| Abstract|| |
Background and Aims: Oral lichen planus (OLP) has varied etiology and clinical expression may be influenced simultaneously by different mechanisms. Psychological disturbances and oxidative stress are some such factors proposed in the etiopathogenesis of OLP. The aim was to assess the possible association of psychological traits like stress, anxiety, depression, serum and salivary uric acid levels with disease expression in OLP patients. Methods: A case-control study was conducted in OLP subjects (n = 43) with a clinical and histopathological diagnosis, age and gender matched healthy controls (n = 42) to evaluate psychometric properties through DASS – 42 scale and uric acid (serum and salivary levels) evaluation through “Modified Trinder Method, End point” method. Results: The mean depression, anxiety, stress scores in OLP group were 16.51 ± 7.21, 15.58 ± 6.78 and 15.05 ± 6.11 and the scores in control group were 6.31 ± 3.48, 5.02 ± 2.70 and 5.69 ± 3.39 respectively. The mean value of serum UA level and salivary UA level in OLP group were 4.70 ± 1.33 mg/dl and 5.25 ± 1.61 mg/dl respectively, while the corresponding scores in control group were 5.86 ± 1.12 mg/dl and 6.18 ± 1.28 mg/dl. Conclusion: OLP group had significantly higher depression, anxiety, stress and total scores. Mean serum and salivary uric acid levels were significantly lower in OLP subjects when compared with controls. Clinical Relevance: Correction of psychological traits in oral lichen planus patients may significantly improve the clinical picture, while uric acid levels can be employed for biochemical evaluation in lichen planus patients to analyse oxidative stress.
Keywords: DASS, oral lichen planus, psychometric evaluation, salivary uric acid, uric acid
|How to cite this article:|
Shaw H, Konidena A, Malhotra A, Yumnam N, Farooq F, Bansal V. Psychological status and uric acid levels in oral lichen planus patients – A case- control study. Indian J Dent Res 2020;31:368-75
|How to cite this URL:|
Shaw H, Konidena A, Malhotra A, Yumnam N, Farooq F, Bansal V. Psychological status and uric acid levels in oral lichen planus patients – A case- control study. Indian J Dent Res [serial online] 2020 [cited 2020 Sep 18];31:368-75. Available from: http://www.ijdr.in/text.asp?2020/31/3/368/291479
| Introduction|| |
Oral lichen planus (OLP) is a chronic mucocutaneous disease, inflammatory and autoimmune in character of unknown etiology, in which T lymphocytes act aggressively on the basal layer cells of the oral mucosa epithelium., The modern view of the etiopathogenesis of most of the diseases suggest them to be influenced by multiple factors, hence requiring a simultaneous evaluation of factors concerned with various etiology. It is likely that both endogenous (genetic) and exogenous (environmental) components interact to elicit the disease. Psychological disturbances, oxidative stress, infections and various mechanisms have been proposed in the etiopathogenesis of OLP.,
Stress, anxiety had been known to be intermediate factors leading to many somatic malfunctions and are the combined results of psychological and environmental social factors. Psychological traits had been assessed through various questionnaires, amongst which Depression Anxiety Stress Scale (DASS) has gained popularity. DASS corresponds with tripartite model of anxiety and depression, which state that anxiety and depression possess common as well as unique features. Psychometric properties of this instrument had been applied to both healthy and psychiatric population, and previous studies had reported satisfactory convergent and divergent validity.
Recently, several researches had proposed the multifactorial role of oxidative stress in pathogenesis of some autoimmune diseases such as oral lichen planus., Reduction of defence mechanisms against free radicals, as well as generation of an excess amount of free radicals due to endogenous or exogenous sources, results in an imbalance between oxidants and antioxidants which is known as oxidative stress. Oxidative stress in OLP releases molecules consisting of granzymes that may result in local tissue damage in the effectors. Also, oxidative stress may activate nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), that may induce expression of interleukin (IL)-2 and tumor necrosis factor (TNF)-α, which play an important role in T cell signalling and proapoptotic pathways.
There is growing evidence indicating role of uric acid as an antioxidant in the body that scavenges reactive oxygen species, chelates metal ions and it is believed that in humans, over half the antioxidant capacity of blood plasma comes from uric acid. Thus, monitoring UA level in serum may be used as an indicator of the antioxidant defence. Thorough literature search had revealed conflicting results regarding the association of serum and salivary uric acid levels in lichen planus patients. The present study was hence conducted to assess the possible association of psychological traits and UA in OLP patients, and to find a correlation, if any, between stress and UA.
| Methods|| |
Study Design: An in vivo case-control study was conducted in the Department of Oral Medicine and Radiology of a dental college in Haryana. Institutional ethical clearance for the study [SDD/Eth/16/03] and written informed consent from participants were obtained. The study procedures were carried out in accordance with Helsinki declaration.
Inclusion and Exclusion criteria: Subjects aged 18 years and above of both genders, with a clinical and histopathological diagnosis of OLP as per WHO criteria without skin lesions were included as study subjects. Subjects on systemic steroid or other immunosuppressive drugs, nonsteroidal anti-inflammatory drugs (NSAIDS) within last 2 months, smokers, alcoholics subjects with dysplasia on histopathology, subjects with possible lichenoid drug reactions and lichenoid contact reactions as determined through history, subjects with systemic diseases (gout, diabetes, hypertension, thyroid disease, heart disease, kidney disease, hepatitis C), or other dermatologic diseases affecting immune system or any malignancy, subjects having febrile illness, obesity, ketosis, familial hyperuricemia, and blood dyscrasias, subjects using drugs that increase uric acid (e.g. antidiuretics), patients with severe mental illnesses like schizophrenia and history of use of psychoactive drugs were excluded from the study. The samples for age and gender matched controls were collected from subjects undergoing routine haematological investigations. The study population consisted of 85 subjects divided into 2 groups:
Group 1: Subjects with clinical and histopathological diagnosis of OLP (n = 43)
Group 2: Age and gender matched healthy controls, free of systemic diseases (n = 42)
Method of collection of data: After obtaining the written informed consent, the selected subjects were subjected to complete clinical examination and the relevant examination findings of the lesions were recorded on a specially designed proforma. The clinical severity of OLP was graded according to criteria given by Thongaprassom et al. Clinical photographs of the lesions were taken. All selected participants were subjected to evaluation by a medical specialist to rule out common systemic disorders.
Assessment of psychological profile using DASS scale: The Depression Anxiety Stress Scale is a 42-item pre validated self-report measure of anxiety, depression and stress developed by Lovibond and Lovibond (1995). The questionnaire has 14 questions consecutively each for depression, anxiety and stress. Each of the three subscales of DASS is intercorrelated with one another. The patients were asked to complete the DASS-42 questionnaire and scores were noted down in the form. The questionnaire was translated to the regional language for subjects who do not understand English.
Saliva and blood sample collection: All study participants were asked to refrain from eating and drinking 90 minutes prior to collection of sample. The whole unstimulated saliva was collected with low forced spitting method for 5 minutes at 1 minute interval into sterile containers. The saliva was centrifuged at 3000 revolution per minute and was used for UA analysis. 5 ml of blood was withdrawn from the antecubital vein with minimal trauma under aseptic conditions, centrifuged at 3000 revolution per minute and was stored at -20°C for UA analysis and other screening haematological investigations like complete Hemogram, Erythrocyte sedimentation rate (ESR), Random blood sugar (RBS), Liver function tests (LFT) and Renal function tests (RFT) to rule out the presence of coexisting systemic diseases. The estimation of serum and salivary uric acid levels was done by “Modified Trinder Method, End point” method described by Trivedi and Kabasakalian., If an abnormality was found in the screening tests, the patient was excluded from the study. After clinical examination and blood investigations, oral lichen planus patients were subjected to incisional biopsy under local anaesthesia. The tissue specimen was subjected to histopathological examination and diagnosis of OLP was made according to diagnostic criteria given by WHO.
Statistical analysis: The data was tabulated and subjected to statistical analysis using Statistical Package For Social Sciences (SPSS) version 22 (Chicago, USA). The variation between means of groups was estimated using Independent samples T test. Comparison of frequencies between the groups was done by Chi-square test. Comparison of multiple variables was done by Mann- Whitney test.
| Results|| |
Descriptive data of the study sample
In the present study, the mean age of OLP patients and healthy controls was 45.95 ± 15.10 years, 44.24 ± 15.47 years respectively, without any statistical difference between the groups. Gender differences, when analysed between the groups with Chi-square test, did not reveal significant differences. 15 patients of OLP group were symptomatic with pain, burning sensation with a mean duration of 6.07 ± 2.52 months [Table 1]. Out of 43 OLP patients, 31 presented with reticular form (72.1%), 5 with plaque type (11.6%), 4 with erythematous type (9.3%), while one patient (2.3%) each presented with annular, papular and ulcerative types [Figure 1]a. When clinical severity was assessed in 43 OLP patients according to Thongprassom grading, 29 subjects (67.4%) had grade 1 involvement, 11 (25.6%) had grade 2 involvement, 2 subjects (4.7%) had grade 3 involvement, and only 1 subject (2.3%) had grade 4 involvement [Figure 1]b.
|Figure 1: a: Distribution of clinical variants in OLP group. b: Pie chart showing the distribution of clinical severity of OLP subjects|
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Comparison of frequency and means of mild/moderate/severe DASS scores between OLP subjects and controls
In the OLP group, when the frequencies of depression, anxiety and stress scores were compared between the groups, highly significant differences were found between the groups (p = 0.000 [Table 2]). The mean depression, anxiety, stress scores in OLP group were 16.51 ± 7.21, 15.58 ± 6.78 and 15.05 ± 6.11 with ranges of 0-28, 0-26, 0-25 respectively. The mean depression, anxiety, stress scores in control group were 6.31 ± 3.48, 5.02 ± 2.70 and 5.69 ± 3.39 with ranges of 0-12, 0-10, 0-11 respectively [Table 3]a. When the variation in scores of depression, anxiety, stress and total scores of the groups were assessed with Mann-Whitney test, it was found that OLP group had significantly higher scores in all the parameters [Table 3]b and [Table 3]c. OLP group had higher mean rank in depression, anxiety and stress scores compared with healthy controls, suggesting higher scores in OLP group. Since the U values of parameters was lesser than the critical U value of 191, the groups significantly differed with respect to attributes of depression, anxiety, stress and total scores.
|Table 2: Frequency of depression, anxiety, stress scores in the study groups|
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Comparison of serum and salivary uric acid levels
The mean value of serum UA level in OLP and control groups were 4.70 ± 1.33 mg/dl, 5.86 ± 1.12 mg/dl. A decrease was observed in the OLP group, with a high significant difference between the groups when the levels were compared between the groups. The mean value of salivary UA level in OLP and control groups were 5.25 ± 1.61 mg/dl, 6.18 ± 1.28 mg/dl, respectively, with a highly significant decrease in OLP group [Table 4]a and [Table 4]b. Correlation between serum and salivary UA levels in both groups showed a strong positive correlation (OLP-r = 0.875; Control- r = 0.968) and showed a highly significant association (p = 0.000, [Table 5]).
|Table 5: Correlation between serum and salivary UA levels in study groups|
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Correlation of mean serum and salivary UA levels DASS scores in OLP subjects
Correlation between serum/salivary uric acid levels and depression, anxiety, stress scores and clinical severity as assessed through Thongprassom grading is depicted in [Table 6]. When serum uric acid levels were correlated with depression, anxiety, stress and total scores of OLP patients, no significant correlations were observed (r = 0.080, P = 0.61; r = 0.261, P = 0.092; r = 0.046, P = 0.77; r = 0.116, P = 0.458, respectively). When salivary uric acid levels were correlated with depression, stress and total scores of OLP patients, no significant correlations were observed (r = 0.205, P = 0.187; r = 0.007, P = 0.966; r = 0.229, P = 0.14; respectively). However, salivary uric acid levels in OLP patients had a significant moderately positive correlation with anxiety scores (r = 0.346, P = 0.023, [Table 6]). Grading of the lesions according to Thongprassom scale showed significant positive correlation with the stress, anxiety, depression and total DASS scores in the OLP patients.
|Table 6: Correlation of mean serum & salivary UA levels with mean duration, clinical type & grading, DASS scores in OLP subjects|
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| Discussion|| |
The mean age, female predilection of OLP patients in the present study was similar to studies reported by Bakhthiari et al., Barikbin B et al., Shiva A et al., Girardi C et al. Stress occurs in middle age women due to poor socio economic status, financial strain, physical inactivity, low social support, or poor physical health. Most of the patients were asymptomatic in whom OLP was an incidental diagnosis, similar to Lowental U et al., who reported that out of 49 OLP patients, patients presenting with non-erosive variants were asymptomatic while patients with erosive variants were symptomatic, similar to our study. In the present study, when the clinical variants were assessed, out of 43 OLP patients, 72.1% presented with reticular form (72.1%), 11.6% with plaque type, 9.3% with erythematous type, while one patient presented with ulcerative type. Gupta A et al., Rahul RRK et al., had reported reticular form to be the most common variant in their studies, similar to the present study.
Depression, anxiety and stress are three psychosocial stressors that are co-related, but have different features. Depression is characterized by low positivity, loss of self-esteem, dysphonic mood (e.g. feelings of sadness or worthlessness), and a sense of hopelessness. Anxiety is characterized by autonomic arousal and fearfulness (physiological hyper arousal), panic attacks, and fear (e.g. trembling or faintness). Stress is characterized by persistent tension, irritability, a low threshold for becoming upset or frustrated (negative affect) and a tendency to overreact to stressful events. Chaudhary et al. further hypothesized that these stressors form a starting point for the initiation of various autoimmune reactions, which have been shown to be contributory to the pathogenesis of OLP.
In the present study, when the frequency of psychological alterations were assessed through DASS scale, in OLP group, 35 subjects out of 43 had some form of depression, 38 had anxiety, 22 subjects had stress with highly significant difference between the groups in terms of frequencies of these traits. Our results were similar to those reported by Gupta A et al. who reported differences in depression and stress but not anxiety with DASS -21 questionnaire. Kaur B et al. also found higher frequencies of depression, anxiety and stress among OLP subjects.
The mean levels of depression, anxiety and stress scores of OLP patients in the present study were significantly higher than controls, which was in accordance to study done by Kaur B et al., who reported similar depression and anxiety scores. The present study population however had higher stress scores. Similar results were obtained for all three psychological stressors (i.e. anxiety, depression, and stress) among LP patients in a study conducted by Chaudhary et al., using General Health questionnaire and Hospital Anxiety and Depression scale. Sonal SS et al. found that mean scores for depression, anxiety and stress through DASS of OLP patients were significantly higher than oral leukoplakia and OSMF patients. During stress, serum corticoid concentrations are significantly elevated potentially leading to an immunosuppressive milieu by their negative effects on mononuclear cells and the production of pro-inflammatory cytokines. The effects of glucocorticoids can be selective and depending on the stage and type of immune activity, glucocorticoids can affect the lymphocyte subsets, thus, inducing a shift between Th1/Th2 cytokines while preferentially inhibiting non-activated lymphocytes, thus favouring IL-2 expression during clonal expansion. This may result in the suppression of cells having little or no affinity for an antigen and favor the clonal expansion of cells for antigen having high affinity.
Major depression has also been associated with activation of the inflammatory response as pro-inflammatory cytokines are potent stimulators of the HPA axis. In particular, IL-6 stimulates production of corticotrophin releasing hormone enhancing HPA activity, and hence the increased levels of adrenocorticotropic hormone and cortisol levels. Paradoxically despite the hypersecretion of glucocorticoids, there is an increase in pro-inflammatory cytokine levels during chronic stress and depression suggesting a hypofunctional state of glucocorticoid receptors on immune cells that fail to suppress key components of cellular immunity. This evidence has led to the hypothesis that cytokines and inflammatory factors may be involved in the pathophysiology of neuropsychiatric disorders such as depression., In OLP patients, saliva and serum IL-6 and TNF-alpha concentrations were suggested to be useful in monitoring disease activity status and therapeutic response, with a reduction associated with significant subjective improvement in discomfort symptoms following treatment. This context suggests that psychobiological mechanisms may contribute to OLP pathogenesis and that psychiatric comorbidity may enhance OLP immunological reactivity.
Antioxidants, like some enzymes, vitamins, uric acid (UA), etc., participate in primary defense mechanisms against oxidative stress. High levels of uric acid are readily detected in the cytosol of normal human and mammalian cells, especially in the liver, vascular endothelial cells, and in human nasal secretions, where it serves as an antioxidant.
In the present study, the mean value of serum UA level in OLP group significantly lower than controls, similar to Shiva A et al., Chakraborty G et al. and Gupta A et al. Our results point out toward a pathological relation of decreased UA levels with LP. In the present study, the mean salivary UA level in OLP group was significantly lower than controls, similar to Bakhthiari S et al., Shiva A et al. Oxidative stress may activate nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), that may induce expression of interleukin (IL)-2 and tumor necrosis factor (TNF)-α, which play an important role in T cell signalling and proapoptotic pathways that may trigger OLP. It may hence be hypothesized that the lowered uric acid levels in OLP subjects observed in the present study may be the result of UA being depleted to counter the oxidative stress in OLP.
The present study showed highly significant strong positive correlation between serum and salivary UA levels in both the groups, indicating that salivary UA acid may be used as a marker of disease activity, with added advantages of being non-invasive with ease of collection over blood sample, no requirement of special equipment for collection. Collection of saliva is associated with fewer compliance problems compared with blood collection. This may also reflect the fact that UA is not actively secreted into the mouth due to local inflammatory conditions and salivary UA levels reflect serum UA levels accurately.
In the present study, serum and salivary uric acid levels did not show significant correlation with depression, stress and total scores of OLP patients, similar to that reported by Gupta A et al. However, in the present study, salivary uric acid levels in OLP patients had a significant moderately positive correlation with anxiety scores. This may signify that OLP may be influenced by multiple factors, hence requiring a simultaneous evaluation of factors concerned with different etiologies. However, the present results may be accepted keeping in mind the limitations of small sample size, estimation of uric acid alone to determine antioxidant status, dietary and body mass influences over uric acid not being considered. Further longitudinal studies with larger sample size, wider range of antioxidants, should be done to confirm the results of this preliminary study.
| Conclusion|| |
To conclude, mean scores and frequency of stress, anxiety, depression were significantly higher, while serum and salivary uric acid levels were lowered in OLP subjects when compared with healthy controls in the present study. There was no correlation between depression, anxiety, stress scores and serum UA levels in OLP, while salivary uric acid levels in OLP patients had a significant moderately positive correlation with anxiety scores.
Compliance with Ethical Standards
All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional ethical committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all individual participants included in the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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] [Full text]
Rekha VR, Sunil S, Rathy R. Evaluation of oxidative stress markers in oral lichen planus. JOMFP 2017;21:387-93.
Dr. Aravinda Konidena
Department of Oral Medicine and Radiology, Swami Devi Dyal Hospital and Dental College, Haryana
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]