Can physical trauma trigger relapsing polychondritis? The first report from a Chinese cohort and comparison with rheumatoid arthritis and psoriatic arthritis

Can physical trauma trigger relapsing polychondritis? 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The first report from a Chinese cohort and comparison with rheumatoid arthritis and psoriatic arthritis Lei Zhang, Shuang Yun, Wei Li, Yujie He, Lishuai Han, Ting Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5467695/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives The triggers of relapsing polychondritis (RPC) are not fully characterized. This study was performed to explore the association between physical trauma and RPC. Methods The history of physical trauma of 208 patients with RPC from a Chinese cohort was reviewed and compared with that of 1134 patients with rheumatoid arthritis (RA) and 369 patients with psoriatic arthritis (PsA). The characteristics and survival of patients with physical trauma were analyzed. Results Eighty patients with RPC (38.5%) ever had physical trauma. This number is considerably higher than that of patients with RA (21.6%, p < 0.0001) and PsA (20.6%, p < 0.0001). A total of 48 patients with RPC (23.1%) had 52 osteochondral injuries, whereas only 58 patients with RA (5.1%, p < 0.0001) and 21 patients with PsA (5.7%, p < 0.0001) ever had osteochondral injuries. We found that more patients with RPC experienced any type of physical trauma, as well as osteochondral trauma, in the preceding one year , and also half a year, before disease onset than patients with RA and PsA. Traumatic events (osteochondral and nonosteochondral) increased in the preceding one year before disease onset, especially in the preceding six months. Patients with osteochondral trauma that occurred at any time before disease onset had a higher rate of airway involvement and lower rates of survival than those without osteochondral trauma. Conclusion Our findings suggest that physical trauma may be triggers of RPC, and that patients with osteochondral trauma seem to have more severe disease than those without. Relapsing polychondritis physical trauma triggers Figures Figure 1 Figure 2 Figure 3 Introduction Relapsing polychondritis (RPC) is a systemic inflammatory disease primarily affecting cartilaginous tissues, including the ears, nose, larynx, tracheobronchial tree, and joints, as well as noncartilaginous tissues (1). The first case of RPC was described in 1923 by Jaksch-Wartenhorst, but little attention was given to the entity until the 1960s, when Pearson et al. introduced the name “relapsing polychondritis” (2). The pathogenesis of RPC remains largely unknown (1,3,4). However, RPC has been postulated to be an autoimmunity-mediated disorder and that cellular and humoral immunities are involved in its pathogenesis(1,3,4). In addition, a strong correlation exists between susceptibility to RPC and the presence of HLA-DR4 (5,6), as well as HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01 (7) . In addition, ultra-rare damaging germline variants in DCBLD2 was reported to be associated with RPC in a recent report(8) Meanwhile, the triggers of this rare disorder are not fully characterized either. Although several case reports suggest that cartilage injury may initiate RPC (9–11), solid evidence from a large case series is unavailable. In the present study, we retrospectively reviewed the history of physical trauma in patients with RPC and compared its incidence with that in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), aiming to establish an association between physical trauma and the onset of RPC. Results Demographic characteristics of patients with RPC, RA, and PsA A total of 100 female patients with RPC and 108 male patients with RPC were included. These patients had an average age of 48.5 ± 13.8 years at diagnosis. The median follow-up duration after diagnosis was 40 months (range 1–189 months). Three patients were lost at follow-up. A total of 22 deaths occurred, and the causes of deaths were pulmonary failure associated with refractory tracheal involvement (n = 14), tracheal involvement accompanied with pulmonary infections (n = 5), brain tumor without tracheal involvement (n = 1), multiple organ failure (n = 1, with tracheal involvement), and unknown cause (n = 1, with tracheal involvement). A total of 1134 patients with RA and 369 patients with PsA were included as controls. Among the patients with RA, 832 were female (73.4%) and 302 were male (26.6%), with 934 cases (82.4%) having moderate-to-high levels of RF and/or anti-CCP antibodies and 200 cases (17.6%) having low or normal levels of RF and anti-CCP antibodies. The average age of patients with RA was 55.1 ± 12.4 years at diagnosis. Among patients with PsA, 145 (39.3%) were female; 224 (60.7%) were male; 349 (94.6%) had a history of psoriasis or family history of psoriasis; and the remaining 20 had typical signs of PsA, such as sausage finger/toe or enthesitis or psoriatic nail lesions but no history of psoriasis or family history of psoriasis. The average age at diagnosis was 42.9 ± 15.1 years. Frequency of physical trauma in patients with RPC , RA and PsA The proportion of patients with RPC (n = 80, 38.5%) that ever experienced physical trauma before disease onset was higher than those of patients with RA (n = 245, 21.6%, p < 0.0001) and patients with PsA (n = 76, 20.6%, p < 0.0001). The proportion of patients with RPC that experienced physical trauma the preceding year before disease onset was greater (n = 37, 17.8%) than those of patients with RA (n = 61, 5.4%, p < 0.0001) and patients with PsA (n = 16, 4.3%, p < 0.0001). This situation was also the case in the preceding half year before disease onset (Table 1). We also compared the incidence of osteochondral injuries in the three groups of patients. For example, 48 patients with RPC (23.1%) experienced osteochondral injuries. This incidence was considerably higher than those in patients with RA (n = 58, 5.1%, p < 0.0001) and patients with PsA (n = 21, 5.7%, p < 0.0001). In the preceding year before disease onset, 27 patients with RPC (13.0%) experienced osteochondral injuries compared with 22 patients with RA (1.9%, p < 0.0001) and 10 patients with PsA (2.7%, p = 0.0003). This situation was also the case in the preceding half year before disease onset (Table 1). Description of physical trauma in patients with RPC As mentioned above, 80 out of 208 patients with RPC (38.5%) had 96 traumatic events. Sixty-six patients experienced one event, 12 patients experienced two events, and two patients experienced three events. A total of 52 osteochondral events were found in 48 patients. These events included 20 cartilage-related events (12 ENT procedures, seven teeth extractions, and one tracheotomy) and 32 bony/articular events (eight bone surgeries, 20 fracture and joint sprain, two skull surgeries, one head trauma, and one chin trauma), as well as 44 nonosteochondral events in 32 patients (13 gastrointestinal procedures, 15 obstetrical–gynecological procedures, six cutaneous injuries, four percutaneous coronary interventions, three breast procedures, one thyroidectomy, one thoracic puncture, and one tympanic membrane repair). Chronological variation of traumatic events The chronological order of osteochondral (including cartilage- and bone/joint-related injuries) and nonosteochondral events are shown in Figure 1 and Supplementary Table 1. The earliest traumatic events occurred 50 years before disease onset, and only occasional traumatic events occurred until one year before disease onset, at which time the events (osteochondral and nonosteochondral) increased, especially in the preceding six months. Fourteen traumatic events in 13 patients occurred between the preceding one year and half a year before disease onset, whereas 26 events in 24 patients occurred in the preceding six months. Apparently, cartilage-related events (seven ENT procedures, three teeth extractions, and one tracheotomy) increased more significantly than bone/joint related (three long bone fractures, two skull procedures, and one chin trauma) and nonosteochondral events (three gastrointestinal procedures, two obstetrical–gynecological procedures, one cutaneous injury, one breast procedure, one percutaneous coronary intervention, and one tympanic membrane repair) in the preceding six months. Characteristics of patients with physical trauma Patients with RPC were divided into different groups in accordance with the types of physical trauma (Table 2 and 3 and Supplementary Figure 1), and their characteristics were compared. Patients with RPC in group A (n = 80) presented similar features as those in group B (n = 128) in terms of clinical manifestations, age, gender, and mortality rate. However, group A patients had slightly more deaths, female prominence, and a higher proportion of airway involvement but a relatively lower proportion of auricular chondritis than other groups , although without a statistical significance(Figure 2A and Supplementary Table 2). Moreover, a significantly higher proportion of airway involvement (64.6% vs 40.6%, p = 0.003) and significantly lower proportion of auricular chondritis (45.8% vs 66.9%, p = 0.008) were observed in group C patients (n = 48) than in group D patients (n = 160) (Figure 2B and Supplementary Table 3). Similarly, patients in group C (n = 48) presented a higher proportion of airway involvement (64.6% vs 28.1%, p = 0.001) and relatively lower incidence of auricular chondritis (45.8% vs 71.9%, p = 0.021) than group E patients (n = 32) (Figure 2C and Supplementary Table 4). Patients with RPC in group F (n = 37) had a slightly higher proportion of airway involvement (54.1% vs 44.4%, p = 0.22), nasal chondritis (21.6% vs 14%, p = 0.246), and fever (29.7% vs 18.7%, p = 0.134); a slightly lower proportion of auricular chondritis (51.4% vs 64.3%, p = 0.14); and a significantly higher proportion of death (24.3% vs 7.6%, p = 0.006) than group G patients (n = 171) (Figure 2D and Supplementary Table 5). Patients in group H (n = 27) presented a slightly higher proportion of airway involvement (59.3% vs 44.2%, p = 0.143), nasal chondritis (22.2% vs 14.4%, p = 0.268), and fever (33.3% vs 18.8%, p = 0.082); a slightly lower proportion of auricular chondritis (48.1% vs 64.1%, p = 0.111) and ocular inflammation (11.1 vs 27.1%, p = 0.095); and a significantly higher rate of deaths (25.9% vs 8.3%, p = 0.012) than group I patients (n = 181) (Figure 2E and Supplementary Table 6). Similarly, compared with group J patients (n = 53), patients in group H (n = 27) were younger (45.3 ± 12.4 years vs 51.8 ± 13.1 years), presented a slightly higher proportion of airway involvement (59.3% vs 45.3%, p = 0.247), nasal chondritis (22.2% vs 15.1%, p = 0.428), and fever (33.3% vs 18.9%, p = 0.151); a slightly lower proportion of auricular chondritis (48.1% vs 60.4%, p = 0.297), ocular inflammation (11.1 vs 24.5%, p = 0.156), and arthritis (18.5% vs 24.5%, p = 0.543); and a higher rate of deaths (25.9% vs 9.4%, p = 0.084) (Figure 2F and Supplementary Table 7). Survival The survival curve of patients with RPC with physical trauma decreased more rapidly than that of patients without. However, this difference was not statistically significant (group A vs group B, log rank test p = 0.076, Figure 3A). The survival curve of group C patients also decreased more rapidly than those of groups D and E but without a statistically significant difference (group C vs group D, log rank test p = 0.097, Figure 3b; group C vs group E, log rank test p = 0.6, Figure 3C). However, the difference between the survival curves of groups F and G (log rank test p = 0.003) and groups H and I (log rank test, p = 0.006) showed statistical significance (Figures 3D, E). Although the survival curve of group H decreased more rapidly than that of group J, this difference did not reach statistical significance (log rank test, p = 0.076, Figure 3F). Discussion The onset of RPC has been speculated to be partly attributable to physical trauma (20). However, no convincing evidence supporting this theory exists. Our study for the first time indicates that physical trauma may trigger the onset of RPC, based on the fact that more patients with RPC ever had physical trauma as well as osteochondral injuries compared with those with RA and PsA. Furthermore, the history of physical trauma was associated with more severe disease, because patients with physical trauma had a significantly higher incidence of airway involvement and lower rate of survival than those without. As far as we know, this is the first cohort study focusing on this topic. Several RPC cases triggered by auricular piercing have been reported (9, 10). However, most of our patients experienced not only auricular injury, but also injury of other chondral sites (nasal cartilage, laryngotracheal cartilage, and external auditory canal) and bones/joints, which expanded the spectrum of triggering factors. Interestingly, some of our patients underwent surgical procedures that did not affect osteochondral tissues, such as surgical intestinal tract procedures and breast, thyroid, obstetric, and ophthalmologic operations. This situation has never been reported. Our findings suggest that osteochondral and nonosteochondral injuries may be triggers of RPC. One reasonable explanation is that these injured structures share the same extracellular matrix antigens, including collagens, COMP, and matrilins (refer to the Online Supplementary Text and Supplementary Table 8), which can be induced after physical trauma, causing activation of the immune system by multiple signaling pathways as hypothesized by Carlos A. C et al. (20). Another point that should be stressed is that some traumatic events occurred many years before disease onset. This situation makes the link between physical trauma and PRC pathogenesis elusive. We postulated that these injuries may be the first strike initiating low-grade immune responses until reaching the threshold to initiate disease onset. Similar scenarios have been noted in different autoimmune inflammatory diseases, such as RA, wherein autoantibodies preceded disease onset many years ago (21, 22). However, we also found that physical trauma (osteochondral- and nonosteochondral-related diseases) peaked one year before disease onset, especially in the preceding six months, and that cartilage-related injuries more significantly increased than bone- and nonosteochondral-related injuries. The same situation occurred in RA and PsA (23,24). Physical trauma has been widely accepted to be a triggering factor of disease onset in RA and PsA (23,24), and the pathogenesis of these diseases includes the release of antigens (such as type II collagen), as well as neuropeptide substance P and deep Koebner’s phenomenon (25, 26). As such, we speculate that physical trauma may also trigger the development of RPC. Nearly two-thirds of our patients never experienced physical trauma, indicating that other triggering factors apart from physical trauma may exist. For example, infection (27, 28) and some drugs (29–32) have been reported to be associated with RPC. Our study also found that patients with physical trauma had more severe disease than those without, indicating that these two groups of patients may experience different pathogenetic processes. Therefore, our study raised another question: Why is physical trauma not associated with any sequelae in most individuals, whereas other individuals develop RPC? The answer may be genetic factors that predispose these patients to the risk of developing RPC. Identifying the genetic, and even epigenetic, differences between these two groups of patients in the future may be interesting. The limitations of the present study are derived from its retrospective nature and are inherent to all retrospective studies. These limitations may have resulted in incomplete information regarding the history of physical trauma. However, the comparison study with patients with RA and PsA made our conclusion more confident. In summary, we report that one-third of our patients ever experienced physical trauma before disease onset. This finding may confirm the triggering role of traumatic events in the pathogenesis of RPC. We believe that our article presents the first report involving a relatively large cohort focusing on this topic. And this study also expanded the spectrum of triggers of RPC. Further prospective study is needed to confirm the causal relationship between physical trauma and RPC. The pathogenesis of this disease needs to be investigated deeply to identify novel effective targets for intervention. Patients and Methods Patients This study included 208 patients with RPC who were hospitalized and followed-up by rheumatologists at our hospital between January 2008 and October 2022. RPC was diagnosed on the basis of the traditional criteria proposed by Michet et al. (12) and Damiani et al. (13). Partial and limited RPC cases were also defined as suggested by Mathew et al. (14) and our previous report (15). Patients younger than 18 years of age and those with positive antineutrophilic cytoplasmic antibodies were excluded as suggested by Piette et al. (16). The history of physical trauma was reviewed and confirmed. The sites and type of physical trauma and intervals between these events and disease onset were recorded. Additionally, demographic data, clinical manifestations, inflammatory indices, and survival data were all recorded during follow-up. Furthermore, 1134 patients with RA and 369 patients with PsA hospitalized between January 2013 and October 2022 were included as controls, and their sites and types of trauma and the intervals between these events and disease onset were recorded. All patients with RA had age > 18 years and met the American College of Rheumatology (ACR) 1987 revised criteria (17) or 2010 ACR/EULAR classification criteria (18), whereas patients with PsA fulfilled the Classification for Psoriatic Arthritis criteria (19) and had age >18 years. The incidences of physical trauma were compared between patients with RPC and RA, as well as between patients with RPC and PsA. The characteristics of RPC with and without physical trauma at different time points were also described. Definition of physical trauma Physical trauma was divided into two categories, osteochondral and nonosteochondral. Osteochondral injuries included bone/joint- and cartilage-related injuries. Injuries that led to bone fracture/joint sprain or bone surgeries were regarded as bone/joint related, whereas cartilage-related injuries referred to injuries or surgeries that led to direct damage at chondral sites. Nonosteochondral injuries referred to injuries that damaged tissues or sites other than bone, joint, or cartilage. Statistical analysis Descriptive statistics were used to describe the type of traumatic events and chronological occurrence, and all results were expressed as mean ± standard deviation or percentage (%) where appropriate. Comparisons of continuous variables were performed by using Student’s t-test. Categorical data were compared through chi-squared or Fisher’s exact test. Kaplan–Meier curves were generated to estimate survival rates by applying log-rank test. Statistical significance was defined as two-sided p < 0.05. Statistical analyses were performed by employing the SPSS version 17.0 software package (IBM). Graphs were created with Graphprism 9.0 software. Abbreviations RPC: relapsing polychondritis; ANCA: anti-neutrophilic cytoplasmic antibody; CRP: C-reactive protein Declarations Ethics approval and consent to participate This retrospective cohort study was approved by the Ethic Committee of Zhengzhou University (2023-KY-0467) and conducted in accordance with the Declaration of Helsinki. Because of the retrospective nature of this study, informed consent was waivered. Consent for publication Not applicable. Availability of data and materials. Not applicable. Competing interests. The authors declare no conflict of interest. Funding No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Acknowledgements We appreciate the constructive comments from the editors and anonymous reviewers. We also appreciate the suggestion and instruction from Dr. Xiaocan Jia from the Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University. We thank our colleagues for their assistance in data collection and analysis. Author Contributions: L.Z., X.L. and S.L. designed the study; LZ., S.Y.,W.L., Y.H., L.H.,T.L.,P.L. and X.L. collected the data; L.Z. and S.Y. analyzed data, performed statistical analysis and wrote the manuscript. All authors read and approved the final manuscript. References Mertz P, Costedoat-Chalumeau N, Ferrada MA, Moulis G, Mekinian A, Grayson PC, et al. Relapsing polychondritis: clinical updates and new differential diagnoses.Nat Rev Rheumatol. 2024 Jun;20(6):347-360. Pearson CM, Kline HM, Newcomer VD. Relapsing polychondritis. N Engl J Med. 1960;263:51-8. Mathian A, Miyara M, Cohen-Aubart F, Haroche J, Hie M, Pha M, et al. 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Tables Table 1 Comparison of frequency of traumatic events in Relapsing polychondritis, Rheumatoid Arthritis and Psoriatic Arthritis patients* RPC(n=208) RA(n=1134) PsA(n=369) P value(RPC vs RA) P value(RPC vs PsA) Any trauma Total trauma 80(38.5) 245(21.6) 76(20.6) <0.0001 <0.0001 Trauma in preceding 1 year 37(17.8) 61(5.4) 16(4.3) <0.0001 <0.0001 Trauma in preceding half a year 24(11.5) 45(4.0) 10(2.7) <0.0001 <0.0001 Osteochondral trauma Total trauma 48(23.1) 58(5.1) 24(6.5) <0.0001 <0.0001 Trauma in preceding 1 year 27(13.0) 22(1.9) 10(2.7) <0.0001 <0.0001 Trauma in preceding half a year 17(8.2) 15(1.3) 7(1.9) <0.0001 0.0003 RPC, Relapsing polychondritis,; RA, Rheumatoid Arthritis ; PsA, Psoriatic Arthritis . *Data presented as numbers(%). Table 2 Different groups according to the types of physical trauma Groups Definition Description A(n=80) Patients with physical trauma B (n=128) Patients without physical trauma C (n=48) Patients with osteochondral injuries D(n=160) patients without osteochondral injuries Including patients with non-osteochondral injuries and patients without any physical trauma E(n=32) Patients with non-osteochondral injuries Patients with non-osteochondral injuries among patients with physical trauma(Group A, n=80), Table 3 Different groups according to the types of physical trauma and whether the trauma occurred in the preceding 1 year before disease onset or not. Groups Definition Description F(n=37) Patients with physical trauma in the preceding 1 year before disease onset G(n=171) Patients without physical trauma in the preceding 1 year before disease onset including patients without physical trauma and those with physical trauma that not occurred in the preceding 1 year before disease onset H (n=27) Patients with osteochondral injuries in the preceding 1 year before disease onset I(n=181) without osteochondral injuries in the preceding 1 year before disease onset Including patients without any physical trauma, patients with non-osteochondral injuries, and patients with osteochondral injuries that not occurred in the preceding 1 year before disease onset. J(n=53) Patients without osteochondral injuries in the preceding 1 year before disease onset among patients with physical trauma(Group A, n=80) Including patients with non-osteochondral injuries and patients with osteochondral injuries that not occurred in the preceding 1year before disease onset Supplementary Files renamed916c4.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5467695","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":399605690,"identity":"5e13b0cb-3e95-44d2-86a0-af971a3ea133","order_by":0,"name":"Lei Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYBAC9gYGBmYQg4+9+QBE6AABLTwHoFrYeI4lkKpFwseASC3shx9/Lqi5Y9cmwfP54882Bjm+GwmMnwvwaeFJMzCecexZcpt07wYDyTYGY8kbCczSM/BosZfgYUjmYTuczCZzdkOCYRtD4oYbCWzMPPhsAWo5zPMPqEUi58GBxDaGemK0MDbzth22A2phbDjYxpBgQFALT5oxM2/f4QRgIBszNpyTMJx55mGzNF4toBDj+XbYnp+9+fHHH2U28nzHkw9+xqcFBhIbILQEEDM2EKEBGHJEqRoFo2AUjIKRCQBPN0dedwqjVAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-4105-0824","institution":"Zhengzhou University First Affiliated Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lei","middleName":"","lastName":"Zhang","suffix":""},{"id":399605691,"identity":"4eb51363-ab7b-45d6-a748-f3f146fd8268","order_by":1,"name":"Shuang Yun","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shuang","middleName":"","lastName":"Yun","suffix":""},{"id":399605692,"identity":"aa9505de-7d57-459d-93ed-ccdcc24495c7","order_by":2,"name":"Wei Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Li","suffix":""},{"id":399605693,"identity":"6fd7da70-882c-4a3f-b512-736429497873","order_by":3,"name":"Yujie He","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yujie","middleName":"","lastName":"He","suffix":""},{"id":399605694,"identity":"19906f05-df71-45a5-9c8c-1b4cae67d203","order_by":4,"name":"Lishuai Han","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Lishuai","middleName":"","lastName":"Han","suffix":""},{"id":399605695,"identity":"a0a15265-2dca-4087-8899-4f5935cb2e98","order_by":5,"name":"Ting Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Ting","middleName":"","lastName":"Li","suffix":""},{"id":399605696,"identity":"8cc7d23d-9c4a-4826-82b4-6c9f96cf2716","order_by":6,"name":"Peiling Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Peiling","middleName":"","lastName":"Liu","suffix":""},{"id":399605697,"identity":"d8868ab1-7da8-4cf1-9ecb-11c30aebc1cd","order_by":7,"name":"Xiaojun Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojun","middleName":"","lastName":"Liu","suffix":""},{"id":399605698,"identity":"c9648993-2087-43c5-b8fc-9cd0e89e7765","order_by":8,"name":"Shengyun Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shengyun","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-11-16 23:36:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5467695/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5467695/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73675151,"identity":"66c7fdbc-800e-4688-b5be-eced0e8625ad","added_by":"auto","created_at":"2025-01-13 13:01:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22946,"visible":true,"origin":"","legend":"\u003cp\u003eChronological order of traumatic events that occurred before RPC onset.\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5467695/v1/5ce8c5be8502d6c216c046c6.png"},{"id":73676216,"identity":"98508879-c0c5-43fd-a5cc-4d7eba82dd54","added_by":"auto","created_at":"2025-01-13 13:09:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":158633,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the characteristics between different groups of patients with RPC. For detailed data, please see Supplementary Tables 2–7.\u003c/p\u003e\n\u003cp\u003eA. Group A (n = 80) vs group B (n = 128)\u003c/p\u003e\n\u003cp\u003eB. Group C (n = 48) vs group D (n = 160)\u003c/p\u003e\n\u003cp\u003eC. Group C (n = 48) vs group E (n = 32)\u003c/p\u003e\n\u003cp\u003eD. Group F (n = 37) vs group G (n = 171)\u003c/p\u003e\n\u003cp\u003eE. Group H (n = 27) vs group I (n = 181)\u003c/p\u003e\n\u003cp\u003eF. Group H (n = 27) vs group J (n = 53)\u003c/p\u003e","description":"","filename":"fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-5467695/v1/3e2c6bbcebd5a8b0d87f77b0.png"},{"id":73675152,"identity":"9d16d7aa-57da-48c3-b03f-9027e7a703e9","added_by":"auto","created_at":"2025-01-13 13:01:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":89715,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Kaplan–Meier survival curves between different groups of patients with RPC.\u003c/p\u003e\n\u003cp\u003eA. Group A (n = 80) vs group B (n = 128)\u003c/p\u003e\n\u003cp\u003eB. Group C (n = 48) vs group D (n = 160)\u003c/p\u003e\n\u003cp\u003eC. Group C (n = 48) vs group E (n = 32)\u003c/p\u003e\n\u003cp\u003eD. Group F (n = 37) vs group G (n = 171)\u003c/p\u003e\n\u003cp\u003eE. Group H (n = 27) vs group I (n = 181)\u003c/p\u003e\n\u003cp\u003eF. Group H (n = 27) vs group J (n = 53)\u003c/p\u003e","description":"","filename":"fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-5467695/v1/b96a754eec6c166fcd6b9ffa.png"},{"id":78801415,"identity":"41ce255c-0c99-4bd4-b937-67961fef083a","added_by":"auto","created_at":"2025-03-19 06:43:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":776351,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5467695/v1/d16cdf5c-885b-47ff-9850-f29af1f05ddf.pdf"},{"id":73675153,"identity":"e8dec40c-e322-48cb-aeac-e4387b7f7aa7","added_by":"auto","created_at":"2025-01-13 13:01:02","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":858849,"visible":true,"origin":"","legend":"","description":"","filename":"renamed916c4.docx","url":"https://assets-eu.researchsquare.com/files/rs-5467695/v1/55fe9f2b19163e314f16625e.docx"}],"financialInterests":"","formattedTitle":"Can physical trauma trigger relapsing polychondritis? The first report from a Chinese cohort and comparison with rheumatoid arthritis and psoriatic arthritis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRelapsing polychondritis (RPC) is a systemic inflammatory disease primarily affecting cartilaginous tissues, including the ears, nose, larynx, tracheobronchial tree, and joints, as well as noncartilaginous tissues (1). The first case of RPC was described in 1923 by Jaksch-Wartenhorst, but little attention was given to the entity until the 1960s, when Pearson et al. introduced the name \u0026ldquo;relapsing polychondritis\u0026rdquo; (2).\u003c/p\u003e\n\u003cp\u003eThe pathogenesis of RPC remains largely unknown (1,3,4). However, RPC has been postulated to be an autoimmunity-mediated disorder and that cellular and humoral immunities are involved in its pathogenesis(1,3,4). In addition, a strong correlation exists between susceptibility to RPC and the presence of HLA-DR4 (5,6), as well as HLA-DRB1*16:02, HLA-DQB1*05:02 and HLA-B*67:01 (7) . In addition, ultra-rare damaging germline variants in DCBLD2 was reported to be associated with RPC in a recent report(8)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeanwhile, the triggers of this rare disorder are not fully characterized either. Although several case reports suggest that cartilage injury may initiate RPC (9\u0026ndash;11), solid evidence from a large case series is unavailable. In the present study, we retrospectively reviewed the history of physical trauma in patients with RPC and compared its incidence with that in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), aiming to establish an association between physical trauma and the onset of RPC.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eDemographic characteristics of patients with RPC, RA, and PsA\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 100 female patients with RPC and 108 male patients with RPC were included. These patients had an average age of 48.5 \u0026plusmn; 13.8 years at diagnosis. The median follow-up duration after diagnosis was 40 months (range 1\u0026ndash;189 months). Three patients were lost at follow-up. A total of 22 deaths occurred, and the causes of deaths were pulmonary failure associated with refractory tracheal involvement (n = 14), tracheal involvement accompanied with pulmonary infections (n = 5), brain tumor without tracheal involvement (n = 1), multiple organ failure (n = 1, with tracheal involvement), and unknown cause (n = 1, with tracheal involvement).\u003c/p\u003e\n\u003cp\u003eA total of 1134 patients with RA and 369 patients with PsA were included as controls. Among the patients with RA, 832 were female (73.4%) and 302 were male (26.6%), with 934 cases (82.4%) having moderate-to-high levels of RF and/or anti-CCP antibodies and 200 cases (17.6%) having low or normal levels of RF and anti-CCP antibodies. The average age of patients with RA was 55.1 \u0026plusmn; 12.4 years at diagnosis. Among patients with PsA, 145 (39.3%) were female; 224 (60.7%) were male; 349 (94.6%) had a history of psoriasis or family history of psoriasis; and the remaining 20 had typical signs of PsA, such as sausage finger/toe or enthesitis or psoriatic nail lesions but no history of psoriasis or family history of psoriasis. The average age at diagnosis was 42.9 \u0026plusmn; 15.1 years.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFrequency of physical trauma in patients with RPC , RA and PsA \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe proportion of patients with RPC (n = 80, 38.5%) that ever experienced physical trauma before disease onset was higher than those of patients with RA (n = 245, 21.6%, p \u0026lt; 0.0001) and patients with PsA (n = 76, 20.6%, p \u0026lt; 0.0001). The proportion of patients with RPC that experienced physical trauma the preceding year before disease onset was greater (n = 37, 17.8%) than those of patients with RA (n = 61, 5.4%, p \u0026lt; 0.0001) and patients with PsA (n = 16, 4.3%, p \u0026lt; 0.0001). This situation was also the case in the preceding half year before disease onset (Table 1).\u003c/p\u003e\n\u003cp\u003eWe also compared the incidence of osteochondral injuries in the three groups of patients. For example, 48 patients with RPC (23.1%) experienced osteochondral injuries. This incidence was considerably higher than those in patients with RA (n = 58, 5.1%, p \u0026lt; 0.0001) and patients with PsA (n = 21, 5.7%, p \u0026lt; 0.0001). In the preceding year before disease onset, 27 patients with RPC (13.0%) experienced osteochondral injuries compared with 22 patients with RA (1.9%, p \u0026lt; 0.0001) and 10 patients with PsA (2.7%, p = 0.0003). This situation was also the case in the preceding half year before disease onset (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDescription of physical trauma in patients with RPC\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAs mentioned above, 80 out of 208 patients with RPC (38.5%) had 96 traumatic events. Sixty-six patients experienced one event, 12 patients experienced two events, and two patients experienced three events.\u003c/p\u003e\n\u003cp\u003eA total of 52 osteochondral events were found in 48 patients. These events included 20 cartilage-related events (12 ENT procedures, seven teeth extractions, and one tracheotomy) and 32 bony/articular events (eight bone surgeries, 20 fracture and joint sprain, two skull surgeries, one head trauma, and one chin trauma), as well as 44 nonosteochondral events in 32 patients (13 gastrointestinal procedures, 15 obstetrical\u0026ndash;gynecological procedures, six cutaneous injuries, four percutaneous coronary interventions, three breast procedures, one thyroidectomy, one thoracic puncture, and one tympanic membrane repair).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eChronological variation of traumatic events \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe chronological order of osteochondral (including cartilage- and bone/joint-related injuries) and nonosteochondral events are shown in Figure 1 and Supplementary Table 1. The earliest traumatic events occurred 50 years before disease onset, and only occasional traumatic events occurred until one year before disease onset, at which time the events (osteochondral and nonosteochondral) increased, especially in the preceding six months. Fourteen traumatic events in 13 patients occurred between the preceding one year and half a year before disease onset, whereas 26 events in 24 patients occurred in the preceding six months. Apparently, cartilage-related events (seven ENT procedures, three teeth extractions, and one tracheotomy) increased more significantly than bone/joint related (three long bone fractures, two skull procedures, and one chin trauma) and nonosteochondral events (three gastrointestinal procedures, two obstetrical\u0026ndash;gynecological procedures, one cutaneous injury, one breast procedure, one percutaneous coronary intervention, and one tympanic membrane repair) in the preceding six months.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCharacteristics of patients with physical trauma\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients with RPC were divided into different groups in accordance with the types of physical trauma (Table 2 and 3 and Supplementary Figure 1), and their characteristics were compared.\u003c/p\u003e\n\u003cp\u003ePatients with RPC in group A (n = 80) presented similar features as those in group B (n = 128) in terms of clinical manifestations, age, gender, and mortality rate. However, group A patients had slightly more deaths, female prominence, and a higher proportion of airway involvement but a relatively lower proportion of auricular chondritis than other groups , although without a statistical significance(Figure 2A and Supplementary Table 2). Moreover, a significantly higher proportion of airway involvement (64.6% vs 40.6%, p = 0.003) and significantly lower proportion of auricular chondritis (45.8% vs 66.9%, p = 0.008) were observed in group C patients (n = 48) than in group D patients (n = 160) (Figure 2B and Supplementary Table 3). Similarly, patients in group C (n = 48) presented a higher proportion of airway involvement (64.6% vs 28.1%, p = 0.001) and relatively lower incidence of auricular chondritis (45.8% vs 71.9%, p = 0.021) than group E patients (n = 32) (Figure 2C and Supplementary Table 4).\u003c/p\u003e\n\u003cp\u003ePatients with RPC in group F (n = 37) had a slightly higher proportion of airway involvement (54.1% vs 44.4%, p = 0.22), nasal chondritis (21.6% vs 14%, p = 0.246), and fever (29.7% vs 18.7%, p = 0.134); a slightly lower proportion of auricular chondritis (51.4% vs 64.3%, p = 0.14); and a significantly higher proportion of death (24.3% vs 7.6%, p = 0.006) than group G patients (n = 171) (Figure 2D and Supplementary Table 5). Patients in group H (n = 27) presented a slightly higher proportion of airway involvement (59.3% vs 44.2%, p = 0.143), nasal chondritis (22.2% vs 14.4%, p = 0.268), and fever (33.3% vs 18.8%, p = 0.082); a slightly lower proportion of auricular chondritis (48.1% vs 64.1%, p = 0.111) and ocular inflammation (11.1 vs 27.1%, p = 0.095); and a significantly higher rate of deaths (25.9% vs 8.3%, p = 0.012) than group I patients (n = 181) (Figure 2E and Supplementary Table 6). Similarly, compared with group J patients (n = 53), patients in group H (n = 27) were younger (45.3 \u0026plusmn; 12.4 years vs 51.8 \u0026plusmn; 13.1 years), presented a slightly higher proportion of airway involvement (59.3% vs 45.3%, p = 0.247), nasal chondritis (22.2% vs 15.1%, p = 0.428), and fever (33.3% vs 18.9%, p = 0.151); a slightly lower proportion of auricular chondritis (48.1% vs 60.4%, p = 0.297), ocular inflammation (11.1 vs 24.5%, p = 0.156), and arthritis (18.5% vs 24.5%, p = 0.543); and a higher rate of deaths (25.9% vs 9.4%, p = 0.084) (Figure 2F and Supplementary Table 7). \u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSurvival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe survival curve of patients with RPC with physical trauma decreased more rapidly than that of patients without. However, this difference was not statistically significant (group A vs group B, log rank test p = 0.076, Figure 3A). The survival curve of group C patients also decreased more rapidly than those of groups D and E but without a statistically significant difference (group C vs group D, log rank test p = 0.097, Figure 3b; group C vs group E, log rank test p = 0.6, Figure 3C).\u003c/p\u003e\n\u003cp\u003eHowever, the difference between the survival curves of groups F and G (log rank test p = 0.003) and groups H and I (log rank test, p = 0.006) showed statistical significance (Figures 3D, E). Although the survival curve of group H decreased more rapidly than that of group J, this difference did not reach statistical significance (log rank test, p = 0.076, Figure 3F).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe onset of RPC has been speculated to be partly attributable to physical trauma (20). However, no convincing evidence supporting this theory exists. Our study for the first time indicates that physical trauma may trigger the onset of RPC, based on the fact that more patients with RPC ever had physical trauma as well as osteochondral injuries compared with those with RA and PsA. Furthermore, the history of physical trauma was associated with more severe disease, because patients with physical trauma had a significantly higher incidence of airway involvement and lower rate of survival than those without. As far as we know, this is the first cohort study focusing on this topic.\u003c/p\u003e\n\u003cp\u003eSeveral RPC cases triggered by auricular piercing have been reported\u0026nbsp;(9, 10). However, most of our patients experienced not only auricular injury, but also injury of other chondral sites (nasal cartilage, laryngotracheal cartilage, and external auditory canal) and bones/joints, which expanded the spectrum of triggering factors. Interestingly, some of our patients underwent surgical procedures that did not affect osteochondral tissues, such as surgical intestinal tract procedures and breast, thyroid, obstetric, and ophthalmologic operations. This situation has never been reported. Our findings suggest that osteochondral and nonosteochondral injuries may be triggers of RPC. One reasonable explanation is that these injured structures share the same extracellular matrix antigens, including collagens, COMP, and matrilins (refer to the Online Supplementary Text and Supplementary Table 8), which can be induced after physical trauma, causing activation of the immune system by multiple signaling pathways as hypothesized by Carlos A. C et al.\u0026nbsp;(20).\u003c/p\u003e\n\u003cp\u003eAnother point that should be stressed is that some traumatic events occurred many years before disease onset. This situation makes the link between physical trauma and PRC pathogenesis elusive. We postulated that these injuries may be the first strike initiating low-grade immune responses until reaching the threshold to initiate disease onset. Similar scenarios have been noted in different autoimmune inflammatory diseases, such as RA, wherein autoantibodies preceded disease onset many years ago\u0026nbsp;(21, 22).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, we also found that physical trauma (osteochondral- and nonosteochondral-related diseases) peaked one year before disease onset, especially in the preceding six months, and that cartilage-related injuries more significantly increased than bone- and nonosteochondral-related injuries. The same situation occurred in RA and PsA (23,24). Physical trauma has been widely accepted to be a triggering factor of disease onset in RA and PsA (23,24), and the pathogenesis of these diseases includes the release of antigens (such as type II collagen), as well as neuropeptide substance P and deep Koebner\u0026rsquo;s phenomenon (25, 26). As such, we speculate that physical trauma may also trigger the development of RPC.\u003c/p\u003e\n\u003cp\u003eNearly two-thirds of our patients never experienced physical trauma, indicating that other triggering factors apart from physical trauma may exist. For example, infection (27, 28) and some drugs (29\u0026ndash;32)\u0026nbsp;have been reported to be associated with RPC. Our study also found that patients with physical trauma had more severe disease than those without, indicating that these two groups of patients may experience different pathogenetic processes. Therefore, our study raised another question: Why is physical trauma not associated with any sequelae in most individuals, whereas other individuals develop RPC? The answer may be genetic factors that predispose these patients to the risk of developing RPC. Identifying the genetic, and even epigenetic, differences between these two groups of patients in the future may be interesting.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe limitations of the present study are derived from its retrospective nature and are inherent to all retrospective studies. These limitations may have resulted in incomplete information regarding the history of physical trauma. However, the comparison study with patients with RA and PsA made our conclusion more confident.\u003c/p\u003e\n\u003cp\u003eIn summary, we report that one-third of our patients ever experienced physical trauma before disease onset. This finding may confirm the triggering role of traumatic events in the pathogenesis of RPC. We believe that our article presents the first report involving a relatively large cohort focusing on this topic. And this study also expanded the spectrum of triggers of RPC. Further prospective study is needed to confirm the causal relationship between physical trauma and RPC. The pathogenesis of this disease needs to be investigated deeply to identify novel effective targets for intervention.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study included 208 patients with RPC who were hospitalized and followed-up by rheumatologists at our hospital between January 2008 and October\u0026nbsp;2022. RPC was diagnosed on the basis of the traditional criteria proposed by Michet et al. (12) and Damiani et al. (13). Partial and limited RPC cases were also defined as suggested by Mathew et al. (14) and our previous report (15). Patients younger than 18 years of age and those with positive antineutrophilic cytoplasmic antibodies were excluded as suggested by Piette et al. (16). The history of physical trauma was reviewed and confirmed. The sites and type of physical trauma and intervals between these events and disease onset were recorded. Additionally, demographic data, clinical manifestations, inflammatory indices, and survival data were all recorded during follow-up. Furthermore, 1134 patients with RA and 369 patients with PsA hospitalized between January 2013 and October 2022 were included as controls, and their sites and types of trauma and the intervals between these events and disease onset were recorded. All patients with RA had age \u0026gt; 18 years and met the American College of Rheumatology (ACR) 1987 revised criteria (17) or 2010 ACR/EULAR classification criteria (18), whereas patients with PsA fulfilled the Classification for Psoriatic Arthritis criteria (19) and had age \u0026gt;18 years. The incidences of physical trauma were compared between patients with RPC and RA, as well as between patients with RPC and PsA. The characteristics of RPC with and without physical trauma at different time points were also described.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDefinition of physical trauma\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePhysical trauma was divided into two categories, osteochondral and nonosteochondral. Osteochondral injuries included bone/joint- and cartilage-related injuries. Injuries that led to bone fracture/joint sprain or bone surgeries were regarded as bone/joint related, whereas cartilage-related injuries referred to injuries or surgeries that led to direct damage at chondral sites. Nonosteochondral injuries referred to injuries that damaged tissues or sites other than bone, joint, or cartilage.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were used to describe the type of traumatic events and chronological occurrence, and all results were expressed as mean \u0026plusmn; standard deviation or percentage (%) where appropriate. Comparisons of continuous variables were performed by using Student\u0026rsquo;s t-test. Categorical data were compared through chi-squared or Fisher\u0026rsquo;s exact test. Kaplan\u0026ndash;Meier curves were generated to estimate survival rates by applying log-rank test. Statistical significance was defined as two-sided p \u0026lt; 0.05. Statistical analyses were performed by employing the SPSS version 17.0 software package (IBM). Graphs were created with Graphprism 9.0 software.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRPC: relapsing polychondritis; ANCA: anti-neutrophilic cytoplasmic antibody; CRP: C-reactive protein\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort study was approved by the Ethic Committee of Zhengzhou University (2023-KY-0467) and conducted in accordance with the Declaration of Helsinki. Because of the retrospective nature of this study, informed consent was waivered.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the constructive comments from the editors and anonymous reviewers. We also appreciate the suggestion and instruction from Dr. Xiaocan Jia from the Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University. We thank our colleagues for their assistance in data collection and analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Author Contributions:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eL.Z., X.L. and S.L. designed the study; LZ., S.Y.,W.L., Y.H., L.H.,T.L.,P.L. and X.L. collected the data; L.Z. and S.Y. analyzed data, performed statistical analysis and wrote the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMertz P, Costedoat-Chalumeau N, Ferrada MA, Moulis G, Mekinian A, Grayson PC, et al. Relapsing polychondritis: clinical updates and new differential diagnoses.Nat Rev Rheumatol. 2024 Jun;20(6):347-360.\u003c/li\u003e\n\u003cli\u003ePearson CM, Kline HM, Newcomer VD. Relapsing polychondritis. N Engl J Med. 1960;263:51-8.\u003c/li\u003e\n\u003cli\u003eMathian A, Miyara M, Cohen-Aubart F, Haroche J, Hie M, Pha M, et al. Relapsing polychondritis: A 2016 update on clinical features, diagnostic tools, treatment and biological drug use. Best Pract Res Clin Rheumatol. 2016;30:316-33.\u003c/li\u003e\n\u003cli\u003eRednic S, Damian L, Talarico R, Scire CA, Tobias A, Costedoat-Chalumeau N, et al. Relapsing polychondritis: state of the art on clinical practice guidelines. RMD Open. 2018;4(Suppl 1):e000788.\u003c/li\u003e\n\u003cli\u003eZeuner M, Straub RH, Rauh G, Albert ED, Scholmerich J, Lang B. Relapsing polychondritis: clinical and immunogenetic analysis of 62 patients. J Rheumatol. 1997;24:96-101.\u003c/li\u003e\n\u003cli\u003eLang, B. et al. Susceptibility to relapsing polychondritis is associated with HLA-DR4.Arthritis Rheum. 1993;36, 660\u0026ndash;664\u003c/li\u003e\n\u003cli\u003eTerao C, Yoshifuji H, Yamano Y, Kojima H, Yurugi K, Miura Y, et al.Genotyping of relapsing polychondritis identified novel susceptibility HLA alleles and distinct genetic characteristics from other rheumatic diseases . Rheumatology (Oxford). 2016 Sep;55(9):1686-92.\u003c/li\u003e\n\u003cli\u003eLuo, Y. et al. Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study. Ann. Rheum. Dis. 83, 253\u0026ndash;260 (2024).\u003c/li\u003e\n\u003cli\u003eAlissa H, Kadanoff R, Adams E. Does mechanical insult to cartilage trigger relapsing polychondritis? Scand J Rheumatol. 2001;30:311.\u003c/li\u003e\n\u003cli\u003eSerratrice J, Ene N, Granel B, Disdier P, deRoux-Serratrice C, Swiader L, et al. Severe relapsing polychondritis occurring after ear piercing. J Rheumatol. 2003;30:2716-7.\u003c/li\u003e\n\u003cli\u003eCanas CA, Gomez AR, Echeverri AF, Quintana-Duque MA, Toro CE, Iglesias-Gamarra A. Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena. Rheumatol Int. 2012;32:541-3.\u003c/li\u003e\n\u003cli\u003eMichet CJ, Jr., McKenna CH, Luthra HS, O\u0026apos;Fallon WM. Relapsing polychondritis. Survival and predictive role of early disease manifestations. Ann Intern Med. 1986;104:74-8.\u003c/li\u003e\n\u003cli\u003eDamiani JM, Levine HL. Relapsing polychondritis--report of ten cases. Laryngoscope. 1979;89:929-46.\u003c/li\u003e\n\u003cli\u003eMathew SD, Battafarano DF, Morris MJ. Relapsing polychondritis in the Department of Defense population and review of the literature. Semin Arthritis Rheum. 2012;42:70-83.\u003c/li\u003e\n\u003cli\u003eZhang L, Wu TG, He YJ, Guo JY, Han LS, Lu JM, et al. Diagnosing relapsing polychondritis remains a common challenge: experience from a Chinese retrospective cohort. Clin Rheumatol. 2020.\u003c/li\u003e\n\u003cli\u003ePiette JC, Dion J, Costedoat-Chalumeau N. News on Relapsing Polychondritis: The Patient\u0026apos;s Experience. Arthritis Care Res (Hoboken). 2018;70:1121-3.\u003c/li\u003e\n\u003cli\u003eArnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum.1988;31:315-24. \u003c/li\u003e\n\u003cli\u003eAletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum.2010;62:2569\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eTaylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54:2665-73. \u003c/li\u003e\n\u003cli\u003eCanas CA, Bonilla Abadia F. Local cartilage trauma as a pathogenic factor in autoimmunity (one hypothesis based on patients with relapsing polychondritis triggered by cartilage trauma). Autoimmune Dis. 2012;2012:453698.\u003c/li\u003e\n\u003cli\u003eNielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004;50:380-6.\u003c/li\u003e\n\u003cli\u003eSokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One. 2012;7:e35296.\u003c/li\u003e\n\u003cli\u003eAl-Allaf AW, Sanders PA, Ogston SA, Marks JS.A case-control study examining the role of physical trauma in the onset of rheumatoid arthritis.Rheumatology (Oxford). 2001 Mar;40(3):262-6. \u003c/li\u003e\n\u003cli\u003eThorarensen SM, Lu N, Ogdie A, Gelfand JM, Choi HK, LoveTJ. Physical trauma recorded in primary care is associated with the onset of psoriatic arthritis among patients with psoriasis.Ann Rheum Dis. 2017 Mar;76(3):521-525. \u003c/li\u003e\n\u003cli\u003ePunzi L, Galozzi P, Luisetto R, et al. Post- traumatic arthritis: overview on pathogenic mechanisms and role of inflammation. RMD Open 2016;2:e000279. \u003c/li\u003e\n\u003cli\u003eOlivieri I, Padula A, D\u0026apos;Angelo S, Scarpa R.Role of trauma in psoriatic arthritis. J Rheumatol. 2008 Nov;35(11):2085-7.\u003c/li\u003e\n\u003cli\u003eHerrera I, Concha R, Molina EG, Schiff ER, Altman RD. Relapsing polychondritis, chronic hepatitis C virus infection, and mixed cryoglobulemia. Semin Arthritis Rheum. 2004;33:388-403.\u003c/li\u003e\n\u003cli\u003eMenge T, Rzepka R, Melchers I. Monoclonal autoantibodies from patients with autoimmune diseases: specificity, affinity and crossreactivity of MAbs binding to cytoskeletal and nucleolar epitopes, cartilage antigens and mycobacterial heat-shock protein 60. Immunobiology. 2002;205:1-16.\u003c/li\u003e\n\u003cli\u003eHernandez MV, Ruiz-Esquide V, Gomez-Caballero ME, Gomez-Puerta JA, Canete JD, Sanmarti R. Relapsing polychondritis: a new adverse event secondary to the use of tumour necrosis factor antagonists? Rheumatology (Oxford). 2011;50:1523-5.\u003c/li\u003e\n\u003cli\u003eFurer V, Wieczorek RL, Pillinger MH. Bilateral pinna chondritis preceded by glucosamine chondroitin supplement initiation. Scand J Rheumatol. 2011;40:241-3.\u003c/li\u003e\n\u003cli\u003eMutoh T, Chikamatsu S, Sasaki T, Seino H, Sakamoto K, Kudo M. Relapsing Polychondritis following PD-1 Blockade by an Immune Checkpoint Inhibitor. JMA J. 2023 Oct 16;6(4):552-555. \u003c/li\u003e\n\u003cli\u003eOgimoto T, Yoshida H, Mizuta M, Hirai, T. Relapsing polychondritis after treatment with PD-1 blockade. Invest. New Drugs 2022;40:389\u0026ndash;391.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 Comparison of frequency of traumatic events in Relapsing polychondritis, Rheumatoid Arthritis and Psoriatic Arthritis patients*\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"945\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003eRPC(n=208)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003eRA(n=1134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003ePsA(n=369)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003eP value(RPC vs RA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003eP value(RPC vs PsA)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003eAny trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Total trauma \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e80(38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e245(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e76(20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma in preceding 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e37(17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e61(5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e16(4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma in preceding half a year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e24(11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e45(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e10(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003eOsteochondral trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Total trauma \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e48(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e58(5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e24(6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma in preceding 1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e27(13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e22(1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e10(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 304px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Trauma in preceding half a year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e17(8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e15(1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e7(1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 170px;\"\u003e\n \u003cp\u003e0.0003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRPC,\u0026nbsp;Relapsing polychondritis,; RA, Rheumatoid Arthritis ; PsA, Psoriatic Arthritis .\u003c/p\u003e\n\u003cp\u003e*Data presented as numbers(%). \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 \u0026nbsp; Different groups according to the types of physical trauma\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eDefinition\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eDescription\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eA(n=80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients with physical trauma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eB (n=128)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients without physical trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eC (n=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients with osteochondral injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eD(n=160)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003epatients without osteochondral injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eIncluding patients with non-osteochondral injuries and patients without any physical trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eE(n=32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients with non-osteochondral injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003ePatients with non-osteochondral injuries among patients with physical trauma(Group A, n=80),\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 \u0026nbsp; Different groups according to the types of physical trauma and whether the trauma occurred in the preceding 1 year before disease onset or not.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eDefinition\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eDescription\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eF(n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients with physical trauma in the preceding 1 year before disease onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eG(n=171)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients without physical trauma in the preceding 1 year before disease onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eincluding patients without physical trauma and those with physical trauma that not occurred in the preceding 1 year before disease onset\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eH (n=27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients with osteochondral injuries in the preceding 1 year before disease onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eI(n=181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ewithout osteochondral injuries in the preceding 1 year before disease onset\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eIncluding patients without any physical trauma, patients with non-osteochondral injuries, and patients with osteochondral injuries that not occurred in the preceding 1 year before disease onset.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eJ(n=53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePatients without osteochondral injuries in the preceding 1 year before disease onset among patients with physical trauma(Group A, n=80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 548px;\"\u003e\n \u003cp\u003eIncluding patients with non-osteochondral injuries and patients with osteochondral injuries that not occurred in the preceding 1year before disease onset\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Relapsing polychondritis, physical trauma, triggers","lastPublishedDoi":"10.21203/rs.3.rs-5467695/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5467695/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe triggers of relapsing polychondritis (RPC) are not fully characterized. This study was performed to explore the association between physical trauma and RPC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe history of physical trauma of 208 patients with RPC from a Chinese cohort was reviewed and compared with that of 1134 patients with rheumatoid arthritis (RA) and 369 patients with psoriatic arthritis (PsA). The characteristics and survival of patients with physical trauma were analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEighty patients with RPC (38.5%) ever had physical trauma. This number is considerably higher than that of patients with RA (21.6%, p \u0026lt; 0.0001) and PsA (20.6%, p \u0026lt; 0.0001). A total of 48 patients with RPC (23.1%) had 52 osteochondral injuries, whereas only 58 patients with RA (5.1%, p \u0026lt; 0.0001) and 21 patients with PsA (5.7%, p \u0026lt; 0.0001) ever had osteochondral injuries. We found that more patients with RPC experienced any type of physical trauma, as well as osteochondral trauma, in the preceding one year , and also half a year, before disease onset than patients with RA and PsA. Traumatic events (osteochondral and nonosteochondral) increased in the preceding one year before disease onset, especially in the preceding six months. Patients with osteochondral trauma that occurred at any time before disease onset had a higher rate of airway involvement and lower rates of survival than those without osteochondral trauma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings suggest that physical trauma may be triggers of RPC, and that patients with osteochondral trauma seem to have more severe disease than those without.\u003c/p\u003e","manuscriptTitle":"Can physical trauma trigger relapsing polychondritis? The first report from a Chinese cohort and comparison with rheumatoid arthritis and psoriatic arthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-13 13:00:57","doi":"10.21203/rs.3.rs-5467695/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4f36fec4-637e-4f0a-9b81-35279dff9779","owner":[],"postedDate":"January 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-19T06:35:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-13 13:00:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5467695","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5467695","identity":"rs-5467695","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}