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.
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References
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 13:1026–1034
Chizzolini C, Brembilla NC, Montanari E, Truchetet ME (2011) Fibrosis and immune dysregulation in systemic sclerosis. Autoimmun Rev 10:276–281
Holick MF. Vitamin D deficiency (2007) N Engl J Med 357:266–281.
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 6:2585–2607
Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med 88:441–450
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 12:127–136
Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y (2013) Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 45:256–266
Wöbke TK, Sorg BL, Steinhilber D (2014) Vitamin D in inflammatory diseases. Front Physiol 5:244
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 56:2143–2149
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 69:1155–1157
Pelajo CF, Lopez-Benitez JM, Miller LC (2010) Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev 9:507–510
Cutolo M (2009) Vitamin D and autoimmune rheumatic diseases. Rheumatology 48:210–212
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 65:343–345
Matsuoka LY, Dannenberg MJ, Wortsman J, Hollis BW, Jimenez SA, Varga J (1991) Cutaneous vitamin D3 formation in progressive systemic sclerosis. J Rheumatol 18:1196–1198
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 1109:385–400
Braun-Moscovici Y, Furst DE, Markovits D et al (2008) Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol 35:2201–2205
Dovio A, Data V, Carignola R et al (2008) Circulating osteoprotegerin and soluble RANK ligand in systemic sclerosis. J Rheumatol 35:2206–2213
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 36:1924–1929
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 37:1355
Caramaschi P, Dalla GA, Ruzzenente O et al (2010) Very low levels of vitamin D in systemic sclerosis patients. Clin Rheumatol 12:1419–1425
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 10:490–494
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 32:3143–3148
Seriolo B, Molfetta L, Cutolo M (2011) Seasonal variations in serum levels of 25-hydroxyvitamin D in patients with systemic sclerosis. Clin Rheumatol 30:445–446
Belloli L, Ughi N, Marasini B (2011) Vitamin D in systemic sclerosis. Clin Rheumatol 30:145–146
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 38:2492–2493
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 31:1075–1080
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 30:905–911
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:e66991
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:e0137912
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
Montabone E, Data V, Carignola R (2016) Vitamin D status and quality of life in systemic sclerosis patients. J Clin Rheumatol 22:229–230
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 56:337–344
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 65:2737–2747
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 96:1911–1930
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 86:59–62
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 17:80–84
Wiersinga WM (2016) Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab 31:213–222
Toubi E, Shoenfeld Y (2010) The role of vitamin D in regulating immune responses. Isr Med Assoc J 12:174–175
Schoindre Y, Benveniste O, Costedoat-Chalumeau N (2013) Vitamin D and autoimmunity. Press Med 42:1358–1363
van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101
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 200:207–221
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 84:18–28
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 118:142–150
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 166:1321–1332
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 23:233–239
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The study was approved by the local Ethical Committee (protocol n. 282/15); moreover, all patients gave their written consents.
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Giuggioli, D., Colaci, M., Cassone, G. et al. Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature. Clin Rheumatol 36, 583–590 (2017). https://doi.org/10.1007/s10067-016-3535-z
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DOI: https://doi.org/10.1007/s10067-016-3535-z