Prevalence of oral manifestations in patients with lupus erythematosus in a sample of the Egyptian population: a hospital based cross-sectional study

Introduction

Lupus erythematosus (LE) is an autoimmune disease subdivided into a cutaneous and a systemic form. The prevalence of mucosal involvement in LE patients is debatable.¹ The mucosal involvement of LE ranges from 9–45% in systemic lupus erythematosus (SLE) and 3–20% in cutaneous lupus erythematosus (CLE).¹ The WHO considers the oral manifestations of LE as a widespread state associated with a significantly increased risk of cancer.²

As mentioned in the WHO digital manual for the early diagnosis of oral neoplasia (2008), several systemic diseases manifest themselves in the oral cavity. These lesions can precede the symptoms and signs of systemic disease or can coexist with it and dentists who are unaware of these lesions will possibly miss them³

According to WHO guides for screening programs (2009),⁴ most programs are selective and target a subset of the population who are considered to be at the highest risk.⁵ Consequently, the present study assessed the prevalence of oral manifestations among a sample of Egyptian patients recently diagnosed with lupus erythematosus as they are considered to be at a high risk of developing oral precancerous lesions.

Methods

The present cross-sectional study was performed to assess the prevalence of oral manifestations in patients with lupus erythematosus in a sample of the Egyptian population. The study was held in the Internal Medicine Department, Rheumatology Clinic in EL Qasr EL Ainy Hospital, Cairo University. Hospital data collection started in March 2019 until March 2020.

Inclusion criteria: Patients recently diagnosed with lupus erythematosus based on American College of Rheumatology (ACR) criteria. Patients with an anti-nuclear antibody (ANA) positive test were only included in the study. The age of patients was 14–70 years old. Both genders were included. Cigarette smoking patients were included.⁶

Exclusion criteria: Patients who had received any previous therapy for lupus erythematosus. Patients suffering from any other systemic diseases known to influence oral and maxillofacial manifestations. Patients on drug therapy who may have oral mucosal manifestations, which eliminate all the potential confounders.

For each eligible participant, a full history was obtained through an interview between the investigator and the patient. Demographical data were collected.⁷ All participants were asked to sign a study-related informed consent. The clinical examination of the oral manifestation was recorded by conventional oral examination (COE) according to the WHO digital manual for physical examination of the oral cavity. The sampled population was classified into two groups. LE patients who had an oral manifestation as true positive oral lesions (TP) and LE patients without oral manifestation as true negative oral lesions (TN).⁵ The oral manifestations were interpreted according to their clinical aspects and their sites in the oral cavity.⁷ The diagnosis of oral candidiasis was made by curd-like patches on the tongue or other oral mucosal surfaces, the presence of classic pseudomembranous lesions characterized by a creamy white pseudomembrane.⁸ Cigarette smoking patients were also assessed.⁹

The primary outcome was the prevalence of intraoral manifestations. The secondary outcome was an extraoral and/or perioral finding. Selection bias was minimized by enrolling the participants in the study in consecutive order of them entering the clinic. Non-respondent bias was minimized by explaining to the participants the aim of the study and their importance and role in the study. Incomplete records were excluded from statistical analysis with the cause of an incomplete record reported.

Ethical approval for the questionnaire and methodology were approved by the Ethics Committee of the Faculty of Dentistry, Cairo University, Cairo, Egypt (approval number: 19/5/6). All participants gave their informed consent to the interviewer verbally, using the telephone interview as a format for data collection. In addition, a link to the consent form was sent electronically.

Sampling was conducted continuously, and the sample size was considered 189 patients with lupus erythematosus with a 95% confidence level, 5% margin of error, and 7.1 maximum deviation of the sample rate. The sample size was calculated using Stats Direct statistical software (version 3.1.17) (An open-access alternative that can provide an equivalent function is the R stats package (RRID:SCR_001905)). Qualitative data were presented as frequencies and percentages. Quantitative data were presented as mean, standard deviation (SD), and 95% confidence interval (95% CI) for the mean values. For qualitative data, Fisher’s Exact Test was used for comparisons regarding qualitative variables. Quantitative data were explored for normality by checking the distribution of data and using tests of normality (Kolmogorov-Smirnov and Shapiro-Wilk tests). Age data showed a parametric distribution. The Student’s t-test was used to compare between patients without and with oral lesions. The significance level was set at P ≤ 0.05. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY: IBM Corp) (RRID:SCR_019096) (An open-access alternative that can provide an equivalent function is the R stats package (RRID:SCR_001905)).

Results

The group of LE patients was composed of 189 patients. All the sampled patients met the ACR criteria for diagnosis of SLE. CLE wasn’t found among the sampled patients.

The mean (SD) values for age were 30.5 (9.7%). Only four patients (2.1%) were smokers. Four women (2.2%) were pregnant.

In this study, the prevalence of oral lesions among SLE patients was 55.6% (105/189 patients). 182 females (96.3%) and 7 males (3.7%). This showed a non-significant relationship in terms of gender in the prevalence of oral manifestations (P-value = 0.465, Effect size = 0.769). There was no statistically significant difference between mean age values in patients with and without oral lesions (P-value = 0.210, Effect size = 0.187). There was no significant relationship between smoking and non- smoking patients. Patient details are summarized in Table 1 and are shown in the underlying data.¹⁰

Of the 105 patients (55.6%) with oral lesions, the most affected site was the tongue 25.7%. Figure 1 displays the site of the oral lesions in descending order. The most common clinical aspect was patches, 53%. Figure 2 displays the clinical aspect of the oral lesions in descending order. Twenty-four patients (22.9%) had a burning sensation while 81 patients (77.1%) were asymptomatic. Seventy-eight out of 105 patients (74.3%) had oral candidiasis.¹⁰

Figure 1. Clinical sites of the oral lesions (n = 105).

Figure 2. Clinical aspects of the oral lesions (n = 105).

The prevalence of skin lesions was 37.6% (71/189 patients). The most common finding was malar rash, 79%.¹⁰ The chart in Figure 3 represents the percentage and descriptions of the skin lesions.

Figure 3. Description and frequency of skin lesions (n = 71).

While the prevalence of patients with oral and skin lesions was 25.4% (48/189 patients). Table 2 shows the difference in the prevalence of oral manifestations among regions and countries.

Discussion

The current study assessed the prevalence of the oral manifestation among LE patients in Egypt.

The present study was conducted on 189 patients: 182 females (96.3%) and seven males (3.7%), and this indicated that LE is more prevalent in Egyptian females than in males. This finding agreed with López-Labady et al.,¹¹ Khatibi et al.,¹² Ali et al.,¹⁶ as well as Barrio-Díaz et al.,¹³ who also found that the majority of LE patients were female.

Despite the variation in sample size between all studies, males were less affected by oral manifestations than females.⁷ There was systemic involvement in all the sampled patients. CLE patients weren’t found in the sampled population. This explains the fact that CLE may be part of the spectrum of SLE or be an entity alone with no systemic features.¹⁴

There was no statistically significant association between the prevalence of gender and oral lesions. Moreover, there was no significant difference between mean age values in patients with and without oral lesions. These findings agreed with Khatibi et al., (2012).¹² There was no statistically significant association between smoking and oral manifestations. This agreed with a study by Bourré-Tessier et al.,¹⁵ who reported that there was no clear association between smoking and the presence of mucosal ulcers or malar rash.

The present study showed that the prevalence of oral manifestations was 55.6% (105/189 patients). In a study conducted in Iran, 102 (54.3%) out of 188 patients had oral lesions, while 86 (45.7%) had none.¹² In addition to that, a study conducted in Ireland showed that 50% of patients had positive oral findings.¹⁶ In Saudi Arabia it was found that mucocutaneous lesions including oral ulcers were reported in 72% of 46 SLE patients.¹⁷ Also, De Rossi et al., in 1998, found the prevalence of oral manifestations ranged from 81.3 to 87.5%.¹² The highest prevalence was reached at 97% in an Argentinian study.¹³ On the other hand, a lower prevalence was shown in a Venezuelan study,¹¹ which reported that of the 90 patients diagnosed with LE only 10 patients (11.1%) showed oral mucosal lesions. Collectively, the higher prevalence of oral manifestations in SLE is probably because all tissues are potentially affected as a result of the disease course.¹

The results of the current study revealed that the most affected site was the tongue (25.7%) in just over one-quarter of the patients followed by the palate, lips, buccal mucosa, the gingiva, and the least affected site was the corner of the mouth. Khatibi et al., in 2012, revealed that the sites most commonly affected by oral lesions were the buccal mucosa and the lips.¹² A Brazilian study reported that the more frequently affected sites were the buccal mucosa then the hard palate and lower lips.¹ While another study found that the commonest site was the hard palate.¹⁶ This variation may be attributed to dissimilarity in the exclusion and inclusion criteria of these studies.

Interestingly, one of our patients reported symptoms of numbness and facial sensory impairment, which indicate the involvement of sensory ganglia of the cranial nerves. Loss of taste and dry mouth were reported as the first manifestation of SLE in this patient. The serological result reported that the antinuclear antibody was present in a titer of 1/320, and the CT scan examination of the brain revealed that the patient had had a stroke. This may be attributed to the autoimmune autoantibodies directed against sensory ganglion.¹⁸

The first trigeminal neuropathy (TN) cases in SLE patients were reported in 1971, where TN was stated as the only neurological manifestation of SLE among two cases in their study.¹⁹ In 1990 two cases of TN in SLE were reported among 81 studied subjects.²⁰ And then in 2017 one case of TN was reported during a 35-year study of SLE in African American female patients in the USA.²¹Finally, in 2020 a case of acute severe sensory ganglionopathy was reported in a 24-year-old male SLE patient.¹⁸

The second most frequently affected site for oral manifestations in this study was the palate and this agreed with a previous study conducted in Brasil.¹ In third place were the lips; the lower lips were more often affected than the upper lips. This may be attributed to the fact that the lower lips are more exposed to sunlight than the upper lips and to the biological mechanisms of ultraviolet rays (UVR), which induce lupus flare.²²

In our study, patches were reported as the most significant morphologic feature (53.3%). This was followed by ulcers (15.2%), plaques (11.4%), white keratotic striae (8.6%), macules (6.7%), linear erythema (6.7%), and the least common clinical feature was erosive lesions in 3.8% of the patients.

Lourenco et al., (2007) reported that oral lesions presented in different clinical aspects, ranging from classic plaques accompanied by central erythema enclosed by a white rim with radiating keratotic striae to a white plaque on a pigmented mucosa and finally to bullous lesions.¹ Menzies et al., reported that LE lesions varied from striated/reticular white patches, erosions, ulceration to homogenous white patches.¹⁶ Recently, Barrio et al., reported that oral lesions were classified into erythematous patches, honeycomb plaques, lupus cheilitis, chronic plaques, oral discoid lesions, LP-like lesions, keratotic lesions, ulcerative plaques, oral ulcers, pebbly red areas, purpuric lesions, erythema and diffuse palatal petechial erythema.¹³

The results of the current study revealed that the clinical appearance of the patches varied from one patient to another. Round erythematous patches were reported in 35.2 % of the lesions. These patches were painless and would bleed on palpation while scaly erythematous patches were observed in 16.2% of the lesions. A scaly white patch was reported in 1.9% of the patients particularly on the lips, these scales were crusted and thick. Barrio et al., (2020) reported that erythematous patches are considered as clinical descriptions of oral lupus lesions.¹³ Nico et al.,¹reported that LE oral lesions manifested as oval non-scarring patches with variable degrees of erosion.¹

The second most significant clinical feature was found to be the ulcer. Ulcers were reported in 15.3% of cases, ranging from ulcers surrounded by a red halo, painless ulcers surrounded by white radiating striae, ulcers surrounded by red radiating striae associated with burning sensation, and round erythematous hemorrhaging ulcers.

Meyer et al., and Ranginwala et al. found that oral ulcers are present in 19% of cases in both of their studies.²³ While Khatibi et al., (2012) and Menzies et al., (2018) found that 28.1% and 23.8% of patients showed oral ulcers respectively.¹² Barrio et al., (2020) found that oral ulcers were present in 11 of 150 patients with lupus (7%).¹³ On the other hand, Ali et al. (2012) reported that oral ulcers were present in 72% of patients.²⁴

The third clinical picture in our study was the plaque. Plaques were reported in 11.4% of the lesions. The clinical appearance ranged from painless red plaques to painful erosive plaques. Lourenço et al., (2007), found that the lesions of the hard palate were red maculae or plaque. In contrast, white lesions were found only in the buccal mucosa.¹ Barrio et al. reported that honeycomb plaques on the palate are only present in lupus patients.¹³ A white plaque on pigmented mucosa was reported by López et al.¹¹ Also, Lourenço et al., reported four cases of classic plaques with central erythema from 46 patients (8.6%).¹

In the current study, painless white keratotic striae came in fourth place at 8.6%. Buccal mucosa was the most affected by white keratotic striae followed by the gingiva. These findings agreed with Lourenço et al., who reported that white lesions (plaque and LP-like striae) were found only in the buccal mucosa.¹

The results of the present study revealed that single and cluster macules were reported in 6.7% of the cases. These red macules were painless, and the palate showed the highest prevalence of macules followed by the gingiva. This was in accordance with López et al., who also reported the presence of red maculae on the hard palate.¹¹ Barrio et al., reported that high activity of the LE was associated with red macules on the soft palate and brown-pigmented macules on the lower gingiva.¹³

In the current study, linear erythema was reported in 6.7% of cases. It was noticed on the gingiva and palate. Similarly, Nico et al., 2008 reported that linear erythema and keratosis were observed on the upper palatal gingiva in the patient.¹

Finally, erosive lesions were observed in 3.8% of the cases in the present study. These lesions showed no statistically significant association with a particular oral site. A Brazilian study reported erosive lesions on the lips and buccal mucosa.¹ Also, erosive and keratotic lesions on the left buccal mucosa were presented in a case report by Nico et al., (2008).¹

In the current study, oral candidiasis was observed in 41% of all the patients. Moreover, (74.3%) patients had oral lesions superinfected by Candida. This agreed with a study conducted in Qatar in which the prevalence of oral Candida was 88.1%.¹⁷ Immune system dysregulation is the main cause of Candida infection. The imbalance between innate and adaptive immunity leads to the consequent secretion of pro-inflammatory cytokines (IL-6, IL-8, IL-10, IL-12, TNF-α) in LE, which affects the immune regulation of antifungal activity and proves a correlation between Candida and LE.²⁵

In the present study, the prevalence of cutaneous lesions in the LE patient was 37.6%. This agreed with Barrio et al., (2020), who also found that 45.3% of patients had cutaneous manifestations.¹³ About 83.1% of the patients who had cutaneous manifestations were affected on the bridge of the nose and cheek. While the least affected site was the perioral area. The morphology of skin lesions varied from a malar rash (butterfly erythema), hyperpigmentation to disc-shaped patches. In the present study, malar rash was observed in 79% of patients.²²

The prevalence of patients with oral and skin lesions was 25.4% (48/189 patients). Whereas, in a study by Ranginwala et al., (2012), 90.47% of patients had oral lesions along with skin lesions.²³

Recommendations

Further studies should be conducted in other regions with a larger sample size and at different time intervals to broaden these findings. Also, additional research could highlight the impact of race, ethnicity, and genetics on the prevalence of oral manifestations of the disease.

Conclusion

The present study emphasizes the importance of early diagnosis of oral lesions in patients recognized with LE as the WHO considers oral manifestations of LE as a widespread state associated with an increased risk of cancer. It is also required in order to implement oral hygiene measures and provide treatment to improve patients’ health-related quality of life. Further studies are needed since research has been conducted in only 1 in 10 countries of the world.

Data availability

Consent

All participants gave their informed consent to the interviewer verbally, using the telephone interview as a format for data collection. In addition, a link to the consent form was sent electronically requesting written consent for publication of the patients’ details.