Evaluation of serum levels of vitamin D and CXCL10 in patients with generalized vitiligo and their relation to disease severity

Mohamed I Seddik; Marwa M Mekkawy; Rofaida R Shehata

doi:10.4103/ejdv.ejdv_13_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 43 | Issue : 2 | Page : 88-92

Evaluation of serum levels of vitamin D and CXCL10 in patients with generalized vitiligo and their relation to disease severity

Mohamed I Seddik¹, Marwa M Mekkawy², Rofaida R Shehata²
¹ Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
² Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Submission	20-Mar-2022
Date of Decision	19-Aug-2022
Date of Acceptance	20-Oct-2022
Date of Web Publication	25-Apr-2023

Correspondence Address:
MD Marwa M Mekkawy
Department of Dermatology, Venereology, and Andrology, Faculty of Medicine, Assiut University, Assiut 71515
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ejdv.ejdv_13_22

Abstract

Background Vitiligo is an acquired, common, autoimmune, pigmentary defect of the skin. Vitamin D (VitD) plays a physiological role in photo-induced melanogenesis in the skin. It was found that VitD levels decline in autoimmune illnesses. Recently, there has been growing interest in the role of vitamin D3 in the pathogenesis of vitiligo and its change after treatment. The chemokine CXCL10 was found to be raised in the serum of patients with vitiligo. Few studies have evaluated its relation to the severity of the disease.
Aims To establish a link between both serum VitD and serum CXCL10 and vitiligo, besides evaluating their possible relation to disease severity.
Patients and methods This study was conducted on 30 patients with generalized vitiligo and 30 healthy individuals without age and sex limitations. Serum VitD and CXCL10 levels were measured for both patients with vitiligo and controls and were re-evaluated after 12 weeks for patients with vitiligo. The Vitiligo Area Scoring Index was calculated for the patient group at baseline and after 12 weeks.
Results Serum VitD was found to be significantly lower in patients with vitiligo than controls, whereas serum CXCL10 was significantly higher in patients than healthy controls. Changes in serum CXCL10 at the end of the study period positively correlated with changes in Vitiligo Area Scoring Index of patients with vitiligo.
Conclusion There is a strong relationship between both serum VitD and CXCL10 and vitiligo. Serum CXCL10 levels change in relation to disease severity.

Keywords: CXCL10, vitamin D, vitiligo

How to cite this article:
Seddik MI, Mekkawy MM, Shehata RR. Evaluation of serum levels of vitamin D and CXCL10 in patients with generalized vitiligo and their relation to disease severity. Egypt J Dermatol Venerol 2023;43:88-92

How to cite this URL:
Seddik MI, Mekkawy MM, Shehata RR. Evaluation of serum levels of vitamin D and CXCL10 in patients with generalized vitiligo and their relation to disease severity. Egypt J Dermatol Venerol [serial online] 2023 [cited 2023 May 31];43:88-92. Available from: http://www.ejdv.eg.net/text.asp?2023/43/2/88/374459

Introduction

Vitiligo is an autoimmune disorder characterized by melanocyte destruction by immune mechanisms. It affects ∼2% of the general population without predilection to a certain skin type, age, or sex [1],[2],[3]. The disease has a great psychological effect and causes social embarrassment, especially in females, exposed sites, and people with dark skin [4].

Different theories have been postulated to explain the pathogenesis of vitiligo. However, the exact cause of the disease remains obscure. The possible theories include familial, autocytotoxic, self-destructive, oxidative stress-mediated, autoimmune, and neural [5].

Vitamin D (VitD) has a crucial role in both innate and adaptive immunity. It has been found to affect melanin formation in the skin [6]. Cutaneous melanocytes express VitD receptors; hence, VitD participates in regulating melanocyte function [7]. It was shown that it maintains the integrity of the epidermal melanin unit by controlling the proliferation and migration of melanocytes and adjusting T-cell activation. These mechanisms are parallel to melanocyte disappearance in vitiligo. The biological actions of VitD receptors on immune cells lead to the identification of it as a possible potent immunomodulator [8]. Moreover, topical VitD analog (calcipotriol) is among the treatment lines of vitiligo as it may help in preventing melanocyte damage [7].

Low serum concentrations of VitD have been linked to many autoimmune disorders [1]. However, there has been a huge controversy on the association between VitD levels and vitiligo, which is still in need of further thorough investigations [7].

Chemokines play an essential role in the regulation of homing, recruitment, and retention of immune cells such as T lymphocytes [9]. Many research studies have reported that an imbalance in the T-helper (Th) cell system, with a dominant Th1 pattern, is in favor of the development of vitiligo [10],[11].

Among the huge chemokine family is CXCL10 (interferon-inducible protein 10), which has a key role in the interferon response and recruitment of CXCR3+ Th1 lymphocytes to sites of inflammation [12]. The chemokine, CXCL10, has been recently identified in patients with vitiligo as opposed to healthy controls [13]. Moreover, higher serum levels of CXCL10 have been reported to be possibly associated with vitiligo activity [14]. However, its exact role in reporting vitiligo progression or predicting treatment response has not been fully elucidated [15].

Although VitD and CXCL10 do not have a direct relationship with each other, both are suggested to affect critical immunoregulatory pathways in vitiligo, particularly T-cell function. The link between them and disease severity could provide an insight into their role as possible biomarkers of the disease, in addition to using them as a follow-up tool with different treatment modalities.

Patients and methods

A prospective, controlled, longitudinal study was conducted in the period from May to September 2020. A total of 30 patients with generalized vitiligo and 30 healthy individuals without age and sex limitations were recruited for the study. Full history and examination of the patients were done, and the diagnosis of vitiligo was confirmed clinically and by Wood’s light examination.

Exclusion criteria

Any patient with a history of autoimmune disease, chronic debilitating diseases, phototherapy treatment, or VitD supplements within the last year and pregnant or lactating females were excluded.

Serum VitD and CXCL10 levels were measured for healthy controls and patients (at baseline and after 12 weeks). The Vitiligo Area Scoring Index (VASI) was calculated for the patient group before and at the end of the study period (12 weeks). The skin photo-type of the study participants was III–IV. All participants were active personnel with adequate sun exposure, and the study was conducted during the sunny season. During the period of study, the patients received different treatment regimens for vitiligo, for example, topical steroids, systemic steroids, and narrow-band ultraviolet B (NB-UVB) therapy. However, the detailed treatment of each patient was not evaluated.

Specific enzyme-linked immunosorbent assay kits were used for quantification of serum VitD (Diagnostics Biochem Canada Inc., London, Ontario, Canada) and CXCL10 (Cat. No SG-15814; SinoGeneClon Biotech Co., Ltd., HangZhou, Zhejiang, China) levels as described by the manufacturer. A whole blood sample (10 ml) was collected from each patient before and after treatment and from each control and processed to obtain serum according to the standard protocol [16].

All participants signed a written consent form before the initiation of the study, in accordance with the standards of the institutional Ethics Committee.

Statistical analysis

Statistical analyses were performed using SPSS (Statistical Package for the Social Sciences), version 26.0 (IBM corp., Armonk, New York, USA). Test of normality (Shapiro–Wilk test), χ² test, independent samples t test, paired samples t test, Wilcoxon signed ranks test, and Spearman correlation test were used for the analysis of data that were expressed in percentage, mean±SE, or median with interquartile range. Statistical significance was considered when P value was less than 0.05.

Results

The entire disease group in our study had generalized vitiligo as established by the bilateral symmetrical distribution of depigmented macules and patches. In total, 30 patients with vitiligo and 30 controls completed the study. The mean age of the patient group was 36.03±2.134 years, whereas that of the control group was 35.90±2.045 years. Patients ranged in age from 17.0 to 62.0 years and controls ranged from 18.0 to 64.0 years. No statistically significant difference was established between the patient and control population in terms of age (P=0.964) and sex (P=0.791).

A blood test was carried out to measure serum 25-hydroxyVitD and CXCL10. At baseline, the mean VitD level in the patient group was 37.00±4.152 nmol/l, and it was 119.03±3.250 nmol/l in the control group, with a statistically significant difference (P<0.001). It fluctuated from 7 to 88 nmol/l in the patient group and from 85 to 140 nmol/l in the control group ([Table 1]). The measurements of serum CXCL10 revealed significantly higher levels in patients with vitiligo (155.50±9.335 pg/ml) than in healthy controls (111.37±6.485 pg/ml) (P<0.001). It ranged from 55 to 290 pg/ml in the patient group and from 55 to 220 pg/ml in the control group ([Table 1]).

Table 1 Serum vitamin D and CXCL10 levels in patients with vitiligo (at baseline) versus healthy controls

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In the patient group, the median VASI was 5.60 (7.47) at the baseline, with a range from 0.3 to 43.2, and it decreased to 2.40 (4.99) after 12 weeks, with a range from 0.3 to 40.1. This change in VASI was statistically significant (P=0.007) ([Table 2]). Evaluation of serum VitD in patients with vitiligo revealed an increase in its mean level from the baseline (37.00±4.152; range, 7–88 nmol/l) to the end of the study period at 12 weeks (54.87±5.203; range, 13–96 nmol/l), with a statistically significant difference (0.001) ([Table 2]). On the contrary, the mean serum CXCL10 level decreased from 155.50±9.335 (range, 55–290 pg/ml) at the baseline to 132.77±10.446 (range, 50–270 pg/ml) after 12 weeks but without a statistically significant difference (P=0.094) ([Table 2]).

Table 2 Evaluation of Vitiligo Area Scoring Index, serum vitamin D, and serum CXCL10 in patients with vitiligo at baseline and after 12 weeks

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An investigation of the associations between different measured variables was conducted, and it declared a barely significant, negative correlation with a moderate degree of strength between changes in VASI and serum VitD along the study period (r=−0.355, P=0.054); a significant, strong, positive correlation between changes in VASI and serum CXCL10 (r=0.541, P=0.002); and a significant, strong, negative correlation between changes in serum VitD and CXCL10 levels (r=−0.741, P<0.001) ([Table 3]).

Table 3 Correlation between changes in Vitiligo Area Scoring Index, serum vitamin D, and serum CXCL10 in patients with vitiligo after 12 weeks

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Discussion

Vitiligo is an acquired pigmentary disorder of the skin. It appears as depigmented white macules and patches. VitD functions as a hormone and is produced in the skin where it plays a role in skin pigmentation by increasing the action of the tyrosinase enzyme, leading to melanin production. In addition, it has immunoregulatory functions [7].

In our study, we compared levels of VitD in healthy controls and patients with generalized vitiligo at baseline, and the results showed significantly lower VitD values in patients compared with controls. Two previous studies of serum VitD levels in patients with vitiligo revealed significantly lower levels in patients than controls, which agrees with our results [17],[18]. Moreover, some studies have demonstrated lower levels of VitD in patients with vitiligo than in healthy controls but without a significant difference [1],[5],[19]. One study that evaluated the VitD level in patients with vitiligo found it to be significantly lower than the established normal levels without a control group [20]. Our findings are consistent with a meta-analysis involving 17 studies, which elucidated that VitD deficiency was positively associated with the incidence and in one study with the onset of vitiligo [17],[21].

On the contrary, Omidian and Asadian [22] have shown that average VitD levels in patients with vitiligo were significantly greater than in the control group. Instead, Pillai and Dinachandran [5] have demonstrated very low levels of circulating VitD in both healthy controls and patients with vitiligo. VitD levels were found to be reduced in different autoimmune diseases and hence, the possible relationship between VitD and vitiligo. Nevertheless, the exact mechanism by which it affects autoimmunity is still not fully understood [7]. Generally, VitD levels may also be influenced by exogenous factors such as inadequate nutrition and others [22].

Our findings reported that measured CXCL10 levels were higher in patients at baseline than in controls with a significant difference. This corresponds with the results of previous studies [13],[15],[23],[24]. It was demonstrated that serum levels of CXCL10 largely vary in different studies in patients with vitiligo. This may be the result of different evaluation methods of vitiligo stability and also higher variations in serum levels of patients with disease activity [15].

Regarding the results of the patient group, it was noticed that the median VASI score decreased and the mean VitD level increased when both were measured at 12 weeks with a significant difference from the baseline measurement. However, the mean serum CXCL10 level was lower at 12 weeks but without significance. Previous research work has shown that treatment with NB-UVB can significantly increase VitD levels relative to baseline [22],[25]. Whether the VitD level increases at the follow-up owing to NB-UVB therapy or disease improvement needs further elucidation. Although our study did not evaluate the detailed treatment regimen for each patient, NB-UVB therapy was reported among the received treatment by most of the participants. One study measured serum, lesional, and perilesional CXCL10 levels in patients with vitiligo before and after different treatment regimens and found that cutaneous CXCL10 levels significantly decreased after all regimens without a significant difference between treatment groups. In addition, the cutaneous levels correlated with serum reduction of CXCL10 after therapy [15].

Assessment of correlations in the present study detected a barely significant, moderate, negative correlation between changes in serum VitD and VASI at the end of the study period. Similarly, a previous study failed to demonstrate a significant correlation between VASI and VitD after NB-UVB therapy [18]. A larger sample size and longer duration of treatment and follow-up may be needed to obtain a significant correlation. Moreover, we found the changes in CXCL10 levels to have a significant, strong, positive correlation with VASI changes after 12 weeks. In accordance with our results, Wang et al. [26] demonstrated a significant positive correlation between serum CXCL10 and VASI, which was in parallel with disease stabilization after treatment in patients with progressive disease. Furthermore, a recent study has considered serum CXCL10 to be a predictor of treatment outcomes in patients with vitiligo [15]. In the current study, there was a significant, strong, negative correlation between changes in CXCL10 and VitD levels at 12 weeks, indicating a probable reverse relationship between them in terms of the pathogenesis of vitiligo disease.

In conclusion, we found significantly lower levels of serum VitD and significantly higher levels of serum CXCL10 in patients with generalized vitiligo than in healthy controls. Changes in serum CXCL10 strongly and significantly correlated with changes in VASI and hence disease severity. Serum VitD had an insignificant correlation with changes in VASI and thus could not be linked to vitiligo severity without further research.

Acknowledgements

All authors acknowledge they have contributed significantly to completing this work and are in agreement with the content of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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