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Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study
  1. Georgios Filippou1,2,
  2. Anna Scanu3,
  3. Antonella Adinolfi4,
  4. Carmela Toscano5,
  5. Dario Gambera6,
  6. Raquel Largo7,
  7. Esperanza Naredo8,
  8. Emilio Calvo9,
  9. Gabriel Herrero-Beaumont8,
  10. Pascal Zufferey10,
  11. Christel Madelaine Bonjour10,
  12. Daryl K MacCarter11,
  13. Stanley Makman11,
  14. Zachary Weber11,
  15. Fabiana Figus12,
  16. Ingrid Möller13,
  17. Marwin Gutierrez14,
  18. Carlos Pineda14,
  19. Denise Clavijo Cornejo14,
  20. Hector Garcia14,
  21. Victor Ilizaliturri14,
  22. Jaime Mendoza Torres14,
  23. Raul Pichardo14,
  24. Luis Carlos Rodriguez Delgado14,
  25. Emilio Filippucci15,
  26. Edoardo Cipolletta15,
  27. Teodora Serban16,
  28. Catalin Cirstoiu16,
  29. Florentin Ananu Vreju17,
  30. Dan Grecu17,
  31. Gaël Mouterde18,
  32. Marcello Govoni1,
  33. Leonardo Punzi19,
  34. Nemanja S Damjanov20,21,
  35. Helen Isobel Keen22,
  36. George AW Bruyn23,
  37. Lene Terslev24,
  38. Maria-Antonietta D'Agostino25,26,
  39. Carlo Alberto Scirè1,
  40. Annamaria Iagnocco12
  1. 1 Section of Rheumatology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
  2. 2 Rheumatology Department, Luigi Sacco University Hospital, Milano, Italy
  3. 3 Department of Medicine-DIMED, Rheumatology Unit, University of Padova, Padova, Italy
  4. 4 Rheumatology Department, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
  5. 5 Rheumatology Department, Azienda Ospedaliera Regionale San Carlo, Potenza, Italy
  6. 6 Orthopedics Department, Rugani Hospital, Monteriggioni, Italy
  7. 7 Joint and Bone Research Unit, Rheumatology Department, IIS-Fundacion Jimenez Diaz, Madrid, Spain
  8. 8 Department of Rheumatology and Joint and Bone Research Unit, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain
  9. 9 Department of Orthopaedic Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
  10. 10 Rheumatology Department, University of Lausanne, CHUV, Lausanne, Switzerland
  11. 11 Rheumatology Department, North Valley Hospital, Whitefish, Montana, USA
  12. 12 Rheumatology Unit, Department of Clinical and Biological Sciences, Università degli Studi di Torino, Torino, Italy
  13. 13 Rheumatology, Instituto Poal de Reumatologia, Barcelona, Spain
  14. 14 Rheumatology Department, Instituto Nacional de Rehabilitacion, Mexico, Mexico
  15. 15 Rheumatology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
  16. 16 Rheumatology Department, Carol Davila University, Bucharest, Romania
  17. 17 Rheumatology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania
  18. 18 Rheumatology, University of Montpellier, Montpellier, France
  19. 19 Department of Medicine, Ospedale SS Giovanni e Paolo Venezia, Venezia, Italy
  20. 20 Rheumatology, University of Belgrade School of Medicine, Belgrade, Serbia
  21. 21 Institute of Rheumatology, University of Belgrade, Belgrade, Serbia
  22. 22 Medicine and Pharmacology Department, The University of Western Australia, Murdoch, Perth, Australia
  23. 23 Department of Rheumatology, Reumakliniek Lelystad, Lelystad, The Netherlands
  24. 24 Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University, Copenhagen, Denmark
  25. 25 Infection et inflammation, Laboratory of Excellence INFLAMEX, Université Paris-Saclay, Montigny-Le-Bretonneux, France
  26. 26 Rheumatology, Ambroise Paré Hospital, Boulogne-Billancourt, France
  1. Correspondence to Dr Georgios Filippou, Rheumatology Department, Via Giovanni Battista Grassi, 74, 20157 Milano, Italy; gf.filippou{at}


Objective To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard.

Methods Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0–3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other’s findings.

Results 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%—sensitivity of 91% (range 71%–87% in single sites) and specificity of 59% (range 68%–92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation.

Conclusion Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

  • ultrasonography
  • chondrocalcinosis
  • osteoarthritis
  • knee

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  • Handling editor Josef S Smolen

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  • Contributors Substantial contributions in planning the work: all authors. Substantial contributions in conducting the work: GF, AS, AA, CT, DG, RL, EN, EC, GH-B, PZ, CMB, DKM, SM, ZW, FF, MG, CP, DCC, HG, VI, JMT, RP, LCRD, EF, EC, TS, CC, FAV, DG, GM, AI. Substantial contributions in reporting the work: all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the local Ethics Committee of the University of Ferrara (principal investigator site, study number 171190 approved on 17 December 2017) and subsequently by local ethics committees of all the participating centres.

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

  • Data availability statement Data are available upon reasonable request. Data of the paper are deidentified participant data and are available upon request to the correspondent author.