Ultrasound and Power Doppler Evaluation of the Hand and Wrist in Patients with Psoriatic Arthritis

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1 Acta Radiologica ISSN: (Print) (Online) Journal homepage: Ultrasound and Power Doppler Evaluation of the Hand and Wrist in Patients with Psoriatic Arthritis J. Milosavljevic, U. Lindqvist & A. Elvin To cite this article: J. Milosavljevic, U. Lindqvist & A. Elvin (2005) Ultrasound and Power Doppler Evaluation of the Hand and Wrist in Patients with Psoriatic Arthritis, Acta Radiologica, 46:4, To link to this article: Published online: 09 Jul Submit your article to this journal Article views: 209 View related articles Full Terms & Conditions of access and use can be found at Download by: [ ] Date: 29 December 2017, At: 11:38

2 ORIGINAL ARTICLE ACTA RADIOLOGICA Ultrasound and Power Doppler Evaluation of the Hand and Wrist in Patients with Psoriatic Arthritis J. MILOSAVLJEVIC, U. LINDQVIST & A. ELVIN Department of Oncology, Radiology and Clinical Immunology, Department of Medical Sciences, Rheumatology, Uppsala University Hospital, Uppsala, Sweden; Karolinska Hospital, Department of Radiology ADR, Stockholm, Sweden Milosavljevic J, Lindqvist U, Elvin A. Ultrasound and power Doppler evaluation of the hand and wrist in patients with psoriatic arthritis. Acta Radiol 2005;46: Purpose: To evaluate the ability of high-resolution and power Doppler sonography in detecting joint and tendon abnormalities in patients with psoriatic arthritis (PsA) of the hands and wrists compared with clinical and radiological findings. Material and Methods: Thirty-six patients with psoriatic arthritis of the hands and wrists and 10 healthy controls were examined with ultrasound (US). The degree of synovial proliferation, tenosynovitis, presence of joint effusion as well as the vascularity of synovial tissue was estimated. US findings were scored using a newly devised scoring system. Results: Thirty-two patients had articular synovial proliferation and/or tenosynovitis/ tendinitis or joint effusion in one or more joints according to US. Twenty-two patients had tendon changes; only five had joint effusion. The synovial, Doppler, and total articular-teno scores were all significantly correlated to the number of swollen joints. The scores, however, did not correlate to other clinical or laboratory measurements of disease activity. Conclusion: US proved effective in demonstrating PsA involvement of the hands and wrists and was more sensitive than clinical examination in detecting pathology. Longterm follow-up studies are needed to evaluate whether this can change the traditional approach for assessing involvement of joints and tendons in PsA. Key words: Arthritis; power Doppler; psoriatic arthritis; ultrasound Jugoslav Milosavljevic, Department of Oncology, Radiology and Clinical Immunology, Radiology, University Hospital SE Uppsala, Sweden (fax , . jugo.milos@deltamed.se) Accepted for publication 24 February 2005 Psoriatic arthritis (PsA) is an inflammatory disease that affects up to 1% of the population (14). It is a clinical entity that can be separated from rheumatoid arthritis (RA) on the basis of its epidemiological, clinical, and radiological features (15), but few of the features are pathognomonic for PsA (4). It has been shown that PsA is not always a mild form of arthritis and that joint deformity, joint destruction, and disability are frequent among patients with PsA (16). It has also been suggested that PsA is as severe as RA (14). Radiological features of PsA differ from those observed in RA in the distribution of the affected joints and the presence of destructive changes and bone proliferation at the same time (55). One of the most typical sites of abnormality in PsA is in the hand and wrist (42). The standard of reference for the detection and quantification of destruction in arthritis is conventional radiography (28 30, 55). Although good quality plain film examination remains a fundamental tool in early analytic and disease activity monitoring in arthritis, the disadvantage of this method is its lack of sensitivity in detecting soft-tissue changes (5, 25). Inflammatory synovitis is the earliest change to occur in arthritis, and its detection is important for both diagnosis and monitoring of disease progression (41). In recent years, magnetic resonance imaging (MRI) and ultrasonography (US) have become greatly appreciated tools in the diagnosis of joint diseases because they allow for the assessment of soft-tissue abnormalities (1, 22, 24, 50, 51). MRI allows visualization of the inflammatory changes in soft tissue in joints with arthritis and provides early evidence of joint destruction (12, 31, 38). Since MRI DOI / # 2005 Taylor & Francis

3 Patients with Psoriatic Arthritis 375 is relatively expensive, time-consuming, and requires i.v. contrast injection, it is not considered ideal for rheumatologic screening (2). US has been shown to allow characterization of the early inflammatory changes in arthritis, especially synovitis and tenosynovitis, as well as detection of bone erosions (3, 6,10, 13, 17 20, 32, 45). Power Doppler sonography (PDS) is a recently developed technique (44), and with enhanced sensitivity it can depict increased soft-tissue vascularity. However, the changes seen on US scans have to be quantified in a precise and reproducible way by the use of a scoring system analogous to the approach established by LARSEN (29) and WASSENBERG (55). The aim of the present study was to evaluate the ability of high-resolution US and PDS in detecting and scoring arthro-synovial finger, wrist joint and tendonous abnormalities in a group of patients with a clinical diagnosis of PsA. Material and Methods Patients Thirty-six patients (24 F and 12 M; w18 years; mean age SD of years) with active PsA diagnosed according to MOLL & WRIGHT (34) were included in the study. They were consecutively selected from the Psoriatic Arthritis Clinic when there was a clinical question about joint inflammation in diagnostic or therapeutic work. The patients represented both early and advanced disease: 11 with early disease (0 2 years disease duration), 10 with w2 years and (5 years disease duration, and 15 with w5 years disease duration. The research ethics committee of Uppsala University approved the project and all patients gave their informed consent. Clinical assessment was performed in all patients by a rheumatologist (U.L.) and the total number and localization of tender (68 sites) and swollen joints (66 sites) were registered. Tenosynovitis of the hand and wrist joints was also documented. The skin lesions were evaluated using the psoriasis area severity index (PASI) score (11), and the patients registered their global pain and total disease activity (0 100 mm visual analog scale [VAS]). Global disease activity was assessed with an overall clinical global assessment (five-step categorical rating scale from inactive to very severe disease) by the rheumatologist. Patient functional ability was assessed using the Swedish version of the Stanford Health Assessment Questionnaire (HAQ; 0 3 scale) (7) for registration of disability. Impairment of the disease was registered using SF 36 (49). In all patients, E-SR (reference range: females 2 15 mm/h, males 2 10 mm/h) and CRP (upper reference level: 10 mg/l) were measured by routine methods. The clinical data are given in Table 1. Ten healthy subjects (6 F and 4 M) with comparable mean age and sex (mean age SD of years), with no history or signs of inflammatory diseases of the hands and wrists, were selected among personnel working in the Radiology Department and served as reference material. Ultrasound examination Two radiologists (J.M. 26 patients, A.E. 10 patients) blinded to the results of the clinical and radiographic examinations performed the US examinations. The Table 1. Clinical characteristics with correlation to ultrasound findings in patients with psoriatic arthritis Clinical demography Total articular score (r/p) Total tendon score (r/p) Total synovial score (r/p) Total Doppler score (r/p) Total score (r/p) Mean age (years) ,267/,1147,131/,4396,245/,1524,212/,2161,239/,1581 Female/male 24 / 12 Disease duration ,119/,4827,063/,7088,117/,4935,149/,3860,110/,5160 Arthritis (years) Disease duration ,234/,1719,111/,5194,212/,2226,317/,0682,247/,1500 Skin (years) No. of swollen ,518/,0022**,331/,0503*,467/,0065**,421/,0142*,445/,0085** joints No. tender joints ,166/,3269,037/,8282,164/,3375,096/,5742,150/,3742 HAQ ,068/,7157,179/,3357,086/,6416,001/,9995,046/,8073 VAS (pain) (mm) 41 31,106/,5875,130/,5073,187/,3416,105/,5913,148/,4498 Total VAS (mm) 44 31,007/,9708,017/,9312,088/,6523,028/,8868,038/,8470 Global disease ,258/,1267,300/,0759,303/,0777,260/,1299,289/,0868 E-SR (mm/h) ,120/,5045,342/,0569,220/,2283,264/,1479,240/,1823 CRP (mg/l) ,055/,7576,167/,3438,100/,5795,084/,6399,076/,6681 Larsen score ,496/,0044**,159/,3611,442/,0124*,463/,0089**,439/,0117* HAQ5the Swedish version of the Stanford Health Assessment Questionnaire, VAS5visual analog scale, E-SR5erythrocyte-sedimentation rate, CRP5C-reactive protein, r5regression coefficient, p5significant level.

4 376 J. Milosavljevic et al. time interval between clinical examination and US evaluation was days (range 0 85). Both hands and wrists of all patients were systematically examined with a 13 MHz linear transducer (Sequoia, Acuson, Mountain View, Calif., USA), even though symptoms were unilateral. A thin acoustic stand-off pad was used (Sonar-Aid, mm; Geistlich, Wolhusen, Switzerland). We chose constant parameters: B-mode frequency of 13 MHz, Power Doppler frequency of 7 MHz, and extra low filter. Color gain was set at a level just below the disappearance of color noise deep to the cortical bone (35). US examination was performed on all metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints, as well as the joints of the carpus and wrist on both sides. The interphalangeal joint (IP) of the thumb was counted as a DIP joint. Each MCP, PIP, and DIP joint was investigated in longitudinal and transversal plane from the dorsal and the palmar aspect with the hand in a neutral position. In addition, both on longitudinal and transverse scans, the transducer was moved over the joint to obtain a careful assessment of the examined area. The carpus-wrist region was divided into six regions as follows: 1 The dorsal part of the wrist joint; 2 the volar part of the wrist joint; 3 the radial part of the radiocarpal joint; 4 the ulnar part of the radiocarpal joint; 5 the carpus dorsal; 6 the carpus volar. All carpo-metacarpal joints were counted as carpal joints. The representative images of each joint were documented in B mode and power Doppler mode. Data were saved on magneto-optical (MO) disks. The following abnormalities were assessed in each patient: joint effusion, articular synovial proliferation, and tenosynovitis of the flexor and extensor tendons. Vascularity in the synovial tissue was assessed and quantified with PDS using a scale from 0 to 3. Joint effusion was defined as an anechoic widening of joint cavity. It was not quantified and was not part of the US score. Articular synovial proliferation was identified as a hypoechoic enlargement of joint cavity. The degree of synovial proliferation was measured and graded on a scale from 0 to 3. Grade 05no signs of synovial proliferation; grade 15mild synovial proliferation ((2 mm); grade 25moderate synovial proliferation ((4 mm); grade 35severe synovial proliferation (w4 mm). The degree of articular synovial tissue vascularity was measured and graded on a scale of 0 to 3. The power Doppler grade attributed to a joint was based on the overall assessment of transverse and longitudinal images of each joint together. Grade 05no detectable power Doppler signal; grade 15mild vascularity ((30% of synovial proliferations area); grade 25moderate vascularity ((60% of synovial proliferations area); grade 35severe vascularity (w60% of synovial proliferations area) (Fig. 1). Tenosynovitis of the flexor and extensor tendons was defined as widening of tendon sheath, tendon widening, loss of normal fibrillar echo structure, and irregularity of the tendon margins. The degree of tendon sheet widening was measured on transversal scans and graded on a scale of 0 to 3. Grade 05no signs of tenosynovitis (tendon sheath diameter (0.3 mm) (19); grade 15mild tenosynovitis (tendon sheath diameter (2 mm); grade 25moderate tenosynovitis (tendon sheath diameter (4 mm); grade 35severe tenosynovitis (tendon sheath diameter w4 mm). The degree of tendinitis was measured on transversal scans and graded from 0 to 3. Grade 05no signs of tendinitis; grade 15mild tendinitis (enlarged tendon diameter (2 mm); grade 25moderate tendinitis (enlarged tendon diameter (4 mm);grade 35severe tendinitis (enlarged tendon diameter w4 mm). Loss of normal fibrillar echo structure and irregularity of the tendon margins was considered a sign of tendinitis and was counted as present or absent. The degree of tendon and synovial tendon sheath tissue vascularity was measured on longitudinal and transversal scans and graded from 0 to 3 as outlined above (Fig. 2). We evaluated arthro-synovitis in each hand and wrist at 20 sites: 5 MCP joints, 4 PIP joints, 5 DIP joints, and 6 sites in the carpus-wrist region. The maximal possible arthro-synovial score for one hand was 60, while the maximal possible arthro- Doppler score was 60. The total articular score was obtained from the sum of arthro-synovial and arthro-doppler scores (maximum possible5120). The tenosynovitis was evaluated in each hand and wrist at 12 sites: 5 flexor and 5 extensor tendons at the metacarpo-interdigital level, all extensor tendons at the wrist level were counted as one site and all flexor tendon at the wrist level as one site. The maximal possible tenosynovial score for one hand was 84; the maximal possible teno-doppler score was 36. The total tendon score was obtained from the sum of tenosynovial and teno-doppler scores (maximum possible5120). The total synovial score was obtained from the sum of arthro-synovial and tenosynovial score (maximum possible5144). The total Doppler score was obtained from the sum

5 Patients with Psoriatic Arthritis 377 Fig. 1. A. Longitudinal scan of the dorsal aspect of the left third DIP joint showing moderate arthro-synovial proliferation with moderate vascularity (white arrowheads) (D5distal phalanx, M5medial phalanx). B. Longitudinal scan of the dorsal aspect of the right fifth PIP joint showing moderate arthro-synovial proliferation (arrowheads) with mild vascularity (arrows) (M5medial phalanx, P5proximal phalanx). C. Transversal scan of the dorsal aspect of the right second MCP joint showing moderate arthro-synovial proliferation in the radial part of the joint (white arrowheads) with mild vascularity (white arrows) (black arrow5radial artery, M5head of the second metacarpal bone). D. Longitudinal scan of the dorsal aspect of the left second MCP joint showing severe arthro-synovial proliferation with mild vascularity (white arrowheads) (black arrowheads5extensor tendon, white arrows5erosions, M5metacarpal head, P5proximal phalanx). E. Longitudinal scan of the dorsal aspect of the left first MCP joint showing severe arthro-synovial proliferation (arrowheads) with mild vascularity (arrows) (M5head of the first metacarpal bone, P5proximal phalanx). F. Longitudinal scan of the dorsal aspect of the right radio-carpal joint showing moderate arthro-synovial proliferation with moderate vascularity (arrowheads) (asterix5extensor tendon, R5radius, S5os scaphoideum). G. Longitudinal scan of the dorsal ulnar aspect of the left radio-carpal joint showing severe arthro-synovial proliferation with moderate vascularity (arrowheads) (U5ulna, C5carpal bone). H. Longitudinal scan of the volar radial aspect of the right radio-carpal joint showing severe arthro-synovial proliferation with moderate vascularity (white arrowheads) (flexor tendon5black arrows, S5os scaphoideum). of arthro-doppler and teno-doppler score (maximum possible596). A total US score for the hand and wrist was derived from the sum of total articular and total tendon score (maximum possible5240) as indicated in Table 2. Radiographic examinations Standard radiographs of the hands and wrists were obtained in posterior-anterior and oblique views and evaluated separately by A.E. and J.M. without knowledge of the clinical or US data. In cases of disagreement of the interpretation of the X-ray findings, a consensus was reached and was taken as the final result. The time interval between radiographic examination and US evaluation was (median 38, range 0 545) days. The X-ray images were evaluated for signs of arthritic involvement (erosions, joint space narrowing, periarticular soft-tissue swelling, and periarticular osteoporosis). Each joint or area was graded on a 0 5 scale in accordance with LARSEN s method (30). Scoring was performed in the following joints or areas: 10 DIP, 8 PIP, 10 MCP, and 4 sites in each wrist. The distal interphalangeal joints were added to the original LARSEN s method, as

6 378 J. Milosavljevic et al. Fig. 2. (A) Longitudinal and (B) transversal scan of the dorsal ulnar aspect of the left radiocarpal joint showing moderate tenosynovitis of the extensor carpi ulnaris tendon with moderate vascularity (white arrowheads) (T5extensor carpi ulnaris tendon, U5ulna). C. Longitudinal and (D) transversal scan of the dorsal ulnar aspect of the left radiocarpal joint showing moderate tenosynovitis of the extensor carpi ulnaris tendon with severe vascularity (white arrowheads) (T5extensor carpi ulnaris tendon, S5ulnar styloid, U5ulna). E. Transversal scan, without Doppler, of the dorsal ulnar aspect of the left radiocarpal joint showing mild tenosynovitis of the extensor carpi ulnaris tendon (white arrowheads) and mild arthrosynovitis around ulnar styloid (black arrowheads) (T5extensor tendon, P5ulnar styloid, U5ulna). F. Same scan with Doppler showing moderate vascularity of the proliferated tenosynovia around the extensor carpi ulnaris tendon (white arrows) and severe vascularity of the proliferated arthro-synovial around ulnar styloid (black arrows) (T5extensor tendon, P5ulnar styloid, U5ulna). G. Longitudinal scan of the volar aspect of the right third finger showing moderate tenosynovitis of the flexor tendon with mild vascularity (white arrowheads) (T5flexor tendon). H. Transversal scan of the volar aspect of the right second, third, and fourth fingers showing moderate tenosynovitis of the flexor tendons with mild vascularity (white arrowheads) (T5flexor tendon). these joints are frequently affected in PsA (55). A total of 36 joints or areas of the hands and wrists were scored, with a maximal possible score per patient of 180. Table 2. Ultrasound scoring system Ultrasound feature Possible scores* No. of sites Maximum score Synovitis Thickening 0,1,2, Doppler 0,1,2, Tendons Sheath 0,1,2, Doppler 0,1,2, Size 0,1,2, Echo structure 0, Total possible score 240 *As detailed in the text. Interobserver and intraobserver agreement Interobserver agreement was tested on 17 patients (1088 sites) and intraobserver agreement on 16 patients (1024 sites) randomly selected from the data files. The patients US images, saved on MO disks, were re-examined. No clinical or radiographical data were known during the evaluation. The two readers (J.M. and A.E.) evaluated the cases independently more than 2 years after the original study. Statistical methods Mean values SD were calculated by conventional methods. A non-parametric Spearman correlation test was performed to test the relation of the US and Doppler score to the clinical parameters describing patient disease activity and ability. The Mann- Whitney U test was used to test continuous data in

7 Patients with Psoriatic Arthritis 379 subgroups of patients. To determine the accuracy of US and Doppler in predicting clinical findings, the sensitivity and specificity were computed. The intra- and interobserver agreement was tested with a cross-table analysis and the Kappa coefficients were calculated at a 95% confidence limit. Overall agreement, defined as the proportion of exact agreement to the overall number of trials, was also calculated. Results Clinical assessment showed that 4 of the patients had an oligoarthric clinical picture; 4 had a combined picture of polyarthritis and axial disease; and 28 had polyarthritis. Thirty-one patients had psoriasis vulgaris, three had palmoplatar pustulosis and two had mixed skin affection. Three patients had no activity of the skin disease, 29 had v5% of the skin involved, and in 3 patients 5 10% of the skin was inflammatory active. Twenty-four patients had no disease-modifying drugs, 7 had methotrexate, 1 had sulphazalasine, and 4 had low-dose (less than 10 mg) prednisolone. Radiographic results Radiographs of the hand were taken in 34 patients. Mean Larsen score was (range 0 47). There was good correlation between the different US scores and Larsen score (see Table 1). Twelve patients had normal X-ray. In all PsA patients and healthy subjects, visualization of the joints and tendons with US was accomplished without difficulty. The time required for examination of both hands was <30 min. Ultrasound findings in healthy control subjects There were no pathological findings (as defined above) in any of the examined joints or tendons, except for one patient who had minimal tenosynovitis (grade 1) of one of the extensor tendons at the level of the left wrist with no detectable PDS. Findings in PsA patients Thirty-two patients out of 36 (89%) had US changes in the form of articular synovial proliferation and/or tenosynovitis/tendinitis or joint effusion in one or more joints of the hands and wrists. Localization of ultrasound detected changes Twenty-eight patients (78%) had changes on both sides, 2 (6%) only on the left side and 1 (3%) only on the right side. Detailed side localization of the US Table 3. Localization of pathological arthro-synovial and tendon ultrasound changes in hands and wrists in 36 patients with PsA Ultrasound changes Only right Only left Both sides No changes Wrist MCP joints PIP joints DIP joints CMC joints Flexor tendons Extensor tendons changes is given in Table 3. Ten patients (28%) had arthro-synovial changes without tendon changes; 1 patient (3%) had tendon changes without arthrosynovial changes. Patients with arthro-synovial proliferation Thirty patients (83%) had signs of arthro-synovial proliferation. Fifteen (44%) had arthro-synovial proliferation in metacarpophalangeal/interphalangeal (MCP/ID) and carpal wrist joints, 12 patients (31%) only in MCP/ID joints, 3 patients (8%) only in the carpal wrist joints. Five patients had arthrosynovial proliferation at all four levels (wrist-carpus, MCP, PIP, and DIP joints), nine patients at three levels (MCP, PIP, and DIP joints), five patients in both MCP and PIP joints, one patient in both MCP and DIP joints, and no patients had arthro-synovial proliferation in PIP and DIP joints without MCP or wrist-carpus joint changes. US arthro-synovial changes in the carpus-wrist region are listed in Table 4. Patients with tendon changes Of 22 patients (61%) who had tendon changes, 7 (19%) had changes at metacarpophalangeal and carpal-wrist level, 8 patients (22%) only at metacarpophalangeal, and 7 patients (19%) only at carpal-wrist level. Most flexor tendon changes were at the metacarpo-interdigital level and most extensor tendon changes at the wrist level, as shown in Table 5. The pathological findings in the group of tendons with the tendon sheath (flexor and extensor tendons Table 4. Ultrasound arthro-synovial changes in carpus-wrist region in 36 patients with PsA Side Wrist dorsal Wrist volar Radiocarpal radial Radiocarpal ulnar Carpus dorsal Carpus volar Right Left Both

8 380 J. Milosavljevic et al. Table 5. Number of patients out of 36 with PsA in hands and wrists showing ultrasound detectable tendon inflammation Ultrasound tendon changes Yes No Flexor tendons in MCP-DIG Extensor tendons in MCP-DIG 5 31 Flexor tendons in wrist 4 32 Extensor tendons in wrist Flexor+extensor in wrist 4 32 Flexor+extensor in MCP-DIG 3 33 at the level of the wrist-carpus and flexor tendons at the MCP/ID level) were only tendon sheath widening with or without synovial tendon sheath tissue vascularity without changes in the tendon structure. The pathological findings in the group of tendons without the tendon sheath (extensor tendons at the MCP/ID level) were widening of the tendon with irregular fibrillar echo structure without irregularity of the tendon margins. Patients with joint effusion Five patients (14%) had joint effusion, four patients (11%) in the metacarpophalangeal joints, one patient (3%) in both metacarpophalangeal and wrist joints. In one patient (3%), the joint effusion was the only US abnormality. Ultrasound findings versus clinical evaluation We examined 1080 joints (72 wrists-carpi, 360 MCP, 288 PIP, and 360 DIP joints) in 36 patients. The outcome of US and clinical evaluation is shown in Fig. 3. The sum of US detected arthro-synovial proliferation in all joints in 36 patients is given in Table 6. When the PDS findings in patient joints were compared to clinical assessment (swollen and/or tender joints), PDS identified a total of 275 joints with Doppler signal, 135 of which were clinically normal, and a total of 805 joints without Doppler signal, 128 of which were found clinically swollen and/or tender (Table 7). In 8 patients (17 sites), US proved arthro-synovitis that clinical examination considered as tenosynovitis, and in 2 patients (5 sites) US proved tenosynovitis that clinical evaluation considered as arthro-synovitis. The total arthro-synovial score was for the whole patient material. There were no significant differences between the patients in the different disease pattern groups. Nor were there any significant differences between patients with early or late disease. The male patients (41 63) had a higher mean score compared to the women (18 27), but not significant. The total tenosynovial score was Fig. 3. The outcome of ultrasound and clinical evaluation.

9 Patients with Psoriatic Arthritis 381 Table 6. Ultrasound-detected arthro-synovial proliferation versus clinical evaluation of all joints in the hands and wrists in 36 patients with PsA Ultrasound Clinical evaluation Swollen and/ or tender Not swollen or tender Total Syn.prolif No syn.prolif Total Syn.prolif.5synovial proliferation. Table 7. PDS findings versus clinical evaluation of all joints in the hands and wrists in 36 patients with PsA Ultrasound Doppler Clinical evaluation Swollen and/or tender Not swollen or tender Total Doppler signal No Doppler signal Total for the whole patient material with no gender or disease pattern differences. The results of the US examination and score correlated significantly only with the total number of swollen joints, and not with any other clinical or laboratory measurements of disease activity, the patients assessment of pain or disability, or with the physician s judgement of total disease activity. The regression coefficient and the significances are given in Table 1. There was a significant relation between the total synovial and total Doppler score (r50.951, Pv0.0001). In 17 patients, clinical examination was performed no more than 30 ( ) days prior to US and power Doppler examination. There was no significant difference in the US, PDS, and total score between the patients examined within 30 days compared with the results of the total group. Likewise, the scores for the 17 patients examined within 30 days correlated only with the total number of swollen joints. The accuracy of US and PDS did not improve significantly, but there was an increase in the sensitivity for US and PDS. Interobserver and intraobserver agreement Interobserver agreement was examined in 17 patients (1088 sites) and intraobserver agreement in 16 patients (1024 sites). The detailed results concerning agreement are presented in Tables 8 and 9. The simple kappa estimation for examined parameters showed good correlation ( ) between the US investigators and between first and second investigation of the same investigator ( ). Overall agreement was high for both interobserver ( ) and intraobserver ( ). An analysis of interobserver and intraobserver agreement, with all sites considered together, is given in Table 10. Discussion This study has shown that high frequency US provides a sensitive and accurate assessment of the soft tissue of hand and wrist joints and tendons in healthy subjects and in PsA patients. We were able to accurately visualize a wide range of focal and diffuse alterations of hand and wrist joints and tendons as articular synovial proliferation, joint effusion, and tenosynovitis of the flexor and extensor tendons. In the present study, vascularity in the synovial tissue was assessed and quantified subjectively with PDS using a scale from 0 to 3. The enhanced sensitivity of PDS makes it possible to depict soft-tissue vascularity, facilitating its role in the evaluation of musculoskeletal inflammatory diseases. A broad range of new and potential applications of PDS in the musculoskeletal system were described including its use in the setting of bursal, tendon, articular, and muscle diseases, and in the evaluation of fluid collections and soft-tissue masses. It depicts and allows measurement of abnormal blood flow (hyperaemia) in the inflammatory joint tissues (23, 35, 36, 39, 43, 54). Synovial hyperemia is a fundamental pathophysiological Table 8. Scoring of synovitis (SP) and synovial tissue vascularity (PDS) in 17 patients (1088 sites) by 2 ultrasound investigators using a 0 3 scale. Values are number of investigated sites. Boldface values are exact agreement between grades by first and second investigator Grade 2nd Grade 1st investigator investigator SP PDS SP PDS SP PDS SP PDS

10 382 J. Milosavljevic et al. Table 9. Scoring of synovitis (SP) and synovial tissue vascularity (PDS) in 16 patients (1024 sites) by one ultrasound investigator, with first and second investigation, using a 0 3 scale. Values are number of investigated sites. Boldface values are where there was exact agreement between grades on first and second investigation Grade 2nd Grade 1st investigation investigation SP PDS SP PDS SP PDS SP PDS feature of the arthritis disease process (8, 9, 40, 47, 48, 53). PDS is thus capable of measuring a fundamental pathophysiological feature of the disease. NEWMAN et al. (36) used this technique on both pre- and post-therapy images with good results. WALTHER et al. (54) found a good correlation between subjective grading of PDS by US and histological findings in the study of the knee joint in patients with osteoarthritis and RA. Our study revealed an excellent reproducibility with good inter- and intraobserver variability. The majority of US-detected pathological changes in patients in our study were bilateral. Our study shows that about 26% of the finger and wrist joints have synovial proliferation. The majority of joints with arthro-synovial proliferation and pathological PDS findings were found at the MCP level followed by joints at wrist-carpus, PIP and DIP, level. Not one patient had arthro-synovial proliferation or pathological PDS findings in PIP and DIP joints without MCP or wrist-carpus joint changes. We were surprised to find that the MCP joints and associated soft tissues were more frequently involved in the US and power Doppler findings, which contrasts with earlier findings on radiology in PsA. But many recent reports on PsA confirm that polyarthritis is as common as oligoarthritis and only about 5% have only distal joint involvement. The high number of patients with polyarticular disease included in our study could partly explain our findings. Most US-detected pathological changes in flexor tendons were at the MCP-DIG level while, on the contrary, the changes in extensor tendons were mainly identified at wristcarpus level. Only five patients had joint effusion. The information which US evaluation of the soft tissue of the hand and wrist in patients with inflammatory arthritis offers is of great clinical importance, but before it can be applied the changes seen on US scans must be quantified precisely and in a reproducible way by the use of a scoring system analogous to the method described by LARSEN (29, 30) and WASSENBERG (55). We have developed a scoring system for quantifying US and PDS softtissue changes in the hand and wrist in patients with PsA. Our system quantifies both arthro-synovial and tendon changes as well as the grade of synovial vascularity. Previous US (23) and MRI (27) studies on patients with RA used a similar scoring system for quantification of arthro-synovial changes. Our system incorporates these features but also quantifies tendon changes, including both tendon sheath and the tendon itself, analogously with the scoring system used by MCQUEEN et al. to quantify MRI tendon changes in patients with RA (33). The scores which we applied (arthro-synovial, arthro-doppler, total articular score, tenosynovial, teno-doppler, total tendon score, total synovial score, total Doppler score, and total US score) were all significantly correlated to the number of swollen joints and not to any other clinical or laboratory measurements of disease activity, patient s assessment of pain or disability, or to the physician s judgment of total disease activity. This is in accordance with previous studies on patients with RA (46, 51). However, US revealed pathological changes in the number of joints without swelling and/or tenderness and there were some joints with normal US findings which were identified as pathological by clinical examination. Patients with Table 10. Interobserver and intraobserver agreement measured using two different statistical methods. Values are simple Kappa, or overall percentage of agreement for the examined parameters Interobserver agreement Intraobserver agreement Syn.prol. PDS Syn.prol. PDS Simple Kappa Overall agreement, % 98,8 99,2 98,7 98,9 Syn.prol.5Synovial proliferation; PDS5synovial tissue vascularity.

11 active PsA often exhibit a subcutaneous edema that makes clinical evaluation difficult. Our results concur with several previous US (51) and MRI studies on patients with RA (2, 26, 27, 32) and PsA (37). They also indicate that US and PDS reflect other aspects of disease than does clinical evaluation. However, the absence of pathological findings in the healthy controls (640 possible evaluation sites) and the well-known interobserver variation in clinical evaluation of joint pathology indicate that US and PDS findings have a pathological relevance in PsA. Proliferative synovitis is the early alteration in RA and PsA (41, 42). In the early phase of the disease, the conventional methods, such as clinical examination, laboratory tests, and radiography, are neither sensitive nor specific and do not allow detailed evaluation of the site of synovial inflammation (4, 22, 25). However, clinical evaluation of the painful hand and wrist need much effort and skill, and it is often difficult to distinguish between arthritis, tenosynovitis, and enthesopathy, which we also showed in the present study. The ability to diagnose and stage joint pathology with radiological methods is well documented (28, 29, 42, 55). Plain radiographs can show bone erosions or other features of joint involvement, usually late findings in PsA, but give little information about early softtissue involvement. An accurate, early diagnosis cannot therefore be made solely on the basis of such an examination (4). In the past 15 years, US and MRI have been introduced in the clinical practice of diagnosing arthritic patients problems, especially in soft-tissue manifestations. Previous studies have shown that MRI and US are more sensitive in assessing soft tissue and bone involvement in inflammatory arthritis than conventional radiography and clinical evaluation (2, 21, 52). A major disadvantage of MRI is expense, particularly when using contrast agents. The limited field of view of the flex coil used in recent studies does not allow the simultaneous examination of both hands and wrists with a high spatial resolution by MRI (2). Morphological and quantitative assessment of synovial proliferation is of major importance for early therapeutic decisions in PsA. Until now, none of the various non-invasive diagnostic methods has proven entirely satisfactory. Although the US method has long been used to diagnose inflammatory joint disease and its value in assessing softtissue changes already confirmed, studies addressing the usefulness of US in evaluating patients with PsA involvement of the hands and wrists are still lacking. These small joints of the hands and wrists are Patients with Psoriatic Arthritis 383 especially important in non-axial PsA, because it is in these joints that the disease often first manifests (42). In accordance with previous reports using MRI (37), our data suggest that involvement of the joints and tendons may be more frequent in PsA patients than has thus far been assumed, even in cases of not particularly aggressive disease, and that clinical evaluation tends to underestimate these manifestations. As few features have so far been found characteristic of PsA, US has the potential to provide additional information on the site and degree of inflammation typical for PsA. The time interval between clinical examination and US evaluation was relatively long, for organizational reasons. Twenty-four of our patients received no disease-modified anti-rheumatic drugs (DMARD). For those patients who did receive DMARD, the treatment was stable for a minimum of 4 weeks before the clinical evaluation and during the interval between the clinical and the US examination. To the best of our knowledge, no dedicated study of the hand and wrist in patients affected by PsA using high frequency (13 Mhz) US transducer and PDS has yet been published. In this study, US proved effective in demonstrating PsA involvement of the hands and wrists. We have developed a scoring system for quantifying US soft-tissue changes in the hand and wrist in PsA which quantifies both arthro-synovial and tendon changes as well as grade of synovial vascularity. We did notice but did not score erosions in the US and Doppler investigation. The reason for this was twofold. Although, in many cases, erosions were readably detectable with US, the predominant finding in those cases was the soft tissue and Doppler findings present in the erosions. The second reason was that some sites are difficult to screen with US for erosions. For example, it is difficult with US to evaluate the entire circumference of MCP joints 3 and 4. The patient material included in this study consisted of both early and late PsA. Some of the patients had advanced disease with assumed radiological findings. The patient with a Larsen score of 47 had very high US and Doppler scores, but even if this patient were excluded there is a correlation between US, Doppler, and Larsen score. The conclusion is that US depicts both early and late disease. The scores that we applied were all significantly correlated with the number of swollen joints, but not with any other clinical or laboratory measurement of disease activity, patient assessment of pain or disability, or to the physician s judgment of total disease activity. The lack of objective

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