Calcinosis in systemic sclerosis: prevalence, clinical picture, management, complications


  • Ye.D. Yehudina MD, PhD in medicine, associate professor, State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro, Ukraine, е-mail:; phone: +38 (099) 059-54-75
  • I.Yu. Golovach MD, PhD in medicine, professor, Head of the Center of rheumatology, Clinical Hospital “Feofaniya” of the Agency of State Aff airs, Kyiv, Ukraine, е-mail:; phone: +38 (050) 654-21-88



calcifications, calcinosis cutis, systemic sclerosis, pathophysiology, clinical picture, management, review


This literature review summarizes current data on the epi­demiology, pathophysiology, diagnosis and treatment of calcinosis cutis in patients with systemic sclerosis (SSc). The article deals with the analysis of observational studies of the frequency of calcinosis in SSc and associated clinical features, molecular research of potential pathogenetic mechanisms, clinical cases describing new diagnostic approaches and methods for the treatment of calcinosis. Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. Calcinosis is one of the main, poorly managed clinical problems in patients with SSc, affecting at least one quarter of patients with SSc. Calcinosis is associated with a longer disease duration, digital ulcers, acro-osteolysis, positive anticentromere and anti-topoisomerase antibodies. Although the pathogenesis of calcification is not fully known, there is evidence supporting the role of local chronic traumatization, chronic inflammation, vascular hypoxia and malregulation of bone matrix proteins as potential mechanisms for the development of this pathological condition in patients with SSc. The diagnosis can be established on the basis of clinical data or using plain X-ray. Several pharmacolo­gical treatment methods have been applied in patients with calcinosis with variable and not so significant results; in turn, surgical excision of calcium deposits remains mainstay of treatment.


Download data is not yet available.


Chander S, Gordon P. Soft tissue and subcutaneous calcification in connective tissue diseases. Curr Opin Rheumatol. 2012 Mar;24(2):158-64. doi: 10.1097/BOR.0b013e32834ff5cd.

Varga J, Denton CP, Wigley FM, Masataka Kuwana YA. Scleroderma from pathogenesis to comprehen-sive management. 2nd ed. New York: Springer Science Business Media; 2017. 739 p.

Reiter N, El-Shabrawi L, Leinweber B, Berghold A, Aberer E. Calcinosis cutis: part I. Diagnostic path-way. J Am Acad Dermatol. 2011 Jul;65(1):1-12; quiz 13-4. doi: 10.1016/j.jaad.2010.08.038.

Gutierrez A Jr, Wetter DA. Calcinosis cutis in autoimmune connective tissue diseases. Dermatol Ther. 2012 Mar-Apr;25(2):195-206. doi: 10.1111/j.1529-8019.2012.01492.x.

Morgan ND, Shah AA, Mayes MD, et al. Clinical and serological features of systemic sclerosis in a multicenter African American cohort: analysis of the genome research in African American scleroder-ma patients clinical database. Medicine (Baltimore). 2017 Dec;96(51):e8980. doi: 10.1097/MD.0000000000008980.

Cruz-Dominguez MP, Garcia-Collinot G, Saavedra MA, et al. Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis. Clin Rheu-matol. 2017 Jan;36(1):111-117. doi: 10.1007/s10067-016-3412-9.

Galluccio F, Allanore Y, Czirjak L, Furst DE, Khanna D, Matucci-Cerinic M. Points to consider for skin ulcers in systemic sclerosis. Rheumatology (Oxford). 2017 Sep 1;56(suppl_5):v67-v71. doi: 10.1093/rheumatology/kex200.

Tolosa-Vilella C, Morera-Morales ML, Simeon-Aznar CP, et al. Digital ulcers and cutaneous subsets of systemic sclerosis: clinical, immunological, nailfold capillaroscopy, and survival differences in the Spanish RESCLE Registry. Semin Arthritis Rheum. 2016 Oct;46(2):200-208. doi: 10.1016/j.semarthrit.2016.04.007.

Valenzuela A, Baron M, Herrick AL, et al. Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: a scleroderma clinical trials consortium study. Semin Arthritis Rheum. 2016 Dec;46(3):344-349. doi: 10.1016/j.semarthrit.2016.05.008.

Pai S, Hsu V. Are there risk factors for scleroderma-related calcinosis? Mod Rheumatol. 2018 May;28(3):518-522. doi: 10.1080/14397595.2017.1349594.

Baron M, Pope J, Robinson D, et al. Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study. Rheumatology (Oxford). 2016 Dec;55(12):2148-2155. doi: 10.1093/rheumatology/kew313.

Herrick AL, Gallas A. Systemic sclerosis-related calcinosis. J Scleroderma Relat Disord. 2016;1(2):194-203. doi: 10.5301%2Fjsrd.5000211.

Makol A, Ytterberg SR. Images in clinical medicine. Calcinosis cutis in systemic sclerosis. N Engl J Med. 2011 Jun 9;364(23):2245. doi: 10.1056/NEJMicm1011692.

Chung L, Valenzuela A, Fiorentino D, et al. Validation of a novel radiographic scoring system for cal-cinosis affecting the hands of patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2015 Mar;67(3):425-30. doi: 10.1002/acr.22434.

Bartoli F, Fiori G, Braschi F, et al. Calcinosis in systemic sclerosis: subsets, distribution and complica-tions. Rheumatology (Oxford). 2016 Sep;55(9):1610-4. doi: 10.1093/rheumatology/kew193.

Freire V, Bazeli R, Elhai M, et al. Hand and wrist involvement in systemic sclerosis: US features. Radi-ology. 2013 Dec;269(3):824-30. doi: 10.1148/radiol.13121994.

Suliman YA, Kafaja S, Fitzgerald J, et al. Ultrasound characterization of cutaneous ulcers in systemic sclerosis. Clin Rheumatol. 2018 Jun;37(6):1555-1561. doi: 10.1007/s10067-018-3986-5.

Freire V, Becce F, Feydy A, et al. MDCT imaging of calcinosis in systemic sclerosis. Clin Radiol. 2013 Mar;68(3):302-9. doi: 10.1016/j.crad.2012.07.009.

Hsu V, Bramwit M, Schlesinger N. Use of dual-energy computed tomography for the evaluation of cal-cinosis in patients with systemic sclerosis. Clin Rheumatol. 2015 Sep;34(9):1557-61. doi: 10.1007/s10067-015-2998-7.

Kimball AB, Summers RM, Turner M, et al. Magnetic resonance imaging detection of occult skin and subcutaneous abnormalities in juvenile dermatomyositis. Implications for diagnosis and therapy. Arthri-tis Rheum. 2000 Aug;43(8):1866-73. doi: 10.1002/1529-0131(200008)43:8<1866::AID-ANR24>3.0.CO;2-6.

Shimizu M, Ueno K, Ishikawa S, Kasahara Y, Yachie A. Role of activated macrophage and inflamma-tory cytokines in the development of calcinosis in juvenile dermatomyositis. Rheumatology (Oxford). 2014 Apr;53(4):766-7. doi: 10.1093/rheumatology/ket360.

Osthoff M, Ngian GS, Dean MM, et al. Potential role of the lectin pathway of complement in the patho-genesis and disease manifestations of systemic sclerosis: a case inverted question mark control and co-hort study. Arthritis Res Ther. 2014 Nov 18;16(6):480. doi: 10.1186/s13075-014-0480-6.

Davies CA, Jeziorska M, Freemont AJ, Herrick AL. The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease subtypes of systemic sclerosis. Hum Pathol. 2006 Feb;37(2):190-7. doi: 10.1016/j.humpath.2005.10.007.

Park JK, Fava A, Carrino J, Del Grande F, Rosen A, Boin F. Association of acroosteolysis with en-hanced osteoclastogenesis and higher blood levels of vascular endothelial growth factor in systemic sclerosis. Arthritis Rheumatol. 2016 Jan;68(1):201-9. doi: 10.1002/art.39424.

Davies CA, Herrick AL, Cordingley L, Freemont AJ, Jeziorska M. Expression of advanced glycation end products and their receptor in skin from patients with systemic sclerosis with and without calcino-sis. Rheumatology (Oxford). 2009 Aug;48(8):876-82. doi: 10.1093/rheumatology/kep151.

Gauhar R, Wilkinson J, Harris J, Manning J, Herrick AL. Calcinosis preferentially affects the thumb compared to other fingers in patients with systemic sclerosis. Scand J Rheumatol. 2016 Jul;45(4):317-20. doi: 10.3109/03009742.2015.1127412.

Cantatore FP, Maruotti N, Corrado A, Ribatti D. Angiogenesis dysregulation in the pathogenesis of sys-temic sclerosis. Biomed Res Int. 2017;2017:5345673. doi: 10.1155/2017/5345673.

Zebboudj AF, Shin V, Bostrom K. Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular cells. J Cell Biochem. 2003 Nov 1;90(4):756-65. doi: 10.1002/jcb.10669.

Wallin R, Wajih N, Greenwood GT, Sane DC. Arterial calcification: a review of mechanisms, animal models, and the prospects for therapy. Med Res Rev. 2001 Jul;21(4):274-301.

Ughi N, Crotti C, Ingegnoli F. Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports. Clin Interv Aging. 2016 Mar 14;11:307-11. doi: 10.2147/CIA.S102577.

Netsch D. Calcinosis cutis: WOC nurse management. J Wound Ostomy Continence Nurs. 2018 Jan/Feb;45(1):83-86. doi: 10.1097/WON.0000000000000403.

Palmieri GM, Sebes JI, Aelion JA, et al. Treatment of calcinosis with diltiazem. Arthritis Rheum. 1995 Nov;38(11):1646-54.

Dolan AL, Kassimos D, Gibson T, Kingsley GH. Diltiazem induces remission of calcinosis in sclero-derma. Br J Rheumatol. 1995 Jun;34(6):576-8.

Farah MJ, Palmieri GM, Sebes JI, Cremer MA, Massie JD, Pinals RS. The effect of diltiazem on calcin-osis in a patient with the CREST syndrome. Arthritis Rheum. 1990 Aug;33(8):1287-93.

Balin SJ, Wetter DA, Andersen LK, Davis MD. Calcinosis cutis occurring in association with autoim-mune connective tissue disease: the Mayo Clinic experience with 78 patients, 1996–2009. Arch Derma-tol. 2012 Apr;148(4):455-62. doi: 10.1001/archdermatol.2011.2052.

Vayssairat M, Hidouche D, Abdoucheli-Baudot N, Gaitz JP. Clinical significance of subcutaneous cal-cinosis in patients with systemic sclerosis: does diltiazem induce its regression? Ann Rheum Dis. 1998 Apr;57(4):252-4. doi: 10.1136/ard.57.4.252.

Li G, Adachi JD, Cheng J, et al. Relationship between calcium channel blockers and skin fibrosis in pa-tients with systemic sclerosis. Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 106(4):56-60.

Dima A, Balanescu P, Baicus C. Pharmacological treatment in calcinosis cutis associated with connec-tive-tissue diseases. Rom J Intern Med. 2014 Apr-Jun;52(2):55-67.

Palaniappan P, Lionel AP, Kumar S. Successful treatment of calcinosis cutis in juvenile dermatomyo-sitis with pamidronate. J Clin Rheumatol. 2014 Dec;20(8):454-5. doi: 10.1097/RHU.0000000000000199.

Canas CA, Bonilla-Abadia F, Mejia M, Tobon GJ. Recovery of severe muscular and fascial calcinosis after treatment with bisphosphonates in a child with juvenile dermatomyositis. J Clin Rheumatol. 2015 Aug;21(5):267-9. doi: 10.1097/RHU.0000000000000264.

Saini I, Kalaivani M, Kabra SK. Calcinosis in juvenile dermatomyositis: frequency, risk factors and outcome. Rheumatol Int. 2016 Jul;36(7):961-5. doi: 10.1007/s00296-016-3467-6.

Fujii N, Hamano T, Isaka Y, Ito T, Imai E. Risedronate: a possible treatment for extraosseous calcifica-tion. Clin Calcium. 2005 Sep;15 Suppl 1:75-8; discussion 78-9. doi: CliCa05S-17579.

Cukierman T, Elinav E, Korem M, Chajek-Shaul T. Low dose warfarin treatment for calcinosis in pa-tients with systemic sclerosis. Ann Rheum Dis. 2004 Oct;63(10):1341-3. doi: 10.1136/ard.2003.014431.

Berger RG, Featherstone GL, Raasch RH, McCartney WH, Hadler NM. Treatment of calcinosis univer-salis with low-dose warfarin. Am J Med. 1987 Jul;83(1):72-6.

Lassoued K, Saiag P, Anglade MC, Roujeau JC, Touraine RL. Failure of warfarin in treatment of cal-cinosis universalis. Am J Med. 1988 Apr;84(4):795-6.

Bair B, Fivenson D. A novel treatment for ulcerative calcinosis cutis. J Drugs Dermatol. 2011 Sep;10(9):1042-4.

Del Barrio-Díaz P, Moll-Manzur C, Álvarez-Veliz S, Vera-Kellet C. Topical sodium metabisulfite for the treatment of calcinosis cutis: a promising new therapy. Br J Dermatol. 2016 Sep;175(3):608-11. doi: 10.1111/bjd.14412.

Goossens J, Courbebaisse M, Caudron E, et al. Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: two cases. Semin Arthritis Rheum. 2017 Dec;47(3):451-455. doi: 10.1016/j.semarthrit.2017.05.013.

Baumgartner-Nielsen J, Olesen AB. Treatment of skin calcifications with intralesional injection of sodi-um thiosulphate: a case series. Acta Derm Venereol. 2016 Feb;96(2):257-8. doi: 10.2340/00015555-2206.

Mageau A, Guigonis V, Ratzimbasafy V, et al. Intravenous sodium thiosulfate for treating tumoral cal-cinosis associated with systemic disorders: report of four cases. Joint Bone Spine. 2017 May;84(3):341-344. doi: 10.1016/j.jbspin.2016.10.009.

Tosounidou S, MacDonald H, Situnayake D. Successful treatment of calcinosis with infliximab in a pa-tient with systemic sclerosis/myositis overlap syndrome. Rheumatology (Oxford). 2014 May;53(5):960-1. doi: 10.1093/rheumatology/ket365.

de Paula DR, Klem FB, Lorencetti PG, Muller C, Azevedo VF. Rituximab-induced regression of CREST-related calcinosis. Clin Rheumatol. 2013 Feb;32(2):281-3. doi: 10.1007/s10067-012-2124-z.

Giuggioli D, Lumetti F, Colaci M, Fallahi P, Antonelli A, Ferri C. Rituximab in the treatment of patients with systemic sclerosis: our experience and review of the literature. Autoimmun Rev. 2015 Nov;14(11):1072-8. doi: 10.1016/j.autrev.2015.07.008.

Hurabielle C, Allanore Y, Kahan A, Avouac J. Flare of calcinosis despite rituximab therapy. Semin Ar-thritis Rheum. 2014 Oct;44(2):e5-6. doi: 10.1016/j.semarthrit.2014.04.007.

Dubos M, Ly K, Martel C, Fauchais AL. Is rituximab an effective treatment of refractory calcinosis? BMJ Case Rep. 2016 May 31;2016. pii: bcr2015213179. doi: 10.1136/bcr-2015-213179.

Robertson LP, Marshall RW, Hickling P. Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline. Ann Rheum Dis. 2003 Mar;62(3):267-9. doi: 10.1136/ard.62.3.267.

Reiter N, El-Shabrawi L, Leinweber B, Aberer E. Subcutaneous morphea with dystrophic calcification with response to ceftriaxone treatment. J Am Acad Dermatol. 2010 Aug;63(2):e53-5. doi: 10.1016/j.jaad.2009.11.016.

Hudson PM, Jones PE, Robinson TW, Dent CE. Extensive calcinosis with minimal scleroderma: treatment of ectopic calcification with aluminum hydroxide. Proc R Soc Med. 1974 Nov;67(11):1166-8.

Hazen PG, Walker AE, Carney JF, Stewart JJ. Cutaneous calcinosis of scleroderma: successful treatment with intralesional adrenal steroids. Arch Dermatol. 1982 May;118(5):366-7.

Fuchs D, Fruchter L, Fishel B, Holtzman M, Yaron M. Colchicine suppression of local inflammation due to calcinosis in dermatomyositis and progressive systemic sclerosis. Clin Rheumatol. 1986 Dec;5(4):527-30.

Schanz S, Ulmer A, Fierlbeck G. Response of dystrophic calcification to intravenous immunoglobulin. Arch Dermatol. 2008 May;144(5):585-7. doi: 10.1001/archderm.144.5.585.

Hsu VM, Chung L, Hummers LK, et al. Risk Factors for Mortality and Cardiopulmonary Hospitaliza-tion in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry. J Rheumatol. 2019 Feb;46(2):176-183. doi: 10.3899/jrheum.180018.

Sultan-Bichat N, Menard J, Perceau G, Staerman F, Bernard P, Reguiaï Z. Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy. J Am Acad Dermatol. 2012 Mar;66(3):424-9. doi: 10.1016/j.jaad.2010.12.035.

Blumhardt S, Frey DP, Toniolo M, Alkadhi H, Held U, Distler O. Safety and efficacy of extracorporeal shock wave therapy (ESWT) in calcinosis cutis associated with systemic sclerosis. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):177-180.

Chamberlain AJ, Walker NP. Successful palliation and significant remission of cutaneous calcinosis in CREST syndrome with carbon dioxide laser. Dermatol Surg. 2003 Sep;29(9):968-70.

Saddic N, Miller JJ, Miller OF 3rd, Clarke JT. Surgical debridement of painful fingertip calcinosis cutis in CREST syndrome. Arch Dermatol. 2009 Feb;145(2):212-3. doi: 10.1001/archderm.145.2.212-b.

Lapner MA, Goetz TJ. High-speed burr debulking of digital calcinosis cutis in scleroderma patients. J Hand Surg Am. 2014 Mar;39(3):503-10. doi: 10.1016/j.jhsa.2013.12.003.



How to Cite

Yehudina, Y., & Golovach, I. (2021). Calcinosis in systemic sclerosis: prevalence, clinical picture, management, complications. PAIN, JOINTS, SPINE, 9(2), 108–119.




Most read articles by the same author(s)

1 2 > >>