Abstract
Objectives
Oral Lichen Planus (OLP) is an immune mediated disease and causes oro-mucosal burning sensation that reduces food intake and hence resulting in nutritional deficiency. The present study was done to evaluate the serum levels of vitamin B12 in patients with symptomatic OLP and establish an association between reduced B12 levels and OLP.
Materials and method
Serum vitamin B12 was assessed in 60 symptomatic cases of oral lichen planus and 60 healthy age and gender matched controls.
Results
Serum vitamin B12 was significantly reduced (p value < 0) in patients with oral lichen planus when compared to healthy individuals. 43.33% of cases (26 out of 60) had B12 levels less than 187 pg/ml.
Conclusion
Oral lichen planus causes serum vitamin B12 deficiency. Vitamin B12 is linked with normal functioning of immune and neuropsychologic system which has a role to play in etiopathogenesis and malignant transformation of oral lichen planus.
Keywords: Nutritional deficiency, Oral lichen planus, Potentially malignant disorder, Symptomatic, Vitamin B12
1. Introduction
Oral lichen planus (OLP) is an autoimmune and chronic immunological disorder that can cause local irritation and discomfort.1 Oral lesions could be the first manifestation in OLP that occurs in 80% of cases.2 Different types of systemic, topical and combined form of treatment modalities have been used successfully, but OLP relapses after sometime. Complete relief is rare and lesions usually recur, hence an immune mediated pathogenesis is suggested and no definitive etiology has been reported. To diagnose these lesions, WHO (world health organisation) has set criteria, which has made things uniform in terms of diagnosis.3
Serum vitamin B12 is a crucial micronutrient and is also called as cobalamin. It plays an important role in maintaining nerve tissue health, brain function and red blood cell synthesis. An average adult needs about 1–2 μg2 of vitamin B 12 per day. It is not synthesized in the body. It is found in food sources like eggs and food of animal origin.2 Most of the cobalamin is stored in liver (4–5 mg). Megaloblastic anemia occurs when body stores go below 0.1 mg.4
Macrocytosis occurs due to cobalamin or folate deficiency that results in ineffective erythropoiesis. B12 is required for normal maturation of all the cells and DNA synthesis. Its deficiency prevents cell division in the marrow. Oral mucosal changes occurs in 50–60% of patients with megaloblastic anemia.5 Oral symptoms can appear in absence of symptomatic anemia or macrocytosis and this may occur prior to any systemic indicators of B12 deficiency. A wide range of oral signs and symptoms appear as a result of basic changes in the metabolism of oral epithelial cells. This results in abnormal cell structure and keratinisation pattern of the oral epithelium leading to a “beefy” red and inflamed tongue, erythematous macular lesions on dorsum and lateral borders because of marked epithelial atrophy and reduced thickness of epithelial layer. Other oral manifestations include erythematous macules on oral mucosa, tongue, soreness of tongue, generalised reduced taste sensation, burning mouth, candidiasis, angular chelitis.5
OLP (symptomatic cases) manifests as oral mucosal ulcerative lesions on multiple oral mucosal sites. These lesions cause burning sensation, discomfort and pain of the lesional oral mucosa on intake of hot, spicy, salty, acidic food stuffs.6,7 This could cause reduced food intake which may lead to deficiency disorders and malnutrition. Considering the above background, the present study was done to evaluate the serum levels of vitamin B12 in patients with symptomatic OLP and ascertain an association between reduced B12 levels and OLP. The objective of the study was to determine the correlation of vitamin B12 levels in OLP with age.
2. Materials and methods
The present study was performed in the department of Oral Medicine and Radiology. One hundred and twenty patients were selected for the study and divided into two groups: Group A having symptomatic OLP (60 patients) and group B had age and gender matched healthy controls (60 patients). Simple random sampling was used for the recruitment of patients in our study. Patients were informed about the study and consent obtained. Ethical clearance for the present study was obtained from the Institutional ethical committee. Patients diagnosed clinically and histopathologically confirmed as OLP were selected for the study. Patients with history of hematological disorders, liver diseases, gastrointestinal disorders, nutritional deficiencies and pregnancy were excluded from the study. Demographic data, proper history and clinical findings were entered in a proforma specially designed for the study. All the patients were subjected to hematological investigations such as serum vitamin B12 assay. Blood samples were collected on an empty stomach in the morning to avoid other confounding factors which could influence the serum B12 levels. Vitamin B12 was analysed by serum/chemiluminicent microparticle immunoassay (CMIA) with the help of Abbott i1000SR (Chicago, USA) automatic analyzer at the institutional laboratory. The biological reference interval set by this lab was 187–883 pg/ml.
2.1. Statistical analysis
All the data obtained were noted in a tabulated manner and subjected to statistical analysis with the help of STATA-15 software. Comparison of the mean values of serum vitamin B12 levels among cases and controls and gender was done with the help of student's t-test. Pearson's correlation was done to determine the relationship of serum vitamin B12 with age. P value was found to be significant at <0.05.
2.2. Demographic data
A total of 120 patients (60 with oral lichen planus and 60 healthy controls) were included in the study. The mean age of the patients was 38.5 years. Lichen planus was predominantly seen in females (38) than males (22).
3. Results
The mean serum vitamin B12 levels of patients with oral lichen planus and healthy controls were 229.23 and 549.63 respectively with a mean difference of 320.4 which was statistically highly significant with p value of 0 [Table 1, Graph 1].
Table 1.
– Comparison of mean serum vitamin B12 levels in patients with oral lichen planus and healthy controls.
| Sample size | Mean Serum Vitamin B12 | Standard Deviation | 95% Confidence interval | p value | |
|---|---|---|---|---|---|
| Oral lichen planus | 60 | 229.23 | 115.06 | 186.26–272.19 | 0 |
| Healthy Controls | 60 | 549.63 | 110.04 | 508.54–590.72 |
Graph 1.
Comparison of serum vitamin B12 levels in cases and controls.
When compared with gender, the mean serum vitamin B12 was slightly higher in males (391.32) than females (388.34) which was statistically non significant with p value of 0.47 [Table 2, Graph 2].
Table 2.
- Comparison of mean serum vitamin B12 levels in patients with oral lichen planus according to gender.
| Sample size | Mean Serum Vitamin B12 | Standard Deviation | 95% Confidence interval | p value | |
|---|---|---|---|---|---|
| Males | 60 | 391.32 | 229.83 | 289.41–493.21 | 0.47 |
| Females | 60 | 388.34 | 177.48 | 330.00–446.68 |
Graph 2.
Comparison of serum vitamin B12 levels in males and females.
Pearson's correlation was performed to determine the association of mean serum vitamin B12 levels with age. Positive correlation was seen with r value – 0.37 which was statistically not significant.
4. Discussion
Oral lichen planus is a chronic inflammatory oral mucosal disease affecting around 1–2% of the population, more commonly middle aged and elderly females. It is a localized autoimmune disease with T cell dysfunction. There are clinically six types of OLP. Two or more types of LP can occur simultaneously. It more commonly occurs on buccal mucosa, tongue and gingiva. It always has a bilateral and symmetric presentation.8 OLP can be associated with concomitant cutaneous lesions in 15% of the cases where 60% of the cutaneous LP has overlapping of mucosal lesions.9
Study by Chiang (2018) found 7% of OLP patients having deficiency of vitamin B12 (reference range of B12 was <200 pg/ml).9 They also found that 9% of major erosive OLP, 7.9% of minor erosive OLP having B12 deficiencies and 3.6% of non erosive OLP having B12 deficiency. They also found serum gastric parietal cell antibody causing significant vitamin B12 deficiency.10, 11, 12 Challancombe found lower B12 levels in 1.9% of 103 OLP patients, more prominent in erosive OLP than non erosive OLP.13 Thongprason et al. found B12 levels of OLP patients within normal range.14 Previous literature suggests that OLP patients might have some kind of hematinic deficiency and need to be supplemented with multivitamins. Jolly and Nobile observed good and some improvement in 20 and 9 of 41 vitamin deficient supplementation respectively.15 However they have not reported complete remission and concluded vitamin deficiency not to be the main cause for OLP.
Our study also found significant vitamin B12 deficiency among symptomatic OLP patients (p value 0). The results of the study done by Chiang and Challancombe were consistent with our findings.9,13 Erosive OLP diseases/OLP diseases itself causes haemoglobin, iron and B12 deficiency. Bilateral erosive/ulcerative lesions on multiple oral mucosal sites causes burning sensation, discomfort and pain of the lesional oral mucosa, when these patients eat hot, salty, acidic and spicy food stuff.9
Vitamin B12 is a controversial member of B complex. Small micro-organisms act as source for this vitamin. Absorption of this vitamin depends on intrinsic factor. Deficiency of vitamin B12 could be multifactorial. The various oral manifestations of B12 deficiency are: angular chelitis, angular scars, glossitis, burning sensation of tongue, altered taste sensation, soreness, oral candidiasis, recurrent oral ulcers, diffuse erythematous mucositis and pale oral mucosa.16, 17, 18, 19 Oral changes can occur in 50–60% of all patients with megaloblastic anemia.4
Oral lichen planus as such is not caused by B12 deficiency, but erosive lesions of OLP can cause B12 deficiency by reducing the food intake and thereby its absorption[Fig. 1]. Study by Sahebjamee (2010) found B12 deficiency in 8 out of 32 cases of OLP (25%) but the results were not statistically significant.20 Our study has found a statistically significant (p value < 0) reduction of vitamin B12 in symptomatic cases of OLP. Our study found 43.33% (26 out of 60 cases) to be B12 deficient (reference range B12 < 187 pg/ml). This is the first study of its kind on Indian population so far.
Fig. 1.
Flow chart showing relationship between OLP and Vitamin B12.d
Vitamin B12 and folic acid are fundamental factors for precise functioning of human immune system.21 Considering OLP as an autoimmune disease, deficient B12 may possibly act as a cofactor in the etiology. By elevating the number of CD8+ cells and NK cells in cellular immunity, B12 acts as an immunomodulator. B12 deficiency causes reduced number of lymphocytes and this impairs the activity of NK cells.22 NK cells are important for destroying cancer cells. B12 also helps in DNA repair and synthesis. This confirms an important role of B12 in symptomatic cases of OLP, since erosive OLP has highest rate of malignant transformation. Also, symptomatic cases of OLP might lead to malnutrition among patients with erosive or atrophic type due to pain during mastication. These findings are suggestive of an important role of B12 in cancer initiation.23,24 Symptomatic OLP (erosive and atropic variants) are more prone for malignant transformation [Fig. 2]. Henceforth, all cases of OLP necessitate investigation for B12 deficiency and should be supplemented by multivitamins.
Fig. 2.
Flow chart showing vitamin B12 deficiency as a cause for malignant transformation.
Vitamin B12 is important for normal function of neuropsychologic system. Vitamin B acts as co-factor in the synthesis and regulation of dopaminergic and seratonergic neurotransmitters. They regulate mood and clinical depression and anxiety.25 Therefore B12 deficiency can cause mood changes and stress related disorders. OLP is also caused by neuropsychologic disturbances such as depression and anxiety which act as predisposing factors.20 Vitmain B 12 and folic acid have been proved to be effective micronutrients for prevention of anxiety and depression.26 [Fig. 1] Hence B12 needs to be supplemented in all cases of OLP and B 12 analysis could be useful too. Along with advantages there were few limitations too with our study that tissue levels of B 12 could be more specific in cases of OLP that could convert into malignant lesion. Future studies to evaluate tissue B 12 levels with larger sample size should be planned and evaluated.
5. Conclusion
The present study found decreased vitamin B 12 levels in OLP that suggests that, we need to supplement cases of OLP with this vitamin. Deficiency of vitamin B 12 could act as a cause for the occurrence of the lesions or OLP could because for B 12 deficiency and this has been explained in the above discussion. Vitamin B12 regulates immune system and the neuropsychologic behaviour. Any disturbance in B12 levels could affect the innate immunity resulting in stress and anxiety disorders. These factors play a vital role in the etiology for OLP, therefore vitamin B12 and OLP are interrelated. This summarizes the need of supplementation with multivitamins in OLP, along with other drugs.
Funding
Nil.
Declaration of competing interest
Nil.
Acknowledgement
We would like to thank Dr. Ritika Jain, PhD (Economics) for her valuable and kind support in statistical analysis.
Contributor Information
Shantala R. Naik, Email: shantala_naik@rediffmail.com.
Prashant Gupta, Email: prashantgupta.omr@gmail.com.
Tanya Khaitan, Email: tanyakhaitan@gmail.com.
Anjani Kumar Shukla, Email: anjanisukla@yahoo.com.
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