Chronicity is associated with the glenohumeral synovitis in patients with a rotator cuff tear

Abstract Synovitis of the glenohumeral joint (GHJ) and subacromial space (SAS) is one of the most common findings during arthroscopic rotator cuff repair (RCR). The purpose of this study is to determine clinical factors associated with the degree of synovitis in patients with a rotator cuff tear and whether macroscopic synovitis affects early clinical outcomes following arthroscopic RCR. Arthroscopic videos of 230 patients treated with arthroscopic RCR were randomly reviewed by two experienced shoulder surgeons. The synovitis scores of the GHJ using Davis's grading system and the SAS using Jo's grading system were rated with a consensus. Univariate and multivariate analyses were used to identify the associations between the synovitis scores and various parameters, including demographics, preoperative, and postoperative clinical outcomes. Univariate analyses revealed that age, side, body mass index, duration of symptoms, preoperative stiffness, diabetes, muscle atrophy, fatty infiltration, tear size, preoperative clinical scores, and preoperative range of motion were significantly associated with the GHJ synovitis score (all p < 0.05). Multivariate analyses revealed that the duration of symptoms, tear size, and diabetes was significantly associated with the GHJ synovitis score (p = 0.048, p = 0.025, p = 0.011, respectively). Longer duration of symptoms, larger tear size, and the presence of diabetes was independently associated with increased GHJ synovitis in patients with a rotator cuff tear. These results suggest that GHJ synovitis might be more involved in the pathogenesis for pain and tear progression of rotator cuff disease compared with SAS synovitis.

progression of tears with minimal or no symptoms. However, the exact etiology and pathogenesis of rotator cuff disease remain unclear.
The rotator cuff is interposed between the glenohumeral joint (GHJ) and subacromial space (SAS) as a mover and stabilizer of the shoulder joint. 6 It is generally recognized that rotator cuff disease involves not only the tendons but also tissues in the GHJ and SAS, including bursa, synovium, ligament, and joint fluid. 1 Jo et al. 1 suggested that rotator cuff disease, like osteoarthritis, is regarded and treated as a "pan-joint disease" of the shoulder.
It is widely accepted that subacromial synovitis is a source of pain in rotator cuff disease. [6][7][8][9][10][11] The subacromial bursa is anatomically vulnerable to friction with the undersurface of the acromion during the range of motion (ROM) and synovitis occurs subsequently into the SAS. 12 Several basic studies reported that overexpression of inflammatory cytokines, enzymes, and proteinases was observed in the subacromial bursa of patients with a rotator cuff tear. [6][7][8]10 These studies highlighted the important role that subacromial synovitis plays in the development of shoulder pain in patients with a rotator cuff tear and noted that its severity is associated with the pain intensity. 6 A growing body of evidence exists for the role of GHJ synovitis in rotator cuff disease 3,4,12,13 ; however, it has not fully elucidated as of yet.
Gotoh et al. 12 noted increased expression of interleukin (IL)-1β in synovial tissue in patients with a full-thickness rotator cuff tear. Subsequently, several laboratory studies revealed that increased synovial inflammation and angiogenesis of the GHJ correlates with the tear size of the supraspinatus tendon and suggested that GHJ synovitis might be involved in the pathogenesis of rotator cuff tear. 3,4,13 Synovial inflammation of the GHJ and SAS is one of the most common findings during arthroscopic surgery for a rotator cuff tear.
Until now, most basic studies have characterized the biochemical and histologic findings of specimens including rotator cuff, synovium, joint fluid, or subacromial bursa. 4,6,7,10,[12][13][14][15] Few studies have examined the macroscopic appearance of the synovial tissue of the GHJ and SAS. 1,16 Furthermore, no prior studies evaluated the potential association between macroscopic synovitis and various clinical factors in patients with a rotator cuff tear.
The primary aim of this study was to determine clinical factors associated with the degree of GHJ and SAS synovitis in patients with a rotator cuff tear. The secondary aim was to determine whether macroscopic synovitis affects early clinical outcomes following arthroscopic rotator cuff repair (RCR). This study was conducted to prove the hypothesis that the degree of macroscopic synovitis would correlate with clinical findings in patients with rotator cuff tear.

| METHODS
This study was approved by the institutional review board of our hospital (IRB No:2020-04-026), and informed consent was obtained from all patients. Two-hundred thirty patients who underwent arthroscopic RCR by a single surgeon at a single institution between October 2013 and February 2018 were included in this study. Inclusion criteria were as follows: (1) patients with arthroscopic RCR; (2) available medical records and arthroscopic findings; (3) available data for serial follow-up periods including 3, 6, and 12 months after surgery. Exclusion criteria included: (1) a history of previous shoulder surgery or major trauma; (2) a history of inflammatory arthritis; (3) corticosteroid injection within 4 weeks before surgery; and (4) antiinflammatory medication within 2 weeks before surgery.

| Macroscopic assessment for synovitis
With patients in the lateral decubitus position, a standard arthroscopic GHJ examination through the posterior and anterior portals to evaluate intra-articular pathology was performed. Next, the arthroscope was placed in the SAS, and RCR was conducted. Using an arthroscopic shaver and radiofrequency device, arthroscopic debridement and ablation for the synovitis of the GHJ and SAS were performed as thoroughly as possible.
Arthroscopic videos of 230 patients treated with arthroscopic RCR were randomly presented to two shoulder surgeons for macroscopic assessment of synovitis. Before the independent assessment, the consensus for synovitis grading of the GHJ and SAS between two observers were generated through a detailed review of the studies reported by Davis et al. 16 and Jo et al. 16 with 30 samples of arthroscopic video. To evaluate intraobserver reliability, this same procedure was repeated 2 weeks after the first round of assessment.
According to the grading system proposed by Davis et al., 16

| Statistical methods
The SPSS statistical package (version 20.0; IBM) was used for data analysis. Intraobserver and interobserver reliability were assessed by calculating the κ correlation coefficient. To identify clinical parameters associated with the degree of synovitis, univariate analysis was conducted using the Pearson correlation test, Spearman correlation test, independent t-test, and one-way 95% confidence intervals were reported to provide the magnitude of the association. Statistical significance was accepted for p values of less than 0.05.  Table 1).
Multivariate analyses revealed that the duration of symptoms, diabetes, and tear size was significantly associated with the GHJ synovitis score (p = 0.048, p = 0.025, p = 0.011, respectively; Table 5).

| DISCUSSION
The present study was conducted to identify clinical factors that may    rotator cuff degeneration and tear progression as well as pain generation in patients with rotator cuff tear. 3,4,12,14 Based on the results from our study, we do not deny that synovial inflammation of the SAS is associated with the pathophysiology of rotator cuff disease.
We think that the pathogenesis for pain in patients with rotator cuff tear may originate from the GHJ synovitis rather than the SAS synovitis.
Gotoh et al. 6 observed that full-thickness rotator cuff tears were associated with greater degrees of synovitis than partial-thickness tears. Shindle et al. 3 reported that increased synovial inflammation and tissue degeneration correlates with the tear size of the supraspinatus tendon. Tajana et al. 15 reported that the total protein concentration of synovial fluid increased with the loss of integrity of the rotator cuff, reaching the highest levels in rotator cuff tear arthropathy. The absolute enzymatic activity of gelatinases was greater in full-thickness tears compared with partial-thickness tears. 15

| CONCLUSION
Longer duration of symptoms, larger tear size, and the presence of diabetes mellitus was independently associated with increased GHJ synovitis in patients with a rotator cuff tear. These results suggest that GHJ synovitis might be more involved in the pathogenesis for pain and tear progression of rotator cuff disease compared with SAS synovitis.

ACKNOWLEDGMENTS
The authors would like to thank Ye-Ji Kim and Eun-Ji Jeon for their support with data collection. This study was supported by the National Research Foundation of Korea, funded by the Korean government (Grant nos. 2017R1D1A1B03035113 and 2014R1A5A2010008).

AUTHOR CONTRIBUTIONS
Du-Han Kim analyzed the data and reviewed the manuscript.
Ki-Cheor Bae reviewed the manuscript and supervision. Jung-Hoon Choi gathered and analyzed the data and reviewed the manuscript.
Sang-Soo Na gathered and analyzed the data. Ilseon Hwang conceived the idea and analyzed the data. Chul-Hyun Cho conceived the idea and wrote the manuscript.