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Original Article

Vitamin D in the Treatment of Oral Lichen Planus: A Pilot

Clinical Study
Juhi Gupta, Anshul Aggarwal, Md. Asadullah, Masood H. Khan, Neha Agrawal1, Kauser Jahan Khwaja
Departments of Oral Pathology/Oral Medicine and Radiology and 1Community Dentistry, Dr. Z.A. Dental College, AMU Aligarh, Uttar Pradesh, India

Abstract
Introduction: Lichen planus is an autoimmune disease with unknown etiology. Vitamin D not only affects the health of the bone but also
has an impact on immunity. To understand the possible role of vitamin D in the pathophysiology of oral lichen planus (OLP), a clinical study
was conducted on patients suffering from OLP who reported to the dental outpatient department of our dental college in Aligarh. Aims: To
evaluate the possible co‑relation between the OLP with vitamin D deficiency and the effect of vitamin D supplementation on the treatment of
the OLP lesion. Settings and Design: A pilot clinical study was conducted in a dental college in Aligarh. Materials and Methods: Patients
with clinical presentation of OLP were included in our study. Patients with drug‑induced oral lesion or lesion associated with dental
restoration (lichenoid reactions) were excluded from the study. Patients were divided into three different groups depending on factors such
as stress, low vitamin D levels, or a combination of the above factors. Patients with severe vitamin D deficiency were supplemented with
vitamin D. Statistical Analysis Used: Fisher’s exact test. Results: There was a statistically significant improvement in both subjective and
objective symptoms in patients who were supplemented with vitamin D with or without psychological counseling apart from topical steroid
application for a short period. Conclusion: Marked improvement and long‑term remission in the symptoms in vitamin D–deficient patients
after restoration of normal vitamin D level suggests its role in pathogenesis of OLP like other autoimmune diseases. Therefore, further study
and research work need to be carried out to understand the pathway through which vitamin D is related to the pathogenesis of OLP.

Keywords: Autoimmune disorder, immune modulator, lichen planus, steroids, vitamin D

Introduction cases may undergo malignant transformation, and the condition

If we define immunity, then by definition it is a condition of
being able to resist a particular disease especially through
preventing the development of a pathogenic microorganism
or by counteracting the effects of its products.[1] Autoimmune
disease is a condition in which the body immune system fails
to recognize its own body cells or the antigen as “self” and
the immune system starts targeting the own body cell leading
to destruction and damage. In an autoimmune disease, the
basic pathology is an interaction between autoreactive T
lymphocytes and body antigen, or autoantibodies and antigen
present on the targeted cells.
Lichen planus is also a type of autoimmune disease where
the cells of the skin and mucosal surface are targeted by our
own immune system. It is a chronic inflammatory disease
which is characterized by cytotoxic T‑cell‑mediated damage
of the basal cell of the epithelium and chronic inflammation.
According to the reports, 1%–2% of oral lichen planus (OLP)
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has categorized under “potentially malignant disorder” by
the World Health Organization.[2] As the etiology and exact
pathogenesis of this condition are still obscure, it has drawn
the attention of the researchers for the past many years.
The role of vitamin D on the immune system is now
well‑established. Vitamin D receptors (VDRs) are found
to be present on immune cells such as B cells, T cells, and
antigen‑presenting cells. Active vitamin D metabolite is
synthesized by these immune cells in the body, and further,
this vitamin D acts upon the immune system and modulates
it in various ways like down‑ or upregulation of immune
Address for correspondence: Dr. Masood H. Khan,
Department of Oral Pathology/Oral Medicine and Radiology, Dr. Z.A Dental
College, AMU Aligarh ‑ 202 002, Uttar Pradesh, India.
E‑mail: dr.masoodkhan2019@gmail.com
This is an open access journal, and articles are distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix,
tweak, and build upon the work non‑commercially, as long as appropriate credit is given and
the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
How to cite this article: Gupta J, Aggarwal A, Asadullah Md, Khan MH,
Agrawal N, Khwaja KJ. Vitamin D in the treatment of oral lichen planus: A
pilot clinical study. J Indian Acad Oral Med Radiol 2019;31:222-7.
Received: 29-04-2019   Accepted: 01-08-2019   Published: 30-09-2019

222 © 2019 Journal of Indian Academy of Oral Medicine & Radiology | Published by Wolters Kluwer - Medknow
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Gupta, et al.: Immune modulator vitamin D and OLP
cell differentiation. Vitamin D is also capable of modulating
innate and adaptive immune responses.[3] There are sufficient
documented studies that relate deficiency of vitamin D to
many autoimmune diseases such as insulin‑dependent diabetes
mellitus, multiple sclerosis, inflammatory bowel disease,
systemic lupus erythematosus (SLE), and rheumatoid arthritis.
But its role in OLP is yet to be established.
With this background, a pilot clinical study was conducted on
patients suffering from OLP reporting to the dental outpatient
department of our dental college in Aligarh.
Materials and Methods
The study was conducted with 150 patients from various age
groups suffering from OLP. The male‑to‑female ratio was
1:4. Informed consent was obtained from the patients. Ethical
clearance from the ethical committee of the institution was
obtained. The study sample was divided into three groups with
even distribution of the number of subjects in each group. Out
of 150 patients, there was a drop out of 44 patients. Hence, the
effective sample size was 106.
Inclusion criteria
• Clinical presentation or histopathological report
compatible with OLP.
• Patients of all age groups and of both genders suffering
from OLP.
Patients with history of aggravation of the lesion due to
stressful episode
• Patients without any history of the treatment of OLP.
Exclusion criteria
• Patients with oral lesion due to fixed dose reaction or
amalgam restoration.
• Patients who were already on vitamin D supplementation
or on systemic steroids.
• Pregnant patient/patients with bone pathology.
• Patients with any systemic disease or under medication.
A detailed history was documented in terms of symptoms
associated with the condition. Aggravating factors such as
stress were recorded. Detailed medical history and history of
any medication were taken. Drug‑induced lichenoid reaction
was excluded by taking the history of the initiation of the lesion
in relation to any drug intake. Complete oral examination was
performed to look for amalgam‑induced lichenoid reaction.
Diagnosis of the condition was based on the clinical
presentation of the disease. The bilateral presentation, the
typical reticular pattern (characteristic of OLP), burning
sensation, and intolerance to spicy food were used as clinical
diagnostic criteria for the disease. But in doubtful cases where
the presentation was gingival desquamation and the reticular
pattern was not clearly visible, biopsy was done to confirm
the diagnosis.
Patients was asked about lower back pain, history of recent
weight gain, fatigue, hair loss, and muscular pain that may
Journal of Indian Academy of Oral Medicine & Radiology  ¦  Volume 31  ¦  Issue 3  ¦  July-September 2019
indicate vitamin D deficiency. Most of the female patients were
in the menopausal state, and none of the female patients was
pregnant. Detailed history regarding any bone‑related disease
or disease affecting the vitamin D level was taken. None of
the patients was on vitamin D supplementation at the onset
of the study. Most of the patients gave a positive history of
chronic lower back pain and recent weight gain (suggestive
of vitamin D deficiency).
Serum vitamin D level estimation was advised for every
patient. Usually, vitamin D deficiency is defined as
25(OH) D <20 ng/mL, insufficiency as 20–29 ng/mL,
and sufficiency as ≥30 ng/mL. In our study, patients with
serum vitamin D level  ≤15  ng/mL were considered as
severe vitamin deficiency. Serum level of vitamin D ≥15
but  ≤20  ng/mL was considered as moderate vitamin D
deficiency. Serum level of vitamin D  ≥30  ng/mL was
considered as normal.
Patients with severe vitamin D deficiency were asked
to consult their endocrinologist regarding the initiation
of vitamin D supplementation. Patients with vitamin D
level  ≥15 but  ≤20  ng/mL were intentionally not advised
for vitamin D supplementation to be used as a control
group for the study. Most of the patients were kept on oral
supplementation of vitamin D of 60,000 IU or more weekly,
depending on the serum vitamin D level. For patients who
were on vitamin D supplement, topical steroids were given
only to control the initial acute condition and severe burning
sensation. For these patients, topical steroid application
was tapered and withdrawn over a period of 4 weeks of the
treatment. Patients from all the three groups were followed
for 12 weeks.
There are many scoring systems for the evaluation of OLP.
In our study, we have followed the scoring system given by
Kaliakatsou et al.[4] for both clinical diagnosis and treatment
outcome of the disease [Table 1].
Table 1: Scoring criteria by Kaliakatsou et al.
Objective morphological findings Subjective findings
(symptoms)
0=no lesion VAS score for burning sensation
1=white striae only and pain [Figure 1]
2=white striae and erosion ≤1 cm2
3=white striae with erosion ≥1 cm2
4=white striae with ulceration ≤1 cm2
5=white striae with ulceration ≥1 cm2
0 1 2 3 4 5 6 7 8 9 10
Moderate Severe
No Burning
Burning Burning
Mild to Moderate Moderate to Severe
Figure 1: VAS Scale for Burning Sensation
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Gupta, et al.: Immune modulator vitamin D and OLP

Depending on the presence of OLP, vitamin D level, and the

Table 2: Pretreatment objective symptom among patients
history of stress, patients were divided into three groups.
in various groups
Group 1. History of stress alone with mild vitamin D deficiency Pretreatment objective symptoms Total
(vitamin D level ≥ 15 ng/mL)
4 5
(Treatment given is topical steroids and psychological Group 1 6 20.0% 24 80.0% 30 100.0%
counseling) Group 2 10 21.7% 36 78.3% 46 100.0%
Group 2. History of severe vitamin D deficiency alone (vitamin Group 3 6 20.0% 24 80.0% 30 100.0%
Total 22 20.8% 84 79.2% 106 100.0%
D level ≤15 ng/mL)
(Treatment given is topical steroids and vitamin D supplements)
Table 3: Posttreatment objective symptom among patients
Group 3. History of stress and severe vitamin D
in various groups
deficiency (vitamin D level ≤ 15 ng/mL and stress)
Posttreatment objective Total
(Treatment given is topical steroids, vitamin D supplements,
and psychological counseling) 0 1 2 3 4
Group 1 0 0.0% 8 26.7% 6 20.0% 10 33.3% 6 20.0% 30 100.0%
Group 2 8 17.4% 12 26.1% 20 43.5% 6 13.0% 0 0.0% 46 100.0%
Results Group 3 4 13.3% 13 43.3% 9 30.0% 3 10.0% 1 3.3% 30 100.0%
Data obtained were tabulated and subjected to statistical Total 12 11.3% 33 31.1% 35 33.0% 19 17.9% 7 6.6% 106 100.0%
analysis. SPSS software version 16 was used for statistical P‑value significant at <0.05 level
analysis. Descriptive statistics and Fisher’s exact test were
applied. Tables 2 and 4 show the pretreatment objective and
Table 4: Pretreatment subjective symptom among
subjective symptoms among various groups, respectively.
patients in various groups
Data analysis showed statistically significant improvement
in symptoms (both subjective and objective) among patients Pretreatment subjective Total
who were kept on vitamin D supplement. It was observed that 8 9 10
the improvement in burning sensation was more significant in Group 1 2 6.7% 6 20.0% 22 73.3% 30 100%
patients who were on vitamin D supplements and psychological Group 2 2 4.3% 12 26.1% 32 69.6% 46 100.0%
counseling [Tables 3 and 5]. Table 3 shows the changes in the Group 3 1 3.3% 6 20.0% 23 76.7% 30 100.0%
score of the objective signs and Table 4 shows the changes Total 5 4.7% 24 22.6% 77 72.6% 106 100.0%
in the score of the subjective signs. The effect of vitamin D
supplement was better in patients who were able to control
their stress [Table 5]. in our body. The role of vitamin D as an immune modulator
came into the light after 1980. An important finding of many
studies related to the expression of VDRs on cells involved
Discussion in immune system such as T and B cells, and the effect of the
The primary outcome of the study was marked improvement hormonal form of vitamin D on these cells indicates its crucial
in burning sensation in patients with OLP who were role in immunity.
supplemented with vitamin D. As the secondary outcome, it
was noticed that in group 3 patients who were able to control The deficiency of vitamin D makes a person susceptible to
their stress levels responded well to vitamin D which shows the autoimmune disease. 1,25‑Dihydroxyvitamin D (1,25(OH)
possible negative/suppressive effect of stress in the treatment 2D3), the active form of vitamin D, is recognized as a pleiotropic
of patients suffering from OLP. It was also surprising to know hormone and possesses comprehensive physiological
that patients were unaware of their vitamin D deficiency state. activities.[5] Bhalla AK et al. found high‑affinity binding sites
for 1,25‑(OH) 2D3 on monocytic cells.[6] Further studies done
As sun rays play a vital role in the synthesis of the active
by Veldman CM et al. found that CD8 lymphocytes may be
metabolite of vitamin D in our skin, it is also known as the
a major site of action of (1,25(OH) 2D3).[7] An in vitro study
sunshine vitamin. The importance of vitamin D for our health
done by Alroy I et al. showed suppression of T‑lymphocyte
is known since ancient age. The emphasis of adequate sun
proliferation by the active metabolite of vitamin D3, and thus
exposure by people in the past was actually to get an adequate
decreases interleukin 2 (IL‑2), gamma interferon (IFN‑γ), and
amount of vitamin D in the body.
granulocyte‑macrophage‑colony‑stimulating factor mRNA
In general, we are aware of the importance of vitamin D in levels. There is a direct inhibition by a nuclear hormone
calcium homeostasis as it is important for the absorption of receptor of transcriptional activators of the IL‑2 gene.[8] The
calcium, and thus improves the health of bone and teeth. But suppressive effect of the active metabolite of vitamin D on
this is just one aspect of the effects of vitamin D the body IFN‑γ promoters was further supported by a study done by
homeostasis. Vitamin D is also found in the hormonal form Cippitelli M et al. on the effect of vitamin D on the immune

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Gupta, et al.: Immune modulator vitamin D and OLP

Table 5: Posttreatment subjective symptom among patients in various groups

Posttreatment subjective Total
0 1 2 3 4 5 6 7 8
Group 1 0 0.0% 0 0.0% 10 33.3% 4 13.3% 6 20.0% 0 0.0% 4 13.3% 4 13.3% 2 6.7% 30 100%
Group 2 14 30.4% 8 17.4% 8 17.4% 6 17.4% 4 8.7% 2 4.3% 4 8.7% 0 0.0% 0 0.0% 46 100.0%
Group 3 12 40.0% 8 26.7% 6 20.0% 0 0.0% 2 6.7% 0 0.0% 1 3.3% 1 3.3% 0 0.0% 30 100.0%
Total 26 24.5% 16 15.1% 24 22.6% 10 9.4% 12 11.3% 2 1.9% 9 8.5% 5 4.7% 2 1.9% 106 100%
P‑value significant at <0.05 level

keratinocytes are activated CD8+ lymphocytes.[11] Activated

vitamin D inhibits the proliferation of T cells specifically
CD8+ cells, and thus the production of IL‑2.[12]
The deficiency of vitamin D leads to dysregulation of T‑cell
proliferation and thus possibly leads to the development
of OLP. Apart from that, a study done by Bin Zhao et al.
indicates that lipopolysaccharide is responsible for VDR
downregulation in oral keratinocytes, which is associated with
OLP development.[13]
Irrespective of developed or developing country, vitamin D
insufficiency or deficiency among the general population has
been noticed by many researchers. It may be due to a variety
of reasons such as increased use of sunscreen, increased
indoor activities, and greater skin coverage with clothing due
Figure 2: Pre treatment images to various cultural beliefs and religious practices or to protect
against skin cancer. In our study, all the patients irrespective
of whether or not there was any clinical sign or symptoms
70
of vitamin D deficiency were advised to undergo vitamin D
60 level estimation. In none of the patients, the vitamin D level
No burning sensation was  ≥20  ng/mL. The lowest vitamin D level in the study
50
sample was 8.8 ng/mL and the maximum was 18 ng/mL.
40
Moderate to severe
burning sensation So there was low vitamin D level/vtamin D deficiency in all
the patients. But none of the patients was aware of their low
30
Sever burning sensation vitamin D level. In our study sample, it may be related to very
20 less sun exposure due to greater skin coverage with clothing
and minimal outdoor activity.
10

In a study conducted by Akanksha Gupta et al., it was found

0
Group 1 Group 2 Group 3
Figure 3: Post treatment subjective score in three different groups
system.[9] Natural killer T (NKT) cells play an important role in
the pathogenesis of autoimmune disease and also cancer. One
important observation made by Yu and Cantorna that vitamin
D not only promotes the proliferation of NKT cells but also
increases IL‑4 and IFN‑γ production of NKT cells.[10] Hence,
the effects of vitamin D on multiple immune cells clearly
indicate its role in immune‑mediated disorders.
Lichen planus is a chronic inflammatory mucocutaneous
disease. Cell‑mediated cytotoxicity is regarded as a major
mechanism of pathogenesis. Autocytotoxic CD8+ T cell
triggers apoptosis of oral epithelial cells, and the subepithelial
infiltration in OLP is composed of T cells and macrophages.
Most T cells in the epithelium and adjacent to the damaged basal
that vitamin D3 deficiency was more in OLP cases (70.6%)
when compared with control group (34.3%). Thus indicating
that deficiency of vitamin D might have a role in the
pathogenesis of OLP.[14]
In our study, patients with severe vitamin D deficiency alone
or with history of stress had a higher Visual Analog Scale score
for burning sensation when compared with patients with mild
to moderate vitamin D deficiency [Table 3]. Apart from that,
erosive lichen planus was a more common presentation in
patients with vitamin D level less than 10 ng/mL [Figure 2]. The
posttreatment improvement in burning sensation was highest in
patients who were on a combination of topical steroids, vitamin D
supplements, and psychological counseling, followed by topical
steroid and vitamin D supplement, and was least in patients
without any vitamin D supplement [Figure 3]. Improvement in
the objective score for the lesion was also higher in study groups
2 and 3 when compared with group 1 [Table 3 and Figure 4].

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Gupta, et al.: Immune modulator vitamin D and OLP
Figure 4: Post treatment images
Figure 5: Hypothesis of the vicious cycle of stress and OLP
Group 1(30)
Group 2(46)
Group 3(30)
Figure 6: Distribution of subjects in three groups
Low vitamin D level is also related to depression, and
supplementation of vitamin D in such patients showed
improvement in mental health. Moreover, although chronic
stress does not decrease the vitamin D level, it increases the
blood cortisol level. A study done by Godschalk M et al.
`226 Journal of Indian Academy of Oral Medicine & Radiology  ¦  Volume 31  ¦  Issue 3  ¦  July-September 2019
found that glucocorticoids alter VDR number. It appears to
decrease VDR mRNA by inhibiting VDR gene transcription
or by affecting the processing of VDR mRNA.[15] Hence, the
stress indirectly suppresses the hormonal effect of vitamin D
on many cells including the cells of the immune system thus
affecting its immune‑modulating effect.
Stress is one of the most common etiological factors associated
with OLP. But how does it bring about its effect is still not
clear. In our study, the second interesting observation was the
effect of the treatment in patients of group 3 where severe
vitamin D deficiency and stress were present. The overall
treatment response was good in this group. But few patients
who were unable to control their stress showed less response
even after vitamin D supplementation. It may be due to the
downregulation of the VDR, thus decreasing the hormonal
effect of vitamin D. Apart from that, patients suffering from
OLP are usually under constant stress due to the burning
sensation and fear of having oral cancer. So it is a vicious
cycle that further aggravates the condition and decreases the
response to the treatment.
If we consider the effects of the stress on the activity of vitamin
D and OLP, then the probable sequence could be hypothesized
as explained in Figure 5.
There are many studies done by researchers that had related
vitamin D level and its effect on immune‑mediated diseases
such as SLE, rheumatoid arthritis, and multiple sclerosis.[16‑18]
But literature regarding the use of vitamin D in the treatment of
OLP is scanty. R Beena Varma et al. have reported an isolated
case of a 40‑year‑old female suffering from erosive lichen
planus in which marked improvement in the condition had
been reported after intramuscular administration of 300,000
units of cholecalciferol.[19] Jie Du et al. in their study concluded
that 1,25(OH) 2 D3 has an anti‑inflammatory role in OLP due
to its effect on NF‑kB signaling pathway.[20]
Therefore, we hypothesized that low vitamin D level plays an
important role in the etiopathogenesis of OLP. The outcomes
of our study somewhat support the potential role of vitamin
D in the treatment of OLP. As correction of vitamin D level
improves sign and symptoms associated with OLP. The
massive effect of hormonal form of vitamin D on the immune
system opened up a new door to investigate the role of vitamin
D in autoimmune disease. Autoimmune origin and infiltration
of T cells into the subepithelial bands in lichen planus lesion
indicates an abnormality in cell‑mediated immune response.
To our best knowledge, it is the first of such kind of study that
indicates the role of vitamin D in the treatment with probable
cure of OLP.
Conclusion
Small sample size and uneven distribution of subject due to the
drop out of cases are the shortcomings of our study [Figure 6].
It was only a small clinical study which indicates the possible
role of vitamin D in pathogenesis and thus treatment of OLP,
and the findings of our study will definitely give a new direction
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Gupta, et al.: Immune modulator vitamin D and OLP
to the research work in the field of management of OLP. It is
important that the role of vitamin D in the treatment of OLP
must be explored more extensively, and randomized control
trial must be conducted on a large sample.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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