Assessment of the Role of Vitamin D in the Treatment of Oral Lichen Planus

INTRODUCTION

Lichen planus is a chronic, inflammatory disease that affects the skin and mucous membranes including the oral mucosa. It is an autoimmune disease in which the skin cells and mucosal surfaces are targeted by the immune system. There is cytotoxic T-cell-mediated damage of the basal layer of the epithelium and chronic inflammation. There are different types of lichen planus such as reticular, plaque, papular, erosive, and ulcerative. Among all, reticular type is commonly seen in patients. Burning sensation is the most common symptom in patient f lichen planus. It is aggravated by ingestion of spicy food.

There are very few cases about 1–2% of oral lichen planus which can undergo malignant transformation. Earlier it was termed as a premalignant condition. Nowadays, it comes under “potentially malignant disorder” (WHO).¹

Vitamin D is said to play an important role in the immune system. The vitamin D receptors (VDRs) are found on immune cells which include B cells, T cells, and antigen-presenting cells. The immune cells in the body synthesize the active metabolite of vitamin D. This active metabolite acts on the immune system and either downregulates or upregulates the differentiation of immune cells.

Vitamin D can also modulate innate and adaptive immune responses. The deficiency of vitamin D has been related to various autoimmune diseases such as systemic lupus erythematosus, oral lichen planus, insulin dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis.²

Vitamin D acts on both B and T lymphocytes. The omnipresent expression of VDRs in myriad of immune cells such as activated T and B cells highlights the role of vitamin D in the modulation of various types of immunity like in the case of lichen planus.

Very few studies have been carried out to assess the role of vitamin D in the treatment of oral lichen planus. Thus, this study was conducted with the aim to assess whether vitamin D aided in the oral lichen planus treatment (Fig. 1).

MATERIALS AND METHODS

A sample size of 450 patients with various age groups having oral lichen planus (reticular) were taken reporting to the Department of Oral Medicine during the course of 6 months. The study was conducted in PDCH, Bihar. The simple random criteria were used for the selection of patients. The male to female ratio was 1:4. Informed consent was obtained from the patients for the study. Ethical approval was obtained from the institutional ethical committee. The study sample was divided into three groups based on their vitamin D level range (Fig. 2).

RESULTS

The data were evaluated and analyzed statistically using IBM SPSS Statistics for Windows, Version 26.0. (IBM Corp, Armonk, NY, USA) using descriptive statistics and ANOVA test with a significance of 0.05.

Table 2 shows that pretreatment objective symptoms score 5 was present in 120 patients in group I, 118 in group II and 120 in group III, score 4 in 30 in group I, 32 in group II and 30 in group III.

Table 3 shows that posttreatment objective following treatment; in group I, there were only five patients with score 4, whereas group II had no patient and group III had 30 patients. Score 0 was seen in 20 patients in group I, 26 in group II, and 0 in group III. There was significant improvement in both group I and II patients as compared to group III patients (p < 0.05). Those patients who regularly took vitamin D supplements weekly had improvement in burning sensation.

Table 4 shows that pretreatment subjective symptoms score 10 was seen in 110 patients in group I, 105 in group II, and 115 in group III, whereas score 8 was seen in 10 patients in group I, 6 in group II, and 5 in group III.

Table 5 shows that posttreatment subjective symptom score 8 was seen in 11 patients in group III, whereas no patient in group I and group II had 8 score. Score 0 was seen in 60 patients in group I, 45 in group II, and no patient in group III. There was significant improvement in both group I and II patients as compared to group III patients (p < 0.05).

Table 6 and Fig. 4 show that mean vitamin D pretreatment level in group I was 13.2 ng/mL, in group II was 13.6 ng/mL, and in group III was 17.5 ng/mL. Posttreatment value was 16.4 ng/mL in group I, 15.6 ng/mL in group II and 17.8 ng/mL in group III. The difference is found to be significant in group I and group II patients. The effect of vitamin D supplementation was much better in group I and group II patients.

DISCUSSION

The results showed that vitamin D supplementation in group I oral lichen planus patients had marked improvement in burning sensation. In group II, there was also improvement in score as compared to group III.

Majority of the population in India is deficient in vitamin D but very few people know about it when they get it tested. Vitamin D is also known as the sunshine vitamin as on exposure to sun rays, the active metabolite of vitamin D is synthesized. The reason of deficiency of vitamin D levels among the population is decreased sun exposure. Also, the changing life style is playing an additional factor as people comparatively prefer to stay indoors than before.

Vitamin D also plays an important role in the homeostasis of calcium, which means it is important for calcium absorption. That is why, it helps in strengthening bones and teeth. Another form of vitamin D which is found in our body is the hormonal form.

In 1980, the role of vitamin D was found as an immune modulator. Various studies have suggested that VDRs on cells are related to immunity and the effect of hormonal form of vitamin D on the immune cells such as T and B cells indicates its importance.

Deficiency of vitamin D is very risky for a person as it makes them susceptible to various autoimmune diseases. The active form of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH)2D3). It is a pleiotropic hormone which possesses comprehensive physiological activities.⁴

A study by Bhalla et al. has shown that monocytic cells have high-affinity binding sites for 1,25(OH)2D3.⁵ Veldman et al. in their study found that CD8 lymphocytes may be the major site of action of 1,25(OH)2D3.⁶ Alroy et al. in their in vitro study showed suppression of T-lymphocyte proliferation by 1,25(OH)2D3 due to which there is a decrease in interleukin 2, gamma interferon, and granulocyte-macrophage-stimulating factor mRNA levels. The transcriptional activators of the interleukin 2 gene are directly inhibited by a nuclear hormone receptor.⁷

The suppressive effect of 1,25(OH)2D3 was supported by another study which was done on the effect of vitamin D on the immune system.⁸ An important role is played by natural killer T (NKT) cells in the pathogenesis of autoimmune diseases as well as cancer. Yu and Cantorna reported that proliferation of NKT cells and increase in interleukin 4 and interferon gamma production of NKT cells are promoted by vitamin D.⁹ Hence, from the aforementioned findings it can be said that vitamin D plays an important role in immune-mediated disorders.

Lichen planus is a chronic inflammatory disease which occurs on skin and mucous membranes including oral mucosa. The main mechanism of pathogenesis of oral lichen planus is cell-mediated cytotoxicity. The apoptosis of oral epithelial cells is triggered by autocytotoxic CD8+ T cell. In oral lichen planus, the subepithelial infiltrates are composed of T cells and macrophages. A majority of the T cells which are present in the epithelium and are present adjacent to the damaged basal keratinocytes are activated by CD8+ lymphocytes.¹⁰ The proliferation of T cells specifically CD8+ cells is inhibited by activated vitamin D resulting in reduction of interleukin 2.¹¹

The vitamin D deficiency causes dysregulation of proliferation of T-cell and might be the reason of development of oral lichen planus.¹² A study by Zhao et al. showed that for the downregulation of VDRs in oral keratinocytes, lipopolysaccharide is responsible which is associated with the development of oral lichen planus.¹³

In this study, every patient was asked to estimate serum vitamin D level. From the 450 patients, none of the patients had vitamin D level more than or equal to 20 ng/mL. The lowest vitamin D level was 7.9 ng/mL and the highest was 17.8 ng/mL. Thus, all the patients exhibited vitamin D deficiency. We found that posttreatment subjective symptom score 8 was less in group I and group II as compared to group III. There was significant difference in group I and group II (p < 0.05).

In this study, we found that mean vitamin D posttreatment value was 16.4 ng/mL in group I, 15.6 ng/mL in group II, and 17.8 ng/mL in group III. The difference was found to be significant in group I and group II. The effect of vitamin D supplementation was much better in group I and group II patients.

In this study, when patients were compared for burning sensation, those patients who had severe vitamin D deficiency and those with a history of stress as well had a higher visual analog scale score as compared to patients with mild and moderate vitamin D deficiency as in group I. Those patients (group II) who were on a combination of topical steroids and vitamin D supplementation showed more posttreatment improvement in burning sensation than in the patients who were not taking vitamin D supplementation (group III).

Low vitamin D levels are also said to have an effect on mental health as such patients show depression. The role of stress in decreasing vitamin D is not as such but it increases the blood cortisol levels. Godschalk et al.¹⁴ found out that the number of VDRs is altered by glucocorticoids by inhibiting VDR gene transcription or by affecting the VDR mRNA processing. Hence, there is an indirect role of the stress in hormonal vitamin D which can affect the immune modulation.

Stress is said to be the most common cause associated with oral lichen planus. But the exact role is yet to be understood. In this study, the patients who had severe vitamin D deficiency had more stress. However, the treatment response was much better in group I than other groups.

Various studies have been carried out which show the effect of vitamin D levels on immune-mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.^15–17

There are various less studies which have reported the use of vitamin D supplementation in oral lichen planus. A case has been reported in a 40-year-old female who showed marked improvement in oral lichen planus after she was injected 300,000 units of cholecalciferol intramuscularly.^18,19

Another study concluded that 1,25(OH)2D3 plays an anti-inflammatory role in oral lichen planus as it has an effect on the NF-kB signaling pathway.

Therefore, from the findings we can conclude that low vitamin D plays a crucial role in causing oral lichen planus. This study supports the fact that vitamin D supplementation can help in treating oral lichen planus better and earlier.

The limitations of the study are the small sample size and follow-up period. Not all forms of lichen planus were included in the study.

CONCLUSION

The study concludes that while treating oral lichen planus, the patient should be asked to get serum vitamin D level tested so that vitamin D supplementation can be started and also patients should be counseled if they show signs and symptoms of stress. From the findings, it can be summarized that vitamin D plays an important role in the treatment of oral lichen planus.

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