Table 1 Serum vitamin D levels in CSU patients

Cross-sectional study

Chandrashekar et al. [20]

45 CSU

45 age-, sex-matched healthy controls

ELISA kit

(Euroimmun AG, Lubeck, Germany)

ng/mL

12.7 ± 2.7

(mean ± SD)

24.3 ± 13.5

(mean ± SD)

(p < 0.0001)

Significant lower vitamin D levels among chronic urticaria patients and controls

Significant lower vitamin D levels in APST positive group (11.1 ± 2.1 ng/mL) compared with APST negative group (15.1 ± 1.3 ng/mL) (p < 0.0001)

Significant negative correlation between vitamin D levels and USS, IL-17, TGF-β1 and ESR (p < 0.0001)

Lee et al. [22]

57 CSU

567 acute urticaria

3159 controls

ND

ng/mL

22.9 ± 4.9

(mean ± SD)

Acute urticaria; 20.5 ± 5.1

(mean ± SD)

(p = 0.069)

Controls; 20.0 ± 5.1

(mean ± SD)

(p = 0.124)

The study was conducted in children

No significant difference in the 25(OH)D levels between CSU patients and acute urticaria patients and controls (p = 0.183)

Rather et al. [33]

110 CSU

110 age-, sex-matched healthy controls

Chemiluminescence method/kit method (Siemens, USA)

ng/mL

19.6 ± 6.9

(mean ± SD)

38.5 ± 6.7

(mean ± SD)

(p < 0.001)

Significant lower vitamin D levels in CSU patients compared with controls

Significant negative correlation between serum vitamin D level and UAS (p < 0.001)

Significant lower vitamin D levels in CSU patients with the ASST positive subjects than in the ASST negative subjects (p < 0.001)

No significant correlation between vitamin D level and duration of the disease

Case–control study

Thorp et al. [28]

25 CSU

25 allergic rhinitis controls

ND

ng/mL

29.4 ± 13.4

(mean ± SD)

39.6 ± 14.7

(mean ± SD)

(p = 0.016)

Significantly reduced vitamin D levels in CSU patients compared with controls

No correlation of vitamin D levels and duration, severity of disease, ASST or thyroid autoantibody testing

No significant difference in the proportion of vitamin D deficiency between CSU groups and controls

Vitamin D status

Vitamin D deficiency (< 30 ng/mL)

48% (12/25)

28% (7/25)

(p = 0.24)

Abdel-Rehim et al. [18]

22 CSU

20 age- and sex-matched controls

Disease severity

8 (36.4%): moderate urticaria

(UAS7 = 16–27)

14 (63.6%): severe urticaria

(UAS7 = 28–42)

ELISA kit (Immundiagnostik AG,

Bensheim, Germany)

nmol/L

28.4 ± 9.09

(mean ± SD)

104.5 ± 76.8

(mean ± SD)

(p < 0.01)

Significantly lower vitamin D levels among patients in comparison to controls

Negative correlation between vitamin D levels and IgE levels (r = 0.45, p < 0.05)

No association between vitamin D levels and duration and the severity of the disease

Grzanka et al. [21]

35 CSU

33 age-, sex- and BMI (< 30) matched healthy controls

An automated direct electrochemiluminescence

immunoassay

(Elecsys, Roche Diagnostic, Mannheim Germany)

ng/mL

26.0

(median)

31.1

(median)

(p = 0.017)

Significantly lower serum 25(OH)D concentration in CSU group compared with the control subjects

No significant differences in serum 25(OH)D concentration between the mild and moderate-severe symptoms patients

Slightly significantly lower 25(OH)D concentrations in moderate-severe CSU than those of the controls (22.6 vs 31.1 ng/mL, p = 0.048)

No significant difference in vitamin D levels between mild CSU and healthy control subjects

Significantly higher proportion of vitamin D deficiency (< 20 ng/mL) in patients with CSU than in the normal population

No significant difference in the prevalence of vitamin D insufficiency (20–29 ng/mL) between CSU patients and the normal subjects

No significant correlations between serum concentration of CRP and 25(OH)D levels

No significant difference in serum 25(OH) concentrations and ASST testing

Vitamin D status

Vitamin D insufficiency (20–< 30 ng/mL)

31.4% (11/35)

39.4% (13/33)

(p = 0.41)

Vitamin D deficiency (< 20 ng/mL)

31.4% (11/35)

6% (2/33)

(p = 0.025)

Severe vitamin D deficiency (< 10 ng/mL)

2.9% (1/35)

0% (0/33)

(p = 0.52)

Movahedi et al. [23]

114 CSU

187 sex- and age-matched healthy controls

Enzyme immunoassay method (EIA) (Immunodiagnostic system; IDS (LTD), UK)

ng/mL

15.8 ± 1.5

22.6 ± 1.6

(p = 0.005)

Significantly lower serum 25(OH)D concentration in CSU group compared to healthy subjects

No significant differences in vitamin D levels between autoimmune chronic urticaria patients and the control group (p = 0.11)

Significant association between vitamin D deficiency and increased susceptibility to CSU (p = 0.001)

A 2.4-fold (95% CI 1.4–4) risk of having CSU in individuals with vitamin D deficiency (< 20 ng/ml)

Significantly lower levels of vitamin D in patients with longer duration of urticaria symptoms (> 24 h) (p = 0.046)

A significant positive correlation between vitamin D levels and UAS (r = 0.2, p = 0.042)

No significant relationship between IgE levels and vitamin D levels

Vitamin D status

Vitamin D sufficiency

8.8% (10/114)

26.2% (49/187)

Vitamin D insufficiency (20–30 ng/mL)

15.8% (18/114)

16.6% (31/187)

Vitamin D deficiency (< 20 ng/mL)

75.4% (86/114)

57.2% (107/187)

Rasool et al. [25]

(Randomized

case–control)

147 moderate-severe CSU

130 healthy controls

Enzyme immunoassay

ng/mL

17.87 ± 1.22

(mean ± SEM)

27.65 ± 1.65

(mean ± SEM)

(p < 0.0001)

Low serum 25(OH)D levels in 91% of CSU patients and 64% of the healthy subjects

Significantly lower vitamin D levels in CSU patients compared with controls

Vitamin D status

Vitamin D insufficiency (20–30 ng/mL)

or Vitamin D deficiency (10–20 ng/mL)

91.3%

63.84%

(p < 0.0001)

Boonpiyathad et al. [31]

(Prospective

case–control)

60 CSU

40 healthy controls

ND

ng/mL

15.0 (7–52)

median (min–max)

30.0 (25–46)

median (min–max)

(p < 0.001)

Significantly lower the median 25(OH)D concentration in the CSU group than the control group

Significantly higher patients with vitamin D deficiency (< 20 ng/mL) in the CSU group than the control group (p < 0.001)

No association between UAS7 and DLQI scores with 25(OH)D levels

Significant correlation between ESR and vitamin D levels (p = 0.001)

Vitamin D status

Vitamin D insufficiency (> 20–< 30 ng/mL)

28%

45%

(p = 0.38)

Vitamin D deficiency (< 20 ng/mL)

55%

0%

(p < 0.001)

Oguz Topal et al. [24]

(Prospective

case–control)

58 CSU

45 healthy age-matched controls

Disease severity

3 (5.2%): mild urticaria

(UAS4^a: 0–8)

15 (25.8%): moderate urticaria

(UAS4: 9–16)

40 (68.9%): severe urticaria

(UAS4: 17–24)

An automated direct electrochemiluminescence immunoassay

(Elecsys, Roche Diagnostic, Mannheim, Germany)

ug/L

All CSU

8.45 (1.1–52.5)

median (min–max)

(p < 0.001)

Mild-moderate CSU

8.95 (3.9–23.0)

median (min–max)

(p = 0.011)

Severe CSU

7.1 (1.1–52.5)

median (min–max)

(p < 0.001)

15.3 (3.1–61.0)

median (min–max)

Significantly lower serum 25(OH)D concentration in total CSU group, mild-moderate CSU group and severe CSU group compared to healthy subjects

Significantly higher prevalence of vitamin D deficiency and insufficiency in CSU patients

No significant differences in 25(OH)D levels between CSU patients with mild-moderate symptoms and severe symptoms

No significant differences between vitamin D-deficient or insufficient group regarding CU-Q2oL and UAS4 scores (p > 0.001)

No association between the anti-TG and the anti-TPO autoantibodies and the levels of vitamin D in CSU patients, (p = 0.641 and p = 0.373, respectively)

No association between the prevalence of high levels of total IgE and the levels of vitamin D in CSU patients (p = 0.5)

Vitamin D status

Vitamin D insufficiency (< 30 μg/L)

98.3% (57/58)

86.7% (39/45)

(p = 0.041)

Vitamin D deficiency (< 20 μg/L)

89.7% (52/58)

68.9% (31/45)

(p = 0.017)

Nasiri-Kalmarzi et al. [14]

110 CSU

110 healthy controls

Specific E LISA

(Monobind Inc., Lake Forest, CA, USA)

ng/mL

19.26 ± 1.26

(mean ± SEM)

31.72 ± 7.14

(mean ± SEM)

(p = 0.006)

Significantly lower serum vitamin D levels in chronic urticaria patients compared to controls

Significantly association between decreased levels of serum vitamin and increased susceptibility to chronic urticaria (p = 0.027)

Significant negative correlation between vitamin D levels with ASST and UAS (p < 0.001 and p = 0.001, respectively)

No significant correlation between vitamin D levels and serum total IgE (p = 0.083)

Higher prevalence of vitamin D deficiency or insufficiency in chronic urticaria patients

No significant correlation between vitamin D levels and total IgE levels

Vitamin D status

Vitamin D deficiency or insufficiency

58.02%

48.89%

Randomized controlled trial

Dabas et al. [32]

241CSU

184 healthy controls

ND

nmol/L

17.47 ± 13.36

(mean ± SD)

22.09 ± 14.06

(mean ± SD)

(p = 0.002)

Significantly lower vitamin D level were in CSU patients than in healthy controls

No correlation between vitamin D deficiency and sex, ASST, APST, serum IgE, angioedema or disease duration

Vitamin D status

Vitamin D sufficiency (> 30 ng/mL)

20.91% (23/110)

64.54% (71/110)

Vitamin D insufficiency (20–30 ng/mL)

15.45% (17/110)

21.82% (24/110)

Vitamin D deficiency (< 20 ng/mL)

63.64% (70/110)

13.64% (15/110)

Retrospective study

Woo et al. [29]

72 CSU

26 acute urticaria

26 atopic dermatitis

72 healthy controls

ND

ng/mL^b

CSU

Acute urticaria

Atopic dermatitis

Healthy controls

Both children and adults were enrolled

Significantly lower serum 25(OH)D₃ levels in CSU group compared to those in the other groups

Significantly higher proportion of patients with critically low vitamin D levels (< 10 ng/mL) in the CSU group than in acute urticaria, atopic dermatitis, and healthy controls

Significant negative associations between the vitamin D levels and urticaria activity score and disease duration (p < 0.001, p = 0.008, respectively)

Significantly more critically low vitamin D status in the moderate/severe UAS group than in the mild UAS group (p = 0.03)

Significantly lower serum vitamin D levels in subjects with a positive ASST than in subjects with a negative result

Significantly higher number of patients with critically low vitamin D in the moderate/severe UAS group than in the mild UAS group (p = 0.03)

Significantly lower vitamin D levels in the ASST positive subjects (9.12 ± 4.25 ng/mL) than in the ASST negative subjects (13.33 ± 7.09 ng/mL) (p = 0.034)

Significantly higher proportion of those with critically low vitamin D status in the ASST positive group (60%) than in the ASST negative group (32%) (p = 0.021)

11.86 ± 7.16

(mean ± SD)

14.12 ± 5.56

(mean ± SD)

(p = 0.024)

16.12 ± 8.09

(mean ± SD)

(p = 0.008)

20.77 ± 9.74

(mean ± SD)

(p < 0.001)

Vitamin D status

Sufficiency (≥ 30 ng/mL)

2% (2/72)

0%

2%

20% (15/72)

Insufficiency (between 20 and 29 ng/mL)

10% (7/72)

11%

24%

27% (20/72)

Deficiency (< 20 ng/mL)

39% (28/72)

63%

46%

45% (32/72)

Critically low (< 10 ng/mL)

49% (35/72)

26% (6/26)

(p < 0.002)

28% (7/26)

(p < 0.004)

8% (5/72)

(p < 0.001)

Wu et al. [30]

225 CSU

1321 healthy controls

ND

nmol/L

CSU

Controls

Significantly higher vitamin D levels in CSU patients than the general population

51.4 ± 27.03

(mean ± SD)

45.4 ± 24.84

(mean ± SD)

(p = 0.001)