Mucosal involvement is prevalent in lupus patients, but since 1997, only ulceration has been expressly included in the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE), and less emphasis has been paid to the remainder of the oral manifestations associated with lupus. (1-3). SLE oral lesions were detected in 5-25% of cases, with some studies indicating rates as high as 80% (4). The clinical descriptions of oral lupus lesions vary considerably between studies and the terminology used to describe oral lesions in the previous literature is sometimes ambiguous. Some of the unspecified terms used are as follows: oral ulceration, honeycomb plaque, keratotic plaque, nonspecific erythema, and purpura (5, 6). As the classification of oral manifestations is inconsistent and the clinical descriptions of the lesions are not meticulous, it is practically difficult to summarize previous studies on the prevalence of various oral lesions in lupus. Other oral problems that are more common in this group of patients than in the general population are mentioned below.
Both xerostomia and hyposalivation predispose these patients to dental caries as well as recurrent non-infectious pharyngitis. Because of the use of corticosteroids for the treatment of SLE, oral candidiasis and other opportunistic infections are also prevalent (5). Gingivitis and periodontitis have also been shown to be more prevalent in SLE cases (7). Previous articles have listed several reasons why health care providers, including physicians and dentists, should pay attention to oral manifestations in patients with lupus and take the time to examine and treat them. Diagnosis and treatment of some oral problems such as periodontal diseases may reduce SLE activity level according to some evidence and therefore make the overall management of lupus easier (8, 9). Other head and neck infections should also be monitored to prevent further development of possible infections in other parts of the body caused by long-term immunosuppressive therapy in these patients (10). Some research has revealed that oral lesions may take precedence over other symptoms and can be used to diagnose lupus. The emergence of oral symptoms in lupus patients has been regarded as a warning sign that patients are entering a phase of increased disease activity (11, 12). Oral ulcers, especially when they become chronic in SLE, pose a risk of developing squamous cell carcinoma. Therefore, it is recommended that a biopsy be performed as soon as possible when the diagnosis is not definitive or the lesions appear to have no improvement. So it is another important reason why the diagnosis and treatment of these lesions should not be delayed (13).
Genetic factors, geographical variations and socioeconomic patterns appear to play an important role in overall manifestations and outcomes of SLE (14, 15) and according to the scarcity of data from Iran, and especially in Yazd province, and considering the importance of oral examination in this group of patients based on all the above reasons, this study aimed to assess the prevalence of oral manifestations in SLE Iranian patients categorized by their types and regions, and their possible association with age, gender, the activity of the disease, and disease duration.

 

In this study of 96 SLE patients, 13 men (13.5%) and 83 women (86.5%) with ages ranging from 17 to 69 years and a mean of 31.9±11.35 years were divided into three groups: 15-30, 30-49, and over 49.
Oral lesions were seen in 62 (64.4%) SLE patients. The age group over 49 years had the highest incidence of lesions, although statistical analysis revealed no significant association between age and the presence of oral lesions (P-value = 0.9) (Table 1).
 

Table 1. The distribution of SLE patients based on oral lesions and other variables

Table 2. Evaluation of related factors to the possibility of oral lesions in SLE patients using logistic regression

Logistic regression analysis, P=0.00, P<0.05 – Statistically significant. P – Probability value, confidence interval

Discussion

In our study, the mean age of the 96 SLE patients was 31.90 ± 11.35 years, and the majority of patients (86.5%) were female. Many studies have shown that the disease is more common in women (18, 19). The female-to-male ratio in this study was 6.5:1, which is similar to the ratio reported in another Iranian study in Fars province in 2008 by Nazarinia (20). Higher female-to-male ratios were reported in the studies of Hammoudeh in Qatar (9.5:1) and China (9.6:1) (10, 21). Furthermore, the mean age of participants in our study was fairly near to some studies (22, 23). For example, in Del Barrio’s study, the average age of patients was stated to be 38.31 ± 10.65 years or about 30.27 years in Nazarinia’s study, but Rezvaninejad et al reported a higher mean age of 42.9 ± 6.1 years in a recent study in Bandar Abbas (6, 20, 24).
In the current study, 64.4% of SLE patients had oral lesions, which was similar to the study done by Zakeri in Zahedan (61.4%) (23). In contrast, the prevalence of oral lesions in our study was higher than in Villamin's study in the Philippines (33%) (25). According to Brennan’s review, the prevalence of oral mucosal lesions in SLE patients ranged from 2-80%, with a mean of 20-30% (26). De Rossi's review, on the other hand, revealed that the frequency of oral lesions in SLE patients was 81.3–87.5%. The differences could be related to a lack of commonality in the types of lesions investigated in De Rossi's review (27).
In our study, oral lesions were diagnosed in 64.4% of patients, with white and red lesions being the most frequent (58%), and the most common regions involved were the buccal mucosa (25.8%). The majority of lesions in Lourenço's study were lichenoid lesions, with the lips and buccal mucosa being the most affected areas (28).In contrast to our study, the most prevalent oral lesions in both Khatibi's study in Tehran and Rezvaninejad's study in Bandar Abbas were ulcers, but the most common sites remained the buccal/labial mucosa and lips, respectively (24, 29). The lower prevalence of ulcers among our participants could be attributable to fewer selected patients having active SLE at the time of the investigation. The Zakeri study found that the most prevalent oral lesions were white and red lesions (56.13%), which was similar to our findings, but the most common site of their lesions was in the soft palate, which contradicted our findings (23). According to our study, the rate of pigmented lesions was 19.4%, while in Chacón-Dulcey’s study in Venezuela, 9.5% of SLE patients had multiple hyper-pigmented macules in the buccal mucosa (18).
In our study, the prevalence of chillitis was 31.9%, candidiasis 25.5%, petechiae 25.5%, and herpetic lesions 17%. Cheilitis and candidiasis were observed in 2.4% of SLE patients in Hammoudeh's study, while petechiae were found in 16.7%, which differed from our results (10). Other findings also show that SLE patients had a higher prevalence of herpetic lesions as a result of immune dysregulation and immunosuppression (30). Oral candidiasis is a frequent problem in SLE patients, according to Leite et al., who reported a much greater frequency than our study (54% versus 25.5%) (31).
One of the side effects of SLE is the development of gingivitis and periodontitis, which directly affect the tooth support structures. In this study, by examining the status of the periodontium in SLE patients, the prevalence of gingivitis and periodontitis was 40.6% and 45.8%, respectively.
While a study in the United Kingdom revealed a greater frequency of periodontitis in SLE patients (85%), the Hammoudeh study found a prevalence of gingivitis and periodontitis of 54.8% and 57.1%, respectively, which is virtually equivalent to our findings (10, 32).
The frequency of decayed, filled, and missing teeth in our study was 91.7%, 69.8%, and 57.3%, respectively. These findings are consistent with previous research, such as the Gofur study, which discovered that 74% of Indonesian patients had decayed teeth, 66% had missing teeth, and 60% had filled teeth (33). In a study conducted by Hammoudeh et al. in Qatar, the prevalence of caries was 88.1%, while the frequency of missing teeth was 64.3% (10). A large number of cariogenic bacteria (Streptococcus sobrinus and Streptococcus mutans) have been foundin supragingival plaque samples from patients with SLE. It seems that lowering both the pH and the flow rate of saliva increases the risk of tooth decay in these patients (34).
In our study, statistical analysis revealed a significant association between the prevalence of oral lesions in SLE patients with female gender, longer SLE duration, higher disease activity, simultaneous presence of periodontal diseases, and the incidence of filled and missing teeth (P < 0.05). However, the association between age, medication type, and caries with oral lesions was not significant (P > 0.05). We would add that there was no comparison with all these variables because there were a limited number of previous studies that listed these related factors, and there was no single study that addressed all of these variables together. There was no significant relationship between the prevalence of oral lesions and gender, age, or disease duration in Zakeri's study (23). In Khatibi's study, age and gender had also no statistically significant association with oral lesions (29). Rezvaninejad, on the other hand, found significant associations with both female sex and being over 45 years old, which was somewhat similar to our findings (24).
In the study of Khatibi, there was a significant association between the presence of oral lesions and SLE duration, daily intake of corticosteroids, and medications used to treat SLE other than corticosteroids (29). According to logistic regression, the presence of oral lesions in SLE patients who took anti-malarial medicines alone was 38.3 times more than in those who used corticosteroids alone. . This may be explained by the fact that antimalarial drugs are mainly effective in reducing oral lesions, and one of the reasons for their prescription is the treatment of oral ulcers, especially those that were not managed by corticosteroids, so perhaps this is the reason for this difference (13).
Interestingly, in conversations with patients, most of them were unaware of the presence of lesions in their oral cavity. As mentioned before, oral lesions were associated with greater disease activity index (SLEDAI) levels in this research (P < 0.05) in contrast to the Kudsi’s study (35) but in agreement with Del Barrio and Aurlene's studies (6, 22). It seems that we need to be more vigilant about the periodic evaluation of oral lesions, especially those that are not associated with significant discomfort in patients. In addition, the type of ulcers among lesions may undergo malignant changes if left untreated (13). Apart from that, oral lesions may be one of the first symptoms of a systemic underlying disorder such as lupus, so physicians and dentists should pay special attention to oral examination in patients with non-specific complaints, and inform patients of the importance of treatment if oral lesions are found. In this way, they will take an important step toward early either diagnosis or controlling of lupus, as well as avoid aggressive tests, increased costs, and incorrect therapeutic choices.
Since the link between skin lesions and the occurrence of some potentially life-threatening complications, such as lupus nephritis, has been established in numerous studies, research into the link between oral lesions and other systemic manifestations, particularly skin lesions, may be useful in predicting the course of the disease (36, 37). Although future longitudinal studies are required to determine causal links with all associated factors.

 

Conclusion

Given the prevalence of oral lesions in more than 60% of patients, as well as the high prevalence of caries and periodontal problems, regular oral examinations of these patients appear to be more important.

 

Acknowledgements

We would like to thank Dr. Seyedeh Tahereh Faezi for her valuable guidance in conducting this study.

 

Conflicts of Interest

Authors declare no conflict of interests.