Early diagnosis of Rheumatoid

26 Original Article Diagnostic Accuracy of Ultrasonography in Detection of Destructive Changes in Small Joints of Hands in Patients of Rheumatoid Arthritis: A Comparison with Magnetic Resonance Imaging Sonal Saran 1, Meenu Bagarhatta 2, Renu Saigal 3 Abstract Background: Ultrasonography can be used in early Rheumatoid Arthritis to determine and to follow parameters of joint inflammation, such as effusion, synovitis, and marginal erosion that can be radiologically occult. We therefore planned a study to investigate whether Ultrasonography could provide information on signs of inflammation and destruction in Rheumatoid Arthritis affected finger joints that was not available with Radiography and compared it to the information provided by Magnetic resonance imaging. Study Design: Hospital Based Descriptive Study. Methods: The study included 30 patients fulfilling American College of Rheumatology 2010 criteria of Rheumatoid Arthritis with no erosions present on radiographs of hands. Erosion, Synovial thickening/vascularity, effusion and Tenosynovitis of Flexor tendon sheath / Extensor tendon sheath were assessed on both Ultrasonography and Magnetic resonance imaging. Statistical Analysis: Considering Magnetic resonance imaging as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of Ultrasonography were calculated. Kappa value was calculated by kappa statistics to show agreement between the two modalities Results: Ultrasonography and Magnetic resonance imaging had near perfect agreement for detecting synovial thickening and vascularity, substantial agreement for detecting effusion, Flexor tendon sheath / Extensor tendon sheath inflammation, and only moderate agreement for detecting erosions in Metacarpophalangeal and Proximal interphalangeal joints. Conclusion: The early diagnosis of Rheumatoid Arthritis by Ultrasonography and MRI is very important to early treatment of Rheumatoid Arthritis. Ultrasonography is a reliable method for assessing inflammatory activity and destructive changes in small joints of hand as the Ultrasonographic findings are comparable to those of MRI. Editorial Viewpoint Detecting early affection of joints is very important in treatment of early RA. USG is a reliable and costeffective tool to determine inflammatory changes in synorium in early RA. This study finds USG and MRI have near perfect agreement for detecting synovial thickening and vascularity in RA. Introduction Early diagnosis of Rheumatoid arthritis (RA) is important because early aggressive treatment reduce the long term disability. For early detection of synovitis conventional radiography, clinical examination and laboratory tests are limited in their usefulness. 1 Musculoskeletal ultrasound has become an essential tool in routine clinical practice for early detection of joint inflammation, assessing ongoing disease activity and monitoring therapeutic responses. 2 Ultrasonography (USG) has been shown to be more sensitive than clinical examination in determining synovitis. USG can be used in early 1 Senior Resident, Department of Radio-diagnosis, All Indian Institute of Medical Science, Jodhpur, Rajasthan; 2 Professor, Department of Radio-diagnosis, Sawai Man Singh Medical College and Attached Group of Hospitals, Jaipur, Rajasthan; 3 Professor, Department of Medicine, Mahatma Gandhi Medical College, Jaipur, Rajasthan Received: 30.10.2015; Revised: 15.03.2016; Accepted: 29.03.2016

27 RA to determine and to follow, more objective parameters of joint inflammation, such as effusion, synovitis, and marginal erosion that can be radiologically occult. 3 Magnetic resonance imaging (MRI) of small joints of hands and wrists can directly visualize the bone and soft tissues in three dimensions, and has the potential to measure inflammatory activity and joint destruction. 3 Since early changes are nonosseous in nature, USG and MRI are superior to conventional radiography in terms of disease detection and therefore are the imaging methods of choice to evaluate synovium directly and to assess inflammation and joint damage. 4 Methods Study Design This hospital based descriptive study was carried out in the Department of Radio-diagnosis of our institute, between April 2012 and October 2013. Institutional ethical clearance was taken and all patients gave written consent. Aims and objectives of the study were : A. Evaluation of small joints of hands in cases of RA by USG (power Doppler and high frequency gray scale) and MRI. B. To investigate whether USG can provide information on signs of inflammation and destruction in RA finger joints (that are not available with conventional radiography), and compare it to the information provided by MRI. Subjects Consecutive patients with Rheumatoid arthritis, attending the outpatient rheumatology clinic, and who gave consent were recruited. Thirty patients fulfilling American College of Rheumatology (ACR) 2010 criteria of rheumatoid arthritis 5 with no erosions present on conventional radiography of hands were selected. This selection was made in order to include only patients whose joints were not damaged on radiographs, that is, the patients in which MRI and USG would be expected to have the greatest clinical value. All patients in whom MRI was contraindicated due to implanted medical devices, uncooperative patients, and patients showing erosions on radiographs were excluded. Disease activity score in 28 joints (DAS28) was calculated at the time of patient s visit to the rheumatology clinic by counting swollen and tender joints, recording ESR and assessing patient s global health. Ultrasound Assessment USG was done using ultrasound machine (Hitachi Color/power Doppler Ultrasound system) with high frequency 6-13 MHz 25-mm broadband linear array transducer. Patients were comfortably seated with both hands placed on a pillow. USG was done on the second to fifth metacarpophalangeal (MCP) joints and the second to fifth proximal interphalangeal (PIP) joints of both hands. Gray scale images of MCP and PIP joints of both hands were obtained in longitudinal and transverse planes followed by power doppler study to assess vascularity. The lowest wall filter was set for the power Doppler to detect any minimal flow. The most prominent power Doppler activity was identified and the images were frozen. Generous amounts of scanning gel was used to obtain acoustic contact and minimum pressure was exerted with the transducer. MRI Assessment Later in the day on which USG was performed, MRI (3 Tesla Philips) of both hands was done. Patients were placed in a prone position with the hands above the head. Sand bags were used to avoid any movement. We used conventional T1-weighted sequences, SE images of repetition time (TR) 600 m-sec, echo time (TE) 15 m-sec. T2-weighted sequences, TSE: TR = 2000 4000 m-sec, TE = 90 130 m-sec. Conventional short time inversion recovery (STIR) sequences. Fluid and pathologic tissues have high signal intensity in comparison to suppressed marrow and fat signal. To increase image quality we require a small field of view (FOV), we typically used an 16 to 18cm FOV for examinations of both hand. Coronal, sagittal and axial views in T2 and fat suppressed short tau inversion recovery (STIR) weighted spin-echo magnetic resonance sequences were performed. Continuous axial and coronal pre-gadolinium (Gd) and post-gadolinium T1- weighted spin-echo magnetic resonance sequences of both hands were performed. While the patient remained motionless in the MRI unit, 0.1 m-moles/kg body weight of gadodiamide (Omniscan) was injected into a vein in one of the arms via a cannula that had been inserted before the examination. Two different observers interpreted the ultrasound and MRI findings to ovoid bias in the interpretation. Total 240 MCP and 240 PIP joints (2 nd to 5 th MCP and PIP joints of both hands in 30 patients) were assessed. Assessment of the 6 parameters- Erosion, Synovial thickening, Synovial effusion, Tenosynovitis of flexor tendon sheath (FTS), Tenosynovitis of extensor tendon sheath (ETS), and Vascularity of synovium were done on both USG and MRI on the basis of sonographic and MRI definitions of the above pathologies given by Outcome measures in rheumatology clinical trials (OMERACT) Rheumatoid Arthritis Imaging Studies system. 6,7 Parameters were graded binarily as present or absent. Statistical Analysis Considering MRI as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of USG were calculated. Kappa value was calculated by kappa statistics to show agreement between the

28 Table 1: Total number of MCP and PIP joints showing erosion, effusion, synovial thickening and synovial vascularity on USG and MRI (n=240) Criteria USG MRI MCP PIP MCP PIP Erosion 35 (14.5%) 24 (10%) 45 (18.7%) 26 (10.8%) Effusion 59 (24.5%) 63 (26.2%) 74 (30.8%) 69 (28.7%) Synovial thickening 73 (30.4%) 61 (25.4%) 75 (31.2%) 61 (25.4%) Synovial vascularity 60 (25%) 56 (23.3%) 63 (26.2%) 55 (22.9%) Table 3: Diagnostic accuracy of USG as compared to MRI Criteria Sensitiviy Specificity PPV NPV Kappa value MCP Erosion 55.5 94.8 71.4 90.2 0.55 Effusion 74.3 97.5 93.2 89.5 0.76 Synovial thickening 93.3 98.2 95.8 97.0 0.92 Synovial vascularity 95.2 100 100 98.3 0.93 Erosion 57.6 95.7 62.5 94.9 0.55 PIP Effusion 79.7 95.3 87.3 92.0 0.77 Synovial thickening 95.0 98.3 95.0 98.3 0.93 Synovial vascularity 90.9 96.7 89.2 97.3 0.87 Flexor tenosynovitis 81.8 94.0 88.8 89.9 0.77 Extensor tenosynovitis 64.4 93.2 81.6 85.0 0.61 two modalities. Our main aim was to determine presence or absence of pathology without quantifying its severity and so scoring for synovitis, erosions, effusion and synovial vascularity according to the OMERACT Rheumatoid Arthritis Imaging Studies system was not performed. 6,7 Results The study included 30 patients (F: M - 4:1) of Rheumatoid arthritis with mean age 42.333±24.92 years. Mean duration of illness in our study was 3.933±2.514 months. Rheumatoid factor (RF) was elevated (>20 IU/ml) in 16 patients (53.3%) with mean titer of 37.85±17.54 IU/ml. Mean ESR(mm/hr), CRP level (mg/l) and ACPA(EU) of the patients in our study were 36.73±30.95, 8.79±10.09 and 45.12±24.32 respectively. DAS28 values ranged from 0 to less than 3.2 in 4 patients, 3.2 to 5.1 in 23 patients and more than 5.1 in 3 patients. On ultrasound and MRI assessment, out of 240 MCP and PIP joints (2 nd to 5 th MCP and PIP joints of both hands in 30 patients) erosion, effusion, synovial thickening and synovial vascularity were present in various number of joints as summarized in Table 1. Similarly out of 240 FTS and ETS (2 nd to 5 th FTS and ETS of both hands in 30 patients) tenosynovitis was present in the tendon sheaths as described in Table 2. Considering MRI as gold standard sensitivity, specificity, positive predictive value, negative predictive value and kappa value of USG were calculated which are shown in Table 3. There was an increase in the average number of joints having erosions (detected on MRI) with increase in the duration of disease as described in Table 4. Discussion This study found lower sensitivity of USG in detecting erosions in MCP and PIP joints. There was only moderate agreement between USG and MRI for detection of erosions. This is similar to the study conducted by Hoving et al. 8 They reported that MRI has significantly increased sensitivity compared with ultrasound for detection of erosions in the hand and wrist. Dohn et al 9 reported sensitivities of only 68% and 42% for MRI and USG in detecting erosions, respectively, although only 17 patients with RA were Table 2: Total number of FTS and ETS showing inflammation (tenosynovitis) on USG and MRI (n=240) Criteria USG MRI FTS 81 (33.75%) 88 (36.6%) inflammation ETS inflammation 60 (25.0%) 76 (31.6%) Table 4: Total no. of joints having erosions on MRI and duration of disease Duration in Average no. of joints having months erosions detected on MRI 2 0 3 1.5 4 2.5 5 3.6 6 4.3 included in the study, however specificity for erosion were high indicating proportion of negatives which were correctly identified as such. Sensitivity of USG for detecting FTS inflammation was higher than that for detecting ETS inflammation however specificity for these criteria were comparable and high. For detection of effusion, FTS and ETS inflammation USG and MRI showed substantial agreement (Figure 1). Backhaus et al 10 found significant correlation between tenosynovitis detected by USG and MRI which agrees with our results. In this study highest sensitivity of USG was found for detecting synovial vascularity in MCP joints. Sensitivity and specificity for detecting synovial thickening in MCP and PIP, and synovial vascularity in PIP were also high indicating that USG can detect synovial inflammatory activity with high sensitivity and specificity. There was near perfect agreement between USG and MRI for detection of synovial thickening and vascularity in MCP and PIP joints (Figure 2). This is important, because in the early stages of RA, the synovitis is the primary pathology and seems to be the best predictive marker of joint damage. 3 Szkudlarek et al. 2004 11 also compared USG and MRI, with

29 Fig. 1: (a and b) USG demonstrates hypo-echoic thickened tissue within the flexor tendon sheath, which is seen in two perpendicular planes (a) longitudinal plane (b) transverse plane suggestive of flexor tendon sheath inflammation (Fts infl) (arrow). (c) MRI demonstrates an area adjacent to flexor tendons with an above-normal Gd enhancement and abnormal thickening of the tendon sheath suggestive of flexor tendon sheath Inflammation (arrow) ETS Fig. 2: USG demonstrates (a) an abnormal hypo-echoic intra-articular tissue that is non-displaceable and poorly compressible and (b) exhibit power Doppler signal suggestive of synovial thickening with increased vascularity. (c) MRI demonstrates an area in the synovial compartment which shows thickness greater than the width of the normal synovium and above normal post-gd enhancement suggestive of synovial thickening with increased vascularity (arrow). ETS : extensor tendon sheath MRI as the reference method, the sensitivity, specificity, and accuracy of USG in detection of synovitis were 87%, 74% and 79%. Farrant et al., 2007 12 found that Doppler USG and early MRI enhancement in rheumatoid joints have been closely correlated; the sensitivity and specificity of Doppler USG, with MRI as a reference, were 89% and 98 % respectively. Above findings indicate that USG is more sensitive in detecting soft tissue changes than bony changes (erosions) when MRI was used as reference method. Our study cohort included only patients having no erosion on hand radiographs this automatically concluded that USG and MRI can detect erosions earlier than radiography. This matched with many of the previous studies. Wakefield, et al 13 reported the superior sensitivity of ultrasound over radiography for the detection of bone erosions in patients with rheumatoid arthritis. McQueen et al 14 reported carpal erosions in 45% of patients on MR images 4 months after the onset of symptoms, while only 15% of patients had erosions on plain radiographs. Conclusion RA is a potentially devastating condition affecting a large proportion of the population. Treatment has significantly progressed in recent years and outcome is significantly improved when disease is diagnosed and treated at an early stage. The early diagnosis of RA by USG and MRI is very important to early treatment and modification of treatment according to activity and severity of RA disease. There are only few published studies directly comparing the sensitivity and specificity of these two modalities, particularly where a valid reference standard has been used. USG is a reliable method for assessing inflammatory activity and destructive changes in small joints of hand as the USG findings are comparable to those of MRI. Clearly defined quantitative measures of synovitis will provide increased accuracy in monitoring disease changes in patients and will also provide a reference standard for clinical trials to compare results in a formal reproducible manner. Future studies are required with increased patient number to determine which one of these two modalities is more appropriate as the imaging modality of choice. Both have advantages and disadvantages and as technology and skills develop they may continue to evolve in terms of sensitivity and availability. The availability is often determining factor for the choice of modality in a given center. In developing countries like India, where there are constraints of finances and availability of MRI centers, USG examinations offering reliable and early diagnosis of disease activity in patients of RA would be very beneficial. This would help the clinicians to monitor the treatment and prevent the debilitation due to this disease. References 1. Naredo E, Collado P, Cruz A, et al. Longitudinal power Doppler ultrasonographic assessment of joint inflammatory activity in early rheumatoid arthritis: Predictive value in disease activity and radiologic progression. Arthritis and Rheumatism 2007; 57:116-24. 2. Kang T, Lanni S, Nam J, et al. The evolution of ultrasound in rheumatology. Ther Adv

30 Musculoskelet Dis 2012; 4:399 411. 3. Sommer OJ, Kladosek A, Weiler V, et al. Rheumatoid Arthritis: A Practical Guide to State-of-the-Art Imaging, Image Interpretation, and Clinical Implications. Radio Graphics 2005; 25:381 398. 4. Majithia V, Geraci SA. Rheumatoid arthritis: diagnosis and management. Am J Med 2007; 120:936 9. 5. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/ European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69:1580 8. 6. Marhadour T, Saraux A. Rheumatoid Arthritis Assessment with Ultrasonography. Dr. Kerry Thoirs, Editor, Sonography: InTech publishers 2012; 173-186. 7. Ostergaard M, Edmonds J, McQueen F, et al. An introduction to EULAR-OMERACT rheumatoid arthritis MRI reference atlas. Ann Rheum Dis 2005; 64(Suppl I):i3 i7. 8. Hoving JL, Buchbinder R, Hall S, et al. A comparison of magnetic resonance imaging, sonography, and radiography of the hand in patients with early rheumatoid arthritis. J Rheum 2004; 31:663 675. 9. Dohn UM, Ejbjerg BJ, Court-Payen M, et al. Are bone erosions detected by magnetic resonance imaging and ultrasonography true erosions? A comparison with computed tomography in rheumatoid Arthritis metacarpophalangeal joints. Arthritis Res Ther 2006; 8:R110. 10. Backhaus M, Ohrndorf S, Kellner H, et al. Evaluation of a Novel 7-Joint Ultrasound Score in Daily Rheumatologic Practice: A Pilot Project. Arthritis and Rheumatism 2009; 61:1194 1201. 11. Szkudlarek M, Klarlund M, Narvestad E, et al. Ultrasonography of the metatarsophalangeal joints in rheumatoid arthritis, compared with magnetic resonance imaging, conventional radiography and clinical examination. Arthritis Res Ther 2006; 8:2103-2112. 12. Farrant JM, O Connor PJ, Grainger AJ. Advanced imaging in rheumatoid arthritis Part 1: synovitis. Skeletal Radiol 2007; 36:269 279. 13. 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 and Rheumatism 2001; 43:2762-70. 14. McQueen FM, Stewart N, Crabbe J, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis 1998; 57:350 356. api Oration Recommendations are invited from members for the following assignment so as to reach, Hon. General Secretary API, Dr. Mangesh Tiwaskar by 20th December 2016. Category No. (iii): All lectureships viz 1. Sanofi Aventis Lectureship in Diabetes 2018 The selected candidate has to deliver his/her lecture at the Annual Conference of API - 2018. The above lectureship will get the award money of Rs. 10000/- (Rupees ten thousand only) and TA by Economy Class airfare from API, Complimentary Registration and complimentary stay of one night in the designated conference hotel by the APICON Organizing Committee Persons are selected from the recommendations received from members of the API. The orator in the discipline of medicine should preferably be a member of API. The recommendations for the above assignments must be accompanied with reasons for recommending a particular person showing the value of his/her research and eight copies each of three of his/her best publications. All relevant papers in connection with the suggestions, such as the bio-data, list of publications etc., should be submitted in 8 sets by the proposer. The recipient of the above oration should deliver a lecture pertaining to his/her work at the Annual Conference in January, 2018. For the above lectureship is open to eminent persons from the discipline of medicine and allied subjects such as Pharmacology, Biochemistry, Pathology and Physiology. All relevant papers in connection with the suggestions, such as the bio-data, list of publications etc., should be submitted in 8 sets by the proposer.. Those who have received Oration / Lectureship in a given category are eligible for application for the other two categories. The members of the Governing Body of API and the Members of the Faculty Council of ICP are not eligible to receive any Oration, Lectureship or Award. The prescribed nomination form for the above orations / Lectureship are on the API website apiindia.org The completed application forms for the above Lectureship should reach to Dr. Mangesh Tiwaskar, Hon. General Secretary of API, Unit No. 6 & 7, Turf Estate, Opp. Shakti Mill Compound, Off. Dr. E. Moses Road, Near Mahalaxmi Station West, Mumbai 400 011 not later than 20th December 2016. Tel. No. 022 66663224; 24912218 Fax 24920263 Email: api.hdo@gmail.com Dr. Mangesh Tiwaskar Hon. General Secretary