Table 4 Outcome of vitamin D supplement in CSU patients

Sindher et al. [27]

Case report

1

Chronic urticaria

Calcium citrate 800 mg/day

Fexofenadine

Aluminium/magnesium antacid

Vitamin D3 (Cholecalciferol 400 IU/day

8 weeks

ND

4.7

ND

Continued to have intermittent urticaria

Then increased to 2000 IU/day)

ND

ND

65

Complete resolution without antihistamine

Rorie et al. [26]

Prospective,double-blinded, randomized controlled trial

(single-center clinical study)

42

CSU receiving high dose vitamin D3 (4000 IU/day) supplementation

(n = 21)

Cetirizine

Ranitidine

Montelukast

Use for intolerable or uncontrolled symptoms

Prednisolone

Hydroxychloroquine

Vitamin D3 4,000 IU/day

12 weeks

USS

Vitamin D status

(mean ± SE)

Decrease total USS scores

(mean ± SE)

28.8 ± 2.2

56.0 ± 3.9

15.0 ± 2.9

(p = 0.02)

CSU receiving low dose vitamin D3 (600 IU/day) supplementation

(n = 21)

Vitamin D3 600 IU/day

37.1 ± 3.4

35.8 ± 2.3

24.1 ± 4.0

Significant decrease in total USS score in the high, but not low, vitamin D3 treatment group by week 12 (p = 0.02)

No correlation between 25(OH)D levels and USS score at baseline (r = 0.07, p = 0.65) or at week 12 (r = 0.13, p = 0.45)

The high vitamin D3 treatment group showed a decreased total USS score compared with the low vitamin D3 treatment group, but this did not reach statistical significance (p = 0.052)

Subjects in the high vitamin D3 treatment group reported decrease body distribution of hives on an average day (p = 0.033), decrease body distribution of hives on the worst day (p = 0.0085), and decrease number of days with hives (p = 0.03) compared with subjects in the low vitamin D3 treatment group.

Rasool et al. [25]

Randomized case–control study

147

CSU

Any vitamin D levels (serum 25(OH)D) from

Group 1

Severe deficiency

Vitamin D levels < 10 ng/mL

Group 2

Deficient levels

Vitamin D levels

10–< 20 ng/mL

Group 3

Insufficient levels

Vitamin D levels

20–30 ng/mL

Group 4

Sufficient levels

Vitamin D levels

> 30 ng/mL)

Then randomized to

Sub-group A (n = 48)

sub-group B

(n = 42)

Sub-group C (n = 57)

6 weeks

VAS

5-D itch score

Vitamin D status

(mean ± SEM)

VAS score

(mean ± SEM)

5-D itch score

(mean)

Before

After

Before

After

Before

After

Sub-group A

Sub-group A

Sub-group A

Sub-group A

None

Vitamin D3 (cholecalciferol) 60,000 IU/week for 4 weeks

16.98 ± 1.43

56.74 ± 3.76

(p < 0 .0001)

6.7 ± 0.043

5.2 ± 0.70

(p = 0.0088)

14.5 ± 0.72

12.06 ± 1.10

(p = 0.0072)

Sub-group B

Sub-group B

Sub-group B

Sub-group B

Hydroxyzine

25 mg/day for 6 weeks

Corticosteroids

(deflazacort)

6 mg/day for 6 weeks

None

17.04 ± 1.54

16.44 ± 1.50

6.6 ± 0.42

3.3 ± 0.50

(p < 0.0001)

13.9 ± 0.77

8.1 ± 1.13

(p < 0.001)

Sub-group C

Sub-group C

Sub-group C

Sub-group C

Hydroxyzine

25 mg/day for 6 weeks

Corticosteroids

6 mg/day for 6 weeks

Vitamin D3 60,000 IU/week for 4 weeks

18.95 ± 1.42

41.73 ± 2.85 (p < 0.0001)

6.68 ± 0.40

1.86 ± 0.39

(p < 0.0001)

13.9 ± 0.68

5.01 ± 0.94

(< 0.0001)

Significantly decreased in VAS in every groups

Significantly decreased in 5D itch score in every groups

Improvement in the CSU symptoms in patients with vitamin D3 as monotherapy

Better improvement of symptoms and quality of life in combinatorial therapy group than standard therapeutic regimen group

Significant difference in VAS in subgroup A compared to subgroup B and C (p = 0.016 and p < 0.0001, respectively)

Significant difference in VAS in subgroup C compare to subgroup B (p = 0.0203)

Significant difference in 5-D score in subgroup A compared to subgroup B and C (p = 0.0116 and p < 0.0001, respectively)

Significant difference in 5-D score in subgroup C compared to subgroup B (p = 0.0382)

130

Healthy control

None

None

6 weeks

Vitamin D levels

Group 1

No change in serum 25(OH)D levels

7.310 ± 0.52

5.899 ± 0.28

Group 2

15.26 ± 0.47

16.96 ± 1.26

Group 3

23.98 ± 0.46

23.15 ± 0.95

Group 4

47.78 ± 2.23

49.18 ± 2.97

Oguz Topal et al. [24]

Prospective case–control study

57

cases

CSU

Serum 25(OH)D < 30ug/L

None

Vitamin D3 300,000 IU/month

12 weeks

UAS4^‡‡

CU-Q2oL

ND

ND

UAS4

(median(min–max))

CU-Q2oL

(median(min–max))

Before

After

Before

After

21

(0–42.0)

6

(0–21.0)

(p < 0.001)

38

(6.5–115.2)

10.8

(0–43.4)

(p < 0.001)

Significant improvements in UAS4 and CU-Q2oL

Boonpiyathad et al. [31]

Prospective case–control study

50

cases

CSU

Serum 25(OH)D < 30 ng/mL

(vitamin D supplement group)

Non-sedative antihistamine

Ergocalciferol (vitamin D2) 20,000 IU/day

6 weeks

UAS7

DLQI

13 (8–29) median (min–max)

40 (28–62) median (min–max)

UAS7

DLQI scores

Before

After

Before

After

27

(6–38)

15

(2–33)

13

(4–31)

6

(1–20)

10 controls

CSU

Serum 25(OH)D ≥ 30 ng/ml

(non-vitamin D supplement group)

ND

None

6 weeks

UAS7

DLQI

37 (33–52)

median

(min–max)

38 (33–52)

median

(min–max)

26

(18–42)

26

(16–44)

12

(5–28)

14

(3–27)

Significant improvements in UAS7 and DLQI scores in the vitamin D supplement group compared with the non-vitamin D supplement group

Significant improvement of the median UAS7 score in the vitamin D supplement group than in the non-vitamin D supplement group

Significantly improvement of the median DLQI score in the vitamin D supplement compared with the non-vitamin D supplement group

None of the patients in the vitamin D supplement group were symptom-free at the optimal vitamin D levels.

Ariaee et al. [19]

Prospective study

20

CSU

Serum vitamin D concentration < 10 ng/mL

ND

Vitamin D 50,000 unit/week

8 weeks

USS

DLQI

ND

ND

USS (mean ± SD)

DLQI scores (mean ± SD)

Before

After

Before

After

235 ± 13.9

11.2 ± 9.6

10.8 ± 1.6

0.9 ± 4.8

Significant reduction in USS after vitamin D supplement

Improvement of DLQI (55%) after vitamin D supplement

Increase FOXP3 gene expression and downregulation of IL-10, TGF-beta and FOXP3, IL-17 after vitamin D supplement

Dabas et al. [32]

Randomized controlled trial

200

CSU

Serum 25(OH)D < 30 nmol/L

Levocetirizine 10 mg/day

Group A

Vitamin D 2000 IU/day

Group B

Vitamin D 60,000 IU/week

Group C

None

12 weeks

UAS4

ND

ND

UAS4 (mean)

Before

After 6 weeks

After 12 weeks

Group A

11.8 ± 7.6

6.6 ± 6.0

5.3 ± 5.2

Group B

13.0 ± 8.0

6.4 ± 5.0

4.2 ± 3.5

Group C

12.9 ± 7.03

8.0 ± 5.7

6.1 ± 4.8

No significant difference in mean UAS4 in the 3 groups after 12 weeks of vitamin D replacement

Vitamin D replacement decreased the severity in most patients.