Skip to main content

Advertisement

SpringerLink
Log in

Serum VEGF-C as an evaluation marker of disease activity in adult-onset Still's disease

  • Observational Research
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

In view of the possible involvement of vascular endothelial growth factor-C (VEGF-C) in pathogenesis of adult-onset Still's disease (AOSD) based on our previous genome-wide association study (GWAS) results, the primary objective of this study, therefore, was to investigate the correlations between the content of VEGF-C in serum and clinical and biochemical markers of AOSD. Blood samples were collected from 80 patients with AOSD, 26 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE) and 31 healthy control subjects. The serum VEGF-C levels were determined using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis and comparisons were conducted. A significantly higher serum VEGF-C level was observed in patients with AOSD than in HC. Serum VEGF-C levels had high AUC value of 0.8145 for distinguishing AOSD group from healthy group with sensitivity of 0.7097 and specificity of 0.8250. It also showed good diagnostic value to differentiate AOSD from other autoinflammatory diseases with sensitivity of 0.7500 and specificity of 0.5500. AOSD patients with fever, arthralgia, skin rash, sore throat, lymphadenopathy, splenomegaly hepatomegaly and pleuritis, had a higher level than those who did not have these symptoms (p = 0.0012, p = 0.0092, p = 0.0056, p = 0.0123, p = 0.0068, p = 0.0030, p = 0.0020, and p = 0.0018, respectively). The serum VEGF-C levels were also positively correlated with laboratory features and several cytokines related to AOSD disease activity. In conclusion, our study unveiled a close association between serum VEGF-C levels and AOSD including disease activity and clinical hematological manifestations, suggesting the potential utility of VEGF-C as a candidate biomarker to assess disease activity in AOSD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ANOVA:

One-way analysis of variance

AOSD:

Adult-onset Still's disease

AUC:

Area under the curve

CRP:

C-reactive protein

DMARDs:

Disease-modifying anti-rheumatic drugs

ELISA:

Enzyme-linked immunosorbent assay

ESR:

Erythrocyte sedimentation rate

FLS:

Fibroblast-like synoviocytes

GD:

Graves’ diseases

GWAS:

Genome-wide association study

HC:

Healthy control

HLA:

Human leukocyte antigen

HT:

Hashimoto's thyroiditis

LDH:

Lactate dehydrogenase

NSAIDs:

Non-steroidal anti-inflammatory drugs

ROC:

Receiver operating characteristic

TNF:

Tumor necrosis factor

VEGF-C:

Vascular endothelial growth factor-C

References

  1. Gerfaud-Valentin M, Jamilloux Y, Iwaz J (2014) Adult-onset Still’s disease. Autoimmun Rev 13(7):708–722. https://doi.org/10.1016/j.autrev.2014.01.058

    Article  CAS  PubMed  Google Scholar 

  2. Fautrel B (2008) Adult-onset Still disease. Best Pract Res Clin Rheumatol 22(5):773–792. https://doi.org/10.1016/j.berh.2008.08.006

    Article  PubMed  Google Scholar 

  3. Feist E, Mitrovic S, Fautrel B (2018) Mechanisms, biomarkers and targets for adult-onset Still’s disease. Nat Rev Rheumatol 14(10):603–618. https://doi.org/10.1038/s41584-018-0081-x

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wouters JM, Reekers P, van de Putte LB (1986) Adult-onset Still’s disease. Disease course and HLA associations. Arthritis Rheum 29(3):415–418. https://doi.org/10.1002/art.1780290316

    Article  CAS  PubMed  Google Scholar 

  5. Miller ML, Aaron S, Jackson J, Fraser P, Cairns L, Hoch S, Borel Y, Larson M, Glass DN (1985) HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis. Arthritis Rheum 28(2):146–150. https://doi.org/10.1002/art.1780280207

    Article  CAS  PubMed  Google Scholar 

  6. Asano T, Furukawa H, Sato S, Yashiro M, Kobayashi H, Watanabe H, Suzuki E, Ito T, Ubara Y, Kobayashi D, Iwanaga N, Izumi Y, Fujikawa K, Yamasaki S, Nakamura T, Koga T, Shimizu T, Umeda M, Nonaka F, Yasunami M, Ueki Y, Eguchi K, Tsuchiya N, Tohma S, Yoshiura KI, Ohira H, Kawakami A, Migita K (2017) Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease. Arthritis Res Ther 19(1):199. https://doi.org/10.1186/s13075-017-1406-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fujita Y, Furukawa H, Asano T, Sato S, Yashiro Furuya M, Kobayashi H, Watanabe H, Suzuki E, Koga T, Shimizu T, Ueki Y, Eguchi K, Tsuchiya N, Kawakami A, Migita K (2019) HLA-DQB1 DPB1 alleles in Japanese patients with adult-onset Still’s disease. Mod Rheumatol 29(5):843–847. https://doi.org/10.1080/14397595.2018.1514999

    Article  CAS  PubMed  Google Scholar 

  8. Li ZQ, Liu HL, Chen JH, Zeng T, He L, Li MH, Luo CN, Liu S, Ding TT, Yimaiti K, Teng JL, Li XW, Ding YH, Cheng XB, Zhou J, Ye JN, Ji J, Su YT, Shi H, Sun Y, Gao CW, Hu QY, Chi HH, Yuan X, Zhou ZC, Wang D, Wang K, Li CG, Sun YC, Niu YJ, Chen LJ, Xu J, Wu LJ, Zhou ZW, Pan D, Niu HT, Shi YY, Yang CD (2020) Both HLA class I and II regions identified as genome-wide significant susceptibility loci for adult-onset Still’s disease in Chinese individuals. Ann Rheum Dis 79(1):161. https://doi.org/10.1136/annrheumdis-2019-215239

    Article  PubMed  Google Scholar 

  9. Secker GA, Harvey NL (2021) Regulation of VEGFR signalling in lymphatic vascular development and disease: an update. Int J Mol Sci 22(14):7760. https://doi.org/10.3390/ijms22147760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhan H, Li H, Liu C, Cheng L, Yan S, Li Y (2021) Association of Circulating Vascular Endothelial Growth Factor Levels with Autoimmune Diseases: a systematic review and meta-analysis. Front Immunol 12:674343. https://doi.org/10.3389/fimmu.2021.674343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen HK, Zhang TY, Gong BL, Cao XH (2015) Association between VEGF-634G/C polymorphism and susceptibility to autoimmune diseases: a meta-analysis. Gene 558(2):181–186. https://doi.org/10.1016/j.gene.2015.01.023

    Article  CAS  PubMed  Google Scholar 

  12. Jia W, Wu W, Yang D, Xiao C, Huang M, Long F, Su Z, Qin M, Liu X, Zhu YZ (2018) GATA4 regulates angiogenesis and persistence of inflammation in rheumatoid arthritis. Cell Death Dis 9(5):503. https://doi.org/10.1038/s41419-018-0570-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Abdel-Maged AE, Gad AM, Wahdan SA, Azab SS (2019) Efficacy and safety of Ramucirumab and methotrexate co-therapy in rheumatoid arthritis experimental model: Involvement of angiogenic and immunomodulatory signaling. Toxicol Appl Pharmacol 380:114702. https://doi.org/10.1016/j.taap.2019.114702

    Article  CAS  PubMed  Google Scholar 

  14. Shushanov S, Bronstein M, Adelaide J, Jussila L, Tchipysheva T, Jacquemier J, Stavrovskaya A, Birnbaum D, Karamysheva A (2000) VEGFc and VEGFR3 expression in human thyroid pathologies. Int J Cancer 86(1):47–52. https://doi.org/10.1002/(sici)1097-0215(20000401)86:1%3c47::aid-ijc7%3e3.0.co;2-r

    Article  CAS  PubMed  Google Scholar 

  15. Kumpers P, David S, Haubitz M, Hellpap J, Horn R, Brocker V, Schiffer M, Haller H, Witte T (2009) The Tie2 receptor antagonist angiopoietin 2 facilitates vascular inflammation in systemic lupus erythematosus. Ann Rheum Dis 68(10):1638–1643. https://doi.org/10.1136/ard.2008.094664

    Article  CAS  PubMed  Google Scholar 

  16. Li Y, Yang B, Bai JY, Xia S, Mao M, Li X, Li N, Chen L (2019) The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis. Int Immunopharmacol 73:362–369. https://doi.org/10.1016/j.intimp.2019.05.024

    Article  CAS  PubMed  Google Scholar 

  17. Cheng CW, Wu CZ, Tang KT, Fang WF, Lin JD (2020) Simultaneous measurement of twenty-nine circulating cytokines and growth factors in female patients with overt autoimmune thyroid diseases. Autoimmunity 53(5):261–269. https://doi.org/10.1080/08916934.2020.1755965

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T et al (1992) Preliminary criteria for classification of adult Still’s disease. J Rheumatol 19(3):424–430

    CAS  PubMed  Google Scholar 

  19. Rau M, Schiller M, Krienke S, Heyder P, Lorenz H, Blank N (2010) Clinical manifestations but not cytokine profiles differentiate adult-onset Still’s disease and sepsis. J Rheumatol 37(11):2369–2376. https://doi.org/10.3899/jrheum.100247

    Article  CAS  PubMed  Google Scholar 

  20. Girard C, Rech J, Brown M, Allali D, Roux-Lombard P, Spertini F, Schiffrin EJ, Schett G, Manger B, Bas S, Del Val G, Gabay C (2016) Elevated serum levels of free interleukin-18 in adult-onset Still’s disease. Rheumatology 55(12):2237–2247. https://doi.org/10.1093/rheumatology/kew300

    Article  CAS  PubMed  Google Scholar 

  21. Meng J, Chi H, Wang Z, Zhang H, Sun Y, Teng J, Hu Q, Liu H, Cheng X, Ye J, Shi H, Wu X, Jia J, Wang M, Ma Y, Zhou Z, Wang F, Liu T, Wan L, Qiao X, Chen X, Yang C, Su Y (2021) Characteristics and risk factors of relapses in patients with adult-onset still’s disease: a long-term cohort study. Rheumatology. https://doi.org/10.1093/rheumatology/keab023

    Article  PubMed  PubMed Central  Google Scholar 

  22. Grievink HW, Luisman T, Kluft C, Moerland M, Malone KE (2016) Comparison of Three Isolation Techniques for Human Peripheral Blood Mononuclear Cells: Cell Recovery and Viability, Population Composition, and Cell Functionality. Biopreserv Biobank 14(5):410–415. https://doi.org/10.1089/bio.2015.0104

    Article  CAS  PubMed  Google Scholar 

  23. Wongpiyabovorn J, Yooyongsatit S, Ruchusatsawat K, Avihingsanon Y, Hirankarn N (2008) Association of the CTG (-2578/-460/+405) haplotype within the vascular endothelial growth factor gene with early-onset psoriasis. Tissue Antigens 72(5):458–463. https://doi.org/10.1111/j.1399-0039.2008.01134.x

    Article  CAS  PubMed  Google Scholar 

  24. Sugiura T, Kawaguchi Y, Harigai M, Terajima-Ichida H, Kitamura Y, Furuya T, Ichikawa N, Kotake S, Tanaka M, Hara M, Kamatani N (2002) Association between adult-onset Still’s disease and interleukin-18 gene polymorphisms. Genes Immun 3(7):394–399. https://doi.org/10.1038/sj.gene.6363922

    Article  CAS  PubMed  Google Scholar 

  25. Kawaguchi Y, Terajima H, Harigai M, Hara M, Kamatani N (2001) Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still’s disease. Arthritis Rheum 44(7):1716–1717. https://doi.org/10.1002/1529-0131(200107)44:7%3c1716::Aid-Art298%3e3.0.Co;2-I

    Article  CAS  PubMed  Google Scholar 

  26. Hoshino T, Ohta A, Yang D, Kawamoto M, Kikuchi M, Inoue Y, Kamizono S, Ota T, Itoh K, Oizumi K (1998) Elevated serum interleukin 6, interferon-gamma, and tumor necrosis factor-alpha levels in patients with adult Still’s disease. J Rheumatol 25(2):396–398

    CAS  PubMed  Google Scholar 

  27. Chen DY, Lan JL, Lin FJ, Hsieh TY, Wen MC (2004) Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still’s disease. Ann Rheum Dis 63(10):1300–1306. https://doi.org/10.1136/ard.2003.013680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Koga T, Sumiyoshi R, Furukawa K, Sato S, Migita K, Shimizu T, Umeda M, Endo Y, Fukui S, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Nonaka F, Yachie A, Kondo H, Maeda T, Kawakami A (2020) Interleukin-18 and fibroblast growth factor 2 in combination is a useful diagnostic biomarker to distinguish adult-onset Still’s disease from sepsis. Arthritis Res Ther 22(1):108. https://doi.org/10.1186/s13075-020-02200-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. MacDonald IJ, Liu SC, Su CM, Wang YH, Tsai CH, Tang CH (2018) Implications of angiogenesis involvement in arthritis. Int J Mol Sci 19(7):2012. https://doi.org/10.3390/ijms19072012

    Article  PubMed Central  Google Scholar 

  30. Osada M, Imaoka S, Funae Y (2004) Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha protein. FEBS Lett 575(1–3):59–63. https://doi.org/10.1016/j.febslet.2004.08.036

    Article  CAS  PubMed  Google Scholar 

  31. Wauke K, Nagashima M, Ishiwata T, Asano G, Yoshino S (2002) Expression and localization of vascular endothelial growth factor-C in rheumatoid arthritis synovial tissue. J Rheumatol 29(1):34–38

    CAS  PubMed  Google Scholar 

  32. Paavonen K, Mandelin J, Partanen T, Jussila L, Li TF, Ristimaki A, Alitalo K, Konttinen YT (2002) Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium. J Rheumatol 29(1):39–45

    CAS  PubMed  Google Scholar 

  33. Cha HS, Bae EK, Koh JH, Chai JY, Jeon CH, Ahn KS, Kim J, Koh EM (2007) Tumor necrosis factor-alpha induces vascular endothelial growth factor-C expression in rheumatoid synoviocytes. J Rheumatol 34(1):16–19

    PubMed  Google Scholar 

  34. Bouta EM, Bell RD, Rahimi H, Xing LP, Wood RW, Bingham CO, Ritchlin CT, Schwarz EM (2018) Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis. Nat Rev Rheumatol 14(2):94–106. https://doi.org/10.1038/nrrheum.2017.205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Palazon A, Tyrakis PA, Macias D, Velica P, Rundqvist H, Fitzpatrick S, Vojnovic N, Phan AT, Loman N, Hedenfalk I, Hatschek T, Lovrot J, Foukakis T, Goldrath AW, Bergh J, Johnson RS (2017) An HIF-1alpha/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression. Cancer Cell 32(5):669-683.e665. https://doi.org/10.1016/j.ccell.2017.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D (1990) Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172(6):1535–1545. https://doi.org/10.1084/jem.172.6.1535

    Article  CAS  PubMed  Google Scholar 

  37. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676. https://doi.org/10.1038/nm0603-669

    Article  CAS  Google Scholar 

  38. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25. https://doi.org/10.1210/edrv.18.1.0287

    Article  CAS  PubMed  Google Scholar 

  39. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ (1996) Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271(2):736–741. https://doi.org/10.1074/jbc.271.2.736

    Article  CAS  PubMed  Google Scholar 

  40. Kwon YW, Kwon KS, Moon HE, Park JA, Choi KS, Kim YS, Jang HS, Oh CK, Lee YM, Kwon YG, Lee YS, Kim KW (2004) Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT. J Invest Dermatol 123(1):152–158. https://doi.org/10.1111/j.0022-202X.2004.22735.x

    Article  CAS  PubMed  Google Scholar 

  41. Malaguarnera L, Imbesi R, Di Rosa M, Scuto A, Castrogiovanni P, Messina A, Sanfilippo S (2005) Action of prolactin, IFN-gamma, TNF-alpha and LPS on heme oxygenase-1 expression and VEGF release in human monocytes/macrophages. Int Immunopharmacol 5(9):1458–1469. https://doi.org/10.1016/j.intimp.2005.04.002

    Article  CAS  PubMed  Google Scholar 

  42. Valter MM, Wiestler OD, Pietsche T (1999) Differential control of VEGF synthesis and secretion in human glioma cells by IL-1 and EGF. Int J Dev Neurosci 17(5–6):565–577. https://doi.org/10.1016/s0736-5748(99)00048-9

    Article  CAS  PubMed  Google Scholar 

  43. McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A (2015) Type I interferons in infectious disease. Nat Rev Immunol 15(2):87–103. https://doi.org/10.1038/nri3787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Boxx GM, Cheng G (2016) The Roles of Type I Interferon in Bacterial Infection. Cell Host Microbe 19(6):760–769. https://doi.org/10.1016/j.chom.2016.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hall JC, Rosen A (2010) Type I interferons: crucial participants in disease amplification in autoimmunity. Nat Rev Rheumatol 6(1):40–49. https://doi.org/10.1038/nrrheum.2009.237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Postal M, Vivaldo JF, Fernandez-Ruiz R, Paredes JL, Appenzeller S, Niewold TB (2020) Type I interferon in the pathogenesis of systemic lupus erythematosus. Curr Opin Immunol 67:87–94. https://doi.org/10.1016/j.coi.2020.10.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ning F, Li X, Yu L, Zhang B, Zhao Y, Liu Y, Zhao B, Shang Y, Hu X (2019) Hes1 attenuates type I IFN responses via VEGF-C and WDFY1. J Exp Med 216(6):1396–1410. https://doi.org/10.1084/jem.20180861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the patients who were involved in the study.

Funding

This research was funded by National Natural Science Foundation of China (81502016).

Author information

Author notes

  1. Xia Chen and Qiong-yi Hu contributed equally.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China

    Xia Chen, Qiong-yi Hu, Mengyan Wang, Jinchao Jia, Jialin Teng, Yue Sun, Xiaobing Cheng, Junna Ye, Yutong Su, Hui Shi, Huihui Chi, Zhuochao Zhou, Tingting Liu, Zhihong Wang, Liyan Wan, Xin Qiao, Fan Wang, Xinyao Wu, Chengde Yang & Hong-Lei Liu

Authors
  1. Xia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiong-yi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mengyan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinchao Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jialin Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaobing Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Junna Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yutong Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hui Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Huihui Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zhuochao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tingting Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Zhihong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Liyan Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Xin Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Fan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Xinyao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Chengde Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Hong-Lei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, CY and HLL; data curation, XC and QH; formal analysis, HLL; methodology, QH; project administration, HLL; resources, MW, JJ, JT, YS, XC, JY, YS, HS, HC, ZZ, TL, ZW, LW, XQ, FW and XW; supervision, CY and HLL; writing original draft, XC and QH.

Corresponding authors

Correspondence to Chengde Yang or Hong-Lei Liu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical statement

The studies involving human participants were reviewed and approved by the Institutional Research Ethics Committee of Ruijin Hospital (identifier 2016–62), Shanghai, China. The patients/participants provided their written informed consent to participate in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Hu, Qy., Wang, M. et al. Serum VEGF-C as an evaluation marker of disease activity in adult-onset Still's disease. Rheumatol Int 42, 149–157 (2022). https://doi.org/10.1007/s00296-021-04978-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-021-04978-1

Keywords

Search

Navigation