EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO)

Yongdong Zhao¹, Melissa S Oliver², Anja Schnabel³, Eveline Y Wu⁴, Zhaoyi Wang⁵, Achille Marino⁶, Cassyanne L Aguiar⁷, Jonathan D Akikusa⁸, Ummusen Kaya Akca⁹, Beverley Almeida¹⁰, Simone Appenzeller¹¹, Erin Balay-Dustrude⁵, Ozge Basaran¹², Matthew L Basiaga¹³, Yelda Bilginer⁹, David A Cabral¹⁴, Martina Capponi¹⁵, Nathan Donaldson¹⁶, Bugra Han Egeli¹⁷, Emily J Fox¹⁸, Antonella Insalaco¹⁹, Ramesh S Iyer²⁰, Annette F Jansson²¹, Inna Kostik²², Mikhail Kostik²³, Leonard K Kovalick⁴, Katia Tomie Kozu²⁴, Sivia K Lapidus²⁵, Tzielan C Lee²⁶, Aleksander Lenert²⁷, Kamran Mahmood¹⁰, Edoardo Marrani²⁸, Doaa Mosad Mosa²⁹, Ian Muse⁵, Alexander Mushkin³⁰, Katherine D Nowicki¹⁶, Farzana Nuruzzaman³¹, Karen Onel³², Manuela Pardeo¹⁹, Trang Sophia Pham⁵, Lauren Potts³³, Athimalaipet V Ramanan³⁴, Angelo Ravelli³⁵, Nathan D Rogers¹⁶, Andrew W Grim³⁶, Micol Romano³⁷, Natalie Rosenwasser⁵, Takashi Shawn Sato³⁸, Gabriele Simonini²⁸, Jennifer B Soep¹⁶, Sara M Stern³⁹, Timmy Strauss³, Angela Taneja Kohli⁴⁰, Alexander C Theos⁴¹, Lori B Tucker¹⁴, Leslie F Vogel⁴², Shima Yasin⁴³, Stephen C Wong⁵, Katerina Bouchalova⁴⁴, Alison M Hendry⁴⁵, Kevin C Cain⁴⁶, Hermann J Girschick⁴⁷, Fatma Dedeoglu¹⁷, Christian M Hedrich⁴⁸, Ronald M Laxer⁴⁹, Polly J Ferguson⁴³, Raymond Naden⁵⁰, Seza Ozen⁹

Affiliations

¹ Pediatric Rheumatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: yongdong.zhao@seattlechildrens.org.
² Division of Pediatric Rheumatology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ Division of Pediatric Rheumatology, Department of Pediatrics, The University of North Carolina at Chapel Hill, NC, USA.
⁵ Pediatric Rheumatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
⁶ Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy.
⁷ Division of Pediatric Rheumatology, Department of Pediatrics, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, VA, USA.
⁸ Rheumatology service, Department of General Medicine, Royal Children's Hospital, Melbourne, VIC, Australia.
⁹ Hacettepe University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey.
¹⁰ Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK.
¹¹ Department of Orthopedics, Rheumatology and Traumatology, School of Medical Science, University of Campinas, Brazil.
¹² Hacettepe University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey; Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA.
¹³ Division of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁴ BC Children's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹⁵ Department of Maternal Sciences and Urological Sciences, Sapienza University of Rome, Rome, Italy.
¹⁶ University of Colorado School of Medicine, Aurora, CO, USA.
¹⁷ Division of Immunology, Rheumatology Program, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁸ Division of Pediatric Rheumatology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO, USA.
¹⁹ Division of Rheumatology, ERN RITA Center, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
²⁰ Pediatric Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
²¹ Division of Pediatric Rheumatology and Immunology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
²² Sanatorium for children 'Detskie Duny', Saint-Petersburg, Russia.
²³ Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russia.
²⁴ Pediatric Rheumatology Unit, Instituto da Criança e do Adolescente, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
²⁵ Pediatric Rheumatology Division, Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center and Hackensack Meridian School of Medicine, Hackensack, NJ, USA.
²⁶ Division of Pediatric Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
²⁷ Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
²⁸ Rheumatology Unit, ERN ReCONNET Center, Meyer Children's Hospital IRCCS, Firenze, Italy.
²⁹ Rheumatology Department, Mansoura University Hospitals, Mansoura University Faculty of Medicine, Mansoura, Egypt.
³⁰ Science-Research Institute of Phthisiopulmonology, Saint-Petersburg, Russia.
³¹ Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
³² Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA.
³³ Patient Research Partner, CA, USA.
³⁴ Bristol Royal Hospital for Children & Translational Health Sciences, University of Bristol, Bristol, UK.
³⁵ IRCCS Istituto Giannina Gaslini and Università degli Studi di Genova, Genoa, Italy.
³⁶ Division of Pediatric Rheumatology, Department of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
³⁷ Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy; Department of Pediatrics, Division of Pediatric Rheumatology, Behcet and Autoinflammatory Disease Center, Western University, London, ON, Canada.
³⁸ Stead Family Children's Hospital, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
³⁹ University of Utah, Salt Lake City, UT, USA.
⁴⁰ Emory University School of Medicine/Children's Healthcare of Atlanta, GA, USA.
⁴¹ Patient/parent partner, Georgetown University, Washington, DC, USA.
⁴² Department of Rehabilitation Seattle Children's Hospital, Seattle, WA, USA.
⁴³ Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
⁴⁴ Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic.
⁴⁵ General Medicine and Rheumatology Service, Division of Medicine, Middlemore Hospital Counties Manukau District Health, Auckland, New Zealand.
⁴⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁴⁷ Department of Pediatrics, Vivantes Clinic Friedrichshain, Berlin, Germany.
⁴⁸ Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK; Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
⁴⁹ The Hospital for Sick Children, St. Michael's Hospital and the University of Toronto, ON, Canada.
⁵⁰ Auckland City Hospital, Auckland, New Zealand.

PMID: 39966038
DOI: 10.1016/j.ard.2024.11.006

Free article

EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO)

Yongdong Zhao et al. Ann Rheum Dis. 2025 Sep.

Free article

. 2025 Sep;84(9):1458-1468.

doi: 10.1016/j.ard.2024.11.006. Epub 2025 Jan 30.

Authors

Affiliations

¹ Pediatric Rheumatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: yongdong.zhao@seattlechildrens.org.
² Division of Pediatric Rheumatology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ Division of Pediatric Rheumatology, Department of Pediatrics, The University of North Carolina at Chapel Hill, NC, USA.
⁵ Pediatric Rheumatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
⁶ Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy.
⁷ Division of Pediatric Rheumatology, Department of Pediatrics, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, VA, USA.
⁸ Rheumatology service, Department of General Medicine, Royal Children's Hospital, Melbourne, VIC, Australia.
⁹ Hacettepe University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey.
¹⁰ Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK.
¹¹ Department of Orthopedics, Rheumatology and Traumatology, School of Medical Science, University of Campinas, Brazil.
¹² Hacettepe University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey; Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA.
¹³ Division of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁴ BC Children's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹⁵ Department of Maternal Sciences and Urological Sciences, Sapienza University of Rome, Rome, Italy.
¹⁶ University of Colorado School of Medicine, Aurora, CO, USA.
¹⁷ Division of Immunology, Rheumatology Program, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁸ Division of Pediatric Rheumatology, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO, USA.
¹⁹ Division of Rheumatology, ERN RITA Center, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
²⁰ Pediatric Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
²¹ Division of Pediatric Rheumatology and Immunology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
²² Sanatorium for children 'Detskie Duny', Saint-Petersburg, Russia.
²³ Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russia.
²⁴ Pediatric Rheumatology Unit, Instituto da Criança e do Adolescente, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
²⁵ Pediatric Rheumatology Division, Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center and Hackensack Meridian School of Medicine, Hackensack, NJ, USA.
²⁶ Division of Pediatric Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
²⁷ Division of Immunology, Department of Internal Medicine, Carver College of Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
²⁸ Rheumatology Unit, ERN ReCONNET Center, Meyer Children's Hospital IRCCS, Firenze, Italy.
²⁹ Rheumatology Department, Mansoura University Hospitals, Mansoura University Faculty of Medicine, Mansoura, Egypt.
³⁰ Science-Research Institute of Phthisiopulmonology, Saint-Petersburg, Russia.
³¹ Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
³² Division of Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA.
³³ Patient Research Partner, CA, USA.
³⁴ Bristol Royal Hospital for Children & Translational Health Sciences, University of Bristol, Bristol, UK.
³⁵ IRCCS Istituto Giannina Gaslini and Università degli Studi di Genova, Genoa, Italy.
³⁶ Division of Pediatric Rheumatology, Department of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA.
³⁷ Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy; Department of Pediatrics, Division of Pediatric Rheumatology, Behcet and Autoinflammatory Disease Center, Western University, London, ON, Canada.
³⁸ Stead Family Children's Hospital, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
³⁹ University of Utah, Salt Lake City, UT, USA.
⁴⁰ Emory University School of Medicine/Children's Healthcare of Atlanta, GA, USA.
⁴¹ Patient/parent partner, Georgetown University, Washington, DC, USA.
⁴² Department of Rehabilitation Seattle Children's Hospital, Seattle, WA, USA.
⁴³ Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
⁴⁴ Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, Olomouc, Czech Republic.
⁴⁵ General Medicine and Rheumatology Service, Division of Medicine, Middlemore Hospital Counties Manukau District Health, Auckland, New Zealand.
⁴⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁴⁷ Department of Pediatrics, Vivantes Clinic Friedrichshain, Berlin, Germany.
⁴⁸ Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK; Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
⁴⁹ The Hospital for Sick Children, St. Michael's Hospital and the University of Toronto, ON, Canada.
⁵⁰ Auckland City Hospital, Auckland, New Zealand.

PMID: 39966038
DOI: 10.1016/j.ard.2024.11.006

Abstract

Objectives: To develop and validate classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR).

Methods: This international initiative had 4 phases: (1) candidate items were proposed in a survey of paediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients.

Results: The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anaemia, C-reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort.

Conclusions: These new classification criteria for paediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.

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Conflict of interest statement

Competing interests YZ: ACR, EULAR, CARRA (Grants to Institution, Finance Committee), Bristol-Myer Squibbs (Grants to Institution), Rheumatology Research Foundation (Grants to Institution), CTIP (Grants to Institution), UpToDate CRMO/CNO (Royalties/Licence), Novartis (Consulting Fees to Self), U.S. Provisional Application No. 63/356977 (Patent Issued), Seattle Children's CRMO Warriors Guild (Leadership/Fiduciary Role), American Board of Pediatrics, Pediatric Rheumatology Subboard (Leadership/Fiduciary Role). Melissa SO: CARRA (AF-Small Grants from 2022 to 2024, Total: $48,399.00). AS: EULAR (Fellow with Funding of €15,000.00, Grants or Contracts). JDA: Novartis (Participation on Advisory Board 2023). MLB: Sjogren Foundation (Grants to Institution), Childhood Arthritis and Rheumatology Research Alliance (Grants to Institution). SKL: Time Hearst Foundation Physician Scientist Award (Grants), ACR (Support for Attending Meetings), Hackensack Meridian Health (Support for Attending Meetings), CARRA PFAPA/Autoinflammatory (Work Group Leader), APMC (Pediatrics Committee). TCL: Crohns & Colitis Congress Talk 2024 (Honoraria for Self, Support for Travel), Packard Children's Health Alliance Board of Directors (Board Member, Unpaid), Lupus Foundation of Northern California (Board Member, Unpaid). AL: National Institution of Health Award Number K23AR082966 (Grants to Institution). TSS: Invicro (Consulting Fees to Institution), Hippo Education (Payment to Self). GS: Sobi (Consulting Fees), Novartis (Consulting Fees), AbbVie (Consulting Fees, Payment/Honoraria). LBT: Cassie & Friends Society (Board Member, Unpaid). LFV: Trinds 2022-2025 (Contract for Trials, Payment to Self), Wolters Kluwer 2021 (Payment for Authorship to Self), Scholar Rock 2024 (Support for Travel). SC-YW: Arthritis Foundation Great West Region (Medical Advisory Board, Unpaid), Aicardi Goutieres Syndrome Advocacy Association (ECHO Faculty, Unpaid). KB: Czech Ministry of Health (DRO FNOl, 00098892, Support for the Manuscript). AMH: Seattle Children's Research Institute (Support for the Manuscript, Consulting Fees). FD: UpToDate (Royalties or Licences), ISSAID (Support for Attending Meetings in 2023, Education Committee Chair). CMH: Merck (Unrestricted Research Grant), Novartis (Unrestricted Research Grant Ended in 2022, Advisory Board on the Use of IL-1 blockers in CNO). RML: UpToDate (Royalties or Licences), Elsevier (Royalties or Licences), Sanofi (Consulting Fees to Institution, Participation on Board), Eli Lilly Canada (Consulting Fees to Self, Participation on Board), Sobi (Consulting Fees to Self), Novartis (Consulting Fees to Self, Participation on Board), Akros Pharma (Consulting Fees to Self), Children's Hospital of Philadelphia (Participation on Board). PJF: American Board of Pediatrics (Chair, Payment or Honoraria to Self), Pediatric Rheumatology Subcommittee (Chair, Payment or Honoraria to Self), Current Opinion in Rheumatology Section Editor (Payment or Honoraria to Self), CARRA (Support for Travel), CNO Meeting in Liverpool 2022 (Support for Travel), PRES Invited Speaker 2022 (Support for Travel). RN: ACR/EULAR Development for Classification for Anti-Phospholipid Syndrome and IgG4-Related Diseases (Consulting Fees), Genentech Development of Pediatric Glucocorticoid Toxicity Index (Consulting Fees, Support for Travel). SO: Novartis (Consulting Fees), Sobi (Consulting Fees). Eveline Yawei Wu, ZW, AM, CLA, UKA, BA, SA, EEB-D, OB, YB, DAC, MC, ND, BHE, EF, AI, RSI, AFJ, IK, MK, LKK, KTK, KM, EM, DMM, IM, AM, KDN, FN, KO, MP, TSP, LP, AVR, AR, NDR, AWG, MR, NR, JBS, SMS, TS, ATK, ACT, SY, KCC, and HJG have no conflicts of interest to disclose.

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EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO)

Affiliations

EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO)

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Research Materials