Table 1 Characteristics and results of the selected studies

Ahmadi et al., 2017 [15]

Cross-sectional

15 ± 4.7

(60)

27.2 ± 8.7

(30)

-

-

-

-

Serum Klotho and vitamin D lower in SSc patients (p < 0.001). Higher intact PTH in SSc patients (p < 0.001).

Arnson et al., 2011 [16]

Cross-sectional

13.5 ± 9

(327)

21.6 ± 9.7

(141)

-

-

-

-

Lower vitamin D levels in SSc patients (p < 0.001). Association with lower DLCO (p < 0.02). Inverse association with skin extent (mRSS> 10; p = 0.02) and RF expression (p < 0.001).

Atteritano et al., 2013 [14]

Cross-sectional

18.3 ± 4.1

(54)

39.6 ± 7.5

(54)

-

-

-

-

Lower vitamin D levels in SSc patients (p < 0.001). Association with PTH (p = 0.001), osteocalcin (p < 0.05), deoxypyridinoline (p < 0.05) and BMD on lumbar spine and femur (p < 0.05).

Atteritano et al., 2016 [17]

Cross-sectional

25.8 ± 12.8

(40)

35.1 ± 9.1

(40)

0

(0)

20

(50)

Lower vitamin D levels in SSc patients (p = 0.0003). Association with skin extent (mRSS> 10; p = 0.02) and PASP> 35 mmHg (p = 0.02). No association with subtype and autoantibodies.

Belloli et al., 2011 [18]

Cross-sectional

18.1 ± 15.2

(43)

17.3 ± 12

(99 - OA)

15

(34.8)

37

(86)

No significantly difference in insufficiency or deficiency between groups, regardless of disease duration, subtype and autoantibodies.

Braun-Moscovici et al., 2008 [19]

Cross-sectional

-

(60)

-

-

26^a

(46)

-

-

High PTH associated with vitamin D deficiency (p = 0.01), calcinosis (p = 0.009), and acrosteolysis (p = 0.015). No significant correlation between supplementation and vitamin D levels.

Caimmi et al., 2019 [20]

Cohort

(65)

-

-

-

Lower vitamin D levels in patients with incident DU in relation to patients with no incident DU over 5 years (− 17.4 vs 13.0, p = 0,018).

Calzolari et al., 2009 [21]

Cross-sectional

23(3–92)^b

(18)(60)

39(14–138)^b

(60)

4

(6.7)

38

(63.4)

Lower vitamin D levels in SSc patients (p < 0.001). No association with disease subtype, cutaneous ulcers, skin extent, gastrointestinal and joint involvement.

Caramaschi et al., 2010 [22]

Cross-sectional

15.8 ± 9.1

(65)

-

-

19

(29.2)

62

(95.4)

Association with lung disease (p = 0.009),longer disease duration (p = 0.026), lower DLCO (p = 0.014), and higher PASP (p = 0.037), ESR (p = 0.001) and CRP (p = 0.004).

Carmel et al., 2015 [23]

Cross-sectional

-

(54)

-

(41)

-

-

39

(82.1)

Anti-25(OH) D IgM antibodies more frequent in SSc patients and in a higher level (p = 0.002). No correlation with severity, other autoantibodies and target organ damage.

Corrado et al., 2015 [12]

Cross-sectional

15.7 ± 10.2

(64)

22.9 ± 9.1

(35)

-

-

-

-

Lower vitamin D levels in patients, especially in diffuse cutaneous SSc (p < 0.001). Negative correlation with mRSS (p < 0.05). No association with any internal organ involvement.

Cruz-Domínguez et al., 2017 [24]

Cohort

-

(109)

-

-

-

-

-

-

Lower vitamin D levels in SSc patients with and without calcinosis (19.1 vs. 13.1; p = 0.56).

Di Liberto et al., 2019 [25]

Cross-sectional

22.1 ± 9.7 (45)

-

-

-

Low vitamin D levels in SSc patients. Similar percentage of regulatory T-cells (Tregs) in SSc patients and control group, with higher percentage in SSc patients taking cholecalciferol. Impaired Tregs capability to suppress T cell proliferation in SSc patients. Increase in IL-10 in vitro production of patients Tregs after treatment with (1,25(OH)2D3).

Gambichler et al., 2011 [26]

Cross-sectional

13.1(4–48)^b

(133)

-

-

49

(35.8)

123

(89.8)

No association with disease subtype, BMI, lung fibrosis, renal involvement, GERD, digital ulcers, mRSS, autoantibodies and therapy.

Giuggioli et al., 2017 [27]

Cross-sectional

9.8 ± 4.1^d

(140)

-

-

40/91^d

(44)

91/91^d

(100)

Lower vitamin D levels in not supplemented patients (9.8 ± 4.1 vs. 26 ± 8.1; p < 0.0001), but only 15/49 (31%) supplemented patients reached the normal range of vitamin D.

Groseanu et al., 2016 [8]

Cross-sectional

17.1 ± 9.1

(51)

-

-

12

(23.5)

46

(90.2)

Positive correlation with DLCO (p = 0.019). Negative correlation of vitamin D with diastolic dysfunction, digital contractures and muscle weakness. No correlation with autoantibodies or skin extent. Higher vitamin D levels in patients with usual supplementation (25.5%), but the difference between groups failed to reach statistical significance (p = 0.488).

Gupta et al., 2018 [28]

Cross-sectional

19.5 ± 77.8^c

(38)

100 ± 31.3^c

(38)

13

(34.2)

23

(60.5)

Lower vitamin D levels in SSc patients (p = 0.001). Inverse correlationwith mRSS. No correlation with age, disease duration, autoantibodies, digital ulcers, or systemic involvement.

Hajialilo et al., 2017 [29]

Cross-sectional

14.9 ± 4.6

(60)

30.4 ± 7.9

(60)

-

-

-

-

Serum ET-1 higher in SSc patients (p = 0.001). Serum α-Klotho and vitamin D lower in SSc patients (p = 0.001). Association of vitamin D with gastrointestinal involvement on Medsger severity scale (p = 0.003).

Hax et al., 2020 [30]

Cross-sectional

23.9 ± 8.5 (50)

30.2 ± 6.2 (35)

2 (4%)

36 (72%)

Lower vitamin D levels in SSc patients compared to control group and lower vitamin D levels in SSc patients not taking vitamin D supplementation. No associations between vitamin D and cytokine levels or between vitamind D levels and disease duration.

Ibn-Yacoub et al., 2012 [13]

Cross-sectional

10.9 ± 2.7

(30)

57.4 ± 4.2

(30)

8

(26.7)

30

(100)

Lower vitamin D levels in SSc patients (p = 0.001). Association with number of painful (p = 0.006) and swollen joints (p = 0.013) and anti-Scl70 (p = 0.027). Association of vitamin D with BMD on lumbar spine (p = 0.002) and femoral neck (p = 0.032).

Kamal et al., 2016 [31]

Cross-sectional

-

(30)

-

(60)

-

-

-

-

No association between VDR polymorphisms (ApaI and TaqI) and SSc susceptibility. Significant association between ApaI and diffuse cutaneous SSc.

Matsuoka et al., 1991 [32]

Cross-sectional

28 ± 3

(19)

29 ± 3

(19)

-

-

-

-

Hypovitaminosis D common in SSc patients and healthy controls. No correlation with skin extent.

Montabone et al., 2016 [33]

Cross-sectional

18.5(7.5–37)^b

(35)

-

-

4

(11)

30

(85)

Association with a worse physical component on SF-36 and physical function (p < 0.04). No association with gastrointestinal, kidney and cardiopulmonary involvement.

Orbach et al., 2007 [34]

Cross-sectional

11 ± 5.8

(229)

-

-

-

-

-

-

Lower vitamin D levels in different autoimmune diseases (SSc, SLE, PM, DM, APS, and RA).

Park et al., 2017 [35]

Cross-sectional

43.7(25–68)^b

(40)

57.5(40–81)^b

(80)

2

(5)

12

(30)

Association with digital ulcers (p = 0.012). No association with arterial stiffness, atherosclerosis, autoantibodies, mRSS, lung disease, PASP, ESR and CRP.

Rios Fernández et al., 2010 [36]

Cross-sectional

-

(48)

-

-

5

(9.5)

39

(81)

No significant vitamin D correlation with PASP or lung fibrosis. Hypovitaminosis D was common, despite 60.4% of patients were taking usual supplementation.

Rios Fernández et al., 2012 [37]

Cross-sectional

-

(90)

-

-

10

(11)

69

(76.7)

Association of vitamin D with calcinosis (p < 0.034), heart involvement (p < 0.012), DLCO (p < 0.006) and positive ANA (p < 0.017). Hypovitaminosis D was common, despite 58.9% of patients were taking usual supplementation. Vitamin D deficiency was not different between groups (52% vs. 66.7%).

Sampaio-Barros et al., 2016 [10]

Cross-sectional

20.7 ± 8.2

(38)

-

-

4

(11)

33

(87)

Vitamin D positive correlation with anti-Scl70 (p = 0.039) and some SF-36 domains (vitality, social function, emotional role and mental health). Negative correlation with HAQ-reach and HAQ-grip strength. Positive correlation of vitamin D with BMI (p = 0.038) and femur BMD (p = 0.037).

Seriolo et al., 2011 [38]

Cross-sectional

21.7 ± 13.4

(53)

39.4 ± 15.4

(35)

13

(24)

47

(88)

Seasonal variation in patients and controls (highest values in summer, p < 0.01). Significantly lower levels in SSc patients in all seasons.

Shinjo et al., 2011 [39]

Cross-sectional

18.1 ± 6.4

(10)

25.1 ± 6.6

(10)

-

-

-

-

Lower vitamin D levels in juvenile SSc patients (p = 0.04). Positive correlation with femur BMD (p = 0.02).

Taylan et al., 2019 [40]

Cross-sectional

8.7(4.5–18)^b

(46)

16.5(9–21)^b

(30)

Lower serum vitamin D levels in SSc patients (p = 0.02). No correlation with mRSS.

Trombetta et al., 2017 [41]

Cross-sectional

18.7 ± 9

(154)

-

-

-

-

124

(80.5)

Association of vitamin D with pulmonary fibrotic changes (p = 0.04). Correlation with some domains of Medsger severity scale (peripheral vascular, renal and gastrointestinal involvement). Vitamin D levels not influenced by usual supplementation (p = 0.81).

Ursini et al., 2017 [42]

Cohort

15.4(8–25)^b

(124)

-

-

-

-

13

(89.5)

Inverse correlation with mRSS (p = 0.03) and subclinical liver fibrosis (evaluated using the aspartate aminotransferase-to-platelet ratio index; p = 0.02). No correlation with age and disease duration.

Vacca et al., 2009 [9]

Cross-sectional

19 ± 11

(156)

-

-

44

(28)

131

(84)

Association of vitamin D with higher PASP (p = 0.004), lung fibrosis (p = 0.04), anticentromere (p = 0.04) and ESR (p = 0.008). No association with calcinosis, HAQ, or Medsger severity score. Negative correlation with EDAS (p = 0.04). Vitamin D levels not influenced by usual supplementation (p = 0.1).

Zhang et al., 2017 [43]

Cross-sectional

26.5 ± 6.3

(60)

36.3 ± 14.2

(60)

-

-

45

(75)

Lower vitamin D levels in SSc patients (p < 0.001). More frequent lung involvement, but without significance (p = 0.08). No difference in joint involvement, autoantibodies, ESR and CRP.