EULAR 2025 classification criteria for haemochromatosis arthropathy

Patrick Dw Kiely¹, Stephanie Finzel², Bayram Farisogullari³, Graeme J Carroll⁴, Geraldine McCarthy⁵, John Stack⁶, Simone Parisi⁷, Graça Porto⁸, Pascal Richette⁹, Gyorgy Nagy¹⁰, Marton Weidl¹¹, Ann Rosenthal¹², Pascal Guggenbuhl¹³, Katarzyna J Banaszkiewicz¹⁴, Svenja Engelhardt¹⁵, Jeremy D Shearman¹⁶, David Mitchell¹⁷, Jane Barker¹⁸, Valerie Brueton¹⁸, Barbara Butzeck¹⁹, Philip Coathup¹⁸, Howard Don²⁰, Jacqueline Dowsett¹⁸, Marie Duncan¹⁸, Tracey Dunleavy¹⁸, Ian Fish¹⁸, Allin Hoggarth¹⁸, Mark McKinnon¹⁸, James Minter¹⁸, Tim Osborne¹⁸, Marguerite Smith¹⁸, Christine Wright¹⁸, Pedro M Machado²¹

Affiliations

¹ Department of Rheumatology, St George's University Hospitals NHS Foundation Trust, London, UK; Institute of Medical and Biomedical Education, City St George's, University of London, London, UK. Electronic address: Patrick.kiely@nhs.net.
² Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
³ Department of Neuromuscular Diseases, University College London, London, UK.
⁴ Department of Rheumatology, Fremantle and Fiona Stanley Hospitals, Perth, Australia.
⁵ Division of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine, University College Dublin, Dublin, Ireland.
⁶ Division of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
⁷ Rheumatology Unit, Department of General and Specialist Medicine, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
⁸ Centro Hospitalar Universitário de Santo António, Unidade Local de Saúde de Santo António, Porto, Portugal.
⁹ Université de Paris, AP-HP Lariboisière, Service de Rhumatologie, Paris, France.
¹⁰ Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary; Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
¹¹ Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary.
¹² Department of Medicine, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA.
¹³ Univ Rennes, INSERM, Inrae, CHU Rennes, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France; Rheumatology Department, Rennes University Hospital, Rennes, France.
¹⁴ Outpatients Endocrinology Clinic, University Clinical Center in Gdańsk, Gdańsk, Poland.
¹⁵ Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Department of Internal Medicine, Cardiology, Klinikum Freising, Germany.
¹⁶ Department of Gastroenterology, South Warwickshire University Foundation Trust and Warwick Medical School, Warwick, UK.
¹⁷ Clongriffin Medical Centre, Dublin, Ireland.
¹⁸ Patient Research Partners.
¹⁹ Patient Research Partners; European Federation of Associations of Patients with Haemochromatosis, Croissy-sur-Seine, France.
²⁰ Patient Research Partners; Haemochromatosis International, Barnstaple, Devon, UK.
²¹ Department of Neuromuscular Diseases, University College London, London, UK; National Institute for Health Research, University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK; Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK.

PMID: 41193334
DOI: 10.1016/j.ard.2025.10.003

Free article

EULAR 2025 classification criteria for haemochromatosis arthropathy

Patrick Dw Kiely et al. Ann Rheum Dis. 2025.

Free article

. 2025 Nov 4:S0003-4967(25)04434-6.

doi: 10.1016/j.ard.2025.10.003. Online ahead of print.

Authors

Affiliations

¹ Department of Rheumatology, St George's University Hospitals NHS Foundation Trust, London, UK; Institute of Medical and Biomedical Education, City St George's, University of London, London, UK. Electronic address: Patrick.kiely@nhs.net.
² Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
³ Department of Neuromuscular Diseases, University College London, London, UK.
⁴ Department of Rheumatology, Fremantle and Fiona Stanley Hospitals, Perth, Australia.
⁵ Division of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine, University College Dublin, Dublin, Ireland.
⁶ Division of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
⁷ Rheumatology Unit, Department of General and Specialist Medicine, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
⁸ Centro Hospitalar Universitário de Santo António, Unidade Local de Saúde de Santo António, Porto, Portugal.
⁹ Université de Paris, AP-HP Lariboisière, Service de Rhumatologie, Paris, France.
¹⁰ Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary; Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
¹¹ Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary.
¹² Department of Medicine, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA.
¹³ Univ Rennes, INSERM, Inrae, CHU Rennes, Institut NuMeCan (Nutrition, Metabolisms and Cancer), Rennes, France; Rheumatology Department, Rennes University Hospital, Rennes, France.
¹⁴ Outpatients Endocrinology Clinic, University Clinical Center in Gdańsk, Gdańsk, Poland.
¹⁵ Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Department of Internal Medicine, Cardiology, Klinikum Freising, Germany.
¹⁶ Department of Gastroenterology, South Warwickshire University Foundation Trust and Warwick Medical School, Warwick, UK.
¹⁷ Clongriffin Medical Centre, Dublin, Ireland.
¹⁸ Patient Research Partners.
¹⁹ Patient Research Partners; European Federation of Associations of Patients with Haemochromatosis, Croissy-sur-Seine, France.
²⁰ Patient Research Partners; Haemochromatosis International, Barnstaple, Devon, UK.
²¹ Department of Neuromuscular Diseases, University College London, London, UK; National Institute for Health Research, University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK; Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK.

PMID: 41193334
DOI: 10.1016/j.ard.2025.10.003

Abstract

Objectives: This study aims to develop classification criteria for haemochromatosis arthropathy (HA).

Methods: A task force was convened per European Alliance of Associations for Rheumatology standardised operating procedures, including physicians experienced in genetic haemochromatosis and its arthropathy and patient research partners. Candidate classification criteria items were selected via systematic literature review, consensus, and Delphi process. Derivation cohorts of patients with C282Y homozygous HFE gene mutation, joint pain, and iron loading, along with disease mimics (primary generalised osteoarthritis or calcium pyrophosphate deposition disease), were recruited from routine care and assessed against candidate items. Group comparison and diagnostic performance analyses identified variables with the greatest discriminatory capacity. A subset of these variables, agreed upon by consensus (considering both statistical results and the HA disease construct), was modelled using multivariable logistic regression and receiver operating characteristic curve analysis to develop classification criteria models. The final model was agreed upon through discussion, voting, and consensus, taking both statistical performance and disease Gestalt (face validity) into account.

Results: A derivation cohort of 154 patients with HA and 120 patients with disease mimics was recruited. A point-based classification model was developed using 8 variables covering age of symptom onset, clinical, and radiographic features at the metacarpophalangeal, distal interphalangeal, and ankle joints, and surgery of hips or ankles. A score ≥5 out of 11 provides 93.3% specificity and 71.4% sensitivity for classifying HA.

Conclusions: An international multicentre task force has developed the first classification criteria for HA from a unique derivation cohort using rigorous methodology. Criteria should be used to include patients in research studies and await external validation in separate cohorts.

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Conflict of interest statement

Competing interests PK has received consulting/speaker’s fees from Alphasigma/Galapagos, Eli Lilly and Novartis, all unrelated to this work. SF has received consulting/speaker’s fees from Abbvie, Alphasigma/Galapagos, AstraZeneca, Biotest, Celltrion, Janssen/J&J, Novartis, NovoNordisk and UCB, all unrelated to this work. PM has received consulting/speaker’s fees from Abbvie, Bristol Myers Squibb, Celgene, Eli Lilly, Alphasigma/Galapagos, Greywolf, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this work.

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EULAR 2025 classification criteria for haemochromatosis arthropathy

Affiliations

EULAR 2025 classification criteria for haemochromatosis arthropathy

Authors

Affiliations

Abstract

Conflict of interest statement

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