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Ultrasound Assessment of Entheses and Correlations Between Disease Activity and Ultrasound Scores in Ankylosing Spondylitis: a Cross Sectional Study

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Ultrasound Assessment of Entheses and Correlations Between Disease Activity and Ultrasound Scores in Ankylosing Spondylitis: a Cross Sectional Study Ultrasound Assessment of Entheses and Correlations Between Disease Activity and Ultrasound Scores in Ankylosing Spondylitis: A Cross Sectional Study HAIQIN XIE Peking University Shenzhen Hospital GENGMIN ZHOU Peking University Shenzhen Hospital BO WEN Peking University Shenzhen Hospital HAIYU LUO Peking University Shenzhen Hospital YUSEN ZHANG Peking University Shenzhen Hospital QIAN DONG U-M: University of Michigan JIANQIU ZHONG Peking University Shenzhen Hospital JIYANG LV Peking University Shenzhen Hospital WEIWEI ZHANG Peking University Shenzhen Hospital HENG LV Peking University Shenzhen Hospital DESHENG SUN Peking University Shenzhen Hospital Qingwen Wang ( [email protected] ) Peking University Shenzhen Hospital https://orcid.org/0000-0003-3723-2414 LIU LI Peking University Shenzhen Hospital Research article Page 1/18 Keywords: Ultrasound, enthesitis, ankylosing spondylitis, disease activity Posted Date: October 27th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-95578/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/18 Abstract Background: An increasing number of studies have applied ultrasound (US) to evaluate enthesitis in spondyloarthritis. However, there is no clear agreement on which sites should be evaluated for enthesitis. Furthermore, there are different opinions on whether US can monitor disease activity. The objectives of this study were to evaluate the common involvement of entheses and correlations between disease activity and US scores in ankylosing spondylitis (AS). Methods: A cross-sectional, monocentric, and controlled study was performed. US was used to scan 34 entheses per person and the Madrid sonography enthesitis index (MASEI) score was used. US scores were used to evaluate the elemental lesions of hypoechogenicity, thickness, erosion, calcication, bursitis, and Doppler signal. Disease activity was assessed by Disease Activity Score–C reactive protein (ASDAS- CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results: 104 patients with AS and 50 control subjects were included. A total of 5236 entheses were assessed. Compared with the control subjects, only three entheses – the Achilles tendon (AT), sternoclavicular joint (SCJ), and costochondral joint (CCJ) – showed signicant differences in the AS group (p < 0.05). Patients with high disease activity (ASDAS-CRP ≥ 2.1) had higher scores than patients with low activity (ASDAS-CRP < 2.1) in erosion (p = 0.02). Patients who were categorized in very high disease activity (ASDAS-CRP ≥ 3.5) had a higher score in erosion (p = 0.02). The erosion score was moderately associated with ASDAS-CRP and BASDAI (r = 0.44, r = 0.21). Conclusions: The commonly involved entheses were the AT, SCJ, and CCJ in AS. Erosion occurred more often in patients with disease activity or high activity. Erosion would be more useful for monitoring disease activity in AS. Background Enthesitis is a characteristic sign of ankylosing spondylitis (AS). It has been validated that enthesitis is important for the diagnosis of AS and monitoring disease activity [1]. AS can cause physical damage and disability, declining the patient’s quality of life and bringing about a nancial burden to both their families and society as a whole [2, 3]. The prevalence of AS ranges from 0.1–0.9% [4]. Early diagnosis and treatment can decrease the probability of disability and improve the outcome. However, the diagnosis of AS was usually delayed by an average of 6–9 years after the onset of clinical symptoms [5, 6]. X-rays are still the rst line of investigation for the evaluation of enthesitis, although the changes may occur in the late phase [7]. Computed tomography (CT) can demonstrate bone erosion, but it is limited by radiation exposure and low resolution for soft tissue. Magnetic resonance imaging (MRI) has been considered more valuable, as it can reveal bone edema and soft tissue swelling. Nonetheless, MRI is limited by its availability and high cost. Additionally, it cannot assess many entheses due to it being a time-consuming process. Ultrasound (US) has many advantages, such as being cheap, portable, non- radioactive, done in real-time, and can be easily compared to the opposite side. It is becoming Page 3/18 increasingly accepted by rheumatologists as a suitable method. Also, some studies reported that US can evaluate enthesitis for disease diagnosis, even in the early stages of spondyloarthritis [8, 9]. Recently, more studies have applied US to evaluate enthesitis in spondyloarthritis, where the main type of spondyloarthritis is AS [8–11]. Nowadays the standardized denition of US enthesitis is in accordance with the denition given by Outcome Measures in Rheumatology (OMERACT) [12]. However, there is no clear agreement on which sites should be evaluated for enthesitis. Most studies have focused on the lower limbs [11, 13, 14], while some others investigated the upper limbs [15, 16]. However, few articles pay attention to the anterior chest wall (ACW) [17]. The ACW has been demonstrated as the second most commonly involved site in spondyloarthritis just behind the sacroiliac joint [18]. Furthermore, there are different opinions on whether US can monitor disease activity [19–21]. More studies are needed to assess whether disease activity is correlated with US elemental lesions. The main objective of the present study was to evaluate the common involvement entheses in AS, including the upper limbs, lower limbs, trunk, and ACW. Second, the correlations between disease activity and US scores were assessed. Further study is needed to determine whether enthesis US can monitor disease activity in AS. Methods Patients and study design. This was a cross-sectional study with health control. The study was performed following the Declaration of Helsinki principles and local regulations. The approval was permitted by the ethical committee of Peking University Shenzhen Hospital. All patients and healthy individuals signed informed consent. Between December 2017 and December 2019, the study nally enrolled 104 patients with AS who fullled the modied New York criteria [22]. All the patients were consecutively enrolled from the Department of Rheumatology and Immunology at Peking University Shenzhen Hospital. The exclusion criteria included the following: a history of joint or ACW surgery; corticoid injection at the enthesis within the last six weeks; peripheral neuropathy; age <18 years; diseases other than AS; and an unwillingness to sign for consent, or did not nish all the examinations or patient-reported outcome measures (PROMs). If patients met one of the above conditions, they were excluded. Controls. Fifty healthy persons were matched with AS patients in age, gender, and body mass index (BMI). They were selected among the hospital workers and healthy volunteers who did not have any symptoms at the entheses, without the diagnosis of spondyloarthritis or family history. Data collection. Page 4/18 Data was collected by PROMs, laboratory data, and US assessments. PROMs and laboratory data. All patients were examined by a qualied rheumatologist. The rheumatologist used PROMs. For each patient, the laboratory tests consisted of C reactive protein (CRP) and human leukocyte antigen B27 (HLA-B27). Disease activity was assessed by Disease Activity Score- CRP (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The interval between each examination was less than one week. The ASDAS-CRP value (VASDAS-CRP) indicated the disease activity of AS. When the value was <1.3, the disease was inactive. When the value was 1.3 ≤ VASDAS-CRP < 2.1, the disease activity was low. When the index was 2.1 ≤ VASDAS-CRP < 3.5, the disease activity was high. When the index was ≥3.5, the disease activity was very high. BASDAI was a self- assessment form to measure disease activity. It had six questions, and each question was scored from 0 to 10. When the overall score was ≥4, it indicated disease activity. Otherwise, it indicated disease inactivity. A higher score reected a more active disease. US assessment. Ultrasonography was performed using Toshiba Aplio 400 equipment with a linear transducer with a frequency of 7-18 MHz by an experienced sonographer who had taken part in musculoskeletal US for more than ve years. All subjects were examined by grey scale and power Doppler ultrasonography. Doppler settings were standard with a pulse repetition frequency of 1000 Hz, low wall lter, and Doppler gain at a level of just below random noise. The sonographer was blinded to clinical information, and people were advised not to talk with the US examiner. US was used to evaluate 34 entheses in the upper limbs, lower limbs, trunk, and ACW. The upper limbs contained three bilateral entheses: common extensor tendon (CET), common exor tendon (CFT), and supraspinatus tendon (SST). The lower limbs were comprised of seven bilateral entheses: quadriceps tendon (QT), proximal patella tendon (PPT), distal patella tendon (DPT), lateral collateral ligament (LCL) on the lateral femoral condyle, medial collateral ligament (MCL) on the medial femoral condyle, Achilles tendon (AT) on the calcaneus, and plantar fascia (PF). The trunk consisted of two entheses: the bilateral anterosuperior iliac spine (ASIS) and the single pubic symphysis (PS). The ACW included three entheses: bilateral sternoclavicular joint (SCJ), single manubriosternal junction (MSJ), and costochondral joint (CCJ), in which the CCJ included eight bilateral entheses from the
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