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Assessment of calcinosis in Portuguese patients with systemic sclerosis — a multicenter study

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Abstract

Introduction/objectives

The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis.

Method

A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed.

Results

We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02–6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28–9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2–14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7–34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001–0477, p = 0.015).

Conclusions

Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors’ variability.

Key Points

• Prevalence of subclinical calcinosis in SSc patients is substantial.

• Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method.

• Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis.

• Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Valenzuela A, Song P, Chung L (2018) Calcinosis in scleroderma. Curr Opin Rheumatol 30:554–561. https://doi.org/10.1097/bor.0000000000000539

    Article  PubMed  Google Scholar 

  2. Davuluri S, Lood C, Chung L (2022) Calcinosis in systemic sclerosis. Curr Opin Rheumatol 34:319–327. https://doi.org/10.1097/bor.0000000000000896

    Article  PubMed  Google Scholar 

  3. Richardson C, Plaas A, Varga J (2020) Calcinosis in systemic sclerosis: updates in pathophysiology, evaluation, and treatment. Curr Rheumatol Rep 22:73. https://doi.org/10.1007/s11926-020-00951-2

    Article  PubMed  Google Scholar 

  4. Bartoli F, Fiori G, Braschi F, Amanzi L, Bruni C, Blagojevic J et al (2016) Calcinosis in systemic sclerosis: subsets, distribution and complications. Rheumatology (Oxford) 55:1610–1614. https://doi.org/10.1093/rheumatology/kew193

    Article  PubMed  Google Scholar 

  5. Muktabhant C, Thammaroj P, Chowchuen P, Foocharoen C (2021) Prevalence and clinical association with calcinosis cutis in early systemic sclerosis. Mod Rheumatol 31:1113–1119. https://doi.org/10.1080/14397595.2021.1886654

    Article  CAS  PubMed  Google Scholar 

  6. [Available from: https://reuma.pt/en_UK/Default.aspx. Accessed 6 Nov 2022

  7. Baron M, Pope J, Robinson D, Jones N, Khalidi N, Docherty P et al (2016) Calcinosis is associated with digital ischaemia in systemic sclerosis—a longitudinal study. Rheumatology (Oxford) 55:2148–2155. https://doi.org/10.1093/rheumatology/kew313

    Article  PubMed  Google Scholar 

  8. Cruz-Domínguez MP, García-Collinot G, Saavedra MA, Medina G, Carranza-Muleiro RA, Vera-Lastra OL et al (2017) Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis. Clin Rheumatol 36:111–117. https://doi.org/10.1007/s10067-016-3412-9

    Article  PubMed  Google Scholar 

  9. Morgan ND, Shah AA, Mayes MD, Domsic RT, Medsger TA Jr, Steen VD et al (2017) Clinical and serological features of systemic sclerosis in a multicenter African American cohort: analysis of the genome research in African American scleroderma patients clinical database. Medicine (Baltimore) 96:e8980. https://doi.org/10.1097/md.0000000000008980

    Article  PubMed  PubMed Central  Google Scholar 

  10. Takagi K, Kawamoto M, Higuchi T, Tochimoto A, Hirose H, Harigai M et al (2021) Characteristics of Japanese patients with systemic sclerosis complicated with calcinosis. Int J Rheum Dis 24:803–808. https://doi.org/10.1111/1756-185x.14121

    Article  CAS  PubMed  Google Scholar 

  11. Valenzuela A, Baron M, Rodriguez-Reyna TS, Proudman S, Khanna D, Young A et al (2020) Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis. Semin Arthritis Rheum 50:891–896. https://doi.org/10.1016/j.semarthrit.2020.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Valenzuela A, Baron M, Herrick AL, Proudman S, Stevens W, Rodriguez-Reyna TS et al (2016) Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: a Scleroderma Clinical Trials Consortium study. Semin Arthritis Rheum 46:344–349. https://doi.org/10.1016/j.semarthrit.2016.05.008

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sakata K, Kaneko Y, Yasuoka H, Takeuchi T (2020) Association of radiographic findings in hand X-ray with clinical features and autoantibodies in patients with systemic sclerosis. Clin Rheumatol 39:113–118. https://doi.org/10.1007/s10067-019-04639-6

    Article  PubMed  Google Scholar 

  14. Host LV, Campochiaro C, Afonso A, Nihtyanova SI, Denton CP, Ong VH (2021) High proton pump inhibitor exposure increases risk of calcinosis in systemic sclerosis. Rheumatology (Oxford) 60:849–854. https://doi.org/10.1093/rheumatology/keaa332

    Article  CAS  PubMed  Google Scholar 

  15. Pai S, Hsu V (2018) Are there risk factors for scleroderma-related calcinosis? Mod Rheumatol 28:518–522. https://doi.org/10.1080/14397595.2017.1349594

    Article  CAS  PubMed  Google Scholar 

  16. Morardet L, Avouac J, Sammour M, Baron M, Kahan A, Feydy A et al (2016) Late nailfold videocapillaroscopy pattern associated with hand calcinosis and acro-osteolysis in systemic sclerosis. Arthritis Care Res (Hoboken) 68:366–373. https://doi.org/10.1002/acr.22672

    Article  CAS  PubMed  Google Scholar 

  17. Avouac J, Mogavero G, Guerini H, Drapé JL, Mathieu A, Kahan A et al (2011) Predictive factors of hand radiographic lesions in systemic sclerosis: a prospective study. Ann Rheum Dis 70:630–633. https://doi.org/10.1136/ard.2010.134304

    Article  CAS  PubMed  Google Scholar 

  18. Fauny M, Bauer E, Albuisson E, Perrier-Cornet J, Deibener J, Chabot F et al (2018) Vertebral fracture prevalence and measurement of the scanographic bone attenuation coefficient on CT-scan in patients with systemic sclerosis. Rheumatol Int 38:1901–1910. https://doi.org/10.1007/s00296-018-4139-5

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Rheumatology Department, Centro Hospitalar de Vila Nova de Gaia E Espinho, Vila Nova de Gaia, Portugal

    Beatriz Samões, Diogo Guimarães da Fonseca, Tiago Beirão, Flávio Costa, Romana Vieira & Joana Abelha-Aleixo

  2. Rheumatology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

    Georgina Terroso & Raquel Miriam Ferreira

  3. Rheumatology Department, Centro Hospitalar Tondela-Viseu, Viseu, Portugal

    Rafaela Nicolau, Inês Genrinho, Maura Couto & Inês Santos

  4. Rheumatology Department, Centro Hospitalar E Universitário de Coimbra, Coimbra, Portugal

    André Saraiva & Maria João Salvador

  5. Rheumatology Department, Hospital Garcia de Orta, Almada, Portugal

    Ana Catarina Duarte & Ana Cordeiro

  6. Rheumatology Department, Centro Hospitalar Baixo Vouga, Aveiro, Portugal

    João Paulo Vilas-Boas

  7. Rheumatology Department, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal

    Ana Bento da Silva, Laura Gago & Ana Filipa Mourão

  8. Comprehensive Health Research Centre (CHRC), NOVA Medical School, Lisbon, Portugal

    Ana Bento da Silva, Laura Gago & Ana Filipa Mourão

  9. Rheumatology Department, Centro Hospitalar e Universitário de Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal

    Catarina Resende & Patricia Martins

  10. Unidade de Investigação Em Reumatologia, Instituto de Medicina Molecular, Centro Académico de Medicina de Lisboa, Lisbon, Portugal

    Patricia Martins

  11. Rheumatology Department, Unidade Local de Saúde da Guarda - Hospital Sousa Martins, Guarda, Portugal

    Nathalie Madeira & Sara Dinis

  12. Rheumatology and Osteoporosis Unit, Hospital de Sant’Ana, SCML, Cascais, Portugal

    Filipe Araújo

  13. Rheumatology Department, Centro Hospitalar Universitário da Cova da Beira, Covilhã, Portugal

    Miguel Gomes Guerra & Margarida Oliveira

  14. Rheumatology Department, Hospital Distrital de Leiria, Leiria, Portugal

    Alexandra Daniel & Marília Rodrigues

  15. Rheumatology Department, Unidade Local de Saúde Do Alto Minho, Ponte de Lima, Portugal

    Catarina Dantas Soares & Hugo Parente

  16. Rheumatology Department, Hospital Do Divino Espírito Santo, Ponta Delgada, Portugal

    Carolina Furtado & Tomás Fontes

Authors
  1. Beatriz Samões
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  2. Diogo Guimarães da Fonseca
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  3. Tiago Beirão
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  4. Flávio Costa
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  5. Romana Vieira
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  6. Georgina Terroso
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  7. Raquel Miriam Ferreira
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  8. Rafaela Nicolau
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  9. André Saraiva
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  10. Maria João Salvador
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  11. Ana Catarina Duarte
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  12. Ana Cordeiro
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  13. João Paulo Vilas-Boas
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  14. Inês Genrinho
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  15. Ana Bento da Silva
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  16. Laura Gago
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  17. Catarina Resende
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  18. Patricia Martins
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  19. Nathalie Madeira
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  20. Sara Dinis
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  21. Maura Couto
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  22. Inês Santos
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  23. Filipe Araújo
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  24. Ana Filipa Mourão
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  25. Miguel Gomes Guerra
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  26. Margarida Oliveira
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  27. Alexandra Daniel
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  28. Marília Rodrigues
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  29. Catarina Dantas Soares
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  30. Hugo Parente
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  31. Carolina Furtado
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  32. Tomás Fontes
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  33. Joana Abelha-Aleixo
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Contributions

Miguel Guerra was the author of the idea for this project. Beatriz Samões, Miguel Guerra, Romana Vieira, and Joana Abelha-Aleixo contributed to the study conception and design. Data collection was performed by all authors. Data analysis and the first draft of the manuscript were written by Beatriz Samões, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Beatriz Samões.

Ethics declarations

Ethical approval

This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and was approved by the Coordinating and Scientific Board of Reuma.pt and by the Ethics Committee of Centro Hospitalar de Vila Nova de Gaia e Espinho. Reuma.pt was approved by the National Data Protection Authority (CNPD).

Consent to participate and publication

All patients provided written informed consent for data collection, analysis, and publication. Analysis was performed on an anonymous dataset.

Disclosures

None.

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Samões, B., Guimarães da Fonseca, D., Beirão, T. et al. Assessment of calcinosis in Portuguese patients with systemic sclerosis — a multicenter study. Clin Rheumatol 42, 2125–2134 (2023). https://doi.org/10.1007/s10067-023-06617-5

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  • DOI: https://doi.org/10.1007/s10067-023-06617-5

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