It is well-known that some oral diseases may have a psychosomatic component (14
). In RAS stress or anxiety, could act as precipitating factor causing the development of new lesions (1
). The real role of this factor is still unknown but it can be probably related with the modifications that anxiety and stress produce in the oral mucosa, the increase of the parafunctional habits or the increase in some habits that causes microtraumatic injuries (1
As a result, Soto-Araya and cols. (15
) studied the prevalence and degree of stress, anxiety and depression among patients with different oral diseases such as burning mouth syndrome, oral lichen planus and RAS. Using the Recent experience test and the HAD scale (Hospital Anxiety scale and depression), they found increased levels of stress (61%) and anxiety (83%) among the 18 patients with RAS of their study group.
Later, Gallo and cols. (16
) studied the stress levels through the questionnaire SSLVAS (Symptoms of Stress List, Institute of Psychology at the University of Sao Paulo, Brasil) in 55 patients with RAS and 25 healthy patients. Soto-Araya and cols. observed a significantly higher level of stress among patients with RAS too. However, they observed no statistically significant relationship between the clinical severity of RAS lesions and stress level.
Salivary cortisol has been shown in several studies (17
) as a safe analytic tool, useful for detecting high stress or anxiety states. The production of cortisol by the adrenal glands is controlled by the secretion of the adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH secretion is regulated by the action of corticotropin releasing hormone (CRH), a hypothalamic hormone, which is stimulated by stress situations (15
). Under normal conditions the secretion of ACTH is rhythmically produced synchronized with the sleep-wake cycle, so the secretion is maximal in the morning and minimal at midnight.This variation is known as circadian rhythm or cycle, and it allows us to maintain a high activity level during the day in contrast to the night.
Anxiety and depression states not only modify the physiological production of cortisol and its concentration in plasma, it also produces a proportional change in the concentration of cortisol in saliva (16
In 1996 McCartan and cols. (9
), compared the levels of salivary cortisol by radioimmunoassay, and the degree of anxiety by the HAD psychometric scale, between two different groups of patients with RAS. In the first group they included 12 patients with persistent oral lesions, no hematological alterations and no improvement in symptoms after oral empirical administration of vitamin B1 and B6. In a second group they included other 12 patients who had improved their oral symptoms after correcting hematological deficiencies, such as deficits of iron or vitamin B12. In this second group they also included patients who had had a positive response after empirical administration of vitamin B1 and B6. After a statistical analysis, they found a significantly higher level of anxiety and salivary cortisol among the patients in the first study group.
Later, Albanidou-Farmaki and cols. (19
) also studied the possible association between anxiety, serum and salivary cortisol, and RAS. They selected a group of 38 patients with RAS and a control group of 38 healthy patients and carried out a determination of cortisol using chemiluminescent immunoassay. To determine the degree of anxiety they used a test consisting of two independent scales, one for the “Status Anxiety” (STAI-S) and other one for the “Trait Anxiety” (STAI-T).After analyzing the results they observed significantly higher cortisol levels, both in saliva and serum in the group of patients with RAS. Furthermore, levels of “trait anxiety” and “status anxiety” were also significantly higher in RAS patients than in healthy individuals.
The determination of salivary cortisol is a widely contrasted method to measure and quantify situations or states of stress and anxiety (6
). In opposition to these previous works that measured salivary cortisol in patients with RAS, our results in this pilot study have not shown a significant increase in salivary cortisol. We don´t Know exactly what causes this difference, but we think they might be due to several reasons. The first one and the most obvious, is the limited sample size of the studies. Moreover, the populations studied are very different, have different epidemiological characteristics and might show differences in the prevalence of stress. In relation to the methodology employed, we do not know exactly how much could some of the important differences that we found have influenced in the results.
In our study, the saliva sample collection was performed in all cases during the active phase of the disease and was always carried out in the morning between 9 and 12 AM. We always collected unstimulated saliva. In the study of Albanidou-Farmaki and cols. (18
), we don´t know if the patients had active lesions at the time of sample collection. In their study the samples were collected from stimulated saliva (with 10% citric acid) and inclusion and exclusion criteria of patients were different. Processing and technical methods and materials used by them were different too.
In the study of McCartan and cols. (9
), sample collection was performed between 1 and 2 PM and using saliva stimulated with a 10% citric acid solution. While in their first group of the study samples were collected during the active phase of the disease in the second it is unclear. We can conclude reading their article that they collected the samples in this second group in patients free of lesions at that moment. In this study, inclusion criteria and processing methods and materials used were different from ours too.
Although our overall results do not show a significant increase of salivary cortisol, we found that patients with the higher salivary cortisol concentrations suffered more severe clinical forms of the disease, according to the number, size and recurrence of lesions.
As a conclusion of this pilot study we can remark that we could not observe the existence of significantly higher salivary cortisol levels among the patients with RAS in our region during periods of active disease than in healthy individuals.
Due to the differences observed between our results and those obtained by other authors, we believe that further studies are needed in other populations with larger sample sizes. In this way we will be able to determine the real role of salivary cortisol and the real importance of stress and anxiety as triggers in the pathogenesis of the RAS.