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ORIGINAL RESEARCH Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 288-292
Evaluation of salivary cortisol and psychological factors in patients with oral lichen planus


Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere - 577 004, India

Click here for correspondence address and email

Date of Submission07-Mar-2008
Date of Decision03-Apr-2008
Date of Acceptance27-Jun-2008
Date of Web Publication30-Oct-2009
 

   Abstract 

Background and Objectives: Lichen planus is a relatively common chronic inflammatory disease of oral mucosa and skin. Cortisol, also called as "stress hormone", has been used as an indicator in various stress evaluation studies. Salivary cortisol measurement is an indicator of free cortisol or biologically active cortisol in human serum and provides noninvasive and easy technique. Recent studies have been conflicting, and hence, in the present study, evaluation of salivary cortisol levels and psychosocial factors in oral lichen planus (OLP) patients was done.
Materials and Methods: A total of 30 patients with clinically and histopathologically proven cases of OLP, along with the age and sex-matched healthy controls were included in the study. Samples of stimulated saliva were collected, centrifuged and analyzed for the level of cortisol with cortisol enzyme linked immunosorbent assay. Psychosocial factors of study and control groups were measured by depression anxiety and stress scale. Student's t-test was used to compare the psychological factors and salivary cortisol levels between patients with the OLP and the control group.
Results: Irrespective of sex, significantly higher depression (83.4 ± 15.4%), anxiety (80.5 ± 11.3%),
and stress (94.2 ± 6.2%) scores were observed in OLP patients compared to controls. Increased cortisol levels were observed among 17 (56.6%) OLP patients in the study group. A positive correlation was found between psychological factors and salivary cortisol levels in the OLP patients. The values of Pearson's correlation coefficient "r", between depression, anxiety, and stress with salivary cortisol was: +0.42,S; +0.27,NS; and +0.65,HS, respectively among the study group.

Keywords: Oral lichen planus, salivary cortisol, depression, anxiety, stress

How to cite this article:
Shah B, Ashok L, Sujatha G P. Evaluation of salivary cortisol and psychological factors in patients with oral lichen planus. Indian J Dent Res 2009;20:288-92

How to cite this URL:
Shah B, Ashok L, Sujatha G P. Evaluation of salivary cortisol and psychological factors in patients with oral lichen planus. Indian J Dent Res [serial online] 2009 [cited 2023 Mar 23];20:288-92. Available from: https://www.ijdr.in/text.asp?2009/20/3/288/57361
Lichen planus, a chronic inflammatory mucocutaneous disease of unknown etiology, occurs in approximately 0.02-4% of the adult population, affecting the skin and/or oral mucosa. [1],[2],[3] Oral lichen planus (OLP) is a relatively common chronic inflammatory disorder affecting stratified squamous epithelia; it is a relatively common disease, affecting approximately 1-2% of the population. Current data suggests that OLP is a T cell-mediated autoimmune disease in which autocytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. [4]

The etiology is not known, but there are several hypothesis involving genetic, infectious, psychogenic, and autoimmune factors. The pathogenesis has been extensively studied and the disease appears to be a result of a cell-mediated immune reaction in which Langerhans cells, keratinocytes, and activated T lymphocytes are involved. [5] Some of the studies have shown that patients with OLP exhibit higher levels of anxiety, greater depression, and increased vulnerability to psychic disorders. [6] OLP patients with erosive LP have found to exhibit higher depression scores than patients with nonerosive LP. [7] In addition to the chronic discomfort that can result in stress, patients with OLP are concerned about the possibility of malignancy, the contagious nature of the disease, and the lack of available patient educational materials. [4] Psychological intervention may be warranted given the fact that the level of anxiety and salivary cortisol of OLP patients are high, supporting the relationship of OLP with stress. [8]

Evidence accumulated in the last two decades supports the idea that psychiatric stress and psychiatric illness can modify immunological functions. Cortisol, which is also called as "stress hormone", has been used as an indicator in the stress evaluation studies. Cortisol is the major glucocorticoid in humans and has a wide range of influences on metabolism, immunoregulation, vascular responsiveness, cognition, and behavior. It also has an impact on numerous pathological conditions including inflammatory autoimmune disorders. [9] Salivary cortisol measurement is an indicator of free cortisol or biologically active cortisol in human serum and provides noninvasive and easy technique. [8] Recent studies have been conflicting, and hence, the present study intends to evaluate the salivary cortisol levels and psychosocial factors in OLP.


   Materials and Methods Top


The study and control population of approximately 60 subjects were considered for this study which were drawn from outpatient department. Clinically [10] and histopathologically diagnosed cases of 30 subjects with OLP, were included in the study group. Patients suffering from any systemic disease(s) such as diabetes, hypertension, cardiovascular disease, renal dysfunction, liver disorders, etc. and patients with any other mucosal disease or any other skin disease which may be associated with oral lesions were excluded. [8] Patients with adverse habits of chewing arecanut, gutkha, and tobacco and with adverse habits of smoking were also excluded from the study. Age and sex matched apparently healthy 30 subjects who had no recent history of systemic conditions were included in the control group.

Assessment of intensity of burning sensation was determined using a Visual Analogue Scale (VAS) of 0-10 (with 1 cm divisions, where '0' is no burning sensation and '10' is worst possible burning sensation). The patients were asked to mark VAS at a point which best represented the level of symptoms. [11] After histological confirmation, the patients were subjected for saliva collection and psychological evaluation. Saliva was collected in the morning hours between 9-10 am to avoid diurnal variations. In each case, approximately 2.0 ml of stimulated saliva was collected from each subject by drawing the saliva with a disposable syringe and later passing it into a sterile glass centrifuge tube. The samples were immediately frozen at −20° C and maintained at that temperature until shortly before assay. During assay the samples were thawed at 37° C, and then immediately centrifuged at 8,000 rpm for 10 minutes. The supernatant fluid, thus obtained, was used for assay of Cortisol estimation using Salivary Cortisol enzyme linked immunosorbent assay (ELISA) kit. The following values of normal samples were used as the primary guidelines:



After the procedure of saliva collection, patients were subjected for psychological evaluation. Psychological evaluation was done with depression, anxiety, and stress scale (DASS). [12] This scale enclosed a self-assessment questionnaire of 42 questions. Each component of depression, anxiety, and stress enclosed 14 questions. For purpose of benefit to the patient, the questionnaire was translated in the regional language of "Kannada".

Statitistical analysis was presented as Mean ± SD for quantitative/continuous data, and number and percentages for categorical data. Student's t-test was used for comparing the means between the groups. Categorical data was analyzed by Chi-square test. Pearson's correlation coefficient was used to assess the relationship between different parameters. Multiple logistic regressions were performed for assessing the association of independent variables and their effect/interaction with OLP. For all the tests, a P value of 0.05 or less was considered for statistical significance.


   Results Top


The patients included in the current study were in the age range of 19-69 years. The mean age ± SD was found to be 40.1 ± 12.6 among OLP patients. Among these, 17 (56.7%) patients were females and 13 (43.3%) were males [Table 1]. About six patients (20%) presented with skin involvement. Among the study group, we found different clinical forms at multiple sites in most of the patients. Most common forms were reticular (11 patients, 36.6%) and erosive (10 patients, 33.3%) patterns [Table 2]. Most of the patients had moderate (10 patients, 33.3%) and severe burning sensation (11 patients, 36.6%). Moderate to severe burning sensation was noted more commonly in patients with reticular, erosive, and combined patterns, 13.3%, 13.3%, and 10.0%, respectively [Table 3].

We found increased levels of depression, anxiety, and stress, 70%, 66.6%, and 100%, respectively among the study group, when compared to controls [Table 4]. All these psychological factors were increased in all forms of OLP, i.e., there was no statistical difference of psychological factors between the erosive and nonerosive groups.

The salivary cortisol levels in OLP patients were found to be increased in 17 subjects (56.6%), and 13 subjects (43.3%) had normal level, i.e., 3-10 ng/ml. In most of the OLP patients, with increased levels of depression, anxiety, and stress were found to have increased levels of salivary cortisol. Patients with reticular, erosive, and combined patterns had increased levels of salivary cortisol, when compared to annular and linear patterns [Table 5]. In the present study we found positive correlation between depression, anxiety, and stress with salivary cortisol levels. Correlation analysis of the study group using Pearson's correlation coefficient showed positive correlation between the salivary cortisol levels and depression (+0.42, S); anxiety (+0.27, NS) and stress (+0.65, HS) respectively [Table 6].

Multivariate analyses with multiple logistic regressions were done. OLP was considered as dependant variable, and other parameters age, sex, psychological factors (depression, anxiety and stress) and salivary cortisol levels were considered as independent variables. On this regression model, we found age and sex having no independent influence on the occurrence of OLP [Table 7]. Whereas, we found depression, anxiety, stress, and salivary cortisol levels had independent influence on occurrence of OLP.


   Discussion Top


OLP is a fairly common disease of adults and has a worldwide distribution. [13] Among Indians, the prevalence is found to be 0.02 to 0.22%, as per recorded in 30,000 dental outpatients. Considerable high prevalence of 1.5% has been reported from door-to-door investigations in 7,369 villagers in a district of Kerala. [13] Various scales were used in the psychological assessment of patients in previous studies, some were self- reported and others assessed by a psychiatrist. [6],[7],[8],[14],[15],[16] In the current study, we used a self-reported scale called DASS, which can assess all the three parameters i.e., depression, anxiety, and stress. [12]

It is very well established in the literature that rise in serum cortisol levels with psychological factors such as depression, anxiety, and stress, due to activation of HPA-axis. Though there are changes in the cortisol levels at different points of time during the day, a positive correlation was observed between the levels of salivary cortisol in the OLP patients. [8],[17],[18] Secretion of cortisol in saliva is a passive one and it is a reliable indicator of serum levels. Since, this is a noninvasive and easy procedure, the measurement of cortisol by salivary sampling was advocated in the present study. The morning levels of salivary cortisol are consistent and could be an accurate pattern, hence in the present study, saliva of all the patients were collected during morning hours between 9-10 am.

In a study of 49 patients with approximately one-third (34.5%) cases with erosive variety were symptomatic, whereas nonerosive varieties were asymptomatic. [19] In contrast to this, we observed burning sensation in all the varieties of OLP. Surprisingly, in the present study, two females with erosive OLP presented with no signs of burning sensation, this could be attributed to the nature of adaptability by the patients. It is very well established in the literature that only patients with erosive lesions experience burning sensation or is always associated with the red component or nonkeratotic pattern of OLP.

In majority of reported studies and surveys, OLP can present with various clinical forms and at multiple oral sites. [2],[4],[18],[20],[21] In a clinical study of 674 patients with OLP, among all cases buccal mucosa was the most predominant site, followed by the tongue and the lower lip, gingival and labial mucosa. [18],[20],[21] OLP can present with variety of clinical forms, most among this is reticular form. [2],[4],[18],[20],[21],[22] Our observation was in agreement with the other studies. [2],[4],[18],[20],[21],[22] In the present study, we found approximately 11 (36.66%) cases with reticular form, 10 (33.33%) with erosive form, 7 (23.33%) with combined form, 1 (3.33%) with linear pattern, and 1 (3.33%) with annular pattern.

The modern view of etiology and pathogenesis of most of the diseases suggest them to be influenced by multiple factors, hence requiring a simultaneous evaluation of factors concerned with various areas. This concept holds true for oral lichen planus. In 1977, Engle GL, described the new biopsychosocial medical model which encompasses biological findings (disease), psychological ones (usually reflecting the "illness"), and social correlatives (sickness). [19] Two of the conditions known to be intermediate agents leading to many somatic malfunctions, stress and anxiety, are the combined results of psychological and environmental social factors. Each of these two factors, have a potential effect on oral health. [19] Preda EG, et al. based on psychological investigations, reported that the oral mucosa is an erogenic zone, and is an extremely complex and vulnerable region i.e., very reactive to certain psychological influences. These authors also included OLP as one of the psychosomatic diseases. [17] Some authors have considered psychological factors as risk factors.

Severely depressed patients have high blood levels of cortisol caused by chronic stress. During periods of active stress, cortisol promotes survival by mobilizing energy reserves. In addition to these short-term adaptive changes, cortisol is also involved in other long-term stress-related adaptive changes such as, shaping and regulating a number of physiological processes, including immune responsiveness and activation of sympathetic nervous system. In the depressed people, cortisol peaks early in the morning and does not decrease as the day progresses. Clinical studies suggest that elevated cortisol may induce clinical depression. [23] In the current study, erosive OLP and nonerosive OLP patients showed similar levels of depression, anxiety, and stress. Irrespective of sex, significantly higher depression (83.4 ± 15.4%), anxiety (80.5 ± 11.3%), and stress (94.2 ± 6.2%) scores was observed in OLP patients compared to controls, but approximately 9 (30%) and 10 (33.3%) OLP patients had normal anxiety and depression scores, respectively.

In the current study, of the 30 patients, we found increased cortisol levels among 17, and among these 9 were females and 8 were males. Very severe levels of depression and stress were found in four patients, each with increased levels of salivary cortisol. Increased cortisol levels were observed in patients with moderate to very severe levels of depression, anxiety, and stress. OLP patients with normal to moderate levels of depression, anxiety, and stress had normal levels of salivary cortisol. Among the study group, depression and salivary cortisol showed a significant positive correlation of +0.42, (P < 0.05). Anxiety and salivary cortisol showed a positive correlation of +0.27, (P = 0.14), but was not statistically significant. Stress levels and salivary cortisol levels a highly significant positive correlation of +0.65, (P < 0.001).

There is a substantial literature that has identified cortisol levels in populations under stress and many investigations have failed to replicate this association. Reasons could be inconsistent methodologies, time factors, etc. Therefore, inherent variability in cortisol levels both between and within individuals could be due to: [24]

  • Gender differences
  • Effect of time of day
  • Medication
  • Food intake
  • Differences in analytical approach


These factors increase the likelihood of variance and inaccuracy in the determination of cortisol, potentially contributing to the apparent equivocal relationship between emotional distress and cortisol. [24] These reasons could have contributed to reduced levels of salivary cortisol in patients with higher levels of psychological factors in the current study group patients. Dehydroepiandrosterone (DHEA) is an adrenal androgen, secreted again by action of HPA-axis, has an antagonist action to cortisol. [24],[25] This has been reported to affect the levels of cortisol in serum, but has not been confirmed by further longitudinal studies.


   Conclusion Top


The present study involved a small sample size and the results of this study needs to be confirmed in larger longitudinal population studies. Due to inconsistent literature regarding the cortisol pattern associated with psychological factors in the OLP patients, it is difficult to compare across the available cortisol studies with different methodologies, among diverse populations and parameters.

Further research can be directed at assessing the psychoimmune interactions, as these may represent the possible avenues by which the psychological status of individual may impact on immune status homeostasis during onset and progression of OLP. Hence, the present study necessitates further larger, longitudinal studies with an improved protocol, in order to prove that psychological state of OLP patients could influence treatment compliances.

 
   References Top

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Correspondence Address:
Bina Shah
Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere - 577 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.57361

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]

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Janaina Silva Martins HUMBERTO,Jefferson Veronezi PAVANIN,Maria José Alves da ROCHA,Ana Carolina Fragoso MOTTA
Brazilian Oral Research. 2018; 32(0)
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28 Comparison of Salivary Cortisol and a-amylase Levels and Psychological Profiles in Patients with Burning Mouth Syndrome
Tahereh Nosratzehi,Saeedeh Salimi,Azadeh Parvaee
Special Care in Dentistry. 2017; 37(3): 120
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29 Comparison of Salivary Cortisol and a-amylase Levels and Psychological Profiles in Patients with Burning Mouth Syndrome
Tahereh Nosratzehi,Saeedeh Salimi,Azadeh Parvaee
Special Care in Dentistry. 2017; 37(3): 120
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30 Clinical Management Protocol for Dental Implants Inserted in Patients with Active Lichen Planus
Moustafa Nabil Aboushelib,Mohammed Hamdy Elsafi
Journal of Prosthodontics. 2017; 26(1): 29
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31 Clinical Management Protocol for Dental Implants Inserted in Patients with Active Lichen Planus
Moustafa Nabil Aboushelib,Mohammed Hamdy Elsafi
Journal of Prosthodontics. 2017; 26(1): 29
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32 The Role of Stress Hormones in Dental Management Behavior Problems
M. DUŠKOVÁ, J. VAŠÁKOVÁ, J. DUŠKOVÁ, J. KAIFEROVÁ, Z. BROUKAL, L. STÁRKA
Physiological Research. 2017; : S317
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33 Stress as an etiologic co-factor in recurrent aphthous ulcers and oral lichen planus
Priyadarshini Karthikeyan,Nalini Aswath
Journal of Oral Science. 2016; 58(2): 237
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34 Stress as an etiologic co-factor in recurrent aphthous ulcers and oral lichen planus
Priyadarshini Karthikeyan,Nalini Aswath
Journal of Oral Science. 2016; 58(2): 237
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35 Burning Mouth Syndrome: A Review of the Etiopathologic Factors and Management
Sajith Vellappally
The Journal of Contemporary Dental Practice. 2016; 17(2): 171
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36 Psychological disorders and oral lichen planus: matched case-control study and literature review
R Pippi,U Romeo,M Santoro,A Del Vecchio,C Scully,S Petti
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37 Psychological disorders and oral lichen planus: matched case-control study and literature review
R Pippi,U Romeo,M Santoro,A Del Vecchio,C Scully,S Petti
Oral Diseases. 2016; 22(3): 226
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38 Salivary changes in oral mucosal diseases
Yazan Hassona,Crispian Scully
Periodontology 2000. 2016; 70(1): 111
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39 Salivary changes in oral mucosal diseases
Yazan Hassona,Crispian Scully
Periodontology 2000. 2016; 70(1): 111
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40 Oral lichen planus: salival biomarkers cortisol, immunoglobulin A, adiponectin
Pia Lopez-Jornet,Cristina Aznar Cayuela,Asta Tvarijonaviciute,Francisco Parra-Perez,Damian Escribano,Jose Ceron
Journal of Oral Pathology & Medicine. 2016; 45(3): 211
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41 Oral lichen planus: salival biomarkers cortisol, immunoglobulin A, adiponectin
Pia Lopez-Jornet,Cristina Aznar Cayuela,Asta Tvarijonaviciute,Francisco Parra-Perez,Damian Escribano,Jose Ceron
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42 Factors associated with clinical characteristics and symptoms in a case series of oral lichen planus
Natália G. Barbosa,Éricka J. D. Silveira,Emeline N. de A. Lima,Patrícia T. Oliveira,Maria Sueli M. Soares,Ana Miryam C. de Medeiros
International Journal of Dermatology. 2015; 54(1): e1
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43 Clinical and laboratory rationale for photodynamic therapy in patients with severe complicated oral lichen planus
O. F. Rabinovich,A. V. Guseva,E. S. Abramova
Stomatologiya. 2015; 94(2): 40
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44 Clinical and laboratory rationale for photodynamic therapy in patients with severe complicated oral lichen planus
O. F. Rabinovich,A. V. Guseva,E. S. Abramova
Stomatologiya. 2015; 94(2): 40
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45 Cutaneous and Mucosal Lichen Planus: A Comprehensive Review of Clinical Subtypes, Risk Factors, Diagnosis, and Prognosis
Farzam Gorouhi,Parastoo Davari,Nasim Fazel
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46 Sleep disturbances, anxiety and depression in patients with oral lichen planus: a case-control study
D. Adamo,E. Ruoppo,S. Leuci,M. Aria,M. Amato,M.D. Mignogna
Journal of the European Academy of Dermatology and Venereology. 2014; : n/a
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47 Oral lichen planus: A retrospective study of 633 patients from Bucharest, Romania
Tovaru, S. and Parlatescu, I. and Gheorghe, C. and Tovaru, M. and Costache, M. and Sardella, A.
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48 Burning Mouth Syndrome
Jaisri R. Thoppay,Scott S. De Rossi,Katharine N. Ciarrocca
Dental Clinics of North America. 2013; 57(3): 497
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49 Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial
Gajin Han, Jae-Woo Park, Seok-Jae Ko, Jihee Son, Jongki Seon, Juyeon Kim, Seulki Kim, Inkwon Yeo, Bongha Ryu, Jinsung Kim
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50 Stress involvement as trigger factor in different skin conditions
Liana Manolache
World Journal of Dermatology. 2013; 2(3): 16
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51 Stress involvement as trigger factor in different skin conditions
Liana Manolache
World Journal of Dermatology. 2013; 2(3): 16
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52 Salivary Cortisol, Salivary Alpha Amylase, and the Dental Anxiety Scale
Hana Sadi,Matthew Finkelman,Morton Rosenberg
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53 Prevalence of oral mucosal disorders in institutionalized and non-institutionalized psychiatric patients: a study from AVBR Hospital in central India
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54 Prevalence of oral mucosal disorders in institutionalized and non-institutionalized psychiatric patients: a study from AVBR Hospital in central India
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55 Psychological stress as a risk factor for postoperative keloid recurrence
Fabianne Furtado, Bernardo Hochman, Paulo Luiz Farber, Marisa Campio Muller, Lilian Fukusima Hayashi, Lydia Masako Ferreira
Journal of Psychosomatic Research. 2012;
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56 The antioxidant potential of saliva: Clinical significance in oral diseases
# Miricescu, D., Greabu, M., Totan, A., Didilescu, A., Rǎdulescu, R.
Therapeutics, Pharmacology and Clinical Toxicology. 2011; 15(2): 139-143
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57 Salivary cortisol and dehydroepiandrosterone (DHEA) levels, psychological factors in patients with oral lichen planus
Carla Girardi, Clarice Luz, Karen Cherubini, Maria Antonia Zancanaro de Figueiredo, Maria Lúcia Tiellet Nunes, Fernanda Gonçalves Salum
Archives of Oral Biology. 2011; 56(9): 864
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58 Herbal treatment for lichen planus
Yarnell, E. and Abascal, K.
Alternative and Complementary Therapies. 2010; 16(4): 217-222
[Pubmed]
59 Herbal Treatment for Lichen Planus
Eric Yarnell,Kathy Abascal
Alternative and Complementary Therapies. 2010; 16(4): 217
[Pubmed] | [DOI]



 

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