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Review
. 2024 Oct 21:23971983241288591.
doi: 10.1177/23971983241288591. Online ahead of print.

Vitamin D association with systemic sclerosis and its clinical features: A systematic review, meta-analysis, and meta-regression

Tarak Dhaouadi  1 , Awatef Riahi  1 , Taïeb Ben Abdallah  1 , Yousr Gorgi  1 , Imen Sfar  1
Affiliations
Review

Vitamin D association with systemic sclerosis and its clinical features: A systematic review, meta-analysis, and meta-regression

Tarak Dhaouadi et al. J Scleroderma Relat Disord. .

Abstract

Objectives: The aim of this review was to summarize existing data on the contribution of Vitamin D level and/or deficiency/insufficiency to systemic sclerosis susceptibility and its clinical features.

Methods: An electronic literature search for eligible studies among all papers published prior to 30 June 2024 was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses estimating pooled raw mean differences, odds ratios, and Pearson r together with subgroup analyses and meta-regressions were performed for the association of Vitamin D with susceptibility to systemic sclerosis and disease presentation.

Results: Combined analysis revealed a significant decrease in Vitamin D level in systemic sclerosis patients comparatively to healthy controls, with raw mean differences 95% CI = -11.68 [-15.43 to -7.92] ng/mL, p < 1 E-10. Likewise, Vitamin D insufficiency (Vitamin D < 30 ng/mL) and deficiency (<10 ng/mL) were significantly associated with systemic sclerosis; odds ratios 95% CI = 3.58 [2.59-4.95], p < 1 E-10 and odds ratios 95% CI = 7.67 [3.97-14.83], p < 1 E-10, respectively. Moreover, decreased Vitamin D level was significantly associated with interstitial lung disease occurrence (raw mean differences 95% CI = -3.61 [-6.93 to -0.3], p = 0.003), while Vitamin D deficiency was associated with increased systolic pulmonary arterial pressure, raw mean differences (95% CI = 4.17 [1.44-6.89], p = 0.003). Besides, Vitamin D level was negatively correlated with the modified Rodnan skin score, r (95% CI = -0.26 [-0.44 to -0.08], p = 0.004). Conversely, Vitamin D level was significantly increased in systemic sclerosis patients with cutaneous calcinosis, raw mean differences (95% CI = 4.18 [1.07-7.28], p = 0.008).

Conclusion: This meta-analysis showed that decreased Vitamin D level was associated with susceptibility to systemic sclerosis, interstitial lung disease occurrence, increased systolic pulmonary arterial pressure, and higher modified Rodnan skin score. Conversely, calcinosis was found to be associated with increased Vitamin D level.

Registration: This review has been registered on PROSPERO: CRD42024565045, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565045.

Keywords: Systemic sclerosis; Vitamin D; meta-analysis; meta-regression; systematic review.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors report that there are no competing interests to declare. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram for study selection.
Figure 2.
Figure 2.
Summary of study risk of bias.
Figure 3.
Figure 3.
Forest plot for the association between Vit D level and susceptibility to SSc.
Figure 4.
Figure 4.
Outlier analysis for the association of Vit D level with susceptibility to SSc: (a) externally standardized residuals; (b) difference-in-fit standardized (DFFITS) statistic; (c) Cook’s distances; (d) Covariance ratios; (e) leave-one-out Tau2 estimates; and (f) leave-one-out (residual) heterogeneity test statistic.
Figure 5.
Figure 5.
Forest plot for the association between Vit D insufficiency and SSc predisposition.
Figure 6.
Figure 6.
Forest plot for the association between Vit D deficiency and SSc predisposition.
Figure 7.
Figure 7.
Forest plot for the association between Vit D level and SSc subtypes.
Figure 8.
Figure 8.
Forest plot for the association between Vit D deficiency and mRSS
Figure 9.
Figure 9.
Forest plot for the correlation between Vit D level and mRSS.
Figure 10.
Figure 10.
Outlier analysis for the correlation of Vit D level with mRSS: (a) externally standardized residuals; (b) difference-in-fit standardized (DFFITS) statistic; (c) Cook’s distances; (d) covariance ratios; (e) leave-one-out Tau2 estimates; and (f) leave-one-out (residual) heterogeneity test statistic.
Figure 11.
Figure 11.
Forest plot for the association between Vit D level and ILD.
Figure 12.
Figure 12.
Forest plot for the association between Vit D deficiency and ILD.
Figure 13.
Figure 13.
Forest plot for the association between Vit D deficiency and sPAP.
Figure 14.
Figure 14.
Forest plot for the association between Vit D deficiency and DU.
Figure 15.
Figure 15.
Forest plot for the association between Vit D level and DU.
Figure 16.
Figure 16.
Forest plot for the association between Vit D level and DTI.
Figure 17.
Figure 17.
Forest plot for the association between Vit D level and calcinosis.
Figure 18.
Figure 18.
Forest plot for the association between Vit D insufficiency and Scl70 Ab.
Figure 19.
Figure 19.
Forest plot for the association between Vit D insufficiency and FVC.
Figure 20.
Figure 20.
Funnel plots assessing publication bias: overall symmetrical funnel plots with no evidence of publication biases. (a) Vit D level in SSc patients vs. controls. (b) Vit D insufficiency in SSc patients vs. controls. (c) Vit D deficiency in SSc patients vs. controls. (d) Vit D level in dSSc vs.lSSc. (e) Vit D deficiency association with mRSS. (f) Correlation between Vit D level and mRSS. (g) Vit D level in patients with or without ILD. (h) Vit D deficiency association with ILD. (i) Vit D deficiency association with sPAP. (j) Vit D deficiency association with digital ulcers. (k) Vit D level in patients with or without digital ulcers. (l) Vit D level association with digestive tract involvement. (m) Vit D level in patients with or without calcinosis. (n) Association of Vit D insufficiency with anti-Scl70 Ab.
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