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Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis
  1. Andrea Di Matteo1,2,
  2. Kulveer Mankia1,3,
  3. Laurence Duquenne1,3,
  4. Edoardo Cipolletta2,
  5. Richard J Wakefield1,3,
  6. Leticia Garcia-Montoya1,3,
  7. Jacqueline Leong Nam1,3,
  8. Paul Emery1,3
  1. 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  2. 2 Clinica Reumatologica, Polytechnic University of Marche, Ancona, Marche, Italy
  3. 3 NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK
  1. Correspondence to Professor Paul Emery, University of Leeds Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds LS7 4SA, UK; p.emery{at}


Objectives To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA).

Methods Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400).

Results BE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p<0.01). A significant correlation between BE and US synovitis in the MTP5 joints was detected (Cramer’s V=0.37, p<0.01). The OR for the development of IA (ever) was highest for the following: BE in >1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01).

Conclusions In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis.

  • ultrasonography
  • early rheumatoid arthritis
  • ant-CCP
  • rheumatoid arthritis

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  • Handling editor Josef S Smolen

  • Contributors ADM was one of the clinicians of the study, collected and analysed the data and wrote the manuscript. KM was one of the clinicians of the study, contributed to design the study, helped with data analysis and write the manuscript. LD, LG-M and JLN were clinicians of the study and collected the data. EC and RJW analysed the data and helped to write the manuscript. PE designed the study, helped to analyse the data and write the manuscript.

  • Funding The study was supported by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (grant number: IS-BRC-1215-20015).

  • Competing interests This study was conducted while ADM was an ARTICULUM Fellow. KM reports personal fees from AbbVie, UCB and Eli Lilly, outside the submitted work. RJW has received honoraria from AbbVie, Novartis and GE for ultrasound-related educational activities. PE reports consultant fees from BMS, AbbVie, MSD, Pfizer, Novartis and Roche, outside the submitted work. He also reports research grants from UCB, AbbVie, BMS, Pfizer, MSD and Roche, outside the submitted work.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the 'Materials and methods' section for further details.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the NHS Health Research Authority National Research Ethics Service Committee Yorkshire & the Humber—Leeds West.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No additional data are available from this study.