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Table 1 Serum vitamin D levels in CSU patients

From: Relationship between vitamin D and chronic spontaneous urticaria: a systematic review

Study, year Study size/population Vitamin D data Outcome
Methods Units Serum 25(OH)D levels
CSU Controls
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
(UAS4a: 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/mLb 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)
  1. 25(OH)D, 25-hydoxyvitamin D; anti-TG, anti-thyroglobulin; anti-TPO, anti-thyroidperoxidase; APST, autologous plasma skin test; ASST, autologous serum skin test; BMI, body mass index; CSU, chronic spontaneous urticaria; CU-Q2oL, chronic urticaria quality of life questionnaire; DLQI, Dermatology Life Quality Index; ELISA, enzyme linked immunesorbent assay; ESR, erythrocyte sedimentation rate; Ig, immunoglobulin; IL, interleukin; ND, not defined; TGF-β1, transforming growth factor β1; UAS, urticaria activity score; USS, urticaria symptom severity
  2. aUAS4 (the Urticaria Activity Score over 4 days; (scale 0–6) calculated as the sum of daily average morning and evening scores for itch severity (0, none; 1, mild; 2, moderate; 3, severe) and number of hives (0, none; 1, < 20 hives; 2, 20–50 hives; and 3, > 50 hives)
  3. bSerum vitamin D was evaluated as 25(OH)D3