Gingivitis on Systemic Lupus Erythematosus (SLE) patients: A Pilot study

 

Kusworini Handono¹, Nanda Rachmad Putra Gofur², Nurdiana³, Handono Kalim⁴,

Cesarius Singgih Wahono⁴, Sri Poeranto⁵

¹Dept of Pathology Clinic, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

²Doctoral Program of Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

³Dept of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

⁴Dept of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

⁵Dept of Parasitology Clinic, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

 

ABSTRACT:

Introduction: Systemic Lupus Erythematosus (SLE) condition have hyperactivity immune which causes decreasing immune ability to fight bacteria, resulting susceptible to infection. Believed that one clinical manifestation in oral cavity is gingivitis. Discovery of gingivitis in SLE patients supports proving that there is an increased risk of infection and inflammation, which is associated with autoimmune disease. Objective of this study is to determine gingivitis and its severity in SLE patients. Methods: A total of 61 SLE patients were recruited in the study in Rheumatology Department Dr. Saiful Anwar Hospital, Malang. Characteristics data as disease duration and treatment duration were recorded. Clinical parameters as Systemic Lupus Erythematosus Activity Index (SLEDAI), gingival index, bleeding on probing were recorded and blood serum were collected for anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody levels in all groups. Anti-dsDNA levels were calculated using Enzyme-Linked Immune-Sorbent Assay (ELISA). Results: SLE patients with normal gingiva was 3 patients (4.91%) with mean gingival index 0, 11 patients (18.03%) was mild inflammation with mean gingival index 0.36±0.13, 17 patients (27.86%) was moderate inflammation with mean gingival index 1.85 ±0.18, and 30 patients (49.18%) was severe inflammation with mean gingival index 2.78±0.28. There was a significant correlation between gingivitis with SLE severity, anti-dsDNA levels, and BOP on SLE patients (p<0.001). No correlation found between gingivitis with disease duration, and treatment duration.
Conclusion: Gingivitis is one of clinical manifestation of SLE. Gingival inflammation related to SLE severity, anti-dsDNA levels and bleeding on probing finding. 

 

 

 

INTRODUCTION:

Gingivitis is gingival tissue inflammation, one of periodontal disease. In Indonesia, prevalence of gingivitis was found to be 60% in young adults, the second largest oral dental disease after dental caries. Based on research data, Indonesia was found that prevalence of periodontal disease was quite high among another country. High prevalence was found in young adults, and its higher with age¹.

 

Clinical finding on gingivitis is generally in gingival color form changing from coral pink to redder. There is bleeding on probing, marginal gingiva with lost attachment often found forming gingiva recession^2,3.

 

Gingival inflammation is an important sign in periodontal disease, manifestation of inflammation is very visible during development of periodontal disease. Normal gingiva has normal contour and there is no bleeding when probing. Patient has no complaints of bleeding while brushing teeth. Severity of gingival inflammation depends on patient's oral hygiene status with poor oral hygiene, bleeding occurs when brushing teeth, or bleeding spontaneously⁴. Gingivitis started with mixed bacterial on gingival tissue, individuals with genetic predisposition and risk factors presence resulting severe inflammation. Risk factors that worsen gingivitis are stress, behaviors related to dental health including oral hygiene and immune conditions. Immune condition is one big chance of developing specific diseases in individuals. Risk factors could expedite disease process and increasing incidence^5,6.

 

Dominant microorganisms contained both anaerobic and aerobic pathogen could activate immune response to gingival tissue. Pathogens trigger neutrophils, macrophages and lymphocytes to gingival sulcus resulting gingivitis. Vulnerability immune condition in individual plays an important role in process of gingivitis, especially in Systemic Lupus Erythematosus (SLE) disease. SLE patients have autoimmune condition, and vulnerable to infection. Inadequate host responses in destroying bacteria can cause destruction of gingiva⁷.

 

SLE patients have hyperactivity immune which causes decreasing immune ability to fight bacteria, inhibits elimination of foreign antigens and is susceptible to infection. Hyperactivity immune also form autoantibodies, especially anti-dsDNA antibody. Anti-dsDNA antibody describes hyperactivity immune system against its own cells develop higher inflammation in many organ and tissue, resulting many clinical manifestations^8,9. Discovery of gingivitis in SLE patients supports assumption that there is an increased risk of infection and inflammation, which is associated with autoimmune disease. Aim of this study is to determine gingivitis, its severity in SLE patients, describing gingival characteristics in SLE patients and correlate gingivitis with anti-dsDNA antibody and SLE severity.

 

MATERIAL AND METHODS:

Methods:

Sample was collected from whole blood using serum collected from 61 SLE patients that fulfilled inclusion criteria. All samples were taken from Rheumatology Department Dr. Saiful Anwar General Hospital Malang, Indonesia. Ethical Clearance has been approved by ethical committees from Dr. Saiful Anwar General Hospital Malang (No. 400/120/K.3/302/2017). The design of this study was an observational analytic study with cross sectional approach, in Biomedical Research Faculty of Medicine Brawijaya University.

 

 In all SLE patient clinical examination of the oral cavity to assess the presence of periodontitis using gingival index (GI). Clinical examination and laboratory tests were conducted to assess the activity of the disease. Severity of SLE measured using SLEDAI index, anti-dsDNA antibody levels using Enzyme-linked immunosorbent assay (ELISA) method.

 

Gingival Index (GI):

Severity of gingival inflammation using gingival index. Measurements on 4 sides of the gingiva including distal-vestibular papillae, edge of vestibular gingiva, the mesial-vestibular papillae and edge of oral gingiva. Gingival index scores each side:

0.     Normal Gingiva

1.     Mild inflammation, slight changes in color and a little edema. There is no bleeding on probing (BOP).

2.     Moderate, reddish, edema and shiny inflammation. There is a BOP.

3.     Severe inflammation, redness, edema, ulceration and spontaneous bleeding.

 

Gingival index is obtained from total score each teeth divided by four sides (4) then divided by total teeth were evaluated¹⁰.

 

Bleeding on Probing:

Bleeding on probing evaluation is performed on 4 sides of the tooth surface, mesial, distal, buccal and palatal/ lingual. If bleeding is found a positive sign, get score 1. The total amount of bleeding on probing is divided by number of sides examined, multiplied by 100%. Each individual could have more than 100 sides¹⁰.

 

Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score:

SLEDAI is an index to determine SLE severity, using Mexican SLEDAI. Scores obtained from total clinical manifestation from observation. Every patient involved in this study was assisted by researchers accompanied by a specialist in rheumatoid¹¹.

 

Anti-dsDNA antibody levels using ELISA:

The levels of anti-dsDNA (anti-dsDNA AccuDiag ELISA Cat#2553-1) were determined using a sandwich ELISA commercial kit. In brief, after coating of non-labelling antibodies and blocking, serum and biotinylated anti-dsDNA, reacting with a different epitope from that recognized by the coating antibody, were added to each microplate well. Optical density (OD) (450nm) was measured on an automated plate reader (Model 3550 UV Microplate Reader; BioRad, Hercules, CA). Levels of anti-dsDNA were determined by comparison with a standard curve obtained in U/mL¹².

 

Data Analysis:

Collected data was analyzed using of SPSS version 25 program and performed by Medical Public Health Department Brawijaya University. The difference of gingivitis severity on SLE patients was analyzed by Kolmogorov Smirnof for normality test, One-way ANNOVA for difference test, and Spearman/Pearson for correlation test¹³.

 

RESULTS:

Our result showed average age was 29 years, average SLE disease duration and treatment duration was 6 and 4 years.  Subject characteristics, SLE severity and gingival condition is shown in table 1. SLE patients with moderate activity disease was 12 subjects, severe activity disease was 48 subjects and mild activity disease was 1 subjects. BOP average subjects was 42%, and average gingivitis with moderate inflammation was found on SLE patients.

 

Table 1: Subject characteristic, SLE severity and gingival condition

 

Many clinical manifestation was appeared both on body and especially oral health is shown in figure 1. Our study found lupus nephritis on 26 subjects (42.6%), mucocutaneous lesion on 28 subjects (45.9%), fatigue on 35 subjects (57.3%), and in oral cavity was BOP on 57 subjects (93.44%), gingivitis on 58 subjects (95.08%).

 

Figure 1: Clinical manifestation on SLE patients

 

 

Gingival inflammation condition shown in figure 2, SLE patients with normal gingiva was 3 patients (4.91%) with mean gingival index 0.08±0.12, 11 patients (18.03%) was mild inflammation with mean gingival index 0.36± 0.13, 17 patients (27.86%) was moderate inflammation with mean gingival index 1.85±0.18, and 30 patients (49.18%) was severe inflammation with mean gingival index 2.78±0.28.

 

 

 

Based on gingival inflammation divided into three groups in table 2, difference SLE severity and anti-dsDNA levels among three group showed significant difference (p<0.001). Gingival inflammation in this index represent gingivitis severity. Results showed difference gingivitis group also showing different SLE severity and anti-dsDNA levels.

 

Figure 2: Gingival inflammation severity on SLE patients.

 

Table 2: SLE severity and Anti-dsDNA levels difference based on gingival inflammation

 

Table 3 showed that was no correlation between gingivitis with disease duration, and treatment duration. There was a significant correlation between gingivitis with SLE severity, anti-dsDNA levels, and BOP on SLE patients (p<0.001).

 

Table 3: Correlation between gingivitis and subject characteristic

*significant p<0.05

 

Correlation between gingivitis using gingival index with SLE severity (using SLEDAI score), anti-dsDNA levels, and BOP showed significant (p<0.001) and strong positive correlation (figure 3).

 

Figure 3: Correlation between gingivitis and subject characteristics

A. Gingival index and SLEDAI score showed significant and strong positive correlation (r=0.897); B. Gingival index and anti-dsDNA levels showed significant and strong positive correlation (r=-0, 919); C. Gingival index and BOP showed significant and strong positive correlation (r=0.937).

 

DISCUSSION:

Results indicate that gingivitis on SLE patients was influenced by SLE activity disease and role of antibody especially anti-dsDNA, but no association with disease duration and treatment duration. Host immune response to inflammation can have an impact on tissue damage and contribute to severity of this disease. Autoimmune disease, especially SLE could induce gingival tissue inflammation, hyperactivity immune causing bacteria elimination failure¹⁴.

 

Autoantibodies in SLE patients and bacterial products increasing, such as LPS and peptidoglycan are recognized by TLR on gingival surface begin an inflammatory response. Mast cells release vasoactive amine and TNFα, which increase vascular permeability and expression of adhesion molecules such as cell-1 (ICAM-1) and P-selectin adhesion molecules on endothelial cells surface. This process triggers the migration of PMN into the tissues, release lysosome enzyme, which contributes to soft tissue degradation. Lymphocytes and macrophages will further migrate periodontal. In this situation, 60−70% of collagen in the gingival connective tissue will be degraded at site of lesion, but alveolar bone mass is still intact¹⁵.

 

Mexican SLEDAI is a modification of SLEDAI developed by researchers from Mexico to reduce laboratory test costs included in SLEDAI, without reducing quality of information obtained. Compared with SLEDAI, it has different weights by giving varying LES manifestations. Mexican SLEDAI has several clinical and laboratory additions removed. Total number of variables in MEXICAN SLEDAI is reduced to ten variables¹². Higher score means greater disease activity. In this study, correlation result between gingivitis and SLEDAI score obtained p <0.001 and r = 0.897, which illustrated a strong and significant correlation. These results indicate severity of gingivitis is comparable to SLE disease activity¹⁶.

 

Correlation of gingivitis and anti-dsDNA levels was p <0.001 and r = 0, 919 showed strong and significant correlation. These results suggest anti-dsDNA contribute also to gingival inflammation. Anti-dsDNA antibodies are very specific to SLE autoantibodies and have a significant role in SLE pathogenesis. Previous studies as evidenced high levels of anti-dsDNA antibodies in SLE patients was found and very low in other autoimmune diseases or normal people. Anti-dsDNA antibodies are result between DNA and immunogenic proteins, derived from apoptotic debris and apoptotic cell surface, which in normal conditions will disappear quickly without an inflammatory response or initiation immune response. These autoantibodies could form immune complexes and are deposited in tissues so that chronic inflammation occurs^17,18. Anti-dsDNA antibodies are specific tests for SLE, rarely found in other diseases and their specificity is almost 100%. High anti-dsDNA titers almost certainly indicate a diagnosis of SLE compared with low titers. If antibodies level is very low it may occur in patients who are not SLE^19,20.

 

Autoimmune process in SLE patient could affect clinical manifestation such as gingivitis. All these condition related changes to immune system, hormonal status, treatment choice and risk to infection. It is also accompanied by oxidant processes almost in all tissues and systems of the body. Further study is needed for finding pathway between gingivitis and SLE. Results of this study were to inform gingivitis and SLE severity, gingivitis is one of clinical manifestation of SLE. Gingival inflammation related to SLE severity, anti-dsDNA levels and bleeding on probing finding.

 

CONFLICT OF INTEREST:

All authors declare no conflict of interest.

 

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Received on 13.11.2019           Modified on 31.01.2020

Accepted on 26.03.2020         © RJPT All right reserved