The prevalence and impact of vitamin D3 deficiency on chronic spontaneous urticaria: insights from a comparative study

To the Editor, Recent studies have shown complex relationships between vitamin D3 and various allergic diseases. Some suggest that vitamin D3 influences the pathophysiology of chronic spontaneous urticaria (CSU) and can improve clinical outcomes, while others indicate that supplementation may increase allergy prevalence [1]. We investigated the relationship between CSU and vitamin D3 to address these conflicting findings This study aimed to assess vitamin D3 levels in patients with CSU and compare them to a control group, examining the relationship between vitamin D3 levels and disease activity in terms of urticaria activity score (UAS7). Vitamin D3 levels were categorized as follows: less than 20 ng/ml indicated deficiency, 20–30 ng/ml indicated insufficiency, and more than 30 ng/ml indicated sufficiency. This hospital-based cross–sectional study, approved by the institutional ethics committee and registered with the Clinical Trial Registry of India (CTRI/2023/08/056420), recruited 110 CSU patients and 80 healthy controls over six months. Inclusion criteria were urticaria episodes at least twice per week for six weeks or more, with or without angioedema. Exclusion criteria included urticaria from physical factors, angioedema without urticaria, recent use of immunosuppressives, Schnitzler’s syndrome, and other conditions like systemic lupus and mastocytosis. Baseline serum vitamin D3 levels were measured using chemiluminescence. Detailed patient history, including age, sex, disease duration, angioedema, atopy, and autoimmune disease, was recorded, and disease severity was assessed using the UAS7 score. Demographic characteristics were similar between CSU patients and controls, with both groups having a higher proportion of females. CSU patients had significantly lower mean serum vitamin D3 levels (15.83±3.35 ng/ml) compared with controls (32.01±2.15 ng/ml), with a P value of less than 0.0001 (Table 1). Table 1 - Comparison of demographic characteristics and vitamin D3 levels between chronic spontaneous urticaria patients and healthy controls Parameters CSU patients (n=110) Healthy controls (n=80) Significance Age in years (Mean±SD) 29.3±10.58 27.85±11.87 0.649‡ Sex distribution- Female 73 (66.36) 45 (56.25) 0.705† Male 37 (33.63) 35 (43.75) Vitamin D3 (ng/ml) Deficiency 53 (48.18) 15 (18.75) <0.0001* Insufficiency 9 (8.18) 17 (21.25) <0.0001* Normal vitamin D3 48 (43.63) 48 (60) 0.51* Mean±SD 15.83±3.35 32.01±2.15 <0.0001‡ ‡Independent t test.*Fisher’s exact test.†Chi square test. In this cross–sectional study of 110 chronic spontaneous urticaria patients, 62 had low vitamin D and 48 had normal levels. Again, those with low vitamin D3 levels (<20 ng/ml) had significantly higher UAS7 scores (30.09±9.24) compared with patients with normal vitamin D levels (14.77±5.77), with a P value of less than 0.0001, indicating greater disease severity. Additionally, the duration of the disease was longer in the low vitamin D3 group (2.68 years) compared with the normal vitamin D3 group (1.61 years), with a P value of less than 0.002 (Table 2). Table 2 - Demographic and clinical parameters among the chronic spontaneous urticaria patients Clinical parameters CSU patients with low vitamin D3 (<20 ng/ml) (n=62) CSU patients with normal vitamin D3 (n=48) Significance UAS7 scores (Mean±SD) 30.09±9.24 14.77±5.77 <0.0001 Age (Mean±SD) 30.12±10.58 34.89±13.16 0.79 Sex, % Female- 40 (64.51) Female-30 (62.5) 0.65 Male-22 (35.48) Male-18 (37.5) Duration of disease (years) 2.68 1.61 <0.002 We also studied the association between vitamin D3 levels of CSU patients with their disease severity in terms of UAS7 scores. The Pearson correlation coefficient was −0.664, suggesting a moderate to strong, statistically significant negative correlation (P<0.0001). This suggests that CSU patients with lower serum vitamin D3 levels had higher UAS7 scores and greater disease severity (Fig. 1).Figure 1: Correlation between serum vitamin D levels of chronic spontaneous urticaria patients and disease severity.Vitamin D3 is considered a biomarker for CSU [2]. Although many studies report lower vitamin D3 levels in CSU patients compared to healthy controls, recent meta-analyses by Tsai et al. and Lee et al. found no significant difference [3,4]. Another study found higher vitamin D3 levels in the CSU population [5]. Current CSU management guidelines do not recommend testing for serum 25-(OH) D levels. However, our findings suggest that addressing vitamin D3 deficiency could positively influence CSU activity due to its potential immunomodulatory and anti-inflammatory properties. Given the high prevalence of vitamin D3 deficiency, screening and supplementation in CSU patients could be a cost-effective approach to improving outcomes. Acknowledgments Contributions- D.C. was involved in the concept, design, data collection, analysis, and manuscript drafting. A.D. and K.G. gave the concept and designed the work as well as reviewed and edited the manuscript. D.G. was involved in data collection. Conflicts of interest There are no conflicts of interest.