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08-01-2025 | Osteoarthrosis | Review Article

Imaging and management of calcium pyrophosphate deposition disease

Authors: Wasim Issa, Ronald Mercer, Janeth Yinh, Ali Guermazi, Mohamed Jarraya

Published in: Skeletal Radiology

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Abstract

The radiological manifestations of calcium pyrophosphate deposition (CPPD) revolve around two main axes: the asymptomatic form and CPPD disease. The latter is a consequence of an immune response to calcium phosphate crystals. Chondrocalcinosis is broadly considered the radiographic manifestation of CPPD regardless of whether it is asymptomatic or associated with inflammatory arthritis. CPPD is associated with osteoarthritis although the direction of such association is still unclear. Apart from the detection of CPP crystals in synovial fluid, imaging (mainly conventional radiography and increasingly ultrasound) plays a central role in the diagnosis of CPPD disease. Recently, CT has been added as a diagnostic tool, especially in deep anatomic locations such as crowned dens. To date, no treatment is effective in dissolving CPP crystals. For now, the focus of current treatment strategies remains inflammation control. Our aim is to review the epidemiology, pathogenesis, and clinical and imaging manifestations of asymptomatic and symptomatic CPPD. We will also discuss recent consensus definitions and classifications of CPPD disease.
Literature
1.
go back to reference Kohn NN. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the ‘pseudogout syndrome’: II. Identification of Crystals Ann Intern Med. 1962;56:738.PubMedCrossRef Kohn NN. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the ‘pseudogout syndrome’: II. Identification of Crystals Ann Intern Med. 1962;56:738.PubMedCrossRef
2.
go back to reference Jarraya M, Roemer F, Kwoh CK, Guermazi A. Crystal arthropathies and osteoarthritis—where is the link? Skeletal Radiol. 2023;52:2037–43.PubMedCrossRef Jarraya M, Roemer F, Kwoh CK, Guermazi A. Crystal arthropathies and osteoarthritis—where is the link? Skeletal Radiol. 2023;52:2037–43.PubMedCrossRef
3.
4.
go back to reference Neame RL. UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte. Ann Rheum Dis. 2003;62:513–8.PubMedPubMedCentralCrossRef Neame RL. UK community prevalence of knee chondrocalcinosis: evidence that correlation with osteoarthritis is through a shared association with osteophyte. Ann Rheum Dis. 2003;62:513–8.PubMedPubMedCentralCrossRef
5.
go back to reference Felson DT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly. Framingham Study Arthritis Rheum. 1997;40:728–33.PubMedCrossRef Felson DT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly. Framingham Study Arthritis Rheum. 1997;40:728–33.PubMedCrossRef
6.
go back to reference Jarraya M, et al. Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study. Osteoarthritis Cartilage. 2023;31:1111–20.PubMedPubMedCentralCrossRef Jarraya M, et al. Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study. Osteoarthritis Cartilage. 2023;31:1111–20.PubMedPubMedCentralCrossRef
7.
go back to reference Ramonda R, et al. Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. (PROgetto Veneto Anziani) study. Clin Exp Rheumatol. 2009;27:981–4.PubMed Ramonda R, et al. Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. (PROgetto Veneto Anziani) study. Clin Exp Rheumatol. 2009;27:981–4.PubMed
8.
go back to reference Salaffi, F., De Angelis, R., Grassi, W., MArche Pain Prevalence, & INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol 2005; 23, 819–828 Salaffi, F., De Angelis, R., Grassi, W., MArche Pain Prevalence, & INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol 2005; 23, 819–828
10.
go back to reference terminology and diagnosis. Zhang, W. et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I. Ann Rheum Dis. 2011;70:563–70.CrossRef terminology and diagnosis. Zhang, W. et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I. Ann Rheum Dis. 2011;70:563–70.CrossRef
11.
go back to reference Cowley S, McCarthy G. Diagnosis and treatment of calcium pyrophosphate deposition (CPPD) disease: a review. Open Access Rheumatol Res Rev. 2023;15:33–41. Cowley S, McCarthy G. Diagnosis and treatment of calcium pyrophosphate deposition (CPPD) disease: a review. Open Access Rheumatol Res Rev. 2023;15:33–41.
12.
go back to reference Cipolletta E, et al. Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints. Rheumatology. 2022;61:3997–4005.PubMedCrossRef Cipolletta E, et al. Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints. Rheumatology. 2022;61:3997–4005.PubMedCrossRef
13.
go back to reference Gibilisco PA, Schumacher HR, Hollander JL, Soper KA. Synovial fluid crystals in osteoarthritis. Arthritis Rheum. 1985;28:511–5.PubMedCrossRef Gibilisco PA, Schumacher HR, Hollander JL, Soper KA. Synovial fluid crystals in osteoarthritis. Arthritis Rheum. 1985;28:511–5.PubMedCrossRef
14.
go back to reference Nalbant S, et al. Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. Osteoarthritis Cartilage. 2003;11:50–4.PubMedCrossRef Nalbant S, et al. Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies. Osteoarthritis Cartilage. 2003;11:50–4.PubMedCrossRef
15.
go back to reference Pattrick M, Hamilton E, Wilson R, Austin S, Doherty M. Association of radiographic changes of osteoarthritis, symptoms, and synovial fluid particles in 300 knees. Ann Rheum Dis. 1993;52:97–103.PubMedPubMedCentralCrossRef Pattrick M, Hamilton E, Wilson R, Austin S, Doherty M. Association of radiographic changes of osteoarthritis, symptoms, and synovial fluid particles in 300 knees. Ann Rheum Dis. 1993;52:97–103.PubMedPubMedCentralCrossRef
16.
17.
go back to reference Flores DV, Mejía Gómez C, Pathria MN. Layered approach to the anterior knee: normal anatomy and disorders associated with anterior knee pain. RadioGraphics. 2018;38:2069–101.PubMedCrossRef Flores DV, Mejía Gómez C, Pathria MN. Layered approach to the anterior knee: normal anatomy and disorders associated with anterior knee pain. RadioGraphics. 2018;38:2069–101.PubMedCrossRef
18.
go back to reference Brower AC, Flemming DJ. Arthritis in Black and White. Philadelphia: Elsevier Saunders; 2012 Brower AC, Flemming DJ. Arthritis in Black and White. Philadelphia: Elsevier Saunders; 2012
20.
go back to reference Yayama T, et al. Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings. Clin Rheumatol. 2008;27:597–604.CrossRef Yayama T, et al. Calcium pyrophosphate crystal deposition in the ligamentum flavum of degenerated lumbar spine: histopathological and immunohistological findings. Clin Rheumatol. 2008;27:597–604.CrossRef
21.
go back to reference Ehioghae M, Lawlor MC, Mesfin A. Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine – a review of the literature. Surg Neurol Int. 2022;13:470.PubMedPubMedCentralCrossRef Ehioghae M, Lawlor MC, Mesfin A. Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine – a review of the literature. Surg Neurol Int. 2022;13:470.PubMedPubMedCentralCrossRef
22.
go back to reference Markiewitz AD, Boumphrey FR, Bauer TW, Bell GR. Calcium pyrophosphate dihydrate crystal deposition disease as a cause of lumbar canal stenosis. Spine. 1996;21:506–11.PubMedCrossRef Markiewitz AD, Boumphrey FR, Bauer TW, Bell GR. Calcium pyrophosphate dihydrate crystal deposition disease as a cause of lumbar canal stenosis. Spine. 1996;21:506–11.PubMedCrossRef
23.
go back to reference Moon AS, Mabry S, Pittman JL. Calcium pyrophosphate deposition disease of the cervical and thoracolumbar spine: a report of two cases. North Am Spine Soc J. 2020;3:100026. Moon AS, Mabry S, Pittman JL. Calcium pyrophosphate deposition disease of the cervical and thoracolumbar spine: a report of two cases. North Am Spine Soc J. 2020;3:100026.
24.
go back to reference Godfrin-Valnet M, et al. Eighteen cases of crowned dens syndrome: presentation and diagnosis. Neurochirurgie. 2013;59:115–20.PubMedCrossRef Godfrin-Valnet M, et al. Eighteen cases of crowned dens syndrome: presentation and diagnosis. Neurochirurgie. 2013;59:115–20.PubMedCrossRef
26.
go back to reference Liu YJ, et al. Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis. Mod Pathol. 2021;34:1373–83.PubMedCrossRef Liu YJ, et al. Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis. Mod Pathol. 2021;34:1373–83.PubMedCrossRef
27.
go back to reference Bernabei I, So A, Busso N, Nasi S. Cartilage calcification in osteoarthritis: mechanisms and clinical relevance. Nat Rev Rheumatol. 2023;19:10–27.PubMedCrossRef Bernabei I, So A, Busso N, Nasi S. Cartilage calcification in osteoarthritis: mechanisms and clinical relevance. Nat Rev Rheumatol. 2023;19:10–27.PubMedCrossRef
28.
go back to reference Pritchard MH, Jessop JD. Chondrocalcinosis in primary hyperparathyroidism Influence of age, metabolic bone disease, and parathyroidectomy. Ann Rheum Dis. 1977;36:146–51.PubMedPubMedCentralCrossRef Pritchard MH, Jessop JD. Chondrocalcinosis in primary hyperparathyroidism Influence of age, metabolic bone disease, and parathyroidectomy. Ann Rheum Dis. 1977;36:146–51.PubMedPubMedCentralCrossRef
29.
go back to reference Richette P, et al. Hypomagnesemia associated with chondrocalcinosis: a cross-sectional study. Arthritis Care Res. 2007;57:1496–501.CrossRef Richette P, et al. Hypomagnesemia associated with chondrocalcinosis: a cross-sectional study. Arthritis Care Res. 2007;57:1496–501.CrossRef
30.
go back to reference Muehleman C, et al. Association between crystals and cartilage degeneration in the ankle. J Rheumatol. 2008;35:1108–17.PubMedPubMedCentral Muehleman C, et al. Association between crystals and cartilage degeneration in the ankle. J Rheumatol. 2008;35:1108–17.PubMedPubMedCentral
31.
go back to reference Foreman SC, et al. Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2020;28:201–7.PubMedCrossRef Foreman SC, et al. Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2020;28:201–7.PubMedCrossRef
32.
go back to reference Liew JW, et al. Intra-articular mineralization on computerized tomography of the knee and risk of cartilage damage: the multicenter osteoarthritis study. Arthritis Rheumatol. 2024;76:1054–61.PubMedPubMedCentralCrossRef Liew JW, et al. Intra-articular mineralization on computerized tomography of the knee and risk of cartilage damage: the multicenter osteoarthritis study. Arthritis Rheumatol. 2024;76:1054–61.PubMedPubMedCentralCrossRef
33.
go back to reference Liew JW, et al. Relation of intra-articular mineralization to knee pain in knee osteoarthritis: a longitudinal analysis in the MOST study. Arthritis Rheumatol. 2023;75:2161–8.PubMedPubMedCentralCrossRef Liew JW, et al. Relation of intra-articular mineralization to knee pain in knee osteoarthritis: a longitudinal analysis in the MOST study. Arthritis Rheumatol. 2023;75:2161–8.PubMedPubMedCentralCrossRef
34.
go back to reference Neogi T, et al. Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis: results of two prospective longitudinal magnetic resonance imaging studies. Arthritis Rheum. 2006;54:1822–8.PubMedCrossRef Neogi T, et al. Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis: results of two prospective longitudinal magnetic resonance imaging studies. Arthritis Rheum. 2006;54:1822–8.PubMedCrossRef
35.
go back to reference McCarthy GM, Dunne A. Calcium crystal deposition diseases — beyond gout. Nat Rev Rheumatol. 2018;14:592–602.PubMedCrossRef McCarthy GM, Dunne A. Calcium crystal deposition diseases — beyond gout. Nat Rev Rheumatol. 2018;14:592–602.PubMedCrossRef
36.
go back to reference Abhishek A. Calcium pyrophosphate deposition disease: a review of epidemiologic findings. Curr Opin Rheumatol. 2016;28:133–9.PubMedCrossRef Abhishek A. Calcium pyrophosphate deposition disease: a review of epidemiologic findings. Curr Opin Rheumatol. 2016;28:133–9.PubMedCrossRef
37.
go back to reference Tedeschi SK, et al. Imaging features of calcium pyrophosphate deposition disease: consensus definitions from an international multidisciplinary working group. Arthritis Care Res. 2023;75:825–34.CrossRef Tedeschi SK, et al. Imaging features of calcium pyrophosphate deposition disease: consensus definitions from an international multidisciplinary working group. Arthritis Care Res. 2023;75:825–34.CrossRef
38.
go back to reference Sirotti S, et al. Reliability and diagnostic accuracy of radiography for the diagnosis of calcium pyrophosphate deposition: performance of the novel definitions developed by an international multidisciplinary working group. Arthritis Rheumatol. 2023;75:630–8.PubMedCrossRef Sirotti S, et al. Reliability and diagnostic accuracy of radiography for the diagnosis of calcium pyrophosphate deposition: performance of the novel definitions developed by an international multidisciplinary working group. Arthritis Rheumatol. 2023;75:630–8.PubMedCrossRef
39.
go back to reference Filippou G, Sirotti S, Cipolletta E, Filippucci E. Optimizing the use of ultrasound in calcium pyrophosphate deposition (CPPD): a review from the ground up. Gout Urate Cryst Depos Dis. 2024;2:17–33.CrossRef Filippou G, Sirotti S, Cipolletta E, Filippucci E. Optimizing the use of ultrasound in calcium pyrophosphate deposition (CPPD): a review from the ground up. Gout Urate Cryst Depos Dis. 2024;2:17–33.CrossRef
40.
go back to reference Cipolletta E, et al. The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis. Osteoarthritis Cartilage. 2021;29:619–32.PubMedCrossRef Cipolletta E, et al. The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis. Osteoarthritis Cartilage. 2021;29:619–32.PubMedCrossRef
41.
go back to reference Sirotti S, et al. Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level. Lancet Rheumatol. 2023;5:e474–82.PubMedCrossRef Sirotti S, et al. Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level. Lancet Rheumatol. 2023;5:e474–82.PubMedCrossRef
42.
go back to reference Guermazi A, et al. Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS). Osteoarthritis Cartilage. 2020;28:802–10.PubMedPubMedCentralCrossRef Guermazi A, et al. Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS). Osteoarthritis Cartilage. 2020;28:802–10.PubMedPubMedCentralCrossRef
43.
go back to reference Mandl P, et al. 2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice. Ann Rheum Dis. 2024;83:752–9.PubMedCrossRef Mandl P, et al. 2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice. Ann Rheum Dis. 2024;83:752–9.PubMedCrossRef
44.
go back to reference Tanikawa H, et al. Detection of calcium pyrophosphate dihydrate crystals in knee meniscus by dual-energy computed tomography. J Orthop Surg. 2018;13:73.CrossRef Tanikawa H, et al. Detection of calcium pyrophosphate dihydrate crystals in knee meniscus by dual-energy computed tomography. J Orthop Surg. 2018;13:73.CrossRef
45.
go back to reference Budzik J, et al. Can dual-energy computed tomography be used to identify early calcium crystal deposition in the knees of patients with calcium pyrophosphate deposition? Arthritis Rheumatol. 2021;73:687–92.PubMedCrossRef Budzik J, et al. Can dual-energy computed tomography be used to identify early calcium crystal deposition in the knees of patients with calcium pyrophosphate deposition? Arthritis Rheumatol. 2021;73:687–92.PubMedCrossRef
46.
go back to reference Tedeschi SK, et al. A prospective study of dual-energy CT scanning, US and X-ray in acute calcium pyrophosphate crystal arthritis. Rheumatology. 2020;59:900–3.PubMedCrossRef Tedeschi SK, et al. A prospective study of dual-energy CT scanning, US and X-ray in acute calcium pyrophosphate crystal arthritis. Rheumatology. 2020;59:900–3.PubMedCrossRef
47.
go back to reference Jarraya M, et al. Dual energy computed tomography cannot effectively differentiate between calcium pyrophosphate and basic calcium phosphate diseases in the clinical setting. Osteoarthr Cartil Open. 2024;6:100436.PubMedPubMedCentralCrossRef Jarraya M, et al. Dual energy computed tomography cannot effectively differentiate between calcium pyrophosphate and basic calcium phosphate diseases in the clinical setting. Osteoarthr Cartil Open. 2024;6:100436.PubMedPubMedCentralCrossRef
48.
go back to reference Døssing A, et al. Dual-energy computed tomography for detection and characterization of monosodium urate, calcium pyrophosphate, and hydroxyapatite: a phantom study on diagnostic performance. Invest Radiol. 2021;56:417–24.PubMedCrossRef Døssing A, et al. Dual-energy computed tomography for detection and characterization of monosodium urate, calcium pyrophosphate, and hydroxyapatite: a phantom study on diagnostic performance. Invest Radiol. 2021;56:417–24.PubMedCrossRef
50.
go back to reference Doherty M, Dieppe PA. Double blind, placebo controlled trial of magnesium carbonate in chronic pyrophosphate arthropathy. Ann Rheum Dis. 1983;42:106–7.PubMedCentralCrossRef Doherty M, Dieppe PA. Double blind, placebo controlled trial of magnesium carbonate in chronic pyrophosphate arthropathy. Ann Rheum Dis. 1983;42:106–7.PubMedCentralCrossRef
51.
go back to reference Parperis K, Papachristodoulou E, Kakoullis L, Rosenthal AK. Management of calcium pyrophosphate crystal deposition disease: a systematic review. Semin Arthritis Rheum. 2021;51:84–94.PubMedCrossRef Parperis K, Papachristodoulou E, Kakoullis L, Rosenthal AK. Management of calcium pyrophosphate crystal deposition disease: a systematic review. Semin Arthritis Rheum. 2021;51:84–94.PubMedCrossRef
52.
go back to reference Cipolletta E, et al. Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review. Clin Exp Rheumatol. 2020;38:1001–7.PubMed Cipolletta E, et al. Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review. Clin Exp Rheumatol. 2020;38:1001–7.PubMed
53.
go back to reference Dumusc A, et al. Anakinra compared to prednisone in the treatment of acute CPPD crystal arthritis: a randomized controlled double-blinded pilot study. Joint Bone Spine. 2021;88:105088.PubMedCrossRef Dumusc A, et al. Anakinra compared to prednisone in the treatment of acute CPPD crystal arthritis: a randomized controlled double-blinded pilot study. Joint Bone Spine. 2021;88:105088.PubMedCrossRef
54.
go back to reference Latourte A, et al. Tocilizumab in symptomatic calcium pyrophosphate deposition disease: a pilot study. Ann Rheum Dis. 2020;79:1126–8.PubMedCrossRef Latourte A, et al. Tocilizumab in symptomatic calcium pyrophosphate deposition disease: a pilot study. Ann Rheum Dis. 2020;79:1126–8.PubMedCrossRef
55.
go back to reference Pascart T, et al. Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial. Lancet Rheumatol. 2023;5:e523–31.PubMedCrossRef Pascart T, et al. Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial. Lancet Rheumatol. 2023;5:e523–31.PubMedCrossRef
56.
go back to reference Finckh A, et al. Methotrexate in chronic-recurrent calcium pyrophosphate deposition disease: no significant effect in a randomized crossover trial. Arthritis Res Ther. 2014;16:458.PubMedPubMedCentralCrossRef Finckh A, et al. Methotrexate in chronic-recurrent calcium pyrophosphate deposition disease: no significant effect in a randomized crossover trial. Arthritis Res Ther. 2014;16:458.PubMedPubMedCentralCrossRef
57.
go back to reference Rothschild B, Yakubov LE. Prospective 6-month, double-blind trial of hydroxychloroquine treatment of CPDD. Compr Ther. 1997;23:327–31.PubMed Rothschild B, Yakubov LE. Prospective 6-month, double-blind trial of hydroxychloroquine treatment of CPDD. Compr Ther. 1997;23:327–31.PubMed
59.
go back to reference Andres M, Sivera F, Pascual E. Methotrexate Is an option for patients with refractory calcium pyrophosphate crystal arthritis. JCR J Clin Rheumatol. 2012;18:234–6.PubMedCrossRef Andres M, Sivera F, Pascual E. Methotrexate Is an option for patients with refractory calcium pyrophosphate crystal arthritis. JCR J Clin Rheumatol. 2012;18:234–6.PubMedCrossRef
Metadata
Title
Imaging and management of calcium pyrophosphate deposition disease
Authors
Wasim Issa
Ronald Mercer
Janeth Yinh
Ali Guermazi
Mohamed Jarraya
Publication date
08-01-2025
Publisher
Springer Berlin Heidelberg
Published in
Skeletal Radiology
Print ISSN: 0364-2348
Electronic ISSN: 1432-2161
DOI
https://doi.org/10.1007/s00256-024-04859-1