Vitiligo vulgaris is a persistent acquired skin disease which is pigmentary in nature and is manifested by appearance of depigmented macules and patches on the skin. It is present in about 0.5-2 percent of the world population and it may cause a heavy psychosocial impact because it is a visible condition. The precise pathogenesis of vitiligo has yet to be fully understood, although there has been a series of theories proposed, such as genetic predisposition, oxidative stress, neural factors and above all autoimmune mechanism. Of these, most people consent with the autoimmune hypothesis, since vitiligo is often concomitant with other autoimmune disorders like autoimmune thyroiditis, diabetes mellitus, and alopecia areata[1,2].

Vitamin D is a fat-soluble secosteroid hormone that has been produced in the skin when, exposed to ultraviolet B (UVB) radiation. Plays a significant role in calcium homeostasis, bone metabolism and immune regulation. The recent studies have shown its importance in skin health, especially in melanogenesis, or the production of melanin by melanocytes. Vitamin D has been known to augment tyrosinase, stimulate melanogenesis and perform immunomodulatory roles and all this could be applicable in vitiligo etiology[1,3,4].

Some observational and case-control studies have evaluated the relationship of serum vitamin D3 (cholecalciferol) status, and vitiligo, with inconsistent results. Others have claimed considerably low serum vitamin D levels in vitiligo sufferers compared to healthy persons indicating in a possible contributory factor of vitamin D deficiency in the onset or development of vitiligo[1,3,5]. However, other studies such as Galloway et al did not find a statistic significance in the levels of vitamin D between the cases and controls hence, further study is required to clear this association[1,2,6].

Vitamin D has also immunomodulatory effects, which are of interest in vitiligo. The vitamin D receptors are expressed in a number of immune cells, and vitamin D has been demonstrated to restrain the development of pro-inflammatory cytokines including interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-a), and interferon-gamma (IFN-a). The cytokines are involved in the autoimmune destruction of melanocytes that fall under vitiligo. More so, vitamin D analogs have also been proved to be effective in the repigmentation of vitiligo lesions in vitiligo, thereby further indicating the role of vitamin D in the treatment of vitiligo[3,4].

Although this shows that vitamin D deficiency in vitiligo was significant, the etiologic or pathogenetic role of this factor has not been ascertained. Inadequate sun exposure, dietary, skin phototype, and cultural factors could be some of the reasons behind low levels of vitamin D in the afflicted. Further, the correlation between the level of vitamin D and the degree or the severity of vitiligo remains unclear at present[2,3].

It is important to shed more light in the relationship between vitiligo vulgaris and the level of serum vitamin D3 due to the possible implication in prevention and management of the disease. This is an observational study that will determine the level of serum vitamin D3 in patients with vitiligo vulgaris and compare them with the healthy controls and as such help in building the expanding evidence on the involvement of vitamin D in the development of vitiligo and its development.

Study Design and Setting

This observational, cross-sectional study was conducted in the dermatology outpatient department at Amaltas Hospital, affiliated with Amaltas Institute of Medical Sciences, Dewas. The primary objective was to assess and compare serum vitamin D3 levels in individuals diagnosed with vitiligo vulgaris and age- and sex-matched healthy controls.

Study Duration

The study was carried out over a period of 18 months.

Study Population

The study population consisted of two groups:

• Group A (Cases): Patients diagnosed with vitiligo vulgaris.
• Group B (Controls): Age- and sex-matched healthy individuals without vitiligo or any known autoimmune or metabolic disorder.

Sample Size and Sampling Technique

A review of dermatology outpatient records from the previous three months identified sixteen patients meeting the inclusion and exclusion criteria. Based on this, it was estimated that approximately five eligible patients per month would present to the dermatology OPD. Over the 18-month study period, a sample size of 90 participants was determined, accounting for an anticipated 20% variation due to fluctuations in OPD visits and potential refusals to participate. Participants were divided into two groups: cases (vitiligo vulgaris) and controls.

Inclusion Criteria

• Cases: Individuals aged 18–60 years with a clinical diagnosis of vitiligo vulgaris confirmed by a dermatologist.
• Controls: Healthy individuals within the same age range, without any history of vitiligo, autoimmune disorders, or dermatological diseases (including hospital staff).

Exclusion Criteria

• Individuals with a history of other dermatological or non-dermatological diseases.
• Individuals with systemic illnesses such as chronic kidney disease, liver disease, or endocrine disorders.
• Patients receiving vitamin D supplementation or immunosuppressive therapy.
• Pregnant or lactating women.
• Individuals with a history of photosensitivity or phototherapy.

Ethical Considerations

Ethical approval was obtained from the Institutional Ethics Committee prior to the commencement of the study. All participants were informed about the study’s purpose, procedures, and confidentiality measures. Written informed consent was obtained from each subject.

Data Collection Procedure

Data collection followed a systematic approach:

• After consent, participants underwent a structured interview and thorough clinical evaluation.
• Demographic data (age, sex, address, occupation), sunlight exposure, clothing habits, and sunscreen use were recorded.
• For vitiligo cases, additional disease-specific information was collected, including age at onset, disease duration, extent and distribution of depigmented patches, history of disease progression or stability, family history of vitiligo or autoimmune conditions, and previous treatments.
• All participants received a comprehensive physical examination. Vitiligo patients underwent detailed skin examinations under proper lighting, with Wood’s lamp examination used in equivocal cases. Controls were similarly evaluated to rule out dermatologic or systemic diseases.
• Controls were matched to cases by age and sex to minimize confounding factors.

Laboratory Procedures

• A venous blood sample (approximately 5 mL) was collected from each participant under aseptic precautions.
• Samples were placed in plain vacutainer tubes, allowed to clot at room temperature, and then centrifuged at 3000 rpm for 10 minutes.
• Separated serum was stored at –20°C in labeled aliquots until analysis.
• Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a standardized chemiluminescent immunoassay (CLIA) method.
• Strict quality control was maintained throughout sample processing and laboratory analysis.

Statistical Analysis

• Data were compiled and analyzed using statistical software.
• Descriptive statistics (mean, standard deviation, frequency distribution) were calculated.
• The independent t-test was used to compare serum vitamin D3 levels between cases and controls.
• A p-value of <0.05 was considered statistically significant.

Table 1: Patient Demographic Profile (Age, Sex, and Occupation)

Table 1 provides an overview of the demographic distribution of both the vitiligo vulgaris and control groups. Age distribution between the two groups was quite similar, with no statistically significant difference (p-value 0.877). The sex distribution shows that males constitute a larger proportion of the vitiligo group (71.1%) compared to the control group (60%), though this difference wasn't significant (p-value 0.267). Occupation-wise, both groups share common professions, with students and farmers being the most prevalent in both groups. The occupational distribution also didn’t show significant differences (p-value 0.333).

Table 2: Clinical Profile (Disease Duration, Fitzpatrick Skin Phototype, Type of Vitiligo)

Table 2 focuses on the clinical characteristics of the vitiligo vulgaris group, such as disease duration, Fitzpatrick skin phototype, and type of vitiligo. Most vitiligo patients have had the condition for more than 5 years (42.2%), reflecting the chronic nature of the disease. Fitzpatrick skin phototypes show that Type V is most common in the vitiligo group (46.7%), followed by Type IV (37.8%), and Type III (15.6%). In terms of disease type, the majority of patients have unstable vitiligo (64.4%), with 35.6% having stable vitiligo.

Table 3: Comorbidities and Vitamin D3 Levels

Table 3 presents data on comorbid conditions (hypertension, diabetes, and hypothyroidism) and vitamin D3 levels between the vitiligo vulgaris and control groups. While comorbidities were slightly more prevalent in the vitiligo group, none of the differences were statistically significant (p-values > 0.05). The table highlights a significant difference in vitamin D3 levels, with the vitiligo group showing much lower mean levels (21.3 ng/mL) compared to the control group (35.4 ng/mL, p < 0.001). Furthermore, vitamin D3 deficiency was significantly more common in the vitiligo group, with only 6.7% having normal levels compared to 57.8% in the control group.

Table 4: VASI Score

Table 4 presents the Vitiligo Area Scoring Index (VASI) score for the vitiligo vulgaris group, which quantifies the extent of skin depigmentation. The mean VASI score for the group was 13.7 ± 7.1, reflecting a moderate to severe level of depigmentation among the patients. The VASI score helps to assess the severity and coverage of vitiligo lesions in affected individuals.

The objective of the current case-control study was to identify the differences in demographic and clinical features of patients with vitiligo vulgaris to that of a matched control group with a particular emphasis on levels of vitamin D 3 and the severity of the disease measured by VASI scores. There were a few key findings, which highlighted the lack of crucial differences in age distribution (p = 0.877), sex (p = 0.267), and occupation (p = 0.333) between categories, with the understanding that only demographic factors cannot define the susceptibility to vitiligo. On a clinical basis chronic disease course was noticeable as 42.2 percent of vitiligo patients had a disease duration of above five years, and 64.4 percent had an unstable disease, which augers therapeutic problems.

Fitzpatrick skin phototype research demonstrated that there were mostly type V (46.7%) and IV (37.8%) skin photos, implying that darker photos can affect the disease manifestation and the anxieties of individuals on repigmentation. The average VASI score of 13.7 7.1 indicates moderate to severe depigmentation, which corresponds to the limits that are reliable and clinically significant in nonsegmental vitiligo (T-VASI 50 and F-VASI 75) [7].

The prevalence of autoimmune thyroid dysfunction and diabetes mellitus was higher (not significantly) in the vitiligo group compared with the Comorbidity assessment group. This confirms earlier Indian findings of 20 % hypothyroidism and 16% diabetes in vitiligo group compared with 2 and 5 respectively in controls, implying mutual autoimmune predisposition [8]. A systematic meta-analysis described them in greater depth, stating that the prevalence of thyroid diseases and diabetes was higher in people with vitiligo than in healthy individuals [9].

The condition of vitamin D3 deficiency became a significant discovery; cuts with vitiligo had a much lower mean 25-hydroxvitamin D concentration (21.3 ng/mL) than the controls (35.4 ng / mL, p < 0.001). It is also backed by several meta-analyses showing that standardized mean differences in circulating levels of vitamin D are between -1.03 to -1.40 between vitiligo patients and controls with a higher incidence of deficiency in indoor workers [10][11]. These findings support the hypothesis that vitamin D 3 deficiency potentially has a pathophysiological or regulating mechanism during the development or prevalence of vitiligo and consider the necessity to investigate the possibility of administering supplements as an adjunctive measure.

On the whole, the findings of the study are in agreement with those of other literature which suggest that:

Vitiligo is often accompanied by autoimmune comorbidity, especially thyroid dysfunction and diabetes mellitus possibly due to common immune-genetic mechanisms [8][9].

A sustained lack of vitamin D 3 is an evident finding in vitiligo patients, and it might affect the possibility of repigmentation and stability in the chemically induced disease [10,11].

• VASI score is a sensitive and specific indicator of disease severity and repigmentation that has well-defined thresholds to define meaningful clinical change [7].

This study shows the significant differences in vitamin D3 levels between vitiligo vulgaris patients and controls, suggesting that vitamin D3 deficiency could play a role in the disease. The findings also emphasize the chronic nature of vitiligo, the importance of considering comorbidities in managing the disease, and the potential for more targeted treatments, such as vitamin D3 supplementation. Future research should aim to further investigate these associations and explore more effective treatment options for vitiligo patients.

Limitations include the relatively small sample size and potential control group homogeneity. Future research should encompass larger, ethnically diverse cohorts and longitudinal designs to assess the impact of vitamin D₃ supplementation on vitiligo progression and repigmentation outcomes.

1. Usha Sri A, Chintada D, Bathina A, et al. (July 07, 2025) Association of Serum Vitamin D3 Levels With Vitiligo: A Case-Control Study at a Tertiary Care Center. Cureus 17(7): e87452. DOI 10.7759/cureus.87452
2. Karagüzel G, et al. The role of serum vitamin D levels in vitiligo. Postepy Dermatol Alergol. 2016 Aug;33(4):300-302.
3. Mahmmod Z, Ismael DK. Vitamin D Deficiency in Patients With Vitiligo: A Cross-Sectional Study From Basrah, Iraq. Cureus. 2021 Dec 27;13(12):e20713.
4. Prakash, D., & Karthikeyan, K. (2017). A case control study of vitamin D levels in patients with vitiligo. International Journal of Research in Dermatology, 3(1), 103–106. https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20170796.
5. Pillai R T, Dinachandran A, A Study to assess the association of vitamin D (serum 25 hydroxy vitamin D3) and vitiligo. Indian J Clin Exp Dermatol 2019;5(1):6-8.
6. Varikasuvu SR, Aloori S, Varshney S, Bhongir AV. Decreased circulatory levels of Vitamin D in Vitiligo: a metaanalysis. An Bras Dermatol. 2021;96:284---94.
7. Lu Y, Chen J, Chen J, et al. Circulating Vitamin D Levels and Risk of Vitiligo: A Meta-analysis. Front Nutr. 2021;8:782270.
8. Mithal A, Saluja P, Garg T. Increased prevalence of thyroid dysfunction and diabetes mellitus in vitiligo: A case-control study from India. Indian J Dermatol Venereol Leprol. 2005;71(2):91–94.
9. Elewski BE, McKenna KE, Hames DR, et al. Psychometric Properties and Meaningful Thresholds of the Vitiligo Area Scoring Index (VASI). JAMA Dermatol. 2025;161(1):12–20.
10. Singh S, Sharma DR, Kumar S, et al. Decreased circulatory levels of Vitamin D in Vitiligo: A meta-analysis. J Dermatol Sci. 2021;101(3):203–211.
11. Lee JH, Ju HJ, Seo JM, et al. Comorbidities in Patients with Vitiligo: A Systematic Review and Meta-Analysis. J Invest Dermatol. 2023;143(5):777–789.e6.