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Erschienen in: Clinical Rheumatology 3/2017

09.01.2017 | Original Article

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature

verfasst von: Dilia Giuggioli, M. Colaci, G. Cassone, P. Fallahi, F. Lumetti, A. Spinella, F. Campomori, A. Manfredi, C. U. Manzini, A. Antonelli, C. Ferri

Erschienen in: Clinical Rheumatology | Ausgabe 3/2017

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Abstract

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = −0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.
Literatur
1.
Zurück zum Zitat Ferri C, Sebastiani M, Lo Monaco A et al (2014) Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimm Rev 13:1026–1034CrossRef Ferri C, Sebastiani M, Lo Monaco A et al (2014) Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients’ population and review of the literature. Autoimm Rev 13:1026–1034CrossRef
2.
Zurück zum Zitat Chizzolini C, Brembilla NC, Montanari E, Truchetet ME (2011) Fibrosis and immune dysregulation in systemic sclerosis. Autoimmun Rev 10:276–281CrossRefPubMed Chizzolini C, Brembilla NC, Montanari E, Truchetet ME (2011) Fibrosis and immune dysregulation in systemic sclerosis. Autoimmun Rev 10:276–281CrossRefPubMed
3.
Zurück zum Zitat Holick MF. Vitamin D deficiency (2007) N Engl J Med 357:266–281. Holick MF. Vitamin D deficiency (2007) N Engl J Med 357:266–281.
4.
Zurück zum Zitat Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C (2009) Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int. J. Environ. Res Public Health 6:2585–2607CrossRefPubMedPubMedCentral Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C (2009) Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int. J. Environ. Res Public Health 6:2585–2607CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88:441–450CrossRefPubMedPubMedCentral Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88:441–450CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Antico A, Tampoia M, Tozzoli R, Bizzaro N (2012) Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimm Rev 12:127–136CrossRef Antico A, Tampoia M, Tozzoli R, Bizzaro N (2012) Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimm Rev 12:127–136CrossRef
7.
Zurück zum Zitat Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y (2013) Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 45:256–266CrossRefPubMed Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y (2013) Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 45:256–266CrossRefPubMed
9.
Zurück zum Zitat Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D (2007) Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 56:2143–2149CrossRefPubMed Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D (2007) Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 56:2143–2149CrossRefPubMed
10.
Zurück zum Zitat Amital H, Szekanecz Z, Szucs G et al (2010) Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis 69:1155–1157CrossRefPubMed Amital H, Szekanecz Z, Szucs G et al (2010) Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis 69:1155–1157CrossRefPubMed
11.
Zurück zum Zitat Pelajo CF, Lopez-Benitez JM, Miller LC (2010) Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev 9:507–510CrossRefPubMed Pelajo CF, Lopez-Benitez JM, Miller LC (2010) Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev 9:507–510CrossRefPubMed
12.
13.
Zurück zum Zitat Serup J, Hagdrup H (1985) Vitamin D metabolites in generalized scleroderma. Evidence of a normal cutaneous and intestinal supply with vitamin D. Acta Derm Venereol 65:343–345PubMed Serup J, Hagdrup H (1985) Vitamin D metabolites in generalized scleroderma. Evidence of a normal cutaneous and intestinal supply with vitamin D. Acta Derm Venereol 65:343–345PubMed
14.
Zurück zum Zitat Matsuoka LY, Dannenberg MJ, Wortsman J, Hollis BW, Jimenez SA, Varga J (1991) Cutaneous vitamin D3 formation in progressive systemic sclerosis. J Rheumatol 18:1196–1198PubMed Matsuoka LY, Dannenberg MJ, Wortsman J, Hollis BW, Jimenez SA, Varga J (1991) Cutaneous vitamin D3 formation in progressive systemic sclerosis. J Rheumatol 18:1196–1198PubMed
15.
Zurück zum Zitat 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 N Y Acad Sci 1109:385–400CrossRefPubMed 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 N Y Acad Sci 1109:385–400CrossRefPubMed
16.
Zurück zum Zitat Braun-Moscovici Y, Furst DE, Markovits D et al (2008) Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol 35:2201–2205CrossRefPubMed Braun-Moscovici Y, Furst DE, Markovits D et al (2008) Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol 35:2201–2205CrossRefPubMed
17.
Zurück zum Zitat Dovio A, Data V, Carignola R et al (2008) Circulating osteoprotegerin and soluble RANK ligand in systemic sclerosis. J Rheumatol 35:2206–2213CrossRefPubMed Dovio A, Data V, Carignola R et al (2008) Circulating osteoprotegerin and soluble RANK ligand in systemic sclerosis. J Rheumatol 35:2206–2213CrossRefPubMed
18.
Zurück zum Zitat 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 36:1924–1929CrossRefPubMed 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 36:1924–1929CrossRefPubMed
19.
Zurück zum Zitat Rios FR, Fernandez RC, Callejas Rubio JL, Ortego CN (2010) Vitamin D deficiency in a cohort of patients with systemic scleroderma from the south of Spain. J Rheumatol 37:1355CrossRef Rios FR, Fernandez RC, Callejas Rubio JL, Ortego CN (2010) Vitamin D deficiency in a cohort of patients with systemic scleroderma from the south of Spain. J Rheumatol 37:1355CrossRef
20.
Zurück zum Zitat Caramaschi P, Dalla GA, Ruzzenente O et al (2010) Very low levels of vitamin D in systemic sclerosis patients. Clin Rheumatol 12:1419–1425CrossRef Caramaschi P, Dalla GA, Ruzzenente O et al (2010) Very low levels of vitamin D in systemic sclerosis patients. Clin Rheumatol 12:1419–1425CrossRef
21.
Zurück zum Zitat Arnson Y, Amital H, Agmon-Levin N et al (2011) Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev 10:490–494CrossRefPubMed Arnson Y, Amital H, Agmon-Levin N et al (2011) Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev 10:490–494CrossRefPubMed
22.
Zurück zum Zitat Ibn Yacoub Y, Amine B, Laatiris A, Wafki F, Znat F, Hajjaj-Hassouni N (2012) Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status. Rheumatol Int 32:3143–3148CrossRefPubMed Ibn Yacoub Y, Amine B, Laatiris A, Wafki F, Znat F, Hajjaj-Hassouni N (2012) Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status. Rheumatol Int 32:3143–3148CrossRefPubMed
23.
Zurück zum Zitat Seriolo B, Molfetta L, Cutolo M (2011) Seasonal variations in serum levels of 25-hydroxyvitamin D in patients with systemic sclerosis. Clin Rheumatol 30:445–446CrossRefPubMed Seriolo B, Molfetta L, Cutolo M (2011) Seasonal variations in serum levels of 25-hydroxyvitamin D in patients with systemic sclerosis. Clin Rheumatol 30:445–446CrossRefPubMed
24.
Zurück zum Zitat Belloli L, Ughi N, Marasini B (2011) Vitamin D in systemic sclerosis. Clin Rheumatol 30:145–146CrossRefPubMed Belloli L, Ughi N, Marasini B (2011) Vitamin D in systemic sclerosis. Clin Rheumatol 30:145–146CrossRefPubMed
25.
Zurück zum Zitat Gambichler T, Chrobok I, Höxtermann S, Kreuter A (2011) Significantly decreased serum 25-hydroxyvitamin d levels in a large German systemic sclerosis cohort. J Rheumatol 38:2492–2493CrossRefPubMed Gambichler T, Chrobok I, Höxtermann S, Kreuter A (2011) Significantly decreased serum 25-hydroxyvitamin d levels in a large German systemic sclerosis cohort. J Rheumatol 38:2492–2493CrossRefPubMed
26.
Zurück zum Zitat Shinjo SK, Bonfá E, de Falco CV, Pereira RM (2011) Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency. Rheumatol Int 31:1075–1080CrossRefPubMed Shinjo SK, Bonfá E, de Falco CV, Pereira RM (2011) Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency. Rheumatol Int 31:1075–1080CrossRefPubMed
27.
Zurück zum Zitat Rios-Fernández R, Callejas-Rubio JL, Fernández-Roldán C et al (2012) Bone mass and vitamin D in patients with systemic sclerosis from two Spanish regions. Clin Exp Rheumatol 30:905–911PubMed Rios-Fernández R, Callejas-Rubio JL, Fernández-Roldán C et al (2012) Bone mass and vitamin D in patients with systemic sclerosis from two Spanish regions. Clin Exp Rheumatol 30:905–911PubMed
28.
Zurück zum Zitat Atteritano M, Sorbara S, Bagnato G et al (2013) Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study. PLoS One 8:e66991CrossRefPubMedPubMedCentral Atteritano M, Sorbara S, Bagnato G et al (2013) Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study. PLoS One 8:e66991CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Corrado A, Colia R, Mele A et al (2015) Relationship between body mass composition, bone mineral density, skin fibrosis and 25(OH) vitamin D serum levels in systemic sclerosis. PLoS One 10:e0137912CrossRefPubMedPubMedCentral Corrado A, Colia R, Mele A et al (2015) Relationship between body mass composition, bone mineral density, skin fibrosis and 25(OH) vitamin D serum levels in systemic sclerosis. PLoS One 10:e0137912CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Zhang L, Duan Y, Zhang TP et al (2015) Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: a case control study. Int J Rheum Dis doi. doi:10.1111/1756-185X.12794 Zhang L, Duan Y, Zhang TP et al (2015) Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: a case control study. Int J Rheum Dis doi. doi:10.​1111/​1756-185X.​12794
31.
Zurück zum Zitat Montabone E, Data V, Carignola R (2016) Vitamin D status and quality of life in systemic sclerosis patients. J Clin Rheumatol 22:229–230CrossRefPubMed Montabone E, Data V, Carignola R (2016) Vitamin D status and quality of life in systemic sclerosis patients. J Clin Rheumatol 22:229–230CrossRefPubMed
32.
Zurück zum Zitat Sampaio-Barros MM, Takayama L, Sampaio-Barros PD, Bonfá E, Pereira RM (2016) Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings. Rev Bras Reumatol 56:337–344CrossRef Sampaio-Barros MM, Takayama L, Sampaio-Barros PD, Bonfá E, Pereira RM (2016) Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings. Rev Bras Reumatol 56:337–344CrossRef
33.
Zurück zum Zitat van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 65:2737–2747CrossRefPubMedPubMedCentral van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 65:2737–2747CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Holick MF, Binkley NC, Bischoff-Ferrari HA, Endocrine Society et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930CrossRefPubMed Holick MF, Binkley NC, Bischoff-Ferrari HA, Endocrine Society et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930CrossRefPubMed
35.
Zurück zum Zitat Lippi G, Nouvenne A, Ticinesi A, Bonelli P, Salvagno GL, Cervellin G, Guidi GC (2015) The burden of vitamin D deficiency in a Mediterranean country without a policy of food fortification. Acta Biomed 86:59–62PubMed Lippi G, Nouvenne A, Ticinesi A, Bonelli P, Salvagno GL, Cervellin G, Guidi GC (2015) The burden of vitamin D deficiency in a Mediterranean country without a policy of food fortification. Acta Biomed 86:59–62PubMed
36.
Zurück zum Zitat Carmel NN, Rotman-Pikielny P, Lavrov A, Levy Y (2015) Vitamin D antibodies in systemic sclerosis patients: findings and clinical correlations. Isr Med Assoc J 17:80–84PubMed Carmel NN, Rotman-Pikielny P, Lavrov A, Levy Y (2015) Vitamin D antibodies in systemic sclerosis patients: findings and clinical correlations. Isr Med Assoc J 17:80–84PubMed
37.
Zurück zum Zitat Wiersinga WM (2016) Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab 31:213–222CrossRef Wiersinga WM (2016) Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab 31:213–222CrossRef
38.
Zurück zum Zitat Toubi E, Shoenfeld Y (2010) The role of vitamin D in regulating immune responses. Isr Med Assoc J 12:174–175PubMed Toubi E, Shoenfeld Y (2010) The role of vitamin D in regulating immune responses. Isr Med Assoc J 12:174–175PubMed
39.
Zurück zum Zitat Schoindre Y, Benveniste O, Costedoat-Chalumeau N (2013) Vitamin D and autoimmunity. Press Med 42:1358–1363CrossRef Schoindre Y, Benveniste O, Costedoat-Chalumeau N (2013) Vitamin D and autoimmunity. Press Med 42:1358–1363CrossRef
40.
Zurück zum Zitat van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101CrossRefPubMed van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101CrossRefPubMed
41.
Zurück zum Zitat 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 200:207–221CrossRefPubMed 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 200:207–221CrossRefPubMed
42.
Zurück zum Zitat Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28PubMed Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28PubMed
43.
Zurück zum Zitat 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 118:142–150CrossRefPubMed 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 118:142–150CrossRefPubMed
44.
Zurück zum Zitat 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 166:1321–1332CrossRefPubMedPubMedCentral 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 166:1321–1332CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat van Halteren AG, Tysma OM, van Etten E, Mathieu C, Roep BO (2004) 1alpha, 25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun 23:233–239CrossRefPubMed van Halteren AG, Tysma OM, van Etten E, Mathieu C, Roep BO (2004) 1alpha, 25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun 23:233–239CrossRefPubMed
Metadaten
Titel
Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature
verfasst von
Dilia Giuggioli
M. Colaci
G. Cassone
P. Fallahi
F. Lumetti
A. Spinella
F. Campomori
A. Manfredi
C. U. Manzini
A. Antonelli
C. Ferri
Publikationsdatum
09.01.2017
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 3/2017
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-016-3535-z

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