rheumatoid arthritis. Genetic factors The genetic predisposition in joint symptoms of psoriatic arthritis is emphasized [Arnett F.C., 1950]. Genetic factors appear to account for about 70% of the sensitivity to psoriasis [Generali, 2017]. As there are a large number of patients with psoriasis (approximately 30%) who develop psoriatic arthritis, psoriasis and psoriatic arthritis share partially overlapping genetic susceptibility [Boutet M.A., 2018]. When patients have a first-degree family with psoriasis, they, without history of a skin disorder, may show clinical features of psoriatic arthritis (sine syndrome) [Olivieri I., 2009]. A paternal transmission bias has been demonstrated for psoriasis and psoriatic arthritis [Pollock RA, 2015]. Twin and family studies Psoriasis and psoriatic arthritis occur in families. About 40% of patients with psoriasis or psoriatic arthritis have a family history of psoriasis in first-degree relatives [Gladman DD, HLA antigens in psoriatic arthritis., 1986]. Twin and family studies of psoriatic arthritis in the European populations have shown a higher concordance rate in the monozygotic twins compared with dizygotic twins [Stuart PE, 2015] [Myers A, 2005]. Also in psoriasis, the concordance of monozygotic twins is higher than that of dizygotic twins [Pedersen OB, 2008]. Major histocompatibility complex (MHC) In psoriatic arthritis, the association of the major histocompatibility complex (MHC) on chromosome 6 has been identified. Both HLA-associated and non-HLA genes play in the pathogenesis of psoriatic arthritis.

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HLA-B Among the HLA-genes, several alleles of HLA-B (B * 08, B * 27, B * 38, and Bw4) are known to be strongly associated with psoriatic arthritis [Boutet M.A., 2018]. HLA-B08 HLA-B*08:01:01–HLA-C*07:01:01 haplotype is associated with joint fusion, deformities, asymmetric sacroiliitis and dactylitis [Haroon M, 2016]. HLA-B27 HLA-B * 27 is recognized to be the most important risk factor for spinal lesions of psoriatic arthritis [Bowes J., 2017]. HLA-B*27:05:02 haplotype is associated with enthesitis, dactylitis, and symmetric sacroiliitis [Haroon M, 2016]. HLA-B27 positivity in psoriatic arthritis is associated with more severe axial inflammation on MRI [Castillo-Gallego C, 2013] [Tsoi LC, 2012]. A high frequency of HLA-B27 antigen is also found in patients with the DIP joint involvement [Eastmond CJ, 1977]. HLA-Bw38 HLA-Bw38 positivity has been observed in patients with psoriatic arthritis [Gerber LH, 1982]. HLA-B38 is associated with polyarthritis in psoriatic arthritis [Gladman DD, HLA antigens in psoriatic arthritis., 1986]. HLA-C HLA-Cw6 HLA-Cw6 positivity is characteristic of sine syndrome in psoriatic arthritis. The presence of HLA-Cw6 is also associated with the DIP arthritis and dactylitis. HLA-DR HLA-DR4 DR4 haplotypes are associated with the rheumatoid arthritis pattern of psoriatic arthritis [Gladman DD, HLA antigens in psoriatic arthritis., 1986]. Immunological aspects There is evidence for immune-related inflammation in the pathogenesis of psoriatic diseases and commonality at different lesion sites in the disease [Veale D.J., 2018]. Similar to rheumatoid arthritis, lymphocyte infiltration, angiogenesis, synovitis, synoviocyte activation, and in particular the production of cytokines such as TNF-alpha and IL-17 are characteristic of psoriatic arthritis [Veale D.J., 2018]. Recently, it has been pointed out that CD8 + T cells and innate immune response could be involved in the pathogenesis of the disease.

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Figure 843. Immunological aspect in psoriatic arthritis. Autoantigens The autoantigen(s) causing the autoimmune responses in psoriatic arthritis has not yet been identified [Boutet M.A., 2018]. Although candidates have been proposed as autoantigens including type I keratin, papilloma virus 5, and heat shock proteins, clear evidence of their pathogenic relevance in psoriasis is still lacking [Boutet M.A., 2018]. Shared autoantigens in joint and skin The relationship between T cell clones in the skin and synovium is revealed, and a common antigen may induce T cell responses working in both target organs [Tassiulas I., 1999]. With regard to enthesitis, Dolcino et al. reported on psoriatic arthritis-specific antibodies that are cross-reactive to peptides expressed in both psoriatic skin and in inflammatory entheses [Dolcino, 2014]. To elucidate whether psoriatic arthritis is caused by autoantigens shared between joint and skin, we need further studies. Immune cells Various immune cells play important roles in the pathophysiology of psoriatic arthritis. The infiltrated immune cells release proinflammatory mediators that activate fibroblast-like synoviocytes and affect the adjacent cartilages and the bones. Acquired immune cells, Lymphocytes Among the immune cells infiltrating in synovium of psoriatic arthritis, lymphocytes are the most abundant. In the synovium of psoriatic arthritis, lymphoid aggregates of T cells and B cells are observed, and the aggregates and disease activity are associated [Baeten D, 2005]. Also, the size of lymphoid aggregates is associated with disease activity [Cañete JD, 2007].

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B cells The exact roles of B cells in the pathogenesis of psoriatic arthritis are unknown. B cells can present antigens to T cells. B cells are possible to be also involved in co-stimulation of T cells and production of soluble mediators. T cells The central roles of T cells in the pathogenesis of psoriatic arthritis have been recognized [Boutet M.A., 2018]. The importance of T cells in psoriatic arthritis is also evident from the strong genetic association of the disease with MHC molecules. Furthermore, CD4 + T cells (Th cells) are divided into several subpopulations, each of which produces characteristic cytokines and has crucial influence on the pathogenesis of psoriatic arthritis.

Figure 844. T cell subpopulations.

Figure 845. Activated dendritic cells differentiate T cells [Nestle FO, 2009] [Capon F, 2012]. The T cell subpopulations including Th1, Th2, Th17, Th9, Th22, and Treg cells (T regulatory cells) secrete proinflammatory or anti-inflammatory cytokines. While the importance of the Th1 cells has been recognized for many years, interest in the Th17 cells, IL-23 and IL-17 has increased in recent years [Ritchlin CT., 2016]. The roles of T cells in the pathogenesis of psoriatic arthritis have been evidenced by the results of increased T cell-produced cytokines such as IFNȖ, IL-2, IL-4, TNFĮ, Il-17A, and granulocyte macrophage -colony stimulating factor (GM-CSF) in the synovial fluid and synovial membrane of patients with psoriatic arthritis [van Kuijk AW, 2006]. T cells are roughly divided into CD4 + T cells, CD8 + T cells, Treg cells, and Ȗį T cells, and play important roles in pathogenesis of psoriatic arthritis.

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Figure 846. T cell subsets in psoriatic arthritis [Belge K, 2014] [Lowes MA, 2013].

Figure 847. Th1 and Th17 cell subsets and IL-17 production in psoriatic arthritis.

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Figure 848. Th subpopulations in psoriatic arthritis. Th1 cells Psoriatic arthritis was originally thought to be a Th1-mediated disease in which large amounts of IFN-gamma, TNF-alpha and IL-2 are produced [Partsch G., 1998] [Ritchlin CT., 2016]. Th9 cells Th9 cells are associated with autoimmune diseases. In the synovium of psoriatic arthritis, IL-9 and its receptors are mainly expressed on fibroblast-like synovial cells, synovial vessels and Th9 cells [Ciccia F, 2016]. Th9 cells increase in peripheral blood and synovial fluid, and the number of Th9 cells correlates with disease activity of psoriatic arthritis [Nowak EC, 2009]. In addition, the number of Th9 cells decreases after treatment with TNF inhibitors and ustekinimab (IL-17 inhibitor) [Nowak EC, 2009]. Th17 cells Th17 cells, characterized by expression of the transcription factor Retinoic acid receptor-Related Orphan receptor-Ȗt (ROR-Ȗt) and the signaling pathway Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT), produce the cytokine IL-17. The importance of Th17 in psoriasis is widely accepted [Di Cesare A, 2009]. Th17 cells produce proinflammatory cytokines such as IL-17A, IL-17F, IL-21, IL-22, and TGF-ȕ [Benham H, 2013] [Kirkham BW, 2014]. IL-23 activated Th17 cells promote autoimmunity and chronic inflammation. Conversely TGF-ȕ and IL-6 induce weakly pathogenic Th17 cells, which are important in tissue defense and integrity [Gaffen SL, 2014]. Accumulation of IL-17-producing cells in the joints induces inflammation and angiogenesis of synovial tissue, and acts synergistically with cytokines such as IL-1ȕ, TNF, and oncostatin M to upregulate matrix metalloproteinases and enhances osteogenic activity [Raychaudhuri SP, 2012] [Moran EM, 2009] [Hwang SY, 2004]. At the entheses,

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resident Th17 cells producing IL-17 and IL-22 act on osteoblasts in a STAT3 dependent manner, affect bone remodeling and are associated with typical bone formation [Sherlock JP, 2012]. Elevated frequencies of IL-17-positive CD4+ T cells have been observed in the synovial fluid compared with the peripheral blood.

Figure 849. Th subpopulations and cytokine production in psoriatic arthritis. [Leung S et al. Cell Mol Immunol. 2010;7:182-189; Zhu J et al. Ann Rev Immunol. 2010;28:445-489; Marwaha A et al. Front Immunol. 2012;3:1-8; Hemdan N et al. Immunol Lett. 2012:148:97-109; Annunziato F, Romagnani S. Blood. 2009;114:2213-2219.] Th22 cells Th22 cells characterized by the expression of IL-22 but not IL-17 are strongly involved in the epidermal immune system and inflammatory response [Eyerich S, 2009]. In the joints, there are fewer IL-22 positive CD4 + T cells compared with the skin, and the absence of expression of IL-22 in synovial tissue [Benham H., 2013]. The differential expression of Th17 and Th22 cell subsets at the sites of diseases suggests that Th17 and Th22 cells may play different roles in the joint and the skin lesions. CD8㸩T cells and Tc17 cells Cytotoxic CD8 + T cells play major roles in the synovium, as they are predominantly presence in the synovial fluids of patients with psoriatic arthritis [Costello PJ, 2001]. Elevated levels of IL-17 + CD8 + T cells (Tc17 cells) are observed in the joints of patients with psoriatic arthritis but not in those with rheumatoid arthritis [Menon B, 2014]. IL-17+ CD8+ T cells are also associated with erosive disease of psoriatic arthritis. CD8+ T cells from synovium of psoriatic arthritis are clonally expanded, but self-peptide antigens or pathogenic antigens for the clonal expansion have not been identified [Costello PJ., 2001] [Choy E., 2007].

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Ȗį T cells Ȗį T cells have innate cell-like features and allow their early activation following recognition of conserved stress-induced ligands [Bonneville M, 2010]. A population of resident dermal Ȗį T cells has been shown to proliferate in situ and to be involved in the regulation of skin immunity [Sumaria N, 2011]. IL-17-producing Ȗį T cells (Ȗį17 cells) are often the main producers of IL-17 in mouse models of inflammatory diseases [Akitsu A, 2018]. Innate immune cells Innate immune system cells such as dendritic cells (DCs), macrophages, innate lymphoid cells (ILCs), mucosal-associated invariant T cells (MAIT cells), natural killer cells (NK cells), and mast cells strongly produce proinflammatory cytokines. Dendritic cells (DCs) Dendritic cells (DCs) contain heterogeneous subsets of antigen presenting cells, linking innate and adaptive immunity. Dendritic cells play a key role in the activation of adaptive immune responses via antigen presentation and cytokine secretion to generate various T cell subsets (Th1, Th2, Th17, Th9, Th22, and Treg cells) [Gierut A, 2010].

Figure 850. Activation of dendritic cells. The ratio of myeloid dendritic cells of plasmacytoid dendritic cells is significantly increased in the synovial fluid in psoriatic arthritis. Among these dendritic cells, it is shown that immature phenotype is predominant, and will continue to respond to Toll-like receptor ligands [Jongbloed SL, 2006] [Lande R, 2004]. The immature phenotype of dendritic cells can further perpetuate the pathology by allowing the cells to respond to synovial microenvironment and arthritogenic antigens. Persistent production of type I IFN by mature pDCs suggests pathogenic relevance in the inflammatory process of psoriatic arthritis [Lande R, 2004].

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Macrophages Histologically, the major cells in the synovium of psoriatic arthritis are macrophages. Activated macrophages function to promote the various inflammatory responses in the synovium. Macrophages that promote inflammation are called M1 acrophages, and M1 macrophages play a central role in host defense against infection. On the other hand, macrophages that reduce inflammation and promote tissue remodeling are called M2 macrophages. Increased secretion of proinflammatory cytokines by macrophages is one of the characteristic features of psoriatic arthritis. In addition, macrophages, an M1 predominant phenotype, secrete large amounts of matrix metalloproteinases and inducible nitric oxide synthase, present antigens to T cells and B cells, and also promote bone resorption [Kurowska-Stolarska M, 2017]. Innate lymphoid cells (ILCs) Innate lymphoid cells (ILCs) are rare innate immune cell populations that are derived from common lymphoid progenitors (CLPs). These cells are defined by the absence of antigen-specific B or T cell receptors due to the absence of a recombinant activation gene (RAG). ILCs do not express myeloid or dendritic cell markers [Pantelyushin S, 2012]. ILCs are divided into three groups, ILC1s, ILC2s, and ILC3s. ILC3s have the capacity to produce cytokines IL-17A and/or IL-22 and show increased expression of CCR6 and NK-p44. ILC3s are enriched in the synovial fluid in patients with psoriatic arthritis compared with rheumatoid arthritis [Leijten EF, 2015]. ILC2s can produce type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. In patients with psoriatic arthritis, a significant increase in circulating ILC3s and a decrease in ILC2s are shown as compared with healthy subjects, and the ratio of ILC2 to ILC3 is significantly correlated with joint inflammation and bone damages [Soare A, 2018]. Various subsets of ILCs, Th17 and IL-22 play important roles in psoriatic arthritis. Mucosal-associated invariant T cells (MAITs) Mucosal-associated invariant T cells (MAIT cells) are also one of the important subsets of T cells in the immune system that displays innate, effector-like qualities and implicates in autoimmune diseases. Stimulated by IL-12, IL-18, and IL-23, MAIT cells can produce and secrete pro-inflammatory cytokines, and MAIT cells in ankylosing spondylitis produce IL-17A as an effect primed by IL-7 and not IL-23 [Gracey E, 2016]. MAIT cells serve as an alternative source of IL-17A at the site of inflammation. An increase in IL-17A producing CD8-positive MAIT cells is observed in psoriatic skin and in synovial fluid of psoriatic arthritis [Teunissen MBM, 2014] [Menon B, 2014]. Natural killer cells Natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system and have both protective and pathogenic roles. NK cells are regulated by activating receptors and inhibitory receptors. NK cells in the synovium of psoriatic arthritis have increased production of IFN-gamma and TNF-alpha as compared with peripheral blood cells, and expression of activation markers CD69 and NK-p44 is also increased [de Matos CT, 2007]. Mast cells Mast cells are resident cells of connective tissue having many granules rich in histamine and heparin. Histamine and tryptase released from mast cells can promote synovial angiogenesis and recruitment of neutrophil, and it is suggested that mast cells may play an active role in the inflammatory cascade. Mast cells expressing IL-17A are present in the

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synovial fluid and synovium in patients with psoriatic arthritis [Noordenbos T, 2012]. Neutrophils Increased neutrophils are seen in synovitis of psoriatic arthritis compared with rheumatoid arthritis [Fitzgerald O., 2005]. The interesting observation of the increased neutrophil infiltration in psoriatic arthritis is consistent with the neutrophil infiltrates found in psoriatic skin. Antigen presenting cells (APCs) Although antigen presenting cells (APCs) play roles in initiating the immune response, they also produce and release proinflammatory cytokines such as IL-2 and IL-23, which promote differentiation of naïve T cells into Th1 cells or Th17 cells. Resident cells The resident cells include synovial fibroblast-like synoviocytes, chondrocytes, osteoblasts, and osteoclasts. The resident cells primarily secrete matrix degrading enzymes and receptor activator of nuclear factor kappa-Ǻ ligand (RANKL), causing cartilage degradation, bone erosion, and joint damage and proinflammatory mediators to recruit more immune cells to persist immune response. IL-23, TNF-alpha, IL-17, and IL-22 are important cytokines which promote inflammation in the joints and at the entheses and activate cells such as synovial fibroblast-like synoviocytes, chondrocytes, osteoblasts, and osteoclasts that reside in the same areas. Cytokines In psoriatic arthritis, activated immune cells release cytokines that cause inflammation. Activated T cells and macrophages produce inflammatory chemokines and cytokines such as IL-17, IL-22, IL-23, IL-1 beta, IL-6, IFN-gamma and TNF-alpha [Perera GK1, 2012] [Coates LC, 2016]. IL-9 IL-9 is a cytokine produced by variety of cells like mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells. Th9 cells are the major CD4+ T cells that produce IL-9. IL-12 IL-12 is a cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. IL-12 promotes Th1 differentiation, inflammation and activation of NK cells. IL-17 IL-17 is a pro-inflammatory cytokine produced by the Th17 subset of T lymphocytes. Other immune cells such as Ȗį T cells and NK cells can also produce IL-17. The IL-17 family includes IL17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. Among them, IL-17A is a major effector of IL-17 related inflammatory activity in psoriatic arthritis. IL-17F also plays an important role and can be closely related to IL-17A and secreted as heterodimers [Sarkar S, 2014].

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Figure 851. IL-17 cytokine family. Increased expression of IL-17A is a characteristic feature in the joints of patients with psoriatic arthritis and is not observed in rheumatoid arthritis. IL-17A levels in synovial fluid are increased in patients with psoriatic arthritis and IL-17 plays an important role in pathogenic angiogenesis, osteoclastogenesis and fibrogenesis [Lin AM, 2011] [Dhodapkar KM, 2008] [Passos ST, 2010]. IL-22 IL-22 is a cytokine that produced by immune cells at a site of inflammation. IL-22 producers are Th1, Th22, Th17 cells, Ȗį T cells, NK T cells, ILC3s, neutrophils and macrophages. Among all T cell subsets, Th17 cells are the major source of IL-22. Thus, IL-22 may contribute to the complex coexistence of bone erosion and bone formation in psoriatic arthritis.

Figure 852. IL-22 and bone proliferations.

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IL-23 IL-23 is a pro-inflammatory cytokine composed of two subunits, p19 and p40, linked by a disulfide bond. The p19 subunit is unique to IL-23, but the p40 subunit is shared with IL-12. It is a heterodimeric cytokine encoded by two separate genes, IL-12B (p40) and IL23A (IL-23p19) subunit. IL-23 induces expansion and maintenance of Th17 cells. When the IL-23 axis is activated, differentiation of naive T cells towards Th17 cells is induced. IL-23 also plays a Th17-independent important role in bone homeostasis and remodeling. IL-23 induces osteoclast differentiation and osteoclastogenesis by inducing RANKL expression in synovial fibroblasts and up-regulating the expression of RANK in osteoclast precursors [Lubberts, 2015].

Figure 853. IL-23 and IL-12. IL-23 is important not only for inducing Th17 cells but also for enhancing the pathogenicity of the Th17 cells [Lubberts, 2015] [Bettelli E, 2008]. IL-23 has also been shown to promote the production of IL-17 by dermal Ȗį T cells and to enhance their pathogenicity [O’Brien RL, 2015]. TNF-alpha TNF-alpha is a proinflammatory cytokine that is overexpressed in the synovium in patients with inflammatory arthritis. References Akitsu AY.Iwakura. (2018). Interleukin-17-producing Ȗį T (Ȗį17) cells in inflammatory diseases. Immunology, 155, 418-426. Arnett F.C.W.B.Bias. (1950). HLA-Bw 38 and Bw 39 in psoriatic arthritis: Relationships and implications for peripheral and axial involvement (abstract). Arthritis Rheum 25:649, 1950. Arthritis Rheum. Baeten DE, De Rycke L, Boots AM, Mielants H, Veys EM, De Keyser F.Kruithof. (2005). Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy. Arthritis Res Ther. Belge KJ, Ghoreschi K.Brück. (2014). Advances in treating psoriasis. F1000Prime Rep. Benham H.P, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, Smith M, Thomas R, Gaston H.Norris. (2013). Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther. Benham HP, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, Smith M, Thomas R, Gaston H.Norris. (2013). Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther. Bettelli ET, Oukka M, Kuchroo VK.Korn. (2008). Induction and effector functions of TH17 cells. Nature. Bonneville MRL, Born WK.O'Brien. (2010). Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol., 10, 467-78. Boutet M.A.A., Gallo Afflitto G., Pitzalis C.Nerviani. (2018). Role of the IL-23/IL-17 Axis in Psoriasis and Psoriatic Arthritis: The Clinical Importance of Its Divergence in Skin and Joints. Int J Mol Sci. Bowes J.J., Dand N., Jalali-najafabadi F., Bellou E., Ho P., Marzo-Ortega H., Helliwell P.S., Feletar M., Ryan A.W., et al. Cross-phenAshcroft. (2017). Cross-phenotype association mapping of the MHC identifies genetic variants

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