Levels of Serum Vitamin D in Oral Lichen Planus Patients in the Twin Cities of Pakistan: A Cross-Sectional Study

By Kanwal Sohail¹, Maryam Rehman², Haris Ahtasham³

Affiliations

1. Department of Oral Medicine, Margalla Institute of Health Sciences, Islamabad, Pakistan
2. Department of Dermatology, Pak-Emirates Military Hospital, Rawalpindi, Pakistan
3. Department of Oral Pathology, Islamic International Dental College and Hospital, Islamabad, Pakistan

doi: 10.29271/jcpsp.2025.08.969

ABSTRACT
Objective: To demonstrate a probable association of the levels of vitamin D with the occurrence and severity of oral lichen planus (OLP).
Study Design: A cross-sectional, descriptive study.
Place and Duration of the Study: Department of Dermatology, Pak-Emirates Military Hospital, Rawalpindi, Pakistan, from October 2023 to February 2024.
Methodology: Respondents diagnosed with OLP were recruited, comprising 44 patients. The severity of the disease was noted via the White-Erosive-Atrophic Modified (WEA-MOD) scoring system. Patients’ serum vitamin D levels were checked. To evaluate the relationship between vitamin D levels and disease severity, the Kruskal-Wallis test was applied. The types of OLP were also compared regarding clinical and laboratory characteristics using the Mann-Whitney U test and the Chi-square test.
Results: The WEA-MOD scoring, that shows severity of disease, showed a mean value of 3.39 ± 0.99. The mean value of Vitamin D levels was 33.64 ± 22.77 ng/ml. With the rising WEA-MOD score indicating increase in disease severity, vitamin D levels tended to fall; however, the interrelation between vitamin D levels and the severity of the pathology was not statistically significant (p-value 0.730). Moreover, the types of oral lichen planus (OLP) also showed no significant association to vitamin D levels, although a slightly lower vitamin D levels was observed.
Conclusion: While serum vitamin D levels appeared to decline with increasing disease severity, as indicated by higher WEA-MOD scores, the association was not statistically significant. Similarly, no significant difference in vitamin D levels was observed among various clinical types of OLP. Patients with the erosive form of OLP tended to exhibit lower serum vitamin D levels compared to those with the reticular form, suggesting a possible but inconclusive link between disease subtype and vitamin D status.

Key Words: Cross-sectional studies, Deficiency, Dermatology, Lichen planus, Pathology, Vitamin D.

INTRODUCTION

Oral lichen planus (OLP), an autoimmune, inflammatory, and chronic pathology, is responsible for 15-30% of recorded lichen planus cases.^1,2 The incidence of OLP varies from region to region, population, and diagnostic criteria. As a non-contagious condition, it may manifest as white, lacy patches, red, inflamed areas, or open sores, accompanied by various clinical signs affecting the skin, nails, hair, and mucous membranes.³ This can be an uncomfortable experience for patients, as painful symptoms, including burning sensations, may interfere with daily activities such as speaking, eating, and maintaining hygiene. These lesions are long-standing and non-responsive, with typical occurrences of exacerbation and remission.⁴

Although the exact aetiology of OLP remains elusive, mounting evidence suggests that a dysfunction the immune system, genetics, stress, infections, and/or medications can influence the growth and progression of this disorder. It mostly affects the female gender over the age of 40 years.⁵

OLP is sometimes controversially cited as a potentially malignant disorder (OPMD). It manifests in patients as a clinical picture ranging from reticular, erosive, atrophic, papular, and bullous.⁶ Cases are diagnosed through clinical examination and detailed medical history following modified WHO diagnostic criteria, with biopsies often used as an aid.

Treatment regimens focus on precluding and relieving symptoms, hastening remissions, enhancing pain-free periods, and reducing further malignant transformations; as no set of therapeutic regimen exists.⁶ Topical agents such as calcineurin inhibitors, TNF-a inhibitors, tetracyclines, and other systemic agents have been employed to manage recalcitrant cases.⁷

Vitamin D is a fat-soluble secosteroid, which plays a vital role in the health of bone, immunity, and inflammation maintenance. Its deficiencies are documented to have a correlation with chronic diseases, including auto-immune disorders. However, its role in OLP remains relatively underexplored. An investigative evidence points towards a decrease in vitamin D levels and increase in auto-immune disease.⁸ A study done in Srinagar, showed a statistically significant relationship between serum vitamin D levels and OLP.⁹ Similarly, efforts carried out by Motahari et al. also concluded that the severity of OLP increases with vitamin D deficiency.¹⁰ Although the study conducted by Bahramian et al. found no association between serum vitamin D levels in patients with from OLP and healthy individuals.¹¹ However, a Pakistani study that used vitamin D adjunctively to cure OLP in peri-menopausal women showed clinical improvement of the pathology.¹²

The literature available, especially in Pakistan, on the association of the status of vitamin D and OLP is scarce and inconsistent. Therefore, this cross-sectional study aimed to determine whether any association exists between vitamin D levels and clinical features of OLP or not.

METHODOLOGY

A cross-sectional, descriptive study was carried out at the Department of Dermatology, Pak-Emirates Military Hospital, Rawalpindi, Pakistan, from October 2023 to February 2024. An ethical approval was granted by the Ethical Committee of the Hospital (Ref. No: A/28/EC/484/2022). The sample size of 44 patients was calculated through the World Health Organization (WHO) calculator, keeping confidence level at 95%, anticipated population proportion for prevalence of OLP at 0.89%, and absolute precision at 1%.¹ Convenience sampling technique was used. OLP patients of all age groups, irrespective of gender, who were clinically diagnosed, with or without histopathological diagnosis, were included. Patients were not considered if they had medicine or restoration-induced lichenoid reactions; congenital or acquired immune deficiencies (AIDS); conditions such as chemotherapy, injectable medicine use, haemophilia, hemodialysis; and the use of medications, including supplements, calcium, or calcium channel blockers, that affect serum vitamin D levels. Moreover, active infections such as hepatitis, HIV, tuberculosis, or COVID-19 were excluded. Additionally, individuals who had been treated for lichen planus in the past two months, those with dysplasia in histopathological evaluations, or those deemed unlikely to comply with future follow-up due to biopsy or infection control concerns were also excluded.

The diagnosis of OLP was established purely on clinical grounds. Clinically, OLP typical lesions were characterised as bilateral and symmetrical lesions, primarily affecting the buccal mucosa. Key features included the presence of Wickham’s striae—a network of fine, white, lace-like lines, with a chronic course marked by periods of exacerbation and remission. The potential for multiple clinical forms (reticular, erosive, plaque-like, and atrophic) to manifest simultaneously. They were non-indurated lesions and lacked signs of invasive growth.

After the selection of the patients according to the set criteria and the modified WHO diagnostic criteria, with proper verbal consent procured from the respondents, a complete history was obtained regarding the OLP, and then their oral cavity was properly screened. The disease severity was assessed using the White-Erosive-Atrophic Modified (WEA-MOD) scoring system, based on the criteria as described in Table I.

The visual analogue scale (VAS) was employed to assess pain with ranges from 0 to 10, where scores of 1-4 indicated mild pain, 5-7 reflected moderate pain, and scores above 8 represented severe discomfort. Patients were also inquired about symptoms potentially related to vitamin D deficiency, including lower back pain, recent weight gain, fatigue, hair loss, and muscle pain. Patients were referred to the Institute of Pathology for determining vitamin D serum levels using chemiluminescence assay. No cost was inflicted upon the patients for the laboratory test. Less than 20 ng/mL serum levels were classified as a deficiency, 20-30 ng/mL as insufficient, and 30-100 ng/mL as sufficient.

Statistical Package for the Social Sciences (SPSS version 26) was used as a data entry and processing tool.  Descriptive analysis was done for age, duration of disease, VAS score, WEA-MOD score, and vitamin D levels. Gender, type of OLP, clinical characteristics, histologically proven, stress, severity of disease, pre- or post-menopause, treatment taken, lower-back pain, hair loss, fatigue, and vitamin D sufficiency were represented as percentages and frequencies. For assessing any relationship between vitamin D levels and severity of disease, the Kruskal-Wallis test was applied. Moreover, Spearman’s correlation was also used to analyse any association between vitamin D levels and severity of disease. The types of OLP were also compared regarding clinical characteristics such as age, gender and duration of disease, and laboratory parameters such as vitamin D levels using the Mann-Whitney U test and the Chi-square test (p = 0.05 - 95% confidence interval).

RESULTS

Forty-four patients were considered for this research. The mean age of the respondents was 49.25 ± 6.77 years. Male participants were 45.5% (n = 20) of the total patients, and 54.5% (n = 24) were female. The mean duration of the OLP disease was 10.36 ± 7.69 years. Regarding the type of OLP, 45.5% (n = 20) were reticular type and 54.5% (n = 24) were erosive type. Clinical characteristics of lichen planus showed all the cases to be bilateral in the oral cavity. Twenty-six (59.1%) patients reported Wickham’s striae, and 63.6% (n = 28) complained about burning due to spicy food. The gravity of the pain was assessed through the visual analogue scale (VAS) score. The mean value of the VAS was 4.00 ± 1.59.

Table  I:  WEA-MOD  scoring  system.

Score 5	White striae with erosive area more than 1 cm2
Score 4	White striae with erosive area less than 1 cm2
Score 3	White striae with atrophic area more than 1 cm2
Score 2	White striae with atrophic area less than 1 cm2
Score 1	Mild white striae, no erythematous area
Score 0	No lesion, normal mucosa

Table II: Vitamin D sufficiency and WEA-MOD scoring.

WEA-MOD scores	Patients n	Deficient n (%)	Insufficient n (%)	Sufficient n (%)
Score 1 = mild white striae, no erythematous area	1	0 (0)	0 (0)	1 (100)
Score 2 = white striae With atrophic area less than 1 cm2	8	4 (50)	1 (12.5)	3 (12.5)
Score 3 = white striae with atrophic area more than 1 cm2	13	2 (15.38)	5 (38.46)	6 (46.15)
Score 4 = white striae with erosive area less than 1 cm2	17	6 (35.29)	6 (35.29)	5 (29.41)
Score 5 = white striae with erosive area more than 1 cm2	5	3 (60)	1 (20)	1 (20)

Table III: Association of vitamin D levels with severity of disease of OLP.

WEA-MOD scores	Number of patients n	Vitamin D levels mean ± SD ng/ml	Vitamin D levels median (IQR)	p-value
Score 1 = mild white striae, no erythematous area	1	45.00	-
Score 2 = white striae with atrophic area less than 1 cm2	8	44.63 ± 38.34	37 (63)
Score 3 = white striae with atrophic area more than 1 cm2	13	33.62 ± 16.18	28 (26)	0.730*
Score 4 = white striae with erosive area less than 1 cm2	17	31.25 ± 20.49	25 (37)
Score 5 = white striae with erosive area more than 1 cm2	5	22.00 ± 8.37	20 (15)

Table IV: Clinical and laboratory parameters between the patients with reticular Type OLP and erosive type OLP.

Reticular type OLP (n = 20)		Erosive type OLP (n = 24)	p-values
Age (years)       Mean       Median (IQR)	- 49.75 ± 7.29 51 (12)	- 48.83 ± 6.44 49 (10)	0.660*
Gender       Male       Female	9 11	11 13	0.956**
Duration of disease (years)       Mean       Median (IQR)	- 10.15 ± 7.08 8 (7)	- 10.54 ± 8.32 8 (6)	0.991*
Vitamin D levels (ng/ml)       Mean       Median (IQR)	- 40.35 ± 27.32 40 (41)	- 28.05 ± 16.77 25 (19)	0.232*
*Mann-Whitney U test, **Chi-square test.

Out of 20 patients, 45.5% had undergone an oral biopsy and had histopathological proof of the findings of OLP. Stress was reported to be an aggravating factor of the disease by 34.1% (n = 15) in the patients. The percentage of patients obtaining treatment for OLP was 72.7% (n = 32).

Female patients in pre-menopause state were 11 (25%), and 13 (29.5%) females were in post-menopause state. Lower back pain was reported in 36.4% (n = 16) of the patients, 31.8% (n = 14) complained of weight gain, 36 (81.8%) had fatigue, 12 (27.3%) reported hair loss, and 10 (22.7%) had muscular pain.

The WEA-MOD scoring showed a mean value of 3.39 ± 0.99 with one patient (2.3%) having score 1, eight (18.2%) patients showed score 2, 13 (29.5%) patients with score 3, 17 (38.6%) having score 4, and 5 (11.4%) showing highest score 5. The mean value of Vitamin D levels was 33.64 ± 22.77 ng/ml. Vitamin D deficient patients laid at 34.1% (n = 15), 29.5% (n = 13) had deficient levels of vitamin D, and 36.4% (n = 16) consisted of satisfactory levels of vitamin D. The vitamin D sufficiency was correlated with WEA-MOD scoring as shown in Table II. With the rising WEA-MOD score which indicates increase in disease severity, the vitamin D values tended to fall, but the link between vitamin D levels and disease severity was found to be analytically insignificant with a p-value of 0.730 as depicted in Table III. Spearman’s correlation was run to determine the relationship between the two variables (vitamin D and OLP), through WEA-MOD score. There was a weak-negative relationship between the vitamin D levels and the pathology, which was statistically not significant (rpb = -0.179, p = 0.246).

Lower serum levels of vitamin D were observed in participants with erosive lichen planus in comparison to the reticular lichen planus; however, the difference held no statistical significance, as shown in Table III. The clinical appearances and lab work of the cases with reticular and erosive lichen planus are observed in Table IV. Statistically insignificant difference between the two types of OLP was noticed.

DISCUSSION

Micronutrients such as trace elements, vitamins, and anti- oxidants are essential against oxidative stress in the tissues in regenerative processes. Researchers observe an association between inflammatory disorders and micronutrient deficiency. Literature has shown that zinc and iron have been studied more commonly regarding OLP.¹³ Others have included folic acid, vitamin B12, and vitamin A as well.^14,15 The correlation of vitamin D with OLP is also under investigation. Potential therapeutic effects on neoplasms, auto-immune diseases, and psoriasis are validated in recent studies with the use of vitamin D.¹¹ Moreover, vitamin A, vitamin C, zinc, and selenium have also shown therapeutic properties regarding OLP.¹⁶

Although the lower limit of sufficient level of vitamin D is 30-100 ng/ml, the results of this study have shown an insignificant correlation with the mean 33.64 ± 22.77 ng/ml vitamin D levels, which shows sufficient levels. With increasing severity of the disease tested through WEA-MOD score, the vitamin D levels were decreasing. Similarly, no difference was found between different types of OLP in terms of vitamin D levels. However, the erosive lichen planus, the more severe type, showed lower levels of vitamin D (28.05 ± 16.77 ng/ml) as compared to the reticular type (40.35 ± 27.32 ng/ml). In contrast to the results of the current study, a randomised controlled trial was conducted in 2022, comprising of 50 subjects divided into two groups: One with lichen planus disease and the other healthy controls. The vitamin D levels were 15.11 ng/ml and 26.10 ng/ml in the disease group and the healthy controls, respectively. The research concluded that the lower serum vitamin D in the disease group suggests that it is a crucial element in the aetiopathogenesis of the respective pathology.¹⁷ A case-control investigation involving 30 sufferers of OLP and 70 healthy persons found that OLP patients exhibited vitamin D deficiency, with a mean level of 18.12 ± 8.7 ng/ml, compared to a mean level of 23.7 ± 9 ng/ml in the controlled population. Hence, a positive association of vitamin D levels with OLP was estab-lished.¹⁸ A study by Tangarpoor et al. compared OLP patients, oral squamous cell carcinoma (OSCC) patients, and healthy individuals with regard to the levels of vitamin D. The mean levels in OLP patients (17.00 ± 14.16 ng/mL) were significantly lesser than those of the control participants (22.99 ± 14.46 ng/mL, p = 0.003). Patients with OSCC displayed a mean vitamin D level of 24.63 ± 16.19 ng/mL, indicating that the deficiency of this vitamin can potentially be a risk factor in OLP and OSCC progression.¹⁹

In similarity to the outcomes of this study, Bahramian et al., who compared vitamin D levels in OLP patients and controlled groups, found that the mean serum vitamin D levels were 30.7 ± 20.38 ng/ml in OLP patients which were very close to the mean value in the present study that is 33.64 ± 22.77 ng/ml, and in healthy participants the levels were 36.45 ± 15.33 ng/ml with the p-value of 0.346, showing no association between vitamin D levels and OLP.¹¹ Another study compared symptomatic and asymptomatic OLP, similar to this study, which compared erosive LP (symptomatic OLP) and reticular LP (asymptomatic OLP). But unlike the results of this study, asymptomatic OLP, symptomatic OLP, and the controls showed significant difference with respect to vitamin D levels, with a p-value of <0.001. However, the findings of this study, the symptomatic OLP, showed lower levels of vitamin D (15.51 ± 5.77 ng/ml) as compared to asymptomatic OLP (23.14 ± 5.28 ng/ml). The results also showed vitamin D levels of 28.05 ± 16.77 ng/ml for erosive lichen planus and 40.35 ± 27.32 ng/ml for the reticular type.²⁰ In accordance with the current findings, an Iranian study showed no association of Vitamin D3 with OLP. However, the study demonstrated that Vitamin D3 levels were increased in the OLP batch in comparison to the controlled one. Unlike the findings in this research regarding the type of OLP, the erosive OLP showed levels of vitamin D3 to be 63.13 ± 29.76ng/ml, and non-erosive OLP had lower vitamin D3 levels (41.49 ± 35.43 ng/ml).²¹ Another Iranian investigation pointed out that out of 66 OLP patients, 39.4% participants had a deficiency of the vitamin D, and 47.0% had insufficient vitamin D levels, while in this study, 34.1% of the patients had deficiency of vitamin D, and 29.5% had insufficient levels, and 36.4% consisted of sufficient levels.²²

Studies have been conducted to comprehend the beneficial effects of vitamin D in patients with OLP. A double blind randomised-clinical-trial including 28 OLP patients with vitamin D insufficiency concluded that the intensity of the disease was significantly lower in the intervention group with p-value of 0.043 after the administration of one capsule (50,000 units) of vitamin D weekly for 8 weeks.²³ Similarly, another pilot clinical study concluded significant improvement in symptoms of OLP after the treatment with vitamin D supplements.²⁴ Similar fruitful outcomes were observed in another study by Nazeer et al.²⁵

Literature consists of mixed reviews regarding role of vitamin D in the progression of OLP. Future recommendations include longitudinal studies and randomised controlled trials with a larger sample size to explore more regarding the role of vitamin D in the progression of OLP. The confines of this research are that a small sample size does not provide very diverse results, and perhaps another study design, rather than a cross-sectional one, could yield a better understanding of the relationships of the two variables.

The limitations of this study include that it was conducted only in the twin cities of Pakistan. It was a cross-sectional study with a small sample size. A more significant approach would be a longitudinal study in which vitamin D could be administered to OLP patients to see their conduction get improved or not, giving a better picture of any association. It is true that on initial testing, over 90% of adults show vitamin D deficiency, however, as OLP is an auto-immune disease, it presents in some of the individuals. Larger-scale studies are required to explore the association between vitamin D deficiency and OLP. International studies show mixed results, providing no definitive verdict. Therefore, more studies are required to validate these results.

CONCLUSION

While vitamin D levels may decrease with the progression of OLP, the association lacks sufficient statistical strength to establish a definitive correlation. Furthermore, when comparing the different clinical forms of OLP, no statistically significant variation in serum vitamin D levels was noted. However, patients exhibiting the erosive form of OLP tended to have comparatively lower vitamin D levels than those of presenting with the reticular variant, suggesting at a possible subclinical relationship between disease subtype and vitamin D deficiency. These findings, although inconclusive, may point towards a potential role of vitamin D in the pathophysiology of OLP, warranting further investigation with larger sample sizes and more robust study designs.

ETHICAL APPROVAL:
This study was conducted after obtaining ethical approval from the Ethical Committee of Pak-Emirates Military Hospital, Rawalpindi, Pakistan. All research procedures adhered to the ethical standards outlined in the Declaration of Helsinki. Ethical clearance was granted prior to the initiation of the research work under the approval number (Ref. No: A/28/ EC/484/2022).

PATIENTS’ CONSENT:
Verbal informed consent was obtained from all patients involved in this study. Patients were clearly informed regarding the purpose of the research, the use of their clinical data, and their right to withdraw at any stage. Consent was specifically obtained for the publication of anonymised clinical information and associated images where applicable.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
KS: Principal investigator, conceptualised the study, supervised the data collection, and finalised the manuscript.
MR: Managed patient’s selection, collected the clinical data, and contributed to the data analysis.
HA: Contributed to the study design, performed the literature review, and assisted in the manuscript writing.
All authors approved the final version of the manuscript to be published.

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