Clinical Rheumatology

, Volume 29, Issue 12, pp 1419–1425 | Cite as

Very low levels of vitamin D in systemic sclerosis patients

  • Paola Caramaschi
  • Alessandra Dalla Gassa
  • Orazio Ruzzenente
  • Alessandro Volpe
  • Viviana Ravagnani
  • Ilaria Tinazzi
  • Giovanni Barausse
  • Lisa M. Bambara
  • Domenico Biasi
Original Article


Vitamin D displays many extraosseous immunomodulatory effects. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis (SSc) and to analyze the associations between the concentration of the vitamin and clinical manifestations. In March-April 2009, 65 consecutive SSc patients underwent evaluation of vitamin D concentrations by the LIAISON immunoassay (normal 30-100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency, while concentrations <10 ng/ml as vitamin D deficiency. None of the patients were receiving vitamin D supplementation at the time of or during the year prior to study entry. The mean level of vitamin D was 15.8 ± 9.1 ng/ml. Only three cases showed normal values; vitamin D insufficiency and deficiency were found in 43 and 19 cases, respectively. Patients with vitamin D deficiency showed longer disease duration (13.1 ± 6.8 versus 9.4 ± 5.5 years, P = 0.026), lower diffusing lung capacity for carbon monoxide (63.7 ± 12.4 versus 76.4 ± 20.2, P = 0.014), higher estimated pulmonary artery pressure (28.9 ± 9.9 versus 22.8 ± 10.4, P = 0.037) and higher values of ESR (40 ± 25 versus 23 ± 13 mm/h, P = 0.001) and of CRP (7 ± 7 and 4 ± 2 mg/l, P = 0.004) in comparison with patients with vitamin D insufficiency; moreover, late nailfold videocapillaroscopic pattern was more frequently found (52.6% versus 18.6%, P = 0.013). None of the patients showed evidence of overt mal-absorption. Low levels of vitamin D are very frequent in patients with SSc. Intestinal involvement is not likely the cause of vitamin D deficit; other factors such as skin hyperpigmentation and reduced sun exposition for psychological and social reasons may be implicated. Patients with vitamin D deficiency showed more severe disease in comparison with patients with vitamin D insufficiency, above all concerning lung involvement. Further trials are awaited to determine whether vitamin D could represent a modifiable factor able to interfere with SSc evolution.


Systemic sclerosis Vitamin D 





  1. 1.
    Nagpal S, Na S, Rathnachalam R (2005) Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 26:662–687CrossRefPubMedGoogle Scholar
  2. 2.
    Szodoray P, Nakken B, Gaal J et al (2008) The complex role of vitamin D in autoimmune diseases. Scand J Immunol 68:261–269CrossRefPubMedGoogle Scholar
  3. 3.
    Wu PW, Rhew EY, Dyer AR et al (2009) 25-hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus. Arthritis Rheum 61:1387–1395CrossRefPubMedGoogle Scholar
  4. 4.
    Wright TB, Shults J, Zemel LMB, BS BJM (2009) Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. J Pediatr 155:260–265CrossRefPubMedGoogle Scholar
  5. 5.
    Veldman CM, Cantorna MT, Luca HF DE (2000) Expression of 1, 25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys 374:334–338CrossRefPubMedGoogle Scholar
  6. 6.
    Morgan JW, Kouttab N, Ford D, Maizel AL (2000) Vitamin D-mediated gene regulation in phenotypically defined B cells sub-populations. Endocrinology 141:3225–3234CrossRefPubMedGoogle Scholar
  7. 7.
    Lemire JM, Archer DC (1991) 1, 25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 87:1103–1107CrossRefPubMedGoogle Scholar
  8. 8.
    de Abreu DA Fernandes, Eyles D, Feron F (2009) Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psyconeuroendocrinology 34(suppl 1):S265–S277CrossRefGoogle Scholar
  9. 9.
    Subcommittee for scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581–590CrossRefGoogle Scholar
  10. 10.
    LeRoy EC, Black CM, Fleischmajer R et al (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205PubMedGoogle Scholar
  11. 11.
    Akesson A, Fiori G, Krieg T, van den Hoogen FHJ, Seibold JR (2003) Assessment of skin, joint, tendon and muscle involvement. Clin Exp Rheumatol 21(suppl 29):S5–S8PubMedGoogle Scholar
  12. 12.
    Valentini G, Della Rossa A, Bombardieri S et al (2001) European multicentre study to define disease activity for systemic sclerosis. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 60:592–8CrossRefPubMedGoogle Scholar
  13. 13.
    Cutolo M, Sulli A, Pizzorni C, Accardo S (2000) Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol 27:155–160PubMedGoogle Scholar
  14. 14.
    Medsger TA Jr, Bombardieri S, Czjriak L, Scorza R, Della Rossa A, Bencivelli W (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21(suppl 29):S42–6PubMedGoogle Scholar
  15. 15.
    Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y (2009) Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with Systemic Sclerosis. J Rheumatol 36:1924–1929CrossRefPubMedGoogle Scholar
  16. 16.
    Dovio A, Data V, Carignola R et al (2008) Circulating osteoprotegerin and soluble RANK ligand in systemic sclerosis. J Rheumatol 35:2206–2213CrossRefPubMedGoogle Scholar
  17. 17.
    Braun-Moscovici Y, Furst DE, Markovits D et al (2008) Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol 35:2201–2205CrossRefPubMedGoogle Scholar
  18. 18.
    Orbach H, Zandman-Goddard G, Amital H et al (2007) Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann NY Acad Sci 1109:385–400CrossRefPubMedGoogle Scholar
  19. 19.
    Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS (2006) Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 5:114–117CrossRefPubMedGoogle Scholar
  20. 20.
    Zold E, Szodoray P, Gaal J et al (2008) Vitamin D deficiency in undifferentiated connective tissue disease. Arthritis Res Ther 10:R123CrossRefPubMedGoogle Scholar
  21. 21.
    Isaia G, Giorgino R, Rini GB, Bevilacqua M, Maugeri D, Adami S (2003) Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int 14:577–582CrossRefPubMedGoogle Scholar
  22. 22.
    Bryan C, Howard Y, Brennan P, Black Cm, Silman A (1996) Survival following the onset of scleroderma: results from a retrospective inception cohort study of the UK patient population. Br J Rheumatol 35:1122–6CrossRefPubMedGoogle Scholar
  23. 23.
    Matucci-Cerinic M, D’Angelo S, Denton CP, Vlachoyannopoulos P, Silver R (2003) Assessment of lung involvement. Clin Exp Rheumatol 21(suppl 29):S19–S23PubMedGoogle Scholar
  24. 24.
    Artaza JN, Norris KC (2009) Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol 200:207–221CrossRefPubMedGoogle Scholar
  25. 25.
    Ramirez AM, Wongtrakool C, Welch T, Steinmeyer A, Zugel U, Roman J (2010) Vitamin D inhibition of pro-fibrotic effects on transforming growth factor β1 in lung fibroblasts and epithelial cells. J Steroid Biochem Mol Biol 118:142–150CrossRefPubMedGoogle Scholar
  26. 26.
    Willis BC, Liebler JM, Luby-Phelps K et al (2005) Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol 166:1321–1332PubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Paola Caramaschi
    • 1
    • 4
  • Alessandra Dalla Gassa
    • 1
  • Orazio Ruzzenente
    • 2
  • Alessandro Volpe
    • 3
  • Viviana Ravagnani
    • 1
  • Ilaria Tinazzi
    • 1
  • Giovanni Barausse
    • 1
  • Lisa M. Bambara
    • 1
  • Domenico Biasi
    • 1
  1. 1.Dipartimento di Medicina Clinica e SperimentaleUniversità di VeronaVeronaItaly
  2. 2.Dipartimento di Scienze Morfologico-BiomedicheUniversità di VeronaVeronaItaly
  3. 3.Dipartimento di Medicina InternaOspedale di Negrar (Verona)VeronaItaly
  4. 4.Dipartimento di Medicina Clinica e SperimentalePoliclinico G.B. RossiVeronaItaly

Personalised recommendations