Background
Methods
Search strategy and selection criteria
Assessment of risk of bias in included studies
Data extraction for serum vitamin D levels and CSU
Data extraction for treatment or supplementation of vitamin D
Results
Literature search
Characteristics of included studies
Risk of bias
Serum vitamin D levels in CSU patients
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) |
Outcome measurement | Pro | Cons | Results | References |
---|---|---|---|---|
Lower serum vitamin D levels in CSU patients than healthy controls | ✓ | One study showed significantly higher levels of vitamin D in CSU patients than that of controls | Wu et al. [30] | |
– | – | One study showed no significant difference in vitamin D levels between CSU patients and that of controls | Lee et al. [22] | |
✓ | Twelve studies showed significant lower levels of vitamin D in CSU patients than that of controls | Thorp et al. [28] Grzanka et al. [21] Chandrashekar et al. [20] Abdel-Rehim et al. [18] Movahedi et al. [23] Woo et al. [29] Rasool et al. [25] Boonpiyathad et al. [31] Oguz Topal et al. [24] Nasiri-Kalmarzi et al. [14] Dabas et al. [32] Rather et al. [33] | ||
Vitamin D insufficiency in CSU patients more than in controls | ✓ | One study showed significantly higher prevalence of vitamin D insufficiency in controls than in CSU | Movahedi et al. [23] | |
✓ | Two studies showed no significant difference in the prevalence of vitamin D insufficiency between CSU patients and controls | Grzanka et al. [21] | ||
✓ | One study showed significant difference in the prevalence of vitamin D insufficiency between CSU patients and controls | Oguz Topal et al. [24] | ||
Vitamin D deficiency in CSU patients more than in controls | – | – | One study showed no significant difference in the prevalence of vitamin D deficiency between CSU patients and controls | Thorp et al. [28] |
✓ | Three studies showed significant difference in the prevalence of vitamin D deficiency between CSU patients and controls | Grzanka et al. [21] Boonpiyathad et al. [31] Oguz Topal et al. [24] | ||
✓ | One study show significant difference in the proportion of critically low vitamin D levels in the CSU patients and in acute urticaria, atopic dermatitis, and healthy controls | Woo et al. [29] | ||
Lower serum vitamin D levels between CSU and acute urticaria | ✓ | One study showed no significant difference levels of vitamin D between CSU and acute urticaria patients | Lee et al. [22] | |
✓ | One study showed significantly lower levels of vitamin D in CSU than acute urticaria patients | Woo et al. [29] | ||
Lower serum vitamin D levels between CSU and atopic dermatitis | ✓ | One study showed significantly lower levels of vitamin D in CSU than atopic dermatitis | Woo et al. [29] | |
Lower serum vitamin D levels between CSU and allergic rhinitis | ✓ | One study showed significantly lower levels of vitamin D in CSU than allergic rhinitis | Thorp et al. [28] | |
Low serum vitamin D levels and higher disease activity | ✓ | One study reported a significant positive correlation between vitamin D levels and urticaria activity score | Movahedi et al. [23] | |
– | – | Six studies reported no association | Thorp et al. [28] Abdel-Rehim et al. [18] Grzanka et al. [21] Rorie et al. [26] Boonpiyathad et al. [31] Oguz Topal et al. [24] | |
✓ | Three study reported significant negative association between vitamin D levels and urticaria activity score One study reported significant negative association between vitamin D levels and urticaria severity score | Woo et al. [29] Nasiri-Kalmarzi et al. [14] Rather et al. [33] Chandrashekar et al. [20] | ||
Low serum vitamin D levels and longer disease duration | – | – | Five studies reported no association | Thorp et al. [28] Abdel-Rehim et al. [18] Grzanka et al. [21] Dabas et al. [32] Rather et al. [33] |
✓ | One studies reported significant negative association | Woo et al. [29] | ||
Low serum vitamin D levels and high ESR | ✓ | Two study reported significant correlation | Chandrashekar et al. [20] Boonpiyathad et al. [31] | |
Low serum vitamin D levels and high CRP levels | – | – | One study reported no association | Grzanka et al. [21] |
Low serum vitamin D levels and high IgE levels | ✓ | One study reported negative association | Abdel-Rehim et al. [18] | |
– | – | Four studies reported no association | Movahedi et al. [23] Oguz Topal et al. [24] Nasiri-Kalmarzi et al. [14] Dabas et al. [32] | |
Low serum vitamin D levels and high IL-17 levels | ✓ | One study reported negative association. | Chandrashekar et al. [20] | |
Low serum vitamin D levels and TGF-β1 | ✓ | One study reported negative association | Chandrashekar et al. [20] | |
Low serum vitamin D levels and thyroid autoantibodies testing | – | – | Two studies reported no association | Thorp et al. [28] Oguz Topal et al. [24] |
Low serum vitamin D levels and a positive ASST or APST | ✓ | One study reported significant lower levels of vitamin D in patients with a positive APST | Chandrashekar et al. [20] | |
✓ | Three study reported significant lower levels of vitamin D in patients with a positive ASST. | Woo et al. [29] Nasiri-Kalmarzi et al. [14] Rather et al. [33] | ||
– | – | Three studies reported no association between the ASST-positive and ASST-negative groups | Thorp et al. [28] Grzanka et al. [21] Dabas et al. [32] |
Degree of severity of serum vitamin D levels in CSU patients
Studies | Thorp et al. [28] | Chandrashekar et al. [20] | Grzanka et al. [21] | Movahedi et al. [23] | Woo et al. [29] | |||||
---|---|---|---|---|---|---|---|---|---|---|
Cases | Allergic rhinitis controls | Cases | Healthy controls | Cases | Healthy controls | Cases | Healthy controls | Cases | Healthy controls | |
N | 25 | 25 | 45 | 45 | 35 | 33 | 114 | 187 | 72 | 72 |
Vitamin D levels | 29.4 (mean) | 39.6 (mean) | 12.7 ± 2.7 | 24.3 ± 13.5 | 26.0 (median) | 31.1 (median) | 15.8 | 22.6 | 11.86 (mean) | 20.77 (mean) |
Sufficiency | ND | ND | ND | 11/45 (24.44%) | ND | ND | 10 (8.8%) | 49 (26.2%) | 2 (2%) | 15 (20%) |
Insufficiency | ND | ND | ND | 18/45 (40%) | 11 (31.4%) | 13 (39.4%) | 18* (15.8%) | 31 (16.6%) | 7 (10%) | 20 (27%) |
Deficiency | 12 (48%) | 7 (28%) | ND | 16/45 (35.55%) | 11* (31.4%) | 2 (6%) | 86 (75.4%) | 107 (57.2%) | 28 (39%) | 32 (45%) |
Severe deficiency | ND | ND | ND | ND | 1 (2.9%) | 0 (0%) | ND | ND | 35* (49%) | 5 (8%) |
Definition | ||||||||||
Sufficiency | ND | > 30 ng/mL | ≥ 30 ng/mL | ND | ≥ 30 ng/mL | |||||
Insufficiency | ND | Between 20 and 30 ng/mL | 20–< 30 ng/mL | 20–30 ng/mL | Between 20 and 29 ng/mL | |||||
Deficiency | < 30 ng/mL | < 20 ng/mL | < 20 ng/mL | < 20 ng/mL | < 20 ng/mL | |||||
Critically low/Severe deficiency | ND | ND | < 10 ng/mL | ND | < 10 ng/mL |
Studies | Rasool et al. [25] | Boonpiyathad et al. [31] | Oguz Topal et al. [24] | Nasiri-Kalmarzi et al. [14] | Rather et al. [33] | |||||
---|---|---|---|---|---|---|---|---|---|---|
Cases | Healthy controls | Cases | Healthy controls | Cases | Healthy controls | Case | Healthy controls | Case | Controls | |
N | 147 | 130 | 60 | 40 | 58 | 45 | 110 | 110 | 110 | 110 |
Vitamin D levels | 17.87 (mean) | 27.65 (mean) | 15.0 (median) | 30.0 (median) | 8.45 (median) | 15.3 (median) | 19.26 ± 1.26 (mean) | 31.72 ± 7.14 (mean) | 19.6 ± 6.9 (mean) | 38.5 ± 6.7 (mean) |
Sufficiency | ND | ND | ND | ND | ND | ND | ND | ND | 23 (20.91%) | 71 (64.54%) |
Insufficiency | 91.3% | 63.84% | 28% | 45% | 57* (98.3%) | 39 (86.7%) | 58.02% | 48.89% | 17 (15.45%) | 24 (21.82%) |
Deficiency | 55%* | 0% | 52* (89.7%) | 31 (68.9%) | 70 (63.64%) | 15 (13.64%) | ||||
Severe deficiency | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
Definition | ||||||||||
Sufficiency | > 30 ng/mL | ND | > 30 µg/L | ND | > 30 ng/mL | |||||
Insufficiency | 20–30 ng/mL | > 20–< 30 ng/mL | < 30 µg/L | ND | 20–30 ng/mL | |||||
Deficiency | 10–< 20 ng/mL | < 20 ng/mL | < 20 µg/L | ND | < 20 ng/mL | |||||
Critically low/Severe deficiency | < 10 ng/mL | ND | ND | ND | ND |
Other effects of vitamin D on CSU
Outcome of vitamin D supplementation on CSU patients
Study, year | Study design | N | Enroll | Concomitant medications | Intervention (Dose, type, duration,source) | Duration | Main outcome measurement | Vitamin D status (ng/mL) | Outcome | |
---|---|---|---|---|---|---|---|---|---|---|
Before | End of treatment | |||||||||
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. |
Study, year | Study design | N | Enroll | Concomitant medications | Intervention (Dose, type, duration, source) | Duration | Main outcome measurement | Vitamin D status (ng/mL) | Outcome | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Before | End of treatment | ||||||||||||
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. |
N | Sindher et al. [27]** | Rorie et al. [26]†† | Rasool et al. [25]§§ | Oguz Topal et al. [24] | Boonpiyathad et al. [31] | Ariaee et al. [19] | Dabas et al. [32] | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 21 | 21 | 48 | 57 | 57 | 50 | 20 | 200 | |||||||||
Intervention | Vitamin D3 400 IU/day | Vitamin D3 2000 IU/day | Vitamin D3 4000 IU/day | Vitamin D3 600 IU/day | Vitamin D3 60,000 IU/week | Vitamin D3 60,000 IU/week, 4 weeks Hydroxyzine 25 mg/day, 6 weeks Corticosteroid 6 mg/day, 6 weeks | Vitamin D3 300,000 IU/month | Vitamin D2 20,000 IU/day | Vitamin D (unknown form) 50,000 unit/week | Vitamin D (unknown form)
Group A
Vitamin D 2000 IU/day
Group B
Vitamin D 60,000 IU/week
Group C
None | |||||||
Duration | 8 weeks | ND | 12 weeks | 12 weeks | 4 weeks | 4 weeks | 12 weeks | 6 weeks | 8 weeks | 12 weeks | |||||||
Vitamin D status (ng/mL)
| |||||||||||||||||
Before treatment | 4.7 | ND | 28.8 ± 2.2 | 37.1 ± 3.4 | 16.98 ± 1.43 | 18.95 ± 1.42 | ND | 13 (8–29) median (min–max) | ND | ND | |||||||
End of treatment | ND | 65 | 56.0 ± 3.9 | 35.8 ± 2.3 | 56.74 ± 3.76 (p < 0 .0001) | 41.73 ± 2.85 (p < 0.0001) | ND | 40 (28–62) median (min–max) | ND | ND | |||||||
Outcome | Continued to have intermittent urticaria | Complete resolution without antihistamine |
Decrease total USS scores
(mean ± SE) |
VAS score
(mean ± SEM)
|
UAS4
(median(min–max))
|
UAS7
|
USS
(mean ± SD)
|
UAS4 (mean)
| |||||||||
15.0 ± 2.9 (p = 0.02) | 24.1 ± 4.0 |
Before
|
After
|
Before
|
After
|
Before
|
After
|
Before
|
After
|
Before
|
After
|
Before
| After 6 weeks | After 12 weeks | |||
6.7 ± 0.04 | 5.2 ± 0.70 p = 0.009 | 6.68 ± 0.40 | 1.86 ± 0.39 p < 0.0001 | 21 (0–42.0) | 6 (0–21.0) p < 0.001 | 27 (6–38) | 15 (2–33) | 235 ± 13.9 | 11.2 ± 9.6 |
GroupA
| |||||||
11.8 ± 7.6 | 6.6 ± 6.0 | 5.3 ± 5.2 | |||||||||||||||
5-D itch score
(mean)
|
CU-Q2oL
(median(min–max))
|
DLQI scores
|
DLQI scores
(mean ± SD)
|
Group B
| |||||||||||||
Before
|
After
|
Before
|
After
|
Before
|
After
|
Before
|
After
|
Before
|
After
| 13.0 ± 8.0 | 6.4 ± 5.0 | 4.2 ± 3.5 | |||||
14.5 ± 0.72 | 12.06 ± 1.10 p = 0.007 | 13.9 ± 0.68 | 5.01 ± 0.94 p < 0.0001 | 38 (6.5–115.2) | 10.8 (0–43.4) p < 0.001 | 13 (4–31) | 6 (1–20) | 10.8 ± 1.6 | 0.9 ± 4.8 |
Group C
| |||||||
12.9 ± 7.03 | 8.0 ± 5.7 | 6.1 ± 4.8 |