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Grading of Ultrasonography in Rheumatoid Arthritis of Wrist and Hand Joints
ARTICLE IN PRESS
Original Investigation
Grading of Ultrasonography in Rheumatoid Arthritis of Wrist and Hand Joints Gehan S. Seifeldein, MD#, Doaa Kabil Moussa, MSc, Marwa A.A. Galal, MD, Mostafa H.M. Othman, MD, Hosam EldeinGalal Mohamed El-Malah, MD Rationale and Objectives: To evaluate the role of musculoskeletal ultrasound (MSUS) in the grading of rheumatoid arthritis (RA) wrist and hand joints and correlate it with clinical, laboratory, and radiological data. Materials and Methods: A cross-sectional study recruited 50 patients in a tertiary care hospital. RA activity was assessed by DAS28. MSUS dorsal longitudinal scan was performed on the wrists, MCPs, and PIPS joints using high frequency (18 MHZ) linear transducer. 100 wrists in three different views, 500 MCPs, 500 PIPs were evaluated using the grayscale ultrasound and power Doppler ultrasound semiquantitative scale and scores ranging from 03. The results were correlated with clinical, laboratory and radiological data. All patients’ wrist and hand joints X-rays were evaluated using the Larsen score. Results: The mean age of the patients (49 females and one male) was 44.58 § 10.07 years, and their mean disease duration was 16.26 § 1.07 years. The mean DAS28 was 5.19 § 0.95. 97.5% of joints had grade I Larsen score, 11.07% of the joints had erosions, 9.2% of the joints had effusions, 23.8% of the joints had synovial thickening, 11.9% of the joints showed PD signals and 3.5% of the joints were accompanied with tenosynovitis. Significant relations (p < 0.05) found among DAS28 and (PD signals, synovial thickening, tenosynovitis, effusion, and Larsen score). A nonsignificant relation (p > 0.05) among DAS28 and erosions detected by MSUS and X-ray. Conclusion: MSUS is powerful in the detection of early RA regarding synovitis, joint effusion, tenosynovitis, and bone erosions, which were correlated with clinical and laboratory parameters. Key Words: MSUS; Power Doppler; Rheumatoid arthritis; DAS28. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
INTRODUCTION
R
heumatoid arthritis (RA) is a long-term autoimmune and chronic inflammatory disease which mostly destructs the joints contents (synovium, cartilage, and bone), causing their deformity (1). Consequently, it has a significant and profound impact on patients' quality of life (2). Therefore, early RA diagnosis is crucial for the application of an active and aggressive treatment, which is anticipated to withhold joint damage and related comorbidities, and thus Acad Radiol 2019; &:1–7 From the Diagnostic and Interventional Radiology Department, Assiut University, Faculty of Medicine, Assiut, 71515, Egypt (G.S.S., D.K.M., M.H.M.O., H.E.M.E.M.); Rheumatology and Rehabilitation Department, Assiut University, Egypt (M.A.A.G.). Received June 25, 2019; revised September 20, 2019; accepted September 21, 2019. Author Contribution: With the submission of this manuscript, I would like to declare that all authors have contributed sufficiently to the scientific work regarding study concepts and design, clinical studies and collecting the data, statistical analysis, manuscript preparation, and editing. All authors of this paper have read and approved the final version submitted. Address correspondence to: G.S.S. e-mail: [email protected] # Web Site: http://www.aun.edu.eg/membercv.php?M_ID=2319, Google scholar link https://scholar.google.com.eg/citations?user=vo_mjFoAAAAJ&hl=en © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.acra.2019.09.033
reducing the functional deterioration and improving the long-term outcome (37). RA follow-up is as important as the early disease diagnosis. Disease activity score 28 (DAS28) is a common simple tool to evaluate the RA course and treatment effectiveness, where rheumatologists aim to reach disease remission or low activity (DAS28 2.6, >2.63.2 respectively) (8,9). In addition to X-ray, imaging techniques, particularly, magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) are progressively more significant in the early diagnosis of RA through quantitatively and qualitatively measurement of inflammation activity. MSUS can directly visualize soft tissue pathologies such as synovial tissue changes (10,11). Our purpose was to evaluate the role of MSUS in the grading of rheumatoid arthritis of wrist joints and hands and correlate it with clinical, laboratory, and radiological data. MATERIALS AND METHODS Study Design and Patient Population
A prospective single-center cross-sectional study carried out in the Diagnostic Radiology and the Rheumatology, Rehabilitation, 1
ARTICLE IN PRESS SEIFELDEIN ET AL
Physical medicine departments in XXX University Hospitals. The protocol was approved by the Ethics Review Board of Faculty of Medicine, and informed consent obtained from all participants according to the Declaration of Helsinki, sixth revision, 2008. From September 2016 to December 2017, consecutive 50 patients were recruited and classified as rheumatoid arthritis according to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria (12). Any patient with arthritis other than RA (such as crystal arthropathies, psoriasis, seronegative spondyloarthropathy) excluded from the study. A full history taking, clinical examination and disease activity assessment (using DAS28) were done for all patients. The DAS28 assessment was based on the following:
Number of tender (TJ) and swollen (SJ) joints (assessing 28 joints which include 10 PIP joints, 10 MCP joints, 2 wrists, 2 elbows, 2 shoulders and 2 knees), ESR (mm/hr), Visual analogue scale score for global heath, through assessment of their general heath with visual analogue scale of 100 mm, DAS28 is calculated based on the following formula: DAS28 ¼ 0:56 x ðTJC28Þ þ 0:28 x ðSJC28Þ þ 0:70 lognatðESRÞ þ 0:014 GH
where,
Remission was reached when DAS28 is 2.6, Low disease activity was recorded when DAS28 is >2.6 to 3.2, Moderate disease activity when DAS28 was (3.2 to 5.1), High disease activity when DAS28 was >5.1 (8,9).
Conventional Radiography
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settings were adjusted to low wall filters, a pulse repetition frequency of 480 Hz and its gain was set below the noise floor. The examination was performed in a minimum of two planes (longitudinal and transverse) and sometimes a longitudinal scan of the flexed diarthrodial joints (metacarpophalangeal (MCP) and proximal interphalangeal joints (PIP)). The wrists were also scanned for longitudinal dorso-radial, dorsoulnar, and mid-carpal views. The joints were evaluated for the presence of synovial thickening, joint effusion, erosions, and tenosynovitis using both grayscale ultrasound and power Doppler (PD), then correlated with clinical, laboratory and radiological data. We assessed 1300 joints (100 wrists in three different views, 500 MCP, 500 PIP) in 50 patients. MSUS Interpretation
The interpretation of MSUS joint assessment based on either a binary scale (present or absent), which was the case with tenosynovitis or a semiquantitative grading (0 to 3) as described by Szkudlark et al. (17) in order to evaluate the joints regarding the following items: Synovial thickening (a noncompressible hypoechoic intracapsular area) where, Grade 0, where no synovial thickening. Grade 1, mild thickening (filling the angle between the periarticular bones, without bulging over the line linking tops of the bones). Grade 2, moderate thickening (bulging over the line linking tops of the periarticular bones but without extension along diaphysis). Grade 3, severe thickening (bulging over the line linking tops of the periarticular bones and with extension to at least one of the bone diaphysis).
Posteroanterior view X-ray of both hands done for all patients, and joint destruction was evaluated according to the modified Larsen score (1316). The radiographs were read by one radiologist who was blinded to the clinical presentation, and ultrasound findings. The modified Larsen score ranged from 0 to 5 as follows:
Joint effusion (a compressible anechoic intracapsular area) as, Grade 0, no effusion. Grade 1, mild effusion. Grade 2, moderate effusion [without capsular distension]. Grade 3, severe effusion [associated with capsular distension].
0 = intact bony outlines and normal joint space. 1 = erosion less than 1 mm in diameter or JSN. 2 = one or several small erosions (diameter more than 1 mm). 3 = marked erosions. 4 = severe erosions (usually no joint space left and the original bony outlines are only partly preserved). 5 = mutilating changes (the original bony outlines have been destroyed).
Bone erosions (changes in the bone surface adjacent to the joint), Grade 0, normal regular bone surface. Grade 1, a surface irregularity where no defect detected in 2 perpendicular planes. Grade 2, a surface defect seen in 2 perpendicular planes. Grade 3, defect forming severe bone destruction.
MSUS Examination
A detailed MSUS examination and recording were done by two radiologists with 6 and 16 years of experience respectively using high frequency (18 MHz) linear array transducer (MyLabSeven eHD; Esaote SpA, Italy), Power Doppler (PD) 2
Power Doppler signal (showing synovial blood vessels flow signal) Grade 0, no synovial flow. Grade 1, single vessel signal. Grade 2, merging vessel signals in less than half of synovial area. Grade 3, signals in more than half of synovial area.
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Statistical Analysis
The statistical analysis of the data done using the statistical package for the social science program (SPSS) version 23 (IBM Corporation, USA). The continuous and categorical data were represented as mean (§SD), or frequencies (n) and percentages (%) respectively. The t-test (Mann-Whitney when necessary) was used to compare differences between groups, while analyses of differences among group means were performed using ANOVA test. Categorical data were compared by the x2 or Fisher exact test. Correlations between variable parameters were detected by Pearson’s correlation coefficient (p > 0.05 nonsignificant, p < 0.05 significant, p < 0.01 moderate significant, and p < 0.001 highly significant). RESULTS Fifty RA patients were recruited, their mean age was 44.58 § 10.07 years, and the mean disease duration was 16.26 § 1.07 years. Table 1 displays demographic, clinical, medications, and laboratory data. The DAS28 values showed that 24 patients suffered high disease activity, 25 had moderate activity, while one patient was in remission. Regarding X-ray findings, 4.6% of joints had erosions; there was no soft tissue edema found. Periarticular osteopenia was observed in 99.8% of the joints, joint space narrowing was observed in 68.9% of joints and 97.5% of the joints were graded one by Larsen’s score. Concerning MSUS findings, 11.07% of the joints had erosions, 9.2% of the joints had effusion, 23.85% of the joints had synovial thickening, 11.9% of the joints had PD signals, and 3.5% of the joints had tenosynovitis. (Table 2) (Figs 14) As regard relations, patients with high disease activity had higher grades of erosions, effusion, synovial thickening, tenosynovitis, and PD signal (Tables 3, 4, 5). Table 6 shows a correlation between PD signals with each of synovial thickening, DAS28, tender joints' numbers, swollen joints' numbers, patient's and physician's global assessment. DISCUSSION MSUS is considered a sensitive tool that could define minimal RA synovitis (mild thickening or effusion) using a TABLE 1. Demographic and Clinical Data in the Study Group Item
Patients (n = 50)
Age (range/ mean § SD) years Sex Male Female Disease duration (range/ mean § SD) years DAS28 (mean § SD) Remission (<2.6) Low activity (2.6 3.2) Moderate activity (3.2 5.1) High activity (˃5.1)
22-65 (44.58 § 10.07) 1 (2.0%) 49 (98.0%) 1-20 (16.26 § 1.07) 5.19 § 0.95 1 (2.6%) 0 25 (50.0%) 24 (48.0%)
ULTRASONOGRAPHY IN RHEUMATOID ARTHRITIS
grayscale, as well as synovial hypervascularity by Doppler mode when compared to clinical examination (1820). Furthermore, it is considered more competent and accurate than X-ray in distinguishing rheumatoid joint erosions as the cortical bone surface, when accessible, is magnified (21). The idea that MSUS carries high practical sensitivity because its power to discriminate even very small erosions in multiple planes (in comparison to bi-dimensional X-ray), and to detect different sources of joint swelling especially periarticular as bursitis and tenosynovitis (22,23). MSUS has the benefit of direct visualization of any pathological changes in the synovium, cartilage, and bone profile, particularly in patients with undifferentiated arthritis when their X-ray is unremarkable (24). Szkudlarek and coworkers demonstrated that MSUS more frequently noticed joint inflammation signs than clinical examination did (17). So, the current study was performed to show the role of ultrasonography in the grading of rheumatoid arthritis (RA) and correlate it with radiological, clinical, and laboratory data. Our study revealed significant statistical relations (p < 0.05) between DAS28 and both synovial thickening, and PD signal, which indicates compatibility between clinical and laboratory parameters (presented in DAS28) on the one hand and those discovered by MSUS on the other hand. Furthermore, these findings were reinforced by a strong positive correlation between the same formerly mentioned variables, agreeing with the results that each of Naredo and colleagues, Ghib and his team, Goher et al., and Huajun and coworkers found (2528). Even though, Damjanov et al. (29) validated a new RA activity score using MSUS that seemed to be effective by Kamel and her team (30). This ascertains the vital relationships among clinical disease assessment and MSUS parameter and how MSUS assessment is a good indicator of disease activity. Concerning bone erosions, most of our patients had a grade I Larsen’s score, which was significantly correlated with DAS28, supporting Drossaers-Bakker et al. findings (31). But this was not the case concerning the relation between the same disease activity measurement (DAS28) and erosions counted by MSUS, as there was no significance as reported by Huajun et al. (25) contradicting the fact that continuous (even subclinical) joint inflammation is a cause of progressive destruction in RA, as well as the results of both Damjanov et al. (29), and Kamel et al. (30). Regarding joint effusion and tenosynovitis, a significant relation was found with DAS28, agreeing with both Ghib et al. and Gohar et al. work (26, 27). All these previously mentioned relations and correlations signify the effective role of MSUS in the diagnosis of RA even in its early or subclinical stages, in follow-up its course, and so defining the treatment strategy and its effectiveness. Some limitations were also found in this study. The patient sample was small. So a larger group of patients would probably have strengthened the results. Addition of a volar view, especially in the detection of PIP synovitis would be better to reinforce our results. 3
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SEIFELDEIN ET AL
TABLE 2. MSUS Finding in Hands’ Joints MSUS Finding in 1300 Joints Erosion grade: 0 1 2 3 Total = 144 (11.07%) joints Effusion. grade: 0 1 2 3 Total = 120 (9.2 %) joints Synovial thickening: 0 1 2 3 Total =310 (23.85%) joints) Power Doppler signals: 0 1 2 3 Total = 155 (11.9%) joints) Tenosynovitis 0 1 Total= 46 (3.5%) joints
Wrists “n = 300”
MCP “n = 500”
PIP “n = 500”
218(72.67%) 70(23.33%) 0(0.0%) 12(4.0%) 82
450(90.0%) 11(2.20%) 13(2.6%) 26(5.2%) 50
488(96.0%) 11(3.67%) 1(0.33%) 0(0.0%) 12
267(89.0%) 21(7.0%) 3(1%) 9(3%) 33
445(89.0%) 34(6.8%) 4(0.8%) 17(3.4%) 55
468(89.33%) 7(2.33%) 12(0.8%) 13(1.2%) 32
202(67.33%) 19(6.33%) 17(5.66%) 62(20.67%) 98
332(66.4%) 77(15.4%) 39(7.8%) 52(10.4%) 168
456(91.2%) 22(4.4%) 6(1.2%) 16(3.2%) 44
226(75.33%) 35(11.67%) 26(8.67%) 13(4.33%) 74
469(93.8%) 17(3.4%) 11(2.2%) 3(0.6%) 31
450(90.0%) 12(2.4%) 24(4.8%) 14(2.8%) 50
279(93.0%) 21(7.0%) 21
488(97.6%) 12(2.4%) 12
487(97.4%) 13(2.6%) 13
In conclusion, MSUS has high reliability in the diagnosis of early RA concerning synovitis, joint effusion, tenosynovitis, and bone erosions. A good correlation was found between MSUS parameters and clinical and laboratory
parameters. Besides, its low cost and convenience, MSUS may be a better choice during the initial RA diagnosis, and its findings may be a more powerful parameter than clinical ones.
Figure 1. (A) A dorsal longitudinal scan of the right wrist (mid carpal view) B-mode, r = radius, l = lunate, cap = capitate, t = tendon, it shows tenosynovitis (red arrowed). (B) A dorsal longitudinal scan of the right wrist (mid carpal view) with power Doppler, r = radius, l = lunate, cap = capitate, t = tendon, it shows tenosynovitis and grade 1 power Doppler signal. (Color version of figure is available online.)
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Figure 2. (A) A dorsal longitudinal scan of the first right metacarpophalangeal joint (B-mode), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon, it shows grade 3 synovial thickening.(astrisk) (B) transverse view of the first right metacarpophalangeal joint, show Grade 2 erosion, e = erosion. (light green arrowed) (C) posteroanterior view of both wrists and hands graded as Larsen score 1. (Color version of figure is available online.)
Hence, the current results discovered that a detailed evaluation of musculoskeletal sonographic data is required to sufficiently raise the value of ultrasound in patients' follow up. The associations between DAS28 and other clinical
parameters with MSUS parameters reflected its value in the assessment of disease activity, severity, and provided a better way to pursuit the therapeutic effectiveness. Also, MSUS can detect small erosions in comparison to X-ray.
Figure 3. A dorsal longitudinal scan of the fourth left metacarpophalangeal joint (B-mode), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon, it shows Grade 3 synovial thickening (asterisk).
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SEIFELDEIN ET AL
Figure 4. (A) A dorsal longitudinal scan of the third left metacarpophalangeal joint (B-mode) Mc = metacarpal bone, Pp = proximal phalanx, t = tendon; it shows grade 3 synovial thickening (asterisk), grade 3 effusion. (B) A dorsal longitudinal scan of third left metacarpophalangeal joint (Power Doppler), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon; it shows grade 3 synovial thickening, grade 1 power Doppler, and grade 3 effusion.
TABLE 3. Relation between DAS28, PD Signals and Synovial Thickening MSUS Finding
Remission “n = 2”
PD signals synovial thickening
2.0 § 0.0 8.0 § 0.0
Moderate “n = 50” 2.44 § 0.58 10.12 § 4.70
High “n = 48” 4.29 § 2.83 14.58 § 5.55
P value p < 0.04* p < 0.01*
Chi-square test was used to find relations among different parameters, and ANOVA analyzed the differences among group means (n = double number of patients for the statistical purpose).
TABLE 4. Relation between DAS28 and Erosion Detected by MUSU MSUS Finding Erosion: -ve +ve Effusion: -ve +ve Tenosynovitis: -ve +ve
Remission “n = 1”
Moderate “n = 25”
High “n = 24”
P value
0(0.0%) 1(100%)
18(72%) 7(28%)
11(45.8%) 13(54.2%)
p = 0.088 (n.s)
1(100%) 0.0
11(44.0%) 14(56.0%)
9(37.5%) 15(62.5%)
p < 0.03*
1(100%) 0.0
20(80%) 5(20%)
16(66.7%) 8(33.3%)
p < 0.03*
Chi-square test was used to find relations among different parameters (n = number of patients).
TABLE 5. Relation between DAS28 and Larsen Score X-ray DAS28
Remission “n = 1”
Moderate “n = 25”
High “n = 24”
P value
Larsen score
10.00 § 0.00
10.04 § 0.87
11.70 § 1.78
p < 0.04*
Using ANOVA test\n = number of patients.
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TABLE 6. Correlation between PD and (Synovial Thickness, DAS28, and Its Parameters) Parameters
Synovial thickening DAS28 Number of tender joint Number of swollen joint Patient global assessment (PGA) Physician global assessment (Phys.GA)
PD Signals r value
P value
0.489 0.468 0.393 0.501 0.282 0.446
0.0001*** 0.001** 0.005** 0.0001*** 0.047* 0.001**
r value Pearson’s correlation coefficient. * Statistically significant correlation (p < 0.05). ** High statistically significant correlation (p < 0.001). *** Very high statistically significant correlation (p < 0.0001).
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13. Kaye JJ. Radiographic methods of assessment (scoring) of rheumatic disease. Rheum Dis Clin North Am 1991; 17:457–470. 14. Plant MJ, Saklatvala J, Borg AA, et al. Measurement and prediction of radiological progression in early rheumatoid arthritis. J Rheumatol 1994; 21:1808–1813. 15. Larsen A. How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in long-term studies. J Rheumatol 1995; 22:1974–1975. 16. Larsen A, Thoen J. Hand radiography of 200 patients with rheumatoid arthritis repeated after an interval of one year. Scand J Rheumatol 1987; 16:395–401. 17. Szkudlarek M, Court-Payen M, Jacobsen S, et al. Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum 2003; 48:955–962. 18. Wakefield RJ, Green MJ, Marzo-Ortega H, et al. Should oligoarthritis be reclassified? Ultrasound reveals a high prevalence of subclinical disease. Ann Rheum Dis 2004; 63:382–385. 19. Brown AK, Conaghan PG, Karim Z, et al. An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum 2008; 58:2958–2967. 20. Newman JS, Adler RS, Bude RO, et al. Detection of soft-tissue hyperemia: value of power Doppler sonography. AJR Am J Roentgenol 1994; 163:385–389. 21. Wakefield RJ, Gibbon WW, Conaghan PG, et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum 2000; 43:2762–2770. 22. Rowbotham EL, Wakefield RJ, Grainger AJ. The technique and application of ultrasound in the diagnosis and management of inflammatory arthritis. Semin Musculoskelet Radiol 2012; 16:360–366. 23. Colebatch AN, Edwards CJ, Ostergaard M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis 2013; 72:804–814. 24. Tamborrini G, Backhaus M, Schmidt W, et al. Ultrasound and arthritis. €r Rheumatologie 2010; 69:889–901. Zeitschrift fu 25. Naredo E, Bonilla G, Gamero F, et al. Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical evaluation with grey scale and power Doppler ultrasonography. Ann Rheum Dis 2005; 64:375–381. 26. Ghib LJ, Tamas MM, Damian LO, et al. The role of ultrasonography in assessing disease activity in patient with rheumatoid arthritis and associated fibromyalgia. Med Ultrason 2015; 17:339–344. 27. Gohar N, Ezzat Y, Naeem N, et al. A comparative study between ultrasonographic hand features in systemic sclerosis and rheumatoid arthritis patients: Relation to disease activity, clinical and radiological findings. Egypt Rheumatol 2015; 37:177–184. 28. Huajun XU, Zhang Y, Zhang H, et al. Comparison of the clinical effectiveness of US grading scoring system VS MRI in the diagnosis of early rheumatoid arthritis (RA). Journal Orthop Surg Res 2017; 12:1–8. 29. Damjanov N, Radunovic G, Prodanovic S, et al. Construct validity and reliability of ultrasound disease activity score in assessing joint inflammation in RA: comparison with DAS-28. Rheumatology 2012; 51:120– 128. 30. Kamel SR, Sadek HA, Mohamed FA, et al. Role of ultrasound disease activity score in assessing inflammatory disease activity in rheumatoid arthritis patient. Egypt Rheumatol 2017; 40:1–5. 31. Drossaers-Bakker KW, Kroon HM, Zwinderman AH, et al. Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to function. Rheumatology 2000; 39:998–1003.
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Original Investigation
Grading of Ultrasonography in Rheumatoid Arthritis of Wrist and Hand Joints Gehan S. Seifeldein, MD#, Doaa Kabil Moussa, MSc, Marwa A.A. Galal, MD, Mostafa H.M. Othman, MD, Hosam EldeinGalal Mohamed El-Malah, MD Rationale and Objectives: To evaluate the role of musculoskeletal ultrasound (MSUS) in the grading of rheumatoid arthritis (RA) wrist and hand joints and correlate it with clinical, laboratory, and radiological data. Materials and Methods: A cross-sectional study recruited 50 patients in a tertiary care hospital. RA activity was assessed by DAS28. MSUS dorsal longitudinal scan was performed on the wrists, MCPs, and PIPS joints using high frequency (18 MHZ) linear transducer. 100 wrists in three different views, 500 MCPs, 500 PIPs were evaluated using the grayscale ultrasound and power Doppler ultrasound semiquantitative scale and scores ranging from 03. The results were correlated with clinical, laboratory and radiological data. All patients’ wrist and hand joints X-rays were evaluated using the Larsen score. Results: The mean age of the patients (49 females and one male) was 44.58 § 10.07 years, and their mean disease duration was 16.26 § 1.07 years. The mean DAS28 was 5.19 § 0.95. 97.5% of joints had grade I Larsen score, 11.07% of the joints had erosions, 9.2% of the joints had effusions, 23.8% of the joints had synovial thickening, 11.9% of the joints showed PD signals and 3.5% of the joints were accompanied with tenosynovitis. Significant relations (p < 0.05) found among DAS28 and (PD signals, synovial thickening, tenosynovitis, effusion, and Larsen score). A nonsignificant relation (p > 0.05) among DAS28 and erosions detected by MSUS and X-ray. Conclusion: MSUS is powerful in the detection of early RA regarding synovitis, joint effusion, tenosynovitis, and bone erosions, which were correlated with clinical and laboratory parameters. Key Words: MSUS; Power Doppler; Rheumatoid arthritis; DAS28. © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
INTRODUCTION
R
heumatoid arthritis (RA) is a long-term autoimmune and chronic inflammatory disease which mostly destructs the joints contents (synovium, cartilage, and bone), causing their deformity (1). Consequently, it has a significant and profound impact on patients' quality of life (2). Therefore, early RA diagnosis is crucial for the application of an active and aggressive treatment, which is anticipated to withhold joint damage and related comorbidities, and thus Acad Radiol 2019; &:1–7 From the Diagnostic and Interventional Radiology Department, Assiut University, Faculty of Medicine, Assiut, 71515, Egypt (G.S.S., D.K.M., M.H.M.O., H.E.M.E.M.); Rheumatology and Rehabilitation Department, Assiut University, Egypt (M.A.A.G.). Received June 25, 2019; revised September 20, 2019; accepted September 21, 2019. Author Contribution: With the submission of this manuscript, I would like to declare that all authors have contributed sufficiently to the scientific work regarding study concepts and design, clinical studies and collecting the data, statistical analysis, manuscript preparation, and editing. All authors of this paper have read and approved the final version submitted. Address correspondence to: G.S.S. e-mail: [email protected] # Web Site: http://www.aun.edu.eg/membercv.php?M_ID=2319, Google scholar link https://scholar.google.com.eg/citations?user=vo_mjFoAAAAJ&hl=en © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.acra.2019.09.033
reducing the functional deterioration and improving the long-term outcome (37). RA follow-up is as important as the early disease diagnosis. Disease activity score 28 (DAS28) is a common simple tool to evaluate the RA course and treatment effectiveness, where rheumatologists aim to reach disease remission or low activity (DAS28 2.6, >2.63.2 respectively) (8,9). In addition to X-ray, imaging techniques, particularly, magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) are progressively more significant in the early diagnosis of RA through quantitatively and qualitatively measurement of inflammation activity. MSUS can directly visualize soft tissue pathologies such as synovial tissue changes (10,11). Our purpose was to evaluate the role of MSUS in the grading of rheumatoid arthritis of wrist joints and hands and correlate it with clinical, laboratory, and radiological data. MATERIALS AND METHODS Study Design and Patient Population
A prospective single-center cross-sectional study carried out in the Diagnostic Radiology and the Rheumatology, Rehabilitation, 1
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Physical medicine departments in XXX University Hospitals. The protocol was approved by the Ethics Review Board of Faculty of Medicine, and informed consent obtained from all participants according to the Declaration of Helsinki, sixth revision, 2008. From September 2016 to December 2017, consecutive 50 patients were recruited and classified as rheumatoid arthritis according to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria (12). Any patient with arthritis other than RA (such as crystal arthropathies, psoriasis, seronegative spondyloarthropathy) excluded from the study. A full history taking, clinical examination and disease activity assessment (using DAS28) were done for all patients. The DAS28 assessment was based on the following:
Number of tender (TJ) and swollen (SJ) joints (assessing 28 joints which include 10 PIP joints, 10 MCP joints, 2 wrists, 2 elbows, 2 shoulders and 2 knees), ESR (mm/hr), Visual analogue scale score for global heath, through assessment of their general heath with visual analogue scale of 100 mm, DAS28 is calculated based on the following formula: DAS28 ¼ 0:56 x ðTJC28Þ þ 0:28 x ðSJC28Þ þ 0:70 lognatðESRÞ þ 0:014 GH
where,
Remission was reached when DAS28 is 2.6, Low disease activity was recorded when DAS28 is >2.6 to 3.2, Moderate disease activity when DAS28 was (3.2 to 5.1), High disease activity when DAS28 was >5.1 (8,9).
Conventional Radiography
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settings were adjusted to low wall filters, a pulse repetition frequency of 480 Hz and its gain was set below the noise floor. The examination was performed in a minimum of two planes (longitudinal and transverse) and sometimes a longitudinal scan of the flexed diarthrodial joints (metacarpophalangeal (MCP) and proximal interphalangeal joints (PIP)). The wrists were also scanned for longitudinal dorso-radial, dorsoulnar, and mid-carpal views. The joints were evaluated for the presence of synovial thickening, joint effusion, erosions, and tenosynovitis using both grayscale ultrasound and power Doppler (PD), then correlated with clinical, laboratory and radiological data. We assessed 1300 joints (100 wrists in three different views, 500 MCP, 500 PIP) in 50 patients. MSUS Interpretation
The interpretation of MSUS joint assessment based on either a binary scale (present or absent), which was the case with tenosynovitis or a semiquantitative grading (0 to 3) as described by Szkudlark et al. (17) in order to evaluate the joints regarding the following items: Synovial thickening (a noncompressible hypoechoic intracapsular area) where, Grade 0, where no synovial thickening. Grade 1, mild thickening (filling the angle between the periarticular bones, without bulging over the line linking tops of the bones). Grade 2, moderate thickening (bulging over the line linking tops of the periarticular bones but without extension along diaphysis). Grade 3, severe thickening (bulging over the line linking tops of the periarticular bones and with extension to at least one of the bone diaphysis).
Posteroanterior view X-ray of both hands done for all patients, and joint destruction was evaluated according to the modified Larsen score (1316). The radiographs were read by one radiologist who was blinded to the clinical presentation, and ultrasound findings. The modified Larsen score ranged from 0 to 5 as follows:
Joint effusion (a compressible anechoic intracapsular area) as, Grade 0, no effusion. Grade 1, mild effusion. Grade 2, moderate effusion [without capsular distension]. Grade 3, severe effusion [associated with capsular distension].
0 = intact bony outlines and normal joint space. 1 = erosion less than 1 mm in diameter or JSN. 2 = one or several small erosions (diameter more than 1 mm). 3 = marked erosions. 4 = severe erosions (usually no joint space left and the original bony outlines are only partly preserved). 5 = mutilating changes (the original bony outlines have been destroyed).
Bone erosions (changes in the bone surface adjacent to the joint), Grade 0, normal regular bone surface. Grade 1, a surface irregularity where no defect detected in 2 perpendicular planes. Grade 2, a surface defect seen in 2 perpendicular planes. Grade 3, defect forming severe bone destruction.
MSUS Examination
A detailed MSUS examination and recording were done by two radiologists with 6 and 16 years of experience respectively using high frequency (18 MHz) linear array transducer (MyLabSeven eHD; Esaote SpA, Italy), Power Doppler (PD) 2
Power Doppler signal (showing synovial blood vessels flow signal) Grade 0, no synovial flow. Grade 1, single vessel signal. Grade 2, merging vessel signals in less than half of synovial area. Grade 3, signals in more than half of synovial area.
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Statistical Analysis
The statistical analysis of the data done using the statistical package for the social science program (SPSS) version 23 (IBM Corporation, USA). The continuous and categorical data were represented as mean (§SD), or frequencies (n) and percentages (%) respectively. The t-test (Mann-Whitney when necessary) was used to compare differences between groups, while analyses of differences among group means were performed using ANOVA test. Categorical data were compared by the x2 or Fisher exact test. Correlations between variable parameters were detected by Pearson’s correlation coefficient (p > 0.05 nonsignificant, p < 0.05 significant, p < 0.01 moderate significant, and p < 0.001 highly significant). RESULTS Fifty RA patients were recruited, their mean age was 44.58 § 10.07 years, and the mean disease duration was 16.26 § 1.07 years. Table 1 displays demographic, clinical, medications, and laboratory data. The DAS28 values showed that 24 patients suffered high disease activity, 25 had moderate activity, while one patient was in remission. Regarding X-ray findings, 4.6% of joints had erosions; there was no soft tissue edema found. Periarticular osteopenia was observed in 99.8% of the joints, joint space narrowing was observed in 68.9% of joints and 97.5% of the joints were graded one by Larsen’s score. Concerning MSUS findings, 11.07% of the joints had erosions, 9.2% of the joints had effusion, 23.85% of the joints had synovial thickening, 11.9% of the joints had PD signals, and 3.5% of the joints had tenosynovitis. (Table 2) (Figs 14) As regard relations, patients with high disease activity had higher grades of erosions, effusion, synovial thickening, tenosynovitis, and PD signal (Tables 3, 4, 5). Table 6 shows a correlation between PD signals with each of synovial thickening, DAS28, tender joints' numbers, swollen joints' numbers, patient's and physician's global assessment. DISCUSSION MSUS is considered a sensitive tool that could define minimal RA synovitis (mild thickening or effusion) using a TABLE 1. Demographic and Clinical Data in the Study Group Item
Patients (n = 50)
Age (range/ mean § SD) years Sex Male Female Disease duration (range/ mean § SD) years DAS28 (mean § SD) Remission (<2.6) Low activity (2.6 3.2) Moderate activity (3.2 5.1) High activity (˃5.1)
22-65 (44.58 § 10.07) 1 (2.0%) 49 (98.0%) 1-20 (16.26 § 1.07) 5.19 § 0.95 1 (2.6%) 0 25 (50.0%) 24 (48.0%)
ULTRASONOGRAPHY IN RHEUMATOID ARTHRITIS
grayscale, as well as synovial hypervascularity by Doppler mode when compared to clinical examination (1820). Furthermore, it is considered more competent and accurate than X-ray in distinguishing rheumatoid joint erosions as the cortical bone surface, when accessible, is magnified (21). The idea that MSUS carries high practical sensitivity because its power to discriminate even very small erosions in multiple planes (in comparison to bi-dimensional X-ray), and to detect different sources of joint swelling especially periarticular as bursitis and tenosynovitis (22,23). MSUS has the benefit of direct visualization of any pathological changes in the synovium, cartilage, and bone profile, particularly in patients with undifferentiated arthritis when their X-ray is unremarkable (24). Szkudlarek and coworkers demonstrated that MSUS more frequently noticed joint inflammation signs than clinical examination did (17). So, the current study was performed to show the role of ultrasonography in the grading of rheumatoid arthritis (RA) and correlate it with radiological, clinical, and laboratory data. Our study revealed significant statistical relations (p < 0.05) between DAS28 and both synovial thickening, and PD signal, which indicates compatibility between clinical and laboratory parameters (presented in DAS28) on the one hand and those discovered by MSUS on the other hand. Furthermore, these findings were reinforced by a strong positive correlation between the same formerly mentioned variables, agreeing with the results that each of Naredo and colleagues, Ghib and his team, Goher et al., and Huajun and coworkers found (2528). Even though, Damjanov et al. (29) validated a new RA activity score using MSUS that seemed to be effective by Kamel and her team (30). This ascertains the vital relationships among clinical disease assessment and MSUS parameter and how MSUS assessment is a good indicator of disease activity. Concerning bone erosions, most of our patients had a grade I Larsen’s score, which was significantly correlated with DAS28, supporting Drossaers-Bakker et al. findings (31). But this was not the case concerning the relation between the same disease activity measurement (DAS28) and erosions counted by MSUS, as there was no significance as reported by Huajun et al. (25) contradicting the fact that continuous (even subclinical) joint inflammation is a cause of progressive destruction in RA, as well as the results of both Damjanov et al. (29), and Kamel et al. (30). Regarding joint effusion and tenosynovitis, a significant relation was found with DAS28, agreeing with both Ghib et al. and Gohar et al. work (26, 27). All these previously mentioned relations and correlations signify the effective role of MSUS in the diagnosis of RA even in its early or subclinical stages, in follow-up its course, and so defining the treatment strategy and its effectiveness. Some limitations were also found in this study. The patient sample was small. So a larger group of patients would probably have strengthened the results. Addition of a volar view, especially in the detection of PIP synovitis would be better to reinforce our results. 3
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TABLE 2. MSUS Finding in Hands’ Joints MSUS Finding in 1300 Joints Erosion grade: 0 1 2 3 Total = 144 (11.07%) joints Effusion. grade: 0 1 2 3 Total = 120 (9.2 %) joints Synovial thickening: 0 1 2 3 Total =310 (23.85%) joints) Power Doppler signals: 0 1 2 3 Total = 155 (11.9%) joints) Tenosynovitis 0 1 Total= 46 (3.5%) joints
Wrists “n = 300”
MCP “n = 500”
PIP “n = 500”
218(72.67%) 70(23.33%) 0(0.0%) 12(4.0%) 82
450(90.0%) 11(2.20%) 13(2.6%) 26(5.2%) 50
488(96.0%) 11(3.67%) 1(0.33%) 0(0.0%) 12
267(89.0%) 21(7.0%) 3(1%) 9(3%) 33
445(89.0%) 34(6.8%) 4(0.8%) 17(3.4%) 55
468(89.33%) 7(2.33%) 12(0.8%) 13(1.2%) 32
202(67.33%) 19(6.33%) 17(5.66%) 62(20.67%) 98
332(66.4%) 77(15.4%) 39(7.8%) 52(10.4%) 168
456(91.2%) 22(4.4%) 6(1.2%) 16(3.2%) 44
226(75.33%) 35(11.67%) 26(8.67%) 13(4.33%) 74
469(93.8%) 17(3.4%) 11(2.2%) 3(0.6%) 31
450(90.0%) 12(2.4%) 24(4.8%) 14(2.8%) 50
279(93.0%) 21(7.0%) 21
488(97.6%) 12(2.4%) 12
487(97.4%) 13(2.6%) 13
In conclusion, MSUS has high reliability in the diagnosis of early RA concerning synovitis, joint effusion, tenosynovitis, and bone erosions. A good correlation was found between MSUS parameters and clinical and laboratory
parameters. Besides, its low cost and convenience, MSUS may be a better choice during the initial RA diagnosis, and its findings may be a more powerful parameter than clinical ones.
Figure 1. (A) A dorsal longitudinal scan of the right wrist (mid carpal view) B-mode, r = radius, l = lunate, cap = capitate, t = tendon, it shows tenosynovitis (red arrowed). (B) A dorsal longitudinal scan of the right wrist (mid carpal view) with power Doppler, r = radius, l = lunate, cap = capitate, t = tendon, it shows tenosynovitis and grade 1 power Doppler signal. (Color version of figure is available online.)
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Figure 2. (A) A dorsal longitudinal scan of the first right metacarpophalangeal joint (B-mode), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon, it shows grade 3 synovial thickening.(astrisk) (B) transverse view of the first right metacarpophalangeal joint, show Grade 2 erosion, e = erosion. (light green arrowed) (C) posteroanterior view of both wrists and hands graded as Larsen score 1. (Color version of figure is available online.)
Hence, the current results discovered that a detailed evaluation of musculoskeletal sonographic data is required to sufficiently raise the value of ultrasound in patients' follow up. The associations between DAS28 and other clinical
parameters with MSUS parameters reflected its value in the assessment of disease activity, severity, and provided a better way to pursuit the therapeutic effectiveness. Also, MSUS can detect small erosions in comparison to X-ray.
Figure 3. A dorsal longitudinal scan of the fourth left metacarpophalangeal joint (B-mode), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon, it shows Grade 3 synovial thickening (asterisk).
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Figure 4. (A) A dorsal longitudinal scan of the third left metacarpophalangeal joint (B-mode) Mc = metacarpal bone, Pp = proximal phalanx, t = tendon; it shows grade 3 synovial thickening (asterisk), grade 3 effusion. (B) A dorsal longitudinal scan of third left metacarpophalangeal joint (Power Doppler), Mc = metacarpal bone, Pp = proximal phalanx, t = tendon; it shows grade 3 synovial thickening, grade 1 power Doppler, and grade 3 effusion.
TABLE 3. Relation between DAS28, PD Signals and Synovial Thickening MSUS Finding
Remission “n = 2”
PD signals synovial thickening
2.0 § 0.0 8.0 § 0.0
Moderate “n = 50” 2.44 § 0.58 10.12 § 4.70
High “n = 48” 4.29 § 2.83 14.58 § 5.55
P value p < 0.04* p < 0.01*
Chi-square test was used to find relations among different parameters, and ANOVA analyzed the differences among group means (n = double number of patients for the statistical purpose).
TABLE 4. Relation between DAS28 and Erosion Detected by MUSU MSUS Finding Erosion: -ve +ve Effusion: -ve +ve Tenosynovitis: -ve +ve
Remission “n = 1”
Moderate “n = 25”
High “n = 24”
P value
0(0.0%) 1(100%)
18(72%) 7(28%)
11(45.8%) 13(54.2%)
p = 0.088 (n.s)
1(100%) 0.0
11(44.0%) 14(56.0%)
9(37.5%) 15(62.5%)
p < 0.03*
1(100%) 0.0
20(80%) 5(20%)
16(66.7%) 8(33.3%)
p < 0.03*
Chi-square test was used to find relations among different parameters (n = number of patients).
TABLE 5. Relation between DAS28 and Larsen Score X-ray DAS28
Remission “n = 1”
Moderate “n = 25”
High “n = 24”
P value
Larsen score
10.00 § 0.00
10.04 § 0.87
11.70 § 1.78
p < 0.04*
Using ANOVA test\n = number of patients.
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TABLE 6. Correlation between PD and (Synovial Thickness, DAS28, and Its Parameters) Parameters
Synovial thickening DAS28 Number of tender joint Number of swollen joint Patient global assessment (PGA) Physician global assessment (Phys.GA)
PD Signals r value
P value
0.489 0.468 0.393 0.501 0.282 0.446
0.0001*** 0.001** 0.005** 0.0001*** 0.047* 0.001**
r value Pearson’s correlation coefficient. * Statistically significant correlation (p < 0.05). ** High statistically significant correlation (p < 0.001). *** Very high statistically significant correlation (p < 0.0001).
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